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 V(2)). 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 V(2) 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(1b)R and V(2) receptor was present, but in ATs, V(2) receptor-immunopositive cells were detected. In conclusion, QPCR analysis did not reveal overexpression of LH, GIP, V(1a), V(1b), or V(2) receptors in the ATs. However, the ectopic expression of GIP and V(2) receptor proteins in tumorous zona fasciculata tissue may play a role in the pathogenesis of canine cortisol-secreting ATs.

ACTH-independent hyperadrenocorticism due to food-dependent hypercortisolemia in a dog: a case report.

In addition to adrenocortical tumours, aberrant expression of functional hormone receptors in the adrenal cortex may cause adrenocorticotrophic hormone (ACTH)-independent hyperadrenocorticism. Here we report on a 6 year old Vizsla dog in which ACTH-independent hyperadrenocorticism was associated with meal-induced hypercortisolemia. Diagnosis was based on history, physical findings, biochemical changes, and elevation of the urinary corticoid/creatinine ratio (UCCR) on two consecutive days (11 and 8.3 x 10(-6), reference range <8.3 x 10(-6)). Basal plasma ACTH concentration was found by repeated measurements to be suppressed (<1 ng/L, reference range 5-85 ng/L) and administration of corticotrophin releasing hormone (CRH) resulted in a minor increase (to 6 ng/L), consistent with ACTH-independent hyperadrenocorticism. Ultrasonography and computed tomography revealed two uniformly enlarged adrenal glands. Magnetic resonance imaging of the pituitary area showed a non-enlarged, normally enhancing pituitary gland. Based on these results, expression of functional aberrant adrenocortical receptors was suspected and the possibility of food-dependent hyperadrenocorticism was explored. The UCCR on two separate occasions rose from 11 and 8 x 10(-6) before a meal to 25 and 23 x 10(-6) at 3 h after ingestion of a meal, respectively. There was a corresponding increase in plasma cortisol concentration (from 90 to 150 nmol/L), while plasma ACTH concentration remained low or undetectable. Consistent with the diagnostic criteria for food-dependent hyperadrenocorticism in humans, administration of octreotide completely prevented meal-induced hypercortisolemia. The dog was treated successfully with the cortisol-synthesis-inhibitor trilostane (2h before meal), and at 26 months after the final diagnosis the dog is still in good condition. The combination of (1) low plasma ACTH concentration in the absence of an adrenocortical tumour, (2) an increase of >100% in UCCR after ingestion of a meal, (3) prevention of the meal-induced increase in plasma cortisol concentration by octreotide, and (4) reversal of signs of hypercortisolism by administration of trilostane a few hours before the meal led to the diagnosis of food-dependent hyperadrenocorticism in this dog.