Monika F. Bayer

Hyperthyroxinemia in patients with acute psychiatric disorders

Thyroid function tests were measured in 645 patients admitted to an acute psychiatric disorders unit. Thirty-three percent had elevated serum thyroxine (T4), and 18 percent had an elevated free T4 index (FTI). Serum triiodothyronine (T3) was low, normal, or minimally elevated in 77 patients, with a high initial free T4 index. Twenty-two patients with an initial elevation of their free T4 index were serially followed (study group). Serum T4, free T4 index, and free T4 fell in every patient: serum T4 from 13.95 +/- 1.93 micrograms/dl (mean +/- standard deviation: SD) to 9.33 +/- 2.4 micrograms/dl (p less than 0.001); free T4 index, from 6.15 +/- 0.83 to 3.79 +/- 1.1 (p less than 0.001); free T4, from 2.43 +/- 0.65 mg/dl to 1.38 +/- 0.35 ng/dl (p less than 0.001). Serum T3 was initially normal or low, and then fell in 17 patients, and rose in five. Serial testing of thyrotropin-releasing hormone (TRH) demonstrated both flat and normal responses in patients with a variety of psychiatric diagnoses and at varying stages of thyroid disease activity.

Serum free thyroxine values in term, premature, and sick infants

Free thyroxine concentrations were determined by radioimmunoassay in 96 infants within an intensive care nursery and in 32 healthy term infants. Sera for free T4 levels were drawn simultaneously with the filter paper specimens for T4 obtained to screen these infants for congenital hypothyroidism. The mean free T4 level in 20 adults was 1.38 +/- 0.03 ng/dl (mean +/- SEM). The mean in the ICN infants was 3.48 +/- 0.18 ng/dl and in healthy term infants, 4.24 +/- 0.23 ng/dl. Like T4, free T4 correlated positively with increasing gestational age and birth weight, and was lower in infants with RDS. Although 66% of the ICN infants had T4 levels below the statistically selected screening level (fifth percentile), all of these infants had free T4 levels greater than 0.8 ng/dl. Two additional infants with untreated congenital hypothyroidism has free T4 levels of 0.3 and 0.4 ng/dl. The measurement of free T4 appears to be an accurate indicator of thyroid function in these infants.

Effective laboratory Evaluation of Thyroid Status

This article focuses on recent developments in thyroid-related laboratory tests, including analytical methods, clinical utility, and limitations of TSH, FT4, T4, FT3/T3, thyroglobulin, and thyroid autoantibodies and the effective use of these tests in the diagnosis of various forms of hypothyroidism or hyperthyroidism, and the management of patients undergoing T4 replacement, T4 suppression, or antithyroid drug therapy.

EFFECT OF HEPARIN ON SERUM FREE THYROXINE LINKED TO POST-HEPARIN LIPOLYTIC ACTIVITY

A possible association between free T4 (fT4) changes, occuring after heparin administration, and the post‐heparin lipolytic activity, i.e., the release of lipases and the lipolysis of triglycerides to non‐esterified fatty acids (NEFAs) was studied. In 19 patients heparin increased mean fT4 values obtained by equilibrium dialysis from 23·4 to 38·6 pmol/l (P<0·01) and mean fT4 values measured by GammaCoat two‐step RIA from 17·0 to 24·1 pmol/l (P < 0·01), the results of the two methods agreeing well (rS= 0·88). Concurrently, NEFAs increased from a mean of 0·55 to 2·20 mmol/l (P < 0·01) and fT4 increases were significantly correlated with post‐heparin NEFAs (rS= 0·69, P < 0·001). In vitro addition of palmitic acid to sera increased fT4 concentrations to values similar to those observed in vivo. Post‐heparin fT4 increases were also strongly correlated to the concentrations of triglycerides (rS= 0·63, P < 0·01). Hypertrig‐lyceridaemia was associated with pronounced fT4 increases after heparin administration, and normolipidaemia with moderate or no changes. These results suggest that the effect of heparin on fT4 is linked to the activation of lipases by heparin and is mediated by NEFAs, which, at high concentrations, compete with thyroxine for binding proteins.

Should a woman taking propylthiouracil breast-feed?

Thyroid function was tested in mother and her son. The mother was taking propylthiouracil for treatment of hyperthyroidism, and she was breast-feeding. Thyroid function was normal in both.

Free thyroxine by solid phase radioimmunoassay: improvement in the laboratory diagnosis of thyroid status in severely ill patients.

During severe systemic illness total thyroid hormone levels are often low, and measurement of total hormones often does not differentiate between euthyroid and hypothyroid patients. Therefore, we examined serum free thyroxine levels by radioimmunoassay (antibody-coated tubes, Clinical Assays) as an alternative diagnostic test in three groups of severely ill patients with subnormal triiodothyronine. Free thyroxine estimates agreed with the clinical impression and TSH in 91% of cases in group 1 (47 patients with no history or clinical evidence of thyroid disorder), in 96% of cases in group 2 (24 euthyroid patients with a previous history of thyroid disease, including some on thyroid replacement) and 90% of cases in group 3 (10 hypothyroid patients). By contrast, the free thyroxine index did so in only 53% (group 1), 46% (group 2) or 100% (group 3). Sequential studies showed little change in free thyroxine and TSH levels in euthyroid patients during illness and recovery, and a good negative correlation between free thyroxine and TSH in hypothyroid patients. Free thyroxine measurements (and TSH) discriminate between euthyroid and hypothyroid sick patients better than other thyroid function tests including the free thyroxine index, and can be employed routinely: a distinct advantage over free thyroxine measured by equilibrium dialysis.

Clinical Experience with a Sensitive Immunoradiometric Assay for Serum Thyrotropin (TSH): Diagnostic and Therapeutic Implications for Hyperthyroid and Thyroid Cancer Patients

A few patients with subtle signs or symptoms of mild hyperthyroidism, concurrent with consistently normal serum thyroid hormone levels, prompted us to adapt highly sensitive TSH measurements (1–4) to routine clinical use. TSH results in over 300 patients were found to be highly consistent with the clinical impressions and of value in several clinical situations. This account will focus on specific clinical applications, while a more complete report will be published separately (5).

IN VITRO EFFECTS OF HEPARIN ADMINISTRATION ON FREE THYROXINE CONCENTRATIONS

We have demonstrated previously that heparin produces an increase in serum free thyroxine (FT4) measured by 2 step radio-immunoassay or equilibrium dialysis in some patients. The mechanism by which heparin administration acts to increase serum concentrations of FT4 was investigated in 12 patients. Blood was collected from each patient before and after an intravenous dose of heparin. Each sample was divided into 2 portions. Paraoxon, an inhibitor of lipase activity, was added to 1 portion. FT4 and non-esterified fatty acids were analyzed. FT4 was 1.4±0.2 (Mean±SD) and 1.4±0.3 ng/dl in the samples before heparin administration with and without paraoxon, respectively. After heparin administration, FT4 was 1.8±0.7 ng/dl in the samples not containing paraoxon (p < 0.01) and 1.5±0.2 ng/dl in the samples containing paraoxon (NS). Non-esterlfied fatty acid concentrations increased 10 fold on the average after heparin administration in the samples without paraoxon (p < 0.01). In the samples containing paraoxon, there was no Increase in non-esterified fatty acid concentrations after heparin administration. There was significant correlation between FT4 and non-esterified fatty acid concentrations (r = 0.93, p <0.01) In serum after heparin administration which did not contain paraoxon. There was a significant correlation between plasma triglyceride concentrations and non-esterified fatty acid concentrations after heparin administration in the samples not containing paraoxon. The effect of heparin administration on non-esterified fatty acids occurs primarily in vitro after blood withdrawal by continued hydrolysis of plasma triglycerides. The resultant elevated non-esterified fatty acids in turn appear to displace thyroxine from its binding sites on plasma proteins. Caution should be exercised in the interpretation of FT4 after administration of heparin.