Sum activity of peripheral deiodinases

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Sum activity of peripheral deiodinases
Synonyms SPINA-GD, GD, deiodination capacity, total deiodinase activity
Reference range 20–40 nmol/s
Test ofMaximum amount of T3 produced from T4 by peripheral deiodinases
MeSH D013960
LOINC 82367-4

The sum activity of peripheral deiodinases (GD, also referred to as deiodination capacity, total deiodinase activity or, if calculated from levels of thyroid hormones, as SPINA-GD [lower-alpha 1] ) is the maximum amount of triiodothyronine produced per time-unit under conditions of substrate saturation. [1] 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.

Contents

How to determine GD

GD can be determined experimentally by exposing a cell culture system to saturating concentrations of T4 and measuring the T3 production. Whole body deiodination activity can be assessed by measuring production of radioactive iodine after loading the organism with marked thyroxine. [2]

However, both approaches are faced with draw-backs. Measuring deiodination in cell culture delivers little, if any, information on total deiodination activity. Using marked thyroxine exposes the body to thyrotoxicosis and radioactivity. Additionally, it is not possible to differentiate step-up reactions resulting in T3 production from the step-down reaction catalyzed by type 3 deiodination, which mediates production of reverse T3. Distinguishing the contribution of distinct deiodinases is possible, however, by sequential approaches using deiodinase-specific blocking agents, but this approach is cumbersome and time-consuming. [2]

In vivo, it may therefore be beneficial to estimate GD from equilibrium levels of T4 and T3. It is obtained with

or

[FT4]: Serum free T4 concentration (in pmol/L)
[FT3]: Serum free T3 concentration (in pmol/L)
[TT3]: Serum total T3 concentration (in nmol/L)
: Dilution factor for T3 (reciprocal of apparent volume of distribution, 0.026 L−1)
: Clearance exponent for T3 (8e-6 sec−1) (i. e., reaction rate constant for degradation)
KM1: Binding constant of type-1-deiodinase (5e-7 mol/L)
K30: Binding constant T3-TBG (2e9 L/mol) [3]

The method is based on mathematical models of thyroid homeostasis. [1] [3] Calculating deiodinase activity with one of these equations is an inverse problem. Therefore, certain conditions (e.g. stationarity) have to be fulfilled to deliver a reliable result.

The product of SPINA-GD times the urinary iodine excretion can be used to assess iodine-independent factors affecting deiodinase activity, e.g. selenium deficiency. [4]

Reference range

Lower limitUpper limitUnit
20 [3] 40 [3] nmol/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. [3]

Clinical significance

Validity

SPINA-GD correlates to the T4-T3 conversion rate in slow tissue pools, as determined with isotope-based measurements in healthy volunteers. [1] It was also shown that GD correlates with resting energy expenditure, [5] body mass index [3] [6] [7] and thyrotropin levels in humans, [8] [9] and that it is reduced in nonthyroidal illness with hypodeiodination. [6] [10] [11] [12] [13] Multiple studies demonstrated SPINA-GD to rise after initiation of substitution therapy with selenium, a trace element that is essential for the synthesis of deiodinases. [14] [15] [16] [17] [18] Conversely, it was observed that SPINA-GD is reduced in persons positive for autoantibodies to selenoprotein P, which is assumed to be involved in transport and storage of selenium. [4]

Clinical utility

Compared to both healthy volunteers and subjects with hypothyroidism and hyperthyroidism, SPINA-GD is reduced in subacute thyroiditis. In this condition, it has a higher specificity, positive and negative likelihood ratio than serum concentrations of thyrotropin, free T4 or free T3. [3] These measures of diagnostic utility are also high in nodular goitre, where SPINA-GD is elevated. [3] Among subjects with subclinical thyrotoxicosis, calculated deiodinase activity is significantly lower in exogenous thyrotoxicosis (resulting from therapy with levothyroxine) than in true hyperthyroidism (ensuing from toxic adenoma, toxic multinodular goitre or Graves' disease). [19] SPINA-GD may therefore be an effective biomarker for the differential diagnosis of thyrotoxicosis. [20] [21]

Compared to healthy subjects, SPINA-GD is significantly reduced in euthyroid sick syndrome. [22]

Pathophysiological and therapeutic implications

Recent research revealed total deiodinase activity to be higher in untreated hypothyroid patients as long as thyroid tissue is still present. [9] This effect may ensue from the existence of an effective TSH-deiodinase axis or TSH-T3 shunt. After total thyroidectomy or high-dose radioiodine therapy (e.g. in treated thyroid cancer) as well as after initiation of substitution therapy with levothyroxine the activity of step-up deiodinases decreases [23] [24] and the correlation of SPINA-GD to thyrotropin concentration is lost. [25] In patients suffering from toxic adenoma, toxic multinodular goitre and Graves’ disease low-dose radioiodine therapy leads to a significant reduction of SPINA-GD as well. [26]

SPINA-GD is elevated in obesity. This applies to both the metabolically healthy obese (MHO) or metabolically unhealthy obese (MUO) phenotypes. [27] In two large population-based cohorts within the Study of Health in Pomerania SPINA-GD was positively correlated to some markers of body composition including body mass index (BMI), waist circumference, fat-free mass and body cell mass, [28] confirming observations in the NHANES dataset [29] and in a Chinese study. [30] This positive association was age-dependent and with respect to BMI significant in young subjects only, but with respect to body cell mass stronger in elderly persons. [28] Generally, SPINA-GD seems to be upregulated in metabolic syndrome, as demonstrated by a significant correlation to the triglyceride-glucose index, a marker of insulin resistance. [31]

SPINA-GD is reduced in low-T3 syndrome [32] and certain chronic diseases, e.g. chronic fatigue syndrome, [33] [4] chronic kidney disease, [34] [35] short bowel syndrome [36] or geriatric asthma. [37] In Graves' disease, SPINA-GD is initially elevated but decreases with antithyroid treatment in parallel to declining TSH receptor autoantibody titres. [5] Although takotsubo syndrome (TTS) results in most cases from psychosocial stressors, thereby reflecting type 2 allostatic load, SPINA-GD has been described to be reduced in TTS. [38] This may result from concomitant non-thyroidal illness syndrome, so that the clinical phenotype represents overlapping type 1 and type 2 allostatic response. In a large register-based study, reduced SPINA-GD predicted a poor outcome of Takotsubo syndrome. [39]

In certain psychiatric diseases, including major depression, bipolar disorder and schizophrenia SPINA-GD is reduced compared to healthy controls. [40] This observation is supported by negative correlation of SPINA-GD with the depression percentiles in the Hospital Anxiety and Depression Scale (HADS). [41]

In hyperthyroid [42] men both SPINA-GT and SPINA-GD negatively correlate to erectile function, intercourse satisfaction, orgasmic function and sexual desire. Substitution with selenomethionine results in increased SPINA-GD in subjects with autoimmune thyroiditis. [14] [15] [16] [17]

In subjects with diabetes mellitus SPINA-GD is positively correlated to several bone resorption markers including the N-mid fragment of osteocalcin and procollagen type I N-terminal propeptide (P1NP), as well as, however in men only, the β-C-terminal cross-linked telopeptides of type I collagen (β-CTX). [43] In the general population it is, however, positively associated with the bone mineral density of the femoral neck and with reduced risk of osteoporosis. [44] In both diabetic and non-diabetic subsjects it correlates (negatively) with age and concentrations of c-reactive protein, troponin T and B-type natriuretic peptide, and (positively) with the concentrations of total cholesterol, low-density lipoprotein and triglycerides. [45]

Deiodination capacity proved to be an independent predictor of substitution dose in several trials that included persons on replacement therapy with levothyroxine. [46] [47]

Probably as a consequence of non-thyroidal illness syndrome, SPINA-GD predicts mortality in trauma [22] and postoperative atrial fibrillation in patients undergoing cardiac surgery. [12] The association to mortality is retained even after adjustment for other established risk factors, including age, APACHE II score and plasma protein binding of thyroid hormones. [22] Correlations were also shown to age, total atrial conduction time, and concentrations of 3,5-diiodothyronine and B-type natriuretic peptide. [12] SPINA-GD also correlates with several components of the kynurenine pathway, which might mirror an assosication to a pro-inflammatory milieu. [48] Accordingly, in a population suffering from pyogenic liver abscess SPINA-GD correlated to markers of malnutrition, inflammation and liver failure. [32] A study on subjects with Parkinson's disease found SPINA-GD to be significantly decreased in tremor-dominant and mixed subtypes compared to the akinetic-rigid type. [49] Euthyroid sick syndrome may be the reason for variations of SPINA-GD in subjects treated with immune checkpoint inhibitors for cancer as well. [50]

Endocrine disruptors may have pronounced effects on step-up deiodinases, as suggested by positive correlation of SPINA-GD to combined exposure to polycyclic aromatic hydrocarbons (PAHs) [51] and urine concentrations of cadmium and phthalate metabolites [52] [53] [54] and negative correlation to paraben, mercury and bisphenol A concentration. [55] [52] [53] In a cohort of manganese-exposed workers, SPINA-GD responded to a tenfold increase in concentrations of titanium, nickel, selenium and strontium. [56]

See also

Notes

  1. SPINA is an acronym for "structure parameter inference approach".

Related Research Articles

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References

  1. 1 2 3 Dietrich JW, Landgrafe-Mende G, Wiora E, Chatzitomaris A, Klein HH, Midgley JE, Hoermann R (9 June 2016). "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. S2CID   14210899.
  2. 1 2 Bianco AC, Anderson G, Forrest D, Galton VA, Gereben B, Kim BW, Kopp PA, Liao XH, Obregon MJ, Peeters RP, Refetoff S, Sharlin DS, Simonides WS, Weiss RE, Williams GR (January 2014). "American Thyroid Association Guide to investigating thyroid hormone economy and action in rodent and cell models". Thyroid. 24 (1): 88–168. doi:10.1089/thy.2013.0109. PMC   3887458 . PMID   24001133.
  3. 1 2 3 4 5 6 7 8 Dietrich JW (2002). Der Hypophysen-Schilddrüsen-Regelkreis. Berlin, Germany: Logos-Verlag Berlin. ISBN   978-3-89722-850-4. OCLC   50451543. OL   24586469M.
  4. 1 2 3 Sun Q, Oltra E, Dijck-Brouwer D, Chillon TS, Seemann P, Asaad S, Demircan K, Espejo-Oltra JA, Sánchez-Fito T, Martín-Martínez E, Minich WB, Muskiet F, Schomburg L (3 July 2023). "Autoantibodies to selenoprotein P in chronic fatigue syndrome suggest selenium transport impairment and acquired resistance to thyroid hormone". Redox Biology. 65: 102796. doi:10.1016/j.redox.2023.102796. PMC   10338150 . PMID   37423160.
  5. 1 2 Kim MJ, Cho SW, Choi S, Ju DL, Park DJ, Park YJ (2018). "Changes in Body Compositions and Basal Metabolic Rates during Treatment of Graves' Disease". International Journal of Endocrinology. 2018: 9863050. doi: 10.1155/2018/9863050 . PMC   5960571 . PMID   29853888. S2CID   44088904.
  6. 1 2 Liu S, Ren J, Zhao Y, Han G, Hong Z, Yan D, Chen J, Gu G, Wang G, Wang X, Fan C, Li J (February 2013). "Nonthyroidal illness syndrome: is it far away from Crohn's disease?". Journal of Clinical Gastroenterology. 47 (2): 153–9. doi:10.1097/MCG.0b013e318254ea8a. PMID   22874844. S2CID   35344744.
  7. Dietrich JW, Landgrafe G, Fotiadou EH (2012). "TSH and Thyrotropic Agonists: Key Actors in Thyroid Homeostasis". Journal of Thyroid Research. 2012: 1–29. doi: 10.1155/2012/351864 . PMC   3544290 . PMID   23365787. S2CID   15996441.
  8. Hoermann R, Midgley JE, Larisch R, Dietrich JW (February 2013). "Is pituitary TSH an adequate measure of thyroid hormone-controlled homoeostasis during thyroxine treatment?". European Journal of Endocrinology. 168 (2): 271–80. doi: 10.1530/EJE-12-0819 . PMID   23184912.
  9. 1 2 Hoermann R, Midgley JE, Giacobino A, Eckl WA, Wahl HG, Dietrich JW, Larisch R (December 2014). "Homeostatic equilibria between free thyroid hormones and pituitary thyrotropin are modulated by various influences including age, body mass index and treatment". Clinical Endocrinology. 81 (6): 907–15. doi: 10.1111/cen.12527 . PMID   24953754. S2CID   19341039.
  10. Rosolowska-Huszcz D, Kozlowska L, Rydzewski A (August 2005). "Influence of low protein diet on nonthyroidal illness syndrome in chronic renal failure". Endocrine. 27 (3): 283–8. doi:10.1385/ENDO:27:3:283. PMID   16230785. S2CID   25630198.
  11. Han G, Ren J, Liu S, Gu G, Ren H, Yan D, Chen J, Wang G, Zhou B, Wu X, Yuan Y, Li J (September 2013). "Nonthyroidal illness syndrome in enterocutaneous fistulas". American Journal of Surgery. 206 (3): 386–92. doi:10.1016/j.amjsurg.2012.12.011. PMID   23809674.
  12. 1 2 3 Dietrich JW, Müller P, Schiedat F, Schlömicher M, Strauch J, Chatzitomaris A, Klein HH, Mügge A, Köhrle J, Rijntjes E, Lehmphul I (June 2015). "Nonthyroidal Illness Syndrome in Cardiac Illness Involves Elevated Concentrations of 3,5-Diiodothyronine and Correlates with Atrial Remodeling". European Thyroid Journal. 4 (2): 129–37. doi:10.1159/000381543. PMC   4521060 . PMID   26279999. S2CID   207639541.
  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. S2CID   14016461.
  14. 1 2 Krysiak R, Szkróbka W, Okopień B (October 2018). "The effect of vitamin D and selenomethionine on thyroid antibody titers, hypothalamic-pituitary-thyroid axis activity and thyroid function tests in men with Hashimoto's thyroiditis: a pilot study". Pharmacological Reports. 71 (2): 243–7. doi:10.1016/j.pharep.2018.10.012. PMID   30818086. S2CID   73481267.
  15. 1 2 Krysiak R, Kowalcze K, Okopień B (December 2018). "Selenomethionine potentiates the impact of vitamin D on thyroid autoimmunity in euthyroid women with Hashimoto's thyroiditis and low vitamin D status". Pharmacological Reports. 71 (2): 367–73. doi:10.1016/j.pharep.2018.12.006. PMID   30844687. S2CID   73486105.
  16. 1 2 Krysiak R, Kowalcze K, Okopień B (20 May 2019). "The Effect of Selenomethionine on Thyroid Autoimmunity in Euthyroid Men With Hashimoto Thyroiditis and Testosterone Deficiency". Journal of Clinical Pharmacology. 59 (11): 1477–1484. doi:10.1002/jcph.1447. PMID   31106856. S2CID   159040151.
  17. 1 2 Krysiak R, Kowalcze K, Okopień B (10 July 2020). "Hyperprolactinaemia attenuates the inhibitory effect of vitamin D/selenomethionine combination therapy on thyroid autoimmunity in euthyroid women with Hashimoto's thyroiditis: A pilot study". Journal of Clinical Pharmacy and Therapeutics. 45 (6): 1334–1341. doi: 10.1111/jcpt.13214 . PMID   32649802. S2CID   220485158.
  18. Krysiak R, Kowalcze K, Szkróbka W, Okopień B (20 June 2023). "Sexual Function and Depressive Symptoms in Young Women with Euthyroid Hashimoto's Thyroiditis Receiving Vitamin D, Selenomethionine and Myo-Inositol: A Pilot Study". Nutrients. 15 (12): 2815. doi: 10.3390/nu15122815 . PMC   10304218 . PMID   37375719.
  19. Hoermann R, Midgley J, Larisch R, Dietrich JW (March 2020). "Heterogenous biochemical expression of hormone activity in subclinical/overt hyperthyroidism and exogenous thyrotoxicosis". Journal of Clinical & Translational Endocrinology. 19: 100219. doi: 10.1016/j.jcte.2020.100219 . PMC   7031309 . PMID   32099819.
  20. Dietrich JW. "SPINA in Science and Research: Year in Review: 2020". sourceforge.net. Retrieved 2 January 2021.
  21. Pattarawongpaiboon C, Srisawat N, Tungsanga K, Champunot R, Somboonjun J, Srichomkwun P (20 November 2023). "Clinical characteristics and outcomes of an exogenous thyrotoxicosis epidemic in prison". BMJ Nutrition, Prevention & Health. 6 (2): 318–325. doi: 10.1136/bmjnph-2023-000789 . PMC   11009531 . PMID   38618547.
  22. 1 2 3 Dietrich JW, Ackermann A, Kasippillai A, Kanthasamy Y, Tharmalingam T, Urban A, Vasileva S, Schildhauer TA, Klein HH, Stachon A, Hering S (19 September 2019). "Adaptive Veränderungen des Schilddrüsenstoffwechsels als Risikoindikatoren bei Traumata". Trauma und Berufskrankheit. 21 (4): 260–267. doi:10.1007/s10039-019-00438-z. S2CID   202673793.
  23. Aweimer A, Schiedat F, Schöne D, Landgrafe-Mende G, Bogossian H, Mügge A, Patsalis PC, Gotzmann M, Akin I, El-Battrawy I, Dietrich JW (23 November 2021). "Abnormal Cardiac Repolarization in Thyroid Diseases: Results of an Observational Study". Frontiers in Cardiovascular Medicine. 8: 738517. doi: 10.3389/fcvm.2021.738517 . PMC   8649843 . PMID   34888359.
  24. Ağbaht K, Pişkinpaşa SV (18 November 2022). "Serum TSH, 25(OH) D and phosphorus levels predict weight loss in individuals with diabetes/prediabetes and morbid obesity: a single-center retrospective cohort analysis". BMC Endocrine Disorders. 22 (1): 282. doi: 10.1186/s12902-022-01202-4 . PMC   9673446 . PMID   36401211.
  25. Hoermann R, Midgley JE, Larisch R, Dietrich JW (2017). "Advances in applied homeostatic modelling of the relationship between thyrotropin and free thyroxine". PLOS ONE. 12 (11): e0187232. Bibcode:2017PLoSO..1287232H. doi: 10.1371/journal.pone.0187232 . PMC   5695809 . PMID   29155897. S2CID   6407766.
  26. Larisch R, Midgley J, Dietrich JW, Hoermann R (23 January 2024). "Effect of Radioiodine Treatment on Quality of Life in Patients with Subclinical Hyperthyroidism: A Prospective Controlled Study". Nuklearmedizin. Nuclear Medicine. 63 (3): 176–187. doi:10.1055/a-2240-8087. PMID   38262472. S2CID   267198748.
  27. Wang Zixiao WZ, Yang Sijue YS, Guan Haixia GH, Wang Wei WW (2023). "甲状腺功能正常人群中甲状腺激素敏感性与肥胖表型的关系". 中华内分泌代谢杂志. 39 (5): 426–429. doi:10.3760/cma.j.cn311282-20221012-00579.
  28. 1 2 Ittermann T, Markus M, Bahls M, Felix SB, Steveling A, Nauck M, Völzke H, Dörr M (18 May 2021). "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.
  29. 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.
  30. Yang L, Sun X, Tao H, Zhao Y (February 2023). "The association between thyroid homeostasis parameters and obesity in subjects with euthyroidism". Journal of Physiology and Pharmacology. 74 (1). doi:10.26402/jpp.2023.1.07. PMID   37245234.
  31. Cheng H, Hu Y, Zhao H, Zhou G, Wang G, Ma C, Xu Y (10 November 2023). "Exploring the association between triglyceride-glucose index and thyroid function". European Journal of Medical Research. 28 (1): 508. doi: 10.1186/s40001-023-01501-z . PMC   10636949 . PMID   37946276.
  32. 1 2 Xu J, Wang L (2019). "Low T3 Syndrome as a Predictor of Poor Prognosis in Patients With Pyogenic Liver Abscess". Frontiers in Endocrinology. 10: 541. doi: 10.3389/fendo.2019.00541 . PMC   6691090 . PMID   31447784. S2CID   199435315.
  33. Ruiz-Núñez B, Tarasse R, Vogelaar EF, Janneke Dijck-Brouwer DA, Muskiet FA (20 March 2018). "Higher Prevalence of "Low T3 Syndrome" in Patients With Chronic Fatigue Syndrome: A Case–Control Study". Frontiers in Endocrinology. 9: 97. doi: 10.3389/fendo.2018.00097 . PMC   5869352 . PMID   29615976. S2CID   4550317.
  34. Chen Y, Zhang W, Wang N, Wang Y, Wang C, Wan H, Lu Y (2020). "Thyroid Parameters and Kidney Disorder in Type 2 Diabetes: Results from the METAL Study". Journal of Diabetes Research. 2020: 4798947. doi: 10.1155/2020/4798947 . PMC   7149438 . PMID   32337292.
  35. Yang S, Lai S, Wang Z, Liu A, Wang W, Guan H (December 2021). "Thyroid Feedback Quantile-based Index correlates strongly to renal function in euthyroid individuals". Annals of Medicine. 53 (1): 1945–1955. doi:10.1080/07853890.2021.1993324. PMC   8567884 . PMID   34726096.
  36. Wan S, Yang J, Gao X, Zhang L, Wang X (22 July 2020). "Nonthyroidal Illness Syndrome in Patients With Short-Bowel Syndrome". Journal of Parenteral and Enteral Nutrition. 45 (5): 973–981. doi:10.1002/jpen.1967. PMID   32697347. S2CID   220698496.
  37. Bingyan Z, Dong W (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. S2CID   195830014.
  38. Aweimer A, El-Battrawy I, Akin I, Borggrefe M, Mügge A, Patsalis PC, Urban A, Kummer M, Vasileva S, Stachon A, Hering S, Dietrich JW (12 November 2020). "Abnormal thyroid function is common in takotsubo syndrome and depends on two distinct mechanisms: results of a multicentre observational study". Journal of Internal Medicine. 289 (5): 675–687. doi: 10.1111/joim.13189 . PMID   33179374.
  39. Aweimer A, Dietrich JW, Santoro F, Fàbregas MC, Mügge A, Núñez-Gil IJ, Vazirani R, Vedia O, Pätz T, Ragnatela I, Arcari L, Volpe M, Corbì-Pascual M, Martinez-Selles M, Almendro-Delia M, Sionis A, Uribarri A, Thiele H, Brunetti ND, Eitel I, Stiermaier T, Hamdani N, Abumayyaleh M, Akin I, El-Battrawy I (18 March 2024). "Takotsubo syndrome outcomes predicted by thyroid hormone signature: insights from cluster analysis of a multicentre registry". eBioMedicine. 102: 105063. doi:10.1016/j.ebiom.2024.105063. PMC   10963195 . PMID   38502972.
  40. Cui T, Qi Z, Wang M, Zhang X, Wen W, Gao S, Zhai J, Guo C, Zhang N, Zhang X, Guan Y, Retnakaran R, Hao W, Zhai D, Zhang R, Zhao Y, Wen SW (April 2024). "Thyroid allostasis in drug-free affective disorder patients". Psychoneuroendocrinology. 162: 106962. doi:10.1016/j.psyneuen.2024.106962. PMID   38277991.
  41. Bazika-Gerasch B, Kumowski N, Enax-Krumova E, Kaisler M, Eitner LB, Maier C, Dietrich JW (29 May 2024). "Impaired autonomic function and somatosensory disturbance in patients with treated autoimmune thyroiditis". Scientific Reports. 14 (1): 12358. Bibcode:2024NatSR..1412358B. doi:10.1038/s41598-024-63158-w. PMC   11137073 . PMID   38811750.
  42. Krysiak R, Marek B, Okopień B (2019). "Sexual function and depressive symptoms in men with overt hyperthyroidism". Endokrynologia Polska. 70 (1): 64–71. doi: 10.5603/EP.a2018.0069 . PMID   30307028.
  43. Chen Y, Zhang W, Chen C, Wang Y, Wang N, Lu Y (31 March 2022). "Thyroid and bone turnover markers in type 2 diabetes: results from the METAL study". Endocrine Connections. 11 (3). doi:10.1530/EC-21-0484. PMC   9010813 . PMID   35196256.
  44. Liu C, Hua L, Liu K, Xin Z (16 February 2023). "Impaired sensitivity to thyroid hormone correlates to osteoporosis and fractures in euthyroid individuals". Journal of Endocrinological Investigation. 46 (10): 2017–2029. doi:10.1007/s40618-023-02035-1. PMID   36795243. S2CID   256899701.
  45. Li W, He Q, Zhang H, Shu S, Wang L, Wu Y, Yuan Z, Zhou J (20 January 2023). "Thyroid-stimulating hormone within the normal reference range has a U-shaped association with the severity of coronary artery disease in nondiabetic patients but is diluted in diabetic patients". Journal of Investigative Medicine. 71 (4): 350–360. doi:10.1177/10815589221149187. PMID   36680358. S2CID   256055662.
  46. Midgley JE, Larisch R, Dietrich JW, Hoermann R (December 2015). "Variation in the biochemical response to l-thyroxine therapy and relationship with peripheral thyroid hormone conversion efficiency". Endocrine Connections. 4 (4): 196–205. doi:10.1530/EC-15-0056. PMC   4557078 . PMID   26335522.
  47. Le Moli R, Malandrino P, Russo M, Tumino D, Piticchio T, Naselli A, Rapicavoli V, Belfiore A, Frasca F (March 2023). "Levothyroxine therapy, calculated deiodinases activity and basal metabolic rate in obese or nonobese patients after total thyroidectomy for differentiated thyroid cancer, results of a retrospective observational study". Endocrinology, Diabetes & Metabolism. 6 (2): e406. doi:10.1002/edm2.406. PMC   10000637 . PMID   36722311.
  48. Krupa A, Łebkowska A, Kondraciuk M, Kaminski KA, Kowalska I (21 March 2024). "Alteration in kynurenine pathway metabolites in young women with autoimmune thyroiditis". Scientific Reports. 14 (1): 6851. Bibcode:2024NatSR..14.6851K. doi:10.1038/s41598-024-57154-3. PMC   10957988 . PMID   38514790.
  49. 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.
  50. Verelst FR, Beyens M, Vandenbroucke E, Forceville K, Th B Twickler M (15 April 2022). "A decrease in peripheral thyroid hormone conversion efficiency in patients treated with immune checkpoint inhibitors and L-T3 as a possible alternative therapeutic escape option". European Journal of Clinical Investigation. 52 (7): e13790. doi:10.1111/eci.13790. PMID   35428986. S2CID   248203797.
  51. Yang S, Sun J, Wang S, E L, Zhang S, Jiang X (9 August 2023). "Association of exposure to polycyclic aromatic hydrocarbons with thyroid hormones in adolescents and adults, and the influence of the iodine status". Environmental Science: Processes & Impacts. 25 (9): 1449–1463. doi:10.1039/d3em00135k. PMID   37555279. S2CID   259916981.
  52. 1 2 Choi S, Kim MJ, Park YJ, Kim S, Choi K, Cheon GJ, Cho YH, Jeon HL, Yoo J, Park J (July 2020). "Thyroxine-binding globulin, peripheral deiodinase activity, and thyroid autoantibody status in association of phthalates and phenolic compounds with thyroid hormones in adult population". Environment International. 140: 105783. Bibcode:2020EnInt.14005783C. doi: 10.1016/j.envint.2020.105783 . PMID   32464474.
  53. 1 2 Kim MJ, Kim S, Choi S, Lee I, Moon MK, Choi K, Park YJ, Cho YH, Kwon YM, Yoo J, Cheon GJ, Park J (December 2020). "Association of exposure to polycyclic aromatic hydrocarbons and heavy metals with thyroid hormones in general adult population and potential mechanisms". Science of the Total Environment. 762: 144227. doi:10.1016/j.scitotenv.2020.144227. PMID   33373756. S2CID   229722026.
  54. 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.
  55. Huang PC, Chen HC, Leung SH, Lin YJ, Huang HB, Chang WT, Huang HI, Chang JW (1 December 2023). "Associations between paraben exposure, thyroid capacity, homeostasis and pituitary thyrotropic function in the general Taiwanese: Taiwan Environmental Survey for Toxicants (TEST) 2013". Environmental Science and Pollution Research. 31 (1): 1288–1303. doi:10.1007/s11356-023-31277-y. PMID   38038926. S2CID   265514578.
  56. Ge X, He J, Lin S, Bao Y, Zheng Y, Cheng H, Cai H, Feng X, Yang W, Hu S, Wang L, Liao Q, Wang F, Liu C, Chen X, Zou Y, Yang X (16 September 2023). "Associations of metal mixtures with thyroid function and potential interactions with iodine status: results from a cross-sectional study in MEWHC". Environmental Science and Pollution Research International. 30 (48): 105665–105674. Bibcode:2023ESPR...30j5665G. doi:10.1007/s11356-023-29682-4. PMID   37715904. S2CID   262013667.