Serum FT4 concentrations

Primary hypothyroidism is easily treated by the daily administration of oral thyroxine. During initial treatment, serum FT4 concentrations adjust quickly, but TSH concentrations remain high. Because the pituitary is slow to register acute changes in thyroid hormone status ( pituitary lag ), 4 to 8 weeks may be needed for serum TSH values to reach a new steady state after dose adjustments. Periodic monitoring of serum TSH, one to three times a year, is recommended to help maintain clinical euthyroidism and a serum TSH concentration within normal limits. Excessive treatment with oral T4 should be avoided to minimize the risk of accelerated bone resorption and/or atrial fibrillation. 

When the TSH concentration is suppressed, the serum FT4 concentration should be measured and will be elevated in most cases of hyperthyroidism. Finding a low TSH concentration and an elevated FT4 concentration is usually sufficient to establish the diagnosis of hyperthyroidism. If the TSH concentration is low but the FT4 concentration is... 

The main finding was the progressive decfine of serum FT4 concentrations in both the ID and the IS mothers with pregnancy advancement. This decline was more evident in the ID compared to the IS mothers (20% vs. 8%). Serum TSH mean values increased over the first half of gestation only in the ID (100% in ADHD+ vs. 30% ADHD— mothers), remaining unmodified in the IS mothers. 

When the serum free thyroxine concentration (FT4) or ultrasensitive TSH result is normal, the hypothalamic-pituitary-thyroid axis is assumed to be intact. If primary hypothyroidism is suspected clinically, however, a single measurement of a basal TSH concentration may be sufficient to confirm the diagnosis. In patients with a history of pituitary disease and secondary hypothyroidism, the serum TSH concentration is frequently normal thus in this situation, an FT4 concentration is tlie better test to gauge normality of the hypothalamic-pituitary-thyroid axis. On occasion a TRH stimulation test is used to distinguish hypothalamic... 

FT4] = concentration of free T4 in serum [TBP] - concentration of unoccupied binding sites on TBP... 

Calculation of T4/TBG and T3/TBG Ratios Measurements of serum TBG concentration have been used in the diagnosis of thyroid disease in two ways. The most common approach is to calculate a T4 TBG or T3 TBG ratio. Such indices are derived from mass action equations and are used to approximate FT4 or FT3 concentrations. These ratios correlate variably with FT4 or FT3 concentrations and are particularly useful in sera with altered TBG concentrations however, they may fail to compensate for TBG variants with reduced T4 affinity or for abnormal albumin binding. The reference interval for T4 TBG ratios is 3.8 to 4.5 when the reference intervals for total T4 and TBG are 4.5 to 12.5 pg/dL and 1.2 to 2.8 mg/dL, respectively. 

Estimates of FT4 or FT3 may be profoundly affected by medications that compete with T4 or T3 for binding to serum proteins. With reference methods that use undiluted serum, the free hormone concentration may rise and eventually return to a new steady state in the presence of T4- or Ts-dis-placing drugs. In contrast, most estimates of FT4 or FT3 use diluted serum in which the drug competitor declines before the free hormone declines. Consequently the hormone-displacing effect of the drug also decreases, leading to a major underestimation of the true FT4 concentration. 

Notes-. Gestationai hypothyroxinemia is defined by serum FT4 ooncentrations beiow the normai range for gestationai age but with normai TSH vaiues. Converseiy, serum TSH concentrations are above the upper iimit of normai range in both overt and subciinicai hypothyroidism. 

The prevalence of subclinical hypothyroidism (SCH), defined as serum thyrotropin (TSH) concentration above the upper limit of the reference range with normal free thyroxine (FT4), in women of child-bearing age may be as high as 5% (Canaris et al., 2000 Hollowell et al., 2002). Of these, approximately 2—5% per year will progress to overt hypothyroidism (OH), defined as low serum FT4 with elevated serum TSH concentration. When iodine nutrition status is adequate, the most frequent cause of hypothyrod is thyroid autoimmunity (Hashimoto s thyroiditis) and, in this respect, if we take into account women with thyroid autoimmunity and normal thyroid function who could become... 

Endocrine The effects of long-term carbamazepine ( = 18) and valproate ( = 14) on thyroid function in newly diagnosed children with epilepsy have been evaluated in a prospective open comparison with 32 sex- and age-matched controls [78. At baseline evaluation, thyroid function was normal. At the 3rd, 6th, and 12th month evaluations, patients taking carbamazepine had serum thyroxine (T4) and free thyroxine (fT4) concentrations significantly lower than baseline and control subjects valproate had no such effect. 

Cardiovascular The serum free thyroxine (fT4) concentration is associated with QT interval prolongation, which is a susceptibility factor for sudden cardiac death. Investigation of a prospective population-based cohort and a case-control study have shown a threefold increased risk of sudden cardiac death in patients taking antithyroid drugs. Although a direct link between the use of thionamides and sudden cardiac death cannot be ruled out, these findings could more readily be explained by underlying poorly controlled hyperthyroidism, since patients who died had low serum TSH concentrations before death [26 ]. 

Numerous methods have been developed for assessing the concentrations of FT4 and FT3 in serum. These methods include direct assays that currently serve as reference methods and indirect assays that are more widely available for general laboratory use. The following section describes the principles of these methods and offers some guidelines for their use. The theoretical basis, analytical validity, and clinical utility of these methods have been discussed. Special reports from the Nomenclature Committee of the American Thyroid Association, the National Academy of Clinical Biochemistry, and the NCCLS also review some of the issues and concerns regarding free thyroid hormone measurements. 

Most routine immunoassay methods for determining FT4 and FT3 concentrations in serum are estimates. These approaches are often more convenient and less expensive than reference methods, and most are available commercially m kit form and on automated immunoassay instruments. Two test strategies are used for estimating the concentrations of free hormones indirect index methods and direct immunoassays. 

---