Correspondence
Proton-Pump Inhibitors and Hypomagnesemic Hypoparathyroidism
N Engl J Med 2006; 355:1834-1836October 26, 2006
- Article
To the Editor:
We report two cases of hypomagnesemic hypoparathyroidism associated with the use of proton-pump inhibitors, in which patients presented with carpopedal spasm in association with severe hypomagnesemia and hypocalcemia without an appropriate increase in the level of parathyroid hormone.
Patient 1 was a 51-year-old premenopausal woman who had been taking omeprazole for more than a year (at a dose of 20 mg twice daily) and who presented with carpopedal and truncal spasm. She began receiving 2.4 g of elemental calcium per day and, later, high-dose magnesium (Figure 1AFigure 1
Changes in Serum Calcium, Serum Magnesium, and Urinary Magnesium Levels in Patient 1 (Panel A) and Patient 2 (Panel B) during Treatment with Proton-Pump Inhibitors.). Fourteen months later, omeprazole was discontinued, and ranitidine initiated. The levels of magnesium in the patient's urine and serum rapidly normalized. However, another proton-pump inhibitor (esomeprazole) was prescribed; within 2 weeks, the levels of magnesium in the patient's urine and serum again fell and remained low until ranitidine was again substituted. All magnesium supplements were then withdrawn, and the patient's magnesium level remained normal while she was taking ranitidine (at a maximum dose of 900 mg daily). Gastroscopy, colonoscopy, biopsy of the small bowel, and an upper gastrointestinal series with small-bowel follow-through revealed Barrett's esophagitis but no other abnormality.Patient 2 was an 80-year-old man who had been taking omeprazole (at a dose of 20 mg daily) for several years and who presented with symptoms similar to those of Patient 1 (Figure 1B). After 10 months of high-dose magnesium supplementation, omeprazole was stopped, and levels of magnesium in both urine and serum rose rapidly to the normal range. The patient began taking ranitidine and had normal levels of magnesium without supplementation of either magnesium or calcium.
At presentation, the level of 25-hydroxyvitamin D was 103 nmol per liter in Patient 1 and 90 nmol per liter in Patient 2 (normal range, 40 to 120). The level of parathyroid hormone was 3.3 pmol per liter in Patient 1 and 3 pmol per liter in Patient 2 (normal range, 2.5 to 7.0), with corrected calcium values of 1.77 and 1.52 mmol per liter, respectively. Both patients had hypomagnesemia, and levels of parathyroid hormone ranged from 1.2 to 2.9 pmol per liter in Patient 1 and 1.4 to 7.1 pmol per liter in Patient 2. Not only was the level of parathyroid hormone inappropriately low at diagnosis in both patients, but the levels remained suppressed. After recovery, levels of parathyroid hormone rose to 3.5 pmol per liter in Patient 1 and 10.0 pmol per liter in Patient 2.
The serum calcium levels normalized before magnesium supplementation was introduced (in the case of Patient 1) and before serum magnesium was corrected (in the case of Patient 2). This sequence of events differed from the typical pattern, which might explain why hypomagnesemic hypoparathyroidism has been unrecognized.
The metabolic abnormalities normalized in both patients with withdrawal of the proton-pump inhibitors, and neither patient required further magnesium or calcium supplementation. We found only one previous report of hypocalcemia associated with proton-pump inhibitors, but there was no mention of magnesium levels, although the level of parathyroid hormone was also inappropriately low.1
We speculate that these two cases probably represent the tip of the iceberg among patients with hypomagnesemia. In this proton-pump era, patients who receive a diagnosis of “idiopathic” hypoparathyroidism should be asked about their medication history. We suggest that magnesium levels should be measured in patients receiving proton-pump inhibitors, particularly those with concomitant cardiac abnormalities.
1 ReferencesMartin Epstein, M.B., B.S.
Shaun McGrath, M.B., B.S.
Florence Law, M.B., B.S.
John Hunter Hospital, Newcastle, NSW 2287, Australia
emepstein@hunterlink.net. au 1
Subbiah V ,Tayek JA . Tetany secondary to the use of a proton-pump inhibitor. Ann Intern Med 2002;137:E219-E219
Web of Science | Medline
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