Thyroid's secretory capacity

{{cs1 config|name-list-style=vanc}} {{Infobox diagnostic | name = Thyroid's secretory capacity | image = File:Reference ranges for TSH, FT4, JTI and SPINA-GT.svg | alt = Reference ranges for TSH, FT4, JTI and SPINA-GT | caption = Reference ranges for SPINA-GT and other thyroid function tests | pronounce = | purpose = | test of = Maximum amount of T4 produced by the thyroid in one second | based on = | synonyms = SPINA-GT, GT, T4 output, thyroid hormone output, thyroid's incretory capacity, functional thyroid capacity<ref>{{cite journal |last1=Hoermann |first1=R |last2=Midgley |first2=JEM |last3=Larisch |first3=R |last4=Dietrich |first4=JW |title=Treatment options for subclinical hypothyroidism. |journal=European Journal of Endocrinology |date=4 August 2021 |volume=185 |issue=3 |pages=L5–L6 |doi=10.1530/EJE-20-1405 |pmid=34243143|doi-access=free }}</ref> | calculator = | DiseasesDB = | ICD10 =  | ICD9 = | ICDO = | MedlinePlus = | eMedicine = | MeshID = D013960 | LOINC = 82368-2 | reference_range = 1.41–8.67 pmol/s }} '''Thyroid's secretory capacity''' ('''''GT''''', also referred to as '''thyroid's incretory capacity''', '''maximum thyroid hormone output''', '''T4 output''' or, if calculated from serum levels of thyrotropin and thyroxine, as '''SPINA-GT'''{{efn|''SPINA'' is an acronym for "structure parameter inference approach".}}) is the maximum stimulated amount of thyroxine that the thyroid can produce in a given time-unit (e.g. one second).<ref name=dietrich2002>{{Cite book |publisher = Logos-Verlag Berlin |isbn = 978-3-89722-850-4 |location = Berlin, Germany |title = Der Hypophysen-Schilddrüsen-Regelkreis |author = Dietrich, J. W. |date = 2002 |oclc = 50451543 |ol = 24586469M }}</ref><ref name = "Dietrich2016">{{cite journal |last1=Dietrich |first1=Johannes W. |last2=Landgrafe-Mende |first2=Gabi |last3=Wiora |first3=Evelin |last4=Chatzitomaris |first4=Apostolos |last5=Klein |first5=Harald H. |last6=Midgley |first6=John E. M. |last7=Hoermann |first7=Rudolf |title=Calculated Parameters of Thyroid Homeostasis: Emerging Tools for Differential Diagnosis and Clinical Research |journal=Frontiers in Endocrinology |date=9 June 2016 |volume=7 |page=57 |doi=10.3389/fendo.2016.00057 |pmc=4899439 |pmid=27375554|doi-access=free }}</ref>

''GT'' is both a theoretical concept that is used in physiological theories of thyroid function and (as a calculated parameter) a biomarker for advanced diagnosis of thyroid disorders.<ref>{{cite book |last1=Hoermann |first1=Rudolf |last2=Dietrich |first2=Johannes W. |chapter=Diagnosis of Hypothyroidism |title=Hypothyroidism |date=2025 |pages=111–132 |doi=10.1007/978-981-96-3682-2_10|isbn=978-981-96-3681-5 }}</ref>

== How to determine GT == Experimentally, ''GT'' can be determined by stimulating the thyroid with a high thyrotropin concentration (e.g. by means of rhTSH, i.e. recombinant human thyrotropin) and measuring its output in terms of T4 production, or by measuring the serum concentration of protein-bound iodine-131 after administration of radioiodine.<ref>{{cite book |last1=Bierich |first1=J. R. |chapter=Endokrinologie |editor=H. Wiesener |title=Einführung in die Entwicklungsphysiologie des Kindes |date=1964 |publisher=Springer |isbn=978-3-642-86507-7 |page=310}}</ref> These approaches are, however, costly and accompanied by significant exposure to radiation.<ref>{{cite journal |last1=Thompson |first1=MA |title=Radiation safety precautions in the management of the hospitalized (131)I therapy patient. |journal=Journal of Nuclear Medicine Technology |date=June 2001 |volume=29 |issue=2 |pages=61–6; test 74–5 |pmid=11376097}}</ref>

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

<math>\hat G_T = {{\beta _T (D_T + [TSH])(1 + K_{41} [TBG] + K_{42} [TBPA])[FT_4 ]} \over {\alpha _T [TSH]}}</math>

<math>\hat G_T = {{\beta _T (D_T + [TSH])[TT_4 ]} \over {\alpha _T [TSH]}}</math>

[''TSH'']: Serum thyrotropin concentration (in mIU/L or μIU/mL) [''FT4'']: Serum free T4 concentration (in pmol/L) [''TT4'']: Serum total T4 concentration (in nmol/L) <math>\hat G_T </math>: Theoretical (apparent) secretory capacity (SPINA-GT) <math>\alpha _T</math>: Dilution factor for T4 (reciprocal of apparent volume of distribution, 0.1 L−1) <math>\beta _T</math>: Clearance exponent for T4 (1.1e-6 sec−1), i. e., reaction rate constant for degradation ''K''41: Binding constant T4-TBG (2e10 L/mol) ''K''42: Binding constant T4-TBPA (2e8 L/mol) ''D''''T'': EC50 for TSH (2.75 mU/L)<ref name=dietrich2002/><ref>{{cite journal |vauthors=Dietrich JW, Stachon A, Antic B, Klein HH, Hering S | date = Oct 2008 | title = The AQUA-FONTIS study: protocol of a multidisciplinary, cross-sectional and prospective longitudinal study for developing standardized diagnostics and classification of non-thyroidal illness syndrome | journal = BMC Endocrine Disorders| volume = 8 | issue = 1| article-number = 13 | doi = 10.1186/1472-6823-8-13 | pmid = 18851740 | pmc=2576461 | doi-access = free }}</ref>

The method is based on mathematical models of thyroid homeostasis.<ref name=dietrich2002/><ref name = "Dietrich2016"/> Calculating the secretory capacity with one of these equations is an inverse problem. Therefore, certain conditions (e.g. stationarity) have to be fulfilled to deliver a reliable result.

===Specific secretory capacity===

The ratio of SPINA-GT and thyroid volume ''V''''T'' (as determined e.g. by ultrasonography)

<math>\hat{G}_{TS}=\frac{\hat{G}_{T}}{{V}_{T}}</math>,

i.e.

<math>\hat{G}_{TS}=\frac{\beta_{T}(D_{T}+[TSH])(1+K_{41}[TBG]+K_{ 42 }[TBPA])[FT_{4}]}{{\alpha_{T}[TSH]{V}_{T}}}</math>

<math>\hat{G}_{TS}=\frac{{{\beta_{T}(D_{T}+[TSH])[TT_{4}]}}}{{\alpha_{T}[TSH]{V}_{T}}}</math>

is referred to as ''specific thyroid capacity'' (SPINA-GTs).<ref name="Hoermann_ETJ_2016">{{cite journal |last1=Hoermann |first1=Rudolf |last2=Midgley |first2=John E.M. |last3=Larisch |first3=Rolf |last4=Dietrich |first4=Johannes W. |title=Relational Stability of Thyroid Hormones in Euthyroid Subjects and Patients with Autoimmune Thyroid Disease |journal=European Thyroid Journal |date=18 August 2016 |pmid=27843807 |doi=10.1159/000447967 |volume=5 |issue=3 |pmc=5091265 |pages=171–179}}</ref> It is a measure for how much one millilitre of thyroid tissue can produce under conditions of maximum stimulation. Thereby, SPINA-GTs is an estimate for the endocrine quality of thyroid tissue.{{citation needed|date=May 2022}}

=== Reference Range === thumb|right|alt=SPINA-GT percentiles|Percentiles for thyroid's secretory capacity (SPINA-GT) along with reference ranges for Jostel's TSH index (TSHI or JTI) 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. {| class="wikitable" |'''Lower limit'''||'''Upper limit'''||'''Unit''' |- | 1.41<ref name=dietrich2002/> || 8.67<ref name=dietrich2002/> || pmol/s |- |}

The equations and their parameters are calibrated for adult humans with a body mass of 70 kg and a plasma volume of ca. 2.5 L.<ref name=dietrich2002/>

== Clinical significance == === Validity === SPINA-GT is elevated in primary hyperthyroidism<ref name="Krysiak_2019_EndPol">{{cite journal |last1=Krysiak |first1=R |last2=Marek |first2=B |last3=Okopień |first3=B |title=Sexual function and depressive symptoms in men with overt hyperthyroidism. |journal=Endokrynologia Polska |date=2019 |volume=70 |issue=1 |pages=64–71 |doi=10.5603/EP.a2018.0069 |pmid=30307028|doi-access=free }}</ref><ref name=Aweimer_2021>{{cite journal |last1=Aweimer |first1=Assem |last2=Schiedat |first2=Fabian |last3=Schöne |first3=Dominik |last4=Landgrafe-Mende |first4=Gabi |last5=Bogossian |first5=Harilaos |last6=Mügge |first6=Andreas |last7=Patsalis |first7=Polykarpos C. |last8=Gotzmann |first8=Michael |last9=Akin |first9=Ibrahim |last10=El-Battrawy |first10=Ibrahim |last11=Dietrich |first11=Johannes W. |title=Abnormal Cardiac Repolarization in Thyroid Diseases: Results of an Observational Study |journal=Frontiers in Cardiovascular Medicine |date=23 November 2021 |volume=8 |article-number=738517 |doi=10.3389/fcvm.2021.738517 |pmid=34888359 |pmc=8649843|doi-access=free }}</ref> and reduced in both primary hypothyroidism<ref name=dietrich1999>{{cite journal |last1=Dietrich |first1=J. |first2=M. |last2=Fischer |first3=J. |last3=Jauch |first4=E. |last4=Pantke |first5=R. |last5=Gärtner |first6=C. R. |last6=Pickardt |title=SPINA-THYR: A Novel Systems Theoretic Approach to Determine the Secretion Capacity of the Thyroid Gland |url=https://www.researchgate.net/publication/233529705 |journal=European Journal of Internal Medicine |volume=10 |issue=Suppl. 1 |pages=S34}}</ref><ref>{{cite journal | author = Dietrich JW | s2cid = 31285541 | date = Sep 2012 | title = Thyroid storm | journal = Medizinische Klinik, Intensivmedizin und Notfallmedizin| volume = 107 | issue = 6| pages = 448–53 | doi = 10.1007/s00063-012-0113-2 | pmid = 22878518 }}</ref><ref name="Wang_2016">{{cite journal |last1=Wang |first1=X |last2=Liu |first2=H |last3=Chen |first3=J |last4=Huang |first4=Y |last5=Li |first5=L |last6=Rampersad |first6=S |last7=Qu |first7=S |title=Metabolic Characteristics in Obese Patients Complicated by Mild Thyroid Hormone Deficiency |journal=Hormone and Metabolic Research |date=21 April 2016 |pmid=27101096 |doi=10.1055/s-0042-105150 |volume=48 |issue=5 |pages=331–7|doi-access=free }}</ref><ref name=Aweimer_2021/> and untreated autoimmune thyroiditis.<ref name="Hoermann_et_al_2018">{{cite journal |last1=Hoermann |first1=R |last2=Midgley |first2=JEM |last3=Larisch |first3=R |last4=Dietrich |first4=JW |s2cid=51698223 |title=The Role of Functional Thyroid Capacity in Pituitary Thyroid Feedback Regulation |journal=European Journal of Clinical Investigation |volume=48 |issue=10 |date=19 July 2018 |article-number=e13003 |doi=10.1111/eci.13003 |pmid=30022470}}</ref> It has been observed to correlate (in positive direction) with thyroglobulin concentration<ref>{{cite journal |last1=Sazumi |first1=Yosuke |last2=Soejima |first2=Yoshiaki |last3=Otsuka |first3=Yuki |last4=Nakano |first4=Yasuhiro |last5=Yamamoto |first5=Koichiro |last6=Suyama |first6=Atsuhito |last7=Takase |first7=Ryosuke |last8=Oguni |first8=Kohei |last9=Yasuda |first9=Miho |last10=Furukawa |first10=Masanori |last11=Otsuka |first11=Fumio |title=Behavior of serum thyroglobulin in relation to thyroid function under low-thyrotropin conditions in general practice |journal=Frontiers in Endocrinology |date=15 May 2026 |volume=17 |article-number=1756863 |doi=10.3389/fendo.2026.1756863 |doi-access=free }}</ref>, resting energy expenditure,<ref name="Kim_2018">{{cite journal |last1=Kim |first1=Min Joo |last2=Cho |first2=Sun Wook |last3=Choi |first3=Sumin |last4=Ju |first4=Dal Lae |last5=Park |first5=Do Joon |last6=Park |first6=Young Joo |title=Changes in Body Compositions and Basal Metabolic Rates during Treatment of Graves' Disease |journal=International Journal of Endocrinology |date=2018 |volume=2018 |article-number=9863050 |doi=10.1155/2018/9863050|pmid=29853888 |pmc=5960571 |doi-access=free }}</ref> resting heart rate,<ref>{{cite journal |last1=Steinberger |first1=Eva |last2=Pilz |first2=Stefan |last3=Trummer |first3=Christian |last4=Theiler-Schwetz |first4=Verena |last5=Reichhartinge |first5=Markus |last6=Benninger |first6=Thomas |last7=Pandis |first7=Marlene |last8=Malle |first8=Oliver |last9=Keppel |first9=Martin H. |last10=Verheyen |first10=Nicolas |last11=Grübler |first11=Martin R. |last12=Voelkl |first12=Jakob |last13=Meinitzer |first13=Andreas |last14=März |first14=Winfried |title=Associations of Thyroid Hormones and Resting Heart Rate in Patients Referred to Coronary Angiography |journal=Hormone and Metabolic Research |date=4 September 2020 |volume=52 |issue=12 |pages=a–1232–7292 |doi=10.1055/a-1232-7292|pmid=32886945|s2cid=221502851 }}</ref> the colour Doppler ultrasound pattern<ref>{{cite journal |last1=Zhang |first1=Lingyun |last2=Li |first2=Jie |last3=Zhang |first3=Suzhen |last4=Su |first4=Chen |last5=Su |first5=Zengcun |last6=Zhang |first6=Yuezhong |last7=Gai |first7=Yonghao |last8=Shao |first8=Shanshan |last9=Li |first9=Jianzhi |last10=Zhang |first10=Guoquan |title=Study of the Associations between Color Doppler Ultrasound Grading of Hyperthyroidism and Biochemical Data on Thyroid Function |journal=International Journal of Endocrinology |date=30 July 2022 |volume=2022 |pages=1–6 |doi=10.1155/2022/9743654|pmid=35942151|pmc=9356896 |doi-access=free }}</ref> and thyroid volume,<ref name=dietrich2002/><ref name="Hoermann_ETJ_2016"/> and (with negative direction) to thyroid autoantibody titres, which reflect organ destruction due to autoimmunity.<ref>{{cite journal |last1=Krysiak |first1=R |last2=Kowalcze |first2=K |last3=Okopień |first3=B |title=The Effect of Selenomethionine on Thyroid Autoimmunity in Euthyroid Men With Hashimoto Thyroiditis and Testosterone Deficiency. |journal=Journal of Clinical Pharmacology |volume=59 |issue=11 |pages=1477–1484 |date=20 May 2019 |doi=10.1002/jcph.1447 |pmid=31106856|s2cid=159040151 }}</ref> Elevated SPINA-GT in Graves' disease is reversible with antithyroid treatment.<ref name="Kim_2018"/> While SPINA-GT is significantly altered in primary thyroid disorders, it is insensitive to disorders of secondary nature (e.g. pure pituitary diseases).<ref name = "Dietrich2016"/>

=== Reliability === In silico experiments with Monte Carlo simulations demonstrated that both SPINA-GT and SPINA-GD can be estimated with sufficient reliability, even if laboratory assays have limited accuracy.<ref name = "Dietrich2016"/> This was confirmed by longitudinal in vivo studies that showed that GT has lower intraindividual variation (i.e. higher reliability) than TSH, FT4 or FT3.<ref>{{cite journal |vauthors=Dietrich JW, Landgrafe G, Fotiadou EH | year = 2012| title = TSH and Thyrotropic Agonists: Key Actors in Thyroid Homeostasis | journal = Journal of Thyroid Research | volume = 2012 | article-number = 351864 | doi = 10.1155/2012/351864 | pmid = 23365787 | pmc=3544290| doi-access = free}}</ref>

=== Clinical utility === In clinical trials SPINA-GT was significantly elevated in patients with Graves' disease and toxic adenoma compared to normal subjects.<ref name=dietrich2002/><ref name="Krysiak_2019_EndPol"/><ref name="Larisch_et_al_2024">{{cite journal |last1=Larisch |first1=R |last2=Midgley |first2=JEM |last3=Dietrich |first3=JW |last4=Hoermann |first4=R |title=Effect of Radioiodine Treatment on Quality of Life in Patients with Subclinical Hyperthyroidism: A Prospective Controlled Study. |journal=Nuklearmedizin. Nuclear Medicine |date=23 January 2024 |volume=63 |issue=3 |pages=176–187 |doi=10.1055/a-2240-8087 |pmid=38262472|s2cid=267198748 }}</ref> It is also elevated in diffuse and nodular goiters, and reduced in untreated autoimmune thyroiditis.<ref name=dietrich2002/><ref name="Hoermann_et_al_2018"/> In patients with toxic adenoma it has higher specificity and positive likelihood ratio for diagnosis of thyrotoxicosis than serum concentrations of thyrotropin, free T4 or free T3.<ref name = "dietrich2002"/> GT's specificity is also high in thyroid disorders of secondary or tertiary origin.<ref name = "Dietrich2016"/>

Calculating SPINA-GT has proved to be useful in challenging clinical situations, e.g. for differential diagnosis of subclinical hypothyroidism and elevated TSH concentration due to type 2 allostatic load (as it is typical for obesity and certain psychiatric diseases).<ref name="Giannakopoulos_2025">{{cite journal |last1=Giannakopoulos |first1=A |last2=Efthymiadou |first2=A |last3=Kritikou |first3=D |last4=Chrysis |first4=D |title=Usefulness of SPINA model in evaluation of the thyroid function in euthyroid pediatric patients children with subclinical hypothyroidism. |journal=Frontiers in Endocrinology |date=2025 |volume=16 |article-number=1365354 |doi=10.3389/fendo.2025.1365354 |doi-access=free |pmid=40230485|pmc=11994427 }}</ref> For this purpose, its usage has been recommended in sociomedical assessment.<ref>{{cite book |last1=Dietrich |first1=Johannes W. |last2=Schifferdecker |first2=Ekkehard |last3=Schatz |first3=Helmut |last4=Klein |first4=Harald |title=Die Ärztliche Begutachtung |chapter=Endokrine und Stoffwechseldiagnostik |series=Springer Reference Medizin |date=2022 |pages=1–13 |doi=10.1007/978-3-662-61937-7_83-1|isbn=978-3-662-61937-7 }}</ref>

=== Pathophysiological and therapeutic implications === In patients suffering from toxic adenoma, toxic multinodular goitre and Graves' disease radioiodine therapy leads to a significant decrease of the initially elevated SPINA-GT.<ref name="Larisch_et_al_2024"/>

In patients undergoing thyroidectomy for thyroid nodules, SPINA-GT is significantly reduced in cases of cancer compared to cases of benign nodules.<ref>{{cite journal |last1=Xu |first1=Huaijin |last2=Liu |first2=Hongzhou |last3=Hu |first3=Xiaodong |last4=Jia |first4=Xiaomeng |last5=Xue |first5=Zhe |last6=Wang |first6=Anning |last7=Kang |first7=Shaoyang |last8=Lyu |first8=Zhaohui |title=Reduced sensitivity to thyroid hormones is associated with differentiated thyroid cancer in the euthyroid thyroidectomy population |journal=Frontiers in Endocrinology |date=4 June 2025 |volume=16 |article-number=1595002 |pmid=40535346 |doi=10.3389/fendo.2025.1595002|doi-access=free |pmc=12173894 }}</ref>

Correlation of SPINA-GT with creatinine clearance suggests a negative influence of uremic toxins on thyroid biology.<ref>{{cite journal |vauthors=Rosolowska-Huszcz D, Kozlowska L, Rydzewski A | date = Aug 2005 | title = Influence of low protein diet on nonthyroidal illness syndrome in chronic renal failure | journal = Endocrine | volume = 27 | issue = 3| pages = 283–8 | pmid = 16230785 | doi=10.1385/endo:27:3:283| s2cid = 25630198 }}</ref><ref>{{cite journal |last1=Yang |first1=S |last2=Lai |first2=S |last3=Wang |first3=Z |last4=Liu |first4=A |last5=Wang |first5=W |last6=Guan |first6=H |title=Thyroid Feedback Quantile-based Index correlates strongly to renal function in euthyroid individuals. |journal=Annals of Medicine |date=December 2021 |volume=53 |issue=1 |pages=1945–1955 |doi=10.1080/07853890.2021.1993324 |pmid=34726096|pmc=8567884 }}</ref> In the initial phase of major non-thyroidal illness syndrome (NTIS) SPINA-GT may be temporarily elevated.<ref name="Liu2012">{{cite journal | pmid = 22874844 | title=Nonthyroidal Illness Syndrome: is it Far Away From Crohn's Disease? | year=2013 |vauthors=Liu S, Ren J, Zhao Y, Han G, Hong Z, Yan D, Chen J, Gu G, Wang G, Wang X, Fan C, Li J | s2cid=35344744 | journal= Journal of Clinical Gastroenterology| volume = 47 | issue = 2 | pages = 153–9 | doi = 10.1097/MCG.0b013e318254ea8a}}</ref><ref>{{cite journal |last1=Wan |first1=S |last2=Yang |first2=J |last3=Gao |first3=X |last4=Zhang |first4=L |last5=Wang |first5=X |title=Nonthyroidal Illness Syndrome in Patients With Short-Bowel Syndrome. |journal=Journal of Parenteral and Enteral Nutrition |date=22 July 2020 |volume=45 |issue=5 |pages=973–981 |doi=10.1002/jpen.1967 |pmid=32697347|s2cid=220698496 }}</ref> In chronic NTIS<ref name="Dietrich_2019">{{cite journal |last1=Dietrich |first1=J. W. |last2=Ackermann |first2=A. |last3=Kasippillai |first3=A. |last4=Kanthasamy |first4=Y. |last5=Tharmalingam |first5=T. |last6=Urban |first6=A. |last7=Vasileva |first7=S. |last8=Schildhauer |first8=T. A. |last9=Klein |first9=H. H. |last10=Stachon |first10=A. |last11=Hering |first11=S. |s2cid=202673793 |title=Adaptive Veränderungen des Schilddrüsenstoffwechsels als Risikoindikatoren bei Traumata |journal=Trauma und Berufskrankheit |volume=21 |issue=4 |pages=260–267 |date=19 September 2019 |doi=10.1007/s10039-019-00438-z}}</ref> as well as in certain non-critical chronic diseases, e.g. chronic fatigue syndrome<ref>{{cite journal|last1=Ruiz-Núñez|first1=Begoña|last2=Tarasse|first2=Rabab|last3=Vogelaar|first3=Emar F.|last4=Janneke Dijck-Brouwer|first4=D. A.|last5=Muskiet|first5=Frits A. J.|title=Higher Prevalence of "Low T3 Syndrome" in Patients With Chronic Fatigue Syndrome: A Case–Control Study|journal=Frontiers in Endocrinology|date=20 March 2018|volume=9|article-number=97|doi=10.3389/fendo.2018.00097|pmid=29615976|pmc=5869352|doi-access=free}}</ref><ref name="Sun_2023">{{cite journal |last1=Sun |first1=Q |last2=Oltra |first2=E |last3=Dijck-Brouwer |first3=DAJ |last4=Chillon |first4=TS |last5=Seemann |first5=P |last6=Asaad |first6=S |last7=Demircan |first7=K |last8=Espejo-Oltra |first8=JA |last9=Sánchez-Fito |first9=T |last10=Martín-Martínez |first10=E |last11=Minich |first11=WB |last12=Muskiet |first12=FAJ |last13=Schomburg |first13=L |title=Autoantibodies to selenoprotein P in chronic fatigue syndrome suggest selenium transport impairment and acquired resistance to thyroid hormone. |journal=Redox Biology |date=3 July 2023 |volume=65 |article-number=102796 |doi=10.1016/j.redox.2023.102796 |pmid=37423160|pmc=10338150 }}</ref> or asthma<ref>{{cite journal |last1=Bingyan |first1=Zhan |last2=Dong |first2=Wei |title=Impact of thyroid hormones on asthma in older adults |journal=Journal of International Medical Research |volume=47 |issue=9 |date=7 July 2019 |pages=4114–4125 |doi=10.1177/0300060519856465 |pmid=31280621|pmc=6753544 }}</ref> SPINA-GT is slightly reduced.

According to the results of a community-based study in China it was associated to sleep duration and exercise habits.<ref name="Wu_2021">{{cite journal |last1=Wu |first1=Kejun |last2=Zhou |first2=Yu |last3=Ke |first3=Sujie |last4=Huang |first4=Jingze |last5=Gao |first5=Xuelin |last6=Li |first6=Beibei |last7=Lin |first7=Xiaoying |last8=Liu |first8=Xiaohong |last9=Liu |first9=Xiaoying |last10=Ma |first10=Li |last11=Wang |first11=Linxi |last12=Wu |first12=Li |last13=Wu |first13=Lijuan |last14=Xie |first14=Chengwen |last15=Xu |first15=Junjun |last16=Wang |first16=Yanping |last17=Liu |first17=Libin |title=Lifestyle is associated with thyroid function in subclinical hypothyroidism: a cross-sectional study |journal=BMC Endocrine Disorders |date=December 2021 |volume=21 |issue=1 |page=112 |doi=10.1186/s12902-021-00772-z|doi-access=free|pmid=34049544 |pmc=8161919 }}</ref> With respect to iodine supply, it showed a complex U-shaped pattern, being reduced in subjects consuming iodine-rich food, but elevated in situations of iodine excess.<ref name="Wu_2021"/> In two other studies from China, SPINA-GT correlated with negative direction to markers of obesity including body mass index, waist circumference and waist to hip ratio.<ref>{{cite journal |last1=Zhou |first1=Yu |last2=Ke |first2=Sujie |last3=Wu |first3=Kejun |last4=Huang |first4=Jingze |last5=Gao |first5=Xuelin |last6=Li |first6=Beibei |last7=Lin |first7=Xiaoying |last8=Liu |first8=Xiaohong |last9=Liu |first9=Xiaoying |last10=Ma |first10=Li |last11=Wang |first11=Linxi |last12=Wu |first12=Li |last13=Wu |first13=Lijuan |last14=Xie |first14=Chengwen |last15=Xu |first15=Junjun |last16=Wang |first16=Yanping |last17=Liu |first17=Libin |title=Correlation between Thyroid Homeostasis and Obesity in Subclinical Hypothyroidism: Community-Based Cross-Sectional Research |journal=International Journal of Endocrinology |date=2021-05-29 |volume=2021 |pages=1–7 |doi=10.1155/2021/6663553|pmid=34135958 |pmc=8179776 |doi-access=free }}</ref><ref>{{cite journal |last1=Yang |first1=L |last2=Sun |first2=X |last3=Tao |first3=H |last4=Zhao |first4=Y |title=The association between thyroid homeostasis parameters and obesity in subjects with euthyroidism. |journal=Journal of Physiology and Pharmacology |date=February 2023 |volume=74 |issue=1 |doi=10.26402/jpp.2023.1.07 |pmid=37245234}}</ref> This doesn't seem to be the case, however, in Western populations.<ref name=Ittermann2021>{{cite journal |last1=Ittermann |first1=T |last2=Markus |first2=MRP |last3=Bahls |first3=M |last4=Felix |first4=SB |last5=Steveling |first5=A |last6=Nauck |first6=M |last7=Völzke |first7=H |last8=Dörr |first8=M |title=Low serum TSH levels are associated with low values of fat-free mass and body cell mass in the elderly. |journal=Scientific Reports |date=2021-05-18 |volume=11 |issue=1 |page=10547 |doi=10.1038/s41598-021-90178-7 |pmid=34006958|pmc=8131378 |bibcode=2021NatSR..1110547I |doi-access=free }}</ref>

In women, therapy with Metformin results in increased SPINA-GT, in parallel to improved insulin sensitivity.<ref>{{cite journal |last1=Krysiak |first1=R |last2=Szkróbka |first2=W |last3=Okopień |first3=B |title=Sex-Dependent Effect of Metformin on Serum Prolactin Levels In Hyperprolactinemic Patients With Type 2 Diabetes: A Pilot Study. |journal=Experimental and Clinical Endocrinology & Diabetes |date=June 2018 |volume=126 |issue=6 |pages=342–348 |doi=10.1055/s-0043-122224 |pmid=29169197|s2cid=43144838 }}</ref><ref>{{cite journal |last1=Krysiak |first1=R |last2=Kowalcze |first2=K |last3=Okopień |first3=B |title=Impact of metformin on hypothalamic-pituitary-thyroid axis activity in women with autoimmune and non-autoimmune subclinical hypothyroidism: a pilot study. |journal=Pharmacological Reports |date=5 December 2023 |volume=76 |issue=1 |pages=195–206 |doi=10.1007/s43440-023-00556-3 |pmid=38051473|doi-access=free |pmc=10830717 }}</ref> This observation was reproducible in men with hypogonadism, but not in men with normal testosterone concentrations,.<ref name="Krysiak_2019_JClinPharm">{{cite journal |last1=Krysiak |first1=R |last2=Szkróbka |first2=W |last3=Okopień |first3=B |title=The Impact of Testosterone on Metformin Action on Hypothalamic-Pituitary-Thyroid Axis Activity in Men: A Pilot Study. |journal=Journal of Clinical Pharmacology |volume=60 |issue=2 |pages=164–171 |date=6 August 2019 |doi=10.1002/jcph.1507 |pmid=31389032|s2cid=199466858 }}</ref> In postmenopausal women this effect was only observed in subjects on oestradiol replacement therapy.<ref>{{cite journal |last1=Krysiak |first1=R |last2=Kowalcze |first2=K |last3=Okopień |first3=B |title=The impact of metformin on hypothalamic-pituitary-thyroid axis activity in postmenopausal women with untreated non-autoimmune subclinical hypothyroidism. |journal=Clinical and Experimental Pharmacology & Physiology |date=November 2021 |volume=48 |issue=11 |pages=1469–1476 |doi=10.1111/1440-1681.13542 |pmid=34145615|s2cid=235481699 }}</ref> Therefore, the described phenomenon seems to depend on an interaction of metformin with sex hormones.<ref name="Krysiak_2019_JClinPharm"/><ref name="Krysiak_2020_JClinPharm">{{cite journal |last1=Krysiak |first1=Robert |last2=Kowalcze |first2=Karolina |last3=Wolnowska |first3=Monika |last4=Okopień |first4=Bogusław |title=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=Journal of Clinical Pharmacy and Therapeutics |date=5 January 2020 |volume=45 |issue=5 |pages=937–945 |doi=10.1111/jcpt.13105| pmid=31903641|s2cid=209895460 |doi-access=free }}</ref> In hyperthyroid<ref name="Krysiak_2019_EndPol"/> men both SPINA-GT and SPINA-GD negatively correlate to erectile function, intercourse satisfaction, orgasmic function and sexual desire. Likewise, in women with thyrotoxicosis elevated thyroid's secretory capacity predicts depression and sexual dysfunction.<ref>{{cite journal |last1=Krysiak |first1=R |last2=Kowalcze |first2=K |last3=Okopień |first3=B |title=Sexual function and depressive symptoms in young women with overt hyperthyroidism. |journal=European Journal of Obstetrics, Gynecology, and Reproductive Biology |date=9 January 2019 |volume=234 |pages=43–48 |doi=10.1016/j.ejogrb.2018.12.035 |pmid=30654201|s2cid=58558358 }}</ref> Conversely, in androgen-deficient men with concomitant autoimmune thyroiditis, substitution therapy with testosterone leads to a decrease in thyroid autoantibody titres and an increase in SPINA-GT.<ref>{{cite journal |last1=Krysiak |first1=Robert |last2=Kowalcze |first2=Karolina |last3=Okopień |first3=Bogusław |title=The effect of testosterone on thyroid autoimmunity in euthyroid men with Hashimoto's thyroiditis and low testosterone levels |journal=Journal of Clinical Pharmacy and Therapeutics |volume=44 |issue=5 |pages=742–749 |date=10 June 2019 |doi=10.1111/jcpt.12987 |pmid=31183891|s2cid=184487697 |doi-access=free }}</ref> In a large study from mainland China, SPINA-GT was elevated in certain psychiatric diseases including bipolar disorder and schizophrenia.<ref name="Cui2024">{{cite journal |last1=Cui |first1=T |last2=Qi |first2=Z |last3=Wang |first3=M |last4=Zhang |first4=X |last5=Wen |first5=W |last6=Gao |first6=S |last7=Zhai |first7=J |last8=Guo |first8=C |last9=Zhang |first9=N |last10=Zhang |first10=X |last11=Guan |first11=Y |last12=Retnakaran |first12=R |last13=Hao |first13=W |last14=Zhai |first14=D |last15=Zhang |first15=R |last16=Zhao |first16=Y |last17=Wen |first17=SW |title=Thyroid allostasis in drug-free affective disorder patients. |journal=Psychoneuroendocrinology |date=April 2024 |volume=162 |article-number=106962 |doi=10.1016/j.psyneuen.2024.106962 |pmid=38277991}}</ref> In bipolar disorder with manic or mixed episodes it was higher than in cases with depressive episodes.<ref name="Cui2024"/>

SPINA-GT is reduced in persons suffering from hidradenitis suppurativa compared to healthy controls with the same sex and age distribution.<ref name="AbuRached_2023">{{cite journal |last1=Abu Rached |first1=Nessr |last2=Dietrich |first2=Johannes W. |last3=Ocker |first3=Lennart |last4=Quast |first4=Daniel R. |last5=Scheel |first5=Christina |last6=Gambichler |first6=Thilo |last7=Bechara |first7=Falk G. |title=Primary Thyroid Dysfunction Is Prevalent in Hidradenitis Suppurativa and Marked by a Signature of Hypothyroid Graves' Disease: A Case–Control Study |journal=Journal of Clinical Medicine |date=4 December 2023 |volume=12 |issue=23 |page=7490 |doi=10.3390/jcm12237490 |pmid=38068542 |doi-access=free |pmc=10707714 }}</ref> This phenomenon has been ascribed to B-cell-mediated hypothyroidism, i.e. hypothyroid Graves' disease due to inhibiting TSH receptor autoantibodies (iTRAb).<ref name="AbuRached_2023"/>

In patients with autoimmune thyroiditis a gluten-free diet results in increased SPINA-GT (in parallel to sinking autoantibody titres).<ref>{{cite journal |last1=Krysiak |first1=R |last2=Szkróbka |first2=W |last3=Okopień |first3=B |s2cid=51874521 |title=The Effect of Gluten-Free Diet on Thyroid Autoimmunity in Drug-Naïve Women with Hashimoto's Thyroiditis: A Pilot Study |journal=Experimental and Clinical Endocrinology & Diabetes |volume=127 |issue=7 |pages=417–422 |date=30 July 2018 |doi=10.1055/a-0653-7108 |pmid=30060266|doi-access=free }}</ref> Statin therapy has the same effect, but only if supply with vitamin D is sufficient.<ref>{{cite journal |last1=Krysiak |first1=R |last2=Szkróbka |first2=W |last3=Okopień |first3=B |title=The Relationship Between Statin Action On Thyroid Autoimmunity And Vitamin D Status: A Pilot Study. |journal=Experimental and Clinical Endocrinology & Diabetes |date=27 August 2018 |volume = 127 |issue = 1 |pages=23–28| doi=10.1055/a-0669-9309 |pmid=30149415|s2cid=52100009 }}</ref> Accordingly, substitution therapy with 25-hydroxyvitamin D leads to rising secretory capacity.<ref name="Krysiak_Selenomethionine_Men_2018">{{cite journal |last1=Krysiak |first1=Robert |last2=Szkróbka |first2=Witold |last3=Okopień |first3=Bogusław |title=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 |journal=Pharmacological Reports |date=October 2018 |volume=71 |issue=2 |pages=243–7 |doi=10.1016/j.pharep.2018.10.012 |pmid=30818086|s2cid=73481267 }}</ref><ref name="Krysiak_Selenomethionine_Women_2018">{{cite journal |last1=Krysiak |first1=Robert |last2=Kowalcze |first2=Karolina |last3=Okopień |first3=Bogusław |title=Selenomethionine potentiates the impact of vitamin D on thyroid autoimmunity in euthyroid women with Hashimoto's thyroiditis and low vitamin D status |journal=Pharmacological Reports |date=December 2018 |volume = 71 |issue = 2 |pages = 367–73 |doi=10.1016/j.pharep.2018.12.006 |pmid=30844687|s2cid=73486105 }}</ref><ref name="Krysiak_PharmRep_2019_04">{{cite journal |last1=Krysiak |first1=Robert |last2=Kowalcze |first2=Karolina |last3=Okopień |first3=Bogusław |title=The effect of vitamin D on thyroid autoimmunity in euthyroid men with autoimmune thyroiditis and testosterone deficiency |journal=Pharmacological Reports |volume=71 |issue=5 |pages=798–803 |date=April 2019 |doi=10.1016/j.pharep.2019.04.010|pmid=31377561 }}</ref><ref>{{cite journal |last1=Krysiak |first1=Robert |last2=Kowalcze |first2=Karolina |last3=Szkróbka |first3=Witold |last4=Okopień |first4=Bogusław |title=Sexual Function and Depressive Symptoms in Young Women with Euthyroid Hashimoto's Thyroiditis Receiving Vitamin D, Selenomethionine and Myo-Inositol: A Pilot Study |journal=Nutrients |date=20 June 2023 |volume=15 |issue=12 |page=2815 |doi=10.3390/nu15122815 |pmid=37375719 |pmc=10304218 |doi-access=free }}</ref> This effect is potentiated by substitution therapy with myo-inositol<ref>{{cite journal |last1=Krysiak |first1=R |last2=Kowalcze |first2=K |last3=Okopień |first3=B |title=The impact of vitamin D on thyroid autoimmunity and hypothalamic-pituitary-thyroid axis activity in myo-inositol-treated and myo-inositol-naïve women with autoimmune thyroiditis: A pilot study. |journal=Journal of Clinical Pharmacy and Therapeutics |date=30 June 2022 |volume=47 |issue=11 |pages=1759–1767 |doi=10.1111/jcpt.13730 |pmid=35775148|s2cid=250174449 |doi-access=free }}</ref> and selenomethionine<ref name="Krysiak_Selenomethionine_Men_2018"/><ref name="Krysiak_Selenomethionine_Women_2018"/><ref>{{cite journal |last1=Saini |first1=Chandanvir |title=Autoimmune thyroiditis and multiple nutritional factors |journal=International Journal of Endocrinology (Ukraine) |date=6 April 2021 |volume=16 |issue=8 |pages=648–653 |doi=10.22141/2224-0721.16.8.2020.222885|doi-access=free }}</ref> or, in women, with dehydroepiandrosterone,<ref>{{cite journal |last1=Krysiak |first1=R |last2=Szkróbka |first2=W |last3=Okopień |first3=B |title=Dehydroepiandrosterone potentiates the effect of vitamin D on thyroid autoimmunity in euthyroid women with autoimmune thyroiditis: A pilot study. |journal=Clinical and Experimental Pharmacology & Physiology |date=February 2021 |volume=48 |issue=2 |pages=195–202 |doi=10.1111/1440-1681.13410 |pmid=33007106|s2cid=222165571 }}</ref> but impaired in males with early-onset androgenic alopecia.<ref>{{cite journal |last1=Krysiak |first1=R |last2=Kowalcze |first2=K |last3=Okopień |first3=B |title=The impact of exogenous vitamin D on thyroid autoimmunity in euthyroid men with autoimmune thyroiditis and early-onset androgenic alopecia. |journal=Pharmacological Reports |date=2021-06-09 |volume=73 |issue=5 |pages=1439–1447 |doi=10.1007/s43440-021-00295-3 |pmid=34106452|pmc=8460519 |doi-access=free }}</ref> The effects of vitamin D and selenomethionine are attenuated in hyperprolactinaemia, suggesting an inhibitory effect of prolactin.<ref>{{cite journal |last1=Krysiak |first1=R |last2=Kowalcze |first2=K |last3=Okopień |first3=B |title=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=Journal of Clinical Pharmacy and Therapeutics |date=10 July 2020 |volume=45 |issue=6 |pages=1334–1341 |doi=10.1111/jcpt.13214 |pmid=32649802|s2cid=220485158 |doi-access=free }}</ref> Although both vitamin D supplementation and gluten-free diet result in increased SPINA-GT, there seems to be a complex interaction between both therapeutic measures, since vitamin D treatment is only able to elevate the thyroid's secretory capacity in subjects not following any dietary recommendation.<ref>{{cite journal |last1=Krysiak |first1=R |last2=Kowalcze |first2=K |last3=Okopień |first3=B |title=Gluten-free diet attenuates the impact of exogenous vitamin D on thyroid autoimmunity in young women with autoimmune thyroiditis: a pilot study. |journal=Scandinavian Journal of Clinical and Laboratory Investigation |date=6 October 2022 |volume=82 |issue=7–8 |pages=518–524 |doi=10.1080/00365513.2022.2129434 |pmid=36200764|s2cid=252736895 }}</ref>

On the other hand, men treated with spironolactone are faced with decreasing SPINA-GT (in addition to rising thyroid antibody titres).<ref name="Krysiak_Spironolactone_2019">{{cite journal |last1=Krysiak |first1=R |last2=Kowalcze |first2=K |last3=Okopień |first3=B |title=The effect of spironolactone on thyroid autoimmunity in euthyroid men with Hashimoto's thyroiditis. |journal=Journal of Clinical Pharmacy and Therapeutics |volume=45 |issue=1 |pages=152–159 |date=14 September 2019 |doi=10.1111/jcpt.13046 |pmid=31520539|doi-access=free }}</ref> It has, therefore, been concluded that spironolactone may aggravate thyroid autoimmunity in men.<ref name="Krysiak_Spironolactone_2019"/>

In subjects with type 2 diabetes, treatment with beta blockers resulted in decreased SPINA-GT, suggesting sympathetic innervation to contribute to the control of thyroid function.<ref>{{cite journal |last1=Yang |first1=Lijuan |last2=Sun |first2=Xiuqin |last3=Zhao |first3=Yi |last4=Tao |first4=Hong |title=Effects of Antihypertensive Drugs on Thyroid Function in Type 2 Diabetes Patients With Euthyroidism |journal=Frontiers in Pharmacology |date=7 March 2022 |volume=13 |article-number=802159 |doi=10.3389/fphar.2022.802159|pmid=35330837 |pmc=8940167 |doi-access=free }}</ref> In diabetic women, but not in men, SPINA-GT shows a positive correlation to the β-C-terminal cross-linked telopeptides of type I collagen (β-CTX), a marker of bone resorption.<ref>{{cite journal |last1=Chen |first1=Y |last2=Zhang |first2=W |last3=Chen |first3=C |last4=Wang |first4=Y |last5=Wang |first5=N |last6=Lu |first6=Y |title=Thyroid and bone turnover markers in type 2 diabetes: results from the METAL study. |journal=Endocrine Connections |date=31 March 2022 |volume=11 |issue=3 |doi=10.1530/EC-21-0484 |pmid=35196256|pmc=9010813 }}</ref> In both diabetic and non-diabetic persons it correlates (negatively) with age and (positively) with the concentrations of troponin T and HbA1c.<ref>{{cite journal |last1=Li |first1=W |last2=He |first2=Q |last3=Zhang |first3=H |last4=Shu |first4=S |last5=Wang |first5=L |last6=Wu |first6=Y |last7=Yuan |first7=Z |last8=Zhou |first8=J |title=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=Journal of Investigative Medicine |date=20 January 2023 |volume=71 |issue=4 |pages=350–360 |doi=10.1177/10815589221149187 |pmid=36680358|s2cid=256055662 }}</ref>

SPINA-GT correlates to mechanical pain sensitivity (MPS) in quantitative sensory testing (QST) and to measures of respiratory arrhythmia in the analysis of heart rate variability, indicating a potential link to both sensorimotor and autonomic neuropathy.<ref name="BazikaGerasch_2024">{{cite journal |last1=Bazika-Gerasch |first1=B |last2=Kumowski |first2=N |last3=Enax-Krumova |first3=E |last4=Kaisler |first4=M |last5=Eitner |first5=LB |last6=Maier |first6=C |last7=Dietrich |first7=JW |title=Impaired autonomic function and somatosensory disturbance in patients with treated autoimmune thyroiditis. |journal=Scientific Reports |date=29 May 2024 |volume=14 |issue=1 |page=12358 |doi=10.1038/s41598-024-63158-w |pmid=38811750|pmc=11137073 |bibcode=2024NatSR..1412358B }}</ref>

A study in euthyroid subjects with structural heart disease found that increased SPINA-GT predicts the risk of malignant arrhythmia including ventricular fibrillation and ventricular tachycardia.<ref name = Mueller_AJC_2020>{{cite journal |last1=Müller |first1=Patrick |last2=Dietrich |first2=Johannes W. |last3=Lin |first3=Tina |last4=Bejinariu |first4=Alexandru |last5=Binnebößel |first5=Stephan |last6=Bergen |first6=Friederike |last7=Schmidt |first7=Jan |last8=Müller |first8=Sarah-Kristin |last9=Chatzitomaris |first9=Apostolos |last10=Kurt |first10=Muhammed |last11=Gerguri |first11=Shqipe |last12=Clasen |first12=Lukas |last13=Klein |first13=Harald H. |last14=Kelm |first14=Malte |last15=Makimoto |first15=Hisaki |title=Usefulness of Serum Free Thyroxine Concentration to Predict Ventricular Arrhythmia Risk in Euthyroid Patients with Structural Heart Disease |journal=The American Journal of Cardiology |date=January 2020 |volume=125 |issue=8 |pages=1162–1169 |doi=10.1016/j.amjcard.2020.01.019 |pmid=32087999|s2cid=211261823 }}</ref> This applies to both incidence and event-free survival.<ref name = Mueller_AJC_2020/> Likewise, SPINA-GT is elevated in a significant subgroup of patients with takotsubo syndrome,<ref>{{cite journal |last1=Aweimer |first1=A |last2=El-Battrawy |first2=I |last3=Akin |first3=I |last4=Borggrefe |first4=M |last5=Mügge |first5=A |last6=Patsalis |first6=PC |last7=Urban |first7=A |last8=Kummer |first8=M |last9=Vasileva |first9=S |last10=Stachon |first10=A |last11=Hering |first11=S |last12=Dietrich |first12=JW |title=Abnormal thyroid function is common in takotsubo syndrome and depends on two distinct mechanisms: results of a multicentre observational study. |journal=Journal of Internal Medicine |date=12 November 2020 |volume=289 |issue=5 |pages=675–687 |doi=10.1111/joim.13189 |pmid=33179374|doi-access=free }}</ref> especially in non-survivors.<ref name="Aweimer_2024">{{cite journal |last1=Aweimer |first1=A |last2=Dietrich |first2=JW |last3=Santoro |first3=F |last4=Fàbregas |first4=MC |last5=Mügge |first5=A |last6=Núñez-Gil |first6=IJ |last7=Vazirani |first7=R |last8=Vedia |first8=O |last9=Pätz |first9=T |last10=Ragnatela |first10=I |last11=Arcari |first11=L |last12=Volpe |first12=M |last13=Corbì-Pascual |first13=M |last14=Martinez-Selles |first14=M |last15=Almendro-Delia |first15=M |last16=Sionis |first16=A |last17=Uribarri |first17=A |last18=Thiele |first18=H |last19=Brunetti |first19=ND |last20=Eitel |first20=I |last21=Stiermaier |first21=T |last22=Hamdani |first22=N |last23=Abumayyaleh |first23=M |last24=Akin |first24=I |last25=El-Battrawy |first25=I |title=Takotsubo syndrome outcomes predicted by thyroid hormone signature: insights from cluster analysis of a multicentre registry. |journal=eBioMedicine |date=18 March 2024 |volume=102 |article-number=105063 |doi=10.1016/j.ebiom.2024.105063 |pmid=38502972|pmc=10963195 }}</ref> A stress-mediated effect on SPINA-GT is also suggested by the observation that it is increased in persons with a history of psychological trauma.<ref>{{cite journal |last1=Aweimer |first1=A |last2=Engemann |first2=L |last3=Amar |first3=S |last4=Ewers |first4=A |last5=Afshari |first5=F |last6=Maiß |first6=C |last7=Kern |first7=K |last8=Lücke |first8=T |last9=Mügge |first9=A |last10=El-Battrawy |first10=I |last11=Dietrich |first11=JW |last12=Brüne |first12=M |title=Stress-Mediated Abnormalities in Regional Myocardial Wall Motion in Young Women with a History of Psychological Trauma. |journal=Journal of Clinical Medicine |date=24 October 2023 |volume=12 |issue=21 |page=6702 |doi=10.3390/jcm12216702 |pmid=37959168 |pmc=10647814 |doi-access=free }}</ref> On the other hand, two studies found negative correlation between SPINA-GT and markers of dispersion in cardiac repolarisation, including Tp-e interval, JT interval, Tp-e/ QT ratio and Tp-e/QTc ratio. These results suggest that reduced thyroid function may trigger cardiovascular mortality as well.<ref>{{cite journal |last1=Gürdal |first1=A |last2=Eroğlu |first2=H |last3=Helvaci |first3=F |last4=Sümerkan |first4=MÇ |last5=Kasali |first5=K |last6=Çetin |first6=Ş |last7=Aksan |first7=G |last8=Kiliçkesmez |first8=K |title=Evaluation of Tp-e interval, Tp-e/QT ratio and Tp-e/QTc ratio in patients with subclinical hypothyroidism. |journal=Therapeutic Advances in Endocrinology and Metabolism |date=March 2017 |volume=8 |issue=3 |pages=25–32 |doi=10.1177/2042018816684423 |pmid=28377800|pmc=5363453 }}</ref><ref name=Aweimer_2021/>

Among subjects with Parkinson's disease, SPINA-GT is significantly elevated in tremor-dominant and mixed subtypes compared to the akinetic-rigid type.<ref>{{cite journal |last1=Tan |first1=Y |last2=Gao |first2=L |last3=Yin |first3=Q |last4=Sun |first4=Z |last5=Man |first5=X |last6=Du |first6=Y |last7=Chen |first7=Y |title=Thyroid hormone levels and structural parameters of thyroid homeostasis are correlated with motor subtype and disease severity in euthyroid patients with Parkinson's disease. |journal=The International Journal of Neuroscience |date=April 2021 |volume=131 |issue=4 |pages=346–356 |doi=10.1080/00207454.2020.1744595 |pmid=32186220|s2cid=212752563 }}</ref>

Specific secretory capacity (SPINA-GTs) is reduced in obesity<ref name=dietrich2002/> and autoimmune thyroiditis.<ref name="Hoermann_ETJ_2016"/><ref>{{cite journal |last1=Hoermann |first1=Rudolf |last2=Midgley |first2=John E. M. |last3=Larisch |first3=Rolf |last4=Dietrich |first4=Johannes W. |title=Relational Stability in the Expression of Normality, Variation, and Control of Thyroid Function |journal=Frontiers in Endocrinology |date=7 November 2016 |volume=7 |pmid=27872610 |pmc=5098235 |doi=10.3389/fendo.2016.00142 |page=142|doi-access=free }}</ref>

Endocrine disruptors may affect stimulated thyroid output, as demonstrated by a positive correlation of SPINA-GT with exposure to 2-hydroxynaphthalene (2-NAP),<ref name = Yang_2023>{{cite journal |last1=Yang |first1=S |last2=Sun |first2=J |last3=Wang |first3=S |last4=E |first4=L |last5=Zhang |first5=S |last6=Jiang |first6=X |title=Association of exposure to polycyclic aromatic hydrocarbons with thyroid hormones in adolescents and adults, and the influence of the iodine status. |journal=Environmental Science: Processes & Impacts |date=9 August 2023 |volume=25 |issue=9 |pages=1449–1463 |doi=10.1039/d3em00135k |pmid=37555279|s2cid=259916981 }}</ref> urinary mercury concentration<ref>{{cite journal |last1=Kim |first1=Min Joo |last2=Kim |first2=Sunmi |last3=Choi |first3=Sohyeon |last4=Lee |first4=Inae |last5=Moon |first5=Min Kyong |last6=Choi |first6=Kyungho |last7=Park |first7=Young Joo |last8=Cho |first8=Yoon Hee |last9=Kwon |first9=Young Min |last10=Yoo |first10=Jiyoung |last11=Cheon |first11=Gi Jeong |last12=Park |first12=Jeongim |title=Association of exposure to polycyclic aromatic hydrocarbons and heavy metals with thyroid hormones in general adult population and potential mechanisms |journal=Science of the Total Environment |date=December 2020 |volume=762 |article-number=144227 |pmid=33373756 |doi=10.1016/j.scitotenv.2020.144227|s2cid=229722026 }}</ref> and the excretion of certain phthalate metabolites,<ref>{{cite journal |last1=Chen |first1=Y |last2=Zhang |first2=W |last3=Chen |first3=J |last4=Wang |first4=N |last5=Chen |first5=C |last6=Wang |first6=Y |last7=Wan |first7=H |last8=Chen |first8=B |last9=Lu |first9=Y |title=Association of Phthalate Exposure with Thyroid Function and Thyroid Homeostasis Parameters in Type 2 Diabetes. |journal=Journal of Diabetes Research |date=2021 |volume=2021 |article-number=4027380 |doi=10.1155/2021/4027380 |pmid=34746318|pmc=8566079 |doi-access=free }}</ref> and negative correlation with combined exposure to polycyclic aromatic hydrocarbons (PAHs)<ref name = Yang_2023/> and nickel.<ref>{{cite journal |last1=Maric |first1=D |last2=Baralic |first2=K |last3=Javorac |first3=D |last4=Mandic-Rajcevic |first4=S |last5=Zarkovic |first5=M |last6=Antonijevic |first6=B |last7=Djukic-Cosic |first7=D |last8=Bulat |first8=Z |last9=Djordjevic |first9=AB |title=Nickel as a potential disruptor of thyroid function: benchmark modelling of human data. |journal=Frontiers in Endocrinology |date=2023 |volume=14 |article-number=1145153 |doi=10.3389/fendo.2023.1145153 |pmid=37800147 |pmc=10549921 |doi-access=free }}</ref> Additionally, SPINA-GT is altered in persons exposed to butylparaben and propylparaben.<ref>{{cite journal |last1=Huang |first1=PC |last2=Chen |first2=HC |last3=Leung |first3=SH |last4=Lin |first4=YJ |last5=Huang |first5=HB |last6=Chang |first6=WT |last7=Huang |first7=HI |last8=Chang |first8=JW |title=Associations between paraben exposure, thyroid capacity, homeostasis and pituitary thyrotropic function in the general Taiwanese: Taiwan Environmental Survey for Toxicants (TEST) 2013 | journal=Environmental Science and Pollution Research | date=1 December 2023 |volume=31 |issue=1 |pages=1288–1303 | doi=10.1007/s11356-023-31277-y |pmid=38038926|s2cid=265514578 }}</ref><ref>{{cite journal |last1=Lee |first1=I |last2=Kim |first2=MJ |last3=Park |first3=YJ |last4=Moon |first4=MK |last5=Choi |first5=S |last6=Park |first6=J |last7=Kim |first7=E |last8=Lee |first8=G |last9=Choi |first9=K |title=Effect of fasting status on association between exposure to phthalate and phenolics, and thyroid hormones in adult women of reproductive age. |journal=Environmental Research |date=17 January 2025 |volume=269 |article-number=120880 |doi=10.1016/j.envres.2025.120880 |pmid=39826653|bibcode=2025ER....26920880L }}</ref>

In a longitudinal evaluation of a large sample of the general US population over 10 years, reduced SPINA-GT significantly predicted all-cause mortality.<ref>{{cite journal |last1=Dietrich |first1=Johannes W. |title=P4-Endokrinologie – Kybernetische Perspektiven eines neuen Ansatzes |journal=Leibniz Online |date=2024 |volume=54 |doi=10.53201/LEIBNIZONLINE54 |url=https://leibnizsozietaet.de/wp-content/uploads/2024/12/03_03_Kybernetik-2024_DietrichLeibniz-Online-Fachbeitrag.pdf |language=de}}</ref>

==Notes== {{notelist | colwidth = | notes = }}

==References== {{Reflist|2}}

== External links == {{Library resources box|by=no|onlinebooks=no|about=yes|wikititle=SPINA-GT}}

* [http://spina.sf.net SPINA Thyr: Open source software for calculating GT and GD] * [https://doi.org/10.5281/zenodo.3596049 Software hosted at CERN's Zenodo] * Package "[https://cran.r-project.org/package=SPINA SPINA]" for the statistical environment R * [https://doi.org/10.5281/zenodo.10481776 Functions for R and S for calculating SPINA-GT]. [https://doi.org/10.5281/zenodo.7479856 (Permanent DOI)]

Category:Clinical chemistry Category:Blood tests Category:Endocrine procedures Category:Thyroidological methods Category:Thyroid homeostasis Category:Structure parameters of thyroid function Category:Static endocrine function tests