Thyroid's secretory capacity

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) is the maximum stimulated amount of thyroxine that the thyroid can produce in a given time-unit (e.g. one second).[1][2]

Thyroid's secretory capacity
SynonymsSPINA-GT, GT, T4 output, thyroid hormone output, thyroid's incretory capacity
Reference range1.41–8.67 pmol/s
Test ofMaximum amount of T4 produced by the thyroid in one second
MeSHD013960
LOINC82368-2

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.[3]

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

or

: Theoretical (apparent) secretory capacity (SPINA-GT)
: Dilution factor for T4 (reciprocal of apparent volume of distribution, 0.1 l−1)
: Clearance exponent for T4 (1.1e-6 sec−1)
K41: Dissociation constant T4-TBG (2e10 l/mol)
K42: Dissociation constant T4-TBPA (2e8 l/mol)
DT: EC50 for TSH (2.75 mU/l)[1][4]

Specific secretory capacity

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

,

i.e.

or

is referred to as specific thyroid capacity (SPINA-GTs).[5] It is a measure for how much one ml of thyroid tissue can produce under conditions of maximum stimulation. Thereby, SPINA-GTs is an estimate for the endocrine quality of thyroid tissue.

Reference Range
Lower limitUpper limitUnit
1.41[1]8.67[1]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.[1]

Clinical significance

Validity

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] resting heart rate[12] and thyroid volume,[1][5] and (with negative direction) to thyroid autoantibody titres, which reflect organ destruction due to autoimmunity.[13] Elevated SPINA-GT in Graves' 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]

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.[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.[14]

Clinical utility

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]

Pathophysiological and therapeutic implications

Correlation of SPINA-GT with creatinine clearance suggested a negative influence of uremic toxins on thyroid biology.[15] In the initial phase of major non-thyroidal illness syndrome (NTIS) SPINA-GT may be temporarily elevated.[16][17] In chronic NTIS[18] as well as in certain non-critical chronic diseases, e.g. chronic fatigue syndrome[19] or asthma[20] SPINA-GT is slightly reduced.

In women, therapy with Metformin results in increased SPINA-GT, in parallel to improved insulin sensitivity.[21] This observation was reproducible in men with hypogonadism, but not in men with normal testosterone concentrations,[22] so that the described effect seems to depend on an interaction of metformin with sex hormones.[22][23] 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.[24] 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.[25]

In patients with autoimmune thyroiditis a gluten-free diet results in increased SPINA-GT (in parallel to sinking autoantibody titres).[26] Statin therapy has the same effect, but only if supply with vitamin D is sufficient.[27] Accordingly, substitution therapy with 25-hydroxyvitamin D leads to rising secretory capacity.[28][29][30] This effect is potentiated by substitution therapy with selenomethionine[28][29] or, in women, with dehydroepiandrosterone.[31] The effects of vitamin D and selenomethionine are attenuated in hyperprolactinaemia, suggesting an inhibitory effect of prolactin.[32]

On the other hand, men treated with spironolactone are faced with decreasing SPINA-GT (in addition to rising thyroid antibody titres).[33] It has, therefore, been concluded that spironolactone may aggravate thyroid autoimmunity in men.[33]

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.[34] This applies to both incidence and event-free survival.[34] Likewise, SPINA-GT is elevated in a significant subgroup of patients with takotsubo syndrome.[35]

Specific secretory capacity (SPINA-GTs) is reduced in obesity[1] and autoimmune thyroiditis.[5][36]

Endocrine disruptors may affect stimulated thyroid output, as demonstrated by a positive correlation of urinary mercury concentration and SPINA-GT.[37]

See also

References
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