[Current findings in thyroid autoimmunity].
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Autoantibodies↗
Biomedical subjects
S Mariotti
Publications and source records attributed to S Mariotti.
The 25 year estimated probability of death from some specific causes as a function of twelve risk factors in middle aged men.
Twelve risk factors previously identified as predictors of all causes of death in a 25-year follow-up of a sample of 1530 men aged 40-59 at entry, have been tested as predictors of specific causes of death. They were age (AGE), mean blood pressure (MBP), cigarette smoking (CIG), forced expiratory volume (FEV), arm circumference (ARM), father-life status (FHAS), mother-life status (MHOS), shoulder-pelvis ratio (SPR), vital capacity (VC), arcus senilis (ARCS), serum cholesterol (CHOL) and xantelasma (XANT). Using the proportional hazards model and considering coronary heart diseases, strokes, cancers, violent deaths, and other causes as end-points, AGE and MBP were significant predictors for all conditions, including violent deaths. CIG predicted coronary heart disease, stroke and cancer; FEV, VC, and ARM were protective for all end-points but significant only for a few of them. FHAS and MHOS were positively associated with all end-points but significant only for a few of them. ARCS and XANT were predictive for only a few conditions and, surprisingly, XANT was a significant risk factor for cancer. Finally CHOL was specifically predictive only for coronary heart disease.
Adult↗
Comparison of complement fixation and radioassay techniques to detect solubilized human thyroid microsomal antigenic activity.
Although recently the human thyroid microsomal antigen (M-Ag) has been possibly identified as the thyroid peroxidase, its nature remained unknown over almost three decades. One of the difficulties encountered in the identification of M-Ag derived from the conflicting data obtained in the attempts to solubilize active antigenic material from thyroid subcellular fractions. In particular, following detergent treatment, M-Ag could not be detected by complement fixation, while a full recovery of the antigen has been observed using a radioassay technique. In the present investigation, the antigenic activity of Triton X-100 solubilized thyroid microsomes was assessed in parallel by complement fixation and radioassay methods employing the same anti-microsomal antibody (anti-M Ab) preparation for antigen detection. In untreated microsomes antigenic activity was detected by both methods. In contrast, detergent solubilized M-Ag was detected by radioassay, but could not be detected by complement fixation. These data indicate that detergent solubilization diminishes the complement fixing capacity of M-Ag, while the solubilized antigen can still be fully detected by its binding reaction with the autoantibody, and explain the discrepant results obtained in previous studies.
Autoantibodies↗
Development of thyroid disease in patients with primary and secondary Sjögren's syndrome.
Autoimmune thyroid disease associated to Sjögren syndrome (SS) may be defined by serological and functional abnormalities. We studied the prevalence of serum anti-thyroid autoantibodies and the development of thyroid functional defects by a follow-up investigation in patients with primary (pSS) and secondary SS (sSS). In keeping with previous literature data, our findings confirmed an increased prevalence of thyroid autoimmune phenomena in the whole series of patients with SS. In addition, evidence was provided for a greater incidence of serological and functional thyroid abnormalities in pSS when compared to sSS. Follow-up study also showed that the rate of thyroid autoimmune disease development was higher in pSS than in sSS. The appearance of circulating anti-thyroid antibodies was particularly frequent in patients with preexisting antibodies against extractable nuclear antigens (anti-ENA). These data indicate the need for a careful monitoring of thyroid function in SS patients, with particular regard to those with pSS and positive anti-ENA tests.
Adult↗
Evaluation of 10 QT prediction formulas in 881 middle-aged men from the seven countries study: emphasis on the cubic root Fridericia's equation.
In 881 middle-aged men from one Italian cohort of the Seven Countries Study, QT and RR intervals were measured in lead 2 from resting ECGs (25 mm/sec) and fitted separately with 10 mathematically different QT prediction formulas. The relative accuracy of fit to data was assessed from the minimum mean-squared residual and the minimum Akaike Information Criterion values. Using the Minnesota code, 588 men had normal (group 1) and 293 had abnormal (group 2) ECGs. A better fit to QT-RR data by all formulas was observed in group 1, compared with group 2. Among one-parameter equations in both groups, the cubic root Fridericia's formula is better suited to fit the data than the Bazett's square root or other formulas. The former compares favorably with multiparameter equations or with the inverse relation and gives the best fit in group 2. Thus the cubic root equation might be more accurate than the square root or several complex formulas for correcting measured QT intervals for cardiac cycle length in middle-aged men.
Arrhythmias, Cardiac↗
Clinical and laboratory indicators of extent of ulcerative colitis. Serum C-reactive protein helps the most.
We estimated the extent of the inflammatory mucosal lesion by colonoscopy and biopsy in 60 patients with their first attack of ulcerative colitis. Proctitis was found in 12, proctosigmoiditis in 19, left-sided colitis in 10, and extensive colitis in 19. Fourteen clinical variables and laboratory measurements (bowel frequency, stool consistency, rectal bleeding, fecal mucus/pus, temperature, pulse rate, white blood cell count, hematocrit, sedimentation rate, serum iron, serum albumin, serum alpha 2-globulin, serum C-reactive protein, and seromucoids) were determined. All the variables except rectal bleeding and hematocrit were correlated (p less than 0.001) with the extent of colitis. On stepwise discriminant analysis, only C-reactive protein distinguished proctosigmoiditis from more improved the discrimination. Cross-validation by the "jack-knife method" showed that 86.7% of patients were correctly classified, the errors consisting in underestimation of disease in 8/29 patients with extensive colitis.
Adolescent↗
Treatment of inappropriate secretion of thyrotropin with somatostatin analog SMS 201-995.
Inappropriate thyrotropin secretion (IST) may originate from either neoplastic disease (nIST) or non-neoplastic resistance to thyroid hormone (nnIST). An inhibitory effect of somatostatin on TSH secretion has been documented. In an attempt to elucidate the possible therapeutic effect of this peptide on nIST and nnIST, a study was conducted in 7 such patients. Sandostatin (SMS 201-995) was administered in daily doses of 100 micrograms for several days to 1 month. Four patients with nIST responded with a fall in circulating TSH as well as alpha-subunit with concomitant normalization of free thyroxine and clear symptomatic improvement. In the 3 nnIST patients this effect was considerably less apparent and a partial TSH escape was observed on long-term treatment in 2 cases. The importance of somatostatin and its analogs in the management of thyroid malignancy is stressed.
Antineoplastic Agents↗
Radioactive iodine thyroid uptake in patients with amiodarone-iodine-induced thyroid dysfunction.
Amiodarone, an iodine-rich drug, represents at the present, at least in Europe, one of the most common sources of iodine-induced thyroid dysfunction. The drug may induce both hypothyroidism and thyrotoxicosis. In spite of the large iodine intake occurring during amiodarone therapy, 131I thyroid uptake is detectable in patients with amiodarone-iodine-induced hypothyroidism, irrespective of the presence or absence of underlying thyroid disease. In contrast, in patients with amiodarone-iodine-induced thyrotoxicosis, 131I thyroid uptake is normal or even elevated in those with co-existent underlying thyroid disorders, whereas it is very low in those with an apparently normal thyroid gland. Perchlorate discharge test was performed in 8 patients with hypothyroidism and in 5 patients with hyperthyroidism induced by amiodarone: a positive test was found in all hypothyroid patients and a negative test in all hyperthyroid patients.
Adult↗
Thyroid autoantibodies in thyroid cancer: incidence and relationship with tumour outcome.
In the present investigation we studied serum anti-thyroglobulin and anti-thyroid microsomal autoantibodies, measured by hemagglutination technique, in 600 patients with thyroid cancer seen by us from 1975 to 1985 (mean follow-up 46 months). Positive thyroglobulin antibodies and/or microsomal antibodies were found in 138 (23%) patients (23.9% with papillary, 25% with follicular, 16.1% with anaplastic, and 4.1% with medullary thyroid carcinomas). The incidence of positive tests was similar in each decade of life (ranging between 21.9% and 27.9%), whereas in a normal sex-matched population with no evidence of thyroid disease, the frequency of positive tests was very low in young people and increased to 23% in people older than 60. In 64 patients with no evidence of residual or metastasic thyroid tissue after surgery and radioiodine, initially positive antibody titres became negative in 54.6%, decreased in 32.8%, did not change in 3.1%, and increased in 9.3%. On the contrary, antibody titres of patients with persistent disease became undetectable in 8.3%, decreased in 16.6%, remained unchanged in 25%, and increased in 50%. The clinical course of differentiated thyroid cancer was unaffected by the presence of thyroid antibodies and no difference was found in the death rate between antibody-positive and antibody-negative patients (11.5% and 13.6%, respectively). In conclusion, our data indicate that: 1) autoimmune phenomena are not an infrequent finding in thyroid cancer; 2) as in non-malignant thyroid diseases, positive-antibody tests are more frequently observed in females than in males; 3) at variance with normal controls, no age-dependent increase in serum anti-thyroid antibodies was found in thyroid cancer; 4) the presence of metastatic thyroid tissue seems to be necessary to perpetuate the autoantibody synthesis, and 5) anti-thyroid autoantibodies are not a protective or worsening factor in the tumour outcome.
Adolescent↗
Recent progress in the study of thyroid autoantigens.
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Autoantibodies↗
The use of multiple logistic function to predict surgical risk.
A method for preoperative assessment of surgical risk, in function of several risk factors, was developed using the multiple logistic function, as a model of multivariate statistical analysis. This model has the advantage to express the two considered outcomes (perioperative complications and death) in numerical terms of probability. The data were obtained from 8630 consecutive patients admitted to 62 hospitals located in various regions of Italy. The patients were divided at random into two groups: group A (6040) was used to develop the method, and group B (2590) was used as control. The method is based on the role played by seven risk factors, that were shown to be significantly related to the two outcomes. These factors are age, systolic blood pressure, pathological changes of renal function, presence of concomitant diseases, estimated duration of surgical procedure, type (major or minor) and timing of surgery, (elective, delayed or emergency). The relative and independent role of each of these factors (beta) and the value of constant alpha were estimated by maximum likelihood method. The surgical risk is assessed by solving the multiple logistic equation, and multiplying the beta values by the corresponding individual coded values of the risk factors represented by the various x's. When the method was tested by applying the computed values of alpha and beta's to assess the outcomes in the control group, the predictions resulted highly accurate (r = 0.99). To simplify the calculation of surgical risk, in appendix a computer program in Basic, already predisposed to receive in code the individual values of x's, is reported.
Adolescent↗
[Thyroid uptake of I131 in iodine-induced thyroid pathology caused by amiodarone].
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Adult↗
Prediction of surgery for obstruction in Crohn's ileitis. A study of 64 patients.
The charts of 64 patients with Crohn's ileitis were reviewed to determine what characteristics at the time of first observation at a specialized center were predictive of surgery for irreversible obstruction, using Cox's proportional hazard model. Individual variables which proved significant (P less than 0.01) included age at presentation to the clinic, serum albumin, sedimentation rate, and the presence of radiologic strictures. Patients eventually requiring surgery were older than the rest because of a later date of symptom onset; furthermore, patients with strictures on initial x-rays had not been ill for a longer period of time than those who did not have strictures. These data suggest that fibrosis and stenosis are characteristic of a subgroup of Crohn's patients, rather than being inevitable phases of disease evolution. Multivariate analysis revealed that patients with low serum albumin, high sedimentation rate, and roentgenologic stenosis at first observation were ten times as likely to require surgery for obstruction at 10 years than those without any of these three unfavorable parameters.
Adult↗
High prevalence of subacute thyroiditis during summer season in Italy.
Eighty consecutive patients with typical subacute thyroiditis were evaluated. Sex distribution showed a higher incidence in females (F/M 3.2/1), with a mean age of 44 yr. In the majority of patients (51/80 = 66%) the onset of the disease was between June and September (46% in July and August). The remaining cases were distributed in the other months without a clear monthly prevalence. These results indicate that the seasonal distribution of subacute thyroiditis is almost superimposable to that of established infections due to some enteroviruses (Echovirus, Coxsackie A and B viruses), suggesting that summer enterovirus infections may be responsible for a large proportion of cases of subacute thyroiditis.
Acute Disease↗
Amiodarone iodine-induced hypothyroidism: risk factors and follow-up in 28 cases.
Amiodarone, an iodine-rich drug widely used for the treatment of cardiac tachyarrhythmias, may induce either hyperthyroidism or hypothyroidism. Of 467 patients chronically treated with this drug referred to our institution, amiodarone iodine-induced hypothyroidism (AIIH) developed in 28 patients (6%). AIIH patients were subdivided into two groups according to the presence (group A) or absence (group B) of underlying thyroid abnormalities. Thyroid autoantibodies were present in 10 of 19 patients from group A and 0 of 9 patients from group B. The thyroid 24-h radioiodine uptake (RAIU) was evaluated in 15 patients: low values (less than 4%) were found in three patients and detectable values (7-50%) were observed in 12. Perchlorate discharge tests were positive in all four patients tested. Follow-up data were available in 20 patients (16 in group A and four in group B). Hypothyroidism was transient in 12 (60%) and persistent for several months after amiodarone withdrawal in eight (40%). While all patients in group B had transient hypothyroidism, 50% of patients with underlying thyroid abnormalities (group A) had persistent hypothyroidism. Thyroid autoantibodies were found in seven of eight patients with persistent hypothyroidism and in only three of 12 patients with transient hypothyroidism. Conversely, seven of 10 patients with positive thyroid autoantibodies had persistent hypothyroidism and 9 of 10 patients with undetectable thyroid autoantibodies had transient hypothyroidism. These data indicate that: (i) AIIH may develop in patients with or without underlying thyroid abnormalities; (ii) RAIU is inappropriately elevated in many patients with AIIH; (iii) intrathyroidal iodine is not organified; (iv) serum thyroid autoantibodies represent a risk factor for the development of AIIH; (v) AIIH spontaneously remits after amiodarone withdrawal in patients without thyroid abnormalities, but may persist in patients with concomitant thyroid disorders, especially those with circulating thyroid autoantibodies.
Adult↗
Determinants of all causes of death in samples of Italian middle-aged men followed up for 25 years.
A total of 1712 men aged 40 to 59 years in two rural cohorts of northern and central Italy have been followed up for 25 years after an entry examination in 1960. Forty one individual characteristics have been considered as possible predictors of death in the next 25 years. After exclusion of 55 men with life threatening diseases (cardiovascular and cancer) and of 161 men because of missing measurements, 1495 men have been analysed for relation between entry factors and subsequent death (n = 670). Twelve factors eventually emerged as powerful predictors of future death: in hierarchical order, age, blood pressure, forced expiratory volume, cigarette smoking, xanthelasma, mother life-status, arm circumference, father life-status, shoulder-pelvis ratio, vital capacity, arcus senilis, and serum cholesterol. Discrimination as provided by logistic modelling placed 19.6% of all cases in the upper decile of the estimated risk, 36.8% in the upper quintile, 2.5% in the lowest decile, and 7.1% in the lowest quintile. Out of those located in the lowest decile of risk, 11.4% died within 25 years while the corresponding percentage in the upper decile was 87.3%. Use of the Cox model yielded slightly better coefficients than logistic function.
Adult↗
Amiodarone: a common source of iodine-induced thyrotoxicosis.
Amiodarone, a iodine-rich drug widely used in the treatment of tachyarrhythmias, represents one of the most common sources of iodine-induced thyrotoxicosis. The data concerning 58 patients with amiodarone-iodine-induced thyrotoxicosis (AIIT) were analyzed in the present study. Prevalence of AIIT was higher in males than in females (M/F = 1.23/l). Thyrotoxicosis occurred either during treatment with or at various intervals after withdrawal of amiodarone. AIIT developed not only in patients with underlying thyroid disorders, but also in subjects with apparently normal thyroid gland. Classical symptoms of thyrotoxicosis were often lacking, the main clinical feature being a worsening of cardiac disorders. Biochemical diagnosis of AIIT was established by the finding of elevated serum total and free triiodothyronine levels, since elevated serum total and free thyroxine could be found also in euthyroid amiodarone-treated subjects. Twenty-four-hour thyroid radioiodine uptake was very low or undetectable in AIIT patients with apparently normal thyroid glands, while it was inappropriately elevated in patients with underlying thyroid disorders, despite iodine contamination. The role of autoimmune phenomena in the pathogenesis of AIIT appeared to be limited, because circulating thyroid autoantibodies were undetectable in AIIT patients without underlying thyroid disorders or with nodular goiter. Conversely, humoral features of thyroid autoimmunity were mostly found in AIIT patients with diffuse goiter. Treatment of AIIT appeared to be a difficult challenge. Among the 11 patients given no treatment, thyrotoxicosis spontaneously subsided in the 5 patients with apparently normal thyroid gland, whereas the 6 patients with nodular or diffuse goiter were still hyperthyroid 6-9 months after discontinuation of the drug. The administration of high doses (40 mg/day) of methimazole alone proved to be ineffective in most (14/16) patients given this treatment. Twenty-seven patients were treated by methimazole combined with potassium perchlorate (1 g/day). With one exception, euthyroidism was restored within 15-90 days in all cases with underlying thyroid abnormalities, and within 6-55 days in subjects with apparently normal thyroid gland. Thus, the combined treatment appears to be the most effective one, but, due to the potential toxicity of potassium perchlorate, it should be reserved to patients with severe thyrotoxicosis and should be carefully monitored.
Adult↗
Thymulin deficiency and low 3,5,3'-triiodothyronine syndrome in infants with low birth weight syndromes.
Experimental and clinical evidence indicates that thymic endocrine function is under neuroendocrine control. Recently, a positive correlation was found between plasma thymulin (a major endocrine product of thymus) and serum thyroid hormone concentrations. Low serum thyroid hormone concentrations are frequently found in premature newborn infants. In this study we measured plasma thymulin by bioassay and serum T3 and T4 in a series of healthy fullterm newborns and in premature infants with various disorders. The study subjects were 26 healthy fullterm infants, 23 fullterm small for gestational age infants, 30 preterm appropriate for gestational age (AGA) infants, 22 preterm small for gestational age infants and 30 infants with respiratory distress syndrome, of whom 15 were fullterm and 15 were preterm AGA. Blood samples were obtained 3, 5, 10, 20, and 40 days after delivery. In the healthy fullterm infants plasma thymulin concentrations were low during the first days of life and subsequently increased, reaching normal values for children aged 1-12 months by the 10th day after birth. Persistently low plasma thymulin and serum T3 levels were found in the majority of infants with pathological conditions; the lowest values for both hormones were found in infants with respiratory distress syndrome. A highly significant positive correlation was present in all groups between mean plasma thymulin and serum T3, but not T4. Short term T3 administration in 6 additional preterm AGA infants caused a significant increase in plasma thymulin titers compared to those in 6 untreated infants. We conclude that plasma thymulin is decreased in premature newborns with the low T3 syndrome and that this abnormality may be reversed by administration of T3. These findings indicate that thymic endocrine activity is modulated by thyroid function in early postnatal life.
Euthyroid Sick Syndromes↗