Approach
The underlying signaling defects are incurable. The main aim of management of parathyroid hormone (PTH) resistance is to maintain levels of calcium and phosphorus within the normal range while avoiding hypercalciuria.[1][2] Symptomatic hypocalcemia is a medical emergency and requires prompt treatment. Asymptomatic hypocalcemia can be managed primarily with oral calcium supplements. Associated endocrinopathies are treated with hormone replacement. Treating patients with diminished mental function requires instructing appropriate caregivers to ensure proper administration of medication.
Patients with symptomatic hypocalcemia
Symptomatic hypocalcemia is an acute medical emergency, and intravenous calcium gluconate should be given as soon as possible. Calcium should be given in an infusion to reduce fluctuations in levels. ECG monitoring is required during the administration of intravenous calcium to detect calcium-induced cardiac conduction defects. If the response to intravenous calcium is inadequate, calcitriol (a vitamin D metabolite) can be added to improve calcium absorption from the gut; this is particularly beneficial in infants.[48] Patients with pseudohypoparathyroidism (PHP) do not usually have vitamin D deficiency, and care must be taken to avoid vitamin D overdosing. Calcitriol is preferred to cholecalciferol or ergocalciferol because PTH-mediated activation is not required, and calcitriol toxicity is easier to reverse as it has a short half-life and is not stored in adipose tissue.
The patient should be transitioned to oral calcium supplements once the acute symptoms have resolved.
Long-term management of hypocalcemia
This involves the reduction of extraskeletal calcification by achieving serum calcium goal at the lower limit of laboratory normal range, and normalization of serum phosphorus. Oral calcium supplements (e.g., calcium carbonate and calcium acetate) are preferred for maintaining a normal serum calcium. The advantage of these supplements is that they also act as phosphate binders and reduce the absorption of phosphate from the gut. They therefore allow calcium levels to be maintained without increasing the risk of extraskeletal calcification. Dietary sources of calcium also contain high levels of phosphate, so increasing calcium intake from this source increases the risk of extraskeletal calcification. Aluminum phosphate binders should be avoided.
Vitamin D enhances the absorption of calcium from the gut; calcitriol can be given to increase calcium levels if normalization of calcium levels is not achieved with calcium supplementation. Thiazide diuretics can reduce calcium loss through the kidney and can be added to further increase calcium levels.
Associated endocrinopathies
Associated endocrinopathies require treatment with hormone replacement. The most common is hypothyroidism, which requires long-term treatment with levothyroxine. In children with short stature, growth hormone therapy may be beneficial. Children with delayed maturation may require exogenous testosterone or estrogen. The onset of growth hormone deficiency in PHP type Ia is variable, making the time interval to treat short stature limited. Attempts to determine the etiology and best treatment regimen are ongoing. The effect of human growth hormone in this group has been studied and researchers demonstrated successful attainment of height velocity in prepubertal children.[49] In this small series only one child attained normal final height. The findings suggested the lack of sufficient growth hormone-releasing hormone effect as a major component of short stature.
For more information on the management of children with delayed maturation and those with growth hormone deficiency, please see Delayed puberty and Growth hormone deficiency in children.
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