Clinical Overview > Condition/ Syndrome
Search for other papers by Rachel Wurth in
Google Scholar
PubMed
Search for other papers by Crystal Kamilaris in
Google Scholar
PubMed
Search for other papers by Naris Nilubol in
Google Scholar
PubMed
Search for other papers by Samira M Sadowski in
Google Scholar
PubMed
Search for other papers by Annabel Berthon in
Google Scholar
PubMed
Search for other papers by Martha M Quezado in
Google Scholar
PubMed
Search for other papers by Fabio R Faucz in
Google Scholar
PubMed
Search for other papers by Constantine A Stratakis in
Google Scholar
PubMed
Search for other papers by Fady Hannah-Shmouni in
Google Scholar
PubMed
Summary
Primary bilateral macronodular adrenal hyperplasia (PBMAH) is a rare cause of ACTH-independent Cushing syndrome (CS). This condition is characterized by glucocorticoid and/or mineralocorticoid excess, and is commonly regulated by aberrant G-protein coupled receptor expression may be subclinical, allowing the disease to progress for years undetected. Inhibin A is a glycoprotein hormone and tumor marker produced by certain endocrine glands including the adrenal cortex, which has not been previously investigated as a potential tumor marker for PBMAH. In the present report, serum inhibin A levels were evaluated in three patients with PBMAH before and after adrenalectomy. In all cases, serum inhibin A was elevated preoperatively and subsequently fell within the normal range after adrenalectomy. Additionally, adrenal tissues stained positive for inhibin A. We conclude that serum inhibin A levels may be a potential tumor marker for PBMAH.
Learning points:
-
PBMAH is a rare cause of CS.
-
PBMAH may have an insidious presentation, allowing the disease to progress for years prior to diagnosis.
-
Inhibin A is a heterodimeric glycoprotein hormone expressed in the gonads and adrenal cortex.
-
Inhibin A serum concentrations are elevated in some patients with PBMAH, suggesting the potential use of this hormone as a tumor marker.
-
Further exploration of serum inhibin A concentration, as it relates to PBMAH disease progression, is warranted to determine if this hormone could serve as an early detection marker and/or predictor of successful surgical treatment.
Search for other papers by Sophie Comte-Perret in
Google Scholar
PubMed
Search for other papers by Anne Zanchi in
Google Scholar
PubMed
Search for other papers by Fulgencio Gomez in
Google Scholar
PubMed
Summary
Medical therapy for Cushing's syndrome due to bilateral macronodular adrenal hyperplasia (BMAH) is generally administered for a limited time before surgery. Aberrant receptors antagonists show inconsistent efficacy in the long run to prevent adrenalectomy. We present a patient with BMAH, treated for 10 years with low doses of ketoconazole to control cortisol secretion. A 48-year-old woman presented with headaches and hypertension. Investigations showed the following: no clinical signs of Cushing's syndrome; enlarged lobulated adrenals; normal creatinine, potassium, and aldosterone; normal urinary aldosterone and metanephrines; elevated urinary free cortisol and steroid metabolites; and suppressed plasma renin activity and ACTH. A screening protocol for aberrant adrenal receptors failed to show any illegitimate hormone dependence. Ketoconazole caused rapid normalisation of cortisol and ACTH that persists over 10 years on treatment, while adrenals show no change in shape or size. Ketoconazole decreases cortisol in patients with Cushing's syndrome, and may prevent adrenal overgrowth. Steroid secretion in BMAH is inefficient as compared with normal adrenals or secreting tumours and can be controlled with low, well-tolerated doses of ketoconazole, as an alternative to surgery.
Learning points
-
Enlarged, macronodular adrenals are often incidentally found during the investigation of hypertension in patients harboring BMAH. Although laboratory findings include low ACTH and elevated cortisol, the majority of patients do not display cushingoid features.
-
Bilateral adrenalectomy, followed by life-long steroid replacement, is the usual treatment of this benign condition, and alternative medical therapy is sought. Therapy based on aberrant adrenal receptors gives disappointing results, and inhibitors of steroidogenesis are not always well tolerated.
-
However, ketoconazole at low, well-tolerated doses appeared appropriate to control adrenal steroid secretion indefinitely, while preventing adrenal overgrowth. This treatment probably constitutes the most convenient long-term alternative to surgery.