Introduction: Cushings syndrome (CS) due to macronodular adrenal hyperplasia ACTH-independent (MAHAI) is rare. Regulation of cortisol secretion by G-protein-coupled receptors (GPCRs) aberrantly expressed is frequently found in MAHAI. Various aberrant receptors have been reported, mostly: GIP, vasopressin, beta-adrenergic, LH/hCG and serotonin.
Case report: 61 years old woman. Medical history: type 2 diabetes, hypertension, obesity, dyslipidaemia and severe sleep apnoea. Treatment: metformin, insulin, lyxisenatide, irbesartan-hydrochlorothiazide, torasemide, diltiazem, acetyl salicylic acid and atorvastatin. Physical examination: moon face, centripetal obesity, abdominal striaes and thin extremities. Laboratory evaluation: HbA1c 8.4%, TSH 2.06 μIU/ml, serum cortisol: at 0800 h:17.2 μg/dl (525), overnight dexamethasone suppression (1 mg): 5.3 μg/dl, after 0.5 mg dexamethasone every 6 h for 48 h suppression: 5.03 μg/dl, after nocturnal 8 mg dexamethasone suppression: 5.7 μg/dl. Urinary free cortisol repeatedly normal (49.4 and 24 μg per day), salivary cortisol repeatedly raised (0.382 and 0.292 ng/ml). ACTH 2.83, others adrenal hormonal profile normal. With these findings, the suspected diagnosis was Cushings syndrome. CT: adrenal glands enlarged with homogeneous hypodense nodules (3.3×2.6 cm right; 3.2×1.9 cm left). Because of the known association between MAHAI and aberrant GPCRs some tests were performed: posture test, standard mixed meal, LHRH (100 mg i.v.), metroclopramide (10 mg orally), glucagon (1 mg i.v.) and AVP (10 IU i.m.). Positive response (50% increase in plasma cortisol levels) in the standard mixed test and metroclopramide test (indicating serotonin and GIP aberrant receptors). Right adrenalectomy is planned.
Conclusion: In patients with MAHAI aberrant GPCRs can be identified. The detection of such aberrant receptors is necessary in all patients with MAHAI. Identification of these receptors can provide specific pharmacological treatment with or without adrenalectomy.