Low Free Thyroxine Index Research Articles

Perinatal Consequences of Maternal Hypothyroidism in Early Pregnancy and Inadequate Replacement

Summary Maternal hypothyroidism may be associated with a variety of pregnancy complications. OBJECTIVE We have evaluated the perinatal consequences of maternal hypothyroidism in early and late gestation. DESIGN Retrospective study of pregnant women, with quasi-experimental design comparing different subjects. SUBJECTS Forty-three pregnancies In 42 women with hypothyroidism - either biochemically hypothyroid or with a history of hypothyroidism on adequate replacement - and no other preexisting medical conditions. MEASUREMENT Free thyroxine index (FTI), TSH, and haematocrit at Initial antepartum presentation and near term gestation. Pregnancy outcome variables Including: rate of Caesarean section performed for fetal distress in labour, neonatal weight percentile, and gestational age at birth. RESULTS Of 42 hypothyroid pregnancies, six were complicated by fetal distress In labour leading to Caesarean section. Five of these six were severely hypothyroid (defined as FTI ≤ 0.6 (normal range 1.1–4.4)) on initial antepartum presentation. In contrast, of the 36 pregnancies without fetal distress, only four initially presented severely hypothyroid (P<0.001). Conversely, 56% (5/9) of pregnancies which Initially presented severely hypothyroid were subsequently complicated by Caesarean section for fetal distress in labour. This compared to 3% (1/33) among those who presented either mildly hypothyroid or euthyroid on replacement (P<0.0001). Fetal distress correlated with low FTI (P<0.001) and high TSH at Initial presentation. However, It was independent of FTI near term. A relation between fetal distress and TSH near term did not reach statistical significance. Fetal distress also correlated with low maternal haematocrit on admission to labour and delivery (P<0.05), but was Independent of haematocrit and gestational age at Initial presentation, neonatal weight percentile, and gestational age at birth. CONCLUSIONS Severe maternal hypothyroidism early in gestation Is strongly associated with fetal distress in labour. This suggests that (1) Inadequate maternal replacement leads to fetal distress and (2) maternal thyroid status in early gestation may exert Irreversible effects on the fetus, the placenta, and/or on subsequent maternal adaptations to pregnancy. Early adequate replacement therapy Is especially prudent in pregnant women presenting with severe hypothyroidism.

Attention-deficit hyperactivity disorder and thyroid function

Attention-deficit hyperactivity disorder (ADHD) is thought to have a biologic basis, but the precise cause is unknown. It is one of the neurodevelopmental abnormalities frequently observed in children with generalized resistance to thyroid hormone (GRTH), suggesting that thyroid abnormalities may be related to ADHD. We report a prospective screening study for thyroid abnormalities in 277 children with ADHD by measurement of serum levels of total thyroxine, free thyroxine index, and thyrotropin. Fourteen children with ADHD had thyroid function test abnormalities: six had a normal free thyroxine index and elevated thyroxine level (group 1); three had a high free thyroxine index and a normal thyrotropin level (group 2); and five had a low free thyroxine index with a normal thyrotropin level (group 3). GRTH could not be demonstrated in a detailed study of four of the subjects in whom it was suspected (groups 1 and 2). Although the prevalence of ADHD in subjects with GRTH has been reported to be 46%, the overall prevalence of GRTH must be less than 1:2500 because we failed to detect GRTH in the 277 children with ADHD studied. We conclude that the prevalence of thyroid abnormalities is higher (5.4%) in children with ADHD than in the normal population (< 1%).

Admission screening by thyroid function tests in an acute general care teaching hospital

To determine the incidence of unrecognized thyroid disease among admissions to a large acute care university teaching hospital, 364 samples taken on consecutive admissions were assayed for thyroid-stimulating hormone (TSH) and free thyroxine index (FTI). Patients with abnormal test results were further evaluated by determination of antimicrosomal and antithyroglobulin antibodies, and charts were reviewed for evidence of prior diagnosis of thyroid disease, especially severe illness, drug treatment that might affect thyroid function tests, and prior diagnosis of thyroid disease. Results of subsequent thyroid function tests performed during the patient's hospitalization were correlated with the admission serum assays, and data on subsequent testing during the following 6 months were also obtained.A total of 3.9% of patients had significantly depressed TSH, and 11.1% of values were significantly elevated. A total of 11.3% of patients had significantly low FTI values, and 1% had significantly elevated values. A total of 7.4% appeared to have the euthyroid sick syndrome, 5.8% appeared to have unrecognized or undertreated primary thyroid failure, 6% had apparent subclinical hypothyroidism, 2% were thyrotoxic, and 2.8% (all women) had suppressed TSH levels for inapparent reasons. Limiting testing to patients over 49 years of age, or to women, would have missed many individuals with abnormal test results. Considering widespread availability of tests, relative costs, and value of the information obtained, it is suggested that the FTI determination would provide an appropriate screening test for patients in a population such as this entering a large, acute care general hospital.

Thyroid function in very preterm infants

Indices of thyroid function were measured in 108 infants born at 23–31 weeks gestation, after birth, at 24 and 72 h, and at 1, 3, 4, 5 and 6 weeks of age. This group was characterised by low serum thyroxine (T4), normal thyroid stimulating hormone (TSH), low-normal thyroid binding globulin (TBG), low free thyroxine index (FTI) and low triiodothyronine (T3). The incidence of hypothyroxinaemia defined as a serum T4 value of less than 65 nmol/1 was 58% after birth, increasing to 84% at 1 week, after which there was progressive reduction to 36% by 6 weeks of age. Mean T4 values were inversely proportional to gestational age during this study period. Infants of 23–28 weeks gestation had significantly lower T4, TBG, FTI and T3 values compared to those of 29–31 weeks gestation. Infants who had hyaline membrane disease (HMD) had significantly lower T4 and FTI values compared to those without HMD for up to 3 weeks of age. Similar differences were found between deaths and survivors in the first week after birth. This study suggests that there is increasing delay in maturation of the hypothalamic-pituitary-thyroid axis control with increasing prematurity. In addition, the data suggest that infants who were extremely preterm or those with HMD had worse and more persistent abnormalities of thyroid function secondary to their illness and metabolic stress. The significance of our findings, in particular that of prolonged hypothyroxinaemia, is uncertain. The role of thyroid replacement therapy in these very preterm infants therefore need to be assessed with a randomised clinical trial.

Endocrine disorders in men infected with human immunodeficiency virus

Gonadal, adrenal, and thyroid functions were evaluated in 70 men seropositive for human immunodeficiency virus (HIV) infection, clinically categorized as asymptomatic (n = 19), AIDS-related complex (ARC) (n = 9), or acquired immunodeficiency syndrome (AIDS) (n = 42). Twenty of 40 men (50 percent) with AIDS were hypogonadal. Mean serum testosterone concentrations in both ARC (292 ± 70 ng/dl) and AIDS (401 ± 30 ng/dl) men were significantly less than in asymptomatic (567 ± 49 ng/dl) or normal men (608 ± 121 ng/dl). Of these hypogonadal men, 18 of 24 (75 percent) had hypogonadotropic hypogonadism. Seven of eight hypogonadal men (88 percent) had a normal gonadotropin response to gonadotropin-releasing hormone administration. Hypogonadism correlated with lymphocyte depletion and weight loss. Adrenal cortisol reserve, evaluated by adrenocorticotropin stimulation, was normal in 36 of 39 patients (92 percent) with AIDS. Indices of thyroid function were normal with the exception of one ARC man with a low free thyroxine index. In conclusion, hypogonadism is common in men with HIV infection and may be the first or most sensitive endocrine abnormality.

Serum Angiotensin-Converting Enzyme in Severe Nonthyroidal Illnesses Associated with Low Serum Thyroxine Concentration

We evaluated serum angiotensin-converting enzyme levels as an index of thyroid hormone action in severe systemic illness. Angiotensin-converting enzyme was elevated in hyperthyroid patients (37.3 +/- 3.2 U/mL, p less than 0.01) and depressed in hypothyroid patients (17.9 +/- 1.4 U/mL, p less than 0.05). Compared with normal controls (22.6 +/- 1.6 U/mL), patients in an intensive care unit with free thyroxine index greater than 5.0 had normal angiotensin-converting enzyme levels (19.1 +/- 2.5 U/mL), but patients with a free thyroxine index less than 5.0 had angiotensin-converting enzyme levels significantly lower than the normal and hypothyroid groups (10.7 +/- 1.0 U/mL, p less than 0.05). A group of patients in an intensive care unit with alcoholic liver disease (known to elevate angiotensin-converting enzyme) and a low free thyroxine index had depressed angiotensin-converting enzyme levels (16.9 +/- 1.5 U/mL, p less than 0.01). A strong correlation was seen in the combined groups of all patients studied between levels of angiotensin-converting enzyme and a free thyroxine index (r = 0.70, p less than 0.01) and free T3 index (r = 0.72, p less than 0.01).

FREQUENCY OF EUTHYROID SICK SYNDROME AS ASSESSED BY FREE THYROXINE INDEX AND A DIRECT FREE THYROXINE ASSAY A Limitation of FT4 Assays

The frequency of the euthyroid sick syndrome (ESS) was assessed in 3444 hospital patients. For the first 6 months the free thyroxine index (FTI) was used: 3·6% of 1674 patients had ESS compared with 17·3% of 1770 in the second 6 months diagnosed by a direct free thyroxine (FT4) assay ('Amerlex'). The relative frequencies of each type of ESS (low triiodothyronine [T3] only, low T3 plus low FT4 or FTI, and high FT4 or FTI with normal or low T3) and the frequencies of hypothyroidism (high TSH) and hyperthyroidism (high FTI/FT4 and T3) were similar in both periods. In the FT4 period requests for T3 assays increased by 300%. Measurements of both FT4 and in 46 patients with ESS confirmed that ESS is diagnosed more frequently with the FT4 assay: the distribution of normal and abnormal T3 and reverse T3 levels were similar in FT4 ESS and FTI ESS. FT4 is labile in illness and thus direct FT4 measurements also fluctuate, not necessarily reflecting thyroid status.

Endocrinology and metabolism: an annotated bibliography of recent literature. References to journal articles and other papers.

Endocrinology and metabolism: an annotated bibliography of recent literature. References to journal articles and other papers.

Serum thyroid hormone abnormalities in psychiatric disease

Psychiatric illness is a cause of “euthyroid sick syndrome” (ESS), defined as abnormal concentrations of circulating iodothyronines in euthyroid subjects with nonthyroidal illness (NTI). We describe a prospective study of 150 consecutive psychiatric admissions studied by endocrine and psychologic techniques. Based on 150 admission blood samples, we found a 7% incidence of ESS and with serial samples (74 patients) the incidence was 27%, demonstrating that ESS can develop after hospital admission. Of the 20 patients with ESS, 11 had elevation of both serum total T4 concentrations (T4) and free thyroxine index (FTI) while their serum total T3 concentrations (T3) remained normal; 5 had elevation of FTI without elevation of T4 or T3; and 4 had low T4 and low FTI and normal TSH. In 2 of the 4 patients in the last category, the T3 was also low. The free T3 index (FT3I) was normal in all but 1 patient who had low FT3I and FTI, low T4 and T3, and normal TSH. The serum thyroid hormone abnormalities were transient in the ESS patients during the 10 day period with 2 exceptions; 1 patient had persistently elevated T4 and FTI with normal T3 and FT3I values while another patient had persistently depressed T4 and FTI without abnormality of FT3I or TSH. Multivariate statistical analysis demonstrated a difference ( P < .06) in the psychologic attributes of somatic and autonomic symptoms in ESS patients compared to controls. We conclude that ESS is as common amongst psychiatric admissions as in general hospital patients previously studied and that blood thyroid function tests should be interpreted cautiously in all hospitalized patients.

Misleadingly Low Free Thyroxine Index and Usefulness of Reverse Triiodothyronine Measurement in Nonthyroidal Illnesses

Nonthyroidal illness is frequently associated with subnormal serum thyroxine (T4) and free T4 index. To unravel the resultant diagnostic problems, we have studied several variables of thyroid function in the sera of 47 patients hospitalized with nonthyroidal illnesses and seven hypothyroid patients encountered during the same period. Of the 47 euthyroid sick patients, 18 had low T4. Among these 18, free T4 index was normal in only five, whereas free T4 concentration measured by equilibrium dialysis was normal or high in 15 and 3,3',5'-triiodothyronine (reverse T3) normal or high in all 18. Reverse T3, free T4 concentration, and free T4 index were subnormal in all seven hypothyroid patients. Thus, measurement of free T4 index may be misleading in evaluation of thyroid function in patients with nonthyroidal illnesses, whereas measurement of serum concentration of reverse T3 and free T4 is quite discriminating.

Hypothalamic endocrine dysfunction in anorexia nervosa.

ABSTRACT The hypothalamic-pituitary function of 21 women with anorexia nervosa, aged 15–34 years, was studied. The tests included, in addition to the usual tests of thyroid function, a TRH stimulation test with 200 μg of synthetic TRH given iv; the response of serum immunoreactive growth hormone to insulin; and the diurnal variation and response of plasma cortisol to insulin hypoglycaemia. The mean serum TSH level of the patients was higher than that of healthy controls. The mean maximal increment of TSH after TRH was similar in the patients and the controls. However, 18 of the patients but none of the controls showed a delayed TSH-response to TRH, i. e. the TSH-level at 60 min was higher than that recorded 20 min after TRH. Four of the patients had a low free thyroxine index, computed from the PBI and T3 Sephadex uptake values, and 3 of these were clinically hypothyroid. The means for PBI, T4 and the free thyroxine index were all significantly below the means for the controls. The basal serum growth hormone levels were increased in 9 out of 17 patients. In 4 of these an inadequate response to insulin or to glucagon was found. In 5 out of the 8 patients with normal basal growth hormone levels a normal response was found, whereas the remaining 3 showed a subnormal response. The serum growth hormone level was correlated with the degree of weight loss but not with the serum albumin concentration. Plasma cortisol at 08.00 was increased in 9 patients and the diurnal variation was inadequate in 6. Four patients showed a subnormal response to insulin-induced hypoglycaemia, and 2 out of 5 patients tested failed to show adequate suppression of plasma cortisol after 1 mg of dexamethasone. Dysfunction of the hypothalamic-pituitary axis is common in anorexia nervosa. A delayed TSH-response to TRH, compatible with hypothalamic dysfunction, seems to be an almost consistent feature of the disorder, and in some of the patients even clinical hypothalamic hypothyroidism may be evident.

Thyroid function in adults with Down's syndrome.

The thyroid status of 82 institutionalized adults with Down's syndrome has been assessed. Compared to age and sex matched control subjects, these patients had significantly lower mean total serum thyroxine (T4) and triiodothyronine (T3) concentrations (T4; 69.1+/-22.2 nmol/1; (mean+/-SD) vs. 100.1+/-19.1, P less than 0.001; T13; 1.61+/-0.47 nmol/1 vs. 1.76+/-0.34, P less than 0.025), lower free thyroxine index (FTI), (FTI; 66.1+/-22.4 vs. 95.1+/-20.2, P less than 0.001), and higher basal serum thyrotrophin (TSH) concentrations (TSH; 7.6+/-10.7 mU/1 vs. 3.8+/-1.5, P less than 0.001). These changes were not related to age or sex. Abnormalities in one or more test of thyroid function were demonstrated in at least 38 (46%) of the 82 patients. Two main patterns of abnormality were defined: 1) subnormal T4, FTI and elevated basal TSH levels (primary hypothyroidism) in 13 (16%). All seven of the 13 patients in whom TRH tests were performed showed the expected exaggerated TSH response, and seven out of the 13 patients (54%) had positive thyroid antibodies, 2) Subnormal T4, subnormal or low normal FTI, and basal TSH levels within the normal range in 18 (22%). The mean basal TSH concentration was, however, significantly higher than in patients with normal T4 and FTI levels, suggesting a minor degree of thyroid failure. Only two of the 18 patients (11%) had positive thyroid antibodies. Of the 17 patients in the group tested, 13 showed a normal TSH response to TRH, three an exagerrated response (all females), and one had an impaired response. Other patterns of abnormal thyroid function were observed occasionally: one female patient had biochemical T3 toxicosis; another had the biochemical pattern of subclinical hypothyroidism, four patients with normal basal T4, FTI and TSH levels showed an exaggerated TSH response to TRH and one patient had an impaired response. These data indicate that htyroid dysfunction, in particular hypothyroidism, is common in adults with Down's syndrome, though specific tests are usually required to make the diagnosis. The general reduction in thyroid function in Down's syndrome may be due to impaired development of the thyroid gland. However, frank chemical hypothyroidism may occur only when thyroiditis is superimposed on preexisting diminished thyroid reserve.