A Case of Apparent Mineralocorticoid Excess Responsible to Dexamethasone Caused By a Novel HSD11B2 Mutation

Presentation Number: SAT 376
Date of Presentation: April 1st, 2017

Tania A Bachega*1, Andresa S Rodrigues2, Rosa Paula Mello Biscolla3, Décio Mion4 and Marcello D Bronstein5
1Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil, 2Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil, 3Grupo Fleury, Sao Paulo, Brazil, 4Faculdade de Medicina, Universidade de São Paulo, Sao Paulo, Brazil, 5Disciplina de Endocrinologia e Metabologia, Unidade de Neuroendocrinologia do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil.


autosomal recessive disorder characterized by early-onset hypokalemic hypertension and low renin and aldosterone levels. The disease is caused by HSD11B2 gene mutations, which result in impaired peripheral metabolism of cortisol to cortisone, leading to increased urinary-free cortisol to cortisone ratio. AMES therapy is based on spironolactone and potassium supplementation; nevertheless, the use of dexamethasone remains controversial. Objective: to report a female patient with AMES responsible to dexamethasone therapy carrying a new HSD11B2 mutation. Subject: a 20 yrs old female patient born with normal weight and height and normal external genitalia. She developed hypertension during childhood and was treated with spironolactone and enalapril, remaining with inadequate blood pressure (BP) control. Menarche occurred at 13 yrs and final height was close to midparental height, 154 and 159cm, respectively. Parents were not consanguineous and presented with “mild essential” hypertension. Methods: free salivary cortisol and free-urinary cortisol and cortisone levels were measured by LC-MS/MS, serum ACTH levels by electrochemiluminometric assay, aldosterone and PRA levels by RIE assays and serum cortisol by competitive electrochemiluminescence assay. DNA samples were available from the proband and mother, HSD11B2 gene having been PCR amplified and submitted to automated sequencing.Results: clinical evaluation identified left ventricular hypertrophy and renal ultrasonography ruled out the presence of arterial stenosis. AMES was diagnosed through the following laboratorial analysis: Na 144 mEq/L, K 2.4 mEq/L, aldosterone 2.0 ng/mL and PRA 0.1 ng/mL/h (aldosterone/PRA ratio: 20). Late-night salivary cortisol and ACTH levels were 329 µg/dL (reference range: <100 µg/dL) and 5 pg/mL (reference range: 7-63 pg/mL), respectively, the 24-h urinary free cortisol to cortisone ratio was significantly increased (9.3/<4). A novel homozygous p.Y295* mutation at HSD11B2 exon 5 (c.885C>A) was identified, also found in heterozygosis in her mother’s DNA sample. The novel mutation was not identified in the 1000 Genomes and in silico three dimensional modeling showed a strongly truncated protein suggesting a severe damage on protein sequence (P=1). At adulthood, despite the use of spironolactone, enalapril and potassium supplemental, patients still remained with low serum potassium levels and inadequate BP control. The dexamethasone therapy (0.75mg) allowed adequate BP control and late-night salivary cortisol decreased to 47 ug/dL. After 6 months, dexamethasone doses decreased to 0.25 mg/day. Conclusion: A new mutation in the HSD11B2gene has been described, expanding the molecular AMES diagnosis. The achievement of clinical control after the introduction of dexamethasone therapy could be related to the patients’ genetic background as previously described in the literature.


Nothing to Disclose: TAB, ASR, RPMB, DM, MDB