Luteinizing hormone-dependent Cushing's syndrome in a pet ferret (Mustela putorius furo)

Hyperadrenocorticism in ferrets is associated with increased circulating concentrations of adrenal androgens, whereas plasma concentrations of cortisol and ACTH are usually not affected. Here, we report on a 5-year-old castrated male pet ferret (Mustela putorius furo) in which the major presenting signs were polyuria and polyphagia. Routine biochemistry values were within their reference ranges. The urinary corticoid:creatinine ratio (UCCR) was increased and the plasma ACTH concentration was suppressed. Abdominal ultrasonography revealed an enlarged right adrenal gland and atrophy of the left adrenal gland. Administration of hCG resulted in an increase of plasma cortisol and androstenedione concentrations. Based on these findings LH/hCG-dependent hypercortisolism and hyperandrogenism were suspected and treatment was started with a depot GnRH-agonist implant containing 9.4mg deslorelin. Within 3 weeks after placement of the implant all clinical signs had disappeared. Three months later the endocrine parameters had normalized, while abdominal ultrasonography revealed that the right adrenal gland had diminished in size and the left adrenal gland was considered of normal size. No recurrences of clinical signs were seen within 2 years after placement of the deslorelin implant. At that time urinary corticoid and plasma hormone concentrations were within their reference ranges, and no further change in the size of the adrenal glands was seen. In conclusion, this is the first confirmed case of LH-dependent hypercortisolism in a ferret that was treated successfully with a depot GnRH-agonist.     

Expression of receptors for luteinizing hormone,gastric-inhibitory polypeptide,and vasopressin in normal adrenal glands and cortisol-secreting adrenocortical tumors in dogs

Hypercortisolism caused by an adrenocortical tumor (AT) results from adrenocorticotropic hormone (ACTH)-independent hypersecretion of glucocorticoids. Studies in humans demonstrate that steroidogenesis in ATs may be stimulated by ectopic or overexpressed eutopic G protein-coupled receptors. We report on a screening of 23 surgically removed, cortisol-secreting ATs for the expression of receptors for luteinizing hormone (LH), gastric-inhibitory polypeptide (GIP), and vasopressin (V_1a, V_1b, and V₂). Normal adrenal glands served as control tissues. Abundance of mRNA for these receptors was quantified using quantitative polymerase chain reaction (QPCR), and the presence and localization of these receptors were determined by immunohistochemistry. In both normal adrenal glands and ATs, mRNA encoding for all receptors was present, although the expression abundance of the V_1b receptor was very low. The mRNA expression abundance for GIP and V₂ receptors in ATs were significantly lower (0.03 and 0.01, respectively) than in normal adrenal glands. The zona fasciculata of normal adrenal glands stained immunonegative for the GIP receptor. In contrast, islands of GIP receptor-immunopositive cells were detected in about half of the ATs. The zona fasciculata of both normal adrenal glands and AT tissue were immunopositive for LH receptor; in ATs in a homogenous or heterogenous pattern. In normal adrenal glands, no immunolabeling for V_1bR and V₂ receptor was present, but in ATs, V₂ receptor-immunopositive cells were detected. In conclusion, QPCR analysis did not reveal overexpression of LH, GIP, V_1a, V_1b, or V₂ receptors in the ATs. However, the ectopic expression of GIP and V₂ receptor proteins in tumorous zona fasciculata tissue may play a role in the pathogenesis of canine cortisol-secreting ATs.     

The effects of hydrocortisone on systemic arterial blood pressure and urinary protein excretion in dogs

BACKGROUND: Hypertension and proteinuria are commonly recognized in dogs with spontaneous hypercortisolism. There is, however, little information regarding the effect of exogenous glucocorticoids on blood pressure (BP) and proteinuria and whether these changes are reversible. HYPOTHESIS: Hydrocortisone administration increases systemic BP and urinary protein excretion, and these effects are reversible after hydrocortisone withdrawal. Animals: Six control dogs and 6 dogs treated with hydrocortisone. METHODS: BP, urine protein : creatinine ratio (UPC), microalbuminuria (MALB), urine albumin : creatinine ratio (UAC), and urine gel electrophoresis were evaluated before, during, and after administration of hydrocortisone (8 mg/kg PO q12h for 12 weeks) or placebo. RESULTS: BP and UPC increased substantially during hydrocortisone administration from 123 mmHg (range 114-136 mmHg) and 0.17 (0.15-0.28) to a maximum of 143 mmHg (128-148 mmHg) and 0.38 (0.18-1.78), respectively, on day 28. MALB developed in 4 dogs and UAC significantly increased in all dogs during hydrocortisone administration with the maximum on day 84. Both increases in BP and proteinuria were reversible and completely resolved within 1 month after stopping hydrocortisone administration. SDS-AGE revealed the proteinuria to be primarily albuminuria with a pronounced increase during hydrocortisone treatment. Furthermore, a protein of 25-30 kDa was found in male dogs, identified by mass spectrometry to be arginine esterase, the major secretory prostatic protein. CONCLUSIONS AND CLINICAL IMPORTANCE: Long-term hydrocortisone treatment results in significant but only mild increases in systemic BP and urinary protein excretion, which are both reversible within 1 month after discontinuation of hydrocortisone.     

A comparative study by age and gender of the pituitary adenoma and ACTH and α-MSH secretion in dogs with pituitary-dependent hyperadrenocorticism

Pituitary-dependent hyperadrenocorticism (PDH) is frequent in dogs. Little is known about its presentation in different age groups and its characteristics. Dividing the population under study (n = 107) into three age groups we observed that 11.2% were young, 51.4% adults and 37.4% aged. Using magnetic resonance, pituitary tumours were intra-sellar (IS) in 30.8% and extra-sellar (ES) in 62.6% and the pars intermedia (PI) was affected in 6.5%. ES are predominant in females and IS in males (p < 0.0001). In the adult-aged population, the ES and PI are predominant, while in the young, the IS predominate (p < 0.0001). ACTH concentration was greater in the ES vs. IS (p < 0.05). α-MSH did not present significant differences according to tumour size, showing a negative correlation (r = −0.47; p < 0.01) vs. ACTH. Differences in adenoma size according to gender and their age-related frequency of apparition could be because of different origins of the corticotrophinoma.     

Expression of the ACTH receptor, steroidogenic acute regulatory protein, and steroidogenic enzymes in canine cortisol-secreting adrenocortical tumors

Studies of human adrenocortical tumors (ATs) causing Cushing's syndrome suggest that hypersecretion of cortisol is caused by altered expression of steroidogenic enzymes and that steroidogenesis can only be maintained when there is expression of the ACTH receptor (ACTH-R). Here we report the screening for the mRNA expression of the ACTH-R, steroidogenic acute regulatory protein (StAR), cholesterol side-chain cleavage enzyme, 3β-hydroxysteroid dehydrogenase, 21-hydroxylase (all in 38 cortisol-secreting ATs), 17α-hydroxylase, and 11β-hydroxylase (both in 28 cortisol-secreting ATs). Real-time PCR (RT-PCR) was applied in all samples and was compared with that in normal canine adrenal glands. Messenger-RNA encoding StAR, steroidogenic enzymes, and ACTH-R were present in both normal adrenal glands and cortisol-secreting ATs. The amounts of mRNA encoding StAR and enzymes of the steroidogenic cluster needed for cortisol production did not differ significantly between either adenomas or carcinomas and normal adrenal glands. The amount of mRNA encoding ACTH-R was significantly lower in carcinomas than in normal adrenal glands (P = 0.008). In conclusion, RT-PCR analysis revealed no overexpression of StAR and steroidogenic enzymes in canine cortisol-secreting ATs. Significant downregulation of ACTH-R in carcinomas might be associated with the malignant character of the AT.     

The Prognostic Value of Perioperative Profiles of ACTH and Cortisol for Recurrence after Transsphenoidal Hypophysectomy in Dogs with Corticotroph Adenomas

Background

Transsphenoidal hypophysectomy is an effective treatment for dogs with pituitary‐dependent hypercortisolism (PDH). However, long‐term recurrence of hypercortisolism is a well‐recognized problem, indicating the need for reliable prognostic indicators.

Objectives

The aim of this study was to evaluate the prognostic value of perioperative plasma ACTH and cortisol concentrations for identifying recurrence of hypercortisolism after transsphenoidal hypophysectomy.

Animals

A total of 112 dogs with PDH that underwent transsphenoidal hypophysectomy met the inclusion criteria of the study.

Methods

Hormone concentrations were measured preoperatively and 1–5 hours after surgery. Both absolute hormone concentrations and postoperative concentrations normalized to preoperative concentrations were included in analyses. The prognostic value of hormone concentrations was studied with Cox''s proportional hazard analysis.

Results

Median follow‐up and disease‐free period were 1096 days and 896 days, respectively. Twenty‐eight percent of patients had recurrence, with a median disease‐free period of 588 days. Both absolute and normalized postoperative cortisol concentrations were significantly higher in dogs with recurrence than in dogs without recurrence. High ACTH 5 hours after surgery, high cortisol 1 and 4 hours after surgery, high normalized ACTH 3 hours after surgery, high normalized cortisol 4 hours after surgery and the random slope of cortisol were associated with a shorter disease‐free period.

Conclusions and clinical importance

Individual perioperative hormone curves provide valuable information about the risk of recurrence after hypophysectomy. However, because no single cutoff point could be identified, combination with other variables, such as the pituitary height/brain area (P/B) ratio, is still needed to obtain a good estimate of the risk for recurrence of hypercortisolism after hypophysectomy.