TSH - Kresser Institute Membership Site

Marker Name: TSH

REFERENCE RANGES FOR SERUM TSH:

Laboratory reference range: 0.45–4.5 µIU/mL

Functional reference range: 0.5–2.0 µIU/mL

DESCRIPTION:

TSH stands for thyroid-stimulating hormone, although it is sometimes called thyrotropin or thyrotropic hormone. TSH stimulates the thyroid gland to produce thyroid hormone. Thyroid hormone, in turn, is critical for the proper function of virtually every type of cell in the human body.¹

TSH is a glycoprotein that consists of alpha and beta subunits. The alpha subunit is virtually identical to that of some gonadotropins, while the beta subunit is unique to TSH.² TSH is secreted from the anterior pituitary gland as separate alpha and beta subunits. The secretion of these subunits by the pituitary is dependent on the presence of thyroid-releasing hormone (TRH), which is secreted by the hypothalamus.³ TRH-stimulated cells in the anterior pituitary secrete TSH into the bloodstream. The circulating TSH binds to and activates the TSH receptor, located predominantly on thyroid follicular cells.⁴ TSH receptor activation stimulates the production and release of thyroid hormone from the thyroid gland.¹

TRH release from the hypothalamus and TSH release from the pituitary gland are under negative feedback control from circulating thyroid hormone levels.⁵ In other words, rising levels of thyroid hormone decrease the release of TRH and TSH. Conversely, decreased levels of thyroid hormone stimulate the hypothalamus and pituitary gland to release more TRH and TSH, respectively.

There is considerable controversy regarding the upper limit of normal for serum TSH.⁵ There is general agreement that age-based normal ranges for serum TSH should be used, given the wide variability of normal levels across the lifespan.⁶

High levels of circulating TSH are usually caused by primary hypothyroidism or subclinical hypothyroidism.^5,7 This is in contrast to secondary hypothyroidism, which usually results in normal or low TSH levels in the presence of low serum T4 and T3 concentrations. Some cases of secondary hypothyroidism may result in slightly elevated levels of functionally abnormal TSH.⁷ That is, serum levels of TSH appear high, but the hormone does not exert an appropriate biological effect. Many cases of elevated TSH are due to transient hypothyroidism, perhaps due to thyroiditis or therapy with radioiodine. Primary deficiencies in the thyroid gland that lead to decreased thyroid hormone production can cause reflexive elevations in TSH. In rare instances, a TRH-secreting tumor can cause excessive secretion of TSH by the pituitary gland, even in the context of normal circulating thyroid levels.

As with elevated levels of TSH, abnormally low levels of circulating TSH are usually caused by primary hyperthyroidism or subclinical hyperthyroidism. Graves’ disease is the most common cause of hyperthyroidism, though Hashimoto thyrotoxicosis (i.e. Hashitoxicosis) is also quite common.^8,9 Certain forms of thyroiditis may also cause low TSH levels in the blood. Amiodarone is well known to cause low TSH levels. Not all causes of low TSH are related to increases in circulating thyroid hormones. For example, euthyroid sick syndrome may lower blood TSH levels along with decreased thyroxine or triiodothyronine levels.^10,11

Several tests are used in addition to serum TSH levels to evaluate thyroid function, including total thyroxine (T4), total triiodothyronine (T3), free T4, free T3, and reverse T3 concentrations in the serum.⁵ Suspected autoimmune thyroiditis may be investigated by examining the blood for the presence of antibodies against thyroid peroxidase (TPO), thyroglobulin (Tg), and the TSH receptor.⁵

PATHOLOGICAL/CONVENTIONAL RANGE INDICATIONS:

High in:⁷

Transient hypothyroidism
- Painless thyroiditis
- Subacute granulomatous thyroiditis
- Postpartum thyroiditis
- Subtotal thyroidectomy
- Radioiodine therapy
Chronic autoimmune thyroiditis
Thyroidectomy
Fibrous thyroiditis
Congenital thyroid agenesis, dysgenesis, or defects in hormone synthesis
Generalized thyroid hormone resistance
Iodine deficiency or excess
External beam radiation therapy
Sarcoidosis
Hemochromatosis
Drugs
- Thionamides
- Lithium
- Amiodarone
- Interferon-alpha
- Interleukin-2
- Perchlorate
- Tyrosine kinase inhibitors

Low in:^9,10

Graves’ disease
Hashitoxicosis
Thyroiditis (e.g., postpartum thyroiditis, de Quervain’s thyroiditis)
Euthyroid sick syndrome
Excessive thyroid hormone replacement therapy
Iodine-induced hyperthyroidism
Autoimmune hypopituitarism
Toxic nodular goiter
Struma ovarii
Amiodarone

FUNCTIONAL RANGE INDICATIONS:

High in:

Hypothyroidism
Iodine, selenium, or zinc deficiency
Functional iron overload

Low in:

Facetious hyperthyroidism (excessive thyroid hormone replacement)
Pituitary hypofunction

References: