Abstract: TH-PO1126

Primary Aldosteronism Associated with a Mutation of CACNA1H

Session Information

Category: Fluid, Electrolytes, and Acid-Base

  • 704 Fluid, Electrolyte, Acid-Base Disorders


  • Wulczyn, Kendra E, University of California San Francisco, San Francisco, California, United States
  • Nussbaum, Robert L, Invitae Corp, San Francisco, California, United States
  • Lo, Lowell J., None, San Francisco, California, United States
  • Perez-Reyes, Edward, University of Virginia, Charlottesville, Virginia, United States
  • Park, Meyeon, UCSF, San Francisco, California, United States

Several genetic mutations have been described in rare forms of primary aldosteronism (PA). We report a case of aldosteronism with hypokalemia and hypotension, found to have a mutation of CACNA1H, encoding a voltage-gated calcium channel (CaV3.2) expressed in adrenal glomerulosa.


A 31 year old female with type III Ehlers-Danlos syndrome and postural orthostatic tachycardia syndrome (POTS) presented for evaluation of chronic hypokalemia. The patient was receiving infusions of potassium every 2-4 weeks (baseline K 2.6-3.6 mmol/L) for profound weakness. Prior evaluation had revealed elevated plasma aldosterone level (38 ng/dL) and suppressed renin (0.17 pg/dl), and MRI demonstrated normal appearing adrenal glands. Low-dose spironolactone was initiated, which improved the hypokalemia, yet the patient still required monthly potassium infusions for symptoms. A laboratory assessment was made pre- and post-hydration with 2L IVF, supplemented with 25 mEq K and 2.5g Mg (shown in table below). Results demonstrated persistently elevated aldosterone level despite volume repletion (of note, patient was unable to stop spironolactone for the testing). During this course, results of whole exome sequencing (Personalis, Inc.) revealed a de novo loss-of-function missense mutation, R890H, in the voltage-sensing domain of the CACNA1H gene.


POTS has been associated with both increased and decreased activity of the RAAS system; however, in this patient, laboratory testing pre- and post-fluid resuscitation suggest aldosterone secretion was independent of volume status. Therefore, the mutation of CACNA1H, not previously described, is the likely cause of pathologic aldosterone secretion. CaV3.2 has been implicated in genetic forms of PA in which a mutation to CACNA1H results in increased intracellular Ca2+, the signal for cholesterol transport into mitochondria and induction of steroidogenesis. Unique to our case is the absence of hypertension experienced by this patient, expanding our understanding of the different phenotypes associated with mutations of CACNA1H.

Aldosterone (ng/dl)1745
Plasma Renin Activity (pg/dl)0.230.27
Potassium, serum (mmol/L)3.84.1
Potassium, 24-hr urine (mmol/d)38.561.4
Sodium, 24-hr urine (mmol/d)9499