Hypothyroidism: Diagnosis

Diagnosis of hypothyroidism should be sought on the basis of family history, clinical signs, age, and pregnancy status (because of risks for the fetus in cases of untreated maternal hypothyroidism). Diagnosis remains somewhat controversial because of variations in acceptable ranges of laboratory values among different labs and institutions. Because of this, thyroid dysfunction in a patient who complains of symptoms but presents with “normal” laboratory values should not be disregarded.

TSH measurement is commonly accepted as the most significant and sensitive measurement for hypothyroidism diagnosis. Elevated thyroid-stimulating hormone identifies patients with primary hypothyroidism regardless of the cause or severity. Primary hypothyroidism presents with a low serum thyroxine with attendant elevation of serum TSH. Subclinical hypothyroidism is marked by normal serum thyroxine levels with slight to moderately increased thyroid-stimulating hormone levels and a normal FTI (Table Biochemical Markers in Thyroid Dysfunction). Laboratory tests are considered generally unnecessary to determine the underlying cause of primary hypothyroidism. Factors such as previous neck/thyroid irradiation or surgery, or other exposure to radiation (e.g., pharmaceutical exposure) postpartum status, or other known contributing factors is adequate. Autoimmune causes can be assumed on the basis of ruling out other possible etiologies. An important note is that serum thyroid-stimulating hormone levels may rise in the recovery phase of illness, mimicking values associated with hypothyroidism. Therefore, measurement of thyroid-stimulating hormone after complete recovery is appropriate. Free thyroxine is required to give an accurate measurement of thyroid hormone activity, given that only 0.03% of total thyroxine hormone is unbound and reflects the thyroid hormone activity of T4. The remaining 99.97% of total thyroxine is bound to carrier proteins and is metabolically inactive. The fT4 or FTI in conjunction with a thyroid-stimulating hormone can be used to categorize most cases of thyroid dysfunction. The exception occurs when FT4 remains normal but FT3 is abnormal, as may occur when there is a deficient conversion of thyroxine to T3.

Biochemical Markers in Thyroid Dysfunction

Overt hypothyroidism >5 mU/L Low FT4
Subclinical hypothyroidism >5 mU/L Normal FT4
Overt hyperthyroidism Low or undetectable Elevated FT4 or FT3
Subclinical hyperthyroidism Low or undetectable Normal FT4 or FT3

Measurement of tri-iodothyronine is controversial. The conventional medical belief is that normal serum tri-iodothyronine levels are maintained until severe hypothyroidism occurs. Recently, however, many physicians have begun to evaluate tri-iodothyronine as a part of thyroid screening. Many test tri-iodothyronine levels only when patients are unresponsive to treatment with T4. Tri-iodothyronine levels can be decreased in primary and secondary hypothyroidism as well as decreased serum TBG, by some medications, low carbohydrate diets, and euthy-roid sick syndrome. Laboratory diagnosis of secondary hypothyroidism is marked by low thyroxine levels and low or normal thyroid-stimulating hormone levels. Many patients need to have tests repeated several times to achieve an accurate and correct diagnosis.

Basal body temperature (BBT) testing has been suggested as a screening test for subclinical hypothyroidism. However, there are many factors other than thyroid hormones that affect basal body temperature and thus by itself, low basal body temperature is not a pathognomonic indicator of thyroid hormone status, although it does indicate lowered metabolic status.