Albright's Hereditary Osteodystrophy Comprising Pseudohypoparathyroidism and Pseudo-pseudohypoparathyroidism

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Abstract
Albright''s hereditary osteodystrophy is a rare genetic disorder which, in its fully developed form, has traditionally been called pseudohypoparathyroidism (PH) and comprises short stature, mental retardation, hypocalcemic tetany refractory to correction with parathyroid extract, a characteristic group of osseous abnormalities, and sometimes other manifestations. A somewhat less common normocalcemic variant, usually termed pseudo-pseudohypoparathyroidism (PPH), is the most clearly delineated of a number of incompletely expressed forms which the disorder may take clinically. Cases exhibiting still fewer of the characteristic features are of relatively frequent occurrence but may be impossible to identify with assurance. In such cases the disorder may simulate certain other syndromes which seem to be genetically quite unrelated. Albright''s hereditary osteodystrophy is often overtly heredofamilial; and it is possible, owing to the relative frequency of cases in which little or no clinical expression of the genetic fault takes place, than an actual familial background has remained occult in some or all of the seemingly sporadic cases which have been encountered. The mode of inheritance has not been definitely established, but transmission as a sex-linked dominant is suggested by the predominance of affected females over males in a 21 ratio, and by the still greater disproportion of females over males transmitting the disease. Whether male-to-male transmission occurs is questioned. Two cases representing the first recorded direct transmission of the fully expressed syndrome (PH) are presented. The pathogenesis is unknown, and the pathophysiology of the hormone-resistant hypocalcemia is not es- tablished. The Ellsworth-Howard Test does not give a reliable estimate of the responsiveness of the renal tubule to parathyroid hormone. The only acceptable proof of refractoriness to the hormone is provided by demonstrating that the low serum calcium concentration is unaffected by a two-week course of daily intramuscular injections of parathyroid extract. The microscopic appearance of parathyroid glands taken from a patient with the fully developed disorder is presented and the findings in 3 other cases reviewed. The histologic hyperplasia which was found in 2 untreated cases suggests parathyroid overactivity, but little is known as yet concerning the gross quantity and appearance of the parathyroid tissue of these patients. Histophysiologic inferences as to the quantity and quality of parathyroid hormone being released by their glands are hazardous.