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[Circulating free T3 in pregnancy, liver diseases, diabetes mellitus and thyroid diseases].

Measurement of serum concentrations of free triiodothyronine (FT3) is considered to be an accurate index of thyroid function in the patient. In this study, we measured serum concentrations of FT3, free thyroxine (FT4) and reverse triiodothyronine (rT3) by radioimmunoassay in blood samples taken from the navel cord of 20 newborns as well as 20 nonpregnant women, 20 pregnant women, 10 patients with liver diseases, 25 patients with diabetes mellitus, 65 patients with hyperthyroidism, 30 patients with primary hypothyroidism and 29 normal subjects. In pregnant women, serum FT3 and FT4 levels gradually decreased as the pregnancy progressed. In cord blood, FT3 levels were less than a quarter of the values found during the first trimester of pregnancy or that of non-pregnant women, whereas serum rT3 levels were drastically increased. In chronic hepatitis, liver cirrhosis and diabetes mellitus, serum FT3 and FT4 levels were significantly lower than that in the controls. In thyroid diseases, serum FT3 levels varied parallel to other thyroid hormone levels. In primary hypothyroidism, however, serum FT3 levels were still lower than these in the controls after treatment with 1-thyroxine, whereas other thyroid hormone levels and TSH levels returned to control levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Thyroid ultrasound in diabetic patients without overt thyroid disease.

PURPOSE: To assess thyroid volume and to evaluate possible lesions in the gland structure using thyroid ultrasound in patients with diabetes mellitus type 1 (DM1) and 2 (DM2) without overt thyroid disease. MATERIAL AND METHODS: Consecutive adult patients with DM2 (n = 98) and DM1 (n = 30) without overt thyroid disease referred to our department because of poorly controlled disease and/or diabetic complications were prospectively analyzed. Thyroid volumes, gland echogenicity, thyroid nodules incidence, and TSH levels were compared with control groups (n = 50 and 38) and matched according to sex and age. RESULTS: Significant increases in median thyroid volume were observed in both subjects with DM1 (17.3 cm3, interquartile range (IR) 13.9-21.6 cm3 versus 14.4 cm3, IR 11.3-18.3 cm3; P < 0.05) and DM2 (20.5 cm3, IR 14.9-27.1 cm3 versus 14.1 cm3, IR 11.3-18.3 cm3; P < 0.001) in comparison to their control groups. Moreover, in the population of type 2 diabetics, thyroid nodules (OR 2.37, 95% CI 1.14-4.93), parenchymatous goiter (OR 5.40, 95% CI 1.20-24.30), and all kinds of thyroid goiter according to the WHO definition (OR 4.18, 95% CI 2.02-8.66) were remarkably more frequent. In our patients, reduced (but within normal range) TSH level occurred in DM1 (median 0.97 mIU/l, IR 0.61-1.58 mIU/l versus median 1.66 mIU/l, IR 0.76-2.09 mIU/l; P < 0.05). The presence of a negative linear correlation between thyroid volume and TSH concentration was noticed in patients with DM2 (RS = -0.38, P < 0.01). CONCLUSION: In individuals with DM1 and DM2 treated for poorly controlled disease and/or diabetic complications, thyroid volumes were significantly higher than in the normal population. Moreover, nodular thyroid structure and parenchymatous goiter occurred more frequently in these type 2 diabetic patients.

Adult↗

[Proliferating cell nuclear antigen (PCNA) on human diseased thyroid cells].

Surgical materials obtained from 5 normal human thyroids and 19 diseased tissues (4 with Grave's disease, 4 adenomatous goiters, 3 follicular adenomas, 2 papillary carcinomas, 4 follicular carcinomas and 2 undifferentiated carcinomas) were investigated immunohistochemically using the avidin-biotin-peroxidase complex technique with anti-proliferating cell nuclear antigen (PCNA) antibody and epidermal growth factor receptor (EGFR) antibody. The results of this study suggested the following: (1) Labeling indexes of PCNA positive cell nuclei were shown in high grade malignant cases accompanied by capsular invasion and lymph node metastasis, in undifferentiated carcinoma cells, and in proliferative lesions of benign diseases. These results suggest that PCNA is indicative of proliferative ability in thyroid diseases. (2) On thyroid tumors, EGFR regions with strong positive staining showed many PCNA positive cell nuclei. EGF appears to have a significant association with proliferative ability in thyroid diseases.

Adult↗

[Autoimmune thyroid diseases complicated with reversible changes of thyroid function].

Autoimmune thyroid disease (AID) with reversible thyroid dysfunction was classified mainly by etiology. Hashimoto thyroiditis itself, pregnancy, cytokine therapy and various drugs, iodine-rich food and AID with TSH receptor antibody (TRAb) were main items. Silent or painless thyroiditis which was termed destructive thyroiditis occurs without clear cause or after adrenectomy for Cushing syndrome. Abnormal human chorionic gonadotropin (hCG) rarely causes transient thyrotoxicosis at early phase of pregnancy and postpartum thyroiditis which has similar symptom as silent thyroiditis is relatively common disorders. Thyroid dysfunction of patients with both TRAb (TSAb and TSBAb) is pathophysiologically unknown and the detection of both antibodies in a patient serum is difficult methodologically. We developed the highly sensitive TSAb assay by patients' IgG precipitated by high concentration PEG (22.5%) using porcine thyroid cell. This assay is also useful for detection of the coexistence cases of TSAb and TSBAb.

Autoimmune Diseases↗

The clinical presentation and operative management of nodular and diffuse substernal thyroid disease.

Patients with substernal thyroid disease, defined by the presence of enlarged thyroid tissue below the plane of the thoracic inlet, were identified from a prospective database maintained for patients who have undergone thyroidectomy at our institution since 1990. Substernal thyroid disease was present in 116 (30%) of 381 patients, anterior mediastinal in 109 (94%), and posterior mediastinal in seven (6%). Indications for surgery included compressive symptoms in 75 (65%) patients, an abnormal fine-needle biopsy in 45 (39%), progressive thyroid enlargement in 41 (35%), thyrotoxicosis in 11 (10%), and superior vena cava syndrome in two (1.7%). A median sternotomy and thoracotomy were performed in one patient each for a primary intrathoracic goiter. In all other patients thyroidectomy was accomplished through a cervical incision. Parathyroid autotransplantation was performed in 41 (37%) patients with retrosternal disease compared with 57 (22%) with disease confined to the neck (P < 0.01). Twenty-five patients (22%) had malignancy; four of these had unresectable disease. Postoperative complications included transient hypocalcemia (n = 46), transient hoarseness (n = 7), recurrent laryngeal nerve injury (n = 1), and wound infection (n = 1). One patient died from aspiration pneumonia. In summary, substernal thyroid disease is typically present in the anterior mediastinum and with rare exceptions can be resected through a cervical incision. Parathyroid devascularization is more common with resection of a substernal goiter and autotransplantation can prevent permanent hypoparathyroidism.

Adolescent↗

A study of thyroid disease in family practice.

Thyroid disease is relatively common in family practice, yet is often undiagnosed or poorly managed. This study examines several aspects of thyroid disease in a large, semirural family practice setting and exemplifies the type of practical clinical research that can be done in family medicine. An overall prevalence of approximately one percent was determined for thyroid disease in this practice. In a series of 85 patients, the ratio of hypothyroidism:hyperthyroidism:euthyroid goiter was 9:2:1 respectively. Initial signs and symptoms recorded for these patients conformed closely to the findings in other large series. Eighty percent of the patients with idiopathic hypothyroidism never had enlarged glands, whereas 100 percent of the patients with hypothyroidism associated with Hashimoto's thyroiditis had enlarged glands. Laboratory aids such as serum thyroid stimulating hormone (TSH), anti-thyroid antibodies, and radioactive iodine uptake (RAIU) and scans were inadequately utilized. Medical and/or surgical consultation was obtained in 17.5 percent of patients with hypothyroidism, 80 percent of patients with hyperthyroidism, and 63 percent of those with euthyroid goiter. Currently 95 percent of the hypothyroid patients and 100 percent of the hyperthyroid patients are euthyroid.

Adolescent↗

Incidence of thyroid hormone autoantibodies in patients with thyroid diseases with respect to diagnosis, other types of autoantibodies, duration of disease and treatment.

Thyroid hormone autoantibodies (THAA] were estimated in a total of 149 patients (139 women and 10 men) with various thyroid diseases. THAA were found in a total of 22 patients (all women), i.e. 14.7%. In 8 of them both T4Ab and T3Ab were found, while T4Ab only were found in 4 patients and T3Ab only in 10 patients. The highest incidence of THAA was found in patients with diffuse lymphocytic thyroiditis (i.e. 11 cases out of a total of 64 patients) and similarly high incidence was in patients with suspected autoimmune goiter but without thin needle biopsy (i.e. 5 cases out of a total of 21 patients). If only the patients with manifested or silent hypothyroidism were selected, T4Ab were found exclusively in this group, while the incidence of T3Ab was 3 times higher as that in patients without hypothyroidism. Though the incidence of T4Ab in patients with positive antithyroglobulin and antimicrosomal antibodies was 3 times higher than in negative ones, the difference was not significant. No correlation was found between the incidence of THAA on one hand and the duration of disease, the duration of treatment and the drug used for treatment on the other. However, a significant correlation was found between the incidence of THAA and the presence of goiter (P less than 0.05).

Autoantibodies↗

Crohn's disease and risk of fracture: does thyroid disease play a role?

AIM: To assess the role of thyroid disease as a risk for fractures in Crohn's patients. METHODS: A cross-sectional study was conducted from 1998 to 2000. The study group consisted of 210 patients with Crohn's disease. A group of 206 patients without inflammatory bowel disease served as controls. Primary outcome was thyroid disorder. Secondary outcomes included use of steroids, immunosuppressive medications, surgery and incidence of fracture. RESULTS: The prevalence of hyperthyroidism was similar in both groups. However, the prevalence of hypothyroidism was lower in Crohn's patients (3.8 % vs 8.2 %, P=0.05). Within the Crohn's group, the use of immunosuppressive agents (0 % vs 11 %), steroid usage (12.5 % vs 37 %), small bowel surgery (12.5 % vs 28 %) and large bowel surgery (12.5 % vs 27 %) were lower in the hypothyroid subset as compared to the euthyroid subset. Seven (3.4 %) Crohn's patients suffered fracture, all of whom were euthyroid. CONCLUSION: Thyroid disorder was not found to be associated with Crohn's disease and was not found to increase the risk for fractures. Therefore, screening for thyroid disease is not a necessary component in the management of Crohn's disease.

Adult↗

Cytokine gene polymorphisms in autoimmune thyroid disease.

Susceptibility to the autoimmune thyroid diseases, Graves' disease (GD) and autoimmune hypothyroidism (AIH), depends on a complex interaction between environmental and genetic factors. The human leukocyte antigen and cytotoxic T lymphocyte-associated-4 regions appear to influence susceptibility to disease, but the effect is not major, and the other genes remain unknown. Cytokines are crucial in the regulation of immune and inflammatory responses and therefore are potential candidate genes for autoimmune thyroid disease. In a case-control study, using a unified method of genotyping, we have examined 15 polymorphisms in 9 cytokine genes in 215 patients with autoimmune thyroid disease (GD, 138; AIH, 77) and 101 normal controls. Polymorphisms in the genes for interleukin-1alpha (IL-1alpha), IL-1beta, IL-1 receptor antagonist, IL-1 receptor 1, IL-4, IL-4 receptor, IL-6, IL-10, and transforming growth factor-beta were investigated. Genotyping was performed using the PCR and sequence-specific primers. Analysis showed a reduced frequency of the variant t allele in the IL-4 promoter polymorphism (position 590) in patients with GD and in the entire patient group (GD and AIH) compared with the control group [corrected P (Pc) = 0.00004 and Pc < 0.00001 for GD and all patients, respectively]. This was reflected in a reduction in the heterozygote genotype in the patient groups compared to the controls [c/t heterozygotes GD, 12%; Pc = 0.06, odds ratio, 0.4 (95% confidence interval, 0.2-0.7); all patients, 11%; Pc = 0.008; odds ratio, 0.4 (95% confidence interval, 0.2-0.7); control subjects, 23%]. There were no significant differences between the study groups for the other polymorphisms examined, and subgroup analysis revealed no association with clinical parameters of disease. These results suggest that an IL-4 variant or a closely linked gene has a modest protective effect against the development of autoimmune thyroid disease, particularly GD. This variation in the IL-4 gene may provide further clues to the pathogenesis of autoimmune thyroid disease and other organ-specific autoimmune diseases. Furthermore, these results suggest that subtle variation in immunoregulatory genes may be associated with autoimmune disease states.

Cohort Studies↗

The involvement of IL-12 in murine experimentally induced autoimmune thyroid disease.

Experimental autoimmune thyroid disease (EAT) can be induced experimentally in mice following immunization with mouse thyroglobulin (mTg) and the adjuvants lipopolysaccharide (LPS) or complete Freund's adjuvant (CFA). EAT can also be transferred to naive recipients by CD4+ T cells from mTg-primed mice. Here we demonstrate a role for IL-12 in the development of EAT by the ability of neutralizing antibody to IL-12 to reduce disease severity and by the lack of significant levels of thyroid infiltration in IL-12p40-deficient mice following immunization with mTg and CFA. A single injection of 300 ng IL-12 at the time of initial immunization with mTg and LPS was able to increase the degree of thyroid infiltration. These data are all consistent with EAT being a Th1-mediated disease. Conversely, however, administration of IL-12 over a prolonged period markedly inhibited the induction of EAT by mTg and CFA and, if given to recipients, inhibited the transfer of EAT by mTg-primed lymph node cells. The development of an autoantibody response to mTg was also inhibited when IL-12 was administered throughout the experimental period, suggesting that sustained exposure to IL-12 can be immunosuppressive.

Adoptive Transfer↗

Thyroid disease in pregnancy.

Thyroid testing during pregnancy should be performed on symptomatic women or those with a personal history of thyroid disease. Overt hypothyroidism complicates up to 3 of 1,000 pregnancies and is characterized by nonspecific signs or symptoms that are easily confused with complaints common to pregnancy itself. Physiologic changes in serum thyroid-stimulating hormone (TSH) and free thyroxine (T(4)) related to pregnancy also confound the diagnosis of hypothyroidism during pregnancy. If the TSH is abnormal, then evaluation of free T(4) is recommended. The diagnosis of overt hypothyroidism is established by an elevated TSH and a low free T(4). The goal of treatment with levothyroxine is to return TSH to the normal range. Overt hyperthyroidism complicates approximately 2 of 1,000 pregnancies. Clinical features of hyperthyroidism can also be confused with those typical of pregnancy. Clinical hyperthyroidism is confirmed by a low TSH and elevation in free T(4) concentration. The goal of treatment with thioamide drugs is to maintain free T(4) in the upper normal range using the lowest possible dosage. Postpartum thyroiditis requiring thyroxine replacement has been reported in 2% to 5% of women. Most women will return to the euthyroid state within 12 months.

Female↗

Routine measurement of serum calcitonin in nodular thyroid diseases allows the preoperative diagnosis of unsuspected sporadic medullary thyroid carcinoma.

To assess whether routine measurement of serum calcitonin (CT) could improve the preoperative diagnosis of sporadic medullary thyroid carcinoma (MTC), 1385 consecutive patients presenting for nodular thyroid disease during the year 1991 were submitted to serum CT determination and fine needle aspiration cytology (FNAC). The clinical diagnosis was nontoxic nodular goiter in 1197 (86.4%) patients, toxic multinodular goiter in 65 (4.7%), autonomously functioning thyroid nodule (AFTN) in 64 (4.6%), and autoimmune thyroid disease (Graves' disease or Hashimoto's thyroiditis) with nodule(s) in 59 (4.3%). As controls, 177 patients with nonnodular thyroid disease and 32 normal subjects were also studied. Patients with FNAC suspicious of any kind of thyroid carcinoma and patients with elevated basal and pentagastrin-stimulated serum CT, regardless of the results of FNAC, were submitted to surgery. Eight (0.57%) patients (7 with nontoxic nodular goiter and 1 with AFTN) had elevated basal serum CT levels, ranging between 55-10,000 pg/mL. The pentagastrin test was abnormal in all of them. FNAC was suggestive of MTC in 2, thyroid carcinoma in 1, benign nodule in 3, and inadequate in 2. By histology, immunohistochemistry, and Northern blot analysis of total tumor RNAs, MTC was confirmed in all patients, including the 1 with AFTN, who had the association of microfollicular adenoma and a small MTC in the same lobe. After surgery, serum CT decreased to undetectable levels in 7 patients and remained undetectable in 6 of them during a mean follow-up of 22 months, although 1 of them had a positive response to pentagastrin. Forty-four patients in the group with normal serum CT levels had FNAC suspicious for differentiated thyroid carcinoma and were treated by surgery. Differentiated thyroid carcinoma, mostly papillary, was confirmed at histology in 43 subjects (3.1% of all thyroid nodules). In conclusion, the results of our study indicate that serum CT measurement is useful for the screening of sporadic MTC in patients with thyroid nodule(s). The prevalence of MTC, diagnosed by serum CT measurement in a 12-month period, among an unselected series of 1385 patients with nodular thyroid disease was surprisingly high: 0.57% of all thyroid nodules and 15.7% of all thyroid carcinomas. Serum CT measurement was superior to FNAC in suggesting the diagnosis of MTC and was devoid of falsely positive results. Increasing the diagnostic accuracy helped the surgeon to perform more radical treatment of MTC, thus achieving frequent normalization of postoperative serum CT levels. Whether this result indicates definitive cure remains to be established on the basis of longer follow-up.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Management of patients with thyroid disease: oral health considerations.

BACKGROUND: The thyroid gland and its hormones play an important role in the regulation of growth, development and metabolic functions of the body. Thyroid diseases include a group of conditions that can affect the delivery of dental care. LITERATURE REVIEWED: The authors conducted a MEDLINE search of the medical and dental literature concerning thyroid disease and its management published between 1980 and 2000. The authors found eight published articles concerning this topic in the dental literature; a few of the articles specifically addressed thyroid disease and dental care. They reviewed the medical literature within the scope of provision of dental care. CONCLUSIONS: The oral health care professional can play a role in the screening of dental patients who have undiagnosed thyroid disease. In addition, to treat patients who have thyroid disease, a thorough understanding of the many related pathological conditions, as well as the signs and symptoms that can occur, is needed. Specific dental treatment protocols for these patients are not found in the medicodental literature published between 1980 and 2000. CLINICAL IMPLICATIONS: As part of a health care team, the dentist plays an important role in detecting thyroid abnormalities. Modifications of dental care must be considered when treating patients who have thyroid disease.

Adrenergic Antagonists↗

Autoimmune thyroid disease in the puerperium. Predictive value of thyroid enlargement and related hormonal changes occurring during pregnancy.

The incidence of goiter detected during pregnancy and its significance as an indicator of autoimmune thyroid disease after delivery was investigated in a sample of 707 pregnant women (81% in their 2nd trimester of gestation). Goiter was detected in 106 subjects (15%). Blood T4, T3, TSH, free T4 index (FT4I), antimicrosomal antibodies (AMA) and urinary iodine excretion were measured in these women and in a control group of gravidas without goiter. These measurements were repeated at 1 and 3 months after delivery. Compared with controls during pregnancy, subjects with goiter had lower FT4I values (11.0 +/- 2.8 vs 9.0 +/- 1.8; p less than 0.01) and higher TSH values (2.9 +/- 0.6 microU/ml vs 4.2 +/- 2.1 microU/ml; p less than 0.01). In contrast, T4, T3, AMA and urinary iodine excretion values were similar in both groups. In subjects with goiter FT4I values increased over pregnancy levels at 1 month (11.2 +/- 2.0; p less than 0.05) and 3 months (14.0 +/- 3.0; p less than 0.05) after delivery; in 29% a biochemical hyperthyroidism (FT4I greater than 13.5) was detected. During the same period TSH values decreased significantly (1 month: 1.9 +/- 0.7 microU/ml; p less than 0.05; 3 months: 2.7 +/- 3.0 microU/ml; p less than 0.05). Frequency of positive AMA increased from 8.6% during pregnancy up to 32.1% in the post-delivery period (p less than 0.01). In the control group no variation in the FT4I, TSH or AMA were observed after delivery. These results indicate that goiter during pregnancy is common in Chilean gravidas and that it has predictive value for the appearance of autoimmune thyroid disease after delivery.

Adolescent↗

SEL1L microsatellite polymorphism in Japanese patients with autoimmune thyroid diseases.

The autoimmune thyroid diseases (AITDs), comprising Graves' disease (GD) and Hashimoto's thyroiditis (HT), appear to develop as a result of complex interactions between predisposing genes and environmental triggers. A recently performed genome-wide linkage study identified six loci that showed evidence for linkage to AITD. One locus, GD-1, on chromosome 14q31 was mapped to within 2 centimorgans (cM) of the recently reported multinodular goiter (MNG)-1 locus. Furthermore, microsatellite markers for the thyroid stimulating hormone receptor gene on chromosome 14q31 were associated with AITDs in the Japanese population. A newly isolated growth factor, SEL1L, was recently mapped to 14q31, and we considered it an interesting candidate gene to examine with respect to both GD and MNG. We therefore have analyzed a dinucleotide (CA)n repeat polymorphism in the intron 20 of the SEL1L gene in patients with AITDs and in normal subjects. The polymorphic marker was analyzed by polymerase chain reaction (PCR) followed by electrophoresis on denaturing polyacrylamide gels. There was no significant difference in the distributions of SEL1L alleles between patients and controls. The present results do not support an association between a dinucleotide repeat polymorphism in intron 20 of the SEL1L gene and AITD in Japanese women.

Female↗

Familial distribution of thyroid disease and diabetes: further evidence for aetiological heterogeneity of diabetes mellitus.

The prevalences of thyroid disease, insulin-dependent and non-insulin-dependent diabetes were compared in first degree relatives of diabetics with and without coexisting autoimmune thyroid disease. Thyroid disease was more common in siblings of diabetics with thyroid disease than in those of diabetics without thyroid disease. Insulin-dependent diabetes was more common in siblings of diabetics with a personal or family history of thyroid disease than in those of diabetics without such a history. The prevalence of non-insulin-dependent diabetes was unrelated to that of thyroid disease but was greater in siblings of non-insulin-dependent diabetics than in those of insulin-dependent diabetics. These findings add further support to the aetiological distinction between insulin-dependent and non-insulin-dependent diabetes and suggest that further heterogeneity exists within the population of insulin-dependent diabetics based on the presence of a personal or family history of thyroid disease.

Adult↗