Acute urticaria: characterized by erythematous-edematous, evanescent, pruritic, evanescent lesions, lasting less than 24 hours, without desquamation. The general condition is usually preserved. In children the annular pattern is more frequent. In both rubella and toxicoderma, the general condition is not preserved. In staphylococcal shock, the general condition is affected and the lesions are blistering. Scabies lesions are preferably interdigital, in the form of papulocoses that can follow linear trajectories.

A 14-year-old female patient in good general condition presents since 4 days ago a very pruritic generalized cutaneous eruption formed by erythematous-edematous plaques between 2 and 15 cm in diameter without desquamation with a tendency to acquire an annular morphology that individually disappear in less than 24 hours. The mucous membranes are respected. Your first diagnostic impression would be:

Pemphigoid

Presentation Primary lesions of small and large blisters, known as vesicles and bullae, are found on the skin and sometimes on the mucous membranes. Non-bullous pemphigoid In some patients, pemphigoid starts off with cutaneous manifestations of BP without bullae, as the only sign of the disease. Pruritic eczematous, papular, or urticaria-like skin lesions may also persist for weeks to months. Bullous phase The bullous stage of BP shows vesicles and bulla, appearing on apparently normal or erythematous skin, predominantly at the flexural aspects of the extremities and the lower trunk. Mucosal lesions, which typically are erosions of the oral mucosa, are present in 10 to 30 percent of patients. Occasionally, the blister fluid becomes blood-tinged. The blisters are tense, about 1–4 cm in diameter, leaving eroded and crusted areas, together with urticarial and infiltrated papules and plaques in an annular or figurate pattern.

Pemphigoid

Other mucous membranes Less common sites that might get involved are nasopharynx, esophagus, and urethra. Nasopharyngeal involvement can lead to ulcerations of the septum and airway obstruction which might require tracheostomy. Esophageal disease may present with ulcerations, dysphagia, odynophagia, and stenosis. Stenosis at urethra, vaginal orifice and rectal have also resulted from chronic inflammation and scarring. Skin disease About 25% of patients have cutaneous lesions, with tense vesicles or bullae, mainly on the face, neck, and scalp. Healing of erosion is either with or without atrophic scars. Cutaneous lesions of mucous membrane pemphigoid presents in 2 subtypes: (1)presents as generalized eruption of tense bullae without scarring (2) presents as localised blisters on an erythematous base, resulting in atrophic scarring.

Pemphigoid

Clinical assessment Presence of tense blisters and erosions that occur on skin without another identifiable cause. Desquamative gingivitis or mucositis involving oral, ocular, nasal, genital, anal, pharyngeal, laryngeal, and/or esophageal mucosae Presence of pruritic eczematous eruptions, or urticarial plaques without identifiable cause. Patient's age over 60 years old. Histopathology Lesional tissue, preferably of an intact vesicle or the edge of an intact bulla is obtained using punch biopsy for Haemotoxylin and Eosin (H&E) staining. The findings are sub-epidermal blister with dermal infiltrated with lymphocytes, neutrophils and eosinophils. Additional findings include sub-epidermal fibrosis which is consistent with the scarring nature of mucous membrane pemphigoid in older lesions and plasma cell infiltration.

Toxic Epidermal Necrolysis -- Differential Diagnosis

Other drug rashes Toxic shock syndrome(usually present with early multiorgan failures and unique cutaneous manifestations in the form of macular rashes affecting palm and soles that later on evolve to desquamation over the period of 14 days) Paraneoplastic pemphigus(as a mucocutaneous manifestation of malignancy) Exfoliative erythroderma(usually affects skin only and spares mucous membrane and is painless in most of the cases) Staphylococcal scalded skin syndrome in children: (evidence of staphylococcal infection, no history of drug intake, and it usually spares mucus membranes) Skin biopsy is also an important tool to differentiate TEN and SJS from these disorders.

Staphylococcal scalded skin syndrome

Staphylococcal scalded skin syndrome (SSSS) is a dermatological condition caused by Staphylococcus aureus. Signs and symptoms The disease presents with the widespread formation of fluid-filled blisters that are thin walled and easily ruptured, and the patient can be positive for Nikolsky's sign. Ritter's disease of the newborn is the most severe form of SSSS, with similar signs and symptoms. SSSS often includes a widespread painful erythroderma, often involving the face, diaper, and other intertriginous areas. Extensive areas of desquamation might be present. Perioral crusting and fissuring are seen early in the course. Unlike toxic epidermal necrolysis, SSSS spares the mucous membranes. It is most common in children under 6 years, but can be seen in adults who are immunosuppressed or have kidney failure.

Erythema multiforme minor

Erythema multiforme is usually a reaction of the skin and mucous membranes that occurs suddenly. It appears as a symmetrical rash and may include the mucous membrane lesions. This means that the body is sensitive to something that causes the skin and mucous membranes to react. The more common mild form is refer to as EM minor. It consists of a skin rash that involve no more than one mucosal surface. The sudden onset will progress rapidly as symmetrical lesions with circular color changes in some or all of the lesions. Rash will spread towards center or trunk of the body. Evenly distributed bumps on the skin become classic iris or target lesions. They have bright red borders and small white bumps in the center.

Skin condition

The physical examination of the skin and its appendages, as well as the mucous membranes, forms the cornerstone of an accurate diagnosis of cutaneous conditions. Most of these conditions present with cutaneous surface changes termed "lesions," which have more or less distinct characteristics. Often proper examination will lead the physician to obtain appropriate historical information and/or laboratory tests that are able to confirm the diagnosis. Upon examination, the important clinical observations are the (1) morphology, (2) configuration, and (3) distribution of the lesion(s). With regard to morphology, the initial lesion that characterizes a condition is known as the "primary lesion", and identification of such a lesions is the most important aspect of the cutaneous examination. Over time, these primary lesions may continue to develop or be modified by regression or trauma, producing "secondary lesions". However, with that being stated, the lack of standardization of basic

[Mucous membrane involvement in the course of autoimmune blistering skin diseases and drug eruptions. Differential diagnosis].

In the following paper the most common drug eruptions and auto-immune, blistering skin diseases in which mucous lesions precede skin lesions development are discussed. Non-characteristic clinical pictures of mucous lesions result in diagnostic difficulties of these diseases, and prognosis is dependent on prompt and precise diagnosis. The aim of the work was to describe clinical features of mucous membranes lesions and point to differential diagnosis.

[Cutaneous loxoscelism with edematous predominance].

Loxoscelism is the clinical condition produced by the venom of spiders belonging to the genus Loxosceles. Human cases of loxoscelism have been observed in diverse countries of different continents in temperate and tropical regions. In Chile loxoscelism is caused by Loxosceles laeta, spider with domestic habits. Loxoscelism can be observed into two well definited clinical variants: cutaneous loxoscelism (CL) and systemic or viscerocutaneous loxoscelism (VCL) which occur in around 83.3 and 16.7% cases respectively. Within the universe of CL patients a clinical modality in which necrotic lesion is not present or is insignificant, but presenting a remarkable edema, particularly when the bite is on the face, which has received the name of CL with an edematous predominance (CLEP). In this paper the individual description and the assambled analysis of 10 cases, four males and six females, age ranging from 6 to 68 years, of CLEP are presented. Nine cases occurred in warm periods spring through fall and one in winter. In six cases the accident causing spider was seen and two of these were identified as L. laeta adult females. In all cases the patients went or were transported to emergency medical services 4-24 h after the bite. The predominant initial symptom was a burning stinging sensation at the site of the bite, followed by intensive pain which expanded the neighbour areas concomitantly with the emerging and progressive edema. In four of the nine patients in who the bite was on the face, the edema involved all of it, closed both eyelids and expanded to the neck and upper part of the thorax. In three cases the enormous edema was the only significant clinical manifestation, whereas in the remaining seven conjunctly with the edema, a small violaceous plaque or a blister of serous content gave place to a little livedoid plaque (diameter 0.3-0.8 cm) which evolved to desquamation without leaving any scarring. The edema was characterized by its brilliant rose color, painful and hard which is not accompanied by regional adenopathy. Treatment of the 10 patients depended on the moment in they were seen by us. It consisted on parenteral administration, according to age and weight, of 5-10 mg of chloroprofenpyridamine maleate every 8 hours for be continued every 12-24 hours until the patient was discharged. Parenteral route was preferred in order that it was going to be adequately absorbed. With the beginning of the antihistaminic treatment a clear diminution of pain and edema was obtained, being possible its total disappearance within 4-10 days. CLEP occurs in about 4% of loxoscelism cases, has a benign prognosis and an early response to adequate medical treatment. Without discarding the sensibility factor of the affected individual, there exist the impression that the edema may abort the necrotic process when it dilutes the enzymatic process produced by L.laeta venom. In Chile, the differential diagnosis must be planted with the following clinical entities: bites of hematophagous insects on the face, bee stings, Chagas' disease with facial port of entry and angioneurotic edema.

Erythema Multiforme -- History and Physical

Mucosal lesions are common, mostly in the mouth, but also in the genital and ocular mucous membranes. They are initially bullous, then quickly turn into painful erosions. Thick hemorrhagic crusts may cover the labial lesions, and a fibrin-whitish coating may line the mucosal erosions of the cheeks, palate, and genitalia. These mucosal lesions occur most often at the same time as the skin lesions but can be shifted a few days before or after the eruption of targets. While skin lesions are nonpainful, mucosal lesions are frequently painful. Pulmonary signs may also be present, such as a cough and dyspnea. They testify to a respiratory attack most often related to the inducing infection of the EM (mainly due to Mycoplasma pneumoniae). When extensive skin involvement occurs, some patients may show signs of dehydration. Others with mucosal involvement may lose weight because of difficulty eating.

Two contrasting post-zoster dermatomal phenomena.

A 29-year-old, normotensive, nondiabetic man presented with a 9-day history of a scaly, pruritic eruption involving the right chest, axilla, and arm. He had a history of herpes zoster involving the same areas about 4 weeks ago. The present eruption started after the herpetic lesions had healed. Examination revealed scaly, erythematous plaques and papules involving the right side of the chest, axilla, and arm in a dermatomal pattern (figure 1). Removal of the scales revealed underlying bleeding points (positive Auspitz sign). The rest of the body, including scalp, palms, soles, and nails, were normal. There was no history suggestive of psoriasis in any family member. Systemic examination and routine investigations were noncontributory. A clinical diagnosis of psoriasis was made and confirmed by histopathologic examination of a skin biopsy sample. The patient was prescribed a topical clobetasol cream and oral levocetirizine. The eruption resolved completely after 3 weeks. A 43-year-old normotensive, nondiabetic woman presented with a 2-day history of fever, arthalgias, and generalized erythematous dermatitis. Five days ago, the patient had a toothache for which she was prescribed injectable ampicillin. After receiving ampicillin for 3 days, she developed fever, myalgias, and arthalgias, which was followed several hours later by an erythematous eruption. The dermatitis started on the trunk and, over a period of several hours, progressed to involve the face and limbs. The eruption was slightly pruritic. History revealed herpes zoster 7 months ago involving left thoracic dermatomes, for which the patient was treated with valacyclovir (1 g thrice a day x 7 days) and analgesics. There was no history of post-zoster neuralgia. On examination, the patient was febrile (oral temperature 102 degrees F), her heart rate was 118 beats per minute, and her blood pressure was 110/70 mm Hg. Cutaneous examination revealed an erythematous, maculopapular dermatitis involving the face and limbs in a bilaterally symmetrical pattern; the palms and soles were also bilaterally involved. The whole of the trunk was involved with erythematous and, in places, violaceous, maculopapular eruption except for a small area on the left side corresponding to T8 and T9 thoracic dermatomes (Figure 2). Complete blood cell counts revealed eosinophilia (9%) and liver function tests, kidney function tests, random blood sugar, routine urine examination, and blood and urine cultures were noncontributory. Histopathologic examination of lesional skin biopsy revealed an intense mononuclear cell infiltration with many eosinophils and an interface dermatitis with hydropic degeneration of basal keratinocytes, while in the spared area, only slight lymphocytic infiltration was present in a perivascular distribution. Based on the history and examination, a diagnosis of ampicillin-induced drug dermatitis was made. The ampicillin was stopped and the patient was put on a short course of oral prednisolone, antipyretics, and topical calamine. The patient was afebrile in 2 days and the eruption resolved completely in 8 days.

InternalMed_Harrison

Staphylococcal scalded-skin syndrome (SSSS) and bullous impetigo are two blistering disorders associated with staphylococcal (phage group II) infection. In SSSS, the initial findings are redness and tenderness of the central face, neck, trunk, and intertriginous zones. This is followed by short-lived flaccid bullae and a slough or exfoliation of the superficial epidermis. Crusted areas then develop, characteristically around the mouth in a radial pattern. SSSS is distinguished from TEN by the following features: younger age group (primarily infants), more superficial site of blister formation, no oral lesions, shorter course, lower morbidity and mortality rates, and an association with staphylococcal exfoliative toxin (“exfoliatin”), not drugs. A rapid diagnosis of SSSS versus TEN can be made by a frozen section of the blister roof or exfoliative cytology of the blister contents. In SSSS, the site of staphylococcal infection is usually extracutaneous (conjunctivitis, rhinorrhea,

Urticarial allergic eruption

Urticarial allergic eruption is a cutaneous condition characterized by annular or gyrate urticarial plaques that persist for greater than 24 hours. See also Urticaria List of cutaneous conditions References External links Urticaria and angioedema

Erythema Multiforme -- Prognosis

The prognosis is mainly related to the body surface area detached. The healing is obtained spontaneously in 2 to 3 weeks for the EMm and 4 to 6 weeks for the EMM. The mucosal lesions always take longer to heal. The healing of the mucocutaneous lesions is without scarring but with frequent dyschromia. Recurrences are seen in less than 5% of cases, mainly in forms due to herpes infection.

Clindamycin-induced Maculopapular Exanthema with Preferential Involvement of Striae Distensae: A Koebner phenomenon?

Clindamycin is a lincomycin-derived antibiotic useful for the treatment of anaerobic and Gram-positive aerobic bacterial infections. Cutaneous adverse reactions are usually maculopapular exanthemas, although hypersensitivity syndrome, acute generalized exanthematous pustulosis, and Stevens-Johnson syndrome have also been reported (1). We report the case of a patient with a maculopapular rash triggered by clindamycin who developed cutaneous lesions on striae distensae (SD). A 47-year-old woman was referred to our clinic for pruritic cutaneous lesions which had started 6 days earlier. Her past clinical history included hypertension, hypothyroidism, hyperuricemia, cholecystectomy, caesarean section, and endometriosis-related abdominal surgery, and she was taking levothyroxine, allopurinol, imidapril, and omeprazole. The skin rash first developed on her neck and back on the 3rd day of clindamycin oral treatment (300 mg every 6 hours), which was prescribed as antibiotic prophylaxis for a tooth implant. General malaise (but not fever) was also reported. Physical examination revealed an erythematous maculopapular eruption symmetrically distributed on the neck, abdomen, and back (Figure 1, A), with isolated lesions involving the proximal upper and lower limbs (Figure 1, B). There was a striking vertical distribution of skin lesions along the SD on the lateral sides of the abdomen (Figure 1, C). No mucosal involvement was found, and laboratory studies showed no abnormalities. Clindamycin withdrawal was followed by prescription of a course of oral deflazacort, starting at 30 mg daily and tapering down during a 9-day period. On the 5th day of treatment, the rash had almost cleared with minimal desquamation (Figure 1, D). Eight weeks after clearance of the skin rash, informed consent was obtained in order to perform an allergological evaluation of clindamycin, including prick and intradermal (ID) tests on the forearm and patch tests on the upper back (2). For patch testing, powder of the commercial capsules (Dalacin®) was diluted in petrolatum (pet.) and water (aq.), resulting in a final 1% clindamycin dilution. Parenteral clindamycin preparations were used in therapeutic concentrations for prick tests (150 mg/mL) and dilutions in saline of 1/100 and 1/10 for the ID test. Other authors have reported that these concentrations do not seem to irritate the skin (3-6). Prick and ID tests were assessed after 20 min and 24 hours, respectively. Patch tests were removed after the 2nd day, and late reactions were evaluated on day 2 and day 4. Prick and ID test results after 20 min were negative. Late results of ID tests with clindamycin (1.5 and 15 mg/mL) were positive: erythematous infiltrated papules about 7×7 mm and 18×15 mm were observed at 24 hours and lasted until the 8th day. Patch tests with clindamycin 1% in pet. and 1% in aq. were also positive (+ on day 2 and day 4). Positive late skin tests suggested delayed-type non-IgE-mediated allergic clindamycin hypersensitivity. Oral challenge tests are considered to be the gold standard to establish or exclude drug hypersensitivity. Due to the positive result of late skin test to clindamycin, oral challenge was not performed in our patient (3,5). The Koebner isomorphic phenomenon has been described in cutaneous reactions induced by drugs, such as antibiotics and chemotherapy. Chronic pressure on the skin is probably involved in the onset of skin lesions in hand-foot eruptions induced by tyrosine kinase inhibitors (sorafenib and sutinib). Solar exposure and cutaneous trauma also seem to play a role in the location of papulopustular eruptions caused by endothelial growth factor receptor inhibitors (erlotinib) (7). More frequent involvement in traumatized skin and surgical scars has been reported in the context of linear IgA bullous dermatosis and leukocytoclastic vasculitis triggered by vancomycin and cefuroxime (8). SD are produced by non-penetrating physical trauma, similar to friction or pressure. Different dermatoses can develop along SD skin lesions (like plaque psoriasis, pustular psoriasis, lichen planus, vitiligo, discoid lupus erythematosus, lupus vasculitis, urticarial vasculitis, or chronic graft-versus-host disease) (9). Bevacizumab, etretinate, and corticosteroid-induced ulcers, hyperpigmentation caused by bleomycin, and urticariform lesions triggered by diclofenac are examples of different type of drug-induced abnormalities involving SD (10). In summary, we identified clindamycin as the cause of the cutaneous reactions that occurred in our patient on the basis of the results of the skin tests and clinical history. Our findings confirmed a delayed-type hypersensitivity reaction, possibly involving a T-cell-mediated immunologic mechanism. Intradermal and patch tests were found to be useful in order to confirm the diagnosis (4,5). We did not find reports in the literature of drug-induced cutaneous eruptions along the SD as a manifestation of a Koebner phenomenon. Clinical underreporting of this phenomenon could explain the scarce literature on this cutaneous adverse reaction.

[Lip synechiae after erythema multiforme].

Mucosal erosions in bullous diseases and leading to mucosal sequelae are widely described in toxic epidermal necrolysis (TEN). These complications cause disfigurement and functional impairment. They are more rarely reported in erythema multiforme (EM). We report a case of lip adhesion following EM induced by Mycoplasma pneumoniae. A 12-year-old boy was hospitalized in a paediatric intensive care unit. He had a prominent target skin rash on the palms and soles. Mucosal injury was associated with conjunctivitis, balanitis without dysuria and hyperalgesic stomatitis. M. pneumoniae serology was positive with immunoglobulin M. We made a diagnosis of EM secondary to M. pneumoniae infection. Two months later, the skin lesions had completely disappeared but the patient's mouth opening was limited to 25 mm and he presented bilateral adhesions between the upper and lower lips of 5mm on the right and 8mm on the left resulting in aesthetic and functional damage. Mucosal damage and its sequelae have been widely described in TEN. Ophthalmic sequelae are more frequent. A case of labial synechiae secondary to TEN has been reported. In EM, mucosal lesions occur in 100% of cases with a further mucosal problem being present in 50% of patients. Mucosal damage has been reported during EM flares but there are no studies of side-effects after the acute episode. Oral mucosal adhesions can cause cosmetic sequelae, but above all they hinder functional prognosis. These complications must be prevented by making gutters of vestibular deepening and lip movements with maximum mouth opening several times a day, starting as soon as possible. Appropriate pain management should be undertaken to ensure patient comfort and avoid the need for analgesics and restriction of movement. Mucosal sequelae exist in EM. Whatever their cause, complications involving the mucosa must be prevented through early, tailored and multidisciplinary treatment. Adequate pain management must not be overlooked.

Annular Lesions: Diagnosis and Treatment.

Annular lesions can present in a variety of diseases. Knowledge of the physical appearance and history of presentation of these skin findings can help in the diagnosis. A pruritic, annular, erythematous patch that grows centrifugally should prompt evaluation for tinea corporis. Tinea corporis may be diagnosed through potassium hydroxide examination of scrapings. Recognizing erythema migrans is important in making the diagnosis of Lyme disease so that antibiotics can be initiated promptly. Plaque psoriasis generally presents with sharply demarcated, erythematous silver plaques. Erythema multiforme, which is due to a hypersensitivity reaction, presents with annular, raised lesions with central clearing. Lichen planus characteristically appears as planar, purple, polygonal, pruritic papules and plaques. Nummular eczema presents as a rash composed of coin-shaped papulovesicular erythematous lesions. Treatment is aimed at reducing skin dryness. Pityriasis rosea presents with multiple erythematous lesions with raised, scaly borders, and is generally self-limited. Urticaria results from the release of histamines and appears as well-circumscribed, erythematous lesions with raised borders and blanched centers. Annular lesions occur less commonly in persons with fixed drug eruptions, leprosy, immunoglobulin A vasculitis, secondary syphilis, sarcoidosis, subacute cutaneous lupus erythematosus, and granuloma annulare.

Life-threatening disorders of mucous membranes.

Oral mucosa is one of the first barriers to the outside world which encounters various antigens, microorganisms and physical agents. Numerous oral pathologies challenge the dermatologists. Some may be the first sign of an underlying immunosuppression, while others are the inevitable serious outcomes of long-lasting mucosal disease. The differential diagnosis is crucial in terms of prompt and effective treatment.

Tumid lupus erythematosus

Tumid lupus erythematosus is a rare, but distinctive entity in which patients present with edematous erythematous plaques, usually on the trunk. Lupus erythematosus tumidus (LET) was reported by Henri Gougerot and Burnier R. in 1930. It is a photosensitive skin disorder, a different subtype of cutaneous lupus erythematosus (CLE) from discoid lupus erythematosus (DLE) or subacute CLE (SCLE). LET is usually found on sun-exposed areas of the body. Skin lesions are edematous, urticarialike annular papules and plaques. Topical corticosteroids are not effective as treatment for LET, but many will respond to chloroquine. LET resolves with normal skin, no residual scarring, no hyperpigmentation or hypopigmentation. Cigarette smokers who have LET may not respond very well to chloroquine. It has been suggested that it is equivalent to Jessner lymphocytic infiltrate of the skin. See also Lupus erythematosus List of cutaneous conditions References Cutaneous lupus erythematosus

Oral mucosa

Mucous Membrane Pemphigoid: Autoimmune disease which affects only mucous membranes with clinical presentation of hard and rigid blisters which then rupture eventually into deep ulcers. Cutaneous Lupus Erythematosus: These present as oral discoid lesions which may be present on the inner cheek and behind the lips. White papules may also be present.

Generalized linear porokeratosis.

A 23-year-old woman was seen for widespread skin lesions present since the age of 2.5 years. Twenty years ago, she developed a brown macular lesion on her right buttock. The lesion became hyperkeratotic and subsequently spread through the posterior aspect of her right leg. It later spread to the right side of the trunk and to the right arm. When she was 9 years old, she developed similar lesions on her left arm and leg. After she was 13 years old, no new skin lesions appeared. There was no family history of similar lesions. On examination, there were numerous linear and whorled, reddish-brown, hyperkeratotic plaques, with central atrophy and raised borders, following Blaschko's lines on all of the extremities. These lesions on the extremities extended to the dorsum of the hands and feet (Fig. 1). She had hyperkeratotic lesions on the pressure points of both of the soles, but no palm involvement. The number of lesions on the right side was greater than that on the left. Reddish-brown annular plaques with central atrophy and raised borders, appearing in zosteriform configuration, and numerous individual 2-3-mm erythematous lichenoid papules were observed on the right side of the thorax and the right inguinal region (Fig. 2). No face, scalp, or mucous membrane involvement was seen. The nails of the second and fifth fingers of the right hand and the nail of the third finger of the left hand showed nail dystrophy with longitudinal ridges and pterygium. All the nails of the right foot and the nails of the first and fifth toes of the left foot showed dystrophic changes with subungual keratosis. The patient was otherwise in good health. Two biopsy specimens taken from a hyperkeratotic plaque and a lichenoid papule showed an epidermal invagination with angulated parakeratotic tier, denoting cornoid lamella. The epidermis just underneath the cornoid lamella displayed vacuolization and the granular layer was absent. The adjacent epidermis was atrophic, and hydropic degeneration within the basal cell layer was seen. In the dermis, a nonspecific, mild, chronic, inflammatory cell infiltrate, telangiectatic vessels, and pigment-laden macrophages were present. These findings were consistent with linear porokeratosis (Fig. 3). Microscopic examinations and mycologic cultures of the nails were negative. We decided to treat our case systemically with retinoids, but the patient refused this therapy. So, topical tretinoin 0.05% was started once a day. A marked improvement was observed in hyperkeratosis through the first 4 weeks of treatment and plateaued at 8 weeks. After 10 weeks, the lesions had almost disappeared. We planned to continue the applications every other day. One year later, she remains stable with application of topical tretinoin 0.05% twice a week and is satisfied with the final appearance. She is under regular follow-up.

[Pepmhigus of the mucous membrane of the mouth].

Pemphigus is a rare autoimmune disease of the skin and mucous membranes. It is characterized by autoantibodies directed against the desmosomal adhesion proteins of epithelial cells (desmoglein type I and III) resulting in acantholysis of the epithelium. Painful blisters or erosions are typical clinical findings. Pemphigus is a severe disease that may be fatal. Early diagnosis of pemphigus is important in order to be able to start the treatment as soon as possible and to halt the progression of the disease and avoid serious secondary infections.

Juvenile mycosis fungoides treated with bexarotene and PUVA.

A 14-year-old Caucasian boy presented with a 4-month history of a slightly pruritic eruption that began on the hips and later extended to the trunk and upper and lower limbs. The patient did not present fever, weight loss, or asthenia. Physical examination revealed multiple, red, desquamative, oval patches with areas of healthy skin between them, which covered nearly 50% of the body surface area. The palms, soles, face, and mucosa were not affected. In addition, he presented two violet-colored infiltrated plaques on the left thigh and right buttock (Fig. 1). There were multiple, > 1 cm, freely mobile, axillary and inguinal nodes. In follow-up, the patient developed two red-colored, mobile, well-delimited cutaneous nodules of 2.5 cm in diameter in the right hemithorax and lumbar area. The lumbar nodule regressed spontaneously before treatment. The clinical diagnosis was mycosis fungoides. We obtained three skin biopsies, one from a patch lesion and the others from a nodule; the third was sent to a reference hospital to determine the rearrangement. Histologic examination was similar in the three biopsies and revealed an atypical lymphoid infiltrate in the superficial dermis with epidermotropism and a tumoral nodule of atypical, small-sized lymphocytes in the deep dermis and subcutaneous level (Fig. 2). The atypical infiltrate was CD3+, CD4+, CD8-, T-cell intracellular antigen (TIA)+/-, Epstein-Barr-encoded RNA (EBER)-, and CD56-. The biopsy of one left axillary adenopathy was compatible with mycosis fungoides (Fig. 3). Amongst the additional tests carried out was a blood analysis showing 5300 leukocytes (neutrophils, 35%; lymphocytes, 40.7%; monocytes, 16.8%; eosinophils, 6.40%) without Sézary cells, normal lactate dehydrogenase (LDH), immunoglobulin E (IgE) of 497 U/mL (normal, 3-100 U/mL), and beta2-microglobulin of 3.09 mg/L (normal, 1.64 +/- 0.58 mg/L). A bone marrow study and a thoraco-abdomino-pelvic scan were normal. The rearrangement in the skin was monoclonal, whereas in peripheral blood and lymph nodes it was polyclonal. With the diagnosis of mycosis fungoides stage IVA (according to the TNM classification), treatment was initiated with psoralen plus ultraviolet light A (PUVA), three times a week, plus oral bexarotene at a dose of 300 mg/m2/day. The parents were informed that this treatment was not approved for this age group and informed consent was obtained. The clinical tolerance to bexarotene was very good, although low doses of atorvastatin (10 mg/day) and 75-100 mg of thyroxine were needed to control the expected adverse reactions to oral retinoid. After 32 sessions of PUVA and 6 months of treatment with oral bexarotene, the skin patches regressed, except for the plaque on the left buttock and the nodule on the right hemithorax (Fig. 4). There was no evidence of lymphadenopathy clinically or via sonographic evaluation. Bexarotene was discontinued after patient clearance and resolution of adenopathies. Nevertheless, 5 months after discontinuation of oral treatment, the patient developed multiple, scaling, nonconfluent macules on the trunk and arms affecting almost 30% of the body surface area, which disappeared with the application of methylprednisolone aceponate. He did not present significant lymphadenopathies.

[Pemphigus vulgaris and benign cicatricial mucous membrane pemphigoid in the upper respiratory tract and esophagus].

Pemphigus vulgaris and benign cicatricial membrane pemphigoid are both autoimmune, blistering, dermatologic diseases characterised clinically by tense bullae on skin or on mucous membranes. Both diseases are rare, but very serious, associated with a high death rate (pemphigus) or high morbidity with cicatricial mucosal lesions (pemphigoid) if untreated. These diseases are discussed and two case stories mentioned where the primary focus was in the upper aerodigestive tract, which is very seldom. The otolaryngologist can make an important contribution to the early recognition, diagnosis, and management of these diseases. The biopsy must undergo immunofluorescence examination.

An 8-month-old boy with purpuric skin lesions. Acute hemorrhagic edema of infancy.

A previously healthy 8-month-old Hispanic boy presented with a 5-day history of an erythematous, non-pruritic papular eruption on both legs. The eruption was initially diagnosed as impetigo by his primary care practitioner but progressed despite trimethoprim / sulfamethoxazole therapy, with extension to the face, trunk, and all extremities. When the patient subsequently developed a fever of 100.8° F, emesis, diarrhea, and upper respiratory symptoms, he was referred to the pediatric dermatology clinic for evaluation. Further questioning revealed a 3-day febrile illness 6 weeks prior to presentation that was treated with ceftriaxone. Review of systems failed to identify any hematuria, blood in stool, or abdominal pain, but the parents did report swelling of the extremities and face, as well as decreased oral intake. On examination, the infant was in no apparent distress, afebrile, and had mild rhinorrhea. His mucous membranes were unaffected, and no lymphadenopathy or hepatosplenomegaly was noted. Cutaneous exam revealed numerous edematous erythematous to violaceous plaques on the cheeks, arms, buttocks, and legs with minimal involvement of the trunk. Several lesions on the arms had a distinct cockade (rosette or iris-like) pattern. There were no vesicles, bullae, or necrosis. Edema of the bilateral lower extremities was noted. Laboratory work up revealed a normal complete blood count (CBC), comprehensive metabolic panel, creatinine, and urinalysis. Platelets were borderline elevated at 439 TH/μL (140-440 TH/μL), and erythrocyte sedimentation rate and C-reactive protein (CRP) were minimally elevated at 22 mm (0-15 mm) and 3.1 mg/dL (0.0-0.99 mg/dL), respectively.

[Changes of laryngeal mucosa in the course of pemphigus vulgaris].

Blister diseases are chronic autoimmune reactions connected with formation of intraepithelial blisters. Pemphigus vulgaris (PV) change is appear most often, almost 80% of all cases. Erosions on mucosa appear as first symptoms at 50-70% patients. Blisters occurring on the skin are typical for this illness and usually come into with weeks or months with delay in relation to the changes on mucous membranes. In this work we have described character and location of changes on mucous membranes at 5 patients with PV, diagnosed based on clinical symptoms and confirmed in immunofluorescent investigations.

Most common clinical presentations of cutaneous mastocytosis.

The term mastocytosis is referred to as an array of uncommon, usually sporadic, heterogeneous clinical illnesses that result from the hyperplasia of tissue mast cells. It comprises many different clinical manifestations varying from indolent cutaneous forms to systemic and malignant conditions. The characteristic presentation of mastocytosis consists of cutaneous manifestations: either a solitary mastocytoma, urticaria pigmentosa, or less commonly, diffuse cutaneous mastocytosis. Urticaria pigmentosa is the most common manifestation of cutaneous mastocytosis that manifests as a generalized eruption of round or oval erythematous macules, papules and plaques with variable amounts of brown pigment, usually on the trunk, but may also occur in all regions of the body including face and mucous membranes. Pruritus, dermographism and Darier's sign are additional features of these eruptions. Mastocytosis may also be manifested as mastocytoma, a rare, benign, pediatric tumor that results from hyperplasia of mast cells in papillary dermis in the first few weeks of life. The clinical course of mastocytosis is variable. The prognosis for the majority of pediatric patients with urticaria pigmentosa is extremely good, and over half of cases clear completely by adolescence, while those with aggressive systemic mastocytosis or mast cell leukemia show a progressive course, usually with a fatal outcome.

Mycoplasma pneumoniae–Induced Rash and Mucositis (MIRM) -- History and Physical

In contrast, EM presents initially as a cutaneous acral rash with macules that evolve into papules, plaques, and subsequently, typical target lesions and/or atypical target lesions (those that are raised). These target lesions spread centripetally to the trunk and face. EM minor has little or no mucous membrane involvement, and EM major has a rash to one or more mucous membranes. SJS/TEN manifests as a rash of macules, purpura, diffuse erythema, atypical target lesions (those that are flat), flaccid blisters that are extensive (not sparse) in number and initially more centrally located and then coalesce and spread to the face and limbs, with extensive mucous membrane involvement to two or more mucosal sites. The amount of skin detachment differentiates the extent of SJS/TEN. SJS has less than 10% skin detachment. Ten to 30% skin detachment is overlap SJS/TEN.  Greater than 30% skin detachment is TEN.

Bullous Pemphigoid Masquerading as Erythema Annulare Centrifugum.

Dear Editor, Bullous pemphigoid (BP), a relatively common autoimmune blistering disease in the elderly, is characterized by large, tense bullae on urticarial, erythematous, or normal skin. However, atypical BP with polymorphic clinical presentations is rarely encountered, leading to misdiagnosis and delayed treatments (1). BP with lesions resembling erythema gyratum repens or figurate erythema has been regarded as a paraneoplastic phenomenon (1). Herein we report a case with erythema annulare centrifugum-like presentation of BP without evidence of underlying malignancy. A 64-year-old woman first presented with multiple large, tense bullae on the trunk and four extremities. She was diagnosed with BP according to the typical clinical, histopathological, and direct immunofluorescence findings. There were no annular lesions at that time. After a treatment course of systemic corticosteroids and azathioprine, the cutaneous symptoms were controlled. One year after discontinuing her medications, a pruritic bullous eruption reappeared with several annular erythematous plaques (Figure 1, a). The patient reported no mucosal involvement and took no new medications before the onset of skin lesions. On physical examination, multiple circular and arcuate erythematous lesions with slightly raised borders were seen on the trunk and both legs. Some erosions and tiny vesicles were noted on the erythematous edges. There were no other systemic symptoms or abnormalities. Laboratory studies, including complete blood count, liver and renal function tests, electrolytes, antinuclear antibody, complement levels, anti-Ro and anti-La antibodies, urine routine, stool routine, and chest X-ray, were normal. The biopsy specimen obtained from the rim of the annular lesions revealed slight vacuolar change at the dermoepidermal junction and perivascular and interstitial lymphocytic infiltration with numerous eosinophils in the upper dermis (Figure 1, b). Direct immunofluorescence showed linear deposits of immunoglobulin G (IgG) and C3 along the basement membrane (Figure 1, c). Histopathological features and immunofluorescence examinations were consistent with BP. There was no evidence of hematological or solid malignancy from further imaging and laboratory testing. The patient was started on oral prednisolone 30 mg/day and azathioprine 150 mg/day, with significant improvement over the following month. Complete regression of all skin lesions was achieved two months later, so the prednisolone dose was gradually tapered and then ceased. Under maintenance monotherapy of azathioprine 100 mg/day, there were no signs of BP recurrence or malignant disease during the one-year follow-up period. The annular erythema variant of BP is extremely rare. Therefore, in this case, erythema multiforme, subacute cutaneous lupus erythematosus, erythema annulare centrifugum, and urticarial vasculitis should be considered in the clinical differential diagnoses. Pathological features and immunofluorescence results can clearly rule out these possibilities. Until now, only 13 cases of BP presenting as annular erythema had been documented in the English literature, described as figurate erythema-like, erythema gyratum repens-like, or erythema annulare centrifugum-like manifestations (1-3). An association with internal malignancy in patients with these types of lesions had been reported (1). Nevertheless, as in most previous case reports (3), malignant diseases were not found in our patient. The precise mechanism of the annular erythema form of BP is unknown. Some authors considered it a variant of pre-bullous phase lesions, usually presenting as itchy erythematous patches or urticarial plaques (4). Based on this case, however, this assumption is less likely because the annular, erythema annulare centrifugum-like skin lesions appeared one year after the initial onset of bullous eruption, and simultaneously with the exacerbation of the bullous phase of BP. The exact pathogenesis of annular BP may be similar to that in erythema annulare centrifugum. Further investigations are warranted to clarify this issue. It should be noted that an erythema annulare centrifugum-like or figurate erythema-like manifestation in the absence of underlying malignancy can occasionally be a feature of BP. Making the correct diagnosis may be difficult if there is no concurrent bullous presentation. Clinicians should be vigilant for the development of this type of BP. The histological and direct immunofluorescence findings and the detection of circulating autoantibodies by indirect immunofluorescence or enzyme-linked immunosorbent assay remain crucial tools for establishing a definitive diagnosis.

Stevens-Johnson syndrome (SJS) and Toxic epidermal necrolysis (TEN) are in the same disease spectrum. The only difference is the severity of skin affection. If epidermal detachment is less than 10% of the total body surface area, it is SJS. While if the affected body surface area is more than 30%, this is considered TEN. Overlap between the two conditions occurs when the affected body surface area is between 10 to 29%. The main differential diagnosis is erythema multiform major (EMM). It mainly affects less than 10% of body surface area and is characterized by the symmetric acral distribution of target lesions with or without blister formation. In contrast, SJS and TEN consist mainly of skin blisters arising on erythematous macules in central distribution (face and trunk). Moreover, 2 or more mucous membranes are involved in 90% of SJS and TEN cases. Other differential diagnoses include: [46]

InternalMed_Harrison

In examining the skin it is usually advisable to assess the patient before taking an extensive history. This approach ensures that the entire cutaneous surface will be evaluated, and objective findings can be integrated with relevant historical data. Four basic features of a skin lesion must be noted and considered during a physical examination: the distribution of the eruption, the types of primary and secondary lesions, the shape of individual lesions, and the arrangement of the lesions. An ideal skin examination includes evaluation of the skin, hair, and nails as well as the mucous membranes of the mouth, eyes, nose, nasopharynx, and anogenital region. In the initial examination, it is important that the patient be disrobed as completely as possible to minimize chances of missing important individual skin lesions and permit accurate assessment of the distribution of the eruption. The patient should first be viewed from a distance of about 1.5–2 m (4–6 ft) so that the general

Skin manifestations of sarcoidosis

Sarcoidosis, an inflammatory disease, involves the skin in about 25% of patients. The most common lesions are erythema nodosum, plaques, maculopapular eruptions, subcutaneous nodules, and lupus pernio. Treatment is not required, since the lesions usually resolve spontaneously in two to four weeks. Although it may be disfiguring, cutaneous sarcoidosis rarely causes major problems. Classification Morphology Ulcerative sarcoidosis is a cutaneous condition affecting roughly 5% of people with sarcoidosis. Annular sarcoidosis is a cutaneous condition characterized by papular skin lesions arranged in annular patterns, usually with a red-brown hue. Pattern Morpheaform sarcoidosis is a very rare cutaneous condition characterized by specific cutaneous skin lesions of sarcoidosis accompanied by substantial fibrosis, simulating morphea. Erythrodermic sarcoidosis is a cutaneous condition and very rare form of sarcoidosis.


We are faced with polyuria. Initially we rule out diabetes mellitus (our patient has a normal blood glucose of 96mg/dl). The analytical data suggest diabetes insipidus (high plasma osm with low urinary osm). Now we must differentiate between central diabetes insipidus (lack of ADH) or nephrogenic diabetes insipidus (ADH does not exert its action at the renal level). This is achieved by the vasopressin test (intravenous administration of ADH and remeasurement of urinary osmolarity). Therefore, the correct answer is option 3.

We are faced with polyuria. Initially we rule out diabetes mellitus (our patient has a normal blood glucose of 96mg/dl). The analytical data suggest diabetes insipidus (high plasma osm with low urinary osm). Now we must differentiate between central diabetes insipidus (lack of ADH) or nephrogenic diabetes insipidus (ADH does not exert its action at the renal level). This is achieved by the vasopressin test (intravenous administration of ADH and remeasurement of urinary osmolarity). Therefore, [HIDDEN].

A 34-year-old woman is admitted for polyuria and polydipsia. In the first 24 hours of admission a diuresis of 8.2 liters is found and a blood test shows a glycemia of 96 mg/dL, natremia of 148 mEq/L and plasma osmolality of 309 mOsm/kg with urinary osmolality of 89 mOsmlkg. What diagnostic test should be performed next?

Hypertonic saline infusion test for serial determination of antidiuretic hormone.

Administration of desmopressin with serial monitoring of urine osmolality.

Determination of antidiuretic hormone in plasma.

Disorders of antidiuretic hormone.

Disorders of thirst and vasopressin secretion present clinically in one of three ways: as hypotonic polyuria (DI), as hypodipsic hyponatremia, and as hyponatremia. In evaluating a patient with DI, the major challenge is to differentiate between primary polydipsia and neurogenic and nephrogenic DI. This is best accomplished through a series of steps that start with simple clinical observation, and progress, as necessary, to more complicated diagnostic procedures (Fig. 1). If the diagnosis is not clear from the clinical setting and the patient's history, the first step is to measure plasma osmolality and sodium under conditions of ad libitum fluid intake. If the results are clearly above the upper limit of normal range, primary polydipsia is excluded and the work-up can proceed directly to administration of vasopressin or DDAVP and/or a measurement of plasma vasopressin levels to differentiate between neurogenic and nephrogenic DI. If basal plasma osmolality and sodium fall within normal range, the standard dehydration test should be performed. If urine osmolality does not increase above that of plasma despite evident dehydration, primary polydipsia is excluded and the effect of vasopressin or DDAVP on urine osmolality should be examined to differentiate between neurogenic and nephrogenic DI. If administration of antidiuretic hormone increases urine osmolality by more than 50 per cent, the patient has severe neurogenic DI. If the increase in urine osmolality is less than 50 per cent, the patient has nephrogenic DI. In patients who do not concentrate urine above that of plasma in response to dehydration, the best approach is to measure plasma vasopressin, osmolality, and sodium after the latter have been increased above normal range by dehydration and/or infusion of hypertonic saline. When these results are plotted on a suitable nomogram (Fig. 2), neurogenic DI can be clearly diagnosed from the relative deficiency of vasopressin. In patients with normal vasopressin levels, primary polydipsia can be differentiated from nephrogenic DI by examining the relationship of urine osmolality to plasma vasopressin (Fig. 3), obtained during dehydration and/or graded vasopressin infusion. In evaluating a patient with sustained hypernatremia, it is only necessary to assess thirst, which can be done by a simple bedside observation. In a patient without obvious neurologic or cognitive impairment, absence of thirst in the face of plasma osmolality above 305 mosm/kg (plasma sodium above 150 mEq/L) is diagnostic for hypodipsic hypernatremia. In a patient who presents with hyponatremia, the main objective is to differentiate between hyper-, hypo-, and euvolemic (SIADH) types

[Partial defect in the secretion of antidiuretic hormone and disproportionate polydipsia (author's transl)].

A 20-year-old patient was evaluated because of polydipsia and polyuria; by means of the dehydration test a partial defect in the secretion of antidiuretic hormone (ADH) was demonstrated, since the urinary osmolality after the administration of exogenous vasopressin was superior by 25 percent to the maximum spontaneous urinary osmolality reached after a period of fluid restriction. Nevertheless, there was also a component of psychogenic polydipsia because the daily basal fluid intake was superior to 15 liters, and in view of the fact that the urinary osmolality could reach 600 mOsm/kg, the endocrine defect cannot totally be responsible for the enormous volume of fluid intake. This is the first case in the world literature in which the association between potomania and deficiency in the secretion of ADH is reported. Since ADH is one of the factors which regulate the behaviour of various animal species it is possible that its deficiency may be directly responsible for the psychic disorder which led to the potomania. It is also possible that an anatomical hypothalamic lesion, too small to be demonstrated, might have a simultaneous effect on the centers regulating thirst and the neurons producing vasopressin.

Differential diagnosis of polyuric/polydipsic syndromes with the aid of urinary vasopressin measurement in adults.

A water deprivation test or a hypertonic saline infusion test with the measurement of plasma osmolality and plasma vasopressin are the gold standard tests in the differential diagnosis of polyuric syndromes. Because commercially available vasopressin kits are too insensitive for this approach, and the concentration of vasopressin in urine is much higher than in plasma, urinary vasopressin measurements may be an alternative to the more difficult plasma vasopressin measurement. The diagnostic value of the measurement of urinary vasopressin with a rather insensitive commercially available vasopressin kit was compared with plasma vasopressin measurement by a highly sensitive radioimmunoassay (RIA). Thirteen normal subjects and 27 patients with polyuria/polydipsia were examined by an 8-h fluid deprivation test. In all blood samples (0800 h, 1200 h, 1400 h and 1600 h) and in all urine collections (2-hourly fractions), osmolality as well as vasopressin were measured. Using plasma vasopressin measurement with a highly sensitive RIA as gold standard test, nine patients were classified as having primary polydipsia, whereas 18 had partial or complete cranial diabetes insipidus. Whereas the substitution of plasma vasopressin measurement by urinary vasopressin measurement alone did not provide 100% separation between both groups, the product of urinary vasopressin and urinary osmolality related to plasma osmolality completely separated the patients with primary polydipsia from those with diabetes insipidus. Urinary measurement of vasopressin and osmolality alone, which was recommended as a noninvasive diagnostic procedure in children, was too insensitive for exact differential diagnosis in our adult patients. The simultaneous measurement of plasma vasopressin and plasma osmolality in a dehydration test is the most powerful diagnostic tool in the differential diagnosis of polyuria/polydipsia. However, if highly sensitive assays for plasma vasopressin measurements are not available, the measurement of urinary vasopressin with commercially available, less sensitive RIAs may be a diagnostic alternative, which showed nearly the same sensitivity as plasma vasopressin measurement in our study population.

X-Linked Recessive form of Nephrogenic Diabetes Insipidus in a 7-Year-Old Boy.

Nephrogenic diabetes insipidus (NDI) is caused by the inability of renal collecting duct cells to respond to arginine vasopressin (AVP)/antidiuretic hormone (ADH). We present the case of a 7-year-old boy with a history of excretion of large amounts of dilute urine and polydipsia since infancy. The boy had several vomiting episodes with mild dehydration during the first 3 years of life. There was no evidence of headaches, dizziness or visual problems. He drinks between 2 and 3 L/day and has 24-hour diuresis of 2 liters, now. He has prepubertal appearance with appropriate weight [+0.85 standard deviation score (SDS)] and height (+0.15 SDS) for his age. His intelligence was also normal. The water deprivation test showed low urine osmolality after 8 hours of dehydration. After desmopressin administration, urine osmolality remained low. Serum osmolality was in the normal range for sex and age before and after desmopressin administration. This indicated a nephrogenic form of diabetes insipidus. Molecular analyses revealed a P286L [p.Pro(CCC)286Leu(CTC)] mutation in the AVPR2 gene, that was inherited from his mother. This patient is the first case with genetically confirmed X-linked inherited form of NDI in the Republic of Macedonia. Molecular analysis confirmed the clinical diagnosis and enabled genetic advice for this family.

Diagnosis of the syndrome of inappropriate secretion of antidiuretic hormone.

Hyponatremia is a frequent condition in elderly patients. In diagnostic workup, a 24-hour urine sample is used to measure urinary osmolality and urinary sodium concentration necessary to confirm the diagnosis of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). This study was undertaken to test the hypothesis that a spot urine sample would be sufficient for urinalysis. In nine patients with SIADH, morning spot and 24-hour urine samples were examined for osmolality and sodium concentration. Levels of arginine vasopressin, atrial natriuretic and brain natriuretic peptides, renin, and aldosterone were measured in the supine and upright positions of patients and compared with nine healthy age-matched control patients. The patients had low plasma osmolality (median 266 mOsm/kg) and measurable levels of arginine vasopressin (median 1.8 pg/mL). Values of osmolality in the spot urine (median 298 mOsm/kg) and in the 24-hour urine (median 215 mOsm/kg) did not differ significantly; neither did sodium concentration (medians 80 mmol/L in the spot urine versus 45 mmol/L in the 24-hour urine). Patients had significantly elevated plasma levels of brain natriuretic peptide (P = 0.007), elevated mean arterial blood pressure (P = 0.03), and lower plasma levels of creatinine (P = 0.002) compared to the controls. A spot urine sample seems to be sufficient to confirm the diagnosis of SIADH.

Arginine Vasopressin Disorder (Diabetes Insipidus) -- Evaluation -- 2. Diagnosis of the type of polyuria-polydipsia syndrome

Urine osmolality reaches the normal reference range. Urine osmolality is stable on two to three consecutive hourly measurements, even with rising plasma osmolality. Plasma osmolality is higher than 295 to 300 mOsm/kg Plasma Na greater than 145 mEq If AVP-R is suspected in newborns and young infants, the diagnostic test of choice is DDAVP (1 mcg subcutaneously or intravenously over 20 minutes, maximum dose of 0.4 mcg/kg). In children, the water deprivation test should be closely monitored. If one of the following endpoints is reached, discontinue the trial: Urine osmolality reaches the normal reference range. Plasma osmolality greater than 295 mOsm/kg to 300 mOsm/kg Plasma sodium greater than 145 meq/L Loss of 5% of body weight or signs of volume depletion

Fluid deprivation test

A fluid or water deprivation test is a medical test which can be used to determine whether the patient has diabetes insipidus as opposed to other causes of polydipsia (a condition of excessive thirst that causes an excessive intake of water). The patient is required, for a prolonged period, to forgo intake of water completely, to determine the cause of the thirst. This test measures changes in body weight, urine output, and urine composition when fluids are withheld. Sometimes measuring blood levels of ADH (a synonym for vasopressin) during this test is also necessary. If there is no change in the water loss despite fluid deprivation, desmopressin may be administered to distinguish between the two types of diabetes insipidus which are central & nephrogenic diabetes insipidus. The time of deprivation may vary from 4 to 18 hours. The serum osmolality and urine osmolality are both measured in the test. Interpretation of WDT The conditions can be distinguished in the following way:

Diagnostic value of the water deprivation test in the polyuria-polydipsia syndrome.

Diabetes insipidus (DI) and primary polydipsia (PP) are characterised by polyuria and polydipsia. It is crucial to differentiate between these two disorders since the treatment is different. The aim of this study was to evaluate the diagnostic value of the short and an extended variant of the water deprivation test (WDT) and of measuring urinary vasopressin (AVP) in patients with polyuria and polydipsia. A retrospective, single-centre study based on WDTs performed between 2004 and 2014 including 104 consecutive patients with the polyuria-polydipsia syndrome. During a strict water deprivation, weight, urinary osmolality, urinary vasopressin and specific gravity were collected until one of the following was reached: i) >3% weight reduction, ii) Urinary specific gravity >1.020 or, urinary osmolality >800 mOsm/L, iii) Intolerable adverse symptoms such as excessive thirst. Out of 104 patients (67 women, 37 men), 21 (20%) were diagnosed with DI and 83 (80%) with PP. The median (interquartile range; range) test duration was 14 hours (10-16; 3-36) in patients with DI and 18 hours (14-24; 7-48) in patients with PP (P=0.011). Of those diagnosed with PP, 22 (26%) did not reach urinary specific gravity >1.020 nor urine osmolality >800 mOsm/L. Urine AVP did not overlap between patients with PP and patients with central DI. The short WDT is of limited value in the diagnostic work-up of polydipsia and polyuria and a partial DI may have been missed in every fourth patient diagnosed with PP. Urinary AVP has excellent potential in discriminating PP from central DI.

A case of syndrome of inappropriate secretion of antidiuretic hormone (SIADH) with low plasma concentrations of antidiuretic hormone.

A 66-year-old Japanese man presented with persistent hyponatremia without polydipsia and polyuria. Laboratory examination showed serum sodium of 117 mEq/l, plasma osmolality 239 mosm/kg, urine sodium 108 mEq/l, urine osmolality 577 mosm/kg, and normal levels (less than 2.0 pg/ml) of serum antidiuretic hormone (ADH). ADH release was regulated normally with changes in plasma osmolality. No obvious cause for the syndrome of inappropriate secretion of ADH (SIADH) could be detected. However, 20 months later, the patient had bouts of hematuria and was found to have cancer of the urinary bladder. Increased renal sensitivity to ADH was suspected as the underlying mechanism of SIADH.

Severe hyperosmolarity and hypernatremia in an adipsic young woman.

Combined deficits in arginine vasopressin secretion (AVP) and thirst sensation can result in life threatening hyperosmolality and hypernatremia. Complications include seizures, profound volume contraction and renal failure. Fortunately, this is an uncommon clinical condition, with approximately 70 cases reported in the literature over the past 47 years [1]. Defects in AVP secretion and/or synthesis produce central diabetes insipidus (DI), polyuria with polydipsia, hypernatremia and hyperosmolality. Most awake and alert patients with an intact thirst stimulus will "drink" themselves back to a normal serum sodium and osmolality. However, if there is concomitant destruction of the osmoreceptors that regulate thirst, osmolal and volume homeostasis cannot be maintained. The relationships between urine osmolarity and serum osmolarity and plasma vasopressin levels are vital for distinguishing a reset osmostat from central DI. After obtaining approval from our institutional review board, we retrospectively reviewed the medical record of a 37-year-old patient who presented to our institution with a serum sodium of 176 mEq/l. Admission laboratory examination revealed: hemoglobin 12.8 g/dl; white blood cell count 4.7 × 103/µl, with a normal differential; random serum glucose 91 mg/dl ; sodium 176 mEq/l; plasma osmolality 366 mOsm/kg; BUN 33 mg/dl; serum creatinine 1 mg/dl; calcium 9.5 mg/dl; urine specific gravity 1.032; and urine osmolality 1,172 mOsm/kg. An MRI with contrast of the sella/ pituitary revealed an enhancing mass centered within the suprasellar cistern and anterior third ventricle, measuring 3.0 × 3.9 × 3.4 cm. The lesion appeared to involve the hypothalamus and displaced the optic chiasm inferiorly. Evaluation of pituitary function revealed normal serum levels of thyroid stimulating hormone, AM cortisol, luteinizing hormone, follicle stimulating hormone and prolactin. Figure 1 illustrates the relationship between measured serum AVP levels and serum osmolality. Figure 2 shows the relationship between measured urine and serum osmolality. If the serum AVP levels were not available, it would appear as though the patient had a reset osmostat. The kidneys appear to appropriately generate maximally concentrated urine at a serum osmolality above 348 but are unable to below this value. When compared with the normal curve, our patient's AVP levels were lower than expected for the corresponding osmolality. This pattern is consistent with a partial central DI. She does not have a reset osmostat. In the presence of significant volume contraction and a reduced GFR, her kidneys produced more concentrated urine despite markedly decreased central vasopressin production. As the volume contraction abated and the GFR improved, polyuria recurred, despite persistent hyperosmolarity and hypernatremia.

[Trials for simplified hypertonic saline test].

Hypertonic saline test is indispensable for the evaluation of posterior pituitary function. However the test is not simple, including water loading, urine sampling and at least 45 min of hypertonic saline infusion, mostly because the test relies on urinary osmolality as an index of ADH secretion. The object of this study is try to simplify the test by directly measuring plasma ADH concentration before and after 10 min of hypertonic saline infusion. Intravenous infusion of hypertonic saline (5% NaCl, 0.24 ml/kg/min, for 10 min) was performed on normal subjects, patients with diabetes insipidus and patients with renal failure under chronic hemodialysis. Venous blood samples were obtained seriously including just before and after 10 min of the infusion. ADH was extracted from plasma using Sep-Pak C18 column and assayed by specific RIA. Minimum sensitivity of the assay was 0.25 pg/ml. The hypertonic saline infusion resulted in an increase of plasma osmolality by about 8 mOsm/kg H2O and plasma sodium concentration by 4 mEq/l. Plasma ADH increased from 0.77 +/- 0.09 to 3.42 +/- 0.73 pg/ml (m +/- SE, n = 8, p less than 0.01) in normal subjects of ad lib. water drinking and from 0.55 +/- 0.33 to 2.34 +/- 0.33 (m +/- SE, n = 4, p less than 0.05) in water loaded normal subjects (20 ml/kg of water, 60 min before hypertonic saline infusion).(ABSTRACT TRUNCATED AT 250 WORDS)

Primary Polydipsia -- Differential Diagnosis

After polyuria (>40-50 ml/kg/24hrs) is confirmed, and urine osmolality is <800 mOsm/kg, serum sodium level has to be checked. If the serum sodium level is <135 meq, it is diagnostic of PP. If the serum sodium levels are >147, it is diagnostic of diabetes insipidus. If the serum sodium is between 135 and 147, the next step would be the water deprivation test. The traditional test that has been utilized by providers for a long time is the indirect water deprivation test that indirectly measures the activity of AVP. This test is started once hypotonic polyuria is confirmed, and serum sodium is between 135 and 147. Polyuria in primary polydipsia decreases with water deprivation (typically >8hrs), and urine osmolality increases (>800 mOsm/kg typically), this is diagnostic of PP. In diabetes insipidus, polyuria does not get better with water deprivation. If the urine osmolality remains <300 mOsm/kg after water deprivation, it is diagnostic of DI.

Altered renal handling of electrolytes in a child with central diabetes insipidus (CDI).

A 12-year-old female child, with a history of polyuria and polydipsia of about three years duration, was admitted to Ethio-Swedish Paediatric Hospital, in Addis Abeba. Urine output in 24 hours averaged 5-6 litres, with a frequency of 15 times during the day and 7-8 times during the night. Random urine analysis showed an osmolality of 60 mOsm/kg, Na+ 27.1 mmol/L and K+ was 7.6 mmol/L. Basal plasma osmolality was 313 mOsm/kg with Na+ being 156 mmol/L and K+ 4.06 mmol/L. Water deprivation for nine hours failed to produce a concentrated urine, which was only 138 mOsm/kg at the end of the test, with a corresponding plasma osmolality of 336 mOsm/kg. After nine hours of water deprivation, urine Na+ increased from 27.1 to 37.3 mmol/L while K+ increased from 7.1 to 18.7 mmol/L. Lypressin, a vasopressin analogue, at a concentration of 0.3 IU/kg injected intramuscularly, resulted in a marked increase in urine osmolality to 586 mOsm/kg within two hours, associated with relief of symptoms. Urinary excretion of K+ was markedly increased during the vasopressin test while Na+ excretion was little affected. A case of central diabetes insipidus of undefined etiology is presented and the possibility of altered renal handling of electrolytes and an abnormal response to vasopressin in such cases is noted. The problem of management and the currently available treatment options are summarized.

Neurohypophysis -- Evaluation -- Diabetic Insipidus

Serum and urine sodium, serum and urine osmolality, hourly urine output, 24-hour urine volume, and specific gravity must be obtained. Central DI must be distinguished from nephrogenic DI. A water deprivation test can be used with or without desmopressin injection. In central DI, the vasopressin will correct urine osmolality while in nephrogenic DI, the correction will be suboptimal. [3] [25] [26] Criteria for the diagnosis of central DI: Polyuria in two consecutive hours of > 300 ml/hr or 4 to 5 ml/kg/hr in two consecutive hours Polyuria > 3L/24 hours or > 2ml/kg/hr in 24 hours Serum osmolality > 300 mOsm/kg Urine osmolality < 300 mOsm/kg Urine/plasma osmolality <  1 The specific gravity of less than 1.005

Transient Antidiuretic Hormone Insufficiency Caused by Severe Hyperosmolar Hyperglycemic Syndrome Based on Nephrogenic Diabetes Insipidus.

The hyperosmolar hyperglycemic state (HHS), an acute complication of diabetes mellitus with plasma hyperosmolarity, promotes the secretion of anti-diuretic hormone (ADH) and reduces the storage of ADH. Magnetic resonance T1-weighted imaging reflects ADH storage in the posterior pituitary lobe, which disappears when the storage is depleted. Whether the HHS induces ADH depletion leading to clinical manifestations has been unclear. A 55-year-old Japanese woman was admitted to our center because of mental disturbance and hypotension. She had received lithium carbonate for bipolar disorder and presented with polydipsia and polyuria from 15 years of age. On admission, she had mental disturbance (Glasgow Coma Scale, E4V1M1), hypotension (systolic blood pressure, 50 mmHg), and tachycardia (pulse rate, 123/min). Plasma glucose was 697 mg/dL osmolality was 476 mOsm/kg•H<sub2</subO, and bicarbonate was 23.7 mmol/L. The diagnoses of HHS and hypovolemic shock were made. During treatment with fluid replacement and insulin therapy, the urine volume continued to be approximately 3 to 4 L/day, and an endocrine examination revealed ADH insufficiency and nephrogenic diabetes insipidus. Desmopressin 10 μg/day and trichlormethiazide 2 mg/day were necessary and administered, and the endogenous ADH secretion improved gradually. The signal intensity of the pituitary posterior lobe, initially decreased on magnetic resonance T1 images, was also improved. This patient had ADH insufficiency associated with ADH depletion due to hyperosmolarity and nephrogenic diabetes insipidus. Clinicians should be aware of the risk of the development of critical HHS and relative ADH insufficiency in patients being treated with lithium carbonate.

Diabetes insipidus

This test measures the changes in body weight, urine output, and urine composition when fluids are withheld to induce dehydration. The body's normal response to dehydration is to conserve water by concentrating the urine. Those with DI continue to urinate large amounts of dilute urine in spite of water deprivation. In primary polydipsia, the urine osmolality should increase and stabilize at above 280 mOsm/kg with fluid restriction, while a stabilization at a lower level indicates diabetes insipidus. Stabilization in this test means, more specifically, when the increase in urine osmolality is less than 30 Osm/kg per hour for at least three hours. Sometimes measuring blood levels of ADH toward the end of this test is also necessary, but is more time consuming to perform.

To differentiate AVP-D and AVP-R and primary polydipsia, perform a water deprivation test and desmopressin (DDAVP) trial. Typically a 7-hour deprivation test is adequate to diagnose DI. Primary polydipsia may require more extended dehydration periods. The basic principle behind the water deprivation test is that in individuals with normal posterior pituitary and renal function (or those with primary polydipsia), an increase in plasma osmolality from dehydration stimulates AVP release from the posterior pituitary, which then leads to water reabsorption in the nephrons, thus resulting in concentration of urine and an increase in urine osmolality. In AVP-D or AVP-R, the urine fails to concentrate optimally with water deprivation, and there is persistent excretion of hypotonic urine. In adults, the water restriction test should be discontinued when one of the following is reached:

Syndrome of inappropriate antidiuretic hormone secretion

Diagnosis Diagnosis is based on clinical and laboratory findings of low serum osmolality and low serum sodium. Urinalysis reveals a highly concentrated urine with a high fractional excretion of sodium (high sodium urine content compared to the serum sodium). A suspected diagnosis is based on a serum sodium under 138. A confirmed diagnosis has seven elements: 1) a decreased effective serum osmolality - <275 mOsm/kg of water; 2) urinary sodium concentration high - over 40 mEq/L with adequate dietary salt intake; 3) no recent diuretic usage; 4) no signs of ECF volume depletion or excess; 5) no signs of decreased arterial blood volume - cirrhosis, nephrosis, or congestive heart failure; 6) normal adrenal and thyroid function; and 7) no evidence of hyperglycemia (diabetes mellitus), hypertriglyceridemia, or hyperproteinia (myeloma).

The relationship between antidiuretic hormone and plasma or urine osmolalities during water restriction test and hypertonic saline loading test in normal children--a change in the apparent tubular response to AVP during these two tests.

We present here the results of water restriction test (WRT) and hypertonic saline loading test (HSLT) in normal children. Maximal urine osmolality during WRT (W-Umax; 1040 +/- 154 mOsm/kg) may be age-dependent (W-Umax = 812 + 23*age, r = 0.52, p < 0.05), although maximal arginine vasopressin (AVP) levels during WRT did not show any correlation with age. The relationship between plasma osmolality (Posm) and AVP during HSLT in children (AVP = 0.31* (Posm-277)) was similar to that in normal adults. A plateau urine osmolality during HSLT (H-Umax) was 713 +/- 109 mOsm/kg. It did not increase with age. AVP levels 3 h after the infusion did not correlate with age. Minimal AVP and Posm values (about 6 pg/ml, 295 mOsm/kg, respectively) for creating H-Umax apparently existed during HSLT. The minimal AVP value (about 6 pg/ml) for H-Umax (during HSLT) was higher than the AVP levels (2.41 +/- 1.37 pg/ml) at W-Umax (during WRT). W-Umax (1040 +/- 154 mOsm/kg) was significantly higher than H-Umax (713 +/- 109 mOsm/kg). Judging from the above comparison of AVP and Uosm (W, H-Umax) at the plateau state of WRT and HSLT in normal children, a change in the apparent tubular response to AVP may be one of the important factors to maintain circulatory volume (CV).

InternalMed_Harrison

Brain MRI Urinary frequency, nocturia, enuresis 24-h urine volume and osmolarity on unrestrictedfluid intake Volume >40 mL/kg Osmolarity <300 mosm/L Basal plasma AVP >1 pg/mL <1 pg/mL Pituitary bright spot Present Absent Anatomy Pathology? GU evaluation Volume <40 mL/kg Osmolarity >300 mosm/L If MRI and/or AVP assays with the requisite sensitivity and specificity are unavailable and a fluid deprivation test is impractical or undesirable, a third way to differentiate between pituitary DI, nephrogenic DI, and primary polydipsia is a trial of desmopressin therapy. Such a trial should be conducted with very close monitoring of serum sodium as well as urine output, preferably in hospital, because desmopressin will produce hyponatremia in 8–24 h if the patient has primary polydipsia.

Plasma osmolality

Osmolality of blood increases with dehydration and decreases with overhydration. In normal people, increased osmolality in the blood will stimulate secretion of antidiuretic hormone (ADH). This will result in increased water reabsorption, more concentrated urine, and less concentrated blood plasma. A low serum osmolality will suppress the release of ADH, resulting in decreased water reabsorption and more concentrated plasma. Syndrome of inappropriate ADH secretion occurs when excessive release of antidiuretic hormone results in inappropriately elevated urine osmolality (>100 mOsmol/L) relative to the blood plasma, leading to hyponatraemia. This ADH secretion may occur in excessive amounts from the posterior pituitary gland, or from ectopic sources such as small-cell carcinoma of the lung. Elevation may be associated with stroke mortality. Calculated osmolarity (CO)

Diabetes insipidus.

Diabetes insipidus (DI) is characterized by hypotonic polyuria greater than 3 liters/24 hours in adults and persisting even during water deprivation. It is mostly due to a defect in arginin-vasopressin (AVP) synthesis (central DI); other causes are: AVP resistance (nephrogenic DI), abnormal thirst regulation (primary polydipsia) or early destruction of AVP by placental enzymes (gestational DI). A thorough medical history is warranted to investigate nocturnal persistence of polyuria (night waking being a good sign of its organic nature) to specify the onset and duration of the trouble, the medication use and the potential hereditary nature of the disorder. The next step is based on weight and blood pressure measurements and especially the quantification of beverages and diuresis over a 24-hour cycle. Assessment of signs of dehydration, bladder distention, pituitary hormone hyper- or hyposecretion, tumor chiasmatic syndrome, granulomatosis and cancer is required. The diagnosis is based on biological assessment, pituitary magnetic resonance imaging (MRI) and results of a desmopressin test. In severe forms of DI, urine osmolality remains below 250 mOsmol/kg and serum sodium greater than 145 mmol/L. In partial forms of DI (urine osmolality between 250 and 750), the water deprivation test demonstrating the incapacity to obtain a maximal urine concentration is valuable, together with vasopressin or copeptin measurement. The pituitary MRI is done to investigate the lack of spontaneous hyperintensity signal in the posterior pituitary, which marks the absence of AVP and supports the diagnosis of central DI rather than primary polydipsia (although not absolute); it can also recognize lesions of the pituitary gland or pituitary stalk. Acquired central DI of sudden onset should suggest a craniopharyngioma or germinoma if it occurs before the age of 30 years, and metastasis after the age of 50 years. Fifteen to 20% of head trauma lead to hypopituitarism, including DI in 2% of cases. Transient or permanent DI is present in 8-9% of endoscopic transphenoidal surgeries. Current advances in DI concern the etiological work-up, with in particular the identification of IgG4-related hypophysitis or many genetic abnormalities, opening the field of targeted therapies in the years to come.

ADIPSIC DIABETES INSIPIDUS AFTER SECOND RESECTION OF A HYPOTHAMIC ASTROCYTOMA.

We report a case of adipsic diabetes insipidus (ADI) post-astrocytoma resection. Clinical and laboratory data are presented. A 16-year-old female with a history of incompletely resected hypothalamic astrocytoma was admitted with a headache. Head magnetic resonance imaging showed an interval increase in a suprasellar lesion with extension to the third ventricle. Following a second stage resection, she developed an increased urine output with diluted urine resulting in a negative fluid balance; however, she was unable to sense thirst. Blood tests showed a serum sodium of 155 mEq/dL (normal, 136 to 145 mEq/dL), serum osmolality at 321 mOs/kg (normal, 285 to 295 mOs/kg) and a urine osmolality of 128 mOsm/kg (normal, 300 to 1,600 mOsm/kg). Serum creatinine and potassium were normal. Pituitary hormone profiles were found to be normal: growth hormone 0.171 ng/mL (normal, 0.123 to 8.05 ng/mL), luteinizing hormone 3.44 mIU/mL (normal, 7.59 to 89.08 mIU/mL), follicle-stimulating hormone 5.60 mIU/mL (normal, 2.55 to 16.69 mIU/mL), thyroid-stimulating hormone 2.9 mIU/mL (normal, 0.35 to 4.94 mIU/mL), free thyroxine 0.92 ng/dL (normal, 0.7 to 1.48 ng/dL), adrenocorticotropic hormone 19.56 pg/mL (normal, 7.2 to 63.3 pg/mL), and prolactin 7.25 ng/mL (normal, 5.18 to 26.53 ng/mL). The patient was treated with desmopressin acetate 120 μg tablets twice daily with a fixed fluid intake of 1.5 to 2.0 L/day with close monitoring of fluid intake, output, and body weight. The response was good with a gradual reduction of serum sodium level of around 7 to 9 mEq/L/day. ADI is a rare entity of central diabetes insipidus, where the absence of polydipsia can be challenging in diagnosing and managing the condition. Cases of ADI are likely under reported and clinicians need to be aware of this condition.

InternalMed_Harrison

Following the correction of hypernatremia and acute renal insufficiency with appropriate hydration (see below), the patient was subjected to a water deprivation test followed by administration of DDAVP. This test helps determine whether an inappropriate water diuresis is caused by CDI or NDI. The patient was water restricted beginning in the early morning, with careful monitoring of vital signs and urine output; overnight water deprivation of patients with diabetes insipidus is unsafe and clinically inappropriate, given the potential for severe hypernatremia. The plasma Na+ concentration, which is more accurate and more immediately available than plasma osmolality, was monitored hourly during water deprivation. A baseline AVP sample was drawn at the beginning of the test, with a second sample drawn once the plasma Na+ reached 148–150 meq/L. At this point, a single 2-μg dose of the V2 AVP receptor agonist DDAVP was administered. An alternative approach would have been to measure AVP

Hyperosmolar hyperglycemic state

Diagnosis Criteria According to the American Diabetes Association, diagnostic features include: Plasma glucose level >30 mmol/L (>600 mg/dL) Serum osmolality >320 mOsm/kg Profound dehydration, up to an average of 9L (and therefore substantial thirst (polydipsia)) Serum pH >7.30 Bicarbonate >15 mEq/L Small ketonuria (~+ on dipstick) and absent-to-low ketonemia (<3 mmol/L) Some alteration in consciousness BUN > 30 mg/dL (increased) Creatinine > 1.5 mg/dL (increased) Imaging Cranial imaging is not used for diagnosis of this condition. However, if MRI is performed, it may show cortical restricted diffusion with unusual characteristics of reversible T2 hypointensity in the subcortical white matter.

The administration of desmopressin differentiates between central and nephrogenic insipidus. If, after the administration of desmopressin, there is an increase of >50% in the urine osmolality, it is diagnostic of central DI. If there is an increase of <50% in the urine osmolality, it is diagnostic of nephrogenic DI. If the urine osmolality is between 300 mOsm/kg and 800 mOsm/kg after the water deprivation test, this could either be partial central DI or PP. To differentiate partial central DI from PP, desmopressin is administered. If the urine osmolality increases by > 9%, it is diagnostic of PP. If the Urine osmolality increases by <9%, it is diagnostic of partial central diabetes insipidus.

Hypertonic saline (3% saline, 1027 mOsm/L) infusion coupled with plasma copeptin measurement is an alternative test that is now being recommended by many experts in the field of DI as the preferred test to be used in place of the water deprivation test.

An assessment of posterior pituitary function in patients with Sheehan's syndrome.

Antidiuretic hormone (ADH) function was assessed in a group of 16 patients with Sheehan's syndrome and 17 controls. All patients were on adequate cortisone and thyroxine replacement therapy before testing. During the dehydration test the patients revealed an impairment of ADH function. The maximum urine osmolalities and the urine-plasma osmolality ratios were significantly lower in the patients with Sheehan's syndrome compared to controls (maximum urine osmolalities 633 +/- 38 (SEM) and 873 +/- 29 (SEM) mOsm/kg, respectively, P less than 0.001; urine-plasma osmolality ratios 2.15 +/- 0.14 (SEM) and 3.01 +/- 0.10 (SEM), respectively, P less than 0.001). Plasma osmolalities were significantly higher in the patients (296.1 +/- 1.2 (SEM) and 290 +/- 0.9 (SEM), respectively, P less than 0.001). The patients took a longer period to achieve these maximum urine osmolalities. Three of the patients with Sheehan's syndrome were diagnosed as having diabetes insipidus since their maximum urine osmolalities were below 600 mOsm/kg and following desmopressin all three had an increment in urine osmolality which exceeded 9%. In addition these three patients had a maximum urine-plasma osmolality ratio below 1.9. Thus, it appears the patients with Sheehan's syndrome have an impairment of ADH function which manifests in some as diabetes insipidus.

[Transient polyuria in pregnancy in diabetes insipidus and gestational diabetes].

Two pregnant women developed overt polyuria (up to 11 l/day) and polydipsia during their second and third trimesters of pregnancy. In one patient hydronephrosis was present. Both patients suffered from mild gestational diabetes mellitus. Plasma sodium was 145 and 162 mmol/l. Polyuria and urinary hypo-osmolality responded well to desmopressin acetate. After delivery, polyuria and polydipsia disappeared in one patient and significantly improved in the other. Infusion of hypertonic saline one and two weeks respectively after delivery led to plasma hyper-osmolality (294 mosmol/kg and 305 mosmol/kg) without detectable stimulation of arginine vasopressin (AVP). Anterior pituitary function was normal. No stimulation of AVP occurred following insulin-induced hypoglycemia. AVP plasma disappearance after i.v. pulse injection of 1 microgram AVP as well as AVP plasma concentration after continuous infusion of 10 ng AVP/min was studied two weeks after delivery in one patient. The results suggested markedly elevated degradation of AVP compared to control subjects, probably due to an increased vasopressin activity. Eight months after delivery, hypertonic saline infusion in one patient led to a plasma-osmolality of 312 mosmol/kg without stimulation of AVP. In the second patient, AVP was not detectable (less than 0.2 pg/ml) six months after delivery when plasma osmolality was 290 mosmol/kg. Our studies demonstrate that a subclinical compensated diabetes insipidus was preexistent in both patients. Exacerbation occurred due to an increased AVP-clearance and presumably due to the hemodynamic and hormonal alterations during pregnancy, including a mild gestational diabetes mellitus.

Copeptin (carboxy-terminal-Pro-vasopressin) is the C-terminal peptide of pro-vasopressin co-secreted with AVP from the posterior pituitary. [8] [53] Unlike plasma AVP measurement, copeptin measurement in the plasma is relatively less cumbersome. It has several advantages: copeptin can remain stable for days after blood sampling and can be measured relatively quickly. [53] Plasma levels of copeptin strongly correlate with plasma AVP levels over a wide range of osmolalities, both in healthy individuals and those with DI or primary polydipsia. [27] [54] Moreover, plasma copeptin demonstrates the same response to plasma osmolality and volume changes as plasma AVP. [9] [27] Several studies have been conducted to validate the utility of plasma copeptin in diagnosing hypotonic polyuric states and to distinguish one form from the other. [8] [9] [11] [38] [27] Hypertonic saline infusion test:

Free water clearance

For example, for an individual with a urine osmolality of 140 mOsm/L, plasma osmolality of 280 mOsm/L, and a urine production of 4 ml/min, the free water clearance is 2 ml/min, obtained from Interpretation Free water clearance can be used as an indicator of how the body is regulating water. A free water clearance of zero means the kidney is producing urine isosmotic with respect to the plasma. Values greater than zero imply that the kidney is producing dilute urine through the excretion of solute-free water. Values less than zero imply that the kidney is conserving water (likely under the influence of antidiuretic hormone, ADH), resulting in the production of concentrated urine. See also Renal clearance Renal physiology External links Overview at mcg.edu Overview at mmi.mcgill.ca Formula at mmi.mcgill.ca Renal physiology

If the level is less than 4.9 pmol/l, it is diagnostic of central DI. 96% of the patients with polyuria were accurately diagnosed with their respective diagnoses by measuring copeptin along with water deprivation/hypertonic saline infusion test. Given the cumbersomeness of the water deprivation test and the long duration involved with it, hypertonic saline infusion gained a reputation. Stimulation with hypertonic saline also requires frequent sodium checks and close monitoring. Keeping this in mind, a study was done with arginine infusion to measure the stimulated levels of copeptin instead of with hypertonic saline, which was promising. [29] More evidence is needed to substantiate this finding, though.