a 12-year - old , male neutered domestic shorthair cat was referred for investigation of suspected hyperaldosteronism due to persistent hypokalaemia , hindlimb ataxia , weakness of 1 month s duration and a left adrenal mass that was detected on abdominal ultrasound .
hyperaldosteronism and concurrent hyperprogesteronism were confirmed on endocrine testing . on computed tomography ( ct ) of the abdomen and thorax
there was no evidence of local vascular invasion by the adrenal mass or of metastatic disease .
ct and magnetic resonance imaging featured a large , focal rim - enhancing extra - axial left forebrain lesion consistent with a meningioma .
the tumours were classified on histopathology as a psammomatous meningioma and an adrenocortical adenocarcinoma , respectively .
in humans , elevated serum progesterone levels have been associated with rapid growth of meningiomas due to the presence of progesterone receptors on the tumour .
this is the first report of a cat with a progesterone and aldosterone - secreting adrenocortical adenocarcinoma and a concurrent meningioma .
clinicians should be aware of the potential effect of elevated progesterone on meningiomas in cats .
in humans , elevated serum progesterone levels have been associated with rapid growth of meningiomas due to the expression of progesterone receptors ( prs ) on tumour cells . here
we report a case of a meningioma in a cat with an adrenocortical carcinoma that was co - secreting aldosterone and progesterone .
a 12 year - old , male neutered , domestic shorthair cat was referred to the valentine charlton cat centre for investigation of persistent hypokalaemia ( 2.53.3 mmol / l ; reference interval [ ri ] 3.55.8 mmol / l ) , hypertension , hindlimb ataxia and weakness of approximately 1 month s duration . a palpable , left - sided
, cranial abdominal mass localised to the left adrenal gland was identified on abdominal ultrasound . on presentation at referral , the cat was agitated , vocalising and pacing compulsively in wide circles to the left .
the cat weighed 6.45 kg ( body condition score [ bcs ] 3/5 ) and had lost 500 g in body weight over the previous 2 months . on physical examination
a grade iii / vi left parasternal systolic heart murmur was auscultated and systolic arterial blood pressure was 220 mmhg ( doppler method ) .
a neurological examination revealed an absent right menace response and a proprioceptive deficit on the right forelimb .
on fundoscopy , there was evidence of hypertensive chorioretinopathy , including a focal , hyper - reflective bullous lesion in the left tapetal fundus and tortuous retinal vessels .
an aldosterone - secreting adrenal neoplasm was suspected , based on clinical history , hypokalaemia , systemic hypertension with evidence of end - organ damage and sonographic findings .
abnormalities on repeat haematology and serum biochemistry were confined to hypokalaemia ( 2.5 mmol / l ; ri 3.55.8
mmol / l ) , metabolic alkalosis ( bicarbonate 25 mmol / l ; ri 1721 mmol / l ) and mildly elevated creatinine kinase ( 460 u / l ; ri 64400 u / l ) .
serum total thyroxine was within normal limits ( 37 nmol / l ; ri 10 - 60
pmol / l ) , while plasma renin activity was low ( < 40 fmol / l / s ; ri 60630 fmol / l / s ) . an adrenocorticotropic hormone ( acth ) stimulation test
progesterone was increased at time zero ( 16.1 nmol / l ; ri 0.192.22 nmol / l ) and 1 h post - acth administration ( 23.2 nmol / l ; ri 2.8614.62 nmol / l ) .
based on these results , an aldosterone and progesterone - secreting adrenal neoplasm was diagnosed .
a repeat abdominal ultrasound confirmed the presence of a 3.1 cm diameter , circumscribed , hypoechoic mass involving the left adrenal gland , with no evidence of metastases or vascular or renal parenchymal invasion .
the right adrenal gland was of normal dimensions and appearance ( 3.9 mm diameter ) .
it was difficult to determine the clinical course of the neurological signs because profound weakness from hypokalaemia was also present . however , major differential diagnoses included metastasis from an adrenal carcinoma , a primary meningioma or a vascular accident secondary to hypertension .
the cat underwent computed tomography ( ct ) of the abdomen , thorax and skull under general anaesthesia ( figure 1 ) .
there was no evidence of vascular invasion of adjacent blood vessels by the adrenal mass .
on ct of the skull , an extra - axial , rim - enhancing , left forebrain lesion was evident after the administration of iohexol ( 2 ml / kg , omnipaque 350 ; ge healthcare ) .
meningioma was suspected and magnetic resonance imaging ( mri ) was performed to further characterise the lesion and to confirm that the tumour was solitary , prior to surgical excision ( figure 2 ) .
postcontrast ( a ) axial and ( b ) dorsal images acquired utilising 0.8 mm slice collimation computed tomography at the level of the cranial pole of the left kidney .
these images have been reconstructed using a maximum - intensity projection technique with osirix software ( v.6.1.1.64-bit ; pixmeo sarl ) .
there is a 2.4 cm ( width )  3 cm ( height )  3.2 cm contrast - enhancing left adrenal mass .
the mass is located immediately caudal to the renal artery and adjacent to the vena cava .
the right adrenal gland can not be visualised in these images t2-weighted ( a ) parasagittal , ( b ) dorsal and ( c ) axial , and t1-weighted precontrast ( d ) axial and ( e ) fluid attenuation inversion recovery ( flair ) axial 4 mm thickness magnetic resonance images .
there is a 2 cm  1.5 cm well - demarcated mass lesion with a broad base towards the periphery within the left parietal brain lobe ( thick arrow ) .
there is evidence of midline shift and impingement of the left lateral ventricle ( thin arrow ) .
the mass is isointense to grey matter in the t1-weighted sequences and hyperintense in t2-weighted and flair sequences .
the mass is consistent with a meningioma with evidence of increased intracranial pressure . on mri the forebrain mass ( 2 cm  1.5 cm )
was well demarcated and had a broad base towards the periphery associated with the left parietal lobe causing a midline shift and impingement of the left lateral ventricle .
the mass was isointense to grey matter in the t1-weighted sequence and hyperintense in t2-weighted and flair sequences .
there was transtentorial herniation of part of the mesencephalon into the caudal fossa and obliteration of the subarachnoid space between the cerebellum and medulla .
anaesthetic recovery was unremarkable and the cat was discharged on amlodipine besylate ( 1.25 mg q24h po , norvasc ; pfizer ) , spironolactone ( 6.25 mg q24h po , aldactone ; pfizer ) and potassium gluconate ( 156 mg q12h po , hypokal ; mavlab ) .
prednisolone ( 7.5 mg q12h po , pred - x 5 ; apex laboratories ) was given to treat suspected cerebral oedema .
twenty - four hours after discharge the cat re - presented with recurrent vocalisation , a left body turn , stilted hindlimb gait and hindlimb weakness .
serum acid  base and electrolytes showed persistent hypokalaemia ( 2.9 mmol / l ) and metabolic alkalosis ( ph 7.482 [ ri : 7.317.46 ] ; bicarbonate 31.3 mmol / l [ ri 1721 mmol / l ] ) .
a potassium chloride infusion ( 0.5 mmol / kg / h iv ) was given , as well as mannitol ( 0.25 g / kg iv over 1 h ) for suspected increased intracranial pressure .
after stabilisation , the intracranial mass was removed 3 days later via a rostrotentorial craniotomy with no complications ( figure 3 ) . on histopathology
the mass was composed of spindle cells with ovoid plump nuclei , vesiculate chromatin and small multiple nucleoli .
immuno - histochemical staining of the meningioma using a mouse monoclonal antibody to human pr previously validated for use in the cat ( bio - genex insite pr antibody [ clone pr88 ] ; bio - genex ) was performed .
there was strong positive labelling of prs in the meningioma tissue ( figure 4 ) .
mammary adenocarcinoma tissue was utilised as a positive tissue control , and an affinity - purified normal mouse igg reagent control ( preimmune serum ) supplied by the manufacturer was used as the negative control .
( b ) cut surface of the resected adrenocortical adenocarcinoma photomicrograph of meningioma tissue ( a ) after immunohistochemical staining for progesterone receptors ( prs ) . note the positive labelling of most nuclei compared with the relative absence of labelling with the negative antibody control ( b ) .
( c ) prs are present within the positive antibody control ( mammary adenocarcinoma tissue ) .
immunohistochemistry was performed using a mouse monoclonal antibody to prs ( bio - genex insite pr antibody [ clone pr88 ] ; bio - genex ) and the peroxidise method with 3,3-diaminobenzidine chromagen and a light haematoxylin counterstain postoperative recovery from the craniotomy was uneventful and neurological status markedly improved over the next 2 weeks , except for persistent weakness .
mmol / l ) and hypertension persisted , while hypertension was controlled ( systolic blood pressure 150 mmhg ) .
histopathology of the adrenal tumour was consistent with a low - grade , encapsulated , adrenocortical carcinoma . at a recheck , 2 weeks after adrenalectomy , serum biochemistry was suggestive of mineralocorticoid deficiency ( mild hyperkalaemia [ 5.9 mmol / l ; ri 3.75.4
mmol / l ] and low na : k [ 24.7 ; ri > 29.0 ] ) .
fludrocortisone ( 0.15 mg daily divided dosage po , florinef ; aspen pharma ) was administered .
this medication was tapered and then ceased over a 3 week period . a week after stopping the fludrocortisone , serum potassium was normal and the cat continued to gain weight .
two years post - initial presentation the cat was clinically normal , normotensive and 1 kg heavier ( 7.5 kg , bcs 4/5 ) .
to our knowledge , this is the first report in a cat of an adrenal mass secreting aldosterone and progesterone with a concurrent meningioma .
the documentation of prs in a meningioma with concurrent elevation of serum progesterone is also novel .
clinical signs associated with hyperprogesteronism may be subtle , or as in this case , absent .
alternatively , hyperprogesteronism can resemble hypercortisolaemia with signs including polyuria , polydipsia , poor coat condition , seborrhoea , thin fragile skin and a pot - bellied appearance .
other co - hormone secretions reported in cats with adrenocortical tumours include androstenedione and testosterone in one case , and testosterone and oestradiol in another .
concurrent cortisol and sex steroid - secreting adrenal tumours have not been reported in cats .
we measured progesterone in this case because of our previous observation of hyperprogesteronism in a cat with concurrent hyperaldosteronism .
we can not rule out the possibility of cortisol or other adrenal steroid hormone secretion , as other adrenal hormones were not measured .
in other cases of feline adrenal progesterone / sex - steroid secreting tumours , low post - acth cortisol concentrations were reported .
potential mechanisms for this response include a lack of enzymes within the adrenal tumour to convert progesterone to cortisol , or hypothalamic  pituitary  adrenal axis suppression from excessive circulating levels of cortisol as a result of displacement from cortisol binding protein by progesterone . in humans , adrenal tumours
have been shown to co - secrete aldosterone with cortisol , testosterone , progesterone and androstenedione .
enhancement of the biosynthetic pathway of aldosterone in an aldosterone - secreting tumour , resulting in increased serum concentrations of the intermediates of aldosterone production , including progesterone , is proposed to account for some cases .
alternatively , neoplastic cells within the zona glomerulosa and fasciculata / reticularis may directly increase secretion of aldosterone and progesterone , respectively .
meningiomas are the most common primary intracranial tumour in cats , dogs and humans . in cats ,
meningiomas are derived from the arachnoid cap cells associated with the venous sinus of the dura . in cats , meningiomas are usually histologically benign , but their behaviour may be malignant .
rapid progression of neurological symptoms due to meningioma in human pregnancy was first reported by cushing and eisenhardt in 1938 , and the association between excessive progesterone secretion and the development , or accelerated growth , of meningiomas is now well established in human medicine , where hormone replacement therapy , contraceptive implants and breast carcinoma are also implicated .
the development of multiple meningiomas during prolonged progesterone agonist therapy that regressed with cessation of treatment is also compelling evidence of this association .
further , the incidence of meningiomas in women is twice as high as in men , especially during their reproductive life period .
there is also a known association between the development of meningioma and carcinoma of the breast .
sex hormone receptor expression in meningiomas from humans , cats and dogs has been reported . in humans ,
( er ) are expressed to a lesser extent . in vitro and in vivo studies
adamo et al reported that feline meningiomas , like human ones , have a high proportion of prs and an absence of ers . to our knowledge serum progesterone levels
pr expression is less likely in more aggressive and atypical meningioma cases in people and dogs . this association has not been definitively established in cats but appears likely .
assay of progesterone and other aldosterone intermediates in cats with aldosterone - producing tumours is recommended as co - hormone secretion may be under - reported . in a survey of laboratory submissions of feline sera for aldosterone assay ,
marked elevations in corticosterone and progesterone were detected in some cats with marked elevation of aldosterone ( > 3000 pmol / l ) .
elevated serum progesterone levels may contribute to muscle weakness and hypertension seen in these patients .
clinicians should maintain an index of suspicion for hyperprogesteronism in cats , particularly where progressive intracranial signs are detected .
 case summarya 12-year - old , male neutered domestic shorthair cat was referred for investigation of suspected hyperaldosteronism due to persistent hypokalaemia , hindlimb ataxia , weakness of 1 month s duration and a left adrenal mass that was detected on abdominal ultrasound . 
 neurological examination findings at referral were suggestive of a concurrent left forebrain lesion . 
 hyperaldosteronism and concurrent hyperprogesteronism were confirmed on endocrine testing . on computed tomography ( ct ) of the abdomen and thorax 
 there was no evidence of local vascular invasion by the adrenal mass or of metastatic disease . 
 ct and magnetic resonance imaging featured a large , focal rim - enhancing extra - axial left forebrain lesion consistent with a meningioma . 
 surgical excision of the forebrain mass was followed by adrenalectomy 2 weeks later . 
 the tumours were classified on histopathology as a psammomatous meningioma and an adrenocortical adenocarcinoma , respectively . 
 immunohistochemical staining of the meningioma confirmed the presence of progesterone receptors . 
 the cat remains well 2 years later.relevance and novel informationin humans , elevated serum progesterone levels have been associated with rapid growth of meningiomas due to the presence of progesterone receptors on the tumour . 
 this is the first report of a cat with a progesterone and aldosterone - secreting adrenocortical adenocarcinoma and a concurrent meningioma . 
 clinicians should be aware of the potential effect of elevated progesterone on meningiomas in cats . 
Case summary
Relevance and novel information
Introduction
Case description
Discussion
Conclusions