Years of hypokalemia: A case report

INTRODUCTION

Gitelman syndrome (GS) is a salt-losing tubulopathy with an estimated prevalence of about 1 in 40,000 individuals. It typically presents during adolescence or adulthood with muscle weakness, fatigue, tetany, or abdominal pain. The symptoms are generally milder and appear later than those of Bartter syndrome (BS). Biochemical findings include hypokalemia, metabolic alkalosis, hypomagnesemia, and often low or normal urinary calcium. The underlying defect involves impaired sodium and chloride reabsorption in the distal tubule, resulting in excessive urinary potassium and magnesium losses.^[1]

Management focuses on correcting electrolyte imbalances and minimizing renal losses. Potassium and magnesium chloride supplementation is the cornerstone of therapy. Potassium-sparing diuretics such as amiloride, spironolactone, or eplerenone can be added to enhance potassium retention and reduce magnesium excretion. Amiloride acts by blocking epithelial sodium channels in the distal nephron, thereby decreasing sodium reabsorption and reducing potassium and magnesium loss. Patients are encouraged to maintain liberal salt intake and to avoid medications that can worsen hypokalemia or prolong the QT interval, such as certain antiarrhythmics, proton pump inhibitors, or aminoglycosides.

CASE REPORT

The patient, born to consanguineous parents, presented with limb cramps, myalgia, and two episodes of loose stools. Initial laboratory investigations revealed a serum potassium level of 2.6 mEq/L. Her mother reported multiple similar, unexplained, and uninvestigated episodes of hypokalemia since childhood. On examination, she was stable with a blood pressure of 112/68 mmHg, and her systemic examination was unremarkable.

Further evaluation showed urinary potassium of 33.1 mEq/L, a transtubular potassium gradient (TTKG) of 8, indicating renal potassium loss, and a venous pH of 7.53, consistent with metabolic alkalosis. Plasma renin activity was markedly elevated (>500 mIU/L), and aldosterone was high-normal. Urinary chloride (163.6 mEq/L) ruled out vomiting-induced hypokalemic alkalosis. Serum magnesium was 1.5 mg/dL (low), whereas urinary calcium excretion was normal (3.2 mmol/day). The patient denied any use of diuretics, laxatives, or herbal medications [Table 1]. A complete endocrine evaluation, including a steroid panel to rule out any mild forms of congenital adrenal hyperplasia (CAH), was normal.

Whole-exome sequencing detected a pathogenic heterozygous mutation in the SLC12A3 gene (exons 14 and 15), confirming GS [Figure 1]. Although the disease is autosomal recessive, the genotype suggested a possible compound heterozygous variant. She was started on amiloride 20 mg once daily along with oral potassium and magnesium supplements, leading to normalization of electrolyte levels and symptomatic improvement.

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Figure 1:

Genetic report.

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DISCUSSION

Hypokalemia, defined as serum potassium < 3.5 mEq/L, can arise from redistribution into cells, decreased intake, or increased losses through the gastrointestinal tract, skin, or kidneys.^[3] It is one of the most common electrolyte abnormalities encountered in everyday clinical practice, affecting about 2–3% of hospitalized patients. Its mechanisms can be categorized into artefactual hypokalemia, intracellular potassium redistribution, and true depletion of body potassium stores, with potassium loss being the predominant cause. Artefactual or pseudohypokalemia, though rare, is usually seen in samples from patients with severe leukocytosis or thrombocytosis, where potassium continues to be taken up by cells after blood collection. Intracellular redistribution of potassium, responsible for approximately 10–15% of hypokalemia cases, is often related to insulin therapy, increased beta-adrenergic activity, metabolic alkalosis, and episodic paralytic disorders such as thyrotoxic periodic paralysis, which is more common among Asian populations.

In contrast, true potassium deficiency results mainly from increased losses through the gastrointestinal tract or the kidneys. Gastrointestinal losses, accounting for 30–40% of cases, are mostly due to diarrhea, often accompanied by non-anion gap metabolic acidosis. Vomiting and prolonged nasogastric suction lead primarily to hypokalemia through extracellular volume contraction and secondary renal potassium excretion. Renal potassium wasting, which accounts for 40–50% of cases, is most frequently associated with the use of loop and thiazide diuretics. Other renal causes include excess mineralocorticoid activity, such as primary hyperaldosteronism, Cushing syndrome, apparent mineralocorticoid excess, and Liddle syndrome, as well as inherited tubular disorders such as BS and GS, renal tubular acidosis, and exposure to nephrotoxic drugs such as Amphotericin B, aminoglycosides, and cisplatin. A urinary potassium < 20 mEq/L suggests extrarenal losses (e.g., diarrhea), whereas values > 20 mEq/L indicate renal potassium wasting. The urinary chloride concentration helps further define the cause, values < 20 mEq/L occur in vomiting or nasogastric suction, while > 30 mEq/L indicate renal tubular causes such as BS or GS. When hypokalemia is accompanied by metabolic alkalosis and normal blood pressure, GS and BS are the primary considerations. Both feature secondary hyperreninemia and hyperaldosteronism due to renal salt wasting, but they differ in age of onset and biochemical profile.

CONCLUSION

This case highlights the importance of considering GS in patients with chronic or recurrent hypokalemia, metabolic alkalosis, and normal blood pressure. Early recognition through clinical suspicion and genetic confirmation enables appropriate management, prevents complications, and improves quality of life.