Ovarian function and the return of potential fertility in lactating women.

OBJECTIVE: Indices of ovarian function and potential fertility have been studied in fully lactating women from the sixth week post-partum to the start of the second menstrual period. PATIENTS: Thirty-four women entered the study and 17 (50%) continued until the first menses. Of these, 16 continued until the second menses. The median time from delivery to day 1 of the first menses was 202 days (range, 85 to 668 days). METHODS: The concentrations of estrone glucuronide (EG) and pregnanediol glucuronide in daily samples of early morning urine were measured by time-resolved fluoroimmunoassay and LH by an immunoradiometric assay. Algorithms were used retrospectively to determine the rise and peak days of all three metabolites. RESULTS: Three cycles were studied relative to day 1 of first menses: (1) premenstrual (days -60 to -31), (2) menstrual (days -30 to -1), and (3) postmenstrual (days 1 to 56). Follicular development occurred in 53%, 100% and 100% of the dated cycles respectively. A peak of LH occurred in 6%, 75% and 80% of cycles, respectively. A period of potential fertility occurred in 11/17 (65%) and 13/16 (81%) of cycles (2) and (3), respectively. The proportion of potentially fertile cycles was higher after the first menses, and after 6 months had elapsed postpartum. CONCLUSION: A test based on the measurement of EG and used prospectively predicted 13/15 (85%) of the periods of potential fertility during the postmenstrual cycle.

Critical assessment of the Amerlite free T4 assay.

The measurement of serum free T4 (FT4) by analogue methods has been severely criticised because the T4 analogue binds to albumin. Amersham have recently introduced a method utilising horseradish peroxidase-labelled-T4 (HRP-T4) designed to overcome this problem and have incorporated it into the Amerlite enhanced luminescence immunoassay system. We have critically evaluated this method for its analytical and clinical validity. Experiments in which anti-albumin was added to normal serum suggested that the HRP-T4 label did not bind to endogenous albumin while the addition of albumin caused no significant change in FT4 concentration. Adding oleic acid up to 5 mmol/L to simulate increased non-esterified fatty acid concentration did not increase the apparent FT4. Serum sampled from subjects independently allocated to clinical groups were compared with an euthyroid group. The untreated hyperthyroid group values were distinctly elevated while the untreated hypothyroid group were appropriately low. Oestrogen therapy, low TBG, familial dysalbuminaemic hyperthyroxinaemia and non-thyroidal illness groups all reflected their euthyroid status, as did pregnancy samples which also showed a tendency to lower values in late pregnancy, consistent with previous observations. In conclusion, the Amerlite FT4 method appears to overcome some of the problems associated with analogue methods. A small survey showed it to be diagnostically valid in a wide variety of clinical states.

Do nonesterified fatty acids displace thyroxin from its plasma binding sites in severe nonthyroidal illnesses?

Severe nonthyroidal illnesses have been associated with increases in nonesterified fatty acids (NEFA) and the dialyzable fraction of thyroxin (T4) in plasma. We have further investigated their possible relationship in severe nonthyroidal illnesses as well as in induced in vivo and in vitro situations involving increased NEFA. We demonstrate that there is no relationship between NEFA and the dialyzable fraction of T4, either in severe nonthyroidal illnesses or in the other situations, unless plasma NEFA concentrations exceed 5 mmol/L in normal persons or 1.7 mmol/L in nonthyroidal illnesses, and that this concentration was not reached in the patients we studied, with one exception. We conclude that NEFA are unlikely to contribute to an inhibition of the binding of T4 to the binding proteins that might be present in plasma of patients with severe nonthyroidal illnesses unless their NEFA concentrations are very high.

A rat model of the 131I-induced changes in thyroid function.

Thyrotoxic patients treated with Iodine-131 (131I) often present with low thyroxine (T4), normal triiodothyronine (T3) and raised thyrotropin (TSH) concentrations in serum. We have developed a rat model of this low T4, raised TSH state. Rats were injected with 50, 150 or 450 mu Ci 131I. A dose of 50 mu Ci 131I caused no significant effect on thyroid function, as assessed by serum parameters whereas both 150 mu Ci and 450 mu Ci 131I caused a significant fall in serum T4 concentration accompanied by a significant rise in TSH concentration. In all groups serum T3 concentration was not significantly altered when compared to controls. The clearance of 131I from the rats showed a single exponential curve (t 1/2 3.38 +/- 0.61 days) over the range of 131I doses used. Differing body weights had no effect on the serum T4 changes induced by 131I.

Slow thyroxine binding globulin in the pathogenesis of increased dialysable fraction of thyroxine in nonthyroidal illnesses.

The expected decreases of serum total T4, total T3, T4 binding prealbumin, and T4 binding globulin (TBG) concentrations were found in a selected series of patients with nonthyroidal illnesses (NTI). An increase in percent dialysable fraction of T4 was also found. Although serum TBG concentrations were decreased, the proportion of a slow moving form of TBG, designated slow TBG (STBG) was increased, the absolute concentration being not significantly different from that measured in controls. Thus the observed decrease in TBG in NTI occurs in the normal TBG fraction which binds T4 much more avidly than does STBG. It is suggested that the increase in the proportion of STBG, due to a decrease in normal TBG, has an important role in the pathogenesis of the increase in percent dialysable fraction of T4 in serum from patients with NTI.

Evaluation of a new free-thyroxin assay.

The Amerlex Free Thyroxin (T4) Radioimmunoassay Kit (Amersham International Ltd.) is a new direct equilibrium radioimmunoassay for free T4 based on an antiserum with very high affinity for T4, and a unique 125I-labeled T4 analog as tracer. It is a very simple single-tube radioimmunoassay, making use of Amerlex particles to separate antibody-bound from free species. Interassay precision (CV) is 3.7% at 13 pmol/L and 2.3% at 30 pmol/L; within-assay precision is 4.2% at 21 pmol/L. The reference interval is 11-22 pmol/L. The assay did not misclassify any patients tested who had untreated myxedema or untreated thyrotoxicosis. The free T4 assay excelled both the free T4 index and the T4/T4-binding globulin ratio in correcting for increased thyroxin-binding globulin from pregnancy, and it was better than the index but not better than the ratio in correcting for increased thyroxin-binding globulin in users of oral contraceptives.