The endocrine system
Laurie K. McCorry, Martin M. Zdanowicz, Cynthia Y. Gonnella in Essentials of Human Physiology and Pathophysiology for Pharmacy and Allied Health, 2019
As mentioned previously, thyroid hormones are secreted at a relatively steady rate. The secretion of hormones from the thyroid gland is regulated by negative feedback in the hypothalamic-pituitary-thyroid axis. The hypothalamus secretes thyrotropin-releasing hormone (TRH), which stimulates the release of TSH from the adenohypophysis of the pituitary. Thyroid-stimulating hormone then stimulates the release of T3 and T4 from the thyroid. In this hormone axis, negative-feedback inhibition is exerted primarily at the level of the pituitary. As the intracellular concentration of T3 in the thyrotrope cells of the pituitary increases, then there is a decrease in the responsiveness of these TSH-producing cells to TRH. The mechanism of this decreased responsiveness involves the downregulation, or a decrease in the number, of TRH receptors. This results in a decrease in the secretion of TSH, and, consequently, a decrease in the secretion of T3 and T4. The excess of intracellular T3, which elicits the negative feedback control of secretion comes from two sources; 80% from the removal of iodine from serum T4 within the thyrotrope cells and 20% from serum T3. Other factors that alter the release of TRH and, therefore, thyroid hormones, include exposure to cold (increased secretion) as well as anxiety (decreased secretion).
The Internal Milieu Brain and Body
Rolland S. Parker in Concussive Brain Trauma, 2016
1. Hypothalamic-pituitary-thyroid axis: Hypothalamic TRH (predominantly the PVN) stimulates the anterior pituitary to release TSH, stimulating hormone secretion by the thyroid gland. TRH is also produced in the hypothalamus and outside the nervous system. Somatostatin and dopamine reduce TRH secretion. Negative feedback is provided by thyroid hormone and cortisol in the PVN and hypothalamic ARC nucleus (Visser & Fliers, 2000). 2. Autoregulation of hormone synthesis in relationship to the gland’s iodine supply, and so forth (Greenspan, 2004). 3. Neural: In addition to input from the suprachiasmal nucleus (SCN), nerves originating from the cervical ganglia and the vagus nerve terminate within the thyroid gland (Young & Landsberg, 1998). 4. Glucocorticoids (cortisol) suppress the thyroid axis during stress at both central and peripheral levels (Visser & Fliers, 2000).
Interpretation
David Woolley, Adam Woolley in Practical Toxicology, 2017
In rats, this hepatic effect is often associated with changes in the thyroid, seen as increased weights and follicular cell hypertrophy; there is usually a dose response for these effects in the thyroid, which may mirror the liver changes. As a result, there may be the long-term consequence of thyroid tumors in carcinogenicity studies. The effects in the thyroid are elicited by increased metabolism of thyroid hormones by the enzymes induced in the liver. Reduced concentrations of thyroid hormones result in reduced negative feedback on the hypothalamic–pituitary–thyroid axis, leading to increased production of thyroid-stimulating hormone (TSH). The result is hypertrophy of the thyroid hormone–producing cells; there may also be a hypertrophic response in the anterior pituitary. Male rats are more commonly and severely affected than females because they have higher circulating concentrations of TSH.
Therapeutic approaches of trophic factors in animal models and in patients with spinal cord injury
Published in Growth Factors, 2020
María del Carmen Díaz-Galindo, Denisse Calderón-Vallejo, Carlos Olvera-Sandoval, J. Luis Quintanar
TRH is a hypothalamic tripeptide with numerous physiological and biochemical actions. Its role in the hypothalamic-pituitary-thyroid axis is well known. TRH induces the synthesis and release of the thyroid stimulating hormone produced by the adenohypophysis, which in turn stimulates the thyroid gland for the synthesis and secretion of thyroid hormones (thyroxine and triiodothyronine) (Fröhlich and Wahl 2019). However, TRH or its analogous, may have neurological functions independent of thyroid hormones (Monga et al. 2008). Numerous preclinical studies have demonstrated that posttraumatic treatment of SCI with TRH or its analogues, improves of motor or sensitive functions. In patients with acute SCI with complete and incomplete injury groups within 12 h of trauma were treated with TRH (0.2 mg/kg intravenous bolus followed by 0.2 mg/kg/h infusion over 6 h). In these patients, clinical examination included motor and sensory testing, as well as assigning a Sunnybrook score based upon level of function. They were examined at 24 h, 72 h, 1 week, 1 month and 4 months after injury. There appeared to be no discernible treatment effect in patients with complete injuries although data were available from only six such patients at 4 months. For the incomplete injury group, a total of six treated and five placebo patients had 4-month evaluations. TRH treatment was associated with significantly higher motor, sensory, and Sunnybrook scores than placebo group (Pitts et al. 1995).
Therapeutic challenges in the application of serum thyroid stimulating hormone testing in the management of patients with hypothyroidism on replacement thyroid hormone therapy: a review
Published in Current Medical Research and Opinion, 2019
Nevertheless, the reference ranges for thyroid biomarkers are broad in physiological terms, having been defined across populations, while the variation of these markers in individual subjects appears to be much lower16. Accordingly, variations in thyroid hormone levels of sufficient size to induce meaningful changes in thyroid function may not exceed the reference ranges16,17. Individuals have their own “set points” for the operation of the hypothalamic–pituitary–thyroid axis that differ from the relationships between TSH and FT4 documented in populations16,18. This means that, for example, an abnormal FT4 level may persist despite TSH being within the normal range, and a normal FT4 level for one patient may be abnormal for another, so that adjustment of TSH levels using LT4 in an attempt to corral thyroid marker levels within reference ranges may result in appropriate thyroid function for that individual19. Levothyroxine therapy appears to shift the position of the set point over time, with a gradual reduction in the dose of LT4 required to lower TSH (where elevated) although some of this change is due to ageing (see below)20.
Hypophysitis related to immune checkpoint inhibitors: An intriguing adverse event with many faces
Published in Expert Opinion on Biological Therapy, 2021
Maria V Deligiorgi, Charis Liapi, Dimitrios T Trafalis
Central hypothyroidism is diagnosed by low fT4 levels and low or inappropriately low normal TSH levels [91]. Low LH and FSH levels simultaneously with low testosterone (males) or estradiol (females) levels are indicative of central hypogonadism. A caveat to diagnosis of central hypothyroidism and/or hypogonadism is that other conditions ‒mainly medications other than ICPi, such as glucocorticoids, and severe illness ‒ can suppress the hypothalamic-pituitary-thyroid axis and/or the hypothalamic-pituitary-gonadal axis, yielding a hormonal status reminiscent of ir hypophysitis. Careful consideration of the clinical context could help the differential diagnosis. Prolactin levels may be low or elevated (less common) [16, 68, 69, 102].
Related Knowledge Centers
- Neuroendocrinology
- Triiodothyronine
- Metabolism
- Thyroid
- Levothyroxine
- Pituitary Gland
- Hypothalamus
- Hypothalamic–Pituitary–Adrenal Axis
- Hypothalamic–Pituitary–Gonadal Axis
- Development of The Human Body