TSH, fT4, and fT3 Serum TSH concentrations vary markedly in response to small changes in blood levels of T4 and T3. A rational approach to assessing thyroid function is to determine TSH, possibly accompanied by the measurement of thyroid hormones. The high sensitivity and specificity of serum TSH assays justify their use in clinical practice as a screening test for thyroid alterations. TSH measurement should be per formed by high-sensitivity immunometric methods.

TSH assay may be required in the following cases:

• Screening of apparently healthy populations

 • Diagnostic assessment of outpatients with clinical symptoms attributable to thyroid dysfunction

 • Diagnostic investigation on the hospitalized patients with clinical symptoms ascribable to thyroid dysfunction

• Monitoring the course of the diagnosed thyroid disease and/or specific therapy (medical and/or surgical)

Adults with any of the following conditions are at high risk for thyroid dysfunction:

 • Previous history of thyroid dysfunction

 • Goiter

• Previous history of thyroid surgery

 • Previous history of cervical radiation therapy

• Autoimmune diseases: diabetes mellitus type 1, celiac disease, etc.

 • Use of drugs: lithium, cytokines, interferon, amiodarone, contrast media

• Family history of thyroid disease or other autoimmune diseases

• Chromosomal alterations: Down’s syndrome, Turner’s syndrome, Klinefelter’s syndrome, etc.

• Alterations in laboratory tests suggestive of thyroid dis ease: hypercholesterolemia, hyponatremia, anemia, hyperprolactinemia, hyper-CK, hyper-LDH, hyper-AST/ ALT, hyper-ALP, etc.

• Comorbidities: sleep apnea, depression, and dementia

For pediatric subjects, the following conditions are associated with a high risk of thyroid dysfunction:

 • Children/adolescents with short stature or low growth

 • Children with pubertal developmental disorders

 • Hyperactive children and adolescents

• Children and adolescents with reduced school performance

With rare exceptions represented by TSH-secreting pituitary adenomas and pituitary resistance to the action of thyroid hormones, the finding of normal TSH values excludes the presence of alterations in glandular secretion.

Finally, when not mandatory, it is desirable to monitor glandular secretion in the elderly, infants, and nursing mothers.

The detection of an altered TSH value should be followed by the measurement of fT4 and possibly fT3 in the same sample (TSH-reflex) (Fig.1). The use of profile or com bination tests is reserved for the rare specific cases in which the TSH test alone has no informative value (TSH-secreting adenoma, thyrostatic drugs, suspected pituitary/hypothalamic diseases, resistance to the action of thyroid hormones).

Fig1. TSH reflex: diagnostic algorithm of the main alterations of the glandular function. (Copyright EDISES 2021. Reproduced with permission)

The widespread availability and pronounced sensitivity of TSH immunoassays have rendered the TRH stimulus test obsolete; the diagnostic significance of non-elevation of TSH after bolus (200–400 μg) is thought to be the same as that of suppressed TSH. Although assays for total T3 and T4 are available, it is appropriate to determine free fractions (fT3 and fT4), unaffected by physiologic and pathologic conditions associated with changes in binding between total hormones and TBG1.

Physiological changes in fT3 and fT4 concentrations are frequently found with age, during pregnancy, and in pro longed fasting.

In some circumstances, TSH determination alone can be misleading, and its use as a screening test is contraindicated. In particular, TSH-secreting pituitary adenomas and pituitary resistance to thyroid hormones can lead to elevated TSH levels without hypothyroidism; on the contrary, TSH suppression can occur during the first trimester of pregnancy as a consequence of hCG secretion, or as a consequence of the pharmacological treatment of hyperthyroidism, or as a consequence of the administration of several other drugs, including dopamine and glucocorticoids. In any case, all serious extra-thyroidal diseases can lead to increased TSH levels.

It should be noted that the TSH value in thyroid function screening is null in the presence of known pituitary disease or only clinical suspicion of it.

Autoantibodies

 The search for autoantibodies can complement the evaluation of thyroid function to make an etiologic diagnosis. Antibodies directed against thyroperoxidase (TPOAb), previously defined as antimicrosomal, have long been used to diagnose hyperthyroidism. Although their use in clinical practice is still widespread, the most updated literature recommends their determination only in subclinical hypothyroidism and in identifying the autoimmune nature of thyroiditis. The assay of TSH anti-receptor anti bodies (TRAb) has reached high standards of analytical performance (third generation TRAb); in patients who do not present an obvious clinic, they are used in the differential diagnosis between Basedow–Graves and other forms of hyperthyroidism. The measurement of TRAb is also indicated in therapy monitoring of hyperthyroidism to distinguish patients with a high probability of remission (80–100%) from those with a very low probability (20%).

It should be noted that TPOAb and TRAb are not infrequently detected in the serum of euthyroid subjects (2–5%).

Today, antibodies directed against thyroglobulin have no diagnostic value, and their determination is never appropriate.

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مواضيع ذات صلة

Diagnosis and Therapy of Thyroid Hormones

total blood volume (TBV, Red blood cell [RBC] volume)

TORCH test

thyroxine-binding globulin (TBG, Thyroid-binding globulin)

Diagnosis and Therapy of neurohypophysis

Laboratory Investigations of neurohypophysis

thyroxine, total and free (T4 , Thyroxine screen, FT4 )

thyroid-stimulating immunoglobulins

thyroid-stimulating hormone stimulation test (TSH stimulation test)

Disorders of ADH secretion and action

Antidiuretic Hormone

Prolactin