title: Thiazide-Associated Hypercalcemia: Incidence and Association With Primary Hyperparathyroidism Over Two Decades.
abstract: BACKGROUND
  Thiazide diuretics, the antihypertensive agent prescribed most frequently worldwide, are commonly associated with hypercalcemia. However, the epidemiology and clinical features are poorly understood.
  
  
  OBJECTIVE
  To update the incidence of thiazide-associated hypercalcemia and clarify its clinical features.
  
  
  METHODS
  In a population-based descriptive study, Olmsted County, Minnesota, residents with thiazide-associated hypercalcemia were identified through the Rochester Epidemiology Project and the Mayo Clinic Laboratory Information System from 2002-2010 and were added to the historical cohort beginning in 1992.
  
  
  RESULTS
  Incidence rates were adjusted to the 2010 United States white population.
  
  
  RESULTS
  Overall, 221 Olmsted County residents were identified with thiazide-associated hypercalcemia an average of 5.2 years after initiation of treatment. Subjects were older (mean age, 67 years) and primarily women (86.4%). The incidence of thiazide-associated hypercalcemia increased after 1997 and peaked in 2006 with an annual incidence of 20 per 100,000, compared to an overall rate of 12 per 100,000 in 1992-2010. Severe hypercalcemia was not observed in the cohort despite continuation of thiazide treatment in 62.4%. Of patients discontinuing thiazides, 71% continued to have hypercalcemia. Primary hyperparathyroidism was diagnosed in 53 patients (24%), including five patients who underwent parathyroidectomy without thiazide discontinuation.
  
  
  CONCLUSIONS
  Many patients with thiazide-associated hypercalcemia have underlying primary hyperparathyroidism. Additionally, a sharp rise in thiazide-associated hypercalcemia incidence began in 1998, paralleling the increase observed in primary hyperparathyroidism in this community. Case ascertainment bias from targeted osteoporosis screening is the most likely explanation.
authors.affiliation: Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Department of Medicine (M.L.G., A.E.K., R.A.W.); and Divisions of Biomedical Statistics and Informatics (E.R., P.T., M.A.H.) and Epidemiology (L.J.M.), Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota 55905; and Sanford University of South Dakota Medical Center (M.L.G.), Sioux Falls, South Dakota 57117.
authors.forename: Marcio L
authors.initials: ML
authors.lastname: Griebeler
authors.affiliation: Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Department of Medicine (M.L.G., A.E.K., R.A.W.); and Divisions of Biomedical Statistics and Informatics (E.R., P.T., M.A.H.) and Epidemiology (L.J.M.), Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota 55905; and Sanford University of South Dakota Medical Center (M.L.G.), Sioux Falls, South Dakota 57117.
authors.forename: Ann E
authors.initials: AE
authors.lastname: Kearns
authors.affiliation: Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Department of Medicine (M.L.G., A.E.K., R.A.W.); and Divisions of Biomedical Statistics and Informatics (E.R., P.T., M.A.H.) and Epidemiology (L.J.M.), Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota 55905; and Sanford University of South Dakota Medical Center (M.L.G.), Sioux Falls, South Dakota 57117.
authors.forename: Euijung
authors.initials: E
authors.lastname: Ryu
authors.affiliation: Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Department of Medicine (M.L.G., A.E.K., R.A.W.); and Divisions of Biomedical Statistics and Informatics (E.R., P.T., M.A.H.) and Epidemiology (L.J.M.), Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota 55905; and Sanford University of South Dakota Medical Center (M.L.G.), Sioux Falls, South Dakota 57117.
authors.forename: Prabin
authors.initials: P
authors.lastname: Thapa
authors.affiliation: Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Department of Medicine (M.L.G., A.E.K., R.A.W.); and Divisions of Biomedical Statistics and Informatics (E.R., P.T., M.A.H.) and Epidemiology (L.J.M.), Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota 55905; and Sanford University of South Dakota Medical Center (M.L.G.), Sioux Falls, South Dakota 57117.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Hathcock
authors.affiliation: Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Department of Medicine (M.L.G., A.E.K., R.A.W.); and Divisions of Biomedical Statistics and Informatics (E.R., P.T., M.A.H.) and Epidemiology (L.J.M.), Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota 55905; and Sanford University of South Dakota Medical Center (M.L.G.), Sioux Falls, South Dakota 57117.
authors.forename: L Joseph
authors.initials: LJ
authors.lastname: Melton
authors.affiliation: Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Department of Medicine (M.L.G., A.E.K., R.A.W.); and Divisions of Biomedical Statistics and Informatics (E.R., P.T., M.A.H.) and Epidemiology (L.J.M.), Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota 55905; and Sanford University of South Dakota Medical Center (M.L.G.), Sioux Falls, South Dakota 57117.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Wermers
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006934:Hypercalcemia / Q000139:chemically induced* / Q000150:complications / Q000453:epidemiology*; D049950:Hyperparathyroidism, Primary / Q000150:complications / Q000453:epidemiology*; D015994:Incidence; D008297:Male; D008875:Middle Aged; D008910:Minnesota / Q000453:epidemiology; D049993:Sodium Chloride Symporter Inhibitors / Q000009:adverse effects*; D049971:Thiazides / Q000009:adverse effects*
chemical_list: D049993:Sodium Chloride Symporter Inhibitors; D049971:Thiazides