Most patients with dwarfism due to growth hormone (GH) deficiency have normal pituitary somatotroph morphology and GH response to GH-releasing hormone (GRH), consistent with decreased GRH synthesis, release, or delivery. Primary pituitary hyposecretion of GH may result from adenohypophysial tissue destruction caused by tumors, such as craniopharyngioma. We report a hitherto undescribed form of primary pituitary dwarfism associated with absence of adenohypophysial GH, prolactin (PRL), and thyrotropin (TSH). Two sisters had dwarfism, hypothyroidism, and hypoglycemia. The first child had craniofacial abnormalities and died at age 11/2 months of fluid overload. The second sibling died at age 4 years of pulmonary congestion. At autopsy, both pituitaries were small and acidophils were conspicuously absent. They contained a normal number of corticotrophs with intense adrenocorticotropin (ACTH) immunoreactivity, and gonadotrophs with normal content of α-subunit and β-subunits of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). No GH, PRL, or β-TSH immunoreactivity was identified. The thyroid glandswere atrophic. Both children had marked pancreatic nesidioblastosis, with an increased number of insulin-containing cells. This clinicopathologic entity appears to represent a familial disorder in which there is defective development of three adenohypophysial cell types: somatotrophs, lactotrophs, and thyrotrophs. A common pituitary transcription factor, Pit-1, has been implicated in the differentiation of these three cell types. The pituitary changes in these two children resemble those described in Snell, Jackson, and Ames dwarf mice, which have recently been shown to be due to abnormalities of the Pit-1 gene. We suggest that this novel human disease is due to deficient or abnormal pituitary transcription factor Pit-1.
Keywords: Dwarf Mouse; Endocrine Pathology Volume; Growth Hormone; Growth Hormone Gene; Isolate Growth Hormone Deficiency.