Measurement of Thyroid Hormone and Its Metabolites in Other Body Fluids and in Tissues
Clinical experience with measurement of thyroid hormone and its metabolites in body fluids other than serum and in tissues is limited for several reasons. Analyses carried out in urine and saliva do not appear to give additional information, not obtained from measurements carried out in serum. Amniotic fluid, cerebrospinal fluid, and tissues are less readily accessible for sampling. Their likely application in the future will depend on information they could provide beyond that obtained from similar analyses in serum.
Because thyroid hormone is filtered in the urine predominantly in free form, measurement of the total amount excreted over 24 hours offers an indirect method for the estimation of the free hormone concentration in serum. The 24-hour excretion of T4 in normal adults ranges from 4 to 13 µg and from 1.8 to 3.7 µg, depending upon whether total or only conjugated T4 is measured. Corresponding normal ranges for T3 are 2.0 - 4.0 µg and 0.4 - 1.9 µg.173-175 Striking seasonal variations have been shown for the urinary excretion of both hormones, with a nadir during the hot summer months, in the absence of significant changes in serum TT4 and TT3. As expected, values are normal in pregnancy and in nonthyroidal illnesses, and are high in thyrotoxicosis and low in hypothyroidism. 174,175 The test may not be valid in the presence of gross proteinuria and impairment of renal function.176
All iodothyronines measured in blood have also been detected in AF. With the exception of T3, 3,3'-T2 and 3'-T2, the concentration at term is lower than that in cord serum.139,140,142,177-179 This fact cannot be fully explained by the low TBG concentration in AF. Although the source of iodothyronines in AF is unknown, the general pattern more closely resembles that found in the fetal than in the maternal circulation.
The TT4 concentration in AF average 0.5 µg/dl (65 nmol/L) with a range of 0.15 - 1.0 µg/dl and is thus very low when compared to values in maternal and cord serum.177-179 The FT4 concentration is, however, twice as high in AF relative to serum. The TT3 concentration is also low relative to maternal serum being on the average 30 ng/dl (0.46 nmol/L) in both AF and cord serum.179 rT3, on the other hand, is very high in AF, on average 330 ng/dl (5.1 nmol/L) during the first half of gestation, declining precipitously at about the 30th week of gestation to an average of 85 ng/dl (1.3 nmol/L) which is also found at term.178,179
T4, T3, and rT3 concentrations have been measured in human CSF.180-182 The concentrations of both TT4 and TT3 are approximately 50-fold lower than those found in serum. However, the concentrations of these iodothyronines in free form are similar to those in serum. In contrast, the level of TrT3 in CSF is only 2.5-fold lower than that of serum, whereas that of FrT3 is 25-fold higher. This is probably due to the presence in CSF of a larger proportion of TTR which has high affinity for rT3.181 All the thyroid hormone-binding proteins present in serum are also found in CSF, although in lower concentrations.181 The concentrations of TT4 and FT4 are increased in thyrotoxicosis and depressed in hypothyroidism. Severe nonthyroidal illness gives rise to increased TrT3 and FrT3 levels.182
TT4 concentration in human milk is of the order of 0.03 - 0.5 µg/dl.183 Analytical artifacts were responsible for the much higher values formerly reported.183,184 TT3 concentrations range from 10 to 200 ng/dl (015 - 3.1 nmol/L).184,185 The concentration of TrT3 ranges from 1 - 30 ng/dl (15 - 460 pmol/L).184 Thus, it is unlikely that milk would provide a sufficient quantity of thyroid hormone to alleviate hypothyroidism in the infant.
It has been suggested that only the free fraction of small nonpeptide hormones which circulate predominantly bound to serum proteins would be transferred to saliva and that their measurement, in this easily accessible body fluid, would provide a simple and direct means to determine their free concentration in blood. This hypothesis was confirmed for steroid hormones,186 not tightly bound to serum proteins. Levels of T4 in saliva range from 4.2 - 35 ng/dl (54 - 450 pmol/L) and do not correlate with the concentration of free T4 in serum.187 This finding is, in part, due to the transfer of T4 bound to the small but variable amounts of serum proteins that reach the saliva.
TT4 measured in fluid obtained from serous cavities bears a direct relationship to the protein content and the serum concentration of T4. Limited experience with Tg measurement in pleural effusions from patients with thyroid cancer metastatic to lungs suggests that it may be of diagnostic value.165
Since the response to thyroid hormone is expressed at the cell level, it is logical to assume that hormone concentration in tissues should correlate best with its action. Methods for extraction, recovery, and measurement of iodothyronines from tissues have been developed but, for obvious reasons, data from thyroid hormone measurements in human tissues are limited. Preliminary work has shown that under several circumstances, hormonal levels in tissues such as liver, kidney, and muscle usually correlate with those found in serum.188
Measurements of T3 in cells most accessible for sampling in humans, namely, red blood cells gave values of 20 - 45 ng/dl (0.31 - 0.69 nmol/L) or one-fourth those found in serum.189 They are higher in thyrotoxicosis and lower in hypothyroidism.
The concentrations of all iodothyronines have been measured in thyroid gland hydrolysates.18,133,139 In normal glands, the molar ratios relative to the concentration of T4 are on average as follows: T4/T3 = 10; T4/rT3 = 80; T4/3,5'-T2 = 1,400; T4/3,3'-T2 = 350; T4/3',5'-T2 = 1,100; and T4/3'-T1 = 4,400. Information concerning the content of iodothyronines in hydrolysates of abnormal thyroid tissue is limited, and the diagnostic value of such measurements has not been established.
Measurement of Tg in metastatic tissue obtained by needle biopsy may be of value in the differential diagnosis, especially when the primary site is unknown and the histological diagnosis is not conclusive.
