Evolution of Skeletal Lesions in Pseudohypoparathyroidism

Abstract

Pseudohypoparathyroidism is a congenital, hereditary abnormality characterized by hypocalcemia and hyperphosphatemia, as in hypoparathyroidism. It does not, however, respond adequately to parathyroid hormone. The parathyroid glands are present and may be hyperplastic, but the hormones produced by them lack the ability to effect phosphate diuresis. This deficiency is the result of end-organ resistance (1), elaboration of defective hormone (6), or the occurrence of anti-enzymes in the serum or tissues (10). In some of these cases changes in bones have been described that indicate osteitis fibrosa cystica and the production of excessive quantities of a bone-resorbing hormone (8, 9). Most of these patients are short in stature, obese, and mentally retarded, and corneal or lenticular opacity and brachydactylia may be encountered (1, 3, 4, 10, 12). In many instances roentgenograms show calcification or ossification of the skin or subcutaneous tissues (5) or calcification of the basal ganglia or other parts of the brain. Evidence of exostosis, accelerated closure of epiphyses, short phalanges, metacarpals and metatarsals, and delayed or defective dentition may also be seen on roentgen studies. In some instances, the skeletal density is diffusely decreased, usually ascribable to osteoporosis. In other cases, the typical subperiosteal erosions and cysts of osteitis fibrosa cystica are observed. Some patients exhibit the physical appearance and roentgen findings of pseudohypoparathyroidism, but blood chemistry levels are normal. Because of this partially different manifestation, this disease has been called “pseudo-pseudohypoparathyroidism” (1). Since in some families (7) evidence of both diseases has been found, the two are obviously related. Cases of pseudohypoparathyroidism have also been observed in which the initially abnormal blood calcium and phosphorus have reverted to normal. Although pseudohypoparathyroidism in childhood is diagnosed frequently, its presence in early infancy has not been reported. Taitz (14) was the first to report the diagnosis in the first year of life; his 4-month-old patient had no skeletal deformities. A case of pseudohypoparathyroidism is presented below, in which the characteristic skeletal lesions, though absent at nine months, had developed by the age of forty-nine months. Case Report This boy was first seen as an out-patient at the Children's Hospital, Karolinska Sjukhuset, Stockholm, in September 1960 at the age of nine months. He was the third child of apparently healthy parents. At birth, his height, weight, and head circumference were normal. A short time after delivery, the patient's mother noticed in the child's left wrist hard, subcutaneous nodules that subsequently enlarged. Other nodules developed on the arms, abdomen, and legs. Otherwise the child was in good health. He had experienced no convulsions. The patient had two healthy older sisters.