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Inadequate production of anterior pituitary hormones leads to features of hypopituitarism. Impaired production of one or more of the anterior pituitary trophic hormones can result from inherited disorders; more commonly, adult hypopituitarism is acquired and reflects the compressive mass effects of tumors or the consequences of local pituitary or hypothalamic traumatic, inflammatory, or vascular damage. These processes also may impair synthesis or secretion of hypothalamic hormones, with resultant pituitary failure (Table 4-1).
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DEVELOPMENTAL AND GENETIC CAUSES OF HYPOPITUITARISM
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Pituitary dysplasia may result in aplastic, hypoplastic, or ectopic pituitary gland development. Because pituitary development follows midline cell migration from the nasopharyngeal Rathke’s pouch, midline craniofacial disorders may be associated with pituitary dysplasia. Acquired pituitary failure in the newborn also can be caused by birth trauma, including cranial hemorrhage, asphyxia, and breech delivery.
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SEPTO-optic dysplasia
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Hypothalamic dysfunction and hypopituitarism may result from dysgenesis of the septum pellucidum or corpus callosum. Affected children have mutations in the HESX1 gene, which is involved in early development of the ventral prosencephalon. These children exhibit variable combinations of cleft palate, syndactyly, ear deformities, hypertelorism, optic nerve hypoplasia, micropenis, and anosmia. Pituitary dysfunction leads to diabetes insipidus, growth hormone (GH) deficiency and short stature, and, occasionally, thyroid-stimulating hormone (TSH) deficiency.
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Tissue-specific factor mutations
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Several pituitary cell–specific transcription factors, such as Pit-1 and Prop-1, are critical for determining the development and committed function of differentiated anterior pituitary cell lineages. Autosomal dominant or recessive Pit-1 mutations cause combined GH, prolactin (PRL), and TSH deficiencies. These patients usually present with growth failure and varying degrees of hypothyroidism. The pituitary may appear hypoplastic on magnetic resonance imaging (MRI).
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Prop-1 is expressed early in pituitary development and appears to be required for Pit-1 function. Familial and sporadic PROP1 mutations result in combined GH, PRL, TSH, and gonadotropin deficiency. Over 80% of ...