hormone disorders

Natalie Cusano, MD, MS, on the Clinical Presentation of Hypoparathyroidism

Hypoparathyroidism, a rare endocrine disorder characterized by hypocalcemia due to insufficient secretion of parathyroid hormone (PTH), has an estimated prevalence of 37 per 100,000 person-years in the United States.1 Hypoparathyroidism is often associated with complications and comorbidities, thus underscoring the importance of awareness among endocrinologists and related clinicians of recent advances in understanding this condition.1

Endocrinology Consultant discussed the clinical presentation of hypoparathyroidism with endocrinologist Natalie Cusano, MD, MS, Director of the Bone Metabolism Program at Lenox Hill Hospital and Associate Professor of Medicine at Zucker School of Medicine at Hofstra/Northwell in New York.

Endocrinology Consultant: What are the risk factors for developing hypoparathyroidism?

Dr Cusano: About 75% of patients with hypoparathyroidism developed the disease as a complication of thyroid or parathyroid surgery, with inadvertent removal of the parathyroid glands or damage to the glands or their blood supply.1,2 As one may expect, high-volume surgeons on average have a lower risk of hypoparathyroidism. Risk factors for hypoparathyroidism during thyroid surgery include total thyroidectomy vs thyroid lobectomy, resection for thyroid cancer, reoperation, and substernal goiter.3 Preoperative localizations studies and intraoperative PTH monitoring for parathyroid surgery have reduced the risk of complications. About 25% of patients will have a medical cause of hypoparathyroidism, the most common being a genetic or autoimmune disease, either isolated or as part of a syndrome.1 In addition, infiltration of the parathyroid glands by iron, copper, or tumor is a rare cause of hypoparathyroidism.3

Endocrinology Consultant: What are the clinical manifestations and complications of hypoparathyroidism in adults?

Dr Cusano: The clinical manifestations of hypoparathyroidism can vary widely and depend on a number of factors, including how fast hypocalcemia develops and the absolute calcium value. Patients with postoperative hypoparathyroidism may be very symptomatic even though their serum calcium is not very low, while patients with an autoimmune cause in which hypocalcemia develops over many years may be asymptomatic, despite having significant hypocalcemia.

Patients commonly have paresthesias—numbness or tingling around the mouth or the fingers and toes.3 Patients with severe hypocalcemia can have life-threatening complications, including seizures, bronchospasm, or laryngospasm.3

Renal complications, including kidney stones and chronic kidney disease, are common in patients with hypoparathyroidism.3 It is very important that patients have regular monitoring of their 24-hour urine calcium excretion, with a change in treatment as needed if hypercalciuria develops (urine calcium >250 mg for women or >300 mg for men).4

Patients are also at risk for a number of other complications, including basal ganglia calcifications, neuropsychiatric disease, and infections.3

Patients with hypoparathyroidism often do not feel like they did before developing the disease. They may describe “brain fog”—a feeling that they are not as cognitively sharp as they used to be.3 They often have significantly altered quality of life, both in mental and physical health domains.3 Because hypoparathyroidism does not usually result in manifestations that other people can see, patients may feel as if their family, friends, and even their doctors do not take their disease seriously. 

Endocrinology Consultant: Does the clinical presentation of hypoparathyroidism vary by patient age?

Dr Cusano: Genetic or autoimmune causes are more likely to present in children.1 There are no other significant differences in presentation by age.

 

Endocrinology Consultant: What is the differential diagnosis for hypoparathyroidism?

Dr Cusano: Magnesium disorders are the only reversible causes of hypoparathyroidism, presenting with low calcium and low PTH concentrations, persisting until correction of the hypo- or hypermagnesemia.2 Hypocalcemia with elevated PTH levels can be due to pseudohypoparathyroidism, malabsorption, or vitamin D deficiency.

Endocrinology Consultant: How do differences in presentation affect selection of management and treatment options?

Dr Cusano: Patients with hypoparathyroidism are treated with calcium and calcitriol supplements with the primary goal of managing symptoms of hypocalcemia, and a secondary goal of maintaining serum calcium between 8 and 9 mg/dL.5 Other goals of treatment include reducing hypercalciuria, maintaining serum phosphate close to normal and the calcium phosphate product lower than 55 mg2/dL2, and reducing risk of extraskeletal complications.5 Patients with hypercalciuria may need hydrochlorothiazide and a low sodium diet to reduce urinary calcium. 5

rhPTH(1-84) was approved by the US Food and Drug Administration in 2015 for treatment of patients with difficult-to-control disease on conventional therapy and subsequently by the European Medicines Agency in 2017.6,7 rhPTH(1-84) is not currently available in the United States, as it was voluntarily recalled in September 2019 due to issues with the delivery device.8

Patients with autosomal dominant hypocalcemia due to mutations in the calcium sensing receptor are especially prone to renal complications.5 These patients should be treated with the lowest possible doses of calcium and/or calcitriol.

—Christina Vogt

References:

  1. Clarke BL, Brown EM, Collins MT, et al. Epidemiology and diagnosis of hypoparathyroidism. J Clin Endocrinol Metab. 2016;101(6):2284-2299. https://doi.org/10.1210/jc.2015-3908.
  2. Bilezikian JP, Khan A, Potts Jr JT, 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. https://doi.org/10.1002/jbmr.483.
  3. Shoback DM, Bilezikian JP, Costa AG, et al. Presentation of hypoparathyroidism: etiologies and clinical features. J Clin Endocrinol Metab. 2016;101(6):2300-2312. https://doi.org/10.1210/jc.2015-3909.
  4. Abate EG, Clarke BL. Review of hypoparathyroidism. Front Endocrinol. 2016;7:172. https://doi.org/10.3389/fendo.2016.00172.
  5. Brandi ML, Bilezikian JP, Shoback D, et al. Management of hypoparathyroidism: summary statement and guidelines. J Clin Endocrinol Metab. 2016;101(6):2273-2283. https://doi.org/10.1210/jc.2015-3907.
  6. Drug trials snapshot: NATPARA (parathyroid hormone). US Food and Drug Administration. https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trials-snapshot-natpara-parathyroid-hormone. Page last reviewed May 9, 2017. Accessed January 15, 2020.
  7. First hormone replacement therapy for parathyroid disorder [press release]. European Medicines Agency. https://www.ema.europa.eu/en/news/first-hormone-replacement-therapy-parathyroid-disorder. February 24, 201 Accessed January 15, 2020.
  8. Takeda issues US recall of NATPARA® (parathyroid hormone) for injection due to the potential for rubber particulate [press release]. US Food and Drug Administration. https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/takeda-issues-us-recall-natparar-parathyroid-hormone-injection-due-potential-rubber-particulate. September 5, 2019. Accessed January 15, 2020.