Hypoparathyroidism is a rare disease characterized by low serum calcium levels, elevated serum phosphorous levels, and inappropriately low levels of PTH.110,111 In treating the disorder, physicians are challenged to manage hypocalcemia and concurrently to avoid hypercalciuria, which can lead to nephrocalcinosis, kidney stones, and even chronic kidney disease.110
It has been estimated that 60-80,000 patients in the US have hypoparathyroidism. This projection was largely based on the analysis of a large proprietary health plan claims database, which identified 8,901 cases (7.6% prevalence) of hypoparathyroidism among 117,342 procedures that may impact the parathyroid glands (e.g., thyroidectomy, neck dissection, radiation).
Most reports indicate that thyroid or neck surgery is infrequently associated to chronic hypoparathyroidism. For example, analysis of the aforementioned database from 2007 to 2008 found that of the 8,901 cases of hypoparathyroidism, 75% were transient and 25% were chronic.112 Similarly, surgeons at the Mayo Clinic reported that among 241 pediatric thyroid surgeries performed between 1993 and 2012, only four led to permanent hypoparathyroidism.113 Among patients who have had thyroid surgery, a study in Poland found that permanent hypoparathyroidism occurred in 8.5% of patients, especially following total thyroidectomy (20.2%), near-total thyroidectomy (6.7%), or subtotal thyroidectomy (4.2%). With respect to complications related to postsurgical hypoparathyroidism, Danish researchers reported such patients did not have increased risks of cataracts, spinal stenosis, fracture, or gastrointestinal cancers, and their risk of upper-extremity fracture was significantly decreased (HR 0.69, 95% CI 0.49–0.97) compared to age- and sex-matched population controls.114 However, they did find that postsurgical hypoparathyroidism was associated with an increased risk of depression, other neuropsychiatric diseases, and infections.
A study in Denmark identified the prevalence of nonsurgical hypoparathyroidism as 2.3 per 100,000.115 Compared to age- and sex-matched population-based controls, patients did not have increased mortality but did have a reduced risk of malignant diseases (HR 0.44). In comparison, however, they had an increased risk of renal insufficiency (HR 6.01), cardiovascular disease (HR 1.91), neuropsychiatric complications (HR 2.45), infections (HR 1.94), seizures (HR 10.05), cataracts (HR 4.21), and upper-extremity fractures (HR 1.93).
A study of the Danish National Patient Registry found no differences in mortality between patients with postsurgical hypoparathyroidism versus age- and gender-matched controls.116
A 1-year cohort study of 120 patients with confirmed hypoparathyroidism reported that rates of stage 3 or higher chronic kidney disease were 17-20 fold higher than those of age-matched norms.117 Because of the frequent presence of hyperphosphatemia, hypoparathyroidism can be associated with deposits of calcium–phosphate complexes in soft tissues.110 Hypoparathyroidism can occur in isolation (e.g., following surgery), as an autoimmune presentation, or in association with hereditary defects that include abnormalities of PTH biosynthesis, PTH secretion, or parathyroid gland development.110
Administering the synthetic or recombinant fragment of human parathyroid hormone 1-34 [PTH (1–34] has been shown to benefit patients with hypoparathyroidism. This truncated form of PTH which has been approved for the treatment of osteoporosis is not approved for the treatment of hypoparathyroidism in the US. The full-length molecule [PTH (1–84)] is approved for the treatment of hypoparathyroidism in the United States.110,111,118 One review expressed optimism that these treatments may lower or eliminate the need for supplemental calcium and vitamin D; the review called for long-term studies of safety and efficacy.118 In 2010, a 24-month open-label study of PTH (1–84) in 30 patients with hypoparathyroidism reported significantly reduced requirements for supplemental calcium and vitamin D (P < .05 for both comparisons).119 A later group of researchers reported that hypoparathyroidism compromised patients’ quality of life; the researchers updated a 1-year study of recombinant human PTH (1–84)120 by conducting a 5-year open-label study of the product.118 In their intention-to-treat analysis, they found that quality of life measures began to improve after 2 months and persisted through 5 years (P = .001), as did biochemical and skeletal indexes (P < .0001). Other researchers conducted a 6-month, double-blind, placebo-controlled study of PTH (1–84) in 62 patients and did not find an improvement in patients’ quality of life, although they noted that the high level of hypercalcemia among their patients may have been a potentially confounding factor.121