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Jostel's TSH index

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Jostel's TSH index
Reference ranges for TSH, FT4, JTI and SPINA-GT
Reference ranges for JTI and other thyroid function tests
SynonymsJostel's thyrotropin index
Reference range1.3–4.1
MeSHD013960

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]

How to determine JTI

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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

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Percentiles of Jostel's TSH index
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.
Parameter Lower limit Upper limit Unit
TSHI 1.3[1] 4.1[1]
sTSHI -2[1] 2[1]

Clinical significance

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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

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References

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  1. ^ a b c d e f g 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. ^ a b 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. ^ a b 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. ^ a b 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. ^ a b 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. ^ a b 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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