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PubMed1986

Discriminative ability of tests for free and total thyroid hormones in diagnosing thyroid disease.

We assessed the sensitivity, specificity, predictive value of a positive result, and efficiency of tests for total thyroxin, free thyroxin index, free thyroxin, total triiodothyronine, free triiodothyronine index, and free triiodothyronine in serum from 1619 consecutive new patients with suspected thyroid dysfunction. Multivariate discriminant analysis was also used. Free thyroxin index and free thyroxin were clearly the most sensitive indicators of hypothyroidism. In contrast, all of these tests identified hyperthyroidism with similar efficiencies. By stepwise discriminant analysis, the free thyroxin index was the most efficient test for distinguishing between euthyroidism and hyperthyroidism and between euthyroidism and hypothyroidism. The combination of tests for total thyroxin, free thyroxin index, triiodothyronine, and free triiodothyronine was optimal for separating euthyroidism, hyperthyroidism, and hypothyroidism. We conclude that the free thyroxin index, despite the introduction of newer technologies, is still the best thyroid hormone test for screening for thyroid disease.

Adult↗
PubMed2001

Lithium toxicity: an iatrogenic problem in susceptible individuals.

OBJECTIVE: Lithium toxicity, manifesting primarily as neurotoxicity, is a significant health problem and is primarily iatrogenic in nature. Despite 50 years of medical experience with lithium, factors contributing to the development of severe neurotoxicity remain poorly documented. We hypothesized that severe neurotoxicity represents the most clinically significant manifestation of lithium toxicity. We proposed that this occurs primarily in the context of chronic therapeutic administration ('chronic poisoning'), rather than in the context of an overdose. Furthermore we hypothesized that patients who developed chronic poisoning did so in the presence of identifiable factors which predictably impair lithium clearance. METHOD: A retrospective analysis of 97 cases of lithium poisoning, treated at a regional centre over a 13-year period was performed. Demographic data and factors considered likely to relate to the risk of developing lithium toxicity were recorded. Patients were classified according to mode of poisoning (acute, acute on chronic, or chronic) and according to severity of neurotoxicity (nil, mild, moderate, severe). The risk of developing severe neurotoxicity as a result of each mode of poisoning was assessed. The association between various risk factors and the development of chronic poisoning was assessed using a logistic regression model. RESULTS: Twenty-eight cases were rated as suffering severe neurotoxicity; in 26 this developed in the context of chronic poisoning and in two in the context of acute on chronic poisoning. All patients who developed severe neurotoxicity had at least one putative risk factor present, regardless of mode of poisoning. Length of stay was significantly longer for cases with severe neurotoxicity compared to those without severe neurotoxicity (12 vs. 2 days, P < 0.001). Peak serum lithium concentrations were significantly higher in cases with severe neurotoxicity compared to those without (2.3 vs. 1.6 mmol/L, P = 0.02). Patients presenting with chronic poisoning had a substantially higher risk of severe neurotoxicity than those presenting after an overdose of lithium (Odds Ratio [OR] 136, 95% CI 23-1300). A logistic regression model showed three factors contributed independently to the risk of chronic poisoning. These were: nephrogenic diabetes insipidus (adjusted OR 26.96, 95% CI 2.89-251.94), age over 50 years (adjusted OR 6.20, 95% CI 1.36-28.32) and thyroid dysfunction (adjusted OR 9.30, 95% CI 1.36-63.66). A fourth factor, baseline endogenous creatinine clearance below normal limits, was significant at the P = 0.05 level (adjusted OR 6.49, 95% CI 0.98-43.01). Hyperparathyroidism was noted in three cases of chronic poisoning suffering severe neurotoxicity. CONCLUSION: Severe lithium neurotoxicity occurs almost exclusively in the context of chronic therapeutic administration of lithium, and rarely results from acute ingestion of lithium, even in patients currently taking lithium. As such it is an iatrogenic illness, occurring in patients who have identifiable clinical risk factors: nephrogenic diabetes insipidus, older age, abnormal thyroid function and impaired renal function. Although administration of drugs which impair lithium clearance appeared to contribute minimally to chronic lithium poisoning in the absence of other factors, these drugs may well 'uncover' the predisposing risk factors and certainly should not be considered safe to use as a consequence of this study. The serious morbidity suffered by lithium toxic patients, and the cost to society due to long hospital stays, might be reduced by careful prescribing, vigilant monitoring and awareness of these factors, as they develop in otherwise stable patients. Review of existing therapeutic guidelines may be warranted.

Aged↗
PubMed1986

Increased erythrocyte catalase activity in patients with hyperthyroidism.

Levels of human erythrocyte catalase activity were determined in 38 patients with thyroidal dysfunction. In patients with hyperthyroidism, erythrocyte catalase activities were found to be higher than the levels of normal subjects (P less than 0.001). In hypothyroidism, erythrocyte catalase activities were of the same order as those of normal subjects. Significantly high positive correlation was found between erythrocytes catalase activity and the levels of thyroxine (r = 0.5794, n = 36, P less than 0.001), and slight positive correlation was detected between catalase activity and the levels of triiodothyronine (r = 0.3978, n = 33, P less than 0.05). A decreased erythrocyte catalase activity was observed when erythrocytes lysate was incubated with thyroid hormones. It was suggested that erythrocyte catalase activity had close relationship with thyroid state, however, direct effect of thyroid hormones were not observed on erythrocyte catalase assay system in vitro.

Adult↗
PubMed1984

Clinical experience with a human thyroid cell bioassay for thyroid-stimulating immunoglobulin.

A sensitive, specific, and practical bioassay for thyroid-stimulating immunoglobulin (TSI) is now available for clinical use. Fifty-seven of 61 patients with untreated hyperthyroid Graves' disease were TSI positive (sensitivity, 93%). TSI was undetectable in all normal subjects and in patients with Hashimoto's thyroiditis (without concurrent Graves' ophthalmopathy), nontoxic goiter, and toxic nodular goiter (specificity, 100%). The prevalence of TSI in serum declined after therapy, particularly during methimazole or propylthiouracil treatment. TSI correlated well with relapse or remission after antithyroid drug therapy. All 12 patients who were TSI negative at the time of discontinuing antithyroid drug therapy remained in remission (average follow-up of 10 months). TSI values in Graves' disease correlated better with thyroid dysfunction than with ophthalmopathy. Prenatal TSI activity tended to be higher in mothers of infants who developed neonatal Graves' disease than in at-risk mothers who delivered normal infants. However, there was considerable overlap between the two groups.

Biological Assay↗
PubMed1975

Thyroid function levels and thyrotropin responses to TRH administration in manic patients receiving lithium carbonate.

To determine the pituitary-thyroid dysfunction in the manic patients receiving lithium carbonate, determination of thyroxine concentration, T3 Resin Uptake, thyrotropin concentration in plasma, and thyrotropin responses to administration of TRH, 500 mug i.v., were made. Eight manic patients were examined before and after lithium treatment, 600-1,200 mg daily, for four weeks. Slight reduction in the plasma levels of thyroxine, and slight increase in the plasma thyrotropin levels were seen following lithium treatment. Significantly enhanced thyrotropin responses to TRH administration were found as compared to the results before lithium treatment. It is assumed that lithium salts decrease both output of thyroid hormones and the sensitivity of the thyroid gland to thyrotropin, and that this action of lithium inhibiting the thyroid gland might be related to its anti-manic effect.

Adult↗
PubMed1979

Tables to estimate total binding capacity of thyroxine-binding globulin from the in vitro thyroid function tests.

Equations for an estimate of the total binding capacity of serum thyroxine-binding globulin (TBG-TC) were developed relating this parameter to serum thyroxine concentration (T4) and in vitro uptake (T3U). This extimate demonstrated a highly significant, positive correlation with TBG-TC as measured by electrophoresis in ten normal subjectdividuals with altered TBG-TC but without thyroid dysfunction (ten normal pregnant women, ten healthy women receiving anovulatories, ten nephrotics, and ten patients with severe malnutrition). True-positive (sensitivity) and true-negative (specificity) ratios were calculated for total and free T4 in serum, T3U, Free T4 Index, and both measured and calculated TBG-TC. False-positive results for free T4 index (12%) were due to altered TBG-TC. In such cases, 93% were recognized by the calculated TBG-TC from the calues of the invitro tests. It is concluded that this estimates should be added to the in vitro thyroid tests for their proper interpretation in cases where altered TBG-TC could be misleading. This estimate applies only to the particular in vitro testing system used herein.

Anovulation↗
PubMed2002

[Hypothyroidism related to excess iodine].

WOLFF-CHAIKOFF'S EFFECT: The thyroid gland has a capacity to reduce thyroid hormone production in the presence of excess iodine by reducing the organification of the iodine. This Wolff-Chaikoff effect is observed after 48 hours and protects the organism from excessive synthesis of the thyroid hormones. This effect is usually temporary and within a few days thyroid hormone synthesis returns to normal through the so-called 'escape' phenomenon. However in a few normal individuals and in some susceptible patients, the escape does not occur. THE CONTEXT OF OCCURRENCE: Iodine-induced hypothyroidism is observed in fetuses, newborn, adults and in the elderly. It is observed in individuals without underlying overt thyroid disorder, and specially in patients with autoimmune thyroiditis or those previously treated for thyroid diseases (Graves' disease, subacute or pospartum thyroiditis, iatrogenic thyroid dysfunction...). FROM A CLINICAL AND PROGRESSIVE POINT OF VIEW: The hormone deficiency is of obvious clinical expression, or sometimes discreet and revealed by hormone exploration. It is usually temporary, regressing with a few days or weeks after iodine withdrawal. Nevertheless, some patients require transient hormone replacement therapy.

Adaptation, Physiological↗
PubMed1995

Thyroid function in patients with mycetoma.

Thyroid function was assessed in seventy two patients with various types of mycetoma. There was no evidence of clinical or biochemical thyroid dysfunction in these patients. The symptoms encountered in some of the mycetoma patients mimic those of hypothyroidism should be attributed to other factors possibly mental depression and apathy.

Adolescent↗
PubMed2000

Plasma cholesteryl ester transfer protein activity is high in infants and is not affected by thyroid hormones.

We investigated the effects of thyroid dysfunction on cholesteryl ester transfer protein (CETP) by studying plasma CETP activity in hypothyroid infants before and after they were rendered euthyroid by L-thyroxine (LT4) replacement therapy. To exclude environmental factors possibly affecting plasma CETP activity, we selected hypothyroid infants to study plasma CETP activity. Plasma CETP activity was measured as the rate of radiolabeled cholesteryl ester transfer from high-density lipoprotein (HDL) to serum apolipoprotein B (apo B)-containing lipoproteins in plasma from 14 hypothyroid infants before and 2 months after LT4 replacement, 23 normal infants, and 61 normal adults. Relationships between CETP and thyroid hormones were examined separately in the 14 hypothyroid infants and 32 euthyroid infants, including the 14 above-described hypothyroid infants and an additional 18 treated hypothyroid infants. Serum levels of thyrotropin (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) were also determined on an autoanalyzer system in our hospital. In contrast to previous reports, we found no differences in plasma CETP activity between hypothyroid infants and age-matched normal infants. LT4 substitution did not cause any changes in plasma CETP activity after therapy. Plasma CETP activity showed no correlation with serum TSH, FT4, and FT3 levels. Both hypothyroid and normal infants were found to have significantly higher plasma CETP activity than normal adults. From these results, we conclude that in infants thyroid hormones do not affect plasma CETP activity, and normal infants have high plasma CETP activity, compared with normal adults.

Apolipoproteins B↗
PubMed1996

Thyroid abnormalities in children infected with human immunodeficiency virus.

OBJECTIVE: To study thyroid function in children infected with human immunodeficiency virus (HIV) and determine whether there are correlates of thyroid dysfunction with disease progression. STUDY DESIGN: Total and free thyroxine, triiodothyronine, reverse triiodothyronine, thyrotropin, and thyroxine binding globulin (TBG) were measured in 167 children with HIV infection (age, 1 to 19 years; mean, 9.15 years). SETTING: Pediatric Branch, National Cancer Institute. RESULTS: Free thyroxine was at or below the lower limit of normal (normal, 1.0 to 1.9 ng/dl) in 18% of the children; thyrotropin and TBG levels were above the normal range in 31% and 30%, respectively. There was an inverse correlation between CD4+ cell count and thyrotropin, and between CD4+ cell count and TBG. No correlation was found between thyroid function and other disease symptoms or medications. CONCLUSION: These findings indicate that thyroid abnormalities occur more frequently in children with HIV infection than was previously reported, have a different profile from the thyroid abnormalities associated with other chronic disease conditions, and correlate with disease progression.

Adolescent↗
PubMed1990

Radiation and hypothalamic-pituitary function.

In adults, hypopituitarism is a common consequence of external radiotherapy. The clinical manifestations may be subtle and develop insidiously many years after radiotherapy. Anterior pituitary deficiencies can therefore only be detected by regular testing, including dynamic tests of GH and ACTH reserve. Although the deficiencies most commonly develop in the order GH, gonadotrophins, ACTH then TSH, this sequence may not be predictable in an individual patient and comprehensive testing is therefore required. The tests should ideally be performed annually for at least 10 years after treatment or until deficiency has been detected and treated. It is not only the patients with pituitary disease who are at risk of developing hypopituitarism after radiotherapy. Any patient who receives a total dose of irradiation of 20 Gy or more to the hypothalamic-pituitary axis is at risk of hypopituitarism, although the threshold dose may be lower than this. This is particularly important in the long-term survivors of malignant disease in whom endocrine morbidity may be relatively common and in whom this can be easily treated, with consequent improvement in quality of life. Whilst patients who receive a high total dose of irradiation are at increased risk of developing multiple deficiencies, a higher fraction size also increases the risk of anterior pituitary failure. There is good evidence that the earliest damage to the hypothalamic-pituitary axis after external radiotherapy is at the level of the hypothalamus. However, patients who undergo pituitary ablation with interstitial radiotherapy or heavy particle beams are likely to sustain direct damage to the pituitary. In these patients, the sequence in which individual pituitary hormone deficiencies develop is generally the same as that observed with the hypothalamic damage after conventional external radiotherapy. The increasing use of radiotherapy as a means of treatment for malignant disease means that new groups of patients with potential for endocrine dysfunction are emerging. Whole body irradiation in the preparation for bone marrow transplant is one such treatment and although hypothalamic-pituitary damage appears to be confined to GH deficiency in children, longitudinal experience is limited to date, particularly in adults. The treatment of malignant disease in childhood is of particular importance in terms of the delayed endocrine sequelae. The hypothalamic-pituitary axis may not be the only endocrine tissue damaged by treatment in these patients and management is therefore more complicated. In the growing child, the potential association of growth hormone deficiency, gonadal failure or premature puberty and thyroid dysfunction mean that expert endocrine supervision is essential for optimum long-term outcome.

Dose-Response Relationship, Radiation↗
PubMed1999

Evaluation of thyroid function in lithium-naive bipolar patients.

A high prevalence of thyroid hypofunction has been found in bipolar patients. However, the samples used in previous studies included a high percentage of patients in treatment with lithium and carbamazepine. Since the use of these drugs may explain the high prevalence of thyroid disturbances found in bipolar patients, we designed the present study to assess thyroid function in a sample of bipolar patients who had not been treated previously with lithium or carbamazepine. Patients included in the sample met Research Diagnostic Criteria for bipolar affective disorder. Assessment included determination of serum levels for total tyroxine (T4), total triiodothyronine (T3), and thyrotropin both basally and in response to infusion of 500 mg of Protilerin. The rate of thyroid hypofunction in the total sample (9.2%) was considerably lower than that reported in other studies with bipolar patients undergoing lithium therapy. Five patients (9.2%) showed some thyroid hyperfunction parameter. Our results do not show significant differences in thyroid function indices between long-term and short-term duration of illness, between outpatients and inpatients, between high and low number of episodes, and between rapid- and non-rapid-cycling cases. Comparison between bipolar I and bipolar II patients shows a statistically significant difference in the values of TSH levels, with the bipolar II group having a higher mean value. Our data suggest that thyroid dysfunction is not related to gender, duration of illness, number of episodes, or rapid-cycling course of illness. The higher TRH-stimulated TSH levels in the bipolar II group could be considered a differential biological feature.

Adult↗
PubMedDate not supplied

Clinical, laboratory and immunogenetic aspects of arthritis associated with chronic lymphocytic thyroiditis.

OBJECTIVE: Synovial fluid effusions and/or arthritis may be found in patients with chronic lymphocytic thyroiditis (CLT), even in the absence of hypothyroidism. Sometimes these arthropathies can be attributed to the rheumatic diseases frequently associated with CLT, but in some instances the arthritis seems to be independent of any of the diseases known to cause arthritis, and therefore remains unclassified. This study was carried out in an attempt to characterize the type and outcome of arthritis associated with CLT. METHODS: We performed a prospective study with a follow-up of 6.42 years (range 4-13) on 33 patients affected with CLT and presenting with arthritis. All conditions known to cause arthritis were previously excluded. Investigations included HLA typing, x-ray of the affected joints and, when possible, synovial fluid (SF) analysis with an interleukin (IL)-1 beta determination. Patients were divided based on their clinical presentation into two groups: those with polyarthritis and those with oligoarthritis. RESULTS: During the follow-up, 8 out of 16 patients with polyarthritis developed severe rheumatoid arthritis, characterized by bone erosions, high levels of SF IL-1 beta and an increased frequency of HLA DR4. The other 8 patients had polyarthritis in a mild, non-erosive form, which responded well to symptomatic drugs. Oligoarthritis, found in 17 patients, also showed a mild evolution, with frequent spontaneous remissions. The non-rheumatoid polyarthritis and oligoarthritis patients were characterised by the absence of bone erosions, low levels of SF IL-1 beta and an increased frequency of HLA DR3. CONCLUSIONS: We conclude that it is possible to find in association with CLT a type of inflammatory arthritis characterized by a mild, non-erosive evolution, low SF levels of IL-1 beta and an increased frequency of HLA-DR3. This arthritis seems to be independent of thyroid dysfunction and shows a clinical pattern similar to the arthritis usually found in connective tissue diseases.

Adult↗
PubMed2006

Is there a need to redefine the upper normal limit of TSH?

Mild forms of hypothyroidism--subclinical hypothyroidism--have recently been discussed as being a risk factor for the development of overt thyroid dysfunction and for a number of clinical disorders. The diagnosis critically depends on the definition of the upper normal limit of serum TSH as, by definition, free thyroxine serum concentrations are normal. Cut-off levels of 4-5 mU TSH/l have been conventionally used to diagnose an elevated TSH serum concentration. Recent data from large population studies have suggested a much lower TSH cut-off with an upper limit of 2-2.5 mU/l but application of strict criteria for inclusion of subjects from the general population studies aiming at assessing TSH reference intervals (no personal or family history of thyroid disease, no thyroid antibodies and a normal thyroid on ultrasonography) did not result in an unequivocal upper limit of normal TSH at 2.0-2.5 mU/l. When summarizing the available evidence for lowered upper TSH cut-off values and their potential therapeutic implications there is presently insufficient justification to lower the upper normal limit of TSH and, for practical purposes, it is still recommended to maintain the TSH reference interval of 0.4-4.0 mU/l. Classifying subjects with a TSH value between 2 and 4 mU/l as abnormal, as well as intervening with thyroxine treatment in such subjects, is probably doing more harm than good.

Chemistry, Clinical↗
PubMed1994

[Combined endocrine autoimmune syndrome--incidence, forms of manifestation and clinical significance].

UNLABELLED: In a retrospective case finding study we collected data from patients with polyglandular autoimmune syndrome type II (PGAS Type II) who had been treated in our endocrine outpatient clinic between 1975 and 1989. 31 adult patients (25 females and 6 males) fulfilled the criteria for PGAS Type II (association of autoimmune endocrine disease with at least one other--usually endocrine--autoimmune disease or autoantibodies against another organ). Among these patients, 18 had hypothyroidism due to autoimmune thyroiditis, 8 were hyperthyroid (Graves' disease), and 4 had silent autoimmune thyroiditis (without thyroid dysfunction). Insulin dependent (type I) diabetes mellitus (IDDM) was seen in 11, Addison's disease in 7, primary hypogonadism in 5, vitiligo in 6 and pernicious anemia in 5 cases. The presence of antiparietal cell antibodies was demonstrated in 21 of 30 investigated patients. These patients also showed other evidence of autoimmune gastritis, such as increased gastrin (in 10 out of 13), diminished vitamin B12 levels (6 out of 13), atrophic gastritis (9 out of 9), pernicious anemia (6 out of 30) and funicular myelosis (2 out of 30). CONCLUSION: The most common endocrine diseases in our patient group were autoimmune thyroid diseases (97%) followed by IDDM (35%) and Addison's disease (23%). A high percentage (70%) of our subjects had elevated titers of antiparietal cell antibodies. Polyglandular autoimmune syndrome must be suspected in all patients with autoimmune endocrine disease, especially in the presence of relatives suffering from PGAS. Patients at risk should be screened regularly by measuring thyrotropin (ultrasensitive assay), fasting blood glucose levels, and by checking red blood count and antiparietal cell antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Hormonal and biochemical disturbances in Down's syndrome.

Clinical and laboratory endocrine variables in 29 adult institutionalized patients with Down's syndrome were compared with those of matched controls consisting of other mentally retarded patients from the same institution. Of the clinical variables, testes volume and body height were significantly lower in patients with Down's syndrome than in control patients. The thyroid function tests documented a higher average TSH level in Down's syndrome than in other mentally retarded patients. However, there was no clear-cut correlation between TSH and thyroid hormone levels. The data indicate that there is a tendency towards primary thyroid dysfunction in Down's syndrome. In addition, there is some evidence indicating a relative failure of TSH secretion. In male patients, estradiol was elevated compared to controls. FSH and LH also seemed slightly higher in the study group, but the differences only reached statistical significance when patients on chronic medication were omitted. Prolactin was significantly greater in the Down's syndrome patients than in the controls, both over the entire sample and in the subgroup of men with Down's syndrome, with P-values of around 0.001. The elevation of prolactin was not due to medication and did not correlate to thyroid function or difficulties during blood sampling. In females, the difference was not statistically significant. Laboratory tests that may be associated with endocrine disease or might indicate disease which could influence the endocrine status, were also included in this study. Compared with the controls, ESR, creatinine and uric acid levels were higher in Down's syndrome patients, while albumin was lower, all with P-values lower than 0.001. Vitamin B12 was moderately lower in Down's syndrome patients than in controls (P less than 0.05).

Adult↗
PubMed1975

[Diagnosis and control of therapy of thyroid disorders by TRH-test (author's transl)].

TSH-measurement before and after stimulation with TRH proved to be of good value in the diagnosis of thyroid dysfunctions, better than other parameters including J-131-test. During treatment of hypothyroid disorder TRH-test, often repeatable, allows estimation of T4 substitution dosis. In Graves disease therapy, furthermore, should be judged by in-vitro or clinical parameters.

Aged↗
PubMed2001

Subclinical thyroid disease.

The term subclinical thyroid disease is used to describe asymptomatic thyroid abnormalities found on imaging studies or laboratory tests. Thyroid nodules not palpable on physical examination but detected on imaging studies performed for other purposes are called incidentalomas. In the absence of risk factors for thyroid cancer, nodules that are less than 1 cm in diameter do not require biopsy. Subclinical hyperthyroidism is defined as suppressed serum sensitive thyrotropin (TSH) and normal serum thyroxine and triiodothyronine levels. This condition may adversely affect the heart and the bones and should be treated, especially in patients older than 60 years. Subclinical hypothyroidism, defined as mildly elevated serum TSH and normal serum thyroxine levels, is the most common thyroid dysfunction. In patients with subclinical hypothyroidism, thyroxine therapy should be given if the serum TSH level is higher than 10 mIU/L. For TSH values between 5 and 10 mIU/L, the decision for therapy should be individualized and depends on the level of TSH, presence of antithyroid antibodies, and clinical factors.

Aged↗