Unilateral Adrenalectomy Improves Insulin Resistance and Diabetes Mellitus in a Patient with ACTH-Independent Macronodular Adrenal Hyperplasia

Abstract

Abstract. ACTH-independent macronodular adrenal hyperplasia (AIMAH) is a rare cause of Cushing's syndrome. Bilateral adrenalectomy is considered to be a standard therapy for AIMAH, although lifetime replacement of glucocorticoids is necessary after the procedure. This paper describes a subject with AIMAH who underwent unilateral adrenalectomy of the predominantly enlarged gland and subsequently displayed an improvement in insulin resistance and diabetes mellitus, the cardinal symptoms before the operation, concomitant with alleviation of abnormal cortisol secretion. The patient was a 61-year-old man with a body mass index of 25.6 kg/m 2 . He was diagnosed as having diabetes mellitus, hypertension, and hyperlipidemia at 50 years of age. Eight years after diagnosis, bilateral enlargement of the adrenal glands was revealed by chance upon computed tomography of the abdomen. Typical manifestations of Cushing's syndrome were not demonstrated. Basal levels of serum and urinary cortisol had not increased, although the serum cortisol level displayed no circadian rhythm and no response to the administration of dexamethasone. Despite sulfonylurea treatment, the patient's HbA 1C level was as high as 7.6% (normal range 4.3-5.8%). Fasting insulin concentration was increased to 42.6 mU/ml, and the homeostasis model insulin resistance index (HOMA-R) was calculated to be 15.5 (with a normal range of less than 2.5), indicating severe insulin resistance. Unilateral adrenalectomy of the predominantly enlarged gland revealed that the resected gland consisted of multiple nodules of various sizes. Based on endocrinological, radiological, and pathological findings, a diagnosis of AIMAH was made. Ten months after the unilateral adrenalectomy, cortisol circadian rhythms were restored, and serum cortisol concentration was suppressed in response to the administration of low doses of dexamethasone, suggesting an improvement in the cortisol secretory pattern. Levels of HbA 1C , fasting insulin, and HOMA-R decreased to 5.7%, 12.7mU/ml, and 2.2, respectively. An improvement in hyperlipidemia was also observed. Insulin resistance and glucose intolerance are recognized as features of mild hypercortisolism. In the present case, unilateral adrenalectomy was effective in ameliorating insulin resistance and improving glycemic control. Unilateral adrenalectomy might be an alternative therapy for improvement of glucose and lipid metabolism in subjects with AIMAH.

Classification, diagnosis and treatment of ACTH-independent macronodular adrenal hyperplasia

“…Ogura and colleagues have reported unilateral or subtotal adrenalectomy as another choice of therapy, which could avoid life-long glucocorticoid replacement and is effective in improving abnormal cortisol secretion. 7 In our opinion, it is reasonable to remove the obviously diseased adrenal gland and first confirm it pathologically. Whether to remove the other adrenal gland depends on clinical and biochemical changes at the later time.…”

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).…”

“…Alternate options include a conservative approach with rigorous management of co-morbidities or excision of the largest lesion, based on observations that the size of the adrenal lesion correlates with the degree of cortisol excess. Unilateral adrenalectomy therefore has been suggested as an attractive option due to its lower complications, but the evidence on its efficacy is scarce (10,11,12). In this study we aimed to compare the biochemical and clinical long-term outcome of unilateral adrenalectomy vs a conservative approach in patients with bilateral AIs.…”

Unilateral adrenalectomy can be an alternative therapy for infantile onset Cushing' s syndrome caused by ACTHindependent macronodular adrenal hyperplasia with McCune-Albright syndrome

“…In adults, unilateral adrenalectomy of the larger gland can be considered as an alternative therapy for AIMAH, when the other gland is not markedly enlarged [7][8][9]. Iacobone et al reviewed seven adult patients with AIMAH who underwent unilateral adrenalectomy of the larger gland.…”

“…This can effectively ameliorate Cushingoid appearance and hypercortisolism; however, lifetime steroid replacement therapy is required after this operation. Recently, there have been several reports of unilateral adrenalectomy for AIMAH in adult patients successfully improving clinical symptoms and endocrinological status in Cushing's syndrome, particularly in cases with definite asymmetric involvement [7][8][9]. However, to our knowledge, there have been no reports of unilateral adrenalectomy for children with AIMAH resulting from MAS.…”