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Dynamic thyroid stimulating hormone tests: do they still have a role?

Modern assays for TSH and for free thyroid hormones have significantly reduced the need for dynamic testing of the hypothalamo-pituitary-thyroid axis in patients with biochemical thyroid dysfunction. However, under certain conditions, such as isolated TSH deficiency, thyrotropinoma and thyroid hormone resistance, the TRH test remains an important adjunctive diagnostic tool. In recent years, the development of recombinant human TSH (rhTSH) has led to a new dynamic test of thyroglobulin (Tg) secretion as a marker of recurrent or metastatic thyroid cancer. RhTSH provides an alternative to thyroid hormone suppression treatment withdrawal in patients who cannot tolerate hypothyroidism and is the agent of choice in patients unable to mount a TSH response.

Feedback, Physiological↗

[Thyroid function in patients with ventricular arrhythmia].

Hyperthyroidism was diagnosed in 4.8% of 21 patients with persistent ventricular arrhythmias (grades 2 to 5 by the Lown-Wolf classification), and latent hypothyroidism was diagnosed in 38.1% of those, using up-to-date radioimmune assays of thyroid hormones and the thyroliberin (TRH) test. It was those conditions that made arrhythmias resistant to antiarrhythmic treatment in most cases. Latent thyroid dysfunction was particularly common in elderly patients with ventricular arrhythmias and aggravated thyroid history or abnormal thyroid scintigraphic findings. Substitution therapy for hypothyroidism was conducive to the disappearance of paroxysms of ventricular tachycardia and the decrease in total number and grades of ventricular extra-systoles in patients with ventricular arrhythmias; moreover, sensitivity to antiarrhythmic agents developed to replace an earlier resistance.

Adult↗

[Lymphedema and hypothyroidism].

The examination covered 1191 lymphedema patients (635 primary and 536 secondary disease cases). Hypothyroidism-like thyroid dysfunction was found in 80% of patients with primary lymphedema. Measurements of thyroid hormones confirmed the above findings. It is hold that lymphedema patients should undergo the thyreoidin test and combined treatment including thyroid hormone therapy.

Adolescent↗

Primary care diagnosis of thyroid disease.

Recent diagnostic advances include sensitive thyroid-stimulating hormone (TSH) assays, more accurate free thyroxine assays, and fine-needle aspiration biopsy. The workup of patients with suspected thyroid dysfunction generally begins with a TSH assay; guidelines are provided for subsequent thyroid tests. Aspiration biopsy is appropriate for those with a nodular goiter.

Autoantibodies↗

[Thyroid malfunction in women].

The prevalence of thyroid dysfunctions is high in women, this female preponderance has been related with a bigger susceptibility to autoimmune abnormalities. Clinical features of thyroid disease have poor specificity and insidious onset. It is recommended to suspect thyroid pathology in the event of postpartum depression, menstrual abnormalities, amenorrhea, galactorrhea, precocious or delayed sexual development, inexplicable sterility or habitual abortus. The difficult in the clinical diagnosis is compensated by the accessibility and relative easiness of the biological diagnosis by means of the thyroid function tests, mainly the measurements of TSH and FT4 levels; thus, gynecological evaluations should be completed by obtaining thyroid function test. An opportune diagnosis of thyroid illness will solve under the best conditions the gynecological dysfunctions.

Adolescent↗

Doppler echocardiographic evaluation of left ventricular diastolic function in acute hypothyroidism.

OBJECTIVE: Left ventricular diastolic dysfunction is an important cause of symptomatic heart failure. Previous studies suggest that thyroid dysfunction affects left ventricular diastolic function but the underlying mechanisms remain controversial. The study was undertaken to asses the influence of acute hypothyroidism on left ventricular diastolic function and to elucidate possible underlying mechanisms by means of Doppler echocardiography in a group of athyreotic patients, whose thyroid state depended only on external thyroid hormone supply and could therefore easily be controlled. PATIENTS: Eleven patients (5 men, 6 women, aged 20-55 years), who had had total thyroidectomy, were investigated during mild hyperthyroidism and during acute hypothyroidism. Additionally, 11 healthy control subjects aged 25-51 years were included in the study. DESIGN: M-mode echocardiography of the left ventricle and pulsed-wave Doppler echocardiography of the transmitral flow velocity pattern were carried out. RESULTS: Acute hypothyroidism produced a decrease of left ventricular end-diastolic diameter from 48 +/- 5 to 46 +/- 5 mm (mean +/- SD P < 0.05), of peak velocity of early diastolic filling from 0.52 +/- 0.10 to 0.42 +/- 0.05 m/s (P < 0.05), of peak velocity of late diastolic filling from 0.42 +/- 0.10 to 0.36 +/- 0.09 m/s (P < 0.05), and a decreased time-velocity integral of early diastolic filling (6.2 +/- 1.8 vs 5.1 +/- 0.7 cm, P < 0.05). The other M-mode and Doppler echocardiographic parameters did not differ between the hyperthyroid and the hypothyroid states. CONCLUSIONS: The observed changes of the trans-mitral flow velocity pattern during acute hypothyroidism can be attributed to a reduction of pre-load. There is no direct evidence that acute hypothyroidism affects the intrinsic diastolic properties of the left ventricle.

Acute Disease↗

Evidence for autoimmune mechanisms in the evolution of invasive fibrous thyroiditis (Riedel's struma).

The etiology of Riedel's invasive fibrous thyroiditis, a rare disorder confused in the past with the more common fibrous variant of Hashimoto's disease, has remained obscure. However, the presence of mononuclear cells in the fibrosclerotic process and the detection of autoantibodies directed against thyroid-specific antigens in a large proportion of patients with invasive fibrous thyroiditis favor an autoimmune pathogenesis of invasive fibrous thyroiditis. Further, an association between invasive fibrous thyroiditis and Hashimoto's thyroiditis has been suggested. Here we report the first two patients in whom invasive fibrous thyroiditis evolved from antecedent Graves' disease, documented by the presence of thyroid dysfunction, bilateral ophthalmopathy, and thyrotropin receptor stimulating autoantibodies. The diagnosis of invasive fibrous thyroiditis was established in both instances on the basis of the established histopathological criteria. The presence of extensive mononuclear cell infiltration within the invasive fibrosclerotic process in these two patients, the close relationship between thyroid-specific autoantibodies, inflammatory parameters, and disease activity, and the response to glucocorticoid therapy all suggest the existence of a link between Graves' disease and invasive fibrous thyroiditis. These findings support the notion of autoimmune mechanisms playing a role in the pathogenesis of Riedel's invasive fibrous thyroiditis.

Adult↗

[Ultrasonography of the thyroid and parathyroid gland].

Ultrasonography is the most important imaging tool in the diagnosis of thyroid disease. The results of real-time B-imaging of the thyroid gland along with physical signs and basal TSH can aid in the diagnosis of thyroid dysfunction, of for instance, a small, hypoechogenic gland in Hashimoto's and radiation thyroiditis, or an enlarged, hypoechogenic and pulsating gland in Graves' disease. Although recent improvements in technology have increased sensitivity of colored duplexsonography, certain sonographic differentiation of benign and malignant lesions as well as of active (hormone secreting) and inactive nodules is not yet possible. Diagnostic interpretation of ultrasonographic findings is feasible only when the history of the patient, physical examination and the laboratory evaluation are taken into account. Ultrasound detects thyroid nodules, is useful for following nodule size, in guiding fine needle biopsies and in the aspiration of cysts. Highly experienced investigators in ultrasound can assist preoperatively in the localization of parathyroid adenomas in primary and tertiary hyperthyroidism (when followed by (99m)Tc szintigraphy plus SPECT).

Humans↗

Acute radiation thyroiditis.

PURPOSE: Radiation-induced thyroid dysfunction is considered a late effect. We prospectively assessed acute reactions of the thyroid to external neck irradiation. METHODS AND MATERIALS: This study included 22 patients in whom the thyroid was incidentally exposed to therapeutic doses of radiation. Thyroid function tests included measurements of serum thyroid stimulating hormone (TSH), free and total triiodothyronine (T3) and thyroxine (T4), thyroglobulin, and antithyroid antibodies. These tests were performed before radiotherapy (baseline values), after approximately 40 Gy had been administrated, 2 weeks after the end of radiotherapy, and 3 and 6 months after the beginning of radiotherapy. RESULTS: Mean serum levels of TSH were 1.53, 0.55, 0.78, 2.14, and 7.57 microU/ml before radiotherapy, after 40 Gy irradiation, 2 weeks after the end of radiotherapy, and 3 and 6 months after radiotherapy, respectively. Thus, levels of TSH exhibited two phases: a significant decrease during radiotherapy (thyrotoxic phase) and an increase after radiotherapy (hypothyroid phase) (baseline vs. 40 Gy: p < 0.0001, baseline vs. 6 months: p = 0.003). Increases of thyroid hormones were subtle during radiotherapy. CONCLUSIONS: We believe that radiation promotes release of excessive amounts of thyroid hormones during radiotherapy owing to suppression of TSH secretion. In addition to the late damage (hypothyroidism), thyrotoxicosis occurs when the thyroid gland receives a therapeutic doses of external radiation.

Acute Disease↗

Autoimmune thyroid disease and pregnancy: relevance for the child.

As a group, the autoimmune thyroid diseases, including Graves' disease, Hashimoto's thyroiditis, and primary myxedema, are among the most common endocrine disorders encountered during pregnancy. Therefore, a substantial number of offspring will grow and develop in utero under conditions of maternal autoimmune thyroid disease and may be exposed to abnormal maternal thyroid function, maternal thyroid antibodies, and/or numerous therapeutic agents used to manage maternal thyroid dysfunction. This article reviews the effects that these various aspects of maternal autoimmune thyroid disorders can have on pregnancy outcome, as well as on the physical growth, neuropsychological development, and thyroid status of the developing fetus and neonate.

Antithyroid Agents↗

Allan-Herndon-Dudley syndrome and the monocarboxylate transporter 8 (MCT8) gene.

Allan-Herndon-Dudley syndrome was among the first of the X-linked mental retardation syndromes to be described (in 1944) and among the first to be regionally mapped on the X chromosome (in 1990). Six large families with the syndrome have been identified, and linkage studies have placed the gene locus in Xq13.2. Mutations in the monocarboxylate transporter 8 gene (MCT8) have been found in each of the six families. One essential function of the protein encoded by this gene appears to be the transport of triiodothyronine into neurons. Abnormal transporter function is reflected in elevated free triiodothyronine and lowered free thyroxine levels in the blood. Infancy and childhood in the Allan-Herndon-Dudley syndrome are marked by hypotonia, weakness, reduced muscle mass, and delay of developmental milestones. Facial manifestations are not distinctive, but the face tends to be elongated with bifrontal narrowing, and the ears are often simply formed or cupped. Some patients have myopathic facies. Generalized weakness is manifested by excessive drooling, forward positioning of the head and neck, failure to ambulate independently, or ataxia in those who do ambulate. Speech is dysarthric or absent altogether. Hypotonia gives way in adult life to spasticity. The hands exhibit dystonic and athetoid posturing and fisting. Cognitive development is severely impaired. No major malformations occur, intrauterine growth is not impaired, and head circumference and genital development are usually normal. Behavior tends to be passive, with little evidence of aggressive or disruptive behavior. Although clinical signs of thyroid dysfunction are usually absent in affected males, the disturbances in blood levels of thyroid hormones suggest the possibility of systematic detection through screening of high-risk populations.

Adolescent↗

Pathogenesis of autoimmune hypothyroidism induced by lymphokine-activated killer (LAK) cell therapy: in vitro inhibition of human thyroid function by interleukin-2 in the presence of autologous intrathyroidal lymphocytes.

Lymphokine-activated killer (LAK) cell therapy frequently results in primary hypothyroidism. To elucidate the responsible mechanism, we investigated the effects of interleukin-2 (IL-2) on thyroid function of cultured human thyroid follicles in the presence or absence of autologous thyroid-derived lymphoid cells (TDLC). Human thyroid follicles, obtained by subtotal thyroidectomy from patients with Graves' disease, were cultured in serum-free medium containing bTSH and various concentrations of human IL-2, with or without TDLC. After 5 days of culture, 125I was added, and after an additional 3 days of culture, 125I incorporated into thyroid follicles and organic 125I (125I-T4 + 125I-T3) released into the culture medium were estimated. In the absence of TDLC, IL-2 did not affect bTSH-induced thyroid function. In the presence of TDLC, however, IL-2 inhibited the bTSH-stimulated thyroid function in a concentration-dependent manner. The minimum IL-2 concentration required to inhibit thyroid function was 1 U/ml. At 100 U/ml, IL-2 inhibited thyroid function completely. IL-2 increased the concentration of IFN-gamma in the culture medium conditioned by TDLC but not by thyroid follicles. When both were cocultured, IL-2 more significantly increased the concentration of IFN-gamma to an extent sufficient for inhibiting thyroid function per se. Furthermore, the addition of anti-IFN-gamma antibody to the medium partially restored the IL-2-inhibited thyroid function. In summary, by coculturing human thyroid follicles and autologous intrathyroidal lymphocytes with IL-2, it was possible to reproduce the thyroid dysfunction associated with LAK cell therapy. Our data indicate that IL-2 inhibits thyroid function, at least partly, by stimulating production of IFN-gamma, a potent inhibitory cytokine for thyroid cells.

Analysis of Variance↗

Investigations of thyroid hormones and antibodies based on a community health survey: the Busselton thyroid study.

OBJECTIVE: Overt or subclinical thyroid dysfunction is common within the community, yet the significance of subtle anomalies in thyroid function tests remains contentious. The aims of this study were to: (a) establish reference intervals for serum-free thyroxine (FT4), thyroid-stimulating hormone (TSH) and thyroid antibodies (antithyroperoxidase, TPOAb and antithyroglobulin, TgAb) in the Busselton community of south-western Western Australia; and (b) determine the prevalence of thyroid hormone anomalies in this community. SUBJECTS AND DESIGN: In 1981, 2115 adults residing in Busselton participated in a cross-sectional health survey that involved blood collection and a questionnaire on lifestyle and general health history. MEASUREMENTS: Serum samples were analysed for FT4, TSH, TPOAb and TgAb by immunochemiluminescent assays. RESULTS: Based on standard statistical approaches and using guidelines recommended by the National Academy of Clinical Biochemistry (NACB), reference intervals were derived for each analyte: 9-23 pmol/l for FT4, 0.4-4.0 mIU/l (TSH), < 35 KIU/l (TPOAb) and < 55 KIU/l (TgAb). The prevalence of elevated thyroid antibodies was 12.4% among subjects without a history of thyroid disease and is more common in women than in men. Elevated thyroid antibody levels were observed at both extremes of TSH abnormality, but were more commonly increased when TSH levels were above 4.0 mIU/l (63% subjects) than for those with TSH levels 0.4-4.0 mIU/l (7.8% subjects). CONCLUSIONS: This study establishes the prevalence of antibodies to thyroperoxidase and thyroglobulin in a community-based sample and reference intervals for free T4 and TSH. When the NACB decision limits are applied to older men or women, there is a markedly increased number with 'elevated' autoantibody levels compared to sex- and age-specific reference intervals.

Adolescent↗

Anti TSH-receptor antibodies in pregnant patients with autoimmune thyroid disorder.

The study was designed to test further the usefulness of the radioreceptor assay of thyroid stimulating hormone (TSH) binding inhibitory immunoglobulins (TBII) and the bioassay of thyroid stimulating antibodies (TSAb) or TSH stimulated cAMP response inhibitory antibodies (TBkAb) in the prediction of neonatal thyroid dysfunction. Of 63 pregnant women with a current or past history of autoimmune thyroid disorder, 11 (one with active and six with a past history of Graves' disease and four with autoimmune thyroiditis) gave birth to a baby with transient hyper or hypo-thyroidism. Only high maternal titres (which could persist after partial thyroidectomy) of anti TSH-receptor antibodies (TRAb) led to neonatal hyperthyroidism. Both types of assay were able to detect the antibodies responsible for transitory neonatal autoimmune thyroid disease. TBII values reflected TSAb titres so that there was a significant correlation between the results of both assays in women with Graves' disease and in neonatal sera. Positive TBII and TBkAb activities were present in 5 of the 28 women with autoimmune thyroiditis. Therefore, when TBII is positive, the functional characterization of the antibodies warrants the use of the bioassay.

Autoantibodies↗

Value of thyroid echography in the long-term follow-up of lithium-treated patients.

Psychiatric patients on long-term lithium (Li) therapy frequently develop goiter and/or hypothyroidism. It has also been suggested that Li may trigger/exacerbate thyroid autoimmunity. Previous studies provided evidence that underlying thyroid diseases represent important predisposing factors for the development of Li-induced thyroid dysfunction. The aim of the present paper was to assess the value of thyroid ultrasound-a simple and reliable tool to detect subtle thyroid abnormalities-in the longitudinal evaluation of 23 Li-treated psychiatric patients without evidence of biochemical thyroid abnormalities before therapy. For this purpose, thyroid ultrasound was associated with a clinical and laboratory (serum thyroxine, serum triiodothyronine, serum TSH, antithyroglobulin (AbTg), antithyroid microsomal (AbM) and antithyroid peroxidase autoantibodies) evaluation prior to and at 6- to 12-month intervals during Li treatment. On the basis of thyroid ultrasound before Li, patients were subdivided into two groups: group A (n = 15, 7 males, 8 females) with a normal echography and group B (n = 8, 5 males, 3 females) with mild ultrasound abnormalities. In group A the development of a small diffuse goiter was confirmed by physical examination during Li therapy; 2 patients displayed a transient increase of serum TSH concentration and none developed detectable serum antithyroid autoantibodies. Beside the small volumetric increase, no other ultrasound abnormalities were observed during the entire follow-up. In all group B patients a mild diffuse goiter was clinically detected before and on Li administration and no significant volumetric changes were observed during follow-up. Two patients developed high titers of AbM and AbTg 12 and 18 months after the beginning of Li, respectively; in 1 a persistent increase of serum TSH concentration was also observed. Thyroid echography before Li displayed different degrees of scattered or diffuse hypoechogenicity and a further decrease in echogenicity was detected during Li therapy in 2 patients. In conclusion, we provided further evidence that long-term Li administration is not associated with de novo appearance of thyroid autoimmune phenomena in humans, but rather with an exacerbation of underlying thyroid autoimmunity. In addition to thyroid autoantibody and TSH measurements, thyroid echography appears to be a sensitive tool in the identification of patients at risk of developing autoimmune hypothyroidism during long-term Li therapy.

Adult↗

Free T4 measurement is preferred to the T4 test for thyroid evaluation in lithium treated patients.

Free T4 (fT4) measurement provides a more sensitive test of thyroid function than the commonly used T4. Recent commercial development of fT4 kit assays has made fT4 assessment widely available. Evaluation of the fT4 Amerlex kit in 26 lithium-treated patients illustrates its utility as a sensitive laboratory test of thyroid function in this group of patients. This finding together with fT4's known superiority over T4 in identifying thyroid dysfunction suggests that fT4 should replace T4 estimations in the routine monitoring of thyroid function in lithium-treated patients.

Adult↗

Randomised trial of thyroxine to prevent postnatal depression in thyroid-antibody-positive women.

BACKGROUND: Women who are positive for thyroid antibodies in early gestation are prone to post-partum depression, apparently independent of thyroid dysfunction, as measured by serum levels of free thyroxine, free triodothyroxine and thyroid-stimulating hormone. This finding may be due to infrequent monitoring of thyroid function, because hyperthyroidism, hypothyroidism and combinations of both may occur post-partum. AIMS: To test the hypothesis that stabilising thyroid function post-partum by administering daily thyroxine reduces the rate of occurrence and severity of associated depression. METHOD: In a randomised double-blind placebo-controlled trial, 100 microg of thyroxine or placebo was given daily to 446 thyroid-antibody-positive women (342 of whom were compliant) from 6 weeks to 6 months post-partum, assessing their psychiatric and thyroid status at 4-weekly intervals. RESULTS: There was no evidence that thyroxine had any effect on the occurrence of depression. The 6-month period prevalence of depression was similar to that reported previously. CONCLUSIONS: The excess of depression in thyroid-antibody-positive women in the post-partum period is not corrected by daily administration of thyroxine.

Adolescent↗

Psychological well-being correlates with free thyroxine but not free 3,5,3'-triiodothyronine levels in patients on thyroid hormone replacement.

CONTEXT AND OBJECTIVE: An association between mood disorders and overt thyroid dysfunction is well established, but there are few data on the potential for thyroid hormone levels closer to the reference range to correlate with psychological well-being. DESIGN, SETTING, AND PATIENTS: We analyzed the relationship between psychological well-being and free T(4) (fT4), free T(3) (fT3), TSH, and total rT(3) in 697 patients on thyroid hormone replacement therapy at entry to a randomized, controlled trial of combined T(4) and T(3) replacement therapy. All patients were on 100 mug or more T(4). INTERVENTIONS AND MAIN OUTCOME MEASURES: Psychological well-being was assessed with General Health Questionnaire-12 (GHQ-12), Thyroid Symptom Questionnaire, and Hospital Anxiety and Depression Scale. RESULTS: fT(4) and TSH showed a strong correlation with GHQ-12 scores (fT4 - b: -0.16, P = 0.005; TSH - b: 0.663, P = 0.04). No correlations were seen between the GHQ scores and fT3 (b: 0.318, P = 0.275), rT(3) (b: 0.095, P = 0.95), rT(3) to fT4 ratio (b: 71.83, P = 0.09) or fT3 to rT(3) ratio (b: 0.05, P = 0.32). The correlations remained when the data set was limited to patients with TSH in the range 0.3-4.0 mIU/liter. Similar correlations were seen with the Thyroid Symptom Questionnaire, although not with the Hospital Anxiety and Depression Scale scores. CONCLUSIONS: Differences in fT4 and TSH concentration, even within the reference range, may be a determinant of psychological well-being in treated hypothyroid patients although not necessarily with symptoms typical of anxiety or depression.

Adult↗