Definition
- This glycoprotein hormone of 28 " 30 kDa is composed of alpha and beta subunits. It is secreted by the anterior pituitary. TSH controls the biosynthesis and release of thyroid hormones T4 and T3.
- Normal range: 0.5 " 6.3 ¼IU/mL, depending on age and sex (Table 16.78).
TABLE 16 " 78Normal Ranges of TSH According to Age and SexView LargeTABLE 16 " 78Normal Ranges of TSH According to Age and Sex Age TSH ( µIU/mL) Male Female 0 " 1 mo 0.5 " 6.5 0.5 " 6.5 (same as in males) 1 " 11 mo 0.8 " 6.3 0.8 " 6.3 (same as in males) 1 y 0.7 " 6.0 0.7 " 5.9 6 y 0.7 " 5.4 0.6 " 5.1 11 y 0.6 " 4.9 0.5 " 4.4 16 y 0.5 " 4.4 0.5 " 3.9 18 y 0.28 " 3.89 0.28 " 3.89 (same as in males)
Use
- Sensitive measure of thyroid function. First line of test for suspected thyroid disorders
- Assessing true metabolic status
- Screening for euthyroidism
- Normal level in stable ambulatory patient not on interfering drugs excludes thyroid hormone excess or deficiency.
- TSH is recommended as the initial test rather than T4.
- Screening is not recommended for asymptomatic persons without suspicion of thyroid disease or for hospital patients with acute medical or psychiatric illness.
- Initial screening and diagnosis for hyperthyroidism (decreased to undetectable levels except in rare TSH-secreting pituitary adenoma) and hypothyroidism
- Especially useful in early or subclinical hypothyroidism before the patient develops clinical findings, goiter, or abnormalities of other thyroid tests
- Differentiation of primary (increased levels) from central (pituitary or hypothalamic) hypothyroidism (decreased levels)
- Monitoring of adequate thyroid hormone replacement therapy in primary hypothyroidism, although T4 may be mildly increased (up to 6 " 8 weeks before TSH becomes normal). Serum TSH suppressed to the normal level is the best monitor of dosage of thyroid hormone for treatment of hypothyroidism
- Monitoring adequate thyroid hormone therapy in the suppression of thyroid carcinoma (should suppress to <0.1 ¼IU/mL) or goiter or nodules (should suppress to subnormal levels) with third- or fourth-generation assays
- Replacement of TRH stimulation test in hyperthyroidism, because most patients with euthyroid TSH level have a normal TSH response and patients with undetectable TSH level almost never respond to TRH stimulation
Interpretation
Increased In
- Primary untreated hypothyroidism. The increase is proportionate to the degree of hypofunction, varying from 3 times normal in mild cases to 100 times normal in severe myxedema. A single determination is usually sufficient to establish the diagnosis.
- Patients with hypothyroidism receiving insufficient thyroid hormone replacement therapy.
- Patients with Hashimoto thyroiditis, including those with clinical hypothyroidism and about one third of those patients who are clinically euthyroid.
- Use of various drugs: amphetamines (abuse), iodine-containing agents (e.g., iopanoic acid, ipodate, amiodarone), and dopamine antagonists (e.g., metoclopramide, domperidone, chlorpromazine, haloperidol).
- Other conditions (test is not clinically useful).
- Iodide deficiency goiter or iodide-induced goiter or lithium treatment
- External neck irradiation
- Postsubtotal thyroidectomy
- Neonatal period; increased in first 2 " 3 days of life due to postnatal TSH surge
- Thyrotoxicosis due to pituitary thyrotroph adenoma or pituitary resistance to thyroid hormone
- Euthyroid sick syndrome, recovery phase
- TSH antibodies
Decreased In
- Toxic multinodular goiter
- Autonomously functioning thyroid adenoma
- Ophthalmopathy of euthyroid Graves disease; treated Graves disease
- Thyroiditis
- Extrathyroidal thyroid hormone source
- Factitious
- Overreplacement of thyroid hormone in treatment of hypothyroidism
- Secondary pituitary or hypothalamic hypothyroidism (e.g., tumor, infiltrates)
- Euthyroid sick patients (some patients)
- Acute psychiatric illness
- Severe dehydration
- Drug effect, especially large doses (use FT4 for evaluation)
- Glucocorticoids, dopamine, dopamine agonists (bromocriptine), levodopa, T4 replacement therapy, apomorphine, and pyridoxine; normal or low T4
- Antithyroid drug for thyrotoxicosis, especially early in treatment; normal or low T4
- Assay interference (e.g., antibodies to mouse IgG, autoimmune disease)
- First trimester of pregnancy
- Isolated deficiency (very rare)
Limitations
- TSH may be normal in
- Central hypothyroidism: In the absence of hypothalamic or pituitary disease, normal TSH excludes primary hypothyroidism.
- Recent rapid correction of hyperthyroidism or hypothyroidism
- Pregnancy
- Phenytoin therapy
- TSH may not be useful to evaluate thyroid status of hospitalized ill patients.
- Approximately 3 months of treatment of hypo- or hyperthyroidism; FT4 is test of choice.
- Lag time of 6 " 8 weeks is required for normalization of TSH after initiation of thyroid hormone replacement therapy.
- Dopamine or high doses of glucocorticoids may cause false normal values in primary hypothyroidism and may suppress TSH in nonthyroid illness.
- Rheumatoid factor, human antimouse antibodies, heterophile antibodies, and thyroid hormone autoantibodies may produce spurious results, especially in patients with autoimmune disorders ( ≤10%).
- Amiodarone may interfere with TSH.
- TSH is not affected by variation in thyroid-binding proteins.
- TSH has a diurnal rhythm, with peaks at 2:00 " 4:00 am and troughs at 5:00 " 6:00 pm with ultradian variations. TSH levels vary diurnally by up to 50% and up to 40% variations on specimens performed serially during the same time of the day.
- Serum levels typically falls below 0.1 mIU/L during first trimester of pregnancy due to thyroid stimulatory effects of HCG and returns to normal in the second trimester.