Case report: Bilateral adrenal macronodular hyperplasia

Abstract

A 62-year old female presented with weight gain, arterial hypertension and an increased sweating. She received only L-thyroxine for autoimmunthyroidism. The patient was postmenopausal and her menses had been regularly before. Previous testings had shown a normal TSH and urinary cortisol excretion. ACTH was low, and cortisol was inadequately suppressed after 1mg and 8mg dexamethasone. A CT scan revealed bilaterally enlarged adrenal glands (4×3cm and 6×3cm). On clinical examination the woman was obese (BMI 38kg/m2) without typical signs of Cushing's syndrome or hyperandrogenism. ACTH was low (5 ng/l), morning cortisol, aldosterone, renin, the aldosterone/renin ratio, urinary cortisol and catecholamine excretion were normal. Cortisol was 241 nmol/l and 187 nmol/l after a 1mg and 8mg dexamethasone overnight test, respectively. 17-OH-progesterone increased after ACTH to 1569 ng/dl, which raised the possibility of congenital adrenal hyperplasia. No mutation, however, in the CYP21 gene could be detected. A rare condition caused by aberrant adrenal receptor expression (e.g. GIP, vasopressin, β-adrenergic, LH/hCG, 5-HT4, angiotensin) has been shown to cause hypercortisolism and adrenocorticotropin-independent bilateral adrenal macronodular hyperplasia (AIMAH). Further investigations revealed no meal- or orthostasis-induced increase of cortisol ruling out e.g. aberrant GIP, vasopressin, β-adrenergic or angiotensin receptor expression. Furthermore, no cortisol stimulation after LHRH administration was observed. However, metoclopramide, which activates 5-HT4 receptors, yielded a marked increase in cortisol (from 104 to 187 ng/ml) with ACTH being suppressed during the test. Taken together, the most likely diagnosis is AIMAH with subclinical Cushing's syndrome caused by an aberrant expression or overexpression of 5-HT4 receptors in the adrenal tissue. Since AIMAH has not been associated with malignancy and since arterial hypertension could be well controlled by standard treatment, we did not recommend surgery but decided to carefully monitor the patient.