bone disorders

Hypoparathyroidism: A Q&A With Dr Natalie E. Cusano

Parathyroid hormone (PTH) helps regulate bone turnover and levels of calcium, phosphorous, and active vitamin D. However, in some individuals, the parathyroid glands in the neck are damaged during surgery or secrete abnormally low levels of PTH from a genetic or autoimmune disease, causing hypoparathyroidism. As a result, these individuals experience a decrease in blood calcium levels, an increase in phosphorous levels, hypercalciuria, and other related complications.1

Consultant360 spoke with Natalie E. Cusano, MD, Director of the Bone Unit in the Division of Endocrinology at Lenox Hill Hospital in New York. Dr Cusano recently presented the session “Hypoparathyroidism: Guidelines and New Treatments” on September 23 at the Endocrine Society’s Clinical Endocrinology Update 2017 in Chicago, Illinois.2

Consultant360: How common is hypoparathyroidism in the United States?

Natalie E Cusano: Hypoparathyroidism has been classified as an orphan disease in the United States. The best estimate we have is that about 77,000 people in the United States have hypoparathyroidism, of whom 75% have post-surgical hypoparathyroidism. While it may be rare, the disease can place a very large burden on patients and their families.

C360: How can health care providers better diagnose hypoparathyroidism? Are there any differential diagnoses that can complicate the diagnosis process?

NEC: All patients after thyroid, parathyroid, or other neck surgery should be followed very closely post-operatively for signs or symptoms of hypocalcemia. Patients with autoimmune or idiopathic hypoparathyroidism that develops over many years may have a wide range of nonspecific symptoms, including weakness, muscle cramps, and anxiety. It is always important to take patients’ symptoms seriously and evaluate with appropriate testing. Magnesium disorders are the only reversible cause of hypoparathyroidism.

C360: What tests can be performed to verify a hypoparathyroidism diagnosis?

NEC: Measurement of albumin-corrected serum calcium or ionized calcium, PTH, and magnesium can easily make the diagnosis. Low calcium with a low or insufficient PTH concentration is consistent with hypoparathyroidism. Again, magnesium disorders are the only reversible cause of hypoparathyroidism.

C360: What consequences might patients face if hypoparathyroidism goes undiagnosed?

NEC: Severe hypocalcemia can lead to a number of life-threatening conditions, including laryngospasm/bronchospasm, heart arrhythmias, and seizures. Chronic hypocalcemia can lead to congestive heart failure.

C360: What treatment options are currently available in the United States? Are there any new medications available?

NEC: Conventional therapy of hypoparathyroidism consists of calcium and calcitriol, often in large doses. There are a number of therapeutic challenges in the management of patients: calcium has to be taken throughout the day to keep serum calcium stable; many factors, including infection, anxiety, and exercise, can change requirements; it can be difficult to control symptoms completely; and there are concerns for the long-term complications of therapy with large doses of calcium and calcitriol, in particular with regard to the renal system and other extraskeletal calcifications.

rhPTH(1-84) was approved by the FDA in January 2015 for “patients who cannot be well-controlled on calcium supplements and active forms of vitamin D alone.” It may be challenging to decide which patients are considered difficult to control. The guidelines from the First International Workshop are very helpful on the subject of indications for rhPTH(1-84) therapy.

C360: In your opinion, are current clinical guidelines effective for the management and treatment of hypoparathyroidism? If not, what needs to change?

NEC: For many years, physicians had no guidance in managing patients with hypoparathyroidism. We now have two sets of guidelines, from the European Society of Endocrinology3 and the First International Workshop on the Management of Hypoparathyroidism,4 published with 3 companion papers.5,6,7 Both offer very effective guidance with regard to conventional therapy of hypoparathyroidism, management goals and monitoring of patients. The guidelines from the First International Workshop are very helpful on the subject of indications for recombinant human parathyroid hormone(1-84) [rhPTH(1-84)] therapy.

It is important to note that there is a lack of evidence-based data in hypoparathyroidism. There are few studies, with only 1 treatment study having a sample size of more than 100 patients. Even though the guidelines are primarily based on expert opinion, they remain highly significant and valuable. Because this disease is so rare, the average practitioner will see very few patients with hypoparathyroidism, and recommendations from experts in the field can be essential.

C360: Other than medication and standard treatments, what else can practitioners recommend to patients for the management of hypoparathyroidism?

NEC: Patients may notice that they have hypocalcemic symptoms consistently at certain times, including after exercise or during their menstrual period. It may be helpful to recommend extra calcium if there are consistent triggers. Anxiety and stress can also increase requirements. Lifestyle changes to reduce stress and anxiety can be helpful.

—Christina Vogt

References:

  1. Hypoparathyroidism. MedlinePlus. https://medlineplus.gov/ency/article/000385.htm. Updated September 5, 2017. Accessed on September 29, 2017.
  2. Cusano N. Hypoparathyroidism: guidelines and new treatments. Presented at: Clinical Endocrinology Update 2017; September 23-25, 2017. Chicago, IL. https://www.endocrine.org/ceu/program/day-one.
  3. 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:G1-G20. doi:10.1530/EJE-15-0628.
  4. 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.
  5. Clarke BL, Brown EM, Collins, MT, et al. Epidemiology and diagnosis of hypoparathyroidism. J Clin Endocrinol Metab. 2016;101(6):2284-2289. https://doi.org/10.1210/jc.2015-3908.
  6. 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.
  7. Bilezikian JP, Brandi ML, Cusano NE, et al. Management of hypoparathyroidism: present and future. J Clin Endocrinol Metab. 2016;101(6):2313-2324. https://doi.org/10.1210/jc.2015-3910.