Hypoparathyroidism Treatment & Management
- Author: Joseph Michael Gonzalez-Campoy, MD, PhD, FACE; Chief Editor: George T Griffing, MD more...
Treatment of patients with hypoparathyroidism involves correcting the hypocalcemia by administering calcium and vitamin D.
Recombinant human parathyroid hormone (rhPTH[1-84], Natpara) is commercially available in the United States and is indicated as an adjunct to calcium and vitamin D to control hypocalcemia in patients with hypoparathyroidism. Its approval was based on the REPLACE trial (n=134). The primary endpoint was patients who achieved a greater than 50% reduction of daily PO calcium and vitamin D from baseline while maintaining serum calcium above baseline concentrations and less than upper limits of normal at week 24. Results showed that 48 (53%) of patients in the rhPTH group achieved the primary endpoint compared with 1 (2%) patient in the placebo group (p< 0.0001).
A prospective study by Rubin et al indicated that in patients with hypoparathyroidism, long-term, continuous therapy with rhPTH(1-84) has a good safety profile, reduces the need for supplemental calcium and calcitriol, leads to stable serum calcium concentration, and reduces urinary calcium excretion. The study included 33 patients, who underwent therapy with the hormone for up to 6 years.
Guidelines on chronic hypoparathyroidism by the European Society of Endocrinology, released in 2015, are below:
Consider a diagnosis of chronic hypoparathyroidism (HypoPT) in a patient with hypocalcemia and inappropriately low parathyroid hormone (PTH) levels.
Consider genetic testing and/or family screening in a patient with HypoPT of unknown etiology.
Treatment targeted to maintain serum calcium level (albumin adjusted total calcium or ionized calcium) in the lower part or slightly below the lower limit of the reference range (target range) is suggested, with patients being free of symptoms or signs of hypocalcemia.
Treat patients with chronic HypoPT with symptoms of hypocalcemia and/or an albumin adjusted serum calcium level <2.0 mmol/L (<8.0 mg/dL/ionized serum calcium levels [S-Ca 2] <1.00 mmol/L).
Offer treatment to asymptomatic patients with chronic HypoPT and an albumin adjusted calcium level between 2.0 mmol/L (8.0 mg/dL/S-Ca 2+ 1.00 mmol/L) and the lower limit of the reference range in order to assess whether this may improve their well-being.
Use activated vitamin D analogues plus calcium supplements in divided doses as the primary therapy.
If activated vitamin D analogues are not available, treat with calciferol (preferentially cholecalciferol).
Titrate activated vitamin D analogues or cholecalciferol in such a manner that patients are without symptoms of hypocalcemia and serum calcium levels are maintained within the target range.
Provide vitamin D supplementations in a daily dose of 400–800 IU to patients treated with activated vitamin D analogues.
In a patient with hypercalciuria, consider a reduction in calcium intake, a sodium-restricted diet, and/or treatment with a thiazide diuretic.
In a patient with renal stones, evaluate renal stone risk factors and management according to relevant international guidelines.
In a patient with hyperphosphatemia and/or an elevated calcium-phosphate product, consider dietary interventions and/or adjustment of treatment with calcium and vitamin D analogues.
In a patient with hypomagnesemia, consider measures that may increase serum magnesium levels.
The routine use of replacement therapy with PTH or PTH analogues is not recommended.
Patients undergoing parathyroidectomy for parathyroid hyperplasia are at high risk of developing permanent primary hypoparathyroidism.
Patients may be treated with an autotransplant of a segment of parathyroid gland to prevent hypoparathyroidism. This autotransplant is usually placed subcutaneously in the forearm or in the neck.
If the autotransplantation fails, patients receive the same treatment that is administered to other patients with hypoparathyroidism.
An endocrinologist should be involved in the care of all patients who have primary hypoparathyroidism or who are at risk of developing it.
A diet rich in calcium content (ie, emphasizing dairy products) is recommended for patients with primary hypoparathyroidism.
Patients with symptomatic hypocalcemia develop tetany. Otherwise, no restriction in activity for these patients is necessary.
Cheung M. Drugs used in paediatric bone and calcium disorders. Endocr Dev. 2009. 16:218-232. [Medline].
Clarke BL, Brown EM, Collins MT, et al. Epidemiology and Diagnosis of Hypoparathyroidism. J Clin Endocrinol Metab. 2016 Jun. 101 (6):2284-99. [Medline].
Bhadada SK, Bhansali A, Upreti V, Subbiah S, Khandelwal N. Spectrum of neurological manifestations of idiopathic hypoparathyroidism and pseudohypoparathyroidism. Neurol India. 2011 Jul-Aug. 59(4):586-9. [Medline].
Assfaw Z, Assefa G. Basal ganglia calcification with hypoparathyroidism: a case report. Ethiop Med J. 2011 Jul. 49(3):273-7. [Medline].
Goswami R, Goel S, Tomar N, et al. Prevalence of clinical remission in patients with sporadic idiopathic hypoparathyroidism. Clin Endocrinol (Oxf). 2009 Jun 22. [Medline].
Rubin MR, Dempster DW, Zhou H, et al. Dynamic and structural properties of the skeleton in hypoparathyroidism. J Bone Miner Res. 2008 Dec. 23(12):2018-24. [Medline]. [Full Text].
Ebrahimi H, Edhouse P, Lundgren CI, et al. Does autoimmune thyroid disease affect parathyroid autotransplantation and survival?. ANZ J Surg. 2009 May. 79(5):383-5. [Medline].
Brown EM. Anti-parathyroid and anti-calcium sensing receptor antibodies in autoimmune hypoparathyroidism. Endocrinol Metab Clin North Am. 2009 Jun. 38(2):437-45, x. [Medline]. [Full Text].
Goltzman D, Cole DEC. Hypoparathyroidism. Favus MJ, ed. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. Philadelphia, Pa: Lippincott-Raven; 1996. 220-3.
Mannstadt M, Clarke BL, Vokes T, Brandi ML, Ranganath L, Fraser WD, et al. Efficacy and safety of recombinant human parathyroid hormone (1-84) in hypoparathyroidism (REPLACE): a double-blind, placebo-controlled, randomised, phase 3 study. Lancet Diabetes Endocrinol. 2013 Dec. 1(4):275-83. [Medline].
Rubin MR, Cusano NE, Fan WW, et al. Therapy of Hypoparathyroidism With PTH(1-84): A Prospective Six Year Investigation of Efficacy and Safety. J Clin Endocrinol Metab. 2016 Jul. 101 (7):2742-50. [Medline].
Bollerslev J, Rejnmark L, Marcocci C, Shoback DM, Sitges-Serra A, van Biesen W, et al. European Society of Endocrinology Clinical Guideline: Treatment of chronic hypoparathyroidism in adults. Eur J Endocrinol. 2015 Aug. 173 (2):G1-G20. [Medline].
Brown EM, Harris HW, Vassilev PM. The biology of the extracellular Ca2+-sensing receptor. Bilezikian JP, ed. Principles of Bone Biology. San Diego, Calif: Academic Press; 1996. 243-62.
Cole DEC, Hendy GN. Hypoparathyroidism and pseudohypoparathyroidism. Endotext.com. 2005, Available at. [Full Text].
Marx SJ. Hyperparathyroid and hypoparathyroid disorders. N Engl J Med. 2000 Dec 21. 343(25):1863-75. [Medline].
Thakker RV. Molecular basis of PTH underexpression. Bilezikian JP, et al, eds. Principles of Bone Biology. San Diego, Calif: Academic Press; 1996. 837-51.