Thyroid hormone pituitary resistance

There are several ways by which TSH secretion can be increased. An increased hepatic enzyme activity may cause an increased metabolism of thyroid hormones, leading to lower semm hormone levels, which in mm leads to increased secretion of TRH, and subsequently increased TSH secretion. Regarding human relevance, the pathways for regulation of the hypothalamo-pituitary-thyroid axis of rats and humans are similar and the mechanism is relevant for humans, but the human system is far more resistant to perturbation. 

Pituitary resistance to thyroid hormone (PRTH) refers to selective resistance of the pituitary thyrotrophs to thyroid hormone. About twice as many women as men have been reported with this rare, probably familial syndrome. Multiple abnormalities have been reported in the initial 50 reported cases including schizophrenia (three patients), mental retardation (two patients), short fourth metacarpals (one patient), and Marfanoid habitus (one patient). About 90% of patients studied have an appropriate increase in TSH in response to TRH conversely, the TSH will be suppressed by T3 administration. 

Two distinct genes encode 2 families of TRs, TRa and TRp, and both genes encode multiple receptor isoforms. Certain isoforms (e.g., TR j and TRPj) are found in virtually all thyroid hormone-responsive tissues, whereas TRp is expressed only in the anterior pituitary. Resistance to thyroid hormone has been described in patients with mutations in the TRp gene. In addition to nuclear receptor-mediated actions, there are several well-characterized, nongenomic actions of thyroid hormones, including those occurring at the plasma membrane and on the cellular cytoarchitecture. 

Generalized resistance to thyroid hormone (GRTH) is a rare form of thyroid disorder and may be a heritable disorder characterized by reduced responsiveness of the pituitary and peripheral tissues to the action of thyroid hormones. Behavioral manifestations include hyperactivity, behavioral problems, and cognitive... 

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