Adrenal Cushing's Syndrome Due to Bilateral Macronodular Adrenal Hyperplasia: Prediction of the Efficacy of .BETA.-blockade Therapy and Interest of Unilateral Adrenalectomy

Abstract

Abstract. Bilateral adrenalectomy is the standard treatment for Cushing's syndrome (CS) related to aCTh-independent bilateral macronodular hyperplasia (AIMAH), although it imposes life-long adrenal insufficiency. This study reports a clinical case in order to discuss the clinical interest of pharmacological β-blockade of illegitimate membrane receptors and unilateral adrenalectomy as alternatives to bilateral adrenalectomy for treatment of CS due to aiMah. evidence for cortisol stimulation by upright posture and insulin-induced hypoglycemia in a patient with CS related to aiMah led us to try β-blockers as a therapeutic test and then as a first line treatment. Thus, a 3-day β-blocker test (320mg/d propranolol) induced normalization of cortisol secretion, with return of hypercortisolism at the end of the test. a long term treatment with 320mg/d propranolol allowed sustained normalization of cortisol secretion and progressive disappearance of Cushingoid features but after 8 months the patient complained of Raynaud's syndrome and fatigue. Lowering propranolol dosage or switching to atenolol was less efficient to reduce cortisol levels. Unilateral adrenalectomy was then performed as a second line treatment, leading to normalisation of the 24h urinary cortisol without adrenal insufficiency. Long term control of blood pressure and glycemia were observed during a 7-year follow-up without β-blocker. In conclusion, a 3-day propranolol test may identify patients with AIMAH who can benefit from a long term β-blocker treatment. In case of intolerance to β-blocking agents, unilateral adrenalectomy may allow for long term control of Cushing's syndrome related to AIMAH without adrenal insufficiency.

Multiple aberrant hormone receptors in Cushing's syndrome

“…Octreotide or pasireotide resulted in shortterm control in a BMAH patient with aberrant expression of GIPR presumably because GIP suppression escapes as downregulation of somatostatin receptors in K cells occurs during chronic administration of the long-acting agonists (41,142,143). Administration of antagonists of V1aR, AT1R or b-AR reduced cortisol levels in patients with aberrant response to upright posture (144,145,146). ACTH-receptor antagonists significantly inhibited cortisol secretion in vitro in perifused BMAH tissues from patients with abnormal plasma cortisol responses to GIP because GIPR activation partially stimulated cortisol secretion by stimulating ACTH secretion in a paracrine way to control cortisol synthesis (34).…”

Biochemical and clinical benefits of unilateral adrenalectomy in patients with subclinical hypercortisolism and bilateral adrenal incidentalomas

“…These studies, however, comprise of either case reports or a small number of patients, most have a short time of follow-up and, importantly, there is no control group. The population included in these studies comprises mainly of patients with overt Cushing's syndrome due to macronodular or micronodular adrenal hyperplasia (11,16,17,18,19). Two studies included patients with subclinical hypercortisolism (12,20).…”

MECHANISMS IN ENDOCRINOLOGY: Autocrine/paracrine regulatory mechanisms in adrenocortical neoplasms responsible for primary adrenal hypercorticism

“…Abnormal sensitivity to catecholamines has been suspected in patients who displayed plasma cortisol responses to tests inducing elevation of endogenous cathecholamines, such as upright posture or insulin-induced hypoglycemia (96). Control of hypercortisolism by administration of propranolol, a b-blocker, as well as increase in plasma cortisol levels in response to infusion of isoproterenol, a b-adrenergic receptor agonist, have revealed the implication of b-adrenergic receptors in the control of steroidogenesis (96,98,99,100). Aberrant expression of b-adrenergic receptors in adenoma and macronodular hyperplasia tissues has been demonstrated in vitro by PCR and binding experiments (93,96,97).…”