[2][3] 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.
[7] It is a measure for how much one millilitre of thyroid tissue can produce under conditions of maximum stimulation.
[citation needed] The equations and their parameters are calibrated for adult humans with a body mass of 70 kg and a plasma volume of ca.
[13] It has been observed to correlate (with positive direction) to resting energy expenditure,[14] resting heart rate,[15] the colour Doppler ultrasound pattern[16] and thyroid volume,[2][7] and (with negative direction) to thyroid autoantibody titres, which reflect organ destruction due to autoimmunity.
[3] 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.
[3] 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.
[18] In clinical trials SPINA-GT was significantly elevated in patients with Graves' disease and toxic adenoma compared to normal subjects.
[2][8][19] It is also elevated in diffuse and nodular goiters, and reduced in untreated autoimmune thyroiditis.
[3] 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).
[19] Correlation of SPINA-GT with creatinine clearance suggests a negative influence of uremic toxins on thyroid biology.
[21][22] In the initial phase of major non-thyroidal illness syndrome (NTIS) SPINA-GT may be temporarily elevated.
[32] In women, therapy with Metformin results in increased SPINA-GT, in parallel to improved insulin sensitivity.
Likewise, in women with thyrotoxicosis elevated thyroid's secretory capacity predicts depression and sexual dysfunction.
[39] In a large study from mainland China, SPINA-GT was elevated in certain psychiatric diseases including bipolar disorder and schizophrenia.
[40] SPINA-GT is reduced in persons suffering from hidradenitis suppurativa compared to healthy controls with the same sex and age distribution.
[41] In patients with autoimmune thyroiditis a gluten-free diet results in increased SPINA-GT (in parallel to sinking autoantibody titres).
[44][45][46][47] This effect is potentiated by substitution therapy with myo-inositol[48] and selenomethionine[44][45][49] or, in women, with dehydroepiandrosterone,[50] but impaired in males with early-onset androgenic alopecia.
[52] 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.
[53] On the other hand, men treated with spironolactone are faced with decreasing SPINA-GT (in addition to rising thyroid antibody titres).
[54] 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.
[55] 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.
[56] In both diabetic and non-diabetic persons it correlates (negatively) with age and (positively) with the concentrations of troponin T and HbA1c.
[57] 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.
[59] Likewise, SPINA-GT is elevated in a significant subgroup of patients with takotsubo syndrome,[60] especially in non-survivors.
[61] 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.
[63][9] Among subjects with Parkinson's disease, SPINA-GT is significantly elevated in tremor-dominant and mixed subtypes compared to the akinetic-rigid type.
[7][65] Endocrine disruptors may affect stimulated thyroid output, as demonstrated by a positive correlation of SPINA-GT with exposure to 2-hydroxynaphthalene (2-NAP),[66] urinary mercury concentration[67] and the excretion of certain phthalate metabolites,[68] and negative correlation with combined exposure to polycyclic aromatic hydrocarbons (PAHs)[66] and nickel.
[70] In a longitudinal evaluation of a large sample of the general US population over 10 years, reduced SPINA-GT significantly predicted all-cause mortality.