Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2015) 37 EP1216 | DOI: 10.1530/endoabs.37.EP1216

ECE2015 Eposter Presentations Clinical Cases–Pituitary/Adrenal (95 abstracts)

ARMC5 mutation in a family with Cushing syndrome due to bilateral macronodular adrenal hyperplasia

Teresa Rego 1 , Fernando Fonseca 1 , Ana Agapito 1 , Stéphanie Espiard 2 , Karine Perlemoine 2 & Jérôme Bertherat 2

1Endocrinology Department, Curry Cabral Hospital, Lisbon, Portugal; 2Endocrinology Department, Hôpital Cochin, Paris, France.

Introduction: Bilateral macronodular adrenal hyperplasia (BMAH) is a rare aetiology of Cushing syndrome. Familial clustering suggests a genetic cause that was recently confirmed, after identification of inactivating germline mutations in armadillo repeat containing 5 (ARMC5) gene.

Clinical case: A 70 years old female admitted due to femoral neck fracture in May 2014, presented central obesity, rubeosis and hypertension. Laboratory work up revealed: ACTH <5 pg/ml; urinary free cortisol (UFC) – 532 ug per day (ref.v. – 20–90); serum cortisol after DST – 21 ug/dl; Abdominal MRI: enlarged nodular adrenals (right – 55×54×30 mm; left – 85×53×35 mm). She was submitted to bilateral adrenalectomy and histology confirmed cortical nodular hyperplasia (adrenal weight: right – 62 g; left – 151 g). In 2006 this patient’s 39 years old daughter had been observed by one of the authors. She presented severe clinical hypercortisolism and ACTH <5 pg/ml; UFC – 204 ug per day; serum cortisol after DST – 16.2 ug/dl; Abdominal CT scan showed bilateral enlarged nodular adrenals with maximal axis of 15 cm for both. Bilateral adrenalectomy was performed (adrenal weight: right – 68 g; left – 104 g) and pathology revealed cortical nodular hyperplasia. In this familial context of severe bilateral disease, genetic study was preformed. Leucocyte DNA genotyping identified in both patients a ARMC5 mutation in exon 1 c.172_173insA p.158Nfs*44.

Comments: The clinical cases herein described have an identical phenotype with severe hypercortisolism and huge adrenal glands, but different ages on diagnosis. Current knowledge of inheritance of this disease, its insidious nature and the well known deleterious effect of hypercortisolism favour genetic study of other family members. Since ARMC5, a tumoral supressor gene, is expressed in many organs and recent findings suggest an association of BMAH and meningeoma, a watchful follow-up is required.

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