Validity SPINA-GT is elevated in primary hyperthyroidism and reduced in both primary hypothyroidism and untreated autoimmune<unk> itis. It has been observed to correlate (with positive direction) to resting energy expenditure, resting heart rate and<unk>  volume, and (with negative direction) to<unk>  autoantibody titres, which reflect organ destruction due to autoimmunity. Elevated SPINA-GT in Graves' disease is reversible with antithyroid treatment. While SPINA-GT is significantly altered in primary<unk>  disorders, it is insensitive to disorders of secondary nature (e.g. pure pituitary diseases). 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. 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. Clinical utility In clinical trials SPINA-GT was significantly elevated in patients suffering from Graves' disease and toxic adenoma compared to normal subjects. It is also elevated in diffuse and nodular goiters, and reduced in untreated autoimmune<unk> itis. 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. GT's specificity is also high in<unk>  disorders of secondary or tertiary origin. Pathophysiological and therapeutic implications Correlation of SPINA-GT with creatinine clearance suggests a negative influence of uremic toxins on<unk>  biology. In the initial phase of major non-thyroidal illness syndrome (NTIS) SPINA-GT may be temporarily elevated. In chronic NTIS as well as in certain non-critical chronic diseases, e.g. chronic fatigue syndrome or asthma 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. 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. In another study from China, SPINA-GT correlated with negative direction to markers of obesity including body mass index, waist circumference and waist to hip ratio. This doesn't seem to be the case, however, in Western populations. In women, therapy with Metformin results in increased SPINA-GT, in parallel to improved insulin sensitivity. This observation was reproducible in men with hypogonadism, but not in men with normal testosterone concentrations,. In postmenopausal women this effect was only observed in subjects on oestradiol replacement therapy. Therefore, the described phenomenon seems to depend on an interaction of metformin with sex hormones. In hyperthyroid men both SPINA-GT and SPINA-GD negatively correlate to erectile function, intercourse satisfaction, orgasmic function and sexual desire. Likewise, in women suffering from thyrotoxicosis elevated<unk>  predicts depression and sexual dysfunction. Conversely, in androgen-deficient men with concomitant autoimmune<unk> itis, substitution therapy with testosterone leads to a decrease in<unk>  autoantibody titres and an increase in SPINA-GT. In patients with autoimmune<unk> itis a gluten-free diet results in increased SPINA-GT (in parallel to sinking autoantibody titres). Statin therapy has the same effect, but only if supply with vitamin D is sufficient. Accordingly, substitution therapy with 25-hydroxyvitamin D leads to rising<unk><unk> . This effect is potentiated by substitution therapy with selenomethionine or, in women, with dehydroepiandrosterone, but impaired in males with early-onset androgenic alopecia. The effects of vitamin D and selenomethionine are attenuated in hyperprolactinaemia, suggesting an inhibitory effect of prolactin. On the other hand, men treated with spironolactone are faced with decreasing SPINA-GT (in addition to rising<unk>  antibody titres). It has, therefore, been concluded that spironolactone may aggravate<unk>  autoimmunity in men. In subjects with type 2 diabetes, treatment with beta blockers resulted in decreased SPINA-GT, suggesting sympathetic innervation to contribute to the control of<unk>  function. 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. 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. This applies to both incidence and event-free survival. Likewise, SPINA-GT is elevated in a significant subgroup of patients with takotsubo syndrome. 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<unk>  function may trigger cardiovascular mortality as well. Among subjects with Parkinson's disease, SPINA-GT is significantly eleveated in tremor-dominant and mixed subtypes compared to the akinetic-rigid type. Specific<unk><unk>  (SPINA-GTs) is reduced in obesity and autoimmune<unk> itis. Endocrine disruptors may affect stimulated<unk>  output, as demonstrated by a positive correlation of SPINA-GT with urinary mercury concentration and the excretion of certain phthalate metabolites.
Thyroid's secretory capacity
Android fat distribution
Hypothalamic–pituitary–thyroid axis
Iodine in biology
Hypothalamic–pituitary–gonadal axis
Hypothalamic–pituitary–prolactin axis
Basal body temperature
Cardiac cycle