Conundrum in the Management of a Rare Cause of Cushing Syndrome

Wee Mee Cheng; Lit Sin Yong; Poh Shean Wong; Nor Afidah binti Karim; Noor Lita Adam

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Conundrum in the Management of a Rare Cause of Cushing Syndrome

Author: Wee Mee Cheng ¹ ; Lit Sin Yong ¹ ; Poh Shean Wong ¹ ; Nor Afidah binti Karim ¹ ; Noor Lita Adam ¹
Author Information

1. Endocrinology Unit, Department of Internal Medicine, Hospital Tuanku Ja’afar Seremban
Publication Type:Journal Article
From: Journal of the ASEAN Federation of Endocrine Societies 2026;41(S1):32-
CountryPhilippines
Language:English
Abstract: Introduction:Primary bilateral macronodular adrenal hyperplasia (PBMAH), characterized by bilateral adrenal macronodules >1 cm, is a rare genetic disease contributing to <2% of Cushing syndrome.
Case:A 56-year-old male with underlying diabetes mellitus and hypertension presented with worsening proximal muscle weakness. Detailed neurological assessment was unremarkable. Re-assessment revealed more apparent cushingoid features, prompting referral to endocrinology. Basal cortisol was markedly elevated at 957 nmol/L (145.4– 619.4 nmol/L). Unsuppressed cortisol after 1 mg overnight dexamethasone and low-dose dexamethasone test confirmed Cushing Syndrome. Suppressed adrenocorticotropic hormone (ACTH <0.33 pmol/L) suggested autonomous cortisol secretion from adrenal glands. Computed tomography adrenal reported massively enlarged hypodense multinodular adrenal glands of varying sizes. Oral ketoconazole, an adrenal steroidogenesis inhibitor, was initiated. Despite careful titration to keep serum cortisol 400–500 nmol/L, he experienced glucocorticoid withdrawal syndrome. Bilateral adrenalectomy was planned but deferred as he continued to lose weight despite persistent hypercortisolism. Extensive investigations were conducted for possible opportunistic infections or malignancy. His chest X-ray revealed a suspicious right lung cavity. Positive serum galactomannan and bronchial alveolar lavage galactomannan suggested pulmonary aspergillosis. Voriconazole was introduced, with drug-drug interaction judiciously addressed. He underwent bilateral adrenalectomy and required lifelong glucocorticoid and mineralocorticoid replacement. Histopathological report confirms bilateral macronodular adrenocortical disease. A referral to a genetic clinic was made to explore the potential hereditary basis.
Conclusion:PBMAH is a highly heterogeneous disease with variable presentation and a wide spectrum of hypercortisolism. Definitive management remained controversial and individualized. Multidisciplinary discussion is crucial, and genetic study is highly recommended for long-term prognostication and familial screening.
Full text:2026072815242536845EP_A025.pdf