Thyroid's secretory capacity

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Thyroid's secretory capacity
Synonyms SPINA-GT, GT, T4 output, thyroid hormone output, thyroid's incretory capacity
Reference range 1.41–8.67 pmol/s
Test ofMaximum amount of T4 produced by the thyroid in one second
LOINC 82368-2

Thyroid's secretory capacity (GT, also referred to as thyroid's incretory capacity, maximum thyroid hormone output, T4 output or, if calculated from serum levels of thyrotropin and thyroxine, as SPINA-GT) is the maximum stimulated amount of thyroxine that the thyroid can produce in a given time-unit (e.g. one second). [1] [2]

Contents

How to determine GT

Experimentally, GT can be determined by stimulating the thyroid with a high thyrotropin concentration (e.g. by means of rhTSH, i.e. recombinant human thyrotropin) and measuring its output in terms of T4 production, or by measuring the serum concentration of protein-bound iodine-131 after administration of radioiodine. [3]

In vivo, GT can also be estimated from equilibrium levels of TSH and T4 or free T4. In this case it is calculated with

or

: Theoretical (apparent) secretory capacity (SPINA-GT)
: Dilution factor for T4 (reciprocal of apparent volume of distribution, 0.1 l−1)
: Clearance exponent for T4 (1.1e-6 sec−1)
K41: Dissociation constant T4-TBG (2e10 l/mol)
K42: Dissociation constant T4-TBPA (2e8 l/mol)
DT: EC50 for TSH (2.75 mU/l) [1] [4]

Specific secretory capacity

The ratio of SPINA-GT and thyroid volume VT (as determined e.g. by ultrasonography)

,

i.e.

or

is referred to as specific thyroid capacity (SPINA-GTs). [5]

Reference Range

Lower limitUpper limitUnit
1.41 [1] 8.67 [1] pmol/s

The equations and their parameters are calibrated for adult humans with a body mass of 70 kg and a plasma volume of ca. 2.5 l. [1]

Clinical significance

Validity

SPINA-GT is elevated in primary hyperthyroidism [6] and reduced in both primary hypothyroidism [7] [8] [9] and untreated autoimmune thyroiditis. [10] It has been observed to correlate (with positive direction) to resting energy expenditure [11] , resting heart rate [12] and thyroid volume, [1] [5] and (with negative direction) to thyroid autoantibody titres, which reflect organ destruction due to autoimmunity. [13] Elevated SPINA-GT in Graves's disease is reversible with antithyroid treatment. [11] While SPINA-GT is significantly altered in primary thyroid disorders, it is insensitive to disorders of secondary nature (e.g. pure pituitary diseases). [2]

Reliability

In silico experiments with Monte Carlo simulations demonstrated that both SPINA-GT and SPINA-GD can be estimated with sufficient reliability, even if laboratory assays have limited accuracy. [2] This was confirmed by longitudinal in vivo studies that showed that GT has lower intraindividual variation (i.e. higher reliability) than TSH, FT4 or FT3. [14]

Clinical utility

In clinical trials SPINA-GT was significantly elevated in patients suffering from Graves' disease and toxic adenoma compared to normal subjects. [1] [6] It is also elevated in diffuse and nodular goiters, and reduced in untreated autoimmune thyroiditis. [1] [10] In patients with toxic adenoma it has higher specificity and positive likelihood ratio for diagnosis of thyrotoxicosis than serum concentrations of thyrotropin, free T4 or free T3. [1] GT's specificity is also high in thyroid disorders of secondary or tertiary origin. [2]

Pathophysiological and therapeutic implications

Correlation of SPINA-GT with creatinine clearance suggested a negative influence of uremic toxins on thyroid biology. [15] In the initial phase of major non-thyroidal illness syndrome (NTIS) SPINA-GT may be temporarily elevated. [16] [17] In chronic NTIS [18] as well as in certain non-critical chronic diseases, e.g. chronic fatigue syndrome [19] or asthma [20] SPINA-GT ist slightly reduced.

In women, therapy with Metformin results in increased SPINA-GT, in parallel to improved insulin sensitivity. [21] This observation was reproducible in men with hypogonadism, but not in men with normal testosterone concentrations, [22] so that the described effect seems to depend on an interaction of metformin with sex hormones. [22] [23] In hyperthyroid [6] men both SPINA-GT and SPINA-GD negatively correlate to erectile function, intercourse satisfaction, orgasmic function and sexual desire. Likewise, in women suffering from thyrotoxicosis elevated thyroid's secretory capacity predicts depression and sexual dysfunction. [24] Conversely, in androgen-deficient men with concomitant autoimmune thyroiditis, substitution therapy with testosterone leads to a decrease in thyroid autoantibody titres and an increase in SPINA-GT. [25]

In patients with autoimmune thyroiditis a gluten-free diet results in increased SPINA-GT (in parallel to sinking autoantibody titres). [26] Statin therapy has the same effect, but only if supply with vitamin D is sufficient. [27] Accordingly, substitution therapy with 25-hydroxyvitamin D leads to rising secretory capacity. [28] [29] [30] This effect is potentiated by substitution therapy with selenomethionine. [28] [29] The effects of vitamin D and selenomethionine are attenuated in hyperprolactinaemia, suggesting an inhibitory effect of prolactin [31] .

On the other hand, men treated with spironolactone are faced with decreasing SPINA-GT (in addition to rising thyroid antibody titres). [32] It has, therefore, been concluded that spironolactone may aggravate thyroid autoimmunity in men. [32]

A study in euthyroid subjects with structural heart disease found that SPINA-GT predicts the risk of malignant arrhythmia including ventricular fibrillation and ventricular tachycardia [33] . This applies to both incidence and event-free survival [33] .

Specific secretory capacity (SPINA-GTs) is reduced in obesity [1] and autoimmune thyroiditis. [5] [34]

See also

Related Research Articles

Thyroid Endocrine gland in the neck; secretes hormones that influence metabolism

The thyroid, or thyroid gland, is an endocrine gland in the neck consisting of two connected lobes. The lower two thirds of the lobes are connected by a thin band of tissue called the thyroid isthmus. The thyroid is located at the front of the neck, below the Adam's apple. Microscopically, the functional unit of the thyroid gland is the spherical thyroid follicle, lined with follicular cells (thyrocytes), and occasional parafollicular cells that surround a lumen containing colloid. The thyroid gland secretes three hormones: the two thyroid hormones – triiodothyronine (T3) and thyroxine (T4) – and a peptide hormone, calcitonin. The thyroid hormones influence the metabolic rate and protein synthesis, and in children, growth and development. Calcitonin plays a role in calcium homeostasis. Secretion of the two thyroid hormones is regulated by thyroid-stimulating hormone (TSH), which is secreted from the anterior pituitary gland. TSH is regulated by thyrotropin-releasing hormone (TRH), which is produced by the hypothalamus.

Graves disease Autoimmune endocrine disease

Graves' disease, also known as toxic diffuse goiter, is an autoimmune disease that affects the thyroid. It frequently results in and is the most common cause of hyperthyroidism. It also often results in an enlarged thyroid. Signs and symptoms of hyperthyroidism may include irritability, muscle weakness, sleeping problems, a fast heartbeat, poor tolerance of heat, diarrhea and unintentional weight loss. Other symptoms may include thickening of the skin on the shins, known as pretibial myxedema, and eye bulging, a condition caused by Graves' ophthalmopathy. About 25 to 80% of people with the condition develop eye problems.

Hypothyroidism Endocrine disease

Hypothyroidism, also called underactive thyroid or low thyroid, is a disorder of the endocrine system in which the thyroid gland does not produce enough thyroid hormone. It can cause a number of symptoms, such as poor ability to tolerate cold, a feeling of tiredness, constipation, slow heart rate, depression, and weight gain. Occasionally there may be swelling of the front part of the neck due to goiter. Untreated cases of hypothyroidism during pregnancy can lead to delays in growth and intellectual development in the baby or congenital iodine deficiency syndrome.

Autoimmunity is the system of immune responses of an organism against its own healthy cells and tissues. Any disease that results from such an aberrant immune response is termed an "autoimmune disease". Prominent examples include celiac disease, post-infectious IBS, diabetes mellitus type 1, Henloch Scholein Pupura (HSP) sarcoidosis, systemic lupus erythematosus (SLE), Sjögren syndrome, eosinophilic granulomatosis with polyangiitis, Hashimoto's thyroiditis, Graves' disease, idiopathic thrombocytopenic purpura, Addison's disease, rheumatoid arthritis (RA), ankylosing spondylitis, polymyositis (PM), dermatomyositis (DM) and multiple sclerosis (MS). Autoimmune diseases are very often treated with steroids.

Thyroid-stimulating hormone (also known as thyrotropin, thyrotropic hormone, or abbreviated TSH) is a pituitary hormone that stimulates the thyroid gland to produce thyroxine (T4), and then triiodothyronine (T3) which stimulates the metabolism of almost every tissue in the body. It is a glycoprotein hormone produced by thyrotrope cells in the anterior pituitary gland, which regulates the endocrine function of the thyroid.

Hashimotos thyroiditis autoimmune disease

Hashimoto's thyroiditis, also known as chronic lymphocytic thyroiditis and Hashimoto's disease, is an autoimmune disease in which the thyroid gland is gradually destroyed. Early on there may be no symptoms. Over time the thyroid may enlarge, forming a painless goiter. Some people eventually develop hypothyroidism with accompanying weight gain, feeling tired, constipation, depression, and general pains. After many years the thyroid typically shrinks in size. Potential complications include thyroid lymphoma.

Thyroid disease type of endocrine disease

Thyroid disease is a medical condition that affects the function of the thyroid gland. The thyroid gland is located at the front of the neck and produces thyroid hormones that travel through the blood to help regulate many other organs, meaning that it is an endocrine organ. These hormones normally act in the body to regulate energy use, infant development, and childhood development.

Thyroid function tests (TFTs) is a collective term for blood tests used to check the function of the thyroid.

Graves ophthalmopathy Thyroid eye disease (TED), often associated with Graves disease.

Graves ophthalmopathy, also known as thyroid eye disease (TED), is an autoimmune inflammatory disorder of the orbit and periorbital tissues, characterized by upper eyelid retraction, lid lag, swelling, redness (erythema), conjunctivitis, and bulging eyes (exophthalmos). It occurs most commonly in individuals with Graves' disease, and less commonly in individuals with Hashimoto's thyroiditis, or in those who are euthyroid.

Postpartum thyroiditis refers to thyroid dysfunction occurring in the first 12 months after pregnancy and may involve hyperthyroidism, hypothyroidism or the two sequentially. It affects about 5-10% of all women within a year after giving birth. The first phase is typically hyperthyroidism. Then, the thyroid either returns to normal or a woman develops hypothyroidism. Of those women who experience hypothyroidism associated with postpartum thyroiditis, one in five will develop permanent hypothyroidism requiring lifelong treatment.

Hypothalamic–pituitary–thyroid axis part of the neuroendocrine system responsible for the regulation of metabolism.

The hypothalamic–pituitary–thyroid axis is part of the neuroendocrine system responsible for the regulation of metabolism and also responds to stress.

Hashimotos encephalopathy human disease

Hashimoto's encephalopathy, also known as steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT), is a neurological condition characterized by encephalopathy, thyroid autoimmunity, and good clinical response to corticosteroids. It is associated with Hashimoto's thyroiditis. It was first described in 1966. It is sometimes referred to as a neuroendocrine disorder, although the condition's relationship to the endocrine system is widely disputed. It is recognized as a rare disease by the NIH Genetic and Rare Diseases Information Center.

Euthyroid sick syndrome (ESS) is a state of adaptation or dysregulation of thyrotropic feedback control wherein the levels of T3 and/or T4 are abnormal, but the thyroid gland does not appear to be dysfunctional. This condition may result from allostatic responses of hypothalamus-pituitary-thyroid feedback control, dyshomeostatic disorders, drug interferences, and impaired assay characteristics in critical illness.

Autoimmune thyroiditis, is a chronic disease in which the body interprets the thyroid glands and its hormone products T3, T4 and TSH as threats, therefore producing special antibodies that target the thyroid's cells, thereby destroying it.

Thyroid disease in pregnancy can affect the health of the mother as well as the child before and after delivery. Thyroid disorders are prevalent in women of child-bearing age and for this reason commonly present as a pre-existing disease in pregnancy, or after childbirth. Uncorrected thyroid dysfunction in pregnancy has adverse effects on fetal and maternal well-being. The deleterious effects of thyroid dysfunction can also extend beyond pregnancy and delivery to affect neurointellectual development in the early life of the child. Due to an increase in thyroxine binding globulin, an increase in placental type 3 deioidinase and the placental transfer of maternal thyroxine to the fetus, the demand for thyroid hormones is increased during pregnancy. The necessary increase in thyroid hormone production is facilitated by high human chorionic gonadotropin (hCG) concentrations, which bind the TSH receptor and stimulate the maternal thyroid to increase maternal thyroid hormone concentrations by roughly 50%. If the necessary increase in thyroid function cannot be met, this may cause a previously unnoticed (mild) thyroid disorder to worsen and become evident as gestational thyroid disease. Currently, there is not enough evidence to suggest that screening for thyroid dysfunction is beneficial, especially since treatment thyroid hormone supplementation may come with a risk of overtreatment. After women give birth, about 5% develop postpartum thyroiditis which can occur up to nine months afterwards.This is characterized by a short period of hyperthyroidism followed by a period of hypothyroidism; 20–40% remain permanently hypothyroid.

Antithyroid autoantibodies (or simply antithyroid antibodies) are autoantibodies targeted against one or more components on the thyroid. The most clinically relevant anti-thyroid autoantibodies are anti-thyroid peroxidase antibodies (anti-TPO antibodies, TPOAb), thyrotropin receptor antibodies (TRAb) and thyroglobulin antibodies (TgAb). TRAb's are subdivided into activating, blocking and neutral antibodies, depending on their effect on the TSH receptor. Anti-sodium/Iodide (Anti–Na+/I) symporter antibodies are a more recent discovery and their clinical relevance is still unknown. Graves' disease and Hashimoto's thyroiditis are commonly associated with the presence of anti-thyroid autoantibodies. Although there is overlap, anti-TPO antibodies are most commonly associated with Hashimoto's thyroiditis and activating TRAb's are most commonly associated with Graves' disease. Thyroid microsomal antibodies were a group of anti-thyroid antibodies; they were renamed after the identification of their target antigen (TPO).

The sum activity of peripheral deiodinases is the maximum amount of triiodothyronine produced per time-unit under conditions of substrate saturation. It is assumed to reflect the activity of deiodinases outside the central nervous system and other isolated compartments. GD is therefore expected to reflect predominantly the activity of type I deiodinase.

Jostel's TSH index, also referred to as Jostel's thyrotropin index or Thyroid Function index (TFI) is a method for estimating the thyrotropic function of the anterior pituitary lobe in a quantitative way. The equation has been derived from the logarithmic standard model of thyroid homeostasis. In a paper from 2014 further study was suggested to show if it is useful, but the 2018 guideline by the European Thyroid Association for the diagnosis of uncertain cases of central hypothyroidism regarded it as beneficial.

SimThyr Medical research simulation software

SimThyr is a free continuous dynamic simulation program for the pituitary-thyroid feedback control system. The open-source program is based on a nonlinear model of thyroid homeostasis. In addition to simulations in the time domain the software supports various methods of sensitivity analysis. It provides a GUI, which allows for visualising time series, modifying constant structure parameters of the feedback loop, storing parameter sets as XML files and exporting results of simulations in various formats that are suitable for statistical software. SimThyr is primarily intended for educational purposes and in-silico research.

The Thyrotroph Thyroid Hormone Sensitivity Index is a calculated structure parameter of thyroid homeostasis. It was originally developed to deliver a method for fast screening for resistance to thyroid hormone. Today it is also used to get an estimate for the set point of thyroid homeostasis, especially to assess dynamic thyrotropic adaptation of the anterior pituitary gland, including non-thyroidal illnesses.

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