"Triple-negative" apparent mineralocorticoid excess

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 53-73-Primary Aldosteronism & Mineralocorticoid Excess
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-53
Dganit Dinour1, Etty Osher2, Elena Dumin3, Naftali Stern2 and Karen Michele Tordjman*2
1Sheba Medical Center, Ramat Gan, Israel, 2Tel Aviv Sourasky Medical Center, Tel Aviv, Israel, 3Rambam Medical Center, Haifa, Israel
Case presentation: A 47 year-old man presented with recently discovered hypertension. He had a positive family history of hypertension. His past medical history included papillary thyroid cancer, and hypercholesterolemia. He had been polyuric (5-7 liters/d) since the age of 18. Office blood pressure was 145/100 mmHg. While a 24-hr ambulatory blood pressure (BP) recording revealed an average BP of 176/100 mmHg under 5 drugs (ACE inhibitor, calcium channel blocker, beta blocker, alpha blocker, and hydralazine). Laboratory evaluation revealed normal kidney function, however serum K+ was consistently between 3.0-3.5 mEq/l. He denied licorice ingestion. Renal artery stenosis, pheochromocytoma, and Cushing's syndrome, were ruled out. Plasma ACTH was normal. However, he repeatedly had unmeasurable plasma renin activity with low plasma aldosterone levels. Given the longstanding history of polyuria, a putative diagnosis of a mild form of apparent mineralocorticoid excess (AME) was entertained.
Methods: Gas chromatography-mass spectrometry of urinary steroid metabolites was performed. Subsequently, genomic DNA was isolated from peripheral blood cells. The coding sequence and splice-sites of HSD11B2 (AME), SCNN1A (ENaCα), SCNN1B (ENaCβ), SCNN1G (ENaCγ), and NR3C2 (MR) were amplified by PCR and directly sequenced.
Results: A normal urinary cortisol to cortisone (THF+5αTHF/THE) ratio excluded typical AME, while a mildly elevated THF+alloTHF/F ratio, indicative of a decreased A ring reduction, suggested AME type 2. Both typical AME and AME type 2 have been ascribed to mutations in the HSD11B2 gene. However, sequencing of the entire coding region of the gene failed to reveal any mutation. Furthermore, sequencing of the 3 genes composing the epithelial sodium channel complex ENaC ruled out the possibility of Liddle's syndrome. Finally, the search for a possible activating mutation in the MR gene was also negative. Spironolactone therapy succeeded in controlling both the hypertension and the hypokalemia.
Conclusions: Sequencing of 3 candidate genes failed to uncover the molecular basis for this case of adult-onset mild AME-like syndrome. This raises the possibility that a previously unidentified factor, possibly one that regulates the function of the HSD11B2 or that of the MR gene, might be the culprit, thus widening the spectrum of conditions that mimic mineralocorticoid excess hypertension. The patient’s whole genome sequencing will next be undertaken.

Nothing to Disclose: DD, EO, ED, NS, KMT

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