Clinical Pearls & Morning Reports

Posted by Carla Rothaus

Published May 1, 2019


What therapies are used for the long-term management of hypoparathyroidism?

Hypoparathyroidism is suspected in patients with a low ionized or albumin-corrected blood calcium level, hyperphosphatemia, and an intact PTH level that is low or that is inappropriately in the normal range. Read the Clinical Practice article here.

Clinical Pearls

Q: What is the most common cause of hypoparathyroidism?

A: Hypoparathyroidism most commonly occurs as a complication of anterior neck surgery (in approximately 78% of cases) and is therefore seen more frequently in older adult women, who are more likely than others in the general population to undergo thyroid surgery. However, there is an expanding list of genetic and nonsurgical acquired causes, including autoimmune causes.

Q: What signs and symptoms are associated with hypoparathyroidism?

A: Most patients with hypoparathyroidism have neuromuscular signs and symptoms of hypocalcemia, ranging from mild paresthesias, muscle cramps, and prolongation of the corrected QT (QTc) interval to severe, life-threatening manifestations such as arrhythmias, laryngospasm, and seizures. In some patients, particularly those with certain genetic forms of hypoparathyroidism, the hypocalcemia may be asymptomatic.

Morning Report Questions

Q: What therapies are used for the long-term management of hypoparathyroidism?

A: In contrast to most hormone deficiencies, for which hormone replacement is the mainstay of therapy, hypoparathyroidism has been conventionally treated with high-dose vitamin D (cholecalciferol or ergocalciferol) and calcium supplements or with activated vitamin D and calcium supplements. Large, randomized, controlled trials evaluating conventional management of hypoparathyroidism have been limited, and standard practice is based on case series, expert opinion, and consensus guidelines. Because PTH is needed for activation of renal 25-hydroxyvitamin D 1α-hydroxylase, vitamin D analogues that have already undergone 1α-hydroxylation (calcitriol and alfacalcidol) are generally preferred; these have a relatively short half-life as compared with other vitamin D analogues, thus decreasing the risk of prolonged hypercalcemia if vitamin D intoxication occurs. However, high doses of cholecalciferol and ergocalciferol, which have a long half-life and were the mainstay of therapy before the availability of 1α-hydroxylated vitamin D analogues, may also be considered. Frequent monitoring of blood calcium, phosphate, magnesium, and creatinine levels and of urinary calcium excretion is essential to avoid overtreatment or undertreatment. Blood calcium levels are targeted at or slightly below the lower limit of the normal range, to the extent possible, while being careful to avoid the neuromuscular symptoms of hypocalcemia. Maintenance of slightly low blood calcium levels is necessary to avoid hypercalciuria, defined by a 24-hour excretion of more than 4 mg of calcium per kilogram of body weight per day (>0.1 mmol per kilogram per day). 

Q: Is recombinant human PTH approved for the treatment of hypoparathyroidism in the United States?

A: Recombinant human PTH 1–84 has been approved for the treatment of hypoparathyroidism in both the United States and (conditionally) in Europe in adults who have disease that is refractory to conventional therapy, with the exception of patients who have autosomal dominant hypocalcemia, who were not included in clinical trials. Many studies have shown that hypocalcemia can be adequately managed in most patients by means of once-daily or twice-daily subcutaneous injections of teriparatide (PTH 1–34 fragment) or intact PTH (PTH 1–84). In a 6-month, placebo-controlled trial, the use of PTH 1–84 also reduced blood phosphate levels, which may be important in preventing ectopic calcifications. However, PTH 1–34 and PTH 1–84 therapies have both shown inconsistent effects on hypercalciuria, and long-term studies to determine whether PTH therapy reduces the development or progression of renal calcifications or renal insufficiency have been limited.

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