How Low Can You Go? Unlocking the Mystery of Persistent Hypokalemia in Pregnancy

Introduction: Geller syndrome is a very uncommon cause of persistent hypokalemia during pregnancy, first described by Geller et al in 2000, which is caused by a gain of function mutation in the mineralocorticoid receptor gene MRS810L which allows progesterone to activate the mineralocorticoid receptor during pregnancy, causing both hypertension and persistent hypokalemia. We present one such case. Case Description: 29-year-old G2P1 female at 33 weeks of gestation admitted for preeclampsia with a BP 180/100, also noted to have persistent asymptomatic hypokalemia despite adequate repletion (serum potassium 2.5mMol/L). Her 24 hour urine protein was 0.6g/day. Her urine potassium was 20 mmol/L, urine creatinine 68 mg/dl and random urine potassium to creatinine ratio was 3.3, suggesting renal potassium wasting. Serum renin 2.6ng/ml/h, Serum aldosterone 1ng/dl, and aldosterone renin ratio was 0.3 signifying suppressed aldosterone. She was managed conservatively, and subsequently underwent cesarean section at 34 weeks of gestation after failed induction of labor. 24 hours after delivery, her blood pressure and potassium level returned to normal without needing antihypertensive medications or further potassium supplementation. Discussion: As mentioned above, Geller syndrome is a rare form of monogenic hypertension, which results from a gain of function mutation in the mineralocorticoid receptor gene MRS810L. It typically presents with hypertension and persistent hypokalemia in the third trimester of pregnancy. In humans, progesterone works as an antagonist on mineralocorticoid receptors but in Geller syndrome, this mutation causes progesterone into an agonist of the mineralocorticoid receptors which causes activation of mineralocorticoid receptors during the third trimester of pregnancy due to high progesterone state, causing hypertension and hypokalemia refractory to correction. Amiloride can be used to treat hypokalemia with some benefit. Interestingly it’s been noted that Spironolactone, even though a mineralocorticoid receptor antagonist, seems to have an agonist effect on the mutated MR receptor gene worsening the hypokalemia. We must consider Geller syndrome in the differential for hypertension and persistent hypokalemia during pregnancy. Recognition of this entity can prevent unnecessary early delivery, especially if the patient does not actually have preeclampsia.