Thyroid's secretory capacity

The ratio of SPINA-GT and thyroid volume V_T (as determined e.g. by ultrasonography)

${\displaystyle {\hat {G}}_{TS}={\frac {{\hat {G}}_{T}}{{V}_{T}}}}$,

i.e.

${\displaystyle {\hat {G}}_{TS}={\frac {\beta _{T}(D_{T}+[TSH])(1+K_{41}[TBG]+K_{42}[TBPA])[FT_{4}]}{\alpha _{T}[TSH]{V}_{T}}}}$

or

${\displaystyle {\hat {G}}_{TS}={\frac {\beta _{T}(D_{T}+[TSH])[TT_{4}]}{\alpha _{T}[TSH]{V}_{T}}}}$

is referred to as specific thyroid capacity (SPINA-GTs).[5]

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.[1]

SPINA-GT is elevated in primary hyperthyroidism[6] and reduced in both primary hypothyroidism[7][8][9] and untreated autoimmune thyroiditis.[10] It has been observed to correlate (with positive direction) to resting energy expenditure[11] and thyroid volume[1][5], and (with negative direction) to thyroid autoantibody titres, which reflect organ destruction due to autoimmunity[12]. Elevated SPINA-GT in Graves's disease is reversible with antithyroid treatment.[11] While SPINA-GT is significantly altered in primary thyroid disorders, it is insensitive to disorders of secondary nature (e.g. pure pituitary diseases).[2]

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.[2] 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.[13]

In clinical trials SPINA-GT was significantly elevated in patients suffering from Graves' disease and toxic adenoma compared to normal subjects.[1][6] It is also elevated in diffuse and nodular goiters, and reduced in untreated autoimmune thyroiditis.[1][10] 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.[1] GT's specificity is also high in thyroid disorders of secondary or tertiary origin.[2]

Correlation of SPINA-GT with creatinine clearance suggested a negative influence of uremic toxins on thyroid biology.[14] In the initial phase of major non-thyroidal illness syndrome (NTIS) SPINA-GT may be temporarily elevated.[15] In chronic NTIS[16] as well as in certain non-critical chronic diseases, e.g. chronic fatigue syndrome[17] or asthma[18] SPINA-GT ist slightly reduced.

In women, therapy with Metformin results in increased SPINA-GT, in parallel to improved insulin sensitivity.[19] This observation was reproducible in men with hypogonadism, but not in men with normal testosterone concentrations[20], so that the described effect seems to depend on androgen levels. In hyperthyroid[6] 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 thyroid's secretory capacity predicts depression and sexual dysfunction.[21] 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[22].

In patients with autoimmune thyroiditis a gluten-free diet results in increased SPINA-GT (in parallel to sinking autoantibody titres).[23] Statin therapy has the same effect, but only if supply with vitamin D is sufficient.[24] Accordingly, substitution therapy with 25-hydroxyvitamin D leads to rising secretory capacity.[25][26][27] This effect is potentiated by substitution therapy with selenomethionine.[25][26]

On the other hand, men treated with spironolactone are faced with decreasing SPINA-GT (in addition to rising thyroid antibody titres)[28]. It has, therefore, been concluded that spironolactone may aggravate thyroid autoimmunity in men[28].

Specific secretory capacity (SPINA-GTs) is reduced in obesity[1] and autoimmune thyroiditis.[5][29]