Hypoparathyroidism: diagnosis, management and emerging therapies

Pasieka, J. L. et al. Etiology and pathophysiology of hypoparathyroidism: a narrative review. J. Bone Miner. Res. 37, 2586–2601 (2022). An excellent review of the various causes of hypoparathyroidism.

Article  PubMed  Google Scholar 

Bjornsdottir, S. et al. Epidemiology and financial burden of adult chronic hypoparathyroidism. J. Bone Miner. Res. 37, 2602–2614 (2022).

Article  PubMed  Google Scholar 

Khan, A. A. et al. Evaluation and management of hypoparathyroidism summary statement and guidelines from the second international workshop. J. Bone Miner. Res. 37, 2568–2585 (2022). The summary statement of the 2022 guidelines on hypoparathyroidism.

Article  PubMed  Google Scholar 

Brandi, M. L. et al. Management of hypoparathyroidism: summary statement and guidelines. J. Clin. Endocrinol. Metab. 101, 2273–2283 (2016).

Article  CAS  PubMed  Google Scholar 

Mannstadt, M. et al. Hypoparathyroidism. Nat. Rev. Dis. Prim. 3, 17055 (2017).

Article  PubMed  Google Scholar 

Puliani, G. et al. Impaired immune function in patients with chronic postsurgical hypoparathyroidism: results of the EMPATHY study. J. Clin. Endocrinol. Metab. 106, e2215–e2227 (2021).

Article  PubMed  Google Scholar 

Rejnmark, L. Treatment of hypoparathyroidism by re-establishing the effects of parathyroid hormone. Endocrinol. Metab. 39, 262–266 (2024).

Article  CAS  Google Scholar 

Winer, K. K., Fulton, K. A., Albert, P. S. & Cutler, G. B. Jr. Effects of pump versus twice-daily injection delivery of synthetic parathyroid hormone 1-34 in children with severe congenital hypoparathyroidism. J. Pediatr. 165, 556–563.e1 (2014).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Winer, K. K. et al. Long-term parathyroid hormone 1-34 replacement therapy in children with hypoparathyroidism. J. Pediatr. 203, 391–399.e1 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Winer, K. K. et al. Effects of once versus twice-daily parathyroid hormone 1-34 therapy in children with hypoparathyroidism. J. Clin. Endocrinol. Metab. 93, 3389–3395 (2008).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Winer, K. K., Yanovski, J. A., Sarani, B. & Cutler, G. B. Jr. A randomized, cross-over trial of once-daily versus twice-daily parathyroid hormone 1-34 in treatment of hypoparathyroidism. J. Clin. Endocrinol. Metab. 83, 3480–3486 (1998).

CAS  PubMed  Google Scholar 

Winer, K. K. et al. Synthetic human parathyroid hormone 1-34 replacement therapy: a randomized crossover trial comparing pump versus injections in the treatment of chronic hypoparathyroidism. J. Clin. Endocrinol. Metab. 97, 391–399 (2012).

CAS  PubMed  Google Scholar 

Mannstadt, M. 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. 1, 275–283 (2013). A landmark trial for the use of PTH (1–84) in patients with hypoparathyroidism.

Article  CAS  PubMed  Google Scholar 

Tay, Y. D. et al. Therapy of hypoparathyroidism with rhPTH(1-84): a prospective, 8-year investigation of efficacy and safety. J. Clin. Endocrinol. Metab. 104, 5601–5610 (2019).

Article  PubMed  PubMed Central  Google Scholar 

Sikjaer, T., Rejnmark, L., Rolighed, L., Heickendorff, L. & Mosekilde, L. The effect of adding PTH(1-84) to conventional treatment of hypoparathyroidism: a randomized, placebo-controlled study. J. Bone Miner. Res. 26, 2358–2370 (2011).

Article  CAS  PubMed  Google Scholar 

US Food and Drug Administration. FDA approves new drug for hypoparathyroidism, a rare disorder. FDA.gov https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-new-drug-hypoparathyroidism-rare-disorder (2024).

Takacs, I. et al. An open-label phase 2 study of eneboparatide, a novel PTH receptor 1 agonist, in hypoparathyroidism. J. Clin. Endocrinol. Metab. 109, 2199–2209 (2024). The most recent study on eneboparatide, an emerging treatment for hypoparathyroidism.

Article  PubMed  Google Scholar 

Gafni, R. I. et al. Efficacy and safety of encaleret in autosomal dominant hypocalcemia type 1. N. Engl. J. Med. 389, 1245–1247 (2023).

Article  PubMed  PubMed Central  Google Scholar 

Carney, P., Cutler, G. B. Jr, Schneider, K., Zhang, F. & DiMarchi, R. MBX 2109, a once-weekly parathyroid hormone replacement therapy prodrug: phase 1, first-in-human, randomized trial. J. Clin. Endocrinol. Metab. https://doi.org/10.1210/clinem/dgae808 (2024).

Zhang, J. et al. 6821 Characterization of a novel oral small molecule PTH1R agonist: proof of concept for an alternative to injectable peptide-based therapy for hypoparathyroidism. J. Endocrine Soc. 8, bvae163.386 (2024).

Article  Google Scholar 

Ish-Shalom, S. et al. Safety and efficacy of oral human parathyroid hormone (1-34) in hypoparathyroidism: an open-label study. J. Bone Miner. Res. 36, 1060–1068 (2021).

Article  CAS  PubMed  Google Scholar 

Sitges-Serra, A. Etiology and diagnosis of permanent hypoparathyroidism after total thyroidectomy. J. Clin. Med. 10, 543 (2021).

Article  PubMed  PubMed Central  Google Scholar 

Bilezikian, J. P. Hypoparathyroidism. J. Clin. Endocrinol. Metab. 105, 1722–1736 (2020).

Article  PubMed  PubMed Central  Google Scholar 

Mannstadt, M. et al. Hypoparathyroidism: genetics and diagnosis. J. Bone Miner. Res. 37, 2615–2629 (2022). An important review of the various genetic causes of hypoparathyroidism and guidelines for diagnosis.

Article  CAS  PubMed  Google Scholar 

Powers, J., Joy, K., Ruscio, A. & Lagast, H. Prevalence and incidence of hypoparathyroidism in the United States using a large claims database. J. Bone Miner. Res. 28, 2570–2576 (2013).

Article  PubMed  Google Scholar 

Lorente-Poch, L., Sancho, J. J., Muñoz-Nova, J. L., Sánchez-Velázquez, P. & Sitges-Serra, A. Defining the syndromes of parathyroid failure after total thyroidectomy. Gland. Surg. 4, 82–90 (2015).

PubMed  PubMed Central  Google Scholar 

Jessie, W., & Harrison, B. Hypocalcemia after thyroidectomy: the need for improved definitions. World J. Endocr. Surg. 2, 17–20 (2010).

Article  Google Scholar 

Mehanna, H. M., Jain, A., Randeva, H., Watkinson, J. & Shaha, A. Postoperative hypocalcemia-the difference a definition makes. Head Neck 32, 279–283 (2010).

Article  PubMed  Google Scholar 

Edafe, O., Antakia, R., Laskar, N., Uttley, L. & Balasubramanian, S. P. Systematic review and meta-analysis of predictors of post-thyroidectomy hypocalcaemia. Br. J. Surg. 101, 307–320 (2014).

Article  CAS  PubMed  Google Scholar 

Bai, B., Chen, Z. & Chen, W. Risk factors and outcomes of incidental parathyroidectomy in thyroidectomy: a systematic review and meta-analysis. PLoS ONE 13, e0207088 (2018).

Article  PubMed  PubMed Central  Google Scholar 

Barrios, L. et al. Incidental parathyroidectomy in thyroidectomy and central neck dissection. Surgery 169, 1145–1151 (2021).

Article  PubMed  Google Scholar 

Siraj, N., Hakami, Y. & Khan, A. Medical hypoparathyroidism. Endocrinol. Metab. Clin. North Am. 47, 797–808 (2018).

Article  PubMed  Google Scholar 

Gylling, M. et al. The hypoparathyroidism of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy protective effect of male sex. J. Clin. Endocrinol. Metab. 88, 4602–4608 (2003).

Article  CAS  PubMed  Google Scholar 

Lankisch, T. O., Jaeckel, E. & Strassburg, C. P. The autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy or autoimmune polyglandular syndrome type 1. Semin. Liver Dis. 29, 307–314 (2009).

Article  CAS  PubMed  Google Scholar 

Aaltonen, J. et al. An autoimmune disease, APECED, caused by mutations in a novel gene featuring two PHD-type zinc-finger domains. Nat. Genet. 17, 399–403 (1997).

Article  Google Scholar 

Husebye, E. S., Anderson, M. S. & Kämpe, O. Autoimmune polyendocrine syndromes. N. Engl. J. Med. 378, 1132–1141 (2018).

Comments (0)

No login
gif