IODINE STATUS IN PREGNANT WOMEN AFTER A DECADE OF UNIVERSAL SALT IODIZATION IN ROMANIA.

OBJECTIVE: To assess iodine status (median urinary iodine concentration) in 118 pregnant women during the third trimester from endemic or non-endemic areas, a decade after implementation of Universal Salt Iodization in Romania. SUBJECTS AND METHODS: One hundred and eighteen pregnant women in the third trimester were included in the study group (age range: 16 - 46 years, mean age: 28.78 years). Median urinary iodine concentration (UIC) and body mass index (BMI) were evaluated. Data regarding region of provenance, smoking habits during pregnancy, education level, iodized salt intake, bread intake, iodine supplements, comorbidities (iron deficiency anemia) and birth weight were assessed. Morning urine was collected to measure median UIC. The study was approved by the Local Ethics Committee. RESULTS: Median UIC in the study group was 206 mcg/L, reflecting iodine sufficiency during pregnancy. There is a statistically significant difference between pregnant women with and without iodine supplements from rural areas (281.5 versus 196.1 mcg/L, respectively, p=0.023). In the subgroup without iodine supplementation, there was a significant difference between overweight and obese subjects vs. normal weight subjects (232.5 versus 194 mcg/L, p=0.012). Only in the subgroup with a daily intake of less than 5 slices of bread (usually containing iodized salt) we found significant differences between those with and without iodine supplements (245.2 versus 128.3 mcg/L). Iron deficiency anemia was found in 29.66% and 19.49% were current smokers during pregnancy. CONCLUSIONS: Median UIC in the study group was 206 mcg/L, reflecting iodine sufficiency during pregnancy. The difference between the subgroup with iodine supplements and the subgroup without iodine supplements was not statistically significant, probably due to the excessive consumption of bread and other bakery products which is traditional in Romania.

THYROID METASTASIS FROM CLEAR CELL CARCINOMA OF THE KIDNEY 16 YEARS AFTER NEPHRECTOMY.

The thyroid gland is one of the most vascularized organs in the body. However, metastatic disease to the thyroid gland is rare. When it does occur kidney is the most common primary tumor site, followed by melanoma, lung, breast, esophagus, uterus and colon carcinoma. We describe the case of an isolated thyroid metastasis from clear cell renal carcinoma occurring 16 years after nephrectomy. An 82 years-old woman presented for the recent growth of a right thyroid nodule, diagnosed 3 years before, when a fine needle aspiration biopsy found a benign cytology suggesting a well-differentiated follicular thyroid adenoma. Her medical history included type 2 diabetes mellitus, atrial fibrillation and a right nephrectomy for a clear cell renal carcinoma done 16 years before. The patient has lost weight but she was otherwise asymptomatic. The right lobe goiter was painless, firm, and mobile with deglutition, without signs of local compression or latero-cervical lymphadenopathy. Thyroid ultrasonography revealed an enlarged (9.9 cm) macronodular right lobe, with multiple cystic areas, with normal left lobe and a thrombus in the right internal jugular vein. Thyroid function tests were normal. The patient was suspected of thyroid carcinoma and underwent a near total thyroidectomy. Histopathological examination revealed a metastasis of clear cell renal carcinoma in the right thyroid gland lobe (8.5/5/5 cm). Further imaging showed no primary tumor or other metastases. Metastatic renal carcinoma to the thyroid should be considered in any patient presenting with a thyroid mass and a medical history of operated renal cell carcinoma, since it can occur up to 25 years after nephrectomy.

Amiodarone-induced thyroid dysfunction in cardiac patients from areas with iodine deficiency.

UNLABELLED: Amiodarone via iodine excess can determine thyroid dysfunction. AIM: to assess thyroid dysfunction in patients treated with amiodarone, according to previous daily iodine intake. MATERIAL AND METHODS: 63 patients treated with amiodarone were assessed. 11 of 63 were resident in a moderate iodine deficient area. Thyroid stimulating hormone (TSH), free and total thyroxine (T4) and total triiodothyronine (T3) were measured. Thyroid ultrasonography, color flow Doppler sonography (CFDS), radioiodine uptake (RAIU) at 2 and 24 hours were also performed. RESULTS: Amiodarone-induced thyrotoxicosis developed in 31 patients (49.2%); 17 patients (27%) remained euthyroid. Patients from iodine deficient areas developed more frequent hyperthyroidism (91% vs. 40.4%), at significant lower cumulative doses of amiodarone, and never hypothyroidism. Overt hyperthyroidism prevails (29/31 patients). Frequency of amiodarone-induced thyrotoxicosis type I was 19% (12/63), type II 12.7% (8/63), and of mixed forms 17.5% (11/63), without significant differences between the two geographical areas. There are no peculiar features of amiodarone-induced thyrotoxicosis versus common hyperthyroidism, but there is a tendency at recurrence of tachyarrhythmias at lower levels of T3 than in common hyperthyroidism. Amiodarone-induced hypothyroidism developed in 15 patients (23.8%) and none was from iodine deficient areas, but almost half show high levels of antithyroid peroxidase antibodies (ATPO). Subclinical hypothyroidism prevails (11/15 patients). CONCLUSION: a predictor for amiodarone-induced thyroid dysfunction is iodine deficiency in nutrition.

Overt and subclinical hypothyroidism and atherosclerotic arteriopathy of the lower limbs (clinical and subclinical).

Hypothyroidism promotes both significant diastolic hypertension and hypercholesterolemia and, as a consequence, their combination has been suggested to accelerate atherosclerosis. Prevalence of elevated LDL-cholesterol is significantly increased not only in overt hypothyroidism, but also in subclinical hypothyroidism. Serum TSH will be determined in all the patients, as a first line test and only the patients with TSH values over 5 microU/ml will be further investigated: serum T4, FT4 and antimicrosomal and antithyroglobulin antibodies. In the study group were not included severe nonthyroid illness, major depression, untreated Addison's disease and the patients using some drugs that interfere with serum TSH level.

Graves'-Basedow's disease--asthma association. Presentation of five cases.

Thyroid hormones have a non-selective permissive action on adrenergic receptors (including beta 2). Asthma is an immune disease in which some pathological pathways include beta 2 adrenergic receptor blockade. In theoretical terms, that would mean that in hyperthyroidism asthma would ameliorate. In 5 cases with Graves-Basedow's disease--asthma association this phenomenon has not appeared. The similar clinical features and follow-up of these patients suggest a narrow etiopathogenic group. In all cases, asthma has occurred previous to Graves-Basedow's disease, and the thyroid disease has been suspected because of paradoxical aggravation of asthma crises. In all cases the immune thyroid disease appeared in women over 40 years of age (two over 60 yrs). The thyromegaly was diffuse but small (and absent in one case), thyroid hormone levels have been expectedly high (T3 slightly higher than in other cases). No eye proptosis over Werner's 3rd degree has been recorded. The therapeutical problems have been as follows: contraindication of non-selective antitachycardia beta-blockers (we have administered reserpine), contraindication of non-selective adrenergic bronchodilatory agents (we have administered very low doses of aminophylline), early radical antithyroid therapy (we have administered 111-185 MBq of 131I). Thyroid function after 6 mos to 7 years follow-up have been within normal range (except one case who became hypothyroid). The asthma ameliorated early after 131I administration.

Effects of radioiodine therapy in hyperthyroidism (thyroid function, thyroid volume, Graves' ophtalmopathy, thyrotoxic heart disease).

The study group consisted of 135 hyperthyroid patients--128 with Graves' disease and 7 with toxic multinodular goiter. A single dose of radioiodine was given in 110 cases (81.48%), two doses in 22 patients (16.3%) and three doses in 3 patients (2.22%); mean total dose was 6.8 mCi (range = 3-24 mCi). The main goal of radio iodine therapy is to achieve euthyroidism; after radioiodine treatment, 61 patients (45.2%) were euthyroid, 60 patients (44.4%) with permanent hypothyroidism and 14 (10.36%) with PERSISTING HYPERTHYROIDISM--the mean duration of follow-up being 4.2 years. After radioiodine therapy, goiter became absent in 30 patients (28%); in those patients, goiter was moderately enlarged or large before therapy. Around 63% (12 cases) of the patients with thyrotoxic atrial fibrillation reverted to sinus rhythm. During the last four years (1990-1994) the patients with Graves' ophthalmopathy from the study group were treated with Prednisone after radioiodine therapy; this corticotherapy contributes to the lower percentage (1.5%) of worsening Graves' ophthalmopathy after radioiodine therapy.

Management of hyperthyroidism due to Graves' disease: a retrospective analysis of 1,000 inpatient cards.

There are three different modalities to treat hyperthyroidism due to Grave's disease: anti-thyroid drugs (ATD), radioiodine and surgery, each of them having its own advantages and disadvantages. The option for one of the three therapeutical approaches has both subjective and objective components. In Europe, a screening on the therapeutical options in Graves' disease was performed at the European Thyroid Association (ETA) initiative, being based on a questionnaire. In the Thyroid Department of the Endocrinology Institute in Bucharest, w analysed the managements of hyperthyroidism due to Graves' disease on 1,000 cards of hyperthyroid patients admitted there during the last five years. In order to diagnose Graves' disease, in vivo tests radioiodine uptake (RIU) at 2 and 24 hrs, 93.39% scintigram (92.93%), thyroid ultrasonography (15%) and reflexogram (98.06%), were carried out. Out of the in vitro tests, PBI (protein bound iodine) was performed prioritarily, while T4, T3 (variable), TSH (13.91%) were performed according to the economic factors. For the patient with moderate hyperthyroidism, antithyroid therapy was alternative with the radioiodine one (51.61% and 48.35%, respectively). The age of the patient played a major role in the decision to take. The frequency of cases treated with radioiodine was considerably higher in the patients with recurrence and in the elderly. The initial dose of antithyroid treatment was high (50-60 mg), and was reduced according to the thyroid function. The therapy duration was not pre-determined. The ATD treatment was prolonged for a time-interval ranging between 2 and 5 years, depending of the clinical status (age, sex, goiter size, exophthalmic syndrome) and the social conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

A retrospective study on the treatment and evolution of Graves' ophthalmopathy.

Although Graves' ophthalmopathy (GO) seems to be unanimously considered as an autoimmune disease, its pathogenesis is still unknown. That is why the different therapeutical formulas led to ambiguous results. We think that a critical retrospective analysis on our therapeutical possibilities in GO will help us to become aware of our limits in treating this pathology. Our study performed on 123 patients with GO-stage III-IV who were admitted several times in the Thyroid Department of our Institute between 1975-1991; mean age 42 yrs (42 in men and 43 in women. One hundred and twelve patients presented GO associated with thyroid hyperfunction and 11 patients--with hypo- and euthyroidism. Thyroid status was evaluated through clinical examination and laboratory investigations (radioiodine uptake--RIU, 2h, 24 hrs, Achillean reflexogram--AR, T4, T3--radioimmunoassay-RIA). Three therapeutical formulas which were available to us were used in our subjects with GO: 1) general corticotherapy (C) was given in 77.6% of the cases; initial doses: 60-40 mg prednisone for 3 weeks followed by decreasing doses for 2 months (number of cures according to GO severity); 2) orbital radiotherapy (RT) alone was administered from the very beginning to the subjects in whom general C was not possible (7.4% of the cases); 3) general C associated with orbital RT were applied in the very severe cases of GO stage IV-VI (15% of the cases). The two available formulas acted particularly on oedematous symptoms (53% with C and 55.55% with RT alone). Muscular changes were improved by C in 30.83% and by RT only in 11.11% of the cases. It was noticed a mild positive effect on protrusion under C in only 11.66%, and under RT in 33% of the cases. The less favourable results in the cases under both C and RT can be explained by the fact that these groups included cases with stages IV-VI of GO with severe evolution. In 24% of the patients we noted an aggravation of the GO evolution regardless the therapy administered. The possible pathological relationship between the exophthalmic syndrome (ES) and hyperthyroidism (HT) is also supported by our data. The onset of ES together with HT occurred in 63% of the cases. On the other hand, we can notice that it was a more severe disease evolution when both ES and HT were associated. The treatment of hyperthyroidism led to GO aggravation (following 131I, thyroidectomy and antithyroid agents (ATD) in 43%, 52% and 29% of the cases, respectively).

The diagnostic and prognostic value of HLA B 35 antigen in viral subacute thyroiditis.

HLA B 35 antigen was assessed in 19 patients with viral subacute thyroiditis. The antigen was present in 68.43% of patients (no = 13). The relative risk (vs 500 health blood donors) is very high (12.27), with X2 = 33.4 and p less than 0.001. Despite the high relative risk, the presence/absence of HLA B 35 antigen showed no correlations with the main clinical features in our patients; no correlations can be made for: erythrocyte sedimentation rate, radioiodine uptake, thyromegaly, hyperthyroidism and evolution.

Radioiodine treatment in recurrences of subacute thyroiditis.

The three cases of subacute thyroiditis treated by radioiodine were refractory to systemic corticoid therapy (2-3 recurrences in a mean duration of 7.6 mos) and to external antiinflammatory radiotherapy (relapses after 2 and 4 mos, respectively). No relapse after radioiodine administration has appeared (mean follow-up period: 3 yrs) and post-iodine hypothyroidism was mild.

The serum osteocalcin levels in patients with thyroid diseases.

The mechanism of bone, calcium, phosphorus and proteins abnormalities observed in hyperthyroidism is rather complex and as yet not wholly understood. Increased serum osteocalcin was recently reported in hyperthyroid patients and its decrease after 4-8 months of treatment. Osteocalcin was measured by RIA in the sera of 211 women and 18 men with thyroid diseases. The patients were divided into 3 groups according to diagnosis: I. polynodular goitre and subacute thyroiditis (59 women, 5 men); II. Graves' disease (70 women, 3 men) and III. thyroid cancer, after treatment by surgery and 131I (82 women, 10 men). The osteocalcin levels in the sera of these patients were: 2.97 +/- 2.63 ng/ml (mean +/- SD) for the women and 3.56 +/- 2.10 ng/ml for the men in the 1st group; 16.31 +/- 11.34 ng/ml for the women and 12.75 +/- 6.09 ng/ml for the man in the IInd group and, 1.01 +/- 0.60 ng/ml for the women and 0.78 +/- 0.46 ng/ml for the men in the IIIrd group. No differences were found between the osteocalcin concentrations in the hyperthyroid female patients treated with antithyroid drugs (no = 58) and the non-treated hyperthyroid women (no = 12): 16.22 +/- 11.40 ng/ml vs 16.74 +/- +/- 11.53 ng/ml. These data suggest that bone resorption stimulated by endogenous thyroid-hormones is a rather resistant processus, persisting even after 6-8 mos of associated anti-thyroid therapy. Further are analyzed the possible causes of the subnormal osteocalcin levels observed in patients with thyroid cancer treated by surgery and radioisotope, whose suppression therapy was discontinued 2-3 weeks before blood sampling.(ABSTRACT TRUNCATED AT 250 WORDS)

Significance of high levels of serum malonyl dialdehyde (MDA) and ceruloplasmin (CP) in hyper- and hypothyroidism.

The lipid peroxidation process is enhanced in both hyperoxygenated or underoxygenated tissues though its mechanism of production is different. Because in thyroid functional diseases there are severe disorders in tissue oxygenation we studied the lipid peroxidation process by using the serum level of malondialdehyde (MDA) as indicator. We also determined the serum ceruloplasmin (CP), an enzymatic protein belonging to the circulating system of antioxidative protection and also playing a role in the cell-mediated immunity. We also followed serum level of uric acid (UA). The determinations were performed on serum samples collected from three groups: 1, adult control subjects: 2. adult untreated hyperthyroid patients, and 3. adult hypothyroid thyroidectomized patients to whom replacement therapy was discontinued for at least 15 days. The mean MDA level was significantly higher in both hyperthyroid and hypothyroid patients by comparison to the control group. CP mean level was significantly lower than in controls. It was concluded that in post thyroidectomy hypothyroidism an enhancement of lipid peroxidation does exist and that its consequences are probably aggravated by the low serum CP level. The enhancement of the process occurs by other mechanisms than for hyperthyroid group. At hypothyroid patients there is an ADP excess which is degenerated to xanthine, the substrate of xanthine oxidase resulting in toxic anion superoxide and UA. In contrast with hyperthyroid group, in hypothyroid patients we observed significant higher values of UA in comparison to the controls. The excess of MDA found in hyperthyroid patients is statistically significant, but its consequences are probably less severe because the serum CP is higher than normal, a rather expected finding for an autoimmune disease.

Thyroglobulin autoantibodies in endocrine diseases.

A simple, rapid haemagglutination laboratory kit was developed for the measurement of the thyroglobulin autoantibodies (Tgl-AAb). The Tgl-AAb kit was applied to the measurement of the AAbs titres in the sera collected from 2861 endocrine patients either hospitalized in the Institute of Endocrinology (about 75%) or endocrine outpatients--the great part of patients (over 90%) being however diagnosed as thyroid disorders. The sex classification showed the F/M ratio 6.61/1 for the whole group and 7.4/1 for the positive cases. The prevalence of the Tgl-AAbs positive sera at low titre (under 1:200) is 11.6% about twofold higher than in a population of 700 blood donors (6.4%), previously reported. Among the significant Tgl-AAbs titres, chosen more or less arbitrarily over 1:200, 30.47% of the patients have titres in the range 1:200-1:5000. The Tgl-AAbs positive and negative sera are classified and analysed according to the endocrine pathology but especially thyroid disorders and the positive thyroid disease are grouped by low, high and very high Tgl-AAbs titres and by Tgl-precipitin positive. Our results are rather similar to those reported for endocrine collectivities in other countries. The technical and methodological sources of some discrepancies between the laboratory Tgl-AAbs results and the clinical symptoms and/or anatomo-pathologic results are commented as well as some of the future perspectives of the laboratory investigation of the thyroid autoimmune diseases. Concluding, a strategy schema for a possible immunogram is presented.

Hyperthyroidism in the elderly. II. Laboratory tests.

The paraclinical findings in 100 elderly hyperthyroid patients were analysed. T3-thyrotoxicosis was found in 26% of the patients and T4-thyrotoxicosis in 7.6%. T3-thyrotoxicosis was found in 50% of the cases of toxic adenoma investigated. Hypomagnesiemia and hypocholesterolemia were found in 40.4% and 20.41%, respectively, and low values of Achilles' reflex test were found in 38.4%.

Hyperthyroidism in the elderly. I. Clinical manifestations.

The most frequent clinical manifestations in 100 elderly hyperthyroid patients entered in our study were: weight loss (83%), palpitations (85%), nodular goiter (71%) and tremor (74%). Association of weight loss with anorexia and constipation was found in 6% of the patients. The apathetic form of thyrotoxicosis was present in 2% of our patients. Thyrotoxic atrial fibrillation and thyrotoxic heart disease were found in 42% and 51% respectively.

Determination of urinary mucopolysaccharides in Graves' disease.

Urinary mucopolysaccharides (u MPZ) were determined in 114 patients with thyroid diseases. The values were elevated in 95.8% of patients with Graves' disease with infiltrative ophthalmopathy, and in 66.6% of patients with Graves' disease without clinically manifest infiltrative ophthalmopathy; in the second group of patients we consider that there is a subclinical infiltrative ophthalmopathy. In conclusion, the determination of u MPZ can be considered as a criterion for the diagnosis of Graves' disease in patients with hyperthyroidism without clinically manifest infiltrative ophthalmopathy; in a number of these cases, infiltrative ophthalmopathy may become clinically manifest. For that reason, increased u MPZ can represent a criterion for an eventual delay of an ablative therapy in Graves' disease. It is not a significant statistic difference (p greater than 0.1) between the values of u MPZ in patients with Graves' disease with clinically manifest ophthalmopathy and in those with subclinical infiltrative ophthalmopathy. The thyroid functional status does not influence in any way the values of u MPZ (p greater than 0.1). There is no correlation between the degree of eye protrusion and the values of u MPZ (r = = -0.05)

Diagnosis and treatment of hyperthyroidism in elderly patients.

The clinical signs of hyperthyroidism in the elderly are often atypical and have an insidious onset. The hyperkinetic form and the exophthalmic syndrome are rare. Apathetic thyreotoxicosis occurs, with few exceptions, in the elderly. Part of the clinical signs of hyperthyroidism may be erroneously attributed to the normal aging process. Most authors consider radioiodine as the treatment of choice in elderly hyperthyroid patient.

A radioimmunoassay system for human myoglobin: method development and applications.

double antibody radioimmunoassay (RIA) system for human myoglobin (hMb) was developed using our own reagents. The antigen (hMb) was isolated from human muscle, purified and stored frozen until needed for immunization, radiolabeling or reference preparation. The anti-hMb serum raised in rabbits was used at 1:2.10(4) dilution (initial). The Chloramine-T method was used for the hMb labeling obtaining at 10-15 muCi/micrograms (370-550 KBq/micrograms) specific activity. Working standards were prepared having concentrations in the range of 2.0 to 500 ng/ml. The reagents were incubated at +4 degrees C for 48 plus 24 hrs. The specificity and accuracy of our hMb-RIA system were validated using for parallel assays an already validated immunochemical system, the hemagglutination inhibition (HI) technique and the parallelism test using serum dilutions from patients with acute myocardial infarction (AMI). The serum hMb concentration in normal subjects (no = 23) was 54.14 +/- 15.08 ng/ml (X +/- SD), being higher in short-term hypothyroidism (no = 13), 87.95 +/- 20.90 ng/ml (p less than 0.0005) or in treated hyperthyroidism (no = 5), 80.03 +/- 21.81 ng/ml. In AMI (no = 6) the serum hMb concentration varied in the range of 123 to 1510 ng/ml. The sensitivity of our hMb-RIA system is 2 ng/ml and the intraassay average error (coefficient of variability % in %B) is 2.26%. Trials to shorten the incubation time showed that adequate binding of labelled Mb may be obtained with 2 plus 4 hr intervals at room temperature. It is necessary to establish, in our conditions, the variation limits for serum hMb in normal subjects according to sex and age as a comparison basis for the study of its physiological and pathological variations.