A longitudinal study of serum TSH, and total and free iodothyronines during normal pregnancy

Abstract

Serum T4, T3, rT3, free T4, free T3 and TSH were measured during and after normal pregnancy in 20 women. Special methodological precautions were taken to avoid interference of other hormones and protein alterations in the assays. Serum T4 and T3 were steadily increasing during the last part of the 1st trimester, and remained high and nearly stable during the 2nd and 3rd trimester of the gestation period. The high levels were approximately 1.5 times the values measured 10 weeks post-partum. Serum rT3 was elevated already during the last part of the 1st trimester and remained high throughout pregnancy, compared to the post-partum value. Serum free T4 and free T3 were slightly elevated in early pregnancy. The values decreased gradually during pregnancy and were slightly depressed during the 3rd trimester. A gradual increase in serum TSH was observed during pregnancy and the 2nd and 3rd trimester values were significantly higher than the post-partum value.The mean values for serum TSH, free T4 and free T3 remained always well within the normal range. Thus small variations in serum free iodothyronines and TSH occur during normal pregnancy, the alterations observed in the last trimester of the gestation period resembling those of a slight thyroid insufficiency. These trends in variation of the reference values are worth to remember in the diagnosis of borderline hypo-or hyperthyroidism and in the balanced treatment of pregnant women with thyroid dysfunction.High levels of thyroid hormones in serum due to increased cirulating TBG is a well known feature during normal pregnancy. Various measures of free thyroid hormones have been introduced in order to aid the diagnosis and control of thyroid dysfunction during pregnancy. Earlier investiga¬ tors have claimed that the amounts of free circulat¬ ing hormones are little affected by pregnancy (Burrow et al. 1975;Pekonen & Lamberg 1978;Ekins 1979). Further, serum TSH has been found nearly unaltered too (Burrow et al. 1975;Pekonen & Lamberg 1978).However, due to high serum levels of hCG, FSH and LH possibly interfering in the TSH assay and methodological difficulties in measuring free T4 and free T3 it is still not firmly established whether minor variations in free hormones and TSH occur during normal pregnancy. It is generally accepted that it is important to keep thyroid function near to normality during pregnancy in patients treated for thyroid disease; it is therefore important to know the normal variations. In the present study we have obtained repeated blood samples from normal women during and after pregnancy and taken special methodological precautions to avoid inter¬ ference of other hormones and protein alterations in the assays. Materials and MethodsTwenty healthy pregnant women were asked to partici¬ pate in the investigation at their first visit to their general practitioner for pregnancy control. They constituted a consequtive series of healthy pregnant women contacting a suburb clinic with 4 general practitioners. Excluded were pregnant women who paid their firs...

ENDOCRINOLOGY IN PREGNANCY: Pregnancy and the incidence, diagnosing and therapy of Graves’ disease

“…The high DIO3 activity leads to a high concentration of the inactive T 4 metabolite reverse T 3 in maternal blood from very early pregnancy (25,26). As judged from experiments performed in perfused human placenta lobes, DIO3 activity is the cause for the rather low transfer of maternal T 4 and T 3 across the placenta.…”

“…2). In the second and especially in the third trimester of pregnancy, the concentrations of free thyroid hormones become lower than non-pregnancy values (25). Correct free T 4 (and free T 3 ) analytical results are obtained with methods that include an initial isolation of the free hormone by ultrafiltration or dialysis followed by direct measurement of hormone in filtrate/dialysate by mass spectrometry (or sensitive radioimmunoassay).…”

“…TBG is the major thyroid hormone binding protein, and in a closed system, an increase in hormone binding will be associated with a decrease in free hormone concentration (Table 1). A gradual doubling in TBG concentration in serum takes place over pregnancy weeks 7-16 (41, 42), and this leads to a 50% increase in the concentrations of total T 4 and T 3 , with a corresponding increase in upper and lower reference ranges for these hormones (25). Thus, as a practical guide, reference limits for total T 4 and total T 3 increase with 5% of non-pregnancy values per week during the 10 pregnancy weeks 7-16, and remain 50% above non-pregnancy values during the remaining pregnancy.…”

Management of subclinical hypothyroidism in pregnancy: are we too simplistic?

“…Placental production of human chorionic gonadotrophin (hCG) and a rise in oestrogen production that increases binding proteins, namely thyroxinebinding globulin affect free TH levels. TSH dips according to most but not all studies within the first trimester, whereas free TH concentrations decrease, albeit very slightly, mainly during the latter part of pregnancy (10,11,14,15,16,17,18,19). These observed alterations are not only due to pathophysiological changes but are, at least in part, due to methodological issues.…”

“…The depth, rate and timing of the first-trimester dip in TSH scatter widely between studies and with marked interindividual variability within studies (10,14,15,17,18,19). Methodological differences amongst TSH assay platforms may explain some of the variation.…”