Hypothalamic–pituitary–thyroid axis control over the hypothalamus as well as anterior pituitary, thus controlling the release of both TRH from hypothalamus and TSH from anterior pituitary gland. The HPA, HPG, and HPT axes are three pathways in which the hypothalamus and pituitary direct neuroendocrine function. Thyroid homeostasis results from a multi-loop feedback system that is found in virtually all higher vertebrates. Proper function of thyrotropic feedback control is indispensable for growth, differentiation, reproduction and intelligence. Very few animals (e.g. axolotls and sloths) have impaired thyroid homeostasis that exhibits a very low set-point that is assumed to underlie the metabolic and ontogenetic anomalies of
Pituitary adenoma interacting protein" ("AIP") gene , and duplications in chromosome Xq26.3 that include the "GPR101" gene that also causes X-linked acrogigantism (X-LAG) syndrome. About 15-20% of FIPA families carry a germline "AIP" gene mutation or deletion, and the disease occurs as autosomal dominant with incomplete penetrance, meaning that about 20% of AIP mutation carriers will develop a pituitary adenoma. "AIP" mutation associated pituitary adenomas (either presenting as FIPA or as individual, non familial cases) are usually growth hormone secreting (acromegaly) or prolactin secreting (prolactinoma) adenomas that are large (macroadenomas) and often occur in children, adolescents and young adults. Daly and colleagues