Hypoparathyroidism: Is It Time for Replacement Therapy?

Endocrine diseases caused by hormone deficiencies are commonly treated by replacement of the deficient hormones. For example, Addison’s disease is treated with oral glucocorticoids, autoimmune hypothyroidism with oral thyroxine, and premature ovarian failure with oral estrogen and progesterone. The availability of orally deliverable drugs makes this straightforward. However, when the deficient hormone in question is a protein, oral treatment presents problems because proteins are generally degraded by proteolytic digestive enzymes when delivered orally. This obstacle commonly is circumvented by sc injection of the peptide hormone in question (i.e. GH, insulin, 1-desamino--D-arginine vasopressin). So what is different abouthypoparathyroidism,whichalsoresultsfromdeficiencyof PTH, a protein hormone? Why is this disorder not routinely treated by replacement of PTH? This is the subject of a series of reportsbyWineretal.(1–4),themostrecentofwhichisincluded in this month’s Journal (4). Hypoparathyroidism results from deficiency of PTH (5–9). This may be a congenital abnormality resulting in failure of the parathyroid glands to form, as exemplified by the DiGeorge syndrome, or may result from inactivating mutations in the parathyroid-specific transcription factor, glial-cell missing B. It may result from mutations in the PTH gene itself. A functional, congenital form of hypoparathyroidism results fromactivatingmutationsinthecalcium-sensingreceptorthat