F Velluzzi

More on smoking habits and Graves' ophthalmopathy.

Since a relationship between cigarette smoking and the occurrence of Graves’ ophthalmopathy has been recently postulated, we reviewed the smoking habits of 1730 women, including subjects without thyroid disease, with nontoxic goiter (NTG), toxic nodular goiter or toxic adenoma (TNG), Hashimoto’s thyroiditis (HT), Graves’ disease without ophthalmopathy (GD) or with ophthalmopathy (GO). The prevalence of smokers in NTG, TNG and HT was about 30%, not different from that of controls. Smokers were 47.9% in GD and 64.2% in GO groups. The latter figures were highly different from those of the other groups and also from each other. The percentage of heavy smokers was higher in patients with more severe ophthalmopathy. No clear explanation for this phenomenon can be offered. The absence of a high prevalence of smokers among patients with nontoxic goiter, nonautoimmune hyperthyroidism and Hashimoto’s thyroiditis, limits the impact that smoking might have had in the pathogenesis of goiter, hyperthyroidism and autoimmune phenomena of GD and GO.

Relationship of the increased serum interleukin-6 concentration to changes of thyroid function in nonthyroidal illness

Variations in the serum concentration of interleukin-6 (IL-6) have been reported concomitantly with thyroid dysfunction: increased serum IL-6 levels have been found in patients with thyroidal destructive processes, such as subacute thyroiditis, some forms of amiodarone-induced thyrotoxicosis, or after percutaneous ethanol injection into “hot” thyroid nodules, as a result of the cytokine release from the damaged thyrocyte. In addition, recent in vitro evidence suggests that IL-6 might account, at least in part, for changes of thyroid economy found in nonthyroidal illness (NTI). In this cross-sectional study we addressed this problem by measuring serum IL-6 levels in 71 patients with NTI, due to neoplasia(n=25), chronic liver disease (n=9), chronic renal failure (n=28), or other chronic nonthyroidal disorders (n=9). These patients had reduced mean serum total T3 (TT3) and free T3 (FT3) concentrations, normal total and free T4 levels, normal TSH values, and increased serum reverse T3 (rT3) concentration (with the exception of chronic renal failure patients, who had normal rT3 levels). Serum IL-6 concentration was increased above normal (i.e. >100 fmol/L) in almost all NTI patients, especially in those with low T3 values (median value: 258 fmol/L, range 73–3210, vs 152 fmol/L, range <12.5–460, in patients with normal TT3 values, p<0.001). Serum IL-6 values in NTI patients were negatively correlated with serum FT3 values (r=0.56, p<0.001), and positively correlated with serum rT3 values (r=0.78, p<0.001). The increased serum IL-6 levels might represent a systemic reaction to disease, possibly mediated by stimulation of IL-6 synthesis and release induced by other cytokines, such as IL-1 and tumor necrosis factor. Whether IL-6 is simply a marker of NTI or is responsible, at least in part, for abnormalities of thyroid function tests, as suggested by previous in vitro evidence, remains to be established.

Thyroid abnormalities during lithium treatment

Thyroid function was evaluated in 150 Sardinian outpatients at different stages of lithium treatment. A visible and/or palpable goitre was found in 51% of patients, and there was no apparent correlation with the duration of treatment. No cases of symptomatic hypothyroidism were observed, but subclinical hypothyroidism was present in 19% of patients. The prevalence of specific antithyroid antibodies was positively correlated with age and duration of lithium treatment, and was higher in women. Subclinical hypothyroidism was observed in 53% of antibody‐positive lithium‐treated patients. Carbamazepine in combination with lithium was associated with significantly lower levels of total T4 and T3 than with lithium alone, and the ratios between total and free hormones were also decreased.

Thyroid and celiac disease: clinical, serological, and echographic study

Abstract Objective: We sought to reevaluate the prevalence of thyroid dysfunction and thyroid autoimmunity in 47 patients with celiac disease; 91 healthy subjects were studied as controls. Both patients and controls were from Sardinia, Italy. Methods: Diagnosis of celiac disease was made on the basis of clinical history, presence of positive antigliadin IgA (AGA-A) and IgG (AGA-G) antibodies, antireticulin antibodies (ARA), antiendomysium antibodies (EMA), and was confirmed by jejunal biopsy. HLA class II typing for DQB1 and DQA1 alleles was performed in 36/47 celiac patients. Thyroid was evaluated by palpation and echography; serum free thyroid hormones (FT4, FT3), thyrotropic hormone (TSH), and antithyroid peroxidase autoantibodies (anti-TPO) were assayed by radioimmunoassays. Results: The prevalence of anti-TPO was higher in celiac patients (29.7%) than in healthy controls (9.6%) (p

Independent expression of serological markers of thyroid autoimmunity and hepatitis virus C infection in the general population: Results of a community-based study in northwestern Sardinia

To assess the relationship between serological markers of thyroid autoimmunity and chronic hepatitis C, we surveyed the general population of two villages in the region of Sardinia, Italy, where infection with hepatitis viruses is endemic and the prevalence of autoimmune diseases is elevated. A total of 1310 subjects aged 6–88 years (65% of the total resident population) participated in the survey, and 1233 (94%; 444 males and 789 females) agreed to provide a blood sample. Autoantibodies to thyroid peroxidase (anti-TPO) were measured by radioimmunoassay; antibodies to HCV (anti-HCV) by a third generation enzyme immunoassay and borderline positive results confirmed by recombinant immunoblot assay. For both anti-HCV and anti-TPO the ageand gender-standardized prevalence rates (SPR) were calculated and the significance of the association between the two antibodies tested by Yates corrected χ2 test. The overall SPR for anti-HCV was 50.7×10−3 (86/1,233), similar between men [49.1×10−3 (22/444)] and women [52.3×10−3 (64/789)]. The overall SPR for anti-TPO was 136.9×10−3 (204/1,233), and that among women [201×10−3 (174/789)] was almost 3-fold that among men [71.6×10−3 (30/444)]. A concurrent anti-HCV and anti-TPO positivity was found in a small minority of subjects [8/1,233 (0.65%)], all women aged 57–81 years. The SPR for the two concurrent events was 3.3×10−3, which was not significantly different (Yates corrected χ2 test = 0.65) from that expected under the assumption of unrelated events. To explore whether HCV infection is a risk factor for anti-TPO positivity, we designed a casecontrol study with anti-TPO positive subjects as the cases, and anti-TPO negative subjects as the controls. The age- and gender-adjusted odd ratio (OR) was 0.4 (95% CI 0.2,0.7), indicating a negative association. In conclusion, no evidence for epidemiological association of circulating thyroid autoantibodies and antibodies to HCV was found. Our findings do not therefore support a pathogenetic link between HCV infection and thyroid autoimmunity.

The course of thyroid abnormalities during lithium treatment: a two-year follow-up study

A total of 116 patients on lithium treatment were followed up for 2 years to determine the course and the clinical relevance of thyroid abnormalities. Elevated thyroid‐stimulating hormone (TSH) concentrations were transitory in most patients, except those with serum antithyroid antibodies. The patients who initially had microsomal antibodies remained positive, with an increase in titre in two‐thirds of cases. Three young patients of both sexes developed thyroid autoimmunity early in the treatment. The risk of developing hypothyroidism was higher in women, especially in the presence of antibodies. TSH concentrations were significantly lower when carbamazepine was combined with lithium.

Fifteen-year follow-up of thyroid function in lithium patients

Objective: To study prospectively the course of clinically relevant thyroid dysfunction in a cohort of patients on long-term lithium treatment. Method: Patients (no.=150) who had undergone a cross-sectional evaluation of their thyroid function in 1989, when they were at different stages of lithium treatment, were followed up for thyroid circulating thyroid antibodies, hypothyroidism, hyperthyroidism, and thyroidectomy, during a further period of lithium exposure of up to 15 yr. Results: Annual rates of newly developed circulating thyroid antibodies and hypothyroidism were 1.7 and 1.5%, respectively. Subjects with thyroid antibodies had a higher chance of requiring substitution treatment with levothyroxine for hypothyroidism compared with subjects with no evidence of thyroid antibodies (6.4% annual rate compared to 0.8%; relative risk: 8.4; 95% confidence interval: 2.9–24.0). One case of hyperthy-roidism was observed over 976 patient-yr. Three patients underwent thyroidectomy during follow-up (two for multinodular goiter and one for multi-centric papillary carcinoma). Conclusions: Lithium may be associated with hypothyroidism in particular in the presence of circulating thyroid antibodies. Incidence of thyroid antibodies is comparable with that reported for the general population. Hyperthyroidism and thyroid cancer are rare.

Six‐year follow‐up of thyroid function during lithium treatment

A cohort of patients at various stages of lithium treatment was followed up for 6 years in order to evaluate the course of thyroid abnormalities. Ultrasonography confirmed that lithium can increase thyroid size, especially in cigarette smokers, and that it can affect the texture of the gland. However, the incidence of clinical hypothyroidism or specific thyroid autoimmunity does not exceed that found in the general population. Repeated determinations of thyrotrophin (TSH) concentrations can prevent clinically relevant consequences. Addition of carbamazepine to lithium can counteract lithium‐induced subclinical hypothyroidism, possibly improving prophylactic efficacy in recurrent affective disorders.

Endemic goiter and thyroid function in Central-Southern Sardinia: Report on an extensive epidemiological survey

Although the existence of endemic goiter and cretinism in Sardinia is known since to ancient time, scanty information collected according to WHO criteria is available. In the present paper the results of an extensive epidemiological survey carried out in juvenile population living in some rural and/or hilly villages in the provinces of Nuoro and Oristano in Central-Southern Sardinia and in urban area of Cagliari, are reported. In the majority of the villages the mean urinary iodine excretion was lower than 60 μg/L; the goiter prevalence ranged between 39% and 61% in the district of Nuoro and between 21% and 56% in the district of Oristano. In the control area the urinary iodine excretion was 105 μg/L with a goiter prevalence of 12%. Goiter prevalence was not always inversely related to urinary iodine excretion. No relevant thyroid function alterations were found. In conclusion: 1) in extraurban areas of Central-Southern Sardinia mild to moderate iodine deficiency and endemic goiter are still a widespread problems; 2) also in urban area endemic goiter prevalence is still higher than 10%; 3) extemporary urinary samples are inadequate for assessing the severity of goiter endemia in mild to moderate iodine deficiency; 4) in mildly affected districts palpation is inaccurate for assessing the prevalence of goiter; 5) no relevant alterations of thyroid function were documented in juvenile population.

SARDINIA : A BATTLEFIELD APPROACH TO TYPE I DIABETES EPIDEMIOLOGY

Sardinia and Finland have the highest incidence of insulin-dependent diabetes mellitus (IDDM) in the world. Therefore, both regions represent ideal observatories for investigating the environmental, genetic and immunological factors which have led to this dramatic increase. We have concentrated our efforts on Sardinia. Among several projects, there is the mapping of the island for hot and cold spots for overt IDDM. In order to map the island for pre-IDDM, we have collected and bled around 10,000 school children (age 6-14 years) and we are now in the process of enrolling around 30,000 new-born babies. We report here our initial results, which show that progression to IDDM is accompanied in both cohorts by the presence of a combination of islet-cell antibodies with either glutamic acid decarboxylase or IA-2 antibodies or both. This approach should lead to the design of reliable models of IDDM prediction in the general population, which will benefit an early insulin treatment and, hopefully, an effective prevention of the disease.