ARMC5 mutation in a Portuguese family with primary bilateral macronodular adrenal hyperplasia (PBMAH)
PBMAH is a rare etiology of Cushing syndrome (CS). Familial clustering suggested a genetic cause that was recently confirmed, after identification of inactivating germline mutations in armadillo repeat-containing 5 (ARMC5) gene. A 70-year-old female patient was admitted due to left femoral neck fr...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Bioscientifica
2017-03-01
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| Series: | Endocrinology, Diabetes & Metabolism Case Reports |
| Online Access: | https://www.edmcasereports.com/articles/endocrinology-diabetes-and-metabolism-case-reports/10.1530/EDM-16-0135 |
| Summary: | PBMAH is a rare etiology of Cushing syndrome (CS). Familial clustering suggested a genetic cause that was recently
confirmed, after identification of inactivating germline mutations in armadillo repeat-containing 5 (ARMC5) gene. A
70-year-old female patient was admitted due to left femoral neck fracture in May 2014, in Orthopedics Department.
During hospitalization, hypertension (HTA) and hypokalemia were diagnosed. She presented with clinical signs of
hypercortisolism and was transferred to the Endocrinology ward for suspected CS. Laboratory workup revealed: ACTH
<5 pg/mL; urinary free cortisol (UFC), 532 μg/24 h (normal range: 20–90); failure to suppress the low-dose dexamethasone
test (0.5 mg every 6 h for 48 h): cortisol 21 μg/dL. Abdominal magnetic resonance imaging (MRI) showed enlarged nodular
adrenals (right, 55 × 54 × 30 mm; left, 85 × 53 × 35 mm), and she was submitted to bilateral adrenalectomy. In 2006, this
patient’s 39-year-old daughter had been treated by one of the authors. She presented with severe clinical and biological
hypercortisolism. Computed tomography (CT) scan showed massively enlarged nodular adrenals with maximal axis of
15 cm for both. Bilateral adrenalectomy was performed. In this familial context of PBMAH, genetic study was performed.
Leucocyte DNA genotyping identified in both patients the same germline heterozygous ARMC5 mutation in exon 1
c.172_173insA p.I58Nfs*45. The clinical cases herein described have an identical phenotype with severe hypercortisolism
and huge adrenal glands, but different ages at the time of diagnosis. Current knowledge of inheritance of this disease, its
insidious nature and the well-known deleterious effect of hypercortisolism favor genetic study to timely identify and treat
these patients. |
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| ISSN: | 2052-0573 2052-0573 |