TSH secretion

The growth and spread of thyroid carcinoma are stimulated by TSH. An important component of thyroid carcinoma management is the use of LT4 to suppress TSH secretion. Early in therapy, patients receive the lowest LT4 dose sufficient to fully suppress TSH to undetectable levels. Controlled trials show that suppressive LT4 therapy reduces tumor growth and improves survival. 

FIGURE 41-1. Hypothalamic-pituitary-thyroid axis. Thyrotropinreleasing hormone (TRH) is synthesized in the neurons within the paraventricular nucleus of the hypothalamus. TRH is released into the hypothalamic-pituitary portal circulation and carried to the pituitary, where it activates the pituitary to synthesize and release thyrotropin (TSH). TSH activates the thyroid to stimulate the synthesis and secretion of thyroxine (T4) and triiodothyronine (T3). T4 and T3 inhibit TRH and TSH secretion, closing the feedback loop. 

Secondary hyperthyroidism TSH-secreting pituitary tumors Trophoblastic (hCG-secreting) tumors Gestational thyrotoxicosis... 

Thyroid hormone is liberated into the bloodstream by the process of proteolysis within thyroid cells. T4 and T3 are transported in the bloodstream by three proteins thyroid-binding globulin, thyroid-binding prealbumin, and albumin. Only the unbound (free) thyroid hormone is able to diffuse into the cell, elicit a biologic effect, and regulate thyroid-stimulating hormone (TSH) secretion from the pituitary. 

Thyroid hormone production is regulated by TSH secreted by the anterior pituitary, which in turn is under negative feedback control by the circulating level of free thyroid hormone and the positive influence of hypothalamic thyrotropin-releasing hormone. Thyroid hormone production is also regulated by extrathyroidal deiodination of T4 to T3, which can be affected by nutrition, nonthyroidal hormones, drugs, and illness. 

TSH-secreting pituitary tumors release biologically active hormone that is unresponsive to normal feedback control. The tumors may cosecrete... 

TSH-secreting pituitary adenomas are diagnosed by demonstrating lack of TSH response to thyrotropin-releasing hormone stimulation, inappropriate TSH levels, elevated TSH a-subunit levels, and radiologic imaging. 

In older patients with goiter due to iodine deficiency there is a risk of provoking hyperthyroidism by increasing iodine intake (p. 247) During chronic maximal stimulation, thyroid follicles can become independent of TSH stimulation ( autonomic tissue"). If the iodine supply is increased, thyroid hormone production increases while TSH secretion decreases due to feedback inhibition. The activity of autonomic tissue, however, persists at a high level thyroxine is released in excess, resulting in iodine-induced hyperthyroidism. 

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. 

Secondary hypothyroidism, or pituitary hypothyroidism, is the consequence of impaired thyroid-stimulating hormone (TSH) secretion and is less common than primary hypothyroidism. It may result from any of the causes of hypopituitarism (e.g., pituitary tumor, postpartum pituitary necrosis, trauma). Patients with secondary hypothyroidism exhibit undetectable or inappropriately low serum TSH concentrations. In secondary hypothyroidism, a normal thyroid gland lacks the normal level of TSH stimulation necessary to synthesize and secrete thyroid hormones. Such patients usually also have impaired secretion of TSH in response to exogenous thyrotropin-releasing hormone (TRH) administration. 

All of these naturally occurring molecules are levo (l) isomers. The synthetic dextro (d) isomer of thyroxine, dextrothyroxine, has approximately 4% of the biologic activity of the L-isomer as evidenced by its lesser ability to suppress TSH secretion and correct hypothyroidism. 

Inhibition of TRH or TSH secretion without induction of hypothyroidism or hyperthyroidism Dopamine, levodopa, corticosteroids, somatostatin, metformin, bexarotene... 

Studies have indicated that HA participates in the hypothalamic regulation of thyrotropin (TSH) secretion by an inhibitory action [for review see 3,14], However, to our knowledge data have not been presented concerning the effect of H3 receptor manipulation of thyrotropin secretion. 

Lattanzi V, Scardapane R, Santoro G, Mongelli S, Glorgino R. 1979. [Chronobiological aspects of TSH secretion in control subjects and in subjects with primary hypothyroidism] In Italian. Boll Soc ItalBiol Sper 55 2358-2364. 

The G protein complexes related to thyrotrophs TRH receptors affect phosphoinositide-specific phospholipase C, which increases intracellular cytoplasmic free calcium, thereby stimulating TSH secretion. 

Stimulating Hormone (TSH) secretion without induction of hypothyroidism Inhibition of thyroid hormone synthesis or release with the induction of hypothyroidism (or occasionally hyperthyroidism)... 

Regulation of secretion Secretion of TSH by the anterior pituitary is stimulated by the hypothalamic TRH. Feedback inhibition of both TRH and TSH secretion occurs with high levels of circulating thyroid hormone or iodide. Most of the hormone (T3 and T4) is bound to thyroxine-binding globulin in the plasma. 

The changes in base-line hormone secretion are useful for interpretation of drug effects, it is often advisable to include dynamic function tests based on stimulation of pituitary hormone secretion, or of gonadal and adrenal hormone secretion. Examples for pituitary testing have been mentioned above and secretion. Typical pituitary function tests are the TRH test for TSH secretion, the LHRH test for secretion of FSH and LH, and the mono iodo-tyrosine (MIT) test for prolactin secretion. Synthetic CRF may be injected to stimulate secretion of corticotropin (ACTH), more frequently the injection of corticotropin is used to stimulate the adrenal directly. At the target organ level, similar... 

Test should include measurement of basal concentrations for TSH, total T3, and total T4 - at several time points during the study. Measurement of the free fractions of T3 and T4 is in our experience not required and does not contribute to interpretation of the organ related findings e.g. in thyroid histology. A TRH test may be included for the stimulation of TSH secretion by subcutaneous injection of TRH. 

Andersson K, Eneroth P (1987) Thyroidectomy and central catecholamine neurons of the male rat. Evidence for the existence of an inhibitory dopaminergic mechanism in the external layer of the median eminence and for a facilitatory noradrenergic mechanism in the paraventricular hypothalamic nucleus regulating TSH secretion. 

Annunziato L, Di Renzo GF, Schettini G, Lombardi G, Scopacasa F, Scapagnini U, Preziosi P (1979) Lack of evidence for an inhibitory role played by tuberoinfundibular dopaminergic neurons on TSH secretion in the rat. Neuroendocrinology 23 435-441. 

Dieguez C, Foord SM, Peters JR, Hall R, Scanlon MF (1984) Interactions among epinephrine, thryotropin (TSH)-releasing hormone, dopamine, and somatostatin in the control of TSH secretion in vitro. Endocrinology 774 957-961. 

Krulich L, Giachetti A (1977) On the role of the central noradrenergic and dopaminergic systems in the regulation of TSH secretion in the rat. Endocrinology 700 496-505. 

Secretion of T3 and T4 is controlled by circulating TSH released from the anterior pituitary gland. When levels of T3 and T4 rise, the secretion of TSH is reduced. TSH secretion is also controlled by thyrotrophin releasing hormone (TRH) from the hypothalamus. 

Q10 Many endocrine secretions are controlled by negative feedback systems. When the thyroid is stimulated and thyroid hormone concentration increases, it inhibits production of TSH to reduce further stimulation of the gland. As thyroid hormone secretion then diminishes, the negative feedback on the anterior pituitary is reduced and TSH secretion increases again. Basically, in... 

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