The spectrum of hypopituitarism caused by PROP1 mutations

Mutations in the PROP1 gene are responsible for a high proportion of cases of multiple or combined anterior pituitary hormone deficiencies in humans. The physical and hormonal phenotypes of affected individuals are not uniform. The diagnosis is seldom considered during the first year of life. Growth failure is usually evident later in childhood. Deficiency of growth hormone (GH) tends to precede deficiency of thyroid-stimulating hormone (TSH). While most affected individuals fail to enter puberty without sex hormone replacement, some enter puberty but then develop pubertal arrest with a loss of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) responses to GnRH. Partial deficiency of corticotrophin (ACTH) is a late finding. Imaging of the pituitary may disclose either a small anterior pituitary gland or an intrapituitary mass. The mechanisms responsible for delayed loss of hormone production and the occasional overgrowth of the pituitary represent important areas for future research.