Causes and laboratory investigation of hypothyroidism

2011 ◽  
pp. 530-537 ◽  
Author(s):  
Ferruccio Santini ◽  
Aldo Pinchera
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Gland ◽  
Thyroid Hormones ◽  
Thyroid Hormone Receptor ◽  
Hormone Secretion ◽  
Thyroid Tissue ◽  
Clinical Manifestations ◽  
Primary Hypothyroidism ◽  
Central Hypothyroidism ◽  
Resistance To Thyroid Hormones

Hypothyroidism is the clinical state that develops as a result of the lack of action of thyroid hormones on target tissues (1). Hypothyroidism is usually due to impaired hormone secretion by the thyroid, resulting in reduced concentrations of serum thyroxine (T4) and triiodothyronine (T3). The term primary hypothyroidism is applied to define the thyroid failure deriving from inherited or acquired causes that act directly on the thyroid gland by reducing the amount of functioning thyroid tissue or by inhibiting thyroid hormone production. The term central hypothyroidism is used when pituitary or hypothalamic abnormalities result in an insufficient stimulation of an otherwise normal thyroid gland. Both primary and central hypothyroidism may be transient, depending on the nature and the extent of the causal agent. Hypothyroidism following a minor loss of thyroid tissue can be recovered by compensatory hyperplasia of the residual gland. Similarly, hypothyroidism subsides when an exogenous inhibitor of thyroid function is removed. Peripheral hypothyroidism may also arise as a consequence of tissue resistance to thyroid hormones due to a mutation in the thyroid hormone receptor. Resistance to thyroid hormones is a heterogeneous clinical entity with most patients appearing to be clinically euthyroid while some of them have symptoms of thyrotoxicosis and others display selected signs of hypothyroidism. The common feature is represented by pituitary resistance to thyroid hormones, leading to increased secretion of thyrotropin that in turn stimulates thyroid growth and function. The variability in clinical manifestations depends on the severity of the hormonal resistance, the relative degree of tissue hyposensitivity, and the coexistence of associated genetic defects (see Chapter 3.4.8).

scholarly journals Hypercholesterolemia in Two Siblings with Resistance to Thyroid Hormones Due to Disease-Causing Variant in Thyroid Hormone Receptor (THRB) Gene

Medicina ◽  
2020 ◽  
Vol 56 (12) ◽  
pp. 699
Author(s):  
Maja Pajek ◽  
Magdalena Avbelj Stefanija ◽  
Katarina Trebusak Podkrajsek ◽  
Jasna Suput Omladic ◽  
Mojca Zerjav Tansek ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Pathogenic Mutation ◽  
Laboratory Findings ◽  
Cholesterol Levels ◽  
Resistance To Thyroid Hormones ◽  
Hormonal Resistance ◽  
Disease Variant

Resistance to thyroid hormone beta (RTHβ) is a syndrome characterized by a reduced response of target tissues to thyroid hormones. In 85% of cases, a pathogenic mutation in the thyroid hormone receptor beta (THRB) gene is found. The clinical picture of RTHβ is very diverse; the most common findings are goiter and tachycardia, but the patients might be clinically euthyroid. The laboratory findings are almost pathognomonic with elevated free thyroxin (fT4) levels and high or normal thyrotropin (TSH) levels; free triiodothyronin (fT3) levels may also be elevated. We present three siblings with THRB mutation (heterozygous disease-variant c.727C>T, p.Arg243Trp); two of them also had hypercholesterolemia, while all three had several other clinical characteristics of RTHβ. This is the first description of the known Slovenian cases with RTHβ due to the pathogenic mutation in the THRB gene. Hypercholesterolemia might be etiologically related with RTHβ, since the severity of hormonal resistance varies among different tissues and hypercholesterolemia in patients with THRB variants might indicate the relatively hypothyroid state of the liver. We suggest that cholesterol levels are measured in all RTHβ patients.

scholarly journals Primary congenital hypothyroidism: defects in iodine pathways

2003 ◽  
pp. 247-256 ◽  
Author(s):  
JJ de Vijlder
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Gland ◽  
Congenital Hypothyroidism ◽  
Primary Hypothyroidism ◽  
Special Importance ◽  
Hormone Production ◽  
Central Hypothyroidism ◽  
Hormone Synthesis ◽  
Diagnosis And Classification ◽  
The Central Nervous System

The thyroid gland is the only source of thyroid hormone production. Thyroid hormone is essential for growth and development, and is of special importance for the development of the central nervous system. It was for that reason that neonatal screening on congenital hypothyroidism was introduced and is now performed in many countries. Defects in thyroid hormone production are caused by several disorders in hormone synthesis and in the development of the thyroid gland (primary hypothyroidism) or of the pituitary gland and hypothalamus (central hypothyroidism).This paper describes defects in the synthesis of thyroid hormone caused by disorders in the synthesis or iodination of thyroglobulin, leakage of iodinated proteins by a stimulated thyroid gland and the presence of abnormal iodoproteins, mainly iodinated albumin, in the thyroid gland and blood circulation. Circulating thyroglobulin and abnormal iodoproteins, as well as the breakdown products of these iodoproteins excreted in urine, are used for etiological diagnosis and classification. Moreover, our finding of an enzyme that catalyses the dehalogenation of iodotyrosines, which is important for iodine recycling and required for economical use of iodine, is also referred to.

Clinical assessment and systemic manifestations of thyrotoxicosis

2011 ◽  
pp. 441-452
Author(s):  
Claudio Marcocci ◽  
Filomena Cetani ◽  
Aldo Pinchera
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Gland ◽  
Thyroid Hormones ◽  
Clinical Manifestations ◽  
Clinical Syndrome ◽  
Graves Disease ◽  
Free Triiodothyronine ◽  
Excessive Secretion ◽  
Almost All ◽  
Symptoms And Signs

The term thyrotoxicosis refers to the clinical syndrome that results when the serum concentrations of free thyroxine, free triiodothyronine, or both, are high. The term hyperthyroidism is used to mean sustained increases in thyroid hormone biosynthesis and secretion by the thyroid gland; Graves’ disease is the most common example of this. Occasionally, thyrotoxicosis may be due to other causes such as destructive thyroiditis, excessive ingestion of thyroid hormones, or excessive secretion of thyroid hormones from ectopic sites; in these cases there is no overproduction of hormone by thyrocytes and, strictly speaking, no hyperthyroidism. The various causes of thyrotoxicosis are listed in Chapter 3.3.5. The clinical features depend on the severity and the duration of the disease, the age of the patient, the presence or absence of extrathyroidal manifestations, and the specific disorder producing the thyrotoxicosis. Older patients have fewer symptoms and signs of sympathetic activation, such as tremor, hyperactivity, and anxiety, and more symptoms and signs of cardiovascular dysfunction, such as atrial fibrillation and dyspnoea. Rarely a patient with ‘apathetic’ hyperthyroidism will lack almost all of the usual clinical manifestations of thyrotoxicosis (1). Almost all organ systems in the body are affected by thyroid hormone excess, and the high levels of circulating thyroid hormones are responsible for most of the systemic effects observed in these patients (Table 3.3.1.1). However, some of the signs and symptoms prominent in Graves’ disease reflect extrathyroidal immunological processes rather than the excessive levels of thyroid hormones produced by the thyroid gland (Table 3.3.1.2).

Lack of effects of circulating thyroid hormone levels on serum leptin concentrations

1997 ◽  
pp. 659-663 ◽  
Author(s):  
S Corbetta ◽  
P Englaro ◽  
S Giambona ◽  
L Persani ◽  
WF Blum ◽  
...  
Keyword(s):  
Thyroid Hormones ◽  
Standard Deviation Score ◽  
Protein Product ◽  
Primary Hypothyroidism ◽  
Central Hypothyroidism ◽  
Serum Leptin ◽  
Thyroxine Therapy ◽  
Significant Difference ◽  
Before And After ◽  
Thyroxine Replacement Therapy

Leptin is the protein product of the ob gene, secreted by adipocytes. It has been suggested that it may play an important role in regulating appetite and energy expenditure. The aim of this study was to evaluate a possible interaction of thyroid hormones with the leptin system. We studied 114 adult patients (65 females and 49 males): 36 were affected with primary hypothyroidism (PH), 38 with central hypothyroidism (CH) and 40 with thyrotoxicosis (TT). Patients with CH were studied both before and after 6 months of L-thyroxine replacement therapy. Body mass index (BMI; kg/m2), thyroid function and fasting serum leptin were assessed in all patients. Since BMI has been proved to be the major influencing variable of circulating leptin levels, data were expressed as standard deviation score (SDS) calculated from 393 male and 561 female controls matched for age and BMI. No difference in SDS was recorded between males and females whatever the levels of circulating thyroid hormones. In males, no significant difference was recorded among the SDSs of PH (-0.36 +/- 1.2), TT (-0.35 +/- 1.2) and CH (0.01 +/- 1.4) patients. Females with PH had an SDSs significantly lower than TT females (-0.77 +/- 1.0 vs -0.06 +/- 1.2; P < 0.02), while no significant differences between CH (-0.34 +/- 0.7) and TT females or between CH and PH females were observed. SDS in CH patients after 6 months of L-thyroxine therapy significantly varied only in females (0.25 +/- 1.4). In conclusion, circulating thyroid hormones do not appear to play any relevant role in leptin synthesis and secretion. However, as females with either overt hypo- or hyper-thyroidism or central hypothyroidism after L-thyroxine therapy show differences in their SDSs, a subtle interaction between sex steroids and thyroid status in modulating leptin secretion, at least in women, may occur.

scholarly journals The thyroid hormone receptor gene (c-erbA alpha) is expressed in advance of thyroid gland maturation during the early embryonic development of Xenopus laevis.

1991 ◽  
Vol 11 (10) ◽  
pp. 5079-5089 ◽  
Author(s):  
D E Banker ◽  
J Bigler ◽  
R N Eisenman
Keyword(s):  
Gene Expression ◽  
Thyroid Hormone ◽  
Thyroid Gland ◽  
Xenopus Laevis ◽  
Hormone Receptor ◽  
Hormone Receptors ◽  
Thyroid Hormone Receptor ◽  
Thyroid Hormone Receptors ◽  
Stages Of Development ◽  
Xenopus Development

The c-erbA proto-oncogene encodes the thyroid hormone receptor, a ligand-dependent transcription factor which plays an important role in vertebrate growth and development. To define the role of the thyroid hormone receptor in developmental processes, we have begun studying c-erbA gene expression during the ontogeny of Xenopus laevis, an organism in which thyroid hormone has well-documented effects on morphogenesis. Using polymerase chain reactions (PCR) as a sensitive assay of specific gene expression, we found that polyadenylated erbA alpha RNA is present in Xenopus cells at early developmental stages, including the fertilized egg, blastula, gastrula, and neurula. By performing erbA alpha-specific PCR on reverse-transcribed RNAs from high-density sucrose gradient fractions prepared from early-stage embryos, we have demonstrated that these erbA transcripts are recruited to polysomes. Therefore, erbA is expressed in Xenopus development prior to the appearance of the thyroid gland anlage in tailbud-stage embryos. This implies that erbA alpha/thyroid hormone receptors may play ligand-independent roles during the early development of X. laevis. Quantitative PCR revealed a greater than 25-fold range in the steady-state levels of polyadenylated erbA alpha RNA across early stages of development, as expressed relative to equimolar amounts of total embryonic RNA. Substantial increases in the levels of erbA alpha RNA were noted at stages well after the onset of zygotic transcription at the mid-blastula transition, with accumulation of erbA alpha transcripts reaching a relative maximum in advance of metamorphosis. We also show that erbA alpha RNAs are expressed unequally across Xenopus neural tube embryos. This differential expression continues through later stages of development, including metamorphosis. This finding suggests that erbA alpha/thyroid hormone receptors may play roles in tissue-specific processes across all of Xenopus development.

Regulation of Mammary Gland Sensitivity to Thyroid Hormones During the Transition from Pregnancy to Lactation

2008 ◽  
Vol 233 (10) ◽  
pp. 1309-1314 ◽  
Author(s):  
A. V. Capuco ◽  
E. E. Connor ◽  
D. L. Wood
Keyword(s):  
Mammary Gland ◽  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Thyroid Hormone Receptor ◽  
Physiological State ◽  
Expression Patterns ◽  
Type I ◽  
Hormone Activity ◽  
Iodothyronine Deiodinase ◽  
Copy Numbers

Thyroid hormones are galactopoietic and help to establish the mammary gland’s metabolic priority during lactation. Expression patterns for genes that can alter tissue sensitivity to thyroid hormones and thyroid hormone activity were evaluated in the mammary gland and liver of cows at 53, 35, 20, and 7 days before expected parturition, and 14 and 90 days into the subsequent lactation. Transcript abundance for the three isoforms of iodothyronine deiodinase, type I ( DIO1), type II ( DIO2) and type III ( DIO3), thyroid hormone receptors alpha1 ( TRα 1), alpha2 ( TRα 2) and beta1 ( TRβ 1), and retinoic acid receptors alpha ( RXRα) and gamma ( RXRγ), which act as coregulators of thyroid hormone receptor action, were evaluated by quantitative RT-PCR. The DIO3 is a 5-deiodinase that produces inactive iodothyronine metabolites, whereas DIO1 and DIO2 generate the active thyroid hormone, triiodothyronine, from the relatively inactive precursor, thyroxine. Low copy numbers of DIO3 transcripts were present in mammary gland and liver. DIO2 was the predominant isoform expressed in mammary gland and DIO1 was the predominant isoform expressed in liver. Quantity of DIO1 mRNA in liver tissues did not differ with physiological state, but tended to be lowest during lactation. Quantity of DIO2 mRNA in mammary gland increased during lactation ( P < 0.05), with copy numbers at 90 days of lactation 6-fold greater than at 35 and 20 days prepartum. When ratios of DIO2/DIO3 mRNA were evaluated, the increase was more pronounced (>100-fold). Quantity of TRβ 1 mRNA in mammary gland increased with onset of lactation, whereas TRα 1 and TRα 2 transcripts did not vary with physiological state. Conversely, quantity of RXRα mRNA decreased during late gestation to low levels during early lactation. Data suggest that increased expression of mammary TRβ 1 and DIO2, and decreased RXRα, provide a mechanism to increase thyroid hormone activity within the mammary gland during lactation.

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