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 [17] , especially in women under oral contraceptives. [18]

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. [19] With the exception of fat mass all correlations were age-dependent. [19] Very similar observations have been made earlier in the NHANES dataset. [20]

In Parkinson's disease, JTI is significantly elevated in early sub-types of the disease compared to an advanced group. [21]

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. [22] This applies to both incidence and event-free survival. [22] A second study in a different population undergoing coronary angiography arrived at similar results [23] . 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. [24]

Jostel's TSH index and the thyroid feedback quantile-based index, another biomarker for the central thyrotropic function, were observed to be elevated in certain psychiatric diseases including schizophrenia [25] .

Another study demonstrated the TSH index to inversely correlate to thyroid's secretory capacity and thyroid volume. [26] 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. [27]

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. [28]

Drugs that reduce the TSH index, probably via effects on the central set point of the feedback loop, include mirtazapine [29] and oxcarbazepine [30] .

A reduction of Jostel's TSH index may predict the development of hypophysitis due to therapy with immune checkpoint inhibitors, e. g. ipilimumab [31] .

See also

Related Research Articles

<span class="mw-page-title-main">Hyperthyroidism</span> Clinical syndrome caused by excessive 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> Insufficient production of thyroid hormones by the thyroid gland

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, extreme fatigue, muscle aches, 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.

<span class="mw-page-title-main">Iodothyronine deiodinase</span> Class of enzymes

Iodothyronine deiodinases (EC 1.21.99.4 and EC 1.21.99.3) are a subfamily of deiodinase enzymes important in the activation and deactivation of thyroid hormones. Thyroxine (T4), the precursor of 3,5,3'-triiodothyronine (T3) is transformed into T3 by deiodinase activity. T3, through binding a nuclear thyroid hormone receptor, influences the expression of genes in practically every vertebrate cell. Iodothyronine deiodinases are unusual in that these enzymes contain selenium, in the form of an otherwise rare amino acid selenocysteine.

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.

<span class="mw-page-title-main">Levothyroxine</span> Thyroid hormone

Levothyroxine, also known as L-thyroxine, is a synthetic form of the thyroid hormone thyroxine (T4). It is used to treat thyroid hormone deficiency (hypothyroidism), including a severe form known as myxedema coma. It may also be used to treat and prevent certain types of thyroid tumors. It is not indicated for weight loss. Levothyroxine is taken orally (by mouth) or given by intravenous injection. Levothyroxine has a half-life of 7.5 days when taken daily, so about six weeks is required for it to reach a steady level in the blood.

Thyroid storm is a rare but severe and life-threatening complication of hyperthyroidism. It occurs when an overactive thyroid leads to hypermetabolism, which can cause 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.

<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.

Deiodinase (monodeiodinase) is a peroxidase enzyme that is involved in the activation or deactivation of thyroid hormones.

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.

<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

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  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.
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  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, R; Kowalcze, K; Szkróbka, W; Okopień, B (20 August 2024). "The Association between Vitamin D Status and the Impact of Metformin on Hypothalamic-Pituitary-Thyroid Axis Activity in Women with Subclinical Hypothyroidism". Pharmaceutics. 16 (8): 1093. doi: 10.3390/pharmaceutics16081093 . PMC   11360748 . PMID   39204438.
  18. ↑ 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.
  19. 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.
  20. ↑ 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.
  21. ↑ 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.
  22. 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.
  23. ↑ Qin, Z; Muhanhali, D; Ling, Y (17 May 2024). "Impaired Thyroid Hormone Sensitivity Increases Risk of Cardiovascular Events in Patients Undergoing Coronary Angiography". The Journal of Clinical Endocrinology and Metabolism. 109 (6): 1550–1564. doi:10.1210/clinem/dgad735. PMID   38103262.
  24. ↑ 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.
  25. ↑ Zhai, D; Bing, J; Shan, X; Luo, H; Wen, W; Gao, S; Niu, K; Cui, T; Li, H; Retnakaran, R; Hao, W; Zhang, R; Zhao, Y; Wen, SW (December 2022). "Higher central set point of thyroid homeostasis in drug-naïve patients affected by first episode schizophrenia". Schizophrenia Research. 250: 62–66. doi:10.1016/j.schres.2022.10.022. PMID   36368279.
  26. ↑ 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.
  27. ↑ 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.
  28. ↑ 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.
  29. ↑ Zhao, Y; Wang, N; Wen, SW; Li, M; Yuan, Y; Retnakaran, R; Hao, W; Zhang, R; Zhai, D (January 2022). "Mirtazapine use may increase the risk of hypothyroxinaemia in patients affected by major depressive disorder". British Journal of Clinical Pharmacology. 88 (1): 214–225. doi:10.1111/bcp.14949. PMID   34155670.
  30. ↑ Zhai, D; Chen, J; Guo, B; Retnakaran, R; Gao, S; Zhang, X; Hao, W; Zhang, R; Zhao, Y; Wen, SW (May 2022). "Oxcarbazepine was associated with risks of newly developed hypothyroxinaemia and impaired central set point of thyroid homeostasis in schizophrenia patients". British Journal of Clinical Pharmacology. 88 (5): 2297–2305. doi:10.1111/bcp.15163. PMID   34855997.
  31. ↑ Siddiqui, MS; Lai, ZM; Spain, L; Greener, V; Turajlic, S; Larkin, J; Morganstein, DL (January 2021). "Predicting development of ipilimumab-induced hypophysitis: utility of T4 and TSH index but not TSH". Journal of Endocrinological Investigation. 44 (1): 195–203. doi:10.1007/s40618-020-01297-3. PMC   7796881 . PMID   32449093.
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