Table of contents
American Journal of Medicine, DOI: http://dx.doi.org/10.1016/j.amjmed.2014.02.044
Received: February 4, 2014; Received in revised form: February 28, 2014; Accepted: February 28, 2014; Published Online: March 20, 2014
Paulette D. Chandler, MD, MPH , Jamil B. Scott, PhD, MPH, Bettina F. Drake, PhD, MPH, Kimmie Ng, MD, MPH, John P. Forman, Andrew T. Chan, MD, Gary G. Bennett, PhD, Bruce W. Hollis, PhD, Edward L. Giovannucci, MD, ScD, Karen M. Emmons, PhD, Charles S. Fuchs, MD, MPH
Hydrochlorothiazide, an effective antihypertensive medication commonly prescribed to blacks, decreases urinary calcium excretion. Blacks have significantly higher rates of hypertension and lower levels of 25-hydroxyvitamin D. Thus, they are more likely to be exposed to vitamin D supplementation and thiazide diuretics. The risk for hypercalcemia among blacks using vitamin D and hydrochlorothiazide is undefined.
We assessed the frequency of hypercalcemia in HCTZ users in a post-hoc analysis of a randomized, double-blind, dose-finding trial of 328 blacks (median age, 51 years) assigned to either placebo, or 1000, 2000, or 4000 international units of cholecalciferol (vitamin D3) daily for 3 months during the winter (2007-2010).
Of the 328 participants, 84 reported hydrochlorothiazide use and had serum calcium levels assessed. Additionally, a comparison convenience group of 44 enrolled participants who were not taking hydrochlorothiazide had serum calcium measurements at 3-months but not at baseline. At 3-months, hydrochlorothiazide participants had higher calcium levels (0.2 mg/dL, p<.001) than non-hydrochlorothiazide participants, but only one participant in the hydrochlorothiazide group had hypercalcemia. In contrast, none of the non-hydrochlorothiazide participants had hypercalcemia. In linear regression model adjusted for age, sex, 25-hydroxyvitamin D at 3-months, and other covariates, only hydrochlorothiazide use [Estimate (SE):0.05(0.01) p=0.01] predicted serum calcium at 3-months.
In summary, vitamin D3 supplementation up to 4000 IU in hydrochlorothiazide users is associated with a rise in serum calcium but a low frequency of hypercalcemia. These findings suggest that participants of this population can use HCTZ with up to 4000 IU of vitamin D3 daily and experience a low frequency of hypercalcemia.
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Am J Ther. 2010 Nov-Dec;17(6):e234-6. doi: 10.1097/MJT.0b013e3181c6c21b.
Desai HV1, Gandhi K, Sharma M, Jennine M, Singh P, Brogan M.
1Department of Medicine, New York Medical College/Westchester Medical Center, Valhalla, NY, USA. haritvdesai at yahoo.com
Most common causes of hypercalcemia are hyperparathyroidism, malignancy, vitamin D-mediated conditions such as sarcoidosis, and vitamin D toxicity. Less commonly, hypercalcemia can be caused by drugs such as thiazide diuretics and lithium. Mild hypercalcemia is usually asymptomatic but severe hypercalcemia is associated with nausea, vomiting, abdominal pain, excessive thirst, muscle weakness, lethargy, confusion, and fatigue. We are reporting a case of abdominal pain and altered mental status caused by thiazide-induced severe hypercalcemia of 19.8 mg/dL. This is the most severe case of thiazide-induced hypercalcemia that we have seen reported. Patients on thiazide diuretics should have their electrolytes frequently checked, especially patients on calcium supplements. Management usually includes hydration and discontinuation of drugs causing hypercalcemia.
101 year-old man (father-in-law) had been a taking 12,000 IU of vitamin D daily, Calcium supplements, and Hydrochlorothiazide for several years. Got a mild case of hypercalcemia when he added tums (Calcium Carbonate) for his upset stomach. He stopped taking the Hydrochlorothiazide, Calcium, and tums and the problem went away in a few weeks.