In 1939, Drake et al. established the following criteria for the diagnosis of hypoparathyroidism: 1) low serum calcium; b) high serum inorganic phosphorus level; c) the absence of renal insufficiency, steatorrhea, chronic diarrhea, and alkalosis; d) exclusion of rickets and osteomalacia.

The disease may result from a deficiency in parathyroid hormone production or an end organ resistance to the action of the hormone. Pseudohypoparathyroidism (PHP) was first described by Albright et al. in 1942. It is a congenital hereditary abnormality that appears to be transmitted as an X-linked dominant trait characterized by hypocalcemia, hyperphosphatemia, basal ganglion and soft tissue calcification.

In PHP, there is a defect in the parathyroid hormone receptor-adenylate cyclase system which accounts for end organ resistance.

In most patients with classic PHP, there is a deficiency of guanyl nucleotide regulatory protein (G-unit) that normally couples receptor activity to adenylate cyclase activity. As a result, the kidney and, less commonly, the bones are unable to respond to parathyroid hormone. There may also be renal inability to hydroxylase 25-hydroxyvitamin D to 1,25 hydroxyvitamin D, the active form.

Pseudopseudohypoparathyroidism (PPHP) was the name selected by Albright and Reifenstein to describe a syndrome in short-statured patients with rounded faces, whose roentgen features simulated exactly those of PHP, the difference being the absence of blood chemical changes.

Osteosclerosis, which may be generalized or localized, is the most common skeletal abnormality of hypoparathyroidism. Typically, radiographic findings include increased radiodensity of the skeleton, calvarial thickening and hypoplastic dentition. Subcutaneous calcification may be seen, especially in the area of the hips and shoulders.

Particularly suggestive of hypoparathyroidism are intracranial calcifications of the basal ganglia that may later coalesce into homogeneous masses. Occasionally, these calcifications develop in the cerebellum.

The clinical syndrome of pseudotumor cerebri in association with hypoparathyroidism was reported as early as 1959 by Palmer et al.

DIFFERENTIAL DIAGNOSIS: Skeletal osteosclerosis is also seen in certain other disorders such as osteoblastic metastasis, myelofibrosis, Paget's disease, fluorosis, renal osteodystrophy, sickle cell anemia, and mastocytosis. In these and other diseases, other radiographic findings are usually apparent, allowing accurate diagnosis. In hypoparathyroidism and PHP, calvarial thickening and hypoplastic dentition are helpful clues, although Paget's disease, sickle cell anemia, and even metastasis may produce increased thickening and sclerosis of the calvarial vault.

Basal ganglion calcification is particularly characteristic of hypoparathyroidism and PHP. It is also seen without known cause in infectious disorders such as toxoplasmosis and cytomegalic inclusion disease, following radiation therapy, and following exposure to toxic substances such as carbon monoxide.

Subcutaneous calcifications are also seen in collagen vascular disease, hypervitaminosis D, milk alkali syndrome, and renal osteodystrophy. Hypoplastic dentition is also seen in cleidocranial dysostosis and pyknodysostosis, hypopituitarism, and hypothyroidism.

Sclerosis of the metaphyseal region of long bones seen in some patients with hypoparathyroidism is not specific. It may be seen in children with systemic illness leading to growth arrest lines, leukemia during treatment, heavy metal poisoning, hypothyroidism, healing scurvy, and hypervitaminosis.