China
Africa
Explore chapters and articles related to this topic
The Syndromes of Reduced Responsiveness to Thyroid Hormone
Published in Geraldo Medeiros-Neto, John Bruton Stanbury, Inherited Disorders of the Thyroid System, 2019
Geraldo Medeiros-Neto, John Bruton Stanbury
All mutations that have been identified in subjects with thyroid hormone resistance have been found in the β gene; none has been definitely associated with the α gene, although mutations in the α gene have been suggested. Thus, mutations in the α gene may be either trivial or lethal. Over 60 different mutations have been described in the TR-β gene in families with thyroid hormone resistance. All but one of these are located near the thyroid hormone binding site. They are either nearly full deletions including part of the hormone-binding domain (the original family),31 or amino acid substitutions or deletions (Figure 4). One mutation has been reported well removed from the LBD near the hinge area of the TR-β, but at a point where it also affects T3 binding at the LBD.32 The mutation in the first family1 with the GRTH syndrome was a virtually complete deletion of the hormone-binding site, and inheritance was autosomal recessive, i.e., both genes on chromosome 3 were virtually completely deleted, both at the LBD and the DBD.32 Thus, complete absence of the gene product is compatible with nearly normal development, and indeed with no thyroid hormone receptor activity the subjects in this family in fact responded to thyroid hormone, but only at a level higher than normal. Yet curiously, in other instances mutations that conform to a recessive pattern may have deleterious developmental effects. There is no clear explanation for this.
Hypothyroidism
Published in David S. Cooper, Jennifer A. Sipos, Medical Management of Thyroid Disease, 2018
Peripheral hypothyroidism is rare, and there is no general agreement on when and how to initiate investigations for these conditions. However, the presence of very high serum TSH levels in association with normal free T4 levels may prompt one to measure serum total T3; a very low serum T3 in these circumstances should lead to imaging for deiodinase expressing tumors causing “consumptive hypothyroidism,” starting with the liver. Tumors producing this syndrome are typically hemangiomas, hemangioblastomas, and gastrointestinal tumors (15). The identification of thyroid hormone resistance syndromes is beyond the scope of this chapter but is discussed in detail elsewhere in this book (see Chapter 4, "Rare Forms of Hyperthyroidism").
Physiology and testing of thyroid function
Published in Demetrius Pertsemlidis, William B. Inabnet III, Michel Gagner, Endocrine Surgery, 2017
Unbound, free T4, and free T3 cross the cell membrane; the T4 is deiodinated to T3; and all the T3 then binds to intracellular T3 receptors, which are located in the cell nucleus and act as transcription factors in a complex network of influences on the genes that regulate cell growth, differentiation, and energy release, among other actions (Figure 5.4) [5]. Four T3 nuclear receptors have been well characterized and designated α1, α2, β1, and β2 isoforms. The β2 receptors are unique to the pituitary gland and central to the phenomenon of TSH suppression by thyroid hormone feedback. The other isoforms are widely distributed, and their varying proportions help explain the different influences of thyroid hormone on multiple tissues. Knocking out these receptors in the mouse has provided important information on thyroid hormone action. For example, the α1 receptor is thought to be important in the influence of thyroid hormone on the heart. In addition, mutations in the thyroid hormone β receptors have helped explain the rare syndrome of thyroid hormone resistance, which may vary from mildly abnormal thyroid function tests to reduced growth and mental retardation, as well as hypothyroidism [6].
A practical approach to the management of thyroid dysfunction during pregnancy
Published in Gynecological Endocrinology, 2022
Costanzo Moretti, Natalia Lazzarin, Elena Vaquero, Alessandro Dal Lago, Luisa Campagnolo, Herbert Valensise
Severe hypothyroidism rarely occurs during pregnancy, given its connection to menstrual disorders and subfertility. Likewise, TSH-secreting pituitary tumors, thyroid hormone resistance or central hypothyroidism, with inactive TSH, are rarely observed in pregnant women. Nonetheless, central hypothyroidism should be excluded in women showing low TSH and T4 levels, with persistent headache and/or visual disturbances [31].
Determination of age and sex specific TSH and FT4 reference limits in overweight and obese individuals in an iodine-replete region: Tehran Thyroid Study (TTS)
Published in Endocrine Research, 2021
Hengameh Abdi, Bita Faam, Safoora Gharibzadeh, Ladan Mehran, Maryam Tohidi, Fereidoun Azizi, Atieh Amouzegar
Previous studies showed that the prevalence of increased TSH levels to be as high as 20% in morbidly obese individuals.21,22 Results of the Marzullo et al. study revealed that morbidly obese individuals had higher levels of TSH associated with lower rates of positive TPOAb than controls.23 Findings of a study investigating thyroid parameters in 144 morbidly obese individuals determined that the prevalence of overt and subclinical hypothyroidism was high (19.5%) and morbidly obese individuals had higher levels of triiodothyronine (T3), free T3 (FT3), T4, and TSH.22 All these studies compared the level of thyroid tests with normal TSH and T4 ranges that may culminate to assigning many normal obese subjects as having subclinical hypothyroidism. The mechanisms leading to the slight thyroid hormonal changes in obesity are not clearly defined. One hypothesis to explain the physiological elevation of TSH in obesity is increased leptin concentration in obese individuals which may be a link between thyroid hormones and weight status; it is suggested that leptin can regulate the secretion of TRH in the hypothalamus and stimulate the T3 production via activation of T4 to T3 conversion.6,24 Changes in TSH and thyroid hormone levels may reflect a state of thyroid hormone resistance, which could be related to the decreased thyroid hormone receptors in circulating mononuclear cells of obese individuals, and decreased negative feedback between TSH and peripheral T3 levels.25 Progressive fat accumulation is associated with a parallel increase in TSH and FT3 levels and a positive association has been reported between the FT3 to FT4 ratio and both BMI and waist circumference,26 suggesting a high T4 to T3 conversion rate in patients with central obesity due to increased deiodinase activity as a compensatory mechanism for fat accumulation to improve energy expenditure. These events result in increased levels of TSH and T3, constituting a condition of thyroid hormone resistance.13,26 A recent small study in Chinese women documented higher serum TSH and lower serum FT4 levels in obese women compared to the non-obese group.3 There are also reports regarding relationships between thyroid hormones and different obesity phenotypes in euthyroid populations from Iran27 and Korea.28