Jostel's TSH index

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Jostel's TSH index
Reference ranges for TSH, FT4, JTI and SPINA-GT.svg
Reference ranges for JTI and other thyroid function tests
Synonyms Jostel's thyrotropin index
Reference range 1.3–4.1
MeSH D013960

Jostel's TSH index (TSHI or JTI), also referred to as Jostel's thyrotropin index or Thyroid Function index (TFI), is a method for estimating the thyrotropic (i.e. thyroid stimulating) function of the anterior pituitary lobe in a quantitative way. [1] [2] The equation has been derived from the logarithmic standard model of thyroid homeostasis. [3] [4] [5] [6] In a paper from 2014 further study was suggested to show if it is useful, [7] but the 2018 guideline by the European Thyroid Association for the diagnosis of uncertain cases of central hypothyroidism regarded it as beneficial. [2] It is also recommended for purposes of differential diagnosis in the sociomedical expert assessment. [8]

Contents

How to determine JTI

Jostel's TSH index can be calculated with

from equilibrium serum concentrations of thyrotropin (TSH), free T4 (FT4) and a correction coefficient derived from the logarithmic standard model (β = 0.1345).

An alternative standardised form (standardised TSH index or sTSHI) is calculated with. [1]

as a z-transformed value incorporating mean (2.7) and standard deviation (0.676) of TSHI in a reference population [5]

Reference ranges

Percentiles for Jostel's TSH index (TSHI or JTI) along with reference ranges for thyroid's secretory capacity (SPINA-GT) and univariable reference ranges for thyrotropin (TSH) and free thyroxine (FT4), shown in the two-dimensional phase plane defined by serum concentrations of TSH and FT4. JTI percentiles.svg
Percentiles for Jostel's TSH index (TSHI or JTI) along with reference ranges for thyroid's secretory capacity (SPINA-GT) and univariable reference ranges for thyrotropin (TSH) and free thyroxine (FT4), shown in the two-dimensional phase plane defined by serum concentrations of TSH and FT4.
ParameterLower limitUpper limitUnit
TSHI1.3 [1] 4.1 [1]
sTSHI-2 [1] 2 [1]

Clinical significance

The TSH index is reduced in patients with secondary hypothyroidism resulting from thyrotropic insufficiency. [1] [9] [10] [11] For this indication, it has, however, up to now only been validated in adults. [12] JTI was also found reduced in cases of TACITUS syndrome (non-thyroidal illness syndrome) as an example of type 1 thyroid allostasis. [13] [14] Conversely, an elevated thyroid function index may serve as a biomarker for type 2 allostasis and contextual stress. [15] [16]

Jostel's TSH index may decrease under therapy with the antidiabetic drug metformin, especially in women under oral contraceptives. [17]

In two large population-based cohorts included in the Study of Health in Pomerania differentially correlated to some markers of body composition. Correlation was positive to body mass index (BMI), waist circumference and fat mass, but negative to body cell mass. [18] With the exception of fat mass all correlations were age-dependent. [18] Very similar observations have been made earlier in the NHANES dataset. [19]

In Parkinson's disease, JTI is significantly elevated in early sub-types of the disease compared to an advanced group. [20]

A longitudinal study in euthyroid subjects with structural heart disease found that JTI predicts the risk of malignant arrhythmia including ventricular fibrillation and ventricular tachycardia. [21] This applies to both incidence and event-free survival. [21] It was therefore concluded that an elevated set point of thyroid homeostasis may contribute to cardiovascular risk. A positive correlation of JTI to SIQALS 2, [16] a score for allostatic load, suggests that thyroid hormones are among the mediators linking stress to major cardiovascular endpoints. [22]

Another study demonstrated the TSH index to inversely correlate to thyroid's secretory capacity and thyroid volume. [23] It is unclear if this finding reflects shortcomings of the index (i.e. low specificity in the setting of subclinical hypothyroidism) or plastic responses of the pituitary gland to beginning hypothyroidism.[ citation needed ]

In subjects with type 2 diabetes, treatment with beta blockers resulted in increased TSH index, but the mechanism is unclear. [24]

Negative correlation of Jostel's TSH index to the urinary excretion of certain phthalates suggests that endocrine disruptors may affect the central set point of thyroid homeostasis. [25]

See also

Related Research Articles

<span class="mw-page-title-main">Hyperthyroidism</span> Thyroid gland disease that involves an overproduction of thyroid hormone

Hyperthyroidism is the condition that occurs due to excessive production of thyroid hormones by the thyroid gland. Thyrotoxicosis is the condition that occurs due to excessive thyroid hormone of any cause and therefore includes hyperthyroidism. Some, however, use the terms interchangeably. Signs and symptoms vary between people and may include irritability, muscle weakness, sleeping problems, a fast heartbeat, heat intolerance, diarrhea, enlargement of the thyroid, hand tremor, and weight loss. Symptoms are typically less severe in the elderly and during pregnancy. An uncommon but life-threatening complication is thyroid storm in which an event such as an infection results in worsening symptoms such as confusion and a high temperature; this often results in death. The opposite is hypothyroidism, when the thyroid gland does not make enough thyroid hormone.

<span class="mw-page-title-main">Hypothyroidism</span> Endocrine disease

Hypothyroidism is a disorder of the endocrine system in which the thyroid gland does not produce enough thyroid hormones. 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 goitre. Untreated cases of hypothyroidism during pregnancy can lead to delays in growth and intellectual development in the baby or congenital iodine deficiency syndrome.

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.

Thyroid storm is a rare but severe and life-threatening complication of hyperthyroidism. It occurs when overactive thyroid activity leads to hypermetabolism, the end result being death from cardiac arrest or multiple organ failure.

Thyroid function tests (TFTs) is a collective term for blood tests used to check the function of the thyroid. TFTs may be requested if a patient is thought to suffer from hyperthyroidism or hypothyroidism, or to monitor the effectiveness of either thyroid-suppression or hormone replacement therapy. It is also requested routinely in conditions linked to thyroid disease, such as atrial fibrillation and anxiety disorder.

Allostasis (/ˌɑːloʊˈsteɪsɪs/) is a physiological mechanism of regulation in which the human body anticipates and adjusts its energy use according to environmental demands. First proposed by Peter Sterling and Joseph Eyer in 1988, the concept of allostasis shifts the focus away from the body maintaining a rigid internal set-point, as in homeostasis, to the brain's ability and role to interpret environmental stress and coordinate changes in the body using neurotransmitters, hormones, and other signaling mechanisms. Allostasis is believed to be not only involved in the body's stress response and adaptation to chronic stress; it may also have a role in the regulation of the immune system as well as in the development of chronic diseases such as hypertension and diabetes.

<span class="mw-page-title-main">Allostatic load</span> Wear and tear on the body due to stress

Allostatic load is "the wear and tear on the body" which accumulates as an individual is exposed to repeated or chronic stress. The term was coined by Bruce McEwen and Eliot Stellar in 1993. It represents the physiological consequences of chronic exposure to fluctuating or heightened neural or neuroendocrine response which results from repeated or prolonged chronic stress.

<span class="mw-page-title-main">Hypothalamic–pituitary–thyroid axis</span> Part of the neuroendocrine system

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

<span class="mw-page-title-main">Reverse triiodothyronine</span> Chemical compound

Reverse triiodothyronine (3,3′,5′-triiodothyronine, reverse T3, or rT3) is an isomer of triiodothyronine (3,5,3′ triiodothyronine, T3).

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.

Myxedema coma is an extreme or decompensated form of hypothyroidism and while uncommon, is potentially lethal. A person may have laboratory values identical to a "normal" hypothyroid state, but a stressful event precipitates the myxedema coma state, usually in the elderly. Primary symptoms of myxedema coma are altered mental status and low body temperature. Low blood sugar, low blood pressure, hyponatremia, hypercapnia, hypoxia, slowed heart rate, and hypoventilation may also occur. Myxedema, although included in the name, is not necessarily seen in myxedema coma. Coma is also not necessarily seen in myxedema coma, as patients may be obtunded without being comatose.

Hypothalamic disease is a disorder presenting primarily in the hypothalamus, which may be caused by damage resulting from malnutrition, including anorexia and bulimia eating disorders, genetic disorders, radiation, surgery, head trauma, lesion, tumour or other physical injury to the hypothalamus. The hypothalamus is the control center for several endocrine functions. Endocrine systems controlled by the hypothalamus are regulated by antidiuretic hormone (ADH), corticotropin-releasing hormone, gonadotropin-releasing hormone, growth hormone-releasing hormone, oxytocin, all of which are secreted by the hypothalamus. Damage to the hypothalamus may impact any of these hormones and the related endocrine systems. Many of these hypothalamic hormones act on the pituitary gland. Hypothalamic disease therefore affects the functioning of the pituitary and the target organs controlled by the pituitary, including the adrenal glands, ovaries and testes, and the thyroid gland.

Prior to the availability of sensitive TSH assays, thyrotropin releasing hormone or TRH stimulation tests were relied upon for confirming and assessing the degree of suppression in suspected hyperthyroidism. Typically, this stimulation test involves determining basal TSH levels and levels 15 to 30 minutes after an intravenous bolus of TRH. Normally, TSH would rise into the concentration range measurable with less sensitive TSH assays. Third generation TSH assays do not have this limitation and thus TRH stimulation is generally not required when third generation TSH assays are used to assess degree of suppression.

<span class="mw-page-title-main">Thyroid's secretory capacity</span>

Thyroid's secretory capacity is the maximum stimulated amount of thyroxine that the thyroid can produce in a given time-unit.

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.

Pulsatile secretion is a biochemical phenomenon observed in a wide variety of cell and tissue types, in which chemical products are secreted in a regular temporal pattern. The most common cellular products observed to be released in this manner are intercellular signaling molecules such as hormones or neurotransmitters. Examples of hormones that are secreted pulsatilely include insulin, thyrotropin, TRH, gonadotropin-releasing hormone (GnRH) and growth hormone (GH). In the nervous system, pulsatility is observed in oscillatory activity from central pattern generators. In the heart, pacemakers are able to work and secrete in a pulsatile manner. A pulsatile secretion pattern is critical to the function of many hormones in order to maintain the delicate homeostatic balance necessary for essential life processes, such as development and reproduction. Variations of the concentration in a certain frequency can be critical to hormone function, as evidenced by the case of GnRH agonists, which cause functional inhibition of the receptor for GnRH due to profound downregulation in response to constant (tonic) stimulation. Pulsatility may function to sensitize target tissues to the hormone of interest and upregulate receptors, leading to improved responses. This heightened response may have served to improve the animal's fitness in its environment and promote its evolutionary retention.

<span class="mw-page-title-main">3,5-Diiodothyronine</span> Chemical compound

3,5-Diiodothyronine (3,5-T2) is an active thyroid hormone within the class of iodothyronines. It has two iodine atoms at positions 3 and 5 of its inner ring.

<span class="mw-page-title-main">SimThyr</span> 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. Its simulation engine is multi-threaded and supports multiple processor cores. SimThyr 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 intended for both 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.

The Thyroid Feedback Quantile-based Index (TFQI) is a calculated parameter for thyrotropic pituitary function. It was defined to be more robust to distorted data than established markers including Jostel's TSH index (JTI) and the thyrotroph thyroid hormone sensitivity index (TTSI).

References

  1. 1 2 3 4 5 6 7 Jostel A, Ryder WD, Shalet SM (October 2009). "The use of thyroid function tests in the diagnosis of hypopituitarism: definition und evaluation of the TSH Index". Clin. Endocrinol. (Oxf). 71 (4): 529–34. doi:10.1111/j.1365-2265.2009.03534.x. PMID   19226261. S2CID   10827131.
  2. 1 2 Persani, L; Brabant, G; Dattani, M; Bonomi, M; Feldt-Rasmussen, U; Fliers, E; Gruters, A; Maiter, D; Schoenmakers, N; van Trotsenburg, ASP (October 2018). "2018 European Thyroid Association (ETA) Guidelines on the Diagnosis and Management of Central Hypothyroidism". European Thyroid Journal. 7 (5): 225–237. doi:10.1159/000491388. PMC   6198777 . PMID   30374425.
  3. ↑ Reichlin S, Utiger RD (February 1967). "Regulation of the pituitary-thyroid axis in man: relationship of TSH concentration to concentration of free and total thyroxine in plasma". J Clin Endocrinol Metab . 27 (2): 251–255. doi:10.1210/jcem-27-2-251. PMID   4163614.
  4. ↑ Cohen, J. L., Thyroid-stimulation hormone and its disorders. In: Becker, K. L. (Hrsg.) Principles and Practice of Endocrinology and Metabolism. S. 144–52, J. B. Lippincott Company, Philadelphia, PA, USA, 1990
  5. 1 2 Dietrich, JW; Landgrafe, G; Fotiadou, EH (2012). "TSH and Thyrotropic Agonists: Key Actors in Thyroid Homeostasis". J Thyroid Res. 2012: 351864. doi: 10.1155/2012/351864 . PMC   3544290 . PMID   23365787..
  6. ↑ Dietrich, Johannes W.; Landgrafe-Mende, Gabi; Wiora, Evelin; Chatzitomaris, Apostolos; Klein, Harald H.; Midgley, John E. M.; Hoermann, Rudolf (2016-06-09). "Calculated Parameters of Thyroid Homeostasis: Emerging Tools for Differential Diagnosis and Clinical Research". Frontiers in Endocrinology. 7: 57. doi: 10.3389/fendo.2016.00057 . PMC   4899439 . PMID   27375554.
  7. ↑ Fliers, Eric; Korbonits, Marta; Romijn, J. A. (2014). Clinical Neuroendocrinology. Elsevier. p. 146. ISBN   978-0-444-62612-7.
  8. ↑ Dietrich, Johannes W.; Schifferdecker, Ekkehard; Schatz, Helmut; Klein, Harald (2022). "Endokrine und Stoffwechseldiagnostik". Die Ärztliche Begutachtung. Springer Reference Medizin. pp. 1–13. doi:10.1007/978-3-662-61937-7_83-1. ISBN   978-3-662-61937-7.
  9. ↑ Chiloiro, Sabrina; Tartaglione, Tommaso; Capoluongo, Ettore Domenico; Angelini, Flavia; Arena, Vincenzo; Giampietro, Antonella; Bianchi, Antonio; Zoli, Angelo; Pontecorvi, Alfredo; Colosimo, Cesare; De Marinis, Laura (1 August 2018). "Hypophysitis outcome and factors predicting responsiveness to glucocorticoid therapy: a prospective and double-arm study". The Journal of Clinical Endocrinology & Metabolism. 103 (10): 3877–3889. doi: 10.1210/jc.2018-01021 . PMID   30085134.
  10. ↑ Persani, L; Cangiano, B; Bonomi, M (1 January 2019). "The diagnosis and management of central hypothyroidism in 2018". Endocrine Connections. 8 (2): R44–R54. doi:10.1530/EC-18-0515. PMC   6373625 . PMID   30645189.
  11. ↑ Marlier, Joke; T'Sjoen, Guy; Kaufman, Jean; Lapauw, Bruno (October 2022). "Central hypothyroidism: are patients undertreated?". European Thyroid Journal. 11 (6): ETJ–21–0128. doi: 10.1530/ETJ-21-0128 . PMC   9641783 . PMID   36205647.
  12. ↑ Schoenmakers, N; Alatzoglou, KS; Chatterjee, VK; Dattani, MT (2015). "Recent advances in central congenital hypothyroidism". J Endocrinol. 227 (3): R51-71. doi:10.1530/JOE-15-0341. PMC   4629398 . PMID   26416826.
  13. ↑ Fan, S; Ni, X; Wang, J; Zhang, Y; Tao, S; Chen, M; Li, Y; Li, J (February 2016). "Low Triiodothyronine Syndrome in Patients With Radiation Enteritis: Risk Factors and Clinical Outcomes an Observational Study". Medicine. 95 (6): e2640. doi:10.1097/MD.0000000000002640. PMC   4753882 . PMID   26871787.
  14. ↑ Bingyan, Zhan; Dong, Wei (7 July 2019). "Impact of thyroid hormones on asthma in older adults". Journal of International Medical Research. 47 (9): 4114–4125. doi:10.1177/0300060519856465. PMC   6753544 . PMID   31280621.
  15. ↑ Lei, MK; Beach, SR; Simons, RL; Barr, AB; Cutrona, CE; Philibert, RA (Mar 2016). "Stress, relationship satisfaction, and health among African American women: Genetic moderation of effects". J Fam Psychol. 30 (2): 221–32. doi:10.1037/fam0000140. PMC   4749476 . PMID   26376424.
  16. 1 2 Dietrich, Johannes Wolfgang; Hoermann, Rudolf; Midgley, John E. M.; Bergen, Friederike; Müller, Patrick (26 October 2020). "The Two Faces of Janus: Why Thyrotropin as a Cardiovascular Risk Factor May Be an Ambiguous Target". Frontiers in Endocrinology. 11: 542710. doi: 10.3389/fendo.2020.542710 . PMC   7649136 . PMID   33193077.
  17. ↑ Krysiak, Robert; Kowalcze, Karolina; Wolnowska, Monika; Okopień, Bogusław (5 January 2020). "The impact of oral hormonal contraception on metformin action on hypothalamic-pituitary-thyroid axis activity in women with diabetes and prediabetes: A pilot study". Journal of Clinical Pharmacy and Therapeutics. 45 (5): 937–945. doi: 10.1111/jcpt.13105 . PMID   31903641. S2CID   209895460.
  18. 1 2 Ittermann, T; Markus, MRP; Bahls, M; Felix, SB; Steveling, A; Nauck, M; Völzke, H; Dörr, M (2021-05-18). "Low serum TSH levels are associated with low values of fat-free mass and body cell mass in the elderly". Scientific Reports. 11 (1): 10547. Bibcode:2021NatSR..1110547I. doi:10.1038/s41598-021-90178-7. PMC   8131378 . PMID   34006958.
  19. ↑ Chatzitomaris, A; Hoermann, R; Midgley, JE; Hering, S; Urban, A; Dietrich, B; Abood, A; Klein, HH; Dietrich, JW (2017). "Thyroid Allostasis-Adaptive Responses of Thyrotropic Feedback Control to Conditions of Strain, Stress, and Developmental Programming". Frontiers in Endocrinology. 8: 163. doi: 10.3389/fendo.2017.00163 . PMC   5517413 . PMID   28775711.
  20. ↑ Tan, Y; Gao, L; Yin, Q; Sun, Z; Man, X; Du, Y; Chen, Y (April 2021). "Thyroid hormone levels and structural parameters of thyroid homeostasis are correlated with motor subtype and disease severity in euthyroid patients with Parkinson's disease". The International Journal of Neuroscience. 131 (4): 346–356. doi:10.1080/00207454.2020.1744595. PMID   32186220. S2CID   212752563.
  21. 1 2 Müller, Patrick; Dietrich, Johannes W.; Lin, Tina; Bejinariu, Alexandru; Binnebößel, Stephan; Bergen, Friederike; Schmidt, Jan; Müller, Sarah-Kristin; Chatzitomaris, Apostolos; Kurt, Muhammed; Gerguri, Shqipe; Clasen, Lukas; Klein, Harald H.; Kelm, Malte; Makimoto, Hisaki (January 2020). "Usefulness of Serum Free Thyroxine Concentration to Predict Ventricular Arrhythmia Risk in Euthyroid Patients with Structural Heart Disease". The American Journal of Cardiology. 125 (8): 1162–1169. doi:10.1016/j.amjcard.2020.01.019. PMID   32087999. S2CID   211261823.
  22. ↑ Tawakol, A; Ishai, A; Takx, RA; Figueroa, AL; Ali, A; Kaiser, Y; Truong, QA; Solomon, CJ; Calcagno, C; Mani, V; Tang, CY; Mulder, WJ; Murrough, JW; Hoffmann, U; Nahrendorf, M; Shin, LM; Fayad, ZA; Pitman, RK (25 February 2017). "Relation between resting amygdalar activity and cardiovascular events: a longitudinal and cohort study". Lancet. 389 (10071): 834–845. doi: 10.1016/S0140-6736(16)31714-7 . PMC   7864285 . PMID   28088338.
  23. ↑ Hoermann, R; Midgley, JEM; Larisch, R; Dietrich, JW (19 July 2018). "The Role of Functional Thyroid Capacity in Pituitary Thyroid Feedback Regulation". European Journal of Clinical Investigation. 48 (10): e13003. doi:10.1111/eci.13003. PMID   30022470. S2CID   51698223.
  24. ↑ Yang, Lijuan; Sun, Xiuqin; Zhao, Yi; Tao, Hong (7 March 2022). "Effects of Antihypertensive Drugs on Thyroid Function in Type 2 Diabetes Patients With Euthyroidism". Frontiers in Pharmacology. 13: 802159. doi: 10.3389/fphar.2022.802159 . PMC   8940167 . PMID   35330837.
  25. ↑ Chen, Y; Zhang, W; Chen, J; Wang, N; Chen, C; Wang, Y; Wan, H; Chen, B; Lu, Y (2021). "Association of Phthalate Exposure with Thyroid Function and Thyroid Homeostasis Parameters in Type 2 Diabetes". Journal of Diabetes Research. 2021: 4027380. doi: 10.1155/2021/4027380 . PMC   8566079 . PMID   34746318.
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