Total colectomy for poorly controlled hypokalaemia due to Gitelman syndrome

Background

Hypokalaemia is commonly due to gastrointestinal or renal loss of potassium and can be due to redistribution resulting in cellular uptake of potassium.1

Gitelman syndrome (GS) is an autosomal recessive renal tubulopathy caused by mutations in the SLC12A3 gene, and results in loss of function of the thiazide-sensitive sodium–chloride cotransporter in the distal convoluted tubule, which leads to impaired sodium reabsorption.2 Subsequently, the high level of sodium is reabsorbed into the renal-collecting ducts in exchange for potassium and hydrogen, resulting in their increased urinary excretion.3 Patients with GS, therefore, present with a wide spectrum of biochemical abnormalities including hypokalaemic metabolic alkalosis, hypomagnesaemia, hypocalciuria and secondary hyperaldosteronism.4

GS is usually managed with oral potassium, potassium-sparing diuretics and occasionally non-steroidal anti-inflammatory drugs, but some patients with GS are refractory to these treatments.5 Clinical features include tetany, muscle weakness, dizziness, periodical paralysis and constipation, which is one of the most frequent complications of GS.5

Although it is often thought that patients with GS have milder symptoms than those with Bartter syndrome, there are some cases with severe symptoms.5 Recently, the prevalence is estimated at ~23 per 10 000 people and accordingly, the prevalence of heterozygotes is approximately ~9.5%, making it no longer a rare disease.6 In addition, hypokalaemia tends to cause drug-resistant constipation7; therefore, the co-occurrence of GS and refractory constipation might not be so rare. We report a case of GS with intractable hypokalaemia and refractory constipation who underwent total colectomy and showed improvement in both disorders without any medication for 3 years or more.

Case presentation

A woman in her 40s presented to our hospital with hypokalaemia of unknown cause. The patient had been followed up and prescribed a potassium preparation by other clinics since her late 20s; however, she was repeatedly transported to the emergency department because of her fatigue and periodical paralysis due to hypokalaemia. She was finally referred to the department of endocrinology and metabolism at our hospital because of the increased frequency of periodical paralysis.

The patient did not use diuretics according to her medication history, but she had polyuria and nocturia. Although the patient was using laxatives, she experienced hard stool once a week. In addition, she had a good appetite (daily intake of 2000 kcal), preferred salt and had no habit of vomiting. She had never smoked, did not use any drugs containing licorice and did not drink alcohol. The patient had developed an anxiety neurosis in her 30s, and she stated that it was caused by repeated periodical paralysis due to hypokalaemia. She had been thin since childhood. The patient was admitted to our hospital for further evaluation.

The patient’s weight was 46 kg, height was 164 cm and body mass index (the weight in kilograms divided by the square of the height in metres) was 17.1 kg/m². Her blood pressure was 84/52 mm Hg. She had no peripheral oedema. The muscle strength was 3/5 in her arms and legs. No abnormalities in her vital signs were found except for slight hypotension. An ECG did not show QT prolongation. An abdominal X-ray showed a large amount of colonic gas, and the bowel sounds were weakened. The patient’s complete blood count was within the normal range. Electrolytes testing showed that the serum potassium level was 2.8 mmol/L and serum magnesium level was 0.5 mmol/L (reference range, 0.7–1.0). The plasma renin activity was 13.6 ng/mL/hour (0.2–3.9), and the plasma aldosterone level was 380 pg/mL (30–159). The blood thyroid-stimulating hormone and free thyroxine levels were 2.1 μIU/mL (0.35–4.94) and 1.3 ng/mL (0.7–1.48), respectively. Arterial blood gas analysis showed that the pH was 7.52 (7.35–7.45), base excess was 2.4 mmol/L (−2.0 to 2.0) and bicarbonate was 31 mmol/L (22–29). The urine calcium level was 50 mg per day (100–300). A detailed examination revealed six clinical symptoms: hypokalaemia, metabolic alkalosis, hyperreninemia/hyperaldosteronism, hypomagnesaemia, slightly low blood pressure and hypocalciuria. Renal function was normal. Genetic analysis revealed a mutation in the SLC12A3 gene, and the patient was diagnosed with GS.

Treatment

As a treatment policy, the patient was prescribed spironolactone and triamterene in addition to the potassium preparation, but the former had a better serum potassium maintenance effect. Furthermore, the serum magnesium level improved with the use of spironolactone. In addition, when combination therapy with a non-steroidal anti-inflammatory drug was administered, a temporary increase in the serum potassium level was observed; however, this therapy was discontinued because of gastrointestinal symptoms and deterioration of renal function. An ACE inhibitor was not prescribed because the patient had hypotension. As a result, the patient was treated with 176 mmol per day of potassium preparation and 200 mg per day of spironolactone. The frequency of her periodical paralysis decreased, but her serum potassium level improved only slightly (average serum potassium level of 2.8–3.2 mmol/L). Since serum potassium levels did not improve to the reference range with prescribed medications, the patient was considered to have refractory hypokalaemia.

While the patient was followed up for hypokalaemia due to GS, our surgery department continued outpatient follow-up because of her drug-resistant constipation. She developed paralytic ileus once every 2–3 months and was hospitalised repeatedly. Abdominal X-rays and CT showed dilation of the colon and stool impaction. In addition, because the peristaltic movement of the intestine was reduced, she was diagnosed with slow transit constipation (STC); surgical treatment was therefore recommended. Because severe constipation and paralytic ileus caused abdominal pain, nausea and vomiting, she underwent a total colectomy with ileorectal anastomosis using laparoscopy. No abnormalities of the resected colon were found in the pathological analysis. After the surgery, her defecation control improved and she was able to defecate two to three times a day; she developed no constipation or paralytic ileus. Her laxatives and bowel peristalsis-promoting drug prescription were discontinued, and an outpatient follow-up in the surgery department was completed 12 months postoperatively.

Outcome and follow-up

The outpatient follow-up in the endocrinology department was continued; however, the serum potassium level gradually improved after the surgery. Although the doses of the potassium preparation and spironolactone were tapered, the serum potassium level continued to increase and finally reached the reference range even after discontinuation of both drugs (the patient’s serum potassium level was 3.6–4.8 mmol/L).

Before the total colectomy, both the sodium and chloride concentrations in the urine were >40 mmol/L, and the daily excretions of each via urine were 139 mmol per day (reference range, 80–250) and 236 mmol per day (110–250), respectively. Both were within the reference range; however, these findings indicated overexcretion because the patient had hypotension, that is, hypovolaemia (table 1). Approximately 2 months after the surgery, the urine concentrations of sodium and chloride gradually decreased, and the daily excretion of each via urine also decreased to 35 and 57 mmol per day, respectively (table 1). Six months postoperatively, the urine sodium and chloride concentrations were low and remained stable (16 and 13 mmol/L, respectively) along with low daily excretion via urine (13 and 7 mmol per day, respectively) (table 1).

The preoperative urine potassium concentration and daily potassium excretion via urine were within the reference range despite the presence of hypokalaemia. Postoperatively, the urine potassium concentration remained within the reference range; however, because of the decrease in urine volume, from 2200 to 710 mL per day, the amount of daily potassium excretion via urine decreased from 85 to 11 mmol per day (reference range, 25–125) (table 1).

At the time of this writing, 3 years after the surgery, the patient was free of hypokalaemia, constipation and paralytic ileus without any medication. An anxiolytic (etizolam) was being continuously prescribed for mild anxiety.