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Transient hypothyroxinaemia in preterm infants.

Thyroid hormones are required for normal development of the brain. Transient hypothyroxinaemia is the most common thyroid dysfunction in preterm infants and is defined by temporary low levels of T4, T3 and normal or low TSH. Low T4 levels in preterm infants are associated with persistent neurodevelopmental deficits in cognitive and motor function. Thyroid hormone substitution trials to date are underpowered and show inconsistent results; the question remains -- are low T4 levels simply an epiphenomenon? The aetiology of transient hypothyroxinaemia is multifactorial and the components amenable to correction form the basis of the therapeutic strategy: rectification of iodine deficiency in parenteral nutrition; a reduction of non-thyroidal illnesses and attenuation of their severity; and substitution of drugs that interfere with the hypothalamic-pituitary-thyroid axis. Thyroxine substitution therapy should only be done in the context of clinical trials and only in those infants who are hypothyroxinaemic.

Humans↗

Thyroid hormone increases plasma cholesteryl ester transfer protein activity and plasma high-density lipoprotein removal rate in transgenic mice.

Thyroid dysfunction produces multiple alterations in plasma lipoprotein levels, including high-density lipoprotein (HDL). Cholesteryl ester transfer protein (CETP) and hepatic lipase (HL) are important proteins that modulate the metabolism of HDL. Thus, the effect of thyroid hormone on the activities of CETP and of HL was investigated using hypothyroid and hyperthyroid CETP transgenic (Tg) and nontransgenic (nTg) mice. Hyperthyroid Tg mice plasma lipoprotein (LP) profile analysis showed a significant increase in the very-low-density lipoprotein (VLDL) fraction (P <.001) and decrease in the HDL fraction (P <.005), whereas in the hypothyroid Tg mice an increase in low-density lipoprotein (LDL) was observed (P <.02). CETP activity was measured as the transfer of (14)C-cholesteryl ester (CE) from labeled HDL to LDL by an isotopic assay indicative of mass. Hyperthyroid Tg mice had twice as much plasma CETP activity as compared with their controls, while in hypothyroid Tg mice plasma CETP activity did not change. The role of CETP in determining the changes in LP profile of hyperthyroid animals was confirmed by showing that nTg wild-type hyperthyroid and euthyroid mice exhibited the same percent cholesterol distribution in LP. Postheparin HL activity measured in hyperthyroid Tg mice was significantly reduced (P <.05). (3)H-cholesteryl oleoyl ether ((3)H-Cet)-HDL plasma fractional removal rate (FRR) was approximately 2-fold faster in the hyperthyroid Tg mice than in controls, but was not modified in hypothyroid animals. Tissue uptake of (3)H-Cet was examined in 10 tissue samples: levels were significantly increased in skeletal muscle and decreased in small intestine in hyperthyroid Tg mice, and decreased in the small intestine of hypothyroid Tg mice. In conclusion, the excess of thyroid hormone accelerates HDL metabolism in CETP transgenic mice mainly due to an increase in plasma CETP activity and independently from the HL activity. Hypothyroid status did not change CETP activity and HDL metabolism.

Animals↗

Increased pituitary thyroxine 5'-deiodinase activity in adult rats rendered hyper- or hypo-thyroid during perinatal life.

Perinatal thyroid dysfunction in the rat leads to permanent alterations in pituitary TSH secretion in the adult animal. Thus, neonatal hyperthyroidism (NH) and perinatal hypothyroidism (PH) both result in apparent increased pituitary sensitivity to the feedback effects of thyroid hormones in the adult rat. To determine if increased intrapituitary generation of triiodothyronine (T3) might account for these observations, we measured thyroxine (T4) 5'-deiodinase activity in pituitary homogenates of adult NH and PH rats. NH was induced by injecting neonatal rats with 12 daily sc injections of T4 (0.4 microgram/g body weight (BW]. Control rats received vehicle alone. PH was induced by administering 0.05% 6-n-propylthiouracil in the drinking water to pregnant dams from the 16th day of gestation through the 12th day postpartum. Thereafter, a normal water supply was substituted. NH and PH rats were allowed to mature and were sacrificed at 105 days of age. Serum T4, T3, and TSH concentrations were measured by radioimmunoassay. Pituitary T4 5'-deiodinase activity was assessed by the measurement of T3 formation by pituitary homogenates incubated in the presence of 0.65 microM T4 and 100 mM dithiothreitol at 37 degrees C for 90 min. Body weights of adult NH and PH rats were slightly but not significantly decreased compared with control rats. Relative pituitary gland weight (milligrams per 100 g BW) was significantly decreased in adult PH rats (P less than 0.005) but not in adult NH rats. In adult NH rats, serum T4 and T3 concentrations were significantly decreased (P less than 0.01) compared with control rats. Serum TSH concentrations were similar.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The relation of thyroid function and ventricular repolarization: decreased serum thyrotropin levels are associated with short rate-adjusted QT intervals.

CONTEXT: The linkage of thyroid dysfunction with ventricular repolarization properties has not been investigated extensively, although alterations might be associated with an increased ventricular vulnerability. OBJECTIVE: The objective of the study was to investigate whether there is an association between functional thyroid status and rate-adjusted QT intervals (QTc). DESIGN, SETTING, AND PARTICIPANTS: The population-based Study of Health in Pomerania included 4310 subjects aged 20-79 yr. Data of 3610 subjects (1862 women and 1748 men) without branch bundle blocks or pacemaker were available for the present analyzes. MAIN OUTCOME MEASURES: QTc with respect to thyroid status. Short QTc was defined below the 25th percentile, and long QTc above the 75th percentile of the gender-specific distribution. RESULTS: TSH levels were positively associated with QTc independent from potential confounders in multivariable analyses (P for trend = 0.001). Subjects with decreased TSH levels had shorter QTc than those with normal TSH levels (426.4 +/- 8.2 vs. 430.2 +/- 8.2; P < 0.001). Adjusted odds ratios for short QTc in subjects with elevated, normal, and decreased TSH were 0.87 (95% confidence interval 0.58-1.31), 1.00 (reference), and 1.53 (95% confidence interval 1.16-2.03), respectively (P for trend = 0.008). CONCLUSION: TSH levels were positively related to QTc in a population-based sample. Subjects with decreased serum TSH levels had an increased risk for short QTc. Whether these findings are of clinical significance has to be investigated by further studies.

Adult↗

A longitudinal study of serum TSH, and total and free iodothyronines during normal pregnancy.

Serum T4, T3, rT3, free T4, free T3 and TSH were measured during and after normal pregnancy in 20 women. Special methodological precautions were taken to avoid interference of other hormones and protein alterations in the assays. Serum T4 and T3 were steadily increasing during the last part of the 1st trimester, and remained high and nearly stable during the 2nd and 3rd trimester of the gestation period. The high levels were approximately 1.5 times the values measured 10 weeks post-partum. Serum rT3 was elevated already during the last part of the 1st trimester and remained high throughout pregnancy, compared to the post-partum value. Serum free T4 and free T3 were slightly elevated in early pregnancy. The values decreased gradually during pregnancy and were slightly depressed during the 3rd trimester. A gradual increase in serum TSH was observed during pregnancy and the 2nd and 3rd trimester values were significantly higher than the post-partum value. The mean values for serum TSH, free T4 and free T3 remained always well within the normal range. Thus small variations in serum free iodothyronines and TSH occur during normal pregnancy, the alterations observed in the last trimester of the gestation period resembling those of a slight thyroid insufficiency. These trends in variation of the reference values are worth to remember in the diagnosis of borderline hypo- or hyperthyroidism and in the balanced treatment of pregnant women with thyroid dysfunction.

Adult↗

Infectious and neoplastic disorders of the thyroid in AIDS patients: an autopsy study.

The course of human immunodeficiency virus infection and the acquired immunodeficiency syndrome can be complicated by a variety of endocrine abnormalities. This article describes the findings of a prospective autopsy study of the thyroid in 100 patients who died of complications of AIDS before the advent of the so-called highly active antiretroviral therapy [corrected]. A wide range of bacterial, fungal, viral, and neoplastic disorders were observed. Mycobacterium tuberculosis was recorded in 23% of the patients, cytomegalovirus in 17%, Cryptococcus in 5%, Mycobacterium avium in 5%, Pneumocystis in 4%, and other bacteria or fungi in 7%. Kaposi's sarcoma was recorded in 2% of patients and occult papillary carcinoma in 4%. Four patients had dual infections of the thyroid. The mean weight of the thyroid was lower than normal, and 1 case of thyroid follicular atrophy is presented. A review of the medical literature on thyroid disorders in HIV-infected patients is included. Physicians caring for HIV patients should be aware of the possibility of thyroid dysfunction in their patients.

Acquired Immunodeficiency Syndrome↗

Abnormalities in measures of liver function and injury in thyroid disorders.

Thyroid hormones exert their effect on all tissue and modulate the rate of metabolic activity appropriate for each situation. As a result of their actions, alterations in thyroid function can affect the liver and perturb measures of hepatic function and injury in the absence of liver disease. These alterations in the measure of hepatic function and injury may be difficult to recognize as being caused by thyroid dysfunction rather than hepatic disease. As a result, they may be quite troublesome for patients and physicians if their cause is not properly identified. Importantly, abnormalities in liver function tests return to normal once the primary thyroid pathology is recognized and treated.

Animals↗

[Clinical and muscular evaluation in patients with subclinical hypothyroidism].

Some symptoms and signs of hypothyroidism, as well as some laboratory abnormalities, may be present in subclinical hypothyroidism (SH). This study evaluates the prevalence of signs and symptoms of hypothyroidism and skeletal muscle dysfunction in 57 patients with SH compared to 37 euthyroid controls. The participants received a clinical score based on signs and symptoms of hypothyroidism. The muscle strength was estimated by manual testing and chair dynamometer and inspiratory force by manuvacuometer. Thyroid hormones and muscle enzymes were measured. The SH group presented with higher score (p< 0.01), complained about myalgia and weakness more frequently (p< 0.05), and showed strength disability in scapular and pelvic girdles (p< 0.05). The median free T4 serum levels were lower in SH (p< 0.001). These findings suggest that signs and symptoms of thyroid dysfunction may be related to lower levels of FT4 in SH and should be taken into account in the decision of beginning LT4 therapy.

Adolescent↗

Cytokines in thyroid autoimmunity.

The role of cytokines in the pathogenesis of autoimmune thyroid disease (ATD) has been extensively investigated over the past years. In patients with ATD, these molecules can be found in both the thyroid and sites of extrathyroidal complications of the disease. Cytokines can affect the autoimmune process through a number of mechanisms including recruitment of inflammatory cells and upregulation of molecules essential for perpetuation of the inflammatory response in the affected site. In addition, cytokines can interfere with thyroid hormone synthesis, implicating them directly in thyroid dysfunction found in ATD patients. Also, these molecules can modulate the function of cells in orbital tissue, which results in localised oedema, indicating a central role for cytokines in the development of proptosis, the cardinal feature of thyroid associated ophthalmopathy.

Cytokines↗

Subclinical hypothyroidism and pregnancy outcomes.

BACKGROUND: Clinical thyroid dysfunction has been associated with pregnancy complications such as hypertension, preterm birth, low birth weight, placental abruption, and fetal death. The relationship between subclinical hypothyroidism and pregnancy outcomes has not been well studied. We undertook this prospective thyroid screening study to evaluate pregnancy outcomes in women with elevated thyrotropin (thyroid-stimulating hormone, TSH) and normal free thyroxine levels. METHODS: All women who presented to Parkland Hospital for prenatal care between November 1, 2000, and April 14, 2003, had thyroid screening using a chemiluminescent TSH assay. Women with TSH values at or above the 97.5th percentile for gestational age at screening and with free thyroxine more than 0.680 ng/dL were retrospectively identified with subclinical hypothyroidism. Pregnancy outcomes were compared with those in pregnant women with normal TSH values between the 5th and 95th percentiles. RESULTS: A total of 25,756 women underwent thyroid screening and were delivered of a singleton infant. There were 17,298 (67%) women enrolled for prenatal care at 20 weeks of gestation or less, and 404 (2.3%) of these were considered to have subclinical hypothyroidism. Pregnancies in women with subclinical hypothyroidism were 3 times more likely to be complicated by placental abruption (relative risk 3.0, 95% confidence interval 1.1-8.2). Preterm birth, defined as delivery at or before 34 weeks of gestation, was almost 2-fold higher in women with subclinical hypothyroidism (relative risk, 1.8, 95% confidence interval 1.1-2.9). CONCLUSION: We speculate that the previously reported reduction in intelligence quotient of offspring of women with subclinical hypothyroidism may be related to the effects of prematurity. LEVEL OF EVIDENCE: II-2.

Adult↗

Thyrotoxicity of the chlorides of cadmium and mercury in rabbit.

Exposure to heavy metals such as cadmium and mercury is of immediate environmental concern. The present study was aimed at establishing a direct relationship between heavy metal poisoning and thyroid dysfunction. Cadmium and mercury treatment at LD50 levels resulted in severe thyrotoxicosis in the rabbit. Within 24 h of intramuscular administration of cadmium chloride 15 mg.kg-1 body weight (bw) and mercury chloride 20 mg.kg-1 bw, thyroid peroxidase activity increased significantly over the control with a concomitant rise in the triiodothyronine (T3) titre. On the other hand, there was a remarkable fall in the thyroxine (T4) level, and the T3/T4 ratio was high as compared with the control. Evidence indicates that acute heavy metal lethality will induce immediate hyperthyroidism. It is suggested that T3-toxicosis may be produced by a preferential synthesis of T3 and/or preferential deiodination of T4 to T3. Measurement of T3 and T4 levels may thus be utilized as a reliable indicator of heavy metal lethality.

Animals↗

Prevalence of thyroid autoantibodies in ambulatory elderly women.

Major improvements in thyroid autoantibody testing have now become widely available. Seventy-five elderly ambulatory women from a senior citizens' center (mean age 74.5 yrs) were studied to reassess the prevalence of thyroid autoantibodies and to demonstrate how such tests related to clinical signs and symptoms of thyroid disease. We used the enzyme-linked immunoassay (ELISA) technique for the measurement of autoantibodies to thyroglobulin (hTg) and thyroid peroxidase (hTPO) (as microsomal antigen), since ELISA systems are economical, highly sensitive and specific for population screening. Autoantibodies to hTPO (hTPO-Ab) were present in 44% and hTg autoantibodies (hTg-Ab) in 32% of the study group. Ten women (13.3%) had elevated thyrotropin (TSH) levels. An elevated serum TSH was associated with the presence of hTPO-Ab in varying concentrations. The mean TSH value of 7.2 microIU/mL in those women with hTPO-Ab was significantly higher than the mean of 4.7 microIU/mL found in those women without thyroid autoantibodies (p < 0.01). However, additional testing for hTg-Ab was of little clinical value. These data indicate the high prevalence of thyroid autoimmune disease in the elderly female population. We conclude that screening for thyroid dysfunction is best achieved by the measurement of serum TSH in all women over the age of 60 years. The measurement of hTPO-Ab, but not hTg-Ab, was helpful in confirming the cause of thyroid failure in the elderly female population.

Aged↗

Decreased thyroidal triiodothyronine secretion in patients with anorexia nervosa: influence of weight recovery.

Basal thyroxin (T4), triiodothyronine (T3), and thyrotropin (TSH) concentrations were significantly lower before weight recovery in 10 patients with anorexia nervosa (AN) than they were in control subjects. After weight recovery, basal T4 and TSH levels were unchanged and significantly lower in AN patients than in control subjects. Basal T3 concentrations increased significantly after weight gain: however, concentrations remained lower than those in the control subjects. The maximum increase in T3 and T3 net secretory response to thyrotropin-releasing hormone (TRH), obtained before and after weight recovery, appeared significantly lower than that in control subjects: however, the increases in TSH responses were not different from those of control subjects. Thus, low T3 concentrations in AN patients may be due not only to impaired peripheral conversion of T4 to T3 associated with the altered nutritional state, but also to decreased thyroidal T3 secretion in response to endogenous TSH, which is indicative of hypothalamic-pituitary-thyroidal dysfunction.

Adolescent↗

Four cases of bronchiolitis obliterans organizing pneumonia associated with thyroid disease.

We present 4 cases of bronchiolitis obliterans organizing pneumonia (BOOP) associated with thyroid diseases. Case 1 had previously undergone surgery for thyroid cancer, and had a secondary hypothyroidism at the onset of BOOP. Case 2 developed Basedow's disease 3 months after the onset of BOOP and BOOP relapsed 21 months after the onset of Basedow's disease. Case 3 developed subacute thyroiditis 33 months after the onset of BOOP, and has had no relapse of BOOP for 7 years. Case 4 had hypothyroidism at the time of diagnosis of BOOP, and her BOOP relapsed 3 months after the initial onset of BOOP. Two of these 4 cases of BOOP with thyroid diseases relapsed, and thyroid dysfunction could modify the pathophysiology of BOOP.

Aged↗

Isolated ACTH deficiency associated with transient thyrotoxicosis and hyperprolactinemia.

A 43-year-old woman with isolated ACTH deficiency in association with transient thyrotoxicosis is reported. The initial evaluation revealed that plasma ACTH and cortisol did not respond to corticotropin-releasing hormone (CRH) in the presence of hyperthyroxinemia and hyperprolactinemia. During the replacement therapy with dexamethasone, she developed transient hypothyroxinemia with persistent hyperprolactinemia. Although thyroid open biopsy did not show any evidence of autoimmune thyroiditis or subacute thyroiditis, the data appear to provide other evidence of a possible relationship between acute adrenal insufficiency and transient thyroid dysfunction.

Adrenocorticotropic Hormone↗

Transient congenital hypothyroidism after amniofetography.

A newborn infant who presented with giotrous congenital hypothyroidism is described. Thyroid dysfunction was due to amniofetography performed 4 days before delivery, during which a total of 5.22 g of iodine as water- and lipid-soluble contrast medium was injected. After oral L-thyroxine treatment hypothyroidism disappeared rapidly. Thyroid function remained normal when treatment was withdrawn after 28 days, underlining the transient character of hypothyroidism.

Adult↗

Medical emergencies in the patient with diabetes during pregnancy.

Although the outcome of pregnancies complicated by diabetes is now approaching the success seen in the normal healthy pregnant population, this improvement is only realized when careful attention is paid to the metabolic, hemodynamic, and vascular perturbations associated with the changes of pregnancy. The diabetic woman must not only pay attention to nutrition but also blunt moment-to-moment swings in blood glucose by taking frequent does of insulin. In addition, she must be under constant surveillance for a host of other complications of pregnancy, such as hypertension, retinopathy, infection, acidosis, thyroid dysfunction, nephropathy, and sudden death in utero. Any or all of these problems become medical emergencies if left untreated. Rigorous vigilance to sustain normoglycemia and normotension, examination of the retina, culture of urine, assays for ketosis, measurements of thyroid function, and monitoring of renal function and fetal status are paramount in the management of pregnancy complicated by diabetes.

Blood Glucose↗

Is coeliac disease more prevalent in young adults with coexisting Type 1 diabetes mellitus and autoimmune thyroid disease compared with those with Type 1 diabetes mellitus alone?

AIM: It is known that patients with Type 1 diabetes mellitus are more prone to develop coeliac disease and that autoimmune thyroid disease occurs more frequently in patients with coeliac disease. We therefore assessed whether coeliac disease, either known or occult, occurs more frequently in young/middle aged adults with Type 1 diabetes and coexisting autoimmune thyroid dysfunction than in adults with Type 1 diabetes alone. METHODS: The prevalence of known coeliac disease was assessed in 509 (301 males, aged 16-55 years) patients with Type 1 diabetes, 28 (5.5%) of whom had treated autoimmune thyroid disease. In a second study 38 patients with Type 1 diabetes and coexisting autoimmune thyroid disease along with 112 patients with Type 1 diabetes alone were then screened for coeliac disease using serum IgA endomysial antibodies and IgA gliadin antibodies. RESULTS: Seven of the 509 patients (1.4%) had been diagnosed with coeliac disease and two of these had later developed autoimmune thyroid disease (both hypothyroid). The subsequent screening exercise found that one of the 38 patients with both Type 1 diabetes and thyroid disease had positive endomysial antibodies on screening. However, duodenal biopsy was negative for coeliac disease. There were two patients with positive endomysial antibodies in the group of 112 patients with diabetes only. Both had duodenal biopsy but only one was consistent with coeliac disease. CONCLUSION: The prevalence of known coeliac disease in this young adult Type 1 diabetes clinic in North-west England was 7/509 (1.4%). Two of these seven patients with coeliac disease were from the group of 28 who had autoimmune thyroid disease as well. Therefore we suggest that patients with known coeliac disease and Type 1 diabetes should be screened for autoimmune thyroid disease. The second screening study then found 3/150 (2%) to have a serological marker for coeliac disease. However, patients with both Type 1 diabetes and autoimmune thyroid disease were not more likely to have occult coeliac disease compared with those with Type 1 diabetes only.

Adolescent↗