Poster Presentation Annual Meetings of the Endocrine Society of Australia and Society for Reproductive Biology and Australia and New Zealand Bone and Mineral Society 2016

Diagnosis of late-presenting 11β-hydroxysteroid dehydrogenase deficiency Type 2 (11βHSD2) by gas-chromatography/mass-spectrometric profiling of urinary cortisol metabolites (#395)

Joseph Montalto 1 , Jan Awadallah 1 , Alan McNeil 1 , Nilika Wijeratne 1 2 , David Mitchell 1 , Anthony Boers 3
  1. Biochemistry, Dorevitch Pathology, Heidelberg, Victoria, Australia
  2. Department of Medicine , Monash University, Clayton, Victoria, Australia
  3. Department of Medicine, Traralgon Hospital, Traralgon, Victoria, Australia

Background: 11βHSD2, also known as Apparent Mineralocorticoid Excess Syndrome (AME) is a rare genetic disorder, typically causing severe hypertension, hypokalaemia, metabolic alkalosis, low renin and low aldosterone.  AME usually manifests early in life with low birth weight, severe hypertension, failure to thrive, polydipsia and polyuria. Its biochemical hallmark is the presence of an abnormal urine steroid pattern, revealing an elevated ratio of tetrahydrocortisol (THF) plus 5α-tetrahydrocortisol (5α-THF) to tetrahydrocortisone (THE). Additionally, chronic licorice ingestion may inhibit 11βHSD2, resulting in an acquired form of AME.

Case:  A 60 yr Caucasian female was admitted to hospital with BP 230/120, conscious collapse, dizziness, declining mobility and weight loss. Background history revealed fatigue, palpitations, poor appetite, nausea with diarrhoea for two months, hypertension over 20 years and hyperthyroidism. There was no history of diuretic, laxative or licorice abuse and no Cushinoid features. Investigations showed Na 142, K 4.2 with chronically low K requiring constant correction, an  aldosterone <50 pmol/L (100-950) and  renin  3 mIU/L (10-50) with normal urinary metanephrines. GC-MS urine steroid profiling demonstrated a significantly elevated THF+5α-THF to THE ratio with a low normal THE.  Given the history of severe HT, low K, low renin and low aldosterone, the steroid pattern was consistent with 11βHSD2 deficiency. Spironolactone was commenced with excellent response in BP and K.

Discussion:  Given that 11βHSD2 typically manifests in childhood, its presentation at a late age is unusual. This case may represent a mild form of 11βHSD2, and the question remains as the extent to which subtle abnormalities in the mineralocorticoid receptor and 11βHSD2 mechanisms may contribute to essential low renin HT in adults.

We recommend that hypertensive patients with low renin and low aldosterone should be screened for abnormal cortisol metabolism to exclude 11βHSD2.