Understanding the etiology and impact of hypoparathyroidism

Hypoparathyroidism (HPT) is a rare and complex endocrine disorder characterized by absent or inappropriately low levels of endogenous parathyroid hormone (PTH).1-3

The symptoms and complications of HPT can be severe and persistent, posing a threat to multiple organ systems. Chronic HPT may also affect patients’ emotional well-being and quality of life.4,5

Watch: An Overview of Hypoparathyroidism

Endogenous PTH is a key regulator of mineral homeostasis.1,2

Image of body showing parathyroid and thyroid glands where PTH is secreted.

Endogenous PTH is secreted from the parathyroid glands in response to falling levels of circulating ionized calcium. When properly regulated, ionized calcium levels should not vary by more than 5%.6,7

Compromised PTH function leads to impaired mineral homeostasis, often resulting in1-3:

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serum calcium

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serum phosphate

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urinary calcium

Patients with HPT that is not adequately controlled can suffer from a high burden of illness.5

Burden of illness

Incidence and etiology

HPT affects

in the United States.8


Damage to the parathyroid glands during thyroidectomy, parathyroidectomy, or other neck surgeries is the most common cause of acquired hypoparathyroidism, accounting for ~75% of cases.9,10




Other causes

Postsurgical HPT may resolve in a short time or become permanent. Chronic hypoparathyroidism can be diagnosed when low levels of endogenous PTH persist for ≥6 months.9,10

Autoimmune hypoparathyroidism

The second most common form in adults, autoimmune HPT may be isolated or part of an autoimmune polyglandular syndrome (APS).3


Genetic mutations may impact parathyroid development, PTH synthesis, or resistance to PTH in the proximal renal tubule. HPT may feature in some complex congenital syndromes, such as DiGeorge syndrome. Excess accumulation of iron (thalassemia or hemochromatosis) or copper (Wilson’s disease) are other less common causes.3

Rare causes

Radiation treatment for cancers of the head or neck, or radioactive iodine treatment may interfere with parathyroid function. In some instances, hypoparathyroidism may be idiopathic in nature.3,9

Chronic HPT is associated with comorbidities that can affect several organ systems—including renal, neuropsychiatric, skeletal, cardiovascular, and ophthalmologic systems.4



1. Mannstadt M, Bilezikian JP, Thakker RV, et al. Hypoparathyroidism. Nat Rev Dis Primers. 2017;3:17055. doi:10.1038/nrdp.2017.55. 2. Shoback D. Hypoparathyroidism [clinical practice]. N Engl J Med. 2008;359(4):391-403. 3. Bilezikian JP, Khan A, Potts JT Jr, et al. Hypoparathyroidism in the adult: epidemiology, diagnosis, pathophysiology, target-organ involvement, treatment, and challenges for future research. J Bone Miner Res. 2011;26(10):2317-2337. 4. Shoback DM, Bilezikian JP, Costa AG, et al. Presentation of hypoparathyroidism: etiologies and clinical features. J Clin Endocrinol Metab. 2016;101(6):2300-2312. 5. Siggelkow H, Clarke BL, Germak J, et al. Burden of illness in not adequately controlled chronic hypoparathyroidism: findings from 13-country patient and caregiver survey. Clin Endocrinol (Oxf). 2020;92(2):159-168. 6. Marieb EN, Hoehn K. The endocrine system. In: Marieb EN, Hoehn K, eds. Human Anatomy & Physiology. 9th ed. Pearson Education; 2012:591-630. 7. Baker SB, Worthley Ll. The essentials of calcium, magnesium and phosphate metabolism: part I. Physiology. Crit Care Resusc. 2002;4(4):301-306. 8. Brandi ML, Bilezikian JP, Shoback D, et al. Management of hypoparathyroidism: summary statement and guidelines. J Clin Endocrinol Metab. 2016;101(6):2273-2283. 9. Khan AA, Koch CA, Van Uum S, et al. Standards of care for hypoparathyroidism in adults: a Canadian and international consensus. Eur J Endocrinol. 2019;180(3):P1-P22. 10. Bollerslev J, Rejnmark L, Marcocci C, et al. European Society of Endocrinology clinical guideline: treatment of chronic hypoparathyroidism in adults. Eur J Endocrinol. 2015;173(2):G1-G20.