Should Free Thyroxine Go Back into the Routine Thyroid Profile?

Many clinical chemistry laboratories offer thyroid-stimulating hormone (TSH) alone as a first-line test of thyroid function, and only reflex a free thyroxine (fT4) test if the TSH result is abnormal (i. e., outside of the laboratory reference range). In secondary hypothyroidism, a low fT4 may be accompanied by a low or a normal TSH level. A testing strategy that measures baseline TSH only risks missing cases of secondary hypothyroidism in which the TSH level is normal.

The current authors examined 26,106 consecutive thyroid function test (TFT) results in our initial analysis. If the TFT results were compatible with hypopituitarism, with fT4 below the reference range (9-20 pmol/L) and a TSH result ≤5 mU/L (reference range: 0.5-5 mU/L), the laboratory performed further tests of pituitary function. The cost of identifying pituitary insufficiency by measuring both fT4 and TSH was estimated for our population (in 2004 and 2013) and compared with 2 other relevant studies.

A total of 121 patients had a normal TSH with a low fT4. 8 new cases of secondary hypopituitarism were identified when fT4 was combined with TSH as the front-line TFT profile. Of these, 5 were found to have pituitary adenomas, 2 of which were macroprolactinomas. The reagent cost of identifying each case by inclusion of fT4 in the TFT profile decreased from £11,568 (€16,089) in 1998 to £1451 (€2018) in 2013.

8 cases of pituitary insufficiency would not have been identified with a strategy of TSH testing alone, which calls for the addition of fT4 to the routine TFT profile. The cost per case of identifying those with pituitary insufficiency by additional measurement of fT4 has become cheaper with time.