Study On Clinical Features And Pathogenesis Of ACTH-independent Bilateral Macronodular Adrenal Hyperplasia

Objectives:To analyze clinical features and pathogenesis of patients with AIMAH.Methods:1. Twenty cases with ACTH-independent bilateral macronodular adrenal hyperplasia (AIMAH) and thirty-three cases with adrenocortical cortisol-producing adenoma (ACS) diagnosed in Chinese PLA General Hospital from 1998 to 2011 were analyzed retrospectively.2. Seven patients with AIMAH and seven patients with ACS were investigated for plasma cortisol responses to various stimuli:upright posture, mixed meal, GnRH, the serotonin 5-HT4 agonist metoclopramide, the vasopressin analogue desmopressin, glucagon, and ACTH. We can deduce the expression of adrenal ectopic hormone receptor.Results:1.①AIMAH was more frequent in males than in females, with a ratio of 3:2. Most cases presented in the fifth decades, and the diagnosis was usually delayed by a mean of 6.8 years from the onset.②Most cases visited hospital because of adrenal incidentaloma, without overt presentation of Cushing's syndrome (CS). The most common clinical presentations were hypertension and IGT/DM. The majority cases were sporadic, familial cases were in the minority.③The most characteristic laboratory findings included partially or totally suppressed ACTH and unsuppressed cortisol secretion following dexamethasone suppression test.④24-hour dynamic plasma ACTH and cortisol monitoring could be a useful diagnostic method for AIMAH with subclinical CS.⑤The level of plasma cortisol and 24hUFC in patients with AIMAH were lower than those in patients with ACS, the suppression ratio of HDDST in patients with AIMAH was higher than those in patients with ACS. ⑥Bilateral adrenal macronodular changes could be visualized through CT scan, with the diameter from 2.0cm to 3.5cm.⑦Pathology feature was macronodular adrenal hyperplasia.⑧Medical therapy and unilateral adrenalectomy could just relieve the symptoms. Bilateral adrenalectomy was the most useful treatment.2.①In AIMAH patients, five cases (5/7) responded to at least one stimuli test, one case (1/7) responded to two stimuli tests. Among the 6 stimuli tests, posture test's positive rate was the highest, with cortisol increase 147%±106%; other stimuli tests showed no positive respond. Five cases (5/5) responded to exogenous ACTH stimulation, with cortisol increase 335%±120%.②In ACS patients,only one case (1/6) responded to posture test, with cortisol increase 128%. Two cases (2/3) responded to exogenous ACTH stimulation test, with cortisol increase 66% and 50%.Conclusions:1. AIMAH is an infrequent cause of CS, the most common clinical presentation is subclinical CS. It's marked clinical features are ACTH-independent CS and macronodular adrenal hyperplasia.2. Patients with AIMAH may express ectopic adrenal receptors of p-adrenergic receptor and/or angiotensin-Ⅱreceptor. The presence of ectopic receptors are found to be less frequently present in ACS.