Epidemiology and Diagnosis of Hypoparathyroidism

Abstract

Context: Hypoparathyroidism is a disorder characterized by hypocalcemia due to insufficient secretion of PTH. Pseudohypoparathyroidism is a less common disorder due to target organ resistance to PTH. This report summarizes the results of the findings and recommendations of the Working Group on Epidemiology and Diagnosis of Hypoparathyroidism.

Evidence acquisition: Each contributing author reviewed the recent published literature regarding epidemiology and diagnosis of hypoparathyroidism using PubMed and other medical literature search engines.

Evidence synthesis: The prevalence of hypoparathyroidism is an estimated 37 per 100 000 person-years in the United States and 22 per 100 000 person-years in Denmark. The incidence in Denmark is approximately 0.8 per 100 000 person-years. Estimates of prevalence and incidence of hypoparathyroidism are currently lacking in most other countries. Hypoparathyroidism increases the risk of renal insufficiency, kidney stones, posterior subcapsular cataracts, and intracerebral calcifications, but it does not appear to increase overall mortality, cardiovascular disease, fractures, or malignancy. The diagnosis depends upon accurate measurement of PTH by second- and third-generation assays. The most common etiology is postsurgical hypoparathyroidism, followed by autoimmune disorders and rarely genetic disorders. Even more rare are etiologies including parathyroid gland infiltration, external radiation treatment, and radioactive iodine therapy for thyroid disease. Differentiation between these different etiologies is aided by the clinical presentation, serum biochemistries, and in some cases, genetic testing.

Conclusions: Hypoparathyroidism is often associated with complications and comorbidities. It is important for endocrinologists and other physicians who care for these patients to be aware of recent advances in the epidemiology, diagnosis, and genetics of this disorder.

Figure 1.. Clinical approach to investigation of causes of hypocalcemia.

CKD, chronic kidney disease; Cr, creatinine; eGFR, estimated glomerular filtration rate; 25(OH)D, 25-hydroxyvitamin D; CK, creatine kinase. [Adapted from R. V. Thakker: The parathyroid glands, hypercalcemia, and hypocalcemia. In: Goldman L, Shafer AI, eds. Goldman-Cecil Medicine. 25th ed. Atlanta, GA: Elsevier Ltd; 2016:1649–1661 (67), with permission.]

Figure 2.. Clinical approach to establishing the genetic etiology of hypoparathyroidism.

The genes for each disorder are indicated in italics, and additional details are provided in Table 1. *, In PHP the plasma PTH is high. [Adapted from Thakker RV, Bringhurst FR, Juppner H. Regulation of calcium homeostasis and genetic disorders that affect calcium metabolism. In: De Groot LJ, Jameson JL, eds. Endocrinology. 7th ed. Philadelphia, PA: Elsevier; 2016:1063–1089 (67) with permission.]