Adenohypophyseal function in dogs with primary hypothyroidism and nonthyroidal illness.

BACKGROUND: A recent study of dogs with induced primary hypothyroidism (PH) demonstrated that thyroid hormone deficiency leads to loss of thyrotropin (TSH) hypersecretion, hypersomatotropism, hypoprolactinemia, and pituitary enlargement with large vacuolated "thyroid deficiency" cells that double-stained for growth hormone (GH) and TSH, indicative of transdifferentiation of somatotropes to thyrosomatropes. HYPOTHESIS: Similar functional changes in adenohypophyseal function occur in dogs with spontaneous PH as do in dogs with induced PH, but not in dogs with nonthyroidal illness (NTI). ANIMALS: Fourteen dogs with spontaneous PH and 13 dogs with NTI. METHODS: Adenohypophyseal function was investigated by combined intravenous administration of 4 hypophysiotropic releasing hormones (4RH test), followed by measurement of plasma concentrations of ACTH, GH, luteinizing hormone (LH), prolactin (PRL), and TSH. In the PH dogs this test was repeated after 4 and 12 weeks of thyroxine treatment. RESULTS: In 6 PH dogs, the basal TSH concentration was within the reference range. In the PH dogs, the TSH concentrations did not increase with the 4RH test. However, TSH concentrations increased significantly in the NTI dogs. Basal and stimulated GH and PRL concentrations indicated reversible hypersomatotropism and hyperprolactinemia in the PH dogs, but not in the NTI dogs. Basal and stimulated LH and ACTH concentrations did not differ between groups. CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs with spontaneous PH hypersecrete GH but have little or no TSH hypersecretion. Development of hyperprolactinemia (and possible galactorrhea) in dogs with PH seems to occur only in sexually intact bitches. In this group of dogs with NTI, basal and stimulated plasma adenohypophyseal hormone concentrations were not altered.

Growth hormone excess and the effect of octreotide in cats with diabetes mellitus.

In this prospective study 16 cats with diabetes mellitus were examined for concurrent acromegaly by measuring plasma growth hormone (GH) and insulin-like growth factor-I concentrations, and magnetic resonance imaging (MRI) of the pituitary fossa. Additionally, the effects of octreotide administration on the plasma concentrations of glucose, GH, alpha-melanocyte-stimulating hormone (alpha-MSH), adrenocorticotrophic hormone (ACTH), and cortisol were measured. Five cats were diagnosed with hypersomatotropism. The pituitary was enlarged in these 5 cats and in 2 other cats. Six cats that required a maximum lente insulin dosage >or=1.5 IU/kg body weight per injection had pituitary enlargement and 5 of these cats had acromegaly. Plasma concentrations of GH, ACTH, and cortisol decreased significantly after single intravenous administration of the somatostatin analogue octreotide in the acromegalic cats. The effect on GH concentrations was more pronounced in some of the acromegalic cats than in others. In the non-acromegalic cats only ACTH concentrations decreased significantly. In both groups plasma glucose concentrations increased slightly but significantly, whereas alpha-MSH concentrations were not significantly affected. In conclusion, the incidence of hypersomatotropism with concomitant pituitary enlargement appears to be high among diabetic cats with severe insulin resistance. Some of these cats responded to octreotide administration with a pronounced decrease in the plasma GH concentration, which suggests that octreotide administration could be used as a pre-entry test for treatment with somatostatin analogues.

Functional and morphological changes in the adenohypophysis of dogs with induced primary hypothyroidism: loss of TSH hypersecretion, hypersomatotropism, hypoprolactinemia, and pituitary enlargement with transdifferentiation.

From case studies in humans it is known that primary hypothyroidism (PH) may be associated with morphological and functional changes of the pituitary. There is no insight into the time scale of these changes. In this study, seven beagle dogs were followed up for 3 years after the induction of primary hypothyroidism. Three of these dogs were followed up for another 1.5 years while receiving l-thyroxine. Adenohypophyseal function was investigated at 2-month intervals with the combined intravenous injection of CRH, GHRH, GnRH, and TRH, and measurement of the plasma concentrations of ACTH, GH, LH, PRL, and TSH. In addition, after 2 years of hypothyroidism a single TRH-stimulation test and a somatostatin test were performed, with measurements of the same pituitary hormones. Every 6 months the pituitary gland was visualized by computed tomography (CT). Induction of PH led to high plasma TSH concentrations for a few months, where after concentrations gradually declined to values no longer significantly different from pre-PH values. A blunted response to stimulation of TSH release preceded this decline. Basal plasma GH concentrations increased during PH and there was a paradoxical hyperresponsiveness to TRH stimulation. Basal GH concentrations remained elevated and returned only to low values during l-thyroxine treatment. Basal PRL concentrations decreased significantly during PH and normalized after several months of l-thyroxine treatment. The pituitary gland became enlarged in all dogs. Histomorphology and immunohistochemical studies in 4 dogs, after 3 years of PH, revealed thyrotroph hyperplasia, large vacuolated thyroid deficiency cells, and decreased numbers of mammotrophs. Several cells stained for both GH and TSH. In conclusion, with time PH led to a loss of the TSH response to low T4 concentrations, hypersecretion of GH, and hyposecretion of PRL. The enlarged pituitaries were characterized by thyrotroph hyperplasia, large vacuolated thyroid deficiency cells, and double-staining cells, which are indicative of transdifferentiation.

Calcium-stimulation test for the assessment of beta-cell function in cats.

To assess the potential of an intravenous calcium-stimulation test (CST) as an indicator of insulin secretion in cats, indices calculated from CST results were compared with indices of insulin secretion derived from an intravenous glucose tolerance test (ivGTT) and hyperglycaemic glucose clamp (HGC) in 11 healthy, normal glucose tolerant, conscious cats. Intravenous administration of 2.5mg/kg Ca(2+) resulted in a significant increase in plasma free Ca(2+) (P<0.001) and plasma insulin (P=0.047) concentrations but did not affect the plasma glucose concentration. The indices of insulin secretion based on the CST did not correlate significantly with corresponding indices based on the ivGTT and HGC. In conclusion, the CST is not a useful test for assessing insulin secretion in cats. Other indices of insulin secretion, such as fasting insulin concentrations and the homeostasis model assessment of beta-cell function (HOMA-B), are easier to obtain and correlate better with indices of insulin secretion derived from the HGC, the gold standard technique for assessing insulin secretion.

Thyrotropin-releasing hormone-induced growth hormone secretion in dogs with primary hypothyroidism.

Primary hypothyroidism in dogs is associated with increased release of growth hormone (GH). In search for an explanation we investigated the effect of intravenous administration of thyrotropin-releasing hormone (TRH, 10 microg/kg body weight) on GH release in 10 dogs with primary hypothyroidism and 6 healthy control dogs. The hypothyroid dogs had a medical history and physical changes compatible with hypothyroidism and were included in the study on the basis of the following criteria: plasma thyroxine concentration < 2 nmol/l and plasma thyrotropin (TSH) concentration > 1 microg/l. In addition, (99m)TcO(4)(-) uptake during thyroid scintigraphy was low or absent. TRH administration caused plasma TSH concentrations to rise significantly in the control dogs, but not in the hypothyroid dogs. In the dogs with primary hypothyroidism, the mean basal plasma GH concentration was relatively high (2.3+/-0.5 microg/l) and increased significantly (P=0.001) 10 and 20 min after injection of TRH (to 11.9+/-3.5 and 9.8+/-2.7 microg/l, respectively). In the control dogs, the mean basal plasma GH concentration was 1.3+/-0.1 microg/l and did not increase significantly after TRH administration. We conclude that, in contrast to healthy control dogs, primary hypothyroid dogs respond to TRH administration with a significant increase in the plasma GH concentration, possibly as a result of transdifferentiation of somatotropic pituitary cells to thyrosomatotropes.

Insulin sensitivity and beta-cell function in healthy cats: assessment with the use of the hyperglycemic glucose clamp.

A hyperglycemic clamp (HGC) was developed for use in conscious cats. In 21 healthy, normal glucose tolerant cats glucose disposal rate (M), insulin sensitivity (ISI (HGC)), and beta-cell response (I) at arterial plasma glucose of 9 mmol.l (-1) were measured. The HGC was tolerated well and steady state glucose infusion was achieved. Compared to values reported for humans, M values for the cats were low, which appeared to relate to both a low ISI (HGC) and a low I. HGC measures correlated with fasting plasma glucose and insulin concentrations as well as with their HOMA (homeostasis model assessment) and QUICKI (quantitative insulin sensitivity check index) counterparts. Also, I and ISI (HGC) correlated with their counterparts derived from intravenous glucose tolerance tests. In conclusion, this is the first report of hyperglycemic glucose clamping in cats. The procedure (HGC) allows for measurements of glucose disposal, beta-cell response and insulin sensitivity. Compared to human data, both insulin sensitivity and insulin secretion appeared to be low in cats. This is compatible with the carnivorous nature of this species, for which insulin resistance would be advantageous during periods of restricted food availability.

Hyperthyroidism due to an intrathoracic tumour in a dog with test results suggesting hyperadrenocorticism.

The elevated urinary corticoid/creatinine ratios of an 11-year-old Jack Russell terrier with polyuria were suppressible in a high-dose dexamethasone suppression test, which was suggestive of pituitary-dependent hyperadrenocorticism. The absence of physical and routine-laboratory changes compatible with hyperadrenocorticism and the relatively high plasma thyroxine concentration were the impetus for additional studies of thyroid and adrenocortical functions. A high plasma thyroxine concentration (62 nmol/l; 5.0 microg/100 ml) suggested the presence of hyperthyroidism. Radiography, (99m)TcO(4) (-) scintigraphy, ultrasonography, computed tomography and cytology revealed a hyperfunctioning intrathoracic thyroid tumour. In the low-dose dexamethasone suppression test, the plasma cortisol concentration exceeded the reference value of 40 nmol/l (1.4 microg/100 ml) at eight hours after dexamethasone administration (0.01 mg/kg intravenously), a test result compatible with hyperadrenocorticism. In conclusion, this report represents the first case of a dog with an autonomously hyperfunctioning thyroid tumour in the thorax. The elevated urinary corticoid excretion and the positive low-dose dexamethasone suppression test may be explained by alterations in cortisol metabolism, the stress of the hyperthyroid state or both.

Assessment of thyroid function in dogs with low plasma thyroxine concentration.

BACKGROUND: Differentiation between hypothyroidism and nonthyroidal illness in dogs poses specific problems, because plasma total thyroxine (TT4) concentrations are often low in nonthyroidal illness, and plasma thyroid stimulating hormone (TSH) concentrations are frequently not high in primary hypothyroidism. HYPOTHESIS: The serum concentrations of the common basal biochemical variables (TT4, freeT4 [fT4], and TSH) overlap between dogs with hypothyroidism and dogs with nonthyroidal illness, but, with stimulation tests and quantitative measurement of thyroidal 99mTcO4(-) uptake, differentiation will be possible. ANIMALS: In 30 dogs with low plasma TT4 concentration, the final diagnosis was based upon histopathologic examination of thyroid tissue obtained by biopsy. Fourteen dogs had primary hypothyroidism, and 13 dogs had nonthyroidal illness. Two dogs had secondary hypothyroidism, and 1 dog had metastatic thyroid cancer. METHODS: The diagnostic value was assessed for (1) plasma concentrations of TT4, fT4, and TSH; (2) TSH-stimulation test; (3) plasma TSH concentration after stimulation with TSH-releasing hormone (TRH); (4) occurrence of thyroglobulin antibodies (TgAbs); and (5) thyroidal 99mTcO4(-) uptake. RESULTS: Plasma concentrations of TT4, fT4, TSH, and the hormone pairs TT4/TSH and fT4/TSH overlapped in the 2 groups, whereas, with TgAbs, there was 1 false-negative result. Results of the TSH- and TRH-stimulation tests did not meet earlier established diagnostic criteria, overlapped, or both. With a quantitative measurement of thyroidal 99mTcO4(-) uptake, there was no overlap between dogs with primary hypothyroidism and dogs with nonthyroidal illness. CONCLUSIONS AND CLINICAL IMPORTANCE: The results of this study confirm earlier observations that, in dogs, accurate biochemical diagnosis of primary hypothyroidism poses specific problems. Previous studies, in which the TSH-stimulation test was used as the "gold standard" for the diagnosis of hypothyroidism may have suffered from misclassification. Quantitative measurement of thyroidal 99mTcO- uptake has the highest discriminatory power with regard to the differentiation between primary hypothyroidism and nonthyroidal illness.

Alopecia in pomeranians and miniature poodles in association with high urinary corticoid:creatinine ratios and resistance to glucocorticoid feedback.

The adrenocortical function of pomeranians and miniature poodles with alopecia was tested by serial measurements of the urinary corticoid:creatinine ratio (uccr) and by an oral low-dose dexamethasone suppression test (lddst) and uccr measurements. In most of the dogs there was day-to-day variation in the uccrs of the 10 sequential urine samples, often with values above or below the upper limit of the range of healthy control dogs. In 22 alopecic pomeranians the basal uccrs were significantly higher than in 18 non-alopecic pomeranians, and the values of both groups were significantly higher than those of 88 healthy pet dogs. The uccrs of 12 alopecic miniature poodles were significantly higher than those of healthy dogs. In 12 alopecic pomeranians and eight alopecic miniature poodles the oral lddst revealed increased resistance to dexamethasone. In six non-alopecic pomeranians the uccrs after the administration of dexamethasone were not significantly different from those in seven healthy dogs at the same time. In an oral high-dose dexamethasone suppression test, using 0.1 mg dexamethasone/kg bodyweight, the uccrs of seven alopecic pomeranians and five alopecic miniature poodles decreased to low levels.

Effect of octreotide on plasma concentrations of glucose, insulin, glucagon, growth hormone, and cortisol in healthy dogs and dogs with insulinoma.

The inhibitory effect of the somatostatin analogue octreotide on the secretion of insulin could be used in the treatment of insulinoma. However, current information on the effectiveness of octreotide in dogs is conflicting. Therefore, the endocrine effects of a single subcutaneous dose of 50 microg octreotide were studied in healthy dogs in the fasting state (n=7) and in dogs with insulinoma (n=12). Octreotide did not cause any adverse effects. In healthy dogs in the fasting state, both plasma insulin and glucagon concentrations declined significantly. Basal (non-pulse related) GH and ACTH concentrations were not affected. A slight but significant decrease in the plasma glucose concentrations occurred. Dogs with insulinoma had significantly higher baseline insulin concentrations and lower baseline glucose concentrations than healthy dogs in the fasting state. Plasma glucagon, GH, ACTH, and cortisol concentrations did not differ from those in healthy dogs. Baseline plasma insulin concentrations decreased significantly in dogs with insulinoma after octreotide administration, whereas plasma concentrations of glucagon, GH, ACTH, and cortisol did not change. In contrast to the effects in the healthy dogs, in the dogs with insulinoma plasma glucose concentrations increased. Thus, the consistent suppression of plasma insulin concentrations in dogs with insulinoma, in the absence of an suppressive effect on counter-regulatory hormones, suggests that further studies on the effectiveness of slow-release preparations in the long-term medical treatment of dogs with insulinoma are warranted.

Melanotroph pituitary adenoma in a cat with diabetes mellitus.

A 13-year-old male, castrated, crossbred cat was referred for insulin-resistant diabetes mellitus. The cat had a ravenous appetite and a dull coat. Basal urinary corticoid/creatinine ratios were normal. In the low-dose dexamethasone suppression test there was no suppression of the (nonelevated) plasma cortisol concentration, whereas the (nonelevated) plasma adrenocorticotropic hormone (ACTH) concentration declined to low values. Basal plasma alpha-melanocyte-stimulating hormone (alpha-MSH) concentrations were highly elevated (> 1,500 ng/liter). Computed tomography revealed a pituitary tumor originating from the pars intermedia (PI). After microsurgical transsphenoidal hypophysectomy, the clinical signs resolved and the cat no longer required insulin administration. Microscopic examination of the surgical specimen revealed a pituitary adenoma originating from the PI with infiltration into the neural lobe. The adenoma immunostained intensely positive for alpha-MSH and only weakly for ACTH. It is concluded that the ACTH-independent cortisol production was probably due to the (weak) glucocorticorticotropic effects of the extremely high plasma concentration of alpha-MSH and related peptides.

Primary hyperaldosteronism, a mediator of progressive renal disease in cats.

In recent years, there has been renewed interest in primary hyperaldosteronism, particularly because of its possible role in the progression of kidney disease. While most studies have concerned humans and experimental animal models, we here report on the occurrence of a spontaneous form of (non-tumorous) primary hyperaldosteronism in cats. At presentation, the main physical features of 11 elderly cats were hypokalemic paroxysmal flaccid paresis and loss of vision due to retinal detachment with hemorrhages. Primary hyperaldosteronism was diagnosed on the basis of plasma concentrations of aldosterone (PAC) and plasma renin activity (PRA), and the calculation of the PAC:PRA ratio. In all animals, PACs were at the upper end or higher than the reference range. The PRAs were at the lower end of the reference range, and the PAC:PRA ratios exceeded the reference range. Diagnostic imaging by ultrasonography and computed tomography revealed no or only very minor changes in the adrenals compatible with nodular hyperplasia. Adrenal gland histopathology revealed extensive micronodular hyperplasia extending from zona glomerulosa into the zona fasciculata and reticularis. In three cats, plasma urea and creatinine concentrations were normal when hyperaldosteronism was diagnosed but thereafter increased to above the upper limit of the respective reference range. In the other eight cats, urea and creatinine concentrations were raised at first examination and gradually further increased. Even in end-stage renal insufficiency, there was a tendency to hypophosphatemia rather than to hyperphosphatemia. The histopathological changes in the kidneys mimicked those of humans with hyperaldosteronism: hyaline arteriolar sclerosis, glomerular sclerosis, tubular atrophy and interstitial fibrosis. The non-tumorous form of primary hyperaldosteronism in cats has many similarities with "idiopathic" primary hyperaldosteronism in humans. The condition is associated with progressive renal disease, which may in part be due to the often incompletely suppressed plasma renin activity.

Urinary corticoid:creatinine ratios in healthy pet dogs after oral low-dose dexamethasone suppression tests.

Eleven dogs were used in a trial to find a suitable dose of dexamethasone for an oral dexamethasone suppression test for the diagnosis of hyperadrenocorticism. Basal urinary corticoid:creatinine ratios were established in all 11 and then groups of seven were given oral doses of 0.02, 0.01 or 0.0075 mg dexamethasone/kg bodyweight and urine samples were collected at two-hour intervals from 08.00 to 22.00. The doses of 0.02 and 0.01 mg/kg consistently suppressed their urinary corticoid:creatinine ratios measured at 16.00 by a mean of more than 50 per cent and those of individual dogs to less than 1.0 x 10(-6), whereas the dose of 0.0075 mg/kg did not.

Urinary aquaporin-2 excretion in dogs: a marker for collecting duct responsiveness to vasopressin.

In humans, the urinary aquaporin-2 (U-AQP2) excretion closely parallels changes in vasopressin (VP) action and has been proposed as a marker for collecting duct responsiveness to VP. This report describes the development of a radioimmunoassay for the measurement of U-AQP2 excretion in dogs. In addition, the localization of AQP2 in the canine kidney was investigated by immunohistochemistry. Basal U-AQP2 excretion was highly variable among healthy dogs. Two hours after oral water loading, the mean U-AQP2/creatinine ratio decreased significantly from (231 +/- 30) x 10(-9) to (60 +/- 15) x 10(-9) (P = 0.01), while the median plasma VP concentration decreased from 4.2 pmol/l (range 2.2-4.8 pmol/l) to 1.2 pmol/l (range 1.0-1.9 pmol/l). Subsequent intravenous administration of desmopressin led to a significantly increased mean U-AQP2/creatinine ratio of (258 +/- 56) x 10(-9) (P = 0.01). Two hours of intravenous hypertonic saline infusion (20% NaCl, 0.03 ml/kg body weight/min) significantly increased the mean U-AQP2/creatinine ratio from (86 +/- 6) x 10(-9) to (145 +/- 23) x 10(-9) (P = 0.045), while the median plasma VP concentration increased significantly from 2.2 pmol/l (range 1.1-6.3 pmol/l) to 17.1 pmol/l (range 8.4-67 pmol/l) (P < 0.001). Immunohistochemistry revealed extensive labeling for AQP2 in the kidney collecting duct cells, predominantly localized in the apical and subapical region. As in humans, U-AQP2 excretion in dogs closely reflects changes in VP exposure. Urinary AQP2 excretion may become a diagnostic tool in dogs for the differentiation of polyuric conditions such as (partial) central or nephrogenic diabetes insipidus, primary polydipsia, and inappropriate VP release.

Pulsatile secretion pattern of vasopressin under basal conditions, after water deprivation, and during osmotic stimulation in dogs.

Measurement of plasma osmolality (Posm) and plasma vasopressin (VP) concentration in response to hypertonicity is regarded as the gold standard for the assessment of VP release in polyuric conditions. Yet the interpretation of the VP curve as a function of Posm may be hampered by the occurrence of VP pulses. To determine whether VP is secreted in a pulsatile fashion in the dog and whether stimulation of VP release changes the secretion pattern of VP, we measured VP at 2-min intervals for 2 h under basal conditions, after 12 h of water deprivation, and during osmotic stimulation with hypertonic saline (20%) in eight healthy dogs. Vasopressin was secreted in a pulsatile fashion with a wide variation in number of VP pulses, VP pulse duration, and VP pulse amplitude and height. After water deprivation, total and basal VP secretion, the number of significant VP pulses, as well as the pulse characteristics did not differ from the basal situation. During osmotic stimulation, there was a large increase in both basal and pulsatile VP secretion, and the number of VP pulses and VP pulse height and amplitude were significantly increased. The VP pulse amplitude correlated significantly with the basal plasma VP concentration during osmotic stimulation. It is concluded that VP is secreted in a pulsatile manner in healthy dogs. The basal and pulsatile VP secretion increases during osmoreceptor-mediated stimulation. The VP pulses may occur to the magnitude that they may be interpreted as erratic bursts, when occurring in the hypertonic saline infusion test.

Urinary glucocorticoid excretion in the diagnosis of hyperadrenocorticism in ferrets.

Hyperadrenocorticism in ferrets is usually associated with unaltered plasma concentrations of cortisol and adrenocorticotropic hormone (ACTH), although the urinary corticoid/creatinine ratio (UCCR) is commonly elevated. In this study the urinary glucocorticoid excretion was investigated in healthy ferrets and in ferrets with hyperadrenocorticism under different circumstances. In healthy ferrets and in one ferret with hyperadrenocorticism, approximately 10% of plasma cortisol and its metabolites was excreted in the urine. High-performance liquid chromatography (HPLC) revealed one third of the urinary corticoids to be unconjugated cortisol; the other peaks mainly represented cortisol conjugates and metabolites. In 21 healthy sexually intact ferrets, the UCCR started to increase by the end of March and declined to initial values halfway the breeding season (June). In healthy neutered ferrets there was no significant seasonal influence on the UCCR. In two neutered ferrets with hyperadrenocorticism the UCCR was increased, primarily during the breeding season. In 27 of 31 privately owned ferrets with hyperadrenocorticism, the UCCR was higher than the upper limit of the reference range (2.1 x 10(-6)). In 12 of 14 healthy neutered ferrets dexamethasone administration decreased the UCCR by more than 50%, whereas in only 1 of the 28 hyperadrenocorticoid ferrets did the UCCR decrease by more than 50%. We conclude that the UCCR in ferrets primarily reflects cortisol excretion. In healthy sexually intact ferrets and in ferrets with hyperadrenocorticism the UCCR increases during the breeding season. The increased UCCR in hyperadrenocorticoid ferrets is resistant to suppression by dexamethasone, indicating ACTH-independent cortisol production.

Morphology of the pituitary gland in ferrets (Mustela putorius furo) with hyperadrenocorticism.

Pituitary tumours are the cause of hyperadrenocorticism in a variety of species, but the role of the pituitary gland in hyperadrenocorticism in ferrets is not known. In this species, the disease is mediated by the action of excess gonadotrophins on the adrenal cortex and is characterized by an excessive secretion of sex steroids. In this study, the pituitary gland of four healthy control ferrets, intact or neutered, and 10 neutered ferrets with hyperadrenocorticism was examined histologically following immunohistochemical labelling for adrenocorticotrophic hormone, alpha-melanocyte-stimulating hormone, growth hormone, thyroid-stimulating hormone, luteinizing hormone, follicle-stimulating hormone, and prolactin. Immunohistochemistry revealed that somatotrophs, thyrotrophs and lactotrophs were the most abundant cell types of the pars distalis of the pituitary gland in the healthy ferrets. The distribution of corticotrophs was similar to that in the dog and man. In ferrets, as in dogs, the melanotrophic cell was almost the only cell type of the pars intermedia. Gonadotrophs were found in the pars distalis of neutered, but not intact ferrets. All the ferrets with hyperadrenocorticism had unilateral or bilateral alterations of the adrenal gland. In addition, in the pituitary gland of two of these ferrets a tumour was detected. These tumours were not immunolabelled by antibodies against any of the pituitary hormones, and had characteristics of the clinically non-functional gonadotroph tumours seen in man. In some of the other ferrets low pituitary immunoreactivity for gonadotrophic hormones was detected, which may have been due to the feedback of autonomous steroid secretion by the neoplastic transformation of the adrenal cortex. It is concluded that initially high concentrations of gonadotrophins resulting from castration may initiate hyperactivity of the adrenal cortex. The low incidence of pituitary tumours and the low density of gonadotrophin-positive cells in non-affected pituitary tissue in this study suggest that persistent hyperadrenocorticism is not dependent on persistent gonadotrophic stimulation.

Somatotroph and corticotroph pituitary adenoma (double adenoma) in a cat with diabetes mellitus and hyperadrenocorticism.

A 9-year-old castrated male European shorthair cat with insulin-resistant diabetes was referred with the preliminary diagnosis of pituitary-dependent hyperadrenocorticism, based on measurements of urinary corticoids. Further studies revealed not only resistance of plasma concentrations of cortisol, adrenocorticotropic hormone (ACTH) and alpha-melanocyte-stimulating hormone (alpha-MSH) to suppression by a low dose of dexamethasone, but also elevated plasma concentrations of growth hormone (GH) and insulin-like growth factor I (IGF-I). Pituitary imaging with dynamic contrast-enhanced computed tomography demonstrated an enlarged pituitary gland and an adenoma. The cat underwent trans-sphenoidal hypophysectomy after which the insulin resistance disappeared. On histopathological and immunocytochemical examination of the surgical specimen a double adenoma was found, consisting of a corticotroph adenoma and a somatotroph adenoma separated by unaffected pituitary tissue.