A 14 year-old male patient with a history of polyuria and polydipsia in the past 2 months was admitted to our hospital. He was prepubertal and of short stature (height SDS: -2.26, parentally adjusted height SDS: -2.64). He ingested 8 L of fluid and urinated 5-6 L daily. At initial evaluation he appeared well hydrated and had normal vital signs. His basal urinary osmolality, serum osmolality and the ratio of urinary osmolality to serum osmolality were, 40 mosm/kg H2O, 299 mosm/kg H2O and 0.13, respectively. Serum sodium, potassium, calcium, phosphorus levels were within normal limits. Water deprivation test and desmopressin (dDAVP) test confirmed the diagnosis of complete CDI. After subcutaneous dDAVP administration, urinary osmolality increase from the baseline was 174%. There was no family history of CDI, no history of head trauma/injury or evidence of systemic diseases such as Langerhans cell hystiocytosis (LCH), sarcoidosis, tuberculosis or neurological deficits.
MRI of the pituitary region showed a thickened pituitary stalk (5 mm) and loss of the hyperintense signal of the posterior pituitary. Transsphenoidal biopsy of the lesion was not done. Desmopressin treatment was initiated. Complete anterior pituitary endocrine function evaluation included measurement of growth hormone response to pharmacological stimulation tests (L-Dopa test and insulin tolerance test-ITT); baseline and ITT stimulated cortisol levels; thyroid function tests; basal testosterone level, luteinizing hormone (LH) and follicle stimulating hormone (FSH) response to gonadotropin releasing hormone (GnRH) stimulation, and prolactin level. The patient did not have central hypothyroidism, adrenocorticotropic hormone (ACTH) deficiency or hyperprolactinemia. He suffered from both complete growth hormone (GH) deficiency (L-Dopa stimulated GH peak was 0.65 ng/mL, ITT stimulated GH peak was 0.38 ng/mL) and hypogonadotropic hypogonadism. At 14 years of age he had bilateral testicular volumes of less than 4 mL, basal testosterone level was within the prepubertal range (13 ng/dL) and GnRH stimulated LH and FSH were 3.38 mIU/mL and 4.22 mIU/mL, respectively. GH stimulation tests were performed after priming with sex steroid. In the differential diagnosis, pituitary tumor (such as germinoma), LCH, sarcoidosis or tuberculosis were considered. High resolution CT of the thorax and a bone survey for LCH were normal. A negative result was obtained for human chorionic gonadotropin (hCG) and a-fetoprotein levels in the cerebrospinal fluid, which were measured to eliminate a diagnosis of germinoma. The patient had no systemic evidence of sarcoidosis, and hyperprolactinemia was not detected. Serum angiotensin converting enzyme was within normal levels. Chest Xray, intradermal tuberculin test, cerebrospinal fluid analysis yielded negative results for tuberculosis.
The patient was followed clinically, backed up with endocrine and MRI evaluation for 4 years, with no treatment other than desmopressin as a hormone substitution therapy.
His pituitary stalk size showed a change over the four years of follow up. Hypophyseal MRI, which was taken every 3 to 4 months, demonstrated that PST enlarged from 5 mm to 7 mm during the first 10 months of follow-up. After that, complete regression of pituitary stalk enlargement occurred over the subsequent 14 months. The time interval between the diagnosis and the complete regression of PST enlargement was 2 years. PST decreased from 7 mm to 2.5 mm, (Figure 1, 2, 3) and retained its normal size for the last 2 years. The loss of bright signal on MRI remained unchanged during the follow-up period.
Despite improvement of the GH deficiency and hypogonadotropic hypogonadism, CDI was persistent. At the most recent evaluation when the patient was 17.9 years of age, GH response to ITT was 20 ng/mL, testicular volume was 20 mL and basal testosterone level was 232 ng/dL. His height was 169.8 cm, height SDS was -0.59, and he had a +1.67 SD height gain without GH treatment. Because of the regression of PST, absence of progression to any systemic disease or pituitary tumor over 4 years, an autoimmune hypophysitis was suspected in this patient.