Etiology and Pathophysiology of Hypoparathyroidism: A Narrative Review

Affiliations

¹ Clinical Professor of Surgery and Oncology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
² Assistant Adjunct Professor of Medicine, University of California, San Francisco, Zuckerberg San Francisco General Hospital, San Francisco, CA, USA.
³ Clinical Lecturer of Surgery and Oncology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
⁴ Associate Professor of Pathology and Cell Biology and Medicine, Vagelos College of Physicians and Surgeons of Columbia University, New York, NY, USA.
⁵ Professor of Clinical Pathology and Cell Biology, Vagelos College of Physicians and Surgeons of Columbia University, New York, NY, USA.
⁶ Specially Appointed Professor, Fujii Memorial Institute of Medical Sciences, Institute of Advanced Medical Sciences, Tokushima University, Tokushima, Japan.
⁷ Professor, Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, New Delhi, India.
⁸ Département de Physiologie, Professor of Physiology, Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université de Paris, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France.
⁹ Professor Emeritus of Pediatrics and Medicine, University of Pennsylvania, Director, Center for Bone Health, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
¹⁰ Endocrine Surgery Section Head, Division of General Surgery, Department of Surgery, University Health Network, University of Toronto, Toronto, ON, Canada.
¹¹ Professor of Surgery, University of Texas MD Anderson Cancer Center, Department of Surgical Oncology, Section of Surgical Endocrinology, Houston, TX, USA.
¹² Emeritus Professor, Universitat Autònoma de Barcelona, Endocrine Surgery, Hospital del Mar, Barcelona, Spain.
¹³ Professor of Medicine, University of California, San Francisco, Endocrine Research Unit, San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA.

PMID: 36153665
PMCID: PMC10364481
DOI: 10.1002/jbmr.4714

Etiology and Pathophysiology of Hypoparathyroidism: A Narrative Review

Janice L Pasieka et al. J Bone Miner Res. 2022 Dec.

. 2022 Dec;37(12):2586-2601.

doi: 10.1002/jbmr.4714. Epub 2022 Nov 23.

Authors

Affiliations

¹ Clinical Professor of Surgery and Oncology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
² Assistant Adjunct Professor of Medicine, University of California, San Francisco, Zuckerberg San Francisco General Hospital, San Francisco, CA, USA.
³ Clinical Lecturer of Surgery and Oncology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
⁴ Associate Professor of Pathology and Cell Biology and Medicine, Vagelos College of Physicians and Surgeons of Columbia University, New York, NY, USA.
⁵ Professor of Clinical Pathology and Cell Biology, Vagelos College of Physicians and Surgeons of Columbia University, New York, NY, USA.
⁶ Specially Appointed Professor, Fujii Memorial Institute of Medical Sciences, Institute of Advanced Medical Sciences, Tokushima University, Tokushima, Japan.
⁷ Professor, Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, New Delhi, India.
⁸ Département de Physiologie, Professor of Physiology, Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université de Paris, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France.
⁹ Professor Emeritus of Pediatrics and Medicine, University of Pennsylvania, Director, Center for Bone Health, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
¹⁰ Endocrine Surgery Section Head, Division of General Surgery, Department of Surgery, University Health Network, University of Toronto, Toronto, ON, Canada.
¹¹ Professor of Surgery, University of Texas MD Anderson Cancer Center, Department of Surgical Oncology, Section of Surgical Endocrinology, Houston, TX, USA.
¹² Emeritus Professor, Universitat Autònoma de Barcelona, Endocrine Surgery, Hospital del Mar, Barcelona, Spain.
¹³ Professor of Medicine, University of California, San Francisco, Endocrine Research Unit, San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA.

PMID: 36153665
PMCID: PMC10364481
DOI: 10.1002/jbmr.4714

Abstract

The approach utilized a systematic review of the medical literature executed with specifically designed criteria that focused on the etiologies and pathogenesis of hypoparathyroidism. Enhanced attention by endocrine surgeons to new knowledge about parathyroid gland viability are reviewed along with the role of intraoperative parathyroid hormone (ioPTH) monitoring during and after neck surgery. Nonsurgical etiologies account for a significant proportion of cases of hypoparathyroidism (~25%), and among them, genetic etiologies are key. Given the pervasive nature of PTH deficiency across multiple organ systems, a detailed review of the skeletal, renal, neuromuscular, and ocular complications is provided. The burden of illness on affected patients and their caregivers contributes to reduced quality of life and social costs for this chronic endocrinopathy. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Keywords: CELL/TISSUE SIGNALING; DISORDERS OF CALCIUM/PHOSPHATE METABOLISM; ENDOCRINE PATHWAYS; HORMONE REPLACEMENT/RECEPTOR MODULATORS; PARATHYROID-RELATED DISORDERS; PTH/VIT D/FGF23; THERAPEUTICS.

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Conflict of interest statement

PH: consultant to Shire/Takeda and Kyowa Kirin, speaker for Shire/Takeda and received research grants from Shire. MAL: consultant to Shire/Takeda and clinical trials investigator for Shire. SC, DD, SF, RG, JLP, NDP, JDP, DMS, AS-S, KW, and CTYeo: nothing to disclose.

Figures

**Fig. 1.**
PRISMA 2020 flow diagram for new systematic reviews which included searches of databases and registers only. The search was executed with the following approach: *PubMed Search Terms. (“Hypoparathyroidism/etiology”[Majr] OR “Hypoparathyroidism/pathology”[Majr] OR ((hypoparathyroidism [ti] OR hypoparathyroidism[ot]) AND (etiology OR pathophysiology OR physiopathology OR pathology))) AND (random* OR control* OR cohort OR case–control OR “clinical trial” OR review[pt] OR systematic[sb]) NOT (letter[pt] OR editorial[pt] OR case reports[pt]) AND ((1980:3000/12/12[pdat]). **Embase Search Terms. ((‘hypoparathyroidism’/exp OR hypoparathyroidism) AND (‘pathophysiology’/exp OR pathophysiology OR ‘etiology’/exp OR etiology) AND [humans]/lim AND [english]/lim AND (‘case control study’/de OR ‘clinical article’/de OR ‘clinical study’/de OR ‘clinical trial’/de OR ‘cohort analysis’/de OR ‘comparative study’/de OR ‘controlled clinical trial’/de OR ‘controlled study’/de OR ‘cross sectional study’/de OR ‘human experiment’/de OR ‘longitudinal study’/de OR ‘major clinical study’/de OR ‘multicenter study’/de OR ‘observational study’/de OR ‘prospective study’/de OR ‘randomized controlled trial’/de OR ‘randomized controlled trial topic’/de OR ‘retrospective study’/de OR ‘systematic review’/de) AND [1980–2021]/py) AND (‘article’/it OR ‘article in press’/it). From: Page and colleagues.⁽⁵⁾ For more information, visit: http://www.prisma-statement.org/.

**Fig. 2.**
An algorithm for management strategies for the evaluation and treatment of postoperative parathyroid gland insufficiency following total thyroidectomy with or without lymph node dissection.

**Fig. 3.**
Iliac crest bone biopsies from a control subject (left) and a hypoparathyroid subject (right), Goldner trichrome stain. Note the higher cortical thickness and cancellous bone volume in the hypoparathyroid subject. Reproduced with permission from Rubin and colleagues.⁽¹³⁶⁾

**Fig. 4.**
Microcomputed tomographic images of cancellous bone from a hypoparathyroid subject (left) and a control subject (right). Note the higher cancellous bone volume and dense trabecular structure in hypoparathyroidism. Reproduced with permission from Dempster.⁽¹³⁷⁾

**Fig. 5.**
Tetracycline labels in a hypoparathyroid (left) and control subject (right). Note reduction in tetracycline uptake in the hypoparathyroid subject reflecting reduced bone turnover. Reproduced with permission from Rubin and colleagues.⁽¹³⁶⁾

**Fig. 6.**
Bone remodeling cycles in hypoparathyroid (upper) and normal (lower) subjects. All phases of the remodeling cycle are elongated in hypoparathyroidism. Reproduced with permission from Langdahl and colleagues.⁽¹⁴²⁾

**Fig. 7.**
Bone formation and resorption in a simulation of the onset of hypoparathyroidism. In the left panel (A), osteocyte mechnaosensitivity is set to 100%. In the panel on the right (B), osteocyte mechanosensitivity is set to 140%. As shown in panel (B), a net greater increase in bone mass will occur under these conditions. Repoduced with permission from Christen and colleagues.⁽¹⁴³⁾

See this image and copyright information in PMC

References

1. Gafni RI, Collins MT. Hypoparathyroidism. N Engl J Med. 2019; 380(18):1738–1747. - PubMed
1. Sitges-Serra A. Etiology and diagnosis of permanent hypoparathyroidism after total thyroidectomy. J Clin Med. 2021;10(3):543. - PMC - PubMed
1. Bilezikian JP. Hypoparathyroidism. J Clin Endocrinol Metab. 2020; 105(6):1722–1736. - PMC - PubMed
1. Kazaure HS, Sosa JA. Surgical hypoparathyroidism. Endocrinol Metab Clin North Am. 2018;47(4):783–796. - PubMed
1. Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. 10.1136/bmj.n71. - DOI - PMC - PubMed

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Etiology and Pathophysiology of Hypoparathyroidism: A Narrative Review

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Etiology and Pathophysiology of Hypoparathyroidism: A Narrative Review

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