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Influences of age, gender, smoking, and family history on autoimmune thyroid disease phenotype.

CONTEXT: Both genetic and environmental factors contribute to susceptibility to Graves' disease (GD) and Hashimoto's thyroiditis (HT), as well as disease manifestations. OBJECTIVE: The objective of the study was to define how endogenous/environmental factors contribute to variation in phenotype. DESIGN/SETTING: This was a multicenter cohort study. PATIENTS/OUTCOME MEASURES: We prospectively collected clinical/biochemical data as part of the protocol for a United Kingdom DNA collection for GD and HT. We investigated, in 2805 Caucasian subjects, whether age at diagnosis, gender, family history (FH), smoking history, and presence of goiter influenced disease manifestations. RESULTS: For 2405 subjects with GD, the presence of goiter was independently associated with disease severity (serum free T4 at diagnosis) (P < 0.001). Free T4 (P < 0.05) and current smoking (P < 0.001) were both independent predictors of the presence of ophthalmopathy. Approximately half of those with GD (47.4% of females, 40.0% of males) and HT (n = 400) (56.4% of females, 51.7% of males) reported a FH of thyroid dysfunction. In GD, a FH of hyperthyroidism in any relative was more frequent than hypothyroidism (30.1 vs. 24.4% in affected females, P < 0.001). In HT, a FH of hypothyroidism was more common than hyperthyroidism (42.1 vs. 22.8% in affected females, P < 0.001). For GD (P < 0.001) and HT (P < 0.05), a FH was more common in maternal than paternal relatives. The reporting of a parent with thyroid dysfunction (hyper or hypo) was associated with lower median age at diagnosis of both GD (mother with hyperthyroidism, P < 0.001) and HT (father with hypothyroidism, P < 0.05). In GD and HT, there was an inverse relationship between the number of relatives with thyroid dysfunction and age at diagnosis (P < 0.01). CONCLUSIONS: Marked associations among age at diagnosis, disease severity, goiter, ophthalmopathy, smoking, and FH provide evidence for interactions between genetic and environmental/endogenous factors; understanding these may allow preventive measures or better tailoring of therapies.

Adolescent↗

Prolactin concentration in milk and plasma of puerperal women and patients with galactorrhea.

Prolactin (PRL) concentration was estimated in milk and blood of women with various types of galactorrhea (n = 53) and was compared with lactating (n = 17) and normally menstruating women (n = 36). Mean milk (+/- SD) PRL concentration in lactating women (160 +/- 66 micrograms/l) was similar to that of galactorrhea due to pituitary adenoma (149 +/- 87 micrograms/l, n = 24), thyroid dysfunction (193 +/- 72 micrograms/l, n = 8), functional causes (192 +/- 91 micrograms/l, n = 10) or recent pregnancy (198 +/- 44 micrograms/l, n = 2), but higher than that of sex steroid-induced galactorrhea (85 +/- 53 micrograms/l, n = 9). Plasma PRL concentration in lactating women (208 +/- 102 micrograms/l) was higher than in normal control women (14 +/- 5 micrograms/l) and patients with galactorrhea due to thyroid dysfunction (36 +/- 15 micrograms/l), functional causes (16 +/- 8 micrograms/l), drugs (20 +/- 4 micrograms/l), recent pregnancy (22 +/- 3 micrograms/l) or pituitary adenoma (145 +/- 53 micrograms/l). The milk to plasma PRL concentration ratio was 0.8 +/- 0.4 in lactating women and 1.1 +/- 0.7 in patients with adenoma but significantly higher (p = 99% two-sided) in galactorrhea due to thyroid dysfunction (4.4 +/- 2.1), drugs (3.4 +/- 1.1) or functional causes (12.3 +/- 4.3). Bromocriptine administration reduced PRL in both fluids. It is concluded that in women with galactorrhea milk PRL concentration is similar to that of nursing mothers, but plasma levels of this hormone are significantly lower than that of the latter group in all but the pituitary adenoma related galactorrheas.

Adenoma↗

Comparative evaluation of serum thyroxine, free thyroxine and thyrotropin determinations in screening of thyroid function.

We assessed a highly sensitive immunoradiometric thyrotropin (TSH) assay in screening thyroid dysfunction in 130 consecutive outpatients from a department of medicine and 224 patients from a municipal health centre. In addition to clinical examination, three routine tests were done: a thyroxine radioimmunoassay, an analogue-based free thyroxine assay and an immunoradiometric TSH assay. Triiodothyronine and the TRH test were done, if the findings were discrepant. Discrepancy existed in 24% of cases. The TSH assay had no false negative results (sensitivity 100%). Therefore TSH could screen all patients with thyroid dysfunction. Free thyroxine was the most specific assay (specificity 96%), but many subclinically or overtly hypothyroid patients would have been missed, if that assay had been used alone. We conclude that TSH(IRMA) is the best first-line measurement for thyroid dysfunction testing among outpatients. An abnormal TSH result alone is not diagnostic, but should be followed by the measurement of thyroxine or free thyroxine.

Adolescent↗

Autoimmune (Hashimoto's) thyroiditis associated with Crohn's disease.

We report the occurrence of autoimmune (Hashimoto's) thyroiditis in three patients with Crohn's disease. Previously, thyroid disease has been described only in association with ulcerative colitis. We review the pertinent literature on thyroid disease in inflammatory bowel disease (IBD) and suggest that this association supports the hypothesis that autoimmunity is involved in the pathogenesis of IBD. Early diagnosis and treatment of thyroid dysfunction in patients with IBD is desirable because thyroid dysfunction worsens the symptoms and course of IBD.

Adult↗

Psychoneuroendocrinology of mood disorders. The hypothalamic-pituitary-thyroid axis.

Abnormal thyroid functioning can affect mood and influence the course of unipolar and bipolar disorder. Even mild thyroid dysfunction has been associated with changes in mood and cognitive functioning. Thyroid hormone supplementation may have role in the treatment of certain mood disorders, particularly rapid-cycling bipolar disorder. Women are more vulnerable to thyroid dysfunction than men and also respond better to thyroid augmentation. This article reviews the relationship between thyroid function and mood, and the use of thyroid hormones in the treatment of mood disorders. The impact of gender on these issues is also discussed.

Antidepressive Agents↗

Follow up of thyroid hormone parameters in chronically ill geriatric patients: screening for thyroid disorders at hospital admission justified.

UNLABELLED: The objective of this study was to investigate if screening of chronically ill geriatric patients for thyroid dysfunction is justified just upon hospital admission. TSH was measured in 124 patients at hospital admission and 11-86 (Median 37) days afterwards. FT4 was measured in cases with subnormal, suppressed or elevated TSH (43 cases). Out of 81 patients with normal (0.5-3.6 mU/l) TSH, the control value was subnormal (0.1-<0.5 mU/l) in 6 and elevated (>3.6 mU/l) in one case, but in none of the patients became suppressed (<0.1 mU/l). In 13/30 patients with subnormal TSH the control value was normal but in none of the patients suppressed or elevated. On the contrary, all cases with suppressed (N=9) or elevated (N=4) TSH remained in the same ranges at follow up. Low (<13 pmol/l, N=3) or elevated (>27 pmol/l, N=5) initial FT4 levels did not change in the follow up as well. Out of 35 patients with normal FT4, one became low and another elevated. Improvement or worsening of the clinical state in the follow up did not correlate to changes of TSH. The prevalence of unsuspected thyroid dysfunctions were 11.3% (hyperthyroidism clinical: 4, subclinical: 5, hypothyroidism clinical: 3, subclinical: 2 cases). All cases except one with subclinical hypothyroidism were detected by the initial screening. Only one patient with clinical hyperthyroidism was initial misinterpreted as having subclinical disease. CONCLUSIONS: In chronically ill geriatric patients investigated at hospital admission, a measurable TSH practically excludes hyperthyroidism in the follow up. Suppressed TSH levels remain suppressed but subnormal levels should be controlled because their normalization frequently occur in the follow up. Screening upon hospital admission is sensitive enough to detect cases of thyroid dysfunction and justified by their high prevalence.

Aged↗

Hypothyroidism in transgenic mice expressing IFN-gamma in the thyroid.

IFN-gamma has been implicated with contradictory results in the pathogenetic process of autoimmune (Hashimoto's) thyroiditis, the most common cause of hypothyroidism in adults. To test whether the local production of IFN-gamma can lead to thyroid dysfunction, we have generated transgenic mice that express constitutively IFN-gamma in the thyroid follicular cells. This expression resulted in severe hypothyroidism, with growth retardation and disruption of the thyroid architecture. The hypothyroidism derived from a profound inhibition of the expression of the sodium iodide symporter gene. Taken together, these results indicate a direct role of IFN-gamma in the thyroid dysfunction that occurs in autoimmune thyroiditis.

Animals↗

Prevalence of erectile dysfunction in thyroid disorders: comparison with control subjects and with obese and diabetic patients.

Diagnosis of erectile dysfunction (ED) requires anamnestic investigation, being rarely spontaneously declared by patients. ED occurs frequently in diabetes mellitus, and anecdotal evidence suggests that ED occurs in obesity and in hypothyroidism. The aim of this study was to evaluate the prevalence of ED in patients affected by thyroid disorders (hypothyroidism and hyperthyroidism), in comparison with control subjects and with patients at risk for ED, such as patients with obesity and with type II diabetes mellitus, and the role of age. Spontaneous deposition and International Index of Erectile Dysfunction (IIEF)-5 questionnaire were considered for control subjects and for all patients. Spontaneous deposition of ED occurred for three diabetic patients, never for obese patients, thyroid patients and controls, confirming the value of IIEF-5 in detecting ED. ED was more frequent in obese subjects (42%), and in patients affected by thyroid diseases (59%), than in controls (30%), although less frequent than in type II diabetes mellitus (81%). Both below and above the age of 50 years, ED score was worse in thyroid patients than in control subjects, while ED was more frequent in obese patients than in control subjects only below the age of 50 years.

Case-Control Studies↗

Amiodarone-induced thyroid gland dysfunction.

Of a population of 400 patients treated with amiodarone, 97 underwent thyroid function evaluation. Of these, 20 patients proved to be thyrotoxic and 16 hypothyroid. In thyrotoxic patients, symptoms developed 2 to 36 months after starting treatment with amiodarone, the most specific laboratory finding being a high total T3 (TT3). No antithyroid treatment proved useful. Thyroid function returned to normal 3 to 7 months after stopping amiodarone therapy. In the hypothyroid group, a high thyroid-stimulating hormone was the most specific laboratory finding. These patients were treated with substitute therapy with or without withdrawal of amiodarone. The iodine content of the thyroid gland in part of this population taking amiodarone was measured by in vivo x-ray fluorescence. Patients in whom thyrotoxicosis developed showed especially high iodine contents. During treatment with amiodarone, patients at high risk of thyrotoxicosis were recognized by increasing TT3 values and higher iodine thyroid levels. A reduction in maintenance dose should be considered in this specific population.

Amiodarone↗

Thyroid function in haemochromatosis.

BACKGROUND: In hereditary haemochromatosis (HH), the thyroid gland is the site of substantial iron deposition. However, there have been relatively few reported cases of thyroid dysfunction in HH. AIM: To evaluate the prevalence of thyroid disorders in a large group of patients with HH. METHODS: A variety of endocrine investigations were undertaken including thyroid function tests and thyroid antibody studies. RESULTS: A total of 154 consecutive patients (123 male, 31 female) were studied. One case of primary hypothyroidism was identified, giving a prevalence of 0.6%. Subclinical hypothyroidism was identified in two females, giving a prevalence of 1.3%. Iatrogenic hypothyroidism was identified in two other cases. No case of hyperthyroidism was identified. CONCLUSION: Thyroid dysfunction is an uncommon occurrence in patients with HH.

Adult↗

When a thyroid abnormality is palpable. What it means and what you should do.

Clinicians faced with a palpable thyroid abnormality should ascertain whether there is evidence of thyroid dysfunction, concern for malignancy, and symptoms of obstruction. In the vast majority of cases, laboratory assessment of the thyroid with an sTSH assay establishes the presence or absence of thyroid dysfunction. In a nodular thyroid gland, fine-needle aspiration biopsy is the method of choice for determining whether malignancy is present. In a large goiter, the presence of obstructive symptoms or findings may be a clear indication that surgery is needed. The absence of these findings may warrant simple observation.

Airway Obstruction↗

Thyroid disease in pregnancy. ACOG Technical Bulletin Number 181--June 1993.

To accurately evaluate thyroid disorders in pregnancy, the physician must understand the physiologic changes that occur both in thyroid gland size and in thyroid function tests. The effect of thyrotoxicosis on pregnancy outcome largely depends on whether metabolic control is achieved. Women who become euthyroid on treatment usually can expect satisfactory outcomes. Propylthiouracil is considered to be the drug of choice for treating thyrotoxicosis during pregnancy. Because of the significant risk of hypothyroidism and obvious goiter in the infant, the use of iodide should be reserved for severe disease, such as thyroid storm or heart failure. Thyrotoxic infants may need antithyroid treatment until TSAbs are metabolized. Since overt hypothyroidism is often associated with infertility, it is uncommon in pregnancy. Hypothyroid women who do become pregnant, however, have an increased risk of low-birth-weight or stillborn infants. These women may require a greater dosage of thyroid hormone during pregnancy. The effects of subclinical hypothyroidism are not well defined. Accordingly, the need for treatment hinges on the woman's clinical history. Infants of hypothyroid mothers usually show no evidence of thyroid dysfunction, but those who are hypothyroid should receive prompt thyroid replacement therapy. To minimize the sequelae of congenital hypothyroidism, mass screening of infants and prompt treatment of those affected is recommended. During pregnancy, thyroid nodules should be evaluated by ultrasound and fine-needle aspiration or tissue biopsy. Radioiodine scanning should be avoided during pregnancy. If thyroid cancer is diagnosed, pregnancy should not delay treatment. Because postpartum thyroid dysfunction is fairly common yet difficult to detect, physicians and patients should be aware of the symptoms and risk factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Brief antiseptic application of iodine in neonatal intensive care units: effects on thyroid function].

BACKGROUND: Transient thyroid dysfunction with its adverse effects of diminished levels of thyroid hormone on mental development has been reported in neonates whose skin has been cleaned with iodine-containing substances. We report the results of thyroid screening in iodine-exposed neonates and controls. POPULATION AND METHODS: Thirty seven neonates admitted to an intensive care unit from 1990 to 1992 and whose medical condition required umbilical catheterization were included in the study. There were 21 neonates (six term and 15 preterm) for whom the area around the umbilicus was cleansed with iodine antiseptic and 16 controls (four term and 12 preterm) for whom the antiseptic used did not contain iodine. Levels of serum free T3 and T4, and TSH were determined by 7 days after catheterization as did urinary iodine and creatinine concentrations. RESULTS: Iodine-exposed neonates had significant high levels of TSH (P < 0.01) and low free T3 (P < 0.05); levels of free T4 were lower than in controls but not significantly. Urinary iodine excretion was significantly increased. The increase in TSH disappeared between 15 and 30 days after iodine application. CONCLUSION: Application of iodine antiseptics may cause transient thyroid dysfunction in neonates leading to propose the use of non iodinated substances with similar antibacterial efficacy.

Anti-Infective Agents, Local↗

Hypothalamic-pituitary-thyroidal axis dysfunction and cortisol secretion in patients with nonclassical congenital adrenal hyperplasia.

OBJECTIVE: The purpose of this study was to evaluate thyroid function and TSH and cortisol (F) secretion in hyperandrogenemic women with nonclassical congenital adrenal hyperplasia (NC-CAH) due to 21-hydroxylase deficiency (Group A) when compared with women with hyperandrogenemic symptoms (menstrual irregularities, hirsutism, acne, seborrhea and sterility) of other etiologies (Group B). METHODS: Seventy-two women were subjected to stimulation of the adrenal cortex with i.v. ACTH administration in the early proliferative phase of the menstrual cycle. Basal plasma TSH, T3, T4, and FTI as well as basal and ACTH-stimulated plasma F and 17-hydroxyprogesterone levels were determined. RESULTS: According to internationally accepted criteria and HLA haplotyping, we diagnosed 28 NC-CAH patients as well as affected heterozygotes of the disease. No significant difference was found in the plasma T3, T4, or FTI or F concentrations between the women of the two groups. On the contrary, plasma TSH levels were significantly lower in patients with 21-hydroxylase deficiency when compared to the women with hyperandrogenemic symptoms of other etiologies. CONCLUSION: The results of this study support a dysfunction of the hypothalamic-pituitary-thyroidal axis due to altered ACTH secretion patterns.

17-alpha-Hydroxyprogesterone↗

The prediction of thyroid function in infants born to mothers with chronic thyroiditis.

To elucidate the relationship between the mother's TSH-receptor antibody activities and the status of thyroid dysfunction in their offspring, blood was taken from 5 mothers with chronic thyroiditis with potent thyrotropin (TSH)-receptor blocking activity, and the potency of TBII and TSBAb activity was assayed more quantitatively. In those mothers whose infants suffered from neonatal hypothyroidism, the 50% inhibition of binding of labeled TSH to its receptors was obtained at more than 30 to 50-fold dilution, while in those mothers whose infants had transiently increased TSH or were euthyroid, the titers were of less than 30-fold dilution. Similarly, in those mother whose infants suffered from neonatal hypothyroidism, the 50% inhibition of TSH-induced cAMP accumulation was obtained at approximately 400 to 3000-fold dilution, while in those mothers whose infants had transiently increased TSH or were euthyroid, the titers were of less than 50-fold dilution. On the other hand TBII activity was much less potent in serum from patients with Graves' disease. These results suggested that the titration of serum with dilution to obtain 50% inhibition of labelled TSH binding to its receptor may be the simplest way to predict thyroid dysfunction of the newborn infants born to mothers with chronic thyroiditis.

Adolescent↗

Autoimmune thyroid disease in pregnancy and the postpartum period: relationship to spontaneous abortion.

The aim of this study was to determine the prevalence of autoimmune thyroid disease and the risk of miscarriage in autoimmune thyroid antibody (ATA)-positive women. Eight hundred seventy-six subjects completed the study, and 12.3% were thyroid antibody-positive (4.5% tested positive for both thyroid peroxidase antibody [TPO-Ab] and thyroglobulin autoantibody [Tg-Ab], 4.79% were TPO-Ab-positive only, and 3.1% were Tg-Ab-positive only). Fifty percent of the ATA-positive women and 14.1% of the ATA-negative group had a history of spontaneous abortion. Forty-eight of the ATA-positive women developed postpartum autoimmune thyroid dysfunction (PATD). Of these, 50% had hypothyroidism alone, 31.3% had transient hyperthyroidism followed by hypothyroidism, and 18.8% had transient thyrotoxicosis alone. Of the 48 PATD subjects, 12.5% developed persistent hypothyroidism. None of the ATA-negative women developed any form of thyroid dysfunction. The thyroid-stimulating hormone (TSH) levels in the ATA-positive group were significantly higher than those in the ATA-negative group, and only the ATA-positive women with a history of abortion had significantly higher TSH and lower free thyroxine (FT4) concentrations than the other subgroups. The results revealed a 5.5% prevalence rate for PATD in the study population. In addition to TPO-Ab, Tg-Ab is a useful marker for autoimmune thyroiditis.

Abortion, Spontaneous↗

Tubulointerstitial nephritis and uveitis syndrome associated with hyperthyroidism.

We report a 17-year-old male patient with tubulointerstitial nephritis and uveitis (TINU) associated with hyperthyroidism. He presented with a 2-month history of fatigue, loss of appetite, low-grade fever, and a 12-kg weight loss when he was admitted to our hospital. He had iritis, which was complicated by fibrin in the anterior chamber, diagnosed by slit-lamp examination. On laboratory examinations, deteriorated renal function (blood urea nitrogen level was 25.9 mg/dl and creatinine level was 2.82 mg/dl) and elevated urinary levels of N-acetyl-beta-D-glucosaminidase (33.1 U/l) and beta2-microglobulin (78,600 microg/l) were observed. Serum thyroid-stimulating hormone (TSH) was undetectable, at less than 0.01 microIU/ml, and free triiodothyronine and free thyroxine were elevated, up to 5.23 pg/ml and 2.85 ng/dl, respectively. The titers of antithyroglobulin and antithyroid microsomal and TSH-receptor antibodies were not elevated. Abdominal and thyroidal ultrasonography showed evident bilateral enlargement of the kidneys and diffuse enlargement of the thyroid gland. Iodine-123 scintigraphy showed low uptake in the thyroid gland. The biopsied renal specimen showed mild edema and severe diffuse infiltration of mononuclear cells and few eosinophils in the interstitium, without any glomerular or vascular abnormalities. Based on the clinical features and pathological findings, a diagnosis of TINU syndrome with associated hyperthyroidism was made. Treatment was started with 30 mg/day of prednisolone. The iritis disappeared, and the patient's clinical status improved remarkably. This case suggests the possibility of thyroid dysfunction in some patients with TINU syndrome, and we believe thyroid function should be measured in all TINU patients. Moreover, histopathological diagnosis of the thyroid glands before treatment is necessary for TINU patients with thyroid dysfunction.

Adolescent↗

Subclinical hypothyroidism and cardiac function.

The cardiovascular system is sensitive to the action of thyroid hormone. However, although a wide spectrum of cardiac abnormalities has long been recognized in patients with overt thyroid dysfunction, the question of cardiac involvement in patients with subclinical thyroid dysfunction has been investigated only in the last two to three decades. Most clinical studies have shown that subclinical hypothyroidism or hyperthyroidism is associated with changes in several cardiac parameters. More specifically, the literature on cardiac involvement in subclinical hypothyroidism consistently shows that patients have resting left ventricular diastolic dysfunction evidenced by delayed relaxation, and impaired systolic dysfunction on effort that results in poor exercise capacity. Whether or not subclinical hypothyroidism also affects left ventricular systolic function at rest remains controversial. Studies of subclinical hypothyroid patients before and after euthyroidism was achieved with levothyroxine replacement provided evidence of impaired resting left ventricular systolic function. Indeed, at-rest left ventricular systolic function was substantially normal in most studies of subclinical hypothyroid patients compared to normal control subjects. Drawing on these data, it appears that subclinical hypothyroidism should be considered a mild form of thyroid failure, associated with initial signs of cardiovascular hypothyroidism. Therefore, it would seem appropriate to initiate timely treatment of patients with mild thyroid failure to prevent cardiac involvement.

Echocardiography, Doppler↗