Hypothyroidism, TSH, and Symptoms: Medical Journals

Purpose of this compilation

To show that people with symptoms of hypothyroidism but a TSH level within the reference range may be hypothyroid (untreated or undertreated) despite their "normal" TSH level — the TSH level often doesn't correlate with symptoms and other lab results. These findings come from various countries.

See also the links in the right column as well as in our T3 References and Desiccated Thyroid sections. For lists of hypothyroidism symptoms, see Fast Facts: Symptoms.

A. Symptoms with a "normal" TSH level
B. Symptoms and poor correlation with the TSH level

A. Symptoms with a "normal" TSH level

1. "Psychological well-being in patients on 'adequate' doses of l-thyroxine: results of a large, controlled community-based questionnaire study" (UK, 2002)

...many patients complain of persistent lethargy and related symptoms on T4 even with normal TSH levels....patients on thyroxine replacement even with a normal TSH display significant impairment in psychological well-being compared to controls of similar age and sex.

2. "What is the optimal treatment for hypothyroidism?" (Australia, 2001)

Recent research suggests that in some patients symptoms of hypothyroidism persist despite standard thyroxine replacement therapy.... Adjusting the thyroxine dose until the serum TSH concentration is in the lower part of the reference range (eg, 0.3-2.0 mU/L) may be beneficial.

3. "Thyroxine should be tried in clinically hypothyroid but biochemically euthyroid patients" (England, 1997)

We wish to question present medical practice, which considers abnormal serum concentrations of free thyroxine and thyroid stimulating hormone — those outside the 95% reference interval — to indicate hypothyroidism but incorrectly considers "normal" free thyroxine and thyroid stimulating hormone concentrations to negate this diagnosis....

The...thyroid stimulating hormone concentrations in 80 patients considered to be hypothyroid on established criteria indicated that...only four patients had thyroid stimulating hormone values above the reference interval of 0.5-5.5 mU/l…the mean concentration of thyroid stimulating hormone was 2.2 (0.4) mU/l.

4. "T3 is at least as important as T4 in All Hypothyroid Patients" (US,1993)

...big double-myth is that (a) an elevated ultrasensitive-TSH level is always required before a diagnosis of hypothyroidism can be made; and that (b) its nearly-complete suppression always means that at-least-adequate treatment is in place. There seem to be subtle failures of TSH response to low thyroid hormone levels that cannot be explained purely by the usual forms of hypopituitarism (with secondary hypothyroidism), or by the euthyroid sick syndrome.

B. Symptoms and poor correlation with the TSH level

1. "Serum thyroid stimulating hormone in assessment of severity of tissue hypothyroidism in patients with overt primary thyroid failure: cross sectional survey" (Switzerland, 2003)

We found no correlations between the different parameters of target tissues and serum TSH. Our findings are in accordance with a cross sectional study showing only a modest correlation between TSH and the percentage of positive hypothyroid symptoms [footnote 4] and data showing discordant responses between the pituitary and peripheral target tissues in patients treated with L-triiodothyronine. [footnote 5]....the biological effects of thyroid hormones at the peripheral tissues and not TSH concentrations reflect the clinical severity of hypothyroidism. A judicious initiation of thyroxine treatment should be guided by clinical and metabolic presentation and thyroid hormone concentrations (free thyroxine) and not by serum TSH concentrations.

2. "Thyroid Insufficiency. Is TSH the Only Diagnostic Tool?" (Belgium, 2000)

From clinical experience we know that the highly celebrated serum thyroid stimulating hormone (TSH) test, even the third generation procedure, as well as the serum free thyroxine (T4) test, correlate poorly with the clinical status of the thyroid diseased patient.

3. "TSH has no clinical correlation" (Canada, 1999)

…there is no correlation except at extremes between the signs and symptoms of thyroid problems and the TSH....The thyroidologists by consensus have decided that this test is the most useful for following treatment when in fact it is unrelated to how the patient feels. The consequences of this have been horrendous....The TSH needs to be scrapped and medical students taught again how to clinically recognize low thyroid conditions.

4. "Serum T4, T3, and TSH levels in primary hypothyroidism during replacement therapy with thyroxine" (1983)

Group I had normal serum T3 levels, normal (or elevated) serum T4 levels, and normal serum TSH levels. Group II had normal serum T3 levels, normal (or elevated) serum T4 levels, but high serum TSH levels. Group II was subdivided further into a group of 13 patients (group IIa) whose dose of thyroxine was deliberately increased until the serum TSH level was normalized; five of these patients became clinically and biochemically hyperthyroid. Group IIb consisted of eight patients with normal serum T3 and T4 levels and high serum TSH levels who were followed up without attempting to normalize their serum TSH levels. None became thyrotoxic, and their serum TSH levels showed little change. These findings suggest that serum TSH levels alone are not adequate to assess the required dose of thyroxine replacement therapy.