NICHD has a long history of work exploring typical and atypical endocrine function in children, adults, and pregnant women, especially within the context of optimal growth and development. In fact, NICHD researchers were the first to explore parathyroid hormone (PTH) as a hormonal replacement therapy for hypoparathyroidism in the early 1990s.
The primary goal of NICHD studies on hypoparathyroidism is to develop and evaluate treatment approaches that normalize blood and urine calcium levels and promote normal bone health in both adults and children.
Unlike most other hormone insufficiencies, hypoparathyroidism has not been treated with replacement of the missing hormone, PTH. Instead, conventional treatment of this disorder includes daily doses of vitamin D analogs (such as calcitriol) and calcium and magnesium supplementation.
In 1992, NICHD researchers began exploring replacement PTH as a treatment for hypoparathyroidism. A series of classic studies evaluated PTH regimens compared to conventional therapy, including once-daily and twice-daily injections. Treatment with PTH improved metabolic control in patients with a wide spectrum of disease severity, including patients with severe congenital hypoparathyroidism. PTH replacement therapy was shown to be safe and effective for children and adults for up to 10 years.
Institute Activities and Advances
Over the past two decades, Pediatric Growth and Nutrition Branch (PGNB) researchers have focused on finding alternatives to conventional therapy (vitamin D analogs and calcium supplementation) for the treatment of chronic hypoparathyroidism. This pioneering work demonstrated that injected PTH replacement therapy provides excellent metabolic control while avoiding the risks to the kidney associated with conventional therapy. Additionally, the researchers demonstrated long-term safety and efficacy for up to 10 years in adults and children.1,2,3,4
More recently, the same NICHD researchers showed that PTH delivery by an insulin pump was effective in adults5 and children.6 Pump delivery had multiple advantages over conventional therapy and over PTH injections, specifically in children with severe congenital hypoparathyroidism and in adults with post-surgical hypoparathyroidism. This work was further reviewed, summarized, and reconfirmed in 2018.7
In 2015, the U.S. Food and Drug Administration (FDA) approved PTH 1-84 for the treatment of hypoparathyroidism, based in part on NICHD research findings. PGNB researchers have consistently shown that PTH 1-34, a synthetic form of PTH, delivered via injection or by pump offers multiple advantages over conventional therapy.
- Winer, K. K, Yanovski, J. A., & Cutler, G. B. Jr. (1996). Synthetic human parathyroid hormone 1-34 vs calcitriol and calcium in the treatment of hypoparathyroidism: Results of a short-term randomized crossover trial. JAMA, 276(8), 631–636. Retrieved May 24, 2019, from https://www.ncbi.nlm.nih.gov/pubmed/8773636
- Winer, K. K., Ko, C. W., Reynolds, J. C., Dowdy, K., Keil, M., Peterson, D., et al. (2003). Long-term treatment of hypoparathyroidism: A randomized controlled study comparing parathyroid hormone-(1-34) versus calcitriol and calcium. Journal of Clinical Endocrinology and Metabolism, 88(9), 4214–4220. Retrieved May 24, 2019, from https://www.ncbi.nlm.nih.gov/pubmed/12970289
- Winer, K. K., Sinaii, N., Reynolds, J., Peterson, D., Dowdy, K., & Cutler, G. B. Jr. (2010). Long-term treatment of 12 children with chronic hypoparathyroidism: A randomized trial comparing synthetic human parathyroid hormone 1-34 versus calcitriol and calcium. Journal of Clinical Endocrinology and Metabolism, 95(6), 2680–2688. Retrieved May 24, 2019, from https://www.ncbi.nlm.nih.gov/pubmed/20392870
- Winer, K. K., Kelly, A., Johns, A., Zhang, B., Dowdy, K., Kim, L., et al. (2018). Long-term parathyroid hormone 1-34 replacement therapy in children with hypoparathyroidism. Journal of Pediatrics, 203, 391–399.e1. Retrieved May 24, 2019, from https://www.ncbi.nlm.nih.gov/pubmed/30470382
- Winer, K. K., Zhang, B., Shrader, J. A., Peterson, D., Smith, M., Albert, P. S., & Cutler, G. B. Jr. (2012). Synthetic human parathyroid hormone 1-34 replacement therapy: A randomized crossover trial comparing pump versus injections in the treatment of chronic hypoparathyroidism. Journal of Clinical Endocrinology and Metabolism, 97(2), 391–399. Retrieved May 3, 2019, from https://www.ncbi.nlm.nih.gov/pubmed/22090268
- Winer, K. K., Fulton, K. A., Albert, P. S., & Cutler, G. B. Jr. (2014). Effects of pump versus twice-daily injection delivery of synthetic parathyroid hormone 1-34 in children with severe congenital hypoparathyroidism. Journal of Pediatrics, 165(3), 556–563.e1. Retrieved May 3, 2019, from https://www.ncbi.nlm.nih.gov/pubmed/24948345
- Winer, K. K. (2019). Advances in the treatment of hypoparathyroidism with PTH 1-34. Bone, 120, 535–541. Retrieved May 3, 2019, from https://www.ncbi.nlm.nih.gov/pubmed/30243992