Management of hypoparathyroidism

Khan, Aliya A.; Guyatt, Gordon; Ali, Dalal S.; Bilezikian, John P.; Collins, Michael T.; Dandurand, Karel; Mannstadt, Michael; Murphy, Deborah; M'Hiri, Iman; Rubin, Mishaela R.; Sanders, Robert; Shrayyef, Muhammad; Siggelkow, Heide; Tabacco, Gaia; Tay, Yu-Kwang Donovan; Van Uum, Stan; Vokes, Tamara; Winer, Karen K.; Yao, Liang; Rejnmark, Lars

Affiliations

¹Division of Endocrinology and Metabolism, McMaster University, Hamilton, Canada

²Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Canada

³Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA

⁴National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA

⁵Endocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA

⁶Hypoparathyroidism Association. Inc., Lemoore, CA, USA

⁷Bone Research and Education Centre, Oakville, Canada

⁸Department of Medicine, University of Toronto, Canada

⁹Clinic of Gastroenterology, Gastrointestinal Oncology and Endocrinology, University Medical Center Goettingen, Goettingen, Germany

¹⁰MVZ Endokrinologikum Goettingen, Goettingen, Germany

¹¹Unit of Metabolic Bone and Thyroid Diseases, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy

¹²Unit of Endocrinology and Diabetes, Campus Bio-Medico University of Rome, Rome, Italy

¹³Department of Medicine, Sengkang General Hospital, Singhealth and Duke-NUS Medical School, Singapore, Singapore

¹⁴Department of Medicine, Western University, London, Canada

¹⁵Department of Medicine, University of Chicago, Chicago, IL, USA

¹⁶Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA

¹⁷Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark

Abstract and keywords

Hypoparathyroidism (HypoPT) is a rare disorder characterized by hypocalcemia in the presence of a low or inappropriately normal parathyroid hormone level. HypoPT is most commonly seen after neck surgery, which accounts for approximately 75% of cases, whereas approximately 25% have HypoPT due to nonsurgical causes. In both groups of patients, conventional therapy includes calcium and active vitamin D analogue therapy aiming to maintain serum calcium concentration in the low normal or just below the normal reference range and normalize serum phosphorus, magnesium concentrations, and urine calcium levels. The limitations of conventional therapy include wide fluctuations in serum calcium, high pill burden, poor quality of life, and renal complications. Parathyroid hormone (PTH) replacement therapy may improve the biochemical profile in those in whom conventional therapy proves unsatisfactory. Based on a systematic review and meta-analysis of the literature, the panel made a graded recommendation suggesting conventional therapy as first line therapy rather than administration of PTH (weak recommendation, low quality evidence). When conventional therapy is deemed unsatisfactory, the panel considers use of PTH. Because pregnancy and lactation are associated with changes in calcium homeostasis, close monitoring is required during these periods with appropriate adjustment of calcium and active vitamin D analogue therapy to ensure that serum calcium remains in the mid to low normal reference range in order to avoid maternal and fetal complications. Emerging therapies include molecules with prolonged PTH action as well as different mechanisms of action that may significantly enhance drug efficacy and safety.

Keywords: PARATHYROID-RELATED DISORDERS; DISORDERS OF CALCIUM/PHOSPHATE METABOLISM; CELL/TISSUE SIGNALING; ENDOCRINE PATHWAYS

Links

DOI: 10.1002/jbmr.4716

PubMed: 36161671

WoS: 000876326400001

History

Received: 2022-02-07

Revised: 2022-09-19

Accepted: 2022-09-22

Cited Works (8)

Year	Entry
2022	Roszko KL, Hu TY, Guthrie LC, Brillante BA, Smith M, Collins MT, Gafni RI. PTH 1-34 replacement therapy has minimal effect on quality of life in patients with hypoparathyroidism. J Bone Miner Res. January 2022;37(1):68-77.
2020	Cusano NE, Rubin MR, Williams JM, Agarwal S, Tabacco G, Tay D, Majeed R, Omeragic B, Bilezikian JP. Changes in skeletal microstructure through four continuous years of rhPTH(1–84) therapy in hypoparathyroidism. J Bone Miner Res. July 2020;35(7):1274-1281.
2020	Karpf DB, Pihl S, Mourya S, Mortensen E, Kovoor E, Markova D, Leff JA. A randomized double‐blind placebo‐controlled first‐in‐human phase 1 trial of TransCon PTH in healthy adults. J Bone Miner Res. August 2020;35(8):1430-1440.
2022	Van Uum S, Shrayyef M, M'Hiri I, Dandurand K, Ali DS, Bilezikian JP, Collins MT, Mannstadt M, Rubin MR, Siggelkow H, Tabacco G, Tay Y-KD, Vokes T, Winer KK, Yao L, Guyatt G, Rejnmark L, Khan AA. Initial assessment and monitoring of patients with chronic hypoparathyroidism: a systematic current practice survey. J Bone Miner Res. December 2022;37(12):2630-2641.
2022	Yao L, Hui X, Li M, Li J, Ahmed MM, Lin C, Kandi M, Sreekanta A, Makhdami N, Tamilselvan D, Ali DS, Dandurand K, Yang K, Bilezikian JP, Brandi ML, Clarke BL, Mannstadt M, Rejnmark L, Khan AA, Guyatt G. Complications, symptoms, presurgical predictors in patients with chronic hypoparathyroidism: a systematic review. J Bone Miner Res. December 2022;37(12):2642-2653.
2022	Yao L, Li J, Li M, Lin C, Hui X, Tamilselvan D, Kandi M, Sreekanta A, Makhdami N, Ali DS, Dandurand K, Yang K, Bilezikian JP, Brandi ML, Clarke BL, Mannstadt M, Rejnmark L, Khan AA, Guyatt G. Parathyroid hormone therapy for managing chronic hypoparathyroidism: a systematic review and meta-analysis. J Bone Miner Res. December 2022;37(12):2654-2662.
2021	Ish-Shalom S, Caraco Y, Khazen NS, Gershinsky M, Szalat A, Schwartz P, Arbit E, Galitzer H, Tang JCY, Burshtein G, Rothner A, Raskin A, Blum M, Fraser WD. Safety and efficacy of oral human parathyroid hormone (1-34) in hypoparathyroidism: an open-label study. J Bone Miner Res. June 2021;36(6):1060-1068.
2021	Winer KK, Ye S, Ferré EM, Schmitt MM, Zhang B, Cutler GB Jr, Lionakis MS. Therapy with PTH 1–34 or calcitriol and calcium in diverse etiologies of hypoparathyroidism over 27 years at a single tertiary care center. Bone. August 2021;149:115977.

Cited By (5)

Year	Entry
2022	Bilezikian JP, Khan AA, Clarke BL, Mannstadt M, Potts JT, Brandi ML. The Fifth International Workshop on the Evaluation and Management of Primary Hyperparathyroidism. J Bone Miner Res. November 2022;37(11):2290-2292.
2022	Bilezikian JP, Khan AA, Silverberg SJ, Fuleihan GE-H, Marcocci C, Minisola S, Perrier N, Sitges-Serra A, Thakker RV, Guyatt G, Mannstadt M, Potts JT, Clarke BL, Brandi ML; International Workshop on Primary Hyperparathyroidism. Evaluation and management of primary hyperparathyroidism: summary statement and guidelines from the Fifth International Workshop. J Bone Miner Res. November 2022;37(11):2293-2314.
2022	Khan AA, Bilezikian JP, Brandi ML, Clarke BL, Potts JJ, Mannstadt M; International Workshop on Primary Hyperparathyroidism. The Second international Workshop on the Evaluation and Management of Hypoparathyroidism. J Bone Miner Res. December 2022;37(12):2566-2567.
2022	Khan AA, Bilezikian JP, Brandi ML, Clarke BL, Gittoes NJ, Pasieka JL, Rejnmark L, Shoback DM, Potts JT, Guyatt GH, Mannstadt M. Evaluation and management of hypoparathyroidism summary statement and guidelines from the second international workshop. J Bone Miner Res. December 2022;37(12):2568-2585.
2022	Van Uum S, Shrayyef M, M'Hiri I, Dandurand K, Ali DS, Bilezikian JP, Collins MT, Mannstadt M, Rubin MR, Siggelkow H, Tabacco G, Tay Y-KD, Vokes T, Winer KK, Yao L, Guyatt G, Rejnmark L, Khan AA. Initial assessment and monitoring of patients with chronic hypoparathyroidism: a systematic current practice survey. J Bone Miner Res. December 2022;37(12):2630-2641.