Hypothyroidism and What the TSH Test Can't Detect: Medical Journals

Purpose of this compilation

To show that using only the TSH (thyroid stimulating hormone) level as a diagnostic and assessment tool for hypothyroidism is inadequate because this test cannot identify numerous conditions. The references on this page name some of them. The point, however, is that using the TSH test for hypothyroidism is like using a magnet to find money — the tool will pick up only some forms of what the seeker is looking for.

The references on this page come from various countries around the world, over a span of a couple of decades.

See also the links in the right column as well as in our T3 References and Desiccated Thyroid sections.

A. The TSH test and central hypothyroidism
B. Other limitations of the TSH test

A. The TSH test and central hypothyroidism

1. "First-line thyroid function tests — TSH alone is not enough" (Scotland, 2003)

...there are two recent reports that cast considerable doubt on the wisdom of adopting the measurement of serum TSH alone as a first-line test of thyroid function (Waise & Belchetz, 2000; Wardle et al., 2001). Together these describe a series of 21 patients with pituitary or hypothalamic disease in which thyroid failure was manifest by a low serum T4 but normal TSH concentration....

...Restricting analysis to TSH alone, rather than T4 and TSH, is unlikely to result in the 50% savings many might anticipate. Indeed, any savings realized by deciding not to include a measurement of T4 at the initial stage are minor when set against the potential costs of litigation, if even a handful of the projected 1500 cases of resultant missed central hypothyroidism each year decide to seek redress.

2. "NACB: Laboratory Support for the Diagnosis and Monitoring of Thyroid Disease: Published Guidelines" (US, 2002)

Despite the clinical sensitivity of TSH, a TSH-centered strategy has inherently two primary limitations. First, it assumes that hypothalamic-pituitary function is intact and normal....If either of these criteria is not met, serum TSH results can be diagnostically misleading. [p. 5]

When the serum FT4 is low and yet the serum TSH is only minimally elevated (<10 mIU/L), a diagnosis of central hypothyroidism should be considered. [p. 10]

3. "Unsuspected central hypothyroidism in neonates" (UK, 2001)

The significance of a low normal TSH level was only apparent when free thyroxine was measured and found to be low normal i.e. an inappropriate response. Further tests confirmed central hypothyroidism as part of hypopituitarism. In 9 of the 12 infants, liver disease resolved following appropriate hormone replacement. In three patients where the diagnosis was delayed, liver dysfunction persisted and one patient eventually required liver transplantation. We would agree with the conclusion of Waise and Belchetz that where hypothyroidism is suspected, at whatever age, both TSH and free thyroxine should be measured.

4. "Pitfalls in the use of thyrotropin concentration as a first-line thyroid-function test" (2001)

Using a combination of thyrotropin [TSH] and thyroxine assays, we analysed 56,000 tests for a population of 471,000 over 12 months. 15 patients with clinically unsuspected hypopituitarism were detected, indicating that the occurrence of hypopituitarism might be underestimated.

5. "Unsuspected central hypothyroidism" (UK, 2000)

Testing only for thyroid stimulating hormone will miss unsuspected cases of central hypothyroidism.

B. Other limitations of the TSH test

1. "Review: molecular thyroidology" (US, 2001)

Novel disorders involving aberrations of the hypothalamic-pituitary-thyroid gland-thyroid hormone axis have been described in the last 5 to 10 years....molecular mutations causing central hypothyroidism...defects in response to TSH...defects in thyroid gland formation...defects in peripheral thyroid hormone metabolism...and defects in tissue response to thyroid hormone....knowledge of the molecular mechanisms of these diseases can greatly enhance the clinical laboratory scientist's ability to advise clinicians about appropriate thyroid testing and to interpret the complex and sometimes confusing results of thyroid function tests.

2. "Hypothyroidism: Treating the Patient not the Laboratory" (2000)

The first problem with assessment of thyroid function...is that T4 is not the only thyroid hormone, nor the most active....The second problem is that feedback regulation of TSH secretion is mediated by T4 rather than T3, so TSH cannot be relied upon for a definitive answer. The third problem is that total thyroid hormone activity is more dependent on T3 than T4, and T4 alone is therefore not a good indicator. The fourth is that thyroid hormone levels can be altered, in terms of both actual in vivo levels and in vitro test results, by a variety of exogenous factors....the problem of 'sub-laboratory' hypothyroidism (patient abnormal, laboratory normal) lacks even a recognizable name.

3. "This is only one of the many pitfalls of present approach" (US, 2000)

...most cases of hypothyroidism (of all types), at least in the US, are undertreated, again because of an over-reliance on this indirect test of thyroid function, the TSH test, no matter how sensitive, which can be suppressed or low for frequent reasons other than excessive thyroid replacement.

4. "[Serum TSH measurement]" [Article in Japanese; abstract in English] (Japan, 1999)

Serum TSH levels do not reflect the thyroid function, i) when thyroid function is changing widely, ii) in low T4-T3 states, iii) in central hyperthyroidism or hypothyroidism, and iv) when antibodies such as heterophile antibodies, rheumatoid factors, and rarely anti-TSH antibodies are present.

5. "Syndrome of resistance to thyroid hormone: insights into thyroid hormone action" (US, 1996)

Resistance to thyroid hormone (RTH) is a rare disorder caused by mutations in the TR beta gene. Biochemically, the syndrome is defined by elevated circulating levels of free thyroid hormones due to reduced target tissue responsiveness and normal, or elevated, levels of thyroid-stimulating hormone (TSH).

6. "Early identification of congenital hypothyroid infants with abnormalities in pituitary setpoint for T4-induced TSH release" (Israel, 1993)

These results suggest that some CH [congenitally hypothyroid] infants might have an abnormal setpoint for T4 control of TSH secretion and that these infants can be detected as early as 1 month after birth. Thus, serum T4, T3 levels and clinical progress are better guides to the adequacy of therapy than serum TSH concentrations in this group of CH infants.