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A comparative analysis of thyrotoxicosis in 180 males and 121 females has shown that during the recent 15 years the number of males operated upon for diffuse toxic goiter (DTG) has become 2.6 times greater. Thyrotoxicosis in men is characterized by an aggressive course, is followed by cardiac complications, ophthalmopathy, impaired sexual function, appearance of foci of malignant growth, spread of diffuse hyperplasia of the thyroid gland behind the breast bone and trachea. Cessation of thyreostatic therapy resulted in quick recurrence of the disease. Repeated courses of treatment with thyreostatics increased the risk of irreversibility of changes in the heart muscle, impairment of regenerative abilities and massive lymphoid infiltration of the thyroid tissue followed by hypothyrosis. Early surgical treatment of men with DTG facilitated a rapid and reliable restoration of vitally important functions and recovery of most operated men and women.

Subclinical hyperthyroidism is a state of increased thyroid function with few or no clinical definitive signs or symptoms of hyperthyroidism. It is characterised by a decrease of serum (TSH) concentration below 0.1 mU/L, when serum levels of total and free thyroxin and triiodothyronin concentration are within normal reference ranges. It is not a rare finding and rates between 0.02% and 11.3% have been reported in different groups. The clinical diagnosis of subclinical hyperthyroidism is very difficult in the absence of the typical symptoms of hyperthyroidism. Therefore the diagnostic evaluation is important, especially with the use of radioisotope scan. In nuclear medicine department we can confirm the provisional diagnosis by the use of thyroid scan. Recent studies reported the effects of subclinical hyperthyroidism on cardiovascular system, skeletal system, cognitive function, on quality of life and life expectancy especially in the elderly patient. Treatment is indicated in the presence of palpitation, or atrial fibrillation, in postmenopausal osteoporosis in women not on hormone replacement therapy, and in elderly patients in whom surgery is contraindicated. According to the opinions of European clinicians and clinician members of the American Thyroid Association, the majority recommend radical treatment for these patients. Radioiodine therapy is considered to be the treatment of choice in most of the patients with nodular goiter.

The aim of the study carried out in 1989-90 and 1998-99 was to define the iodine deficiency state and goiter prevalence in adult population of Cracow. The analysis included data obtained from 230 individuals (143 females and 87 males). The mean age was 36 +/- 15 years. The thyroid size and morphology was determined by ultrasound method using Aloka unit equipped with 7.5 MHz linear transducer. The concentration of iodine in casual morning urine sample was measured using Sandell-Kolthoff's method. The 10- year observation revealed an insignificant decrease in prevalence of goiter from 26.2% to 21.8%. We observed statistically significant (p = 0.001) decrease in the parenchymal goiter prevalence from 22.7% to 11.7 in the same period of time. The significant increase in incidence of nodular goiter was found (6.5% vs 20.8%, p < 0.001). In all groups investigated through 1989-99, there was an increase in medians of ioduria over the 10-year period. The level of urinary iodine excretion was not essential element for risk of nodular goitre. Thus, the results indicate the beneficial effect of iodine prophylaxis which reflects in decrease of prevalence of parenchymal goiter. No clear effect of iodine prophylaxis was noticed regarding rise in nodular goiter incidence.

Background: Because controversy still continuous to surround use of total thyroidectomy for the management of benign multinodular goiter, the present study aims to prospectively compare the safety and efficacy of total thyroidectomy with subtotal thyroidectomy., Methods: A total of 200 consecutive patients with benign multinodular goiter were assigned to have either total thyroidectomy (n = 105) or subtotal thyroidectomy (n = 95) based on preoperative evaluation, intraoperative macroscopic findings and nodular dissemination. The patients with no healthy tissue or nodules localized in the dorsal part of the gland, which are usually left during normal subtotal resection, were assigned to the total thyroidectomy group. Demographic details, biochemical findings, indications for operation, operating time, specimen weight, complications and hospital stay were noted., Results: There was no significant difference in the sex, hormonal status or duration of goiter between the two groups (P = 0.74, P = 0.59 and P = 0.59, respectively). The mean operating time was longer (148.52 min +/- 51.10 vs 135.10 min +/- 32.47, P = 0.03), and the mean weight of the specimens was greater (228.40 g +/- 229.91 vs 157.01 g +/- 151.23, P = 0.01) for total rather than subtotal thyroidectomy. Either temporary recurrent laryngeal nerve (RLN) palsy or hypoparathyroidism occurred in 10 (9.3%) or 12 (11.4%) of the patients undergoing total compared with six (6.3%) or nine (9.5%) of the patients undergoing subtotal thyroidectomy (P = 0.40 and P = 0.65, respectively). Either permanent RLN palsy or hypoparathyroidism was observed in one patient undergoing total thyroidectomy (P = 0.34 for each comparison). The mean hospital stay was longer in the total thyroidectomy group (2.24 days +/- 1.18 vs 1.89 days +/- 0.72 for subtotal thyroidectomy, P = 0.01)., Conclusions: The present study shows that total thyroidectomy can be performed without increasing risk of complication, and it is an acceptable alternative for benign multinodular goiter, especially in endemic regions, where patients present with a huge multinodular goiter.

Surgery for recurrent nodular goiter is associated with a significant risk of parathyroid and recurrent laryngeal nerve (RLN) morbidity. Total thyroidectomy for benign disease is assessed. The aim of this study was to evaluate the risk factors for recurrence and the morbidity associated with reoperation. From 1969 to 1996 a total of 4334 thyroidectomies were performed, of which 122 were for recurrent nodular goiter (group I: 116 women, 6 men). A matched case-control study of 122 patients operated on for nonrecurrent multinodular goiter was performed (group II: 112 women, 10 men). Age, family history, initial surgery, pathology, and morbidity were compared in the two groups by chi2 test, Fisher's exact test, and the Mantel-Haenszel test. The mean age was 39.88 years in group I and 47.89 years in group II. There was no statistical difference in relation to the extent of thyroidectomy or morbidity after initial surgery. Statistical differences were identified regarding age (p = 0.000002) and the multinodular nature of the initial goiter (p = 0.005). Bilaterality and family history were less significant (p = 0.09 andp = 0.08, respectively). Temporary RLN palsy and temporary hypoparathyroidism were higher in group I (12.3% vs. 5.7%,p = 0.0737; 10.6% vs. 1.7%, p = 0.00337). Permanent RLN palsy was found in 0.8% in group I and in none in group II (p = 0.5, NS). Young age and multiple nodules at initial surgery are risk factors for recurrence. A higher rate of temporary morbidity was demonstrated after surgery for recurrent goiter. Total thyroidectomy for multinodular goiter is advisable.

Up to 15 % of the adult German population display an enlarged thyroid gland and up to 30 % present thyroid nodules. Iodine deficiency is the most important factor in the etiology of nodular goiter. Insulin-like growth factor-I is overexpressed in thyroids in severely iodine deficient areas. There is evidence that iodolactones are mediators of thyroid hormone autoregulation. However familial and twin studies demonstrated a genetic component in the etiology of nodular goiter. Linkage analysis identified two chromosomal regions (MNG-1, Xp 22) in multinodular goiter. Other possible candidate genes or markers such as TG, TPO, NIS, PDS and TSH-R were not identified. Nodular goiter certainly comprises a number of genotypes. TSH receptor mutations result in activation of the cAMP cascade. Cells with a constitutively activated cAMP cascade have an increased growth advantage due to their TSH independent cAMP stimulation. Alimentary iodine supply should be the first choice in primary prevention of nodular thyroid disease in iodine deficient areas, because prevalence of nodular goiter is negative correlated with individual iodine status in epidemiological surveys. Surgical removal of nodular goiters should include nearly the hold thyroid tissue to avoid recurrent goiter.

An optimal supply of iodine--150-200 microg/day--has not yet been secured in all regions and in all phases of life. The appreciable diminishment in thyroid gland mass in children and adolescents is, however, indicative of an improvement in this situation. In elderly persons, however, prophylactic measures do not result in struma or nodule regression. Nodules are found in some 40% of women and 28% of men older than 45. Medical treatment of nodular goiter is aimed at achieving a reduction in size or preservation of the status quo. Depending on the size of the goiter, iodine-deficiency goiter is treated with iodine or a combination of iodine and levothyroxine. In view of the pathogenesis and the marginal alimentary lack that still persists, there are no adequate arguments for L-thyroxine monotherapy of uncomplicated iodine-deficiency goiter.

Thyroid carcinoma (TC) is a relatively rare tumour, but it represents the most frequent form of cancer of the endocrine glands. Epidemiologically ascertained risk factors are ionising radiation, the presence of thyroid adenoma and multinodular goiter (MNG). Multinodularity of goiter should no longer be considered an indicator of probable benign disease. A retrospective analysis was performed on patients operated of MNG at the Unit of Otolaryngology, Sanremo Hospital (Italy) from January 1st 1995 to December 31st 2002, in order to establish the incidence of carcinoma. The results of this retrospective study, demonstrate that in 13.7% of the patients operated for goiter, the presence of a carcinoma was noticed in the definitive histopathologic examination. Such incidence percentage of MNG is in accordance with the data reported in published reports. Thus, the authors conclude that the risk of malignancy in MNG has not to be underestimated, and that a dominant nodule in MNG should be valued as if it were a solitary nodule in an otherwise normal gland.

Aims: To investigate RET and p53 expression in local thyroid lesions, in order to shed light on the pathogenesis of papillary carcinoma and explain the high prevalence of this condition among the nodular hyperplasia (multi-nodular goitre) cases., Methods: Archival thyroid tissue was retrieved from Hospital Universiti Sains Malaysia (HUSM) Pathology Department files and studied by immunohistochemistry for RET and p53 mutant protein. Normal tissues from 74 cases served as controls., Results: Fifty follicular adenoma, 66 nodular hyperplasia and 53 papillary carcinoma cases were studied. RET was expressed in 5.4% of normal thyroid tissue, 18% of follicular adenomas, 22.7% of nodular hyperplasia cases and 71.7% of papillary carcinomas. Its expression in papillary carcinoma was not associated with the coexistence of nodular hyperplasia lesions. p53 was expressed by 17% of papillary carcinomas. No association was found between p53 expression of nodular hyperplasia with or without co-existing papillary carcinoma. p53, rather than RET, was an excellent predictor of tumour lymph node metastasis and capsular invasion. p53 was also a significant prognosticator of survival outcome., Conclusions: RET expression is highly prevalent in local papillary carcinoma, indicating a significant role in the pathogenesis of this tumour, with no apparent role in tumour behaviour and survival outcome. p53 on the other hand appears to be a significant factor in the latter events. The two genes appear to act in two different pathways: the former being an initiator, and the later a propagator of papillary carcinoma.

Investigations within the framework of the thyroid gland initiative "Papillon" turned up an unexpectedly high level of pathogenic findings. Determination of TSH and sonography are considered the pillars of the diagnostic evaluation of the thyroid gland. Useful further investigations aimed at excluding functional disorders are, for example, the determination of FT3 and FT4 or a search for autoantibodies. To investigate suspicious nodules and to exclude malignant processes, additional scintigraphy and, were indicated, fine-needle puncture can be applied. Depending on the individual situation of the patient, the therapeutic option of choice is surgical operation or treatment with iodine-31 therapy. Medical treatment of nodular goiter is currently still controversial.

The Hospital de Clínicas organized a free program of goiter detection by palpation. This campaign was aimed at the population of the metropolitan area of Greater Buenos Aires (11 million inhabitants), with the prerequisite that each participant should be quite unaware whether he/she was a carrier of any thyroid disease. Attendees were split into two groups, i.e., Random and Induced. The former consisted of 542 individuals who came to consultation due to mere curiosity, while the latter involved 500 subjects, comprising consanguineous family members of patients with thyroid disorders and also individuals who suffered from other ailments. Ages ranged from 2 to 85 years. In the Random Group, goiter prevalence of 8.7% was observed, while in the Induced Group it climbed to 14.4%. Since both groups were mostly made up of women (87.2%), a correction based on the masculinity index was applied to members of the Random Group. Thus, the total observed prevalence of goiter was 6%, diffuse goiters corresponding to 3.5% and nodular ones to 2.5%. The frequency of nodules increased with age, 90.5% occurring in those over 40 years. In the Induced Group, goiter prevalence among relatives of patients with thyroid disorders proved to be 13.1%, rising to 17.8% in those who suffered from other complaints. The epidemic data presented herein are the first arising from a screening survey carried out in a large iodine-sufficient population of the southernmost tip of the American continent. These results are useful to build up the world map of goiter prevalence in non-endemic areas.

The study was performed to evaluate the prevalence of thyroid abnormalities detected by ultrasonography and, in particular, of multinodular nontoxic goiter in primary aldosteronism. We analyzed 80 consecutive of patients with primary hyperaldosteronism (40 with unilateral adenoma and 40 with idiopathic hyperaldosteronism) and 80 normotensive healthy controls, comparable for age, sex, iodine intake, and geographical area. Blood pressure, thyroid palpation, thyroid function, and ultrasonography were evaluated. The prevalence of ultrasonographic thyroid abnormalities was 60% in primary aldosteronism and 27% in controls (p < 0.0001). There was a statistically significant difference in prevalence of these abnormalities in unilateral adenoma and idiopathic hyperaldosteronism with respect to controls (p < 0.05 and p < 0.0001, respectively). The prevalence of multinodular nontoxic goiter in idiopathic hyperaldosteronism was higher than in controls (p < 0.001) and, in particular, in female patients. From these data it seems to be worth considering the existence of primary hyperaldosteronism in patients with multinodular goiter and hypertension.

Background: Hyperthyroidism is a common disease in the elderly. Although some studies on the prevalence of this thyroid disorder have been performed in the aged population, several aspects of hyperthyroidism, such as etiology and treatment effectiveness, have not been fully characterized in large series of aged patients., Objective: The aims of the present study were to determine the frequency of the diverse etiologies of hyperthyroidism, and to assess the effectiveness of therapy in adult patients older than 55 years., Methods: We performed a descriptive, observational, cross-sectional study in the setting of a hospital endocrinology clinic. We studied a group of 313 patients with hyperthyroidism. There were 246 women (78.6%, age 67.02 +/- 8.35 years) and 67 men (21.4% age 63.34 +/- 7.63 years). Overt hyperthyroidism was diagnosed in 167 patients (53.4%) and subclinical hyperthyroidism in the remaining 146 subjects (46.6%). In every patient we studied: the etiology; presence or absence of goiter; time of evolution from diagnosis; previously and presently used treatments; current thyroid functional status (free thyroxine and thyrotropin concentrations); adequacy of disease control, and thyroid autoimmune status., Results: The different etiologies of hyperthyroidism were as follows: toxic multinodular goiter 43.1%; Graves' disease 21.4%; iatrogenic thyrotoxicosis 16.0%; toxic adenoma 11.8%; iodine-induced thyrotoxicosis 1.2%; subacute thyroiditis 1.0%; painless thyroiditis 0.3%; factitious thyrotoxicosis 0.3%; TSH-secreting pituitary adenoma 0.6%, and unknown etiology 3.8%. Etiology was related to age, sex, presence of goiter, degree of hyperthyroidism and autoimmune status. 77.6% of patients had been diagnosed in the last 5 years, and 91.3% in the last 10 years. Preferred therapies were thionamide drugs in patients with Graves' disease and radioiodine in patients with hyperthyroidism due to nodular disease. Surgery was performed in a limited number of patients. Periodic follow-up was used in patients with subclinical hyperthyroidism. Control of the disease was adequate in 65.3% and inadequate in 34.7% of patients who received any kind of previous therapy. In this group of patients, logistic regression analysis showed that the probability of attaining good control of hyperthyroidism was greater in patients with overt thyrotoxicosis compared to patients with subclinical thyrotoxicosis., Conclusion: In patients older than 55 years, toxic multinodular goiter is the most frequent etiology of spontaneous hyperthyroidism, followed by Graves' disease and toxic adenoma. Most patients with thyroid hyperfunction can be adequately controlled, provided that effective therapy is administered. Patients with overt hyperthyroidism seem to have a higher probability of attaining adequate control of their disease than patients with subclinical hyperthyroidism, regardless of age, sex or etiology., (Copyright 2003 S. Karger AG, Basel)

Chronic infections that caused by hepatitis B and C viruses, are important all of the world as a public health problem. Despite intensive control measurements, the incidences of chronic hepatitis B and C virus infections in our country are estimated as 5-7% and 3%, respectively. There are accumulating data of especially autoimmune mediated extrahepatic manifestations of hepatitis B and C virus infections, such as Diabetes Mellitus (DM), Behçet's Disease (BD), hypo- or hyper-thyroiditis and autoimmune diseases. The aim of this study was the retrospective evaluation of 400 chronic B hepatitis (CBH) and 35 C hepatitis (CCH) patients by means of the presence of extrahepatic manifestations. As a result, the positivity rates of extrahepatic manifestations detected in CBH and CCH patients were as follows respectively; 1.5% and 8.5% for DM, 1.5% and 5.7% for hypothyroiditis, 0.75% and 2.8% for hyperthyroiditis, 2% and 20% for nodular goitre, 0.25% and 5.7% for BD, 1% and 0% for systemic lupus, 1% and 5.7% for Rheumatoid Arthritis (RA), and 22% and 11.4% for iron deficiency anemia. DM, thyroid diseases and RA were the most common extrahepatic manifestations detected in both of the patient groups, while the rates of DM, BD and nodular goitre were found higher in CCH patients than CBH patients (p < 0.05). As a result, the extrahepatic manifestations should be carefully followed in patients with chronic hepatitis B and C infections, for an early diagnosis and appropriate treatment.

In the framework of the Thyroid initiative Papillon 2001 - 2002 thyroid nodules and sonographically detectable focal lesions with a diameter more than 5 mm were verified in 23.1% of 64.123 persons without a history of thyroid disease. The frequency of such findings was with 33.0% in 46-65 years old persons three times higher then in persons aged 18-30 years (9.6%). In the diagnostic workup thyroid cancer was detected in 15 patients operated on up to now (6 women and 9 men; papillary cancers in 12 cases, follicular cancers in 3 cases) The smallest tumor had a diameter of 1.3 cm, the mean diameter was 2.3 +/- 91 cm. In 3 patients the tumor had invaded the tissue beyond the thyroid capsule, in 4 cases multicentric growth was detected. Lymph node metastases were found in 7/15 cases and distant metastases in 2/15 cases. These result reveal, that thyroid cancer detected by chance may be relatively aggressive. In daily routine, sonographically detectable lesions with poor echogenicity, irregular margins or internal calcifications with a diameter of more than 1 cm should be clarified by fine needle aspiration biopsy.

The simple nodular goiter, the etiology of which is multifactorial, encompasses the spectrum from the incidental asymptomatic small solitary nodule to the large intrathoracic goiter, causing pressure symptoms as well as cosmetic complaints. Its management is still the cause of considerable controversy. The mainstay in the diagnostic evaluation is related to functional and morphological characterization with serum TSH and (some kind of) imaging. Because malignancy is just as common in patients with a multinodular goiter as patients with a solitary nodule, we support the increasing use of fine-needle aspiration biopsy (cytology). Most patients need no treatment after malignancy is ruled out. In case of cosmetic or pressure symptoms, the choice in multinodular goiter stands between surgery, which is still the first choice, and radioiodine if uptake is adequate. In addition to surgery, the solitary nodule, whether hot or cold, can be treated with percutaneous ethanol injection therapy. If hot, radioiodine is the therapy of choice. Randomized studies are scarce, and the side effects of nonsurgical therapy are coming into focus. Therefore, the use of the optimum option in the individual patient cannot at present be based on evidence. However, we are of the view that levothyroxine, although widely used, should no longer be recommended routinely for this condition. Within a few years, the introduction of recombinant human TSH and laser therapy may profoundly alter the nonsurgical treatment of simple nodular goiter.

Iodine deficiency is widely known to be the main cause of nodular goiter (NG). In iodine deficient areas subclinical and overt hyperthyroidism is the major cause of morbidity and it is mainly due to toxic NG rather than Graves' disease. Toxic NG, including toxic multinodular goiter and toxic thyroid adenoma is usually encountered in subjects with long-standing NG, in whom thyrotoxicosis is usually preceded by a long phase of euthyroidism and then subclinical hyperthyroidsm (abnormally low TSH with normal circulating thyroid hormones). Epidemiological studies indicate that, compared to Graves' disease, the incidence and prevalence of non-autoimmune hyperthyroidism due to toxic adenoma and toxic multinodular goiter differ in different regions of the world, being much more frequent in areas of iodine deficiency. Recently, mutations of the TSH receptor (TSHr) gene causing permanent activation of the thyroid follicular cell adenylate-cyclase, have been shown to be the most probable cause of the hyperfunction and growth of toxic adenoma. In this review we will focus our attention on the role of external factors (i.e. iodine deficiency) with respect to individual factors (i.e. genetic mutations) in the pathogenesis of toxic NG.

Despite the observation that parity may increase the risk of thyroid carcinoma, very few studies have investigated the possible repercussion of parity on thyroid benign pathology. Recently, parity has been identified as one of the factors contributing to a larger thyroid size in healthy females. The aim of this work was to investigate a possible role for parity on the prevalence of multinodular goiter in iodine deficient areas. For this purpose, the reproductive histories of 2 cohorts of women, normal (Group I, 235 cases) and non-toxic multinodular goiter (NTMNG) affected (Group II, 274 cases) were compared. All subjects were euthyroid and had no previous history of thyroid function abnormalities. The number of full-term previous pregnancies (2.55+/-0.11 vs 1.77+/-0.10) and age (47.7+/-0.76 vs 42.3+/-0.83 yr) were found significantly higher (p<0.001) in multinodular goiter (MNG) patients than controls. Parity and age were found to be directly correlated (p<0.001), nevertheless the partial correlation coefficients demonstrated an independent and statistically significant difference for both variables between normal and NTMNG. Therefore, the independent effects of parity and age were further investigated. The effect of age on NTMNG prevalence seems to be weaker, in fact significant differences (p<0.001) for age between patients and controls were detected only when the effect of parity was absent (nulliparous), while with increasing gestations the effect of age disappeared. Our results indicate that age plays a minor role compared to parity which can therefore be considered as a stronger risk factor. In conclusion, the present study shows that, at least in iodine deficient regions, non-toxic multinodular goiter women show a statistically significant higher parity rate than healthy controls. Age may play a certain role but only when additional stronger risk factors are absent.

Aim: To study fracture risk in patients with hyperthyroidism and hypothyroidism., Subjects and Methods: All patients with hyperthyroidism or autoimmune hypothyroidism diagnosed for the first time between 1983 and 1996 in Denmark were identified through the National Patient Discharge Register. Each patient was compared with three age- and gender-matched controls randomly selected from the general population. Fracture occurrence before and after diagnosis was compared between patients and controls., Results: 11,776 patients with hyperthyroidism (6301 patients with diffuse toxic goiter, mean age, 52.1 +/- 18.6 years, and 5475 with nodular toxic goiter, mean age, 60.4 +/- 15.9 years), and 4473 patients with hypothyroidism (mean age, 66.1 +/- 17.3) were identified. In patients with hyperthyroidism, fracture risk was only significantly increased around the time of diagnosis (incidence rate ratio [IRR] between 1.26 and 2.29), but decreased to normal levels after diagnosis. Surgical treatment of hyperthyroidism was associated with a decreased fracture risk after diagnosis (RR = 0.66, 95% confidence interval [CI]: 0.55-0.78). In hypothyroidism, fracture risk was significantly increased both before and after diagnosis with a peak around the time of diagnosis (IRR between 2.17 and 2.35)., Conclusions: Fracture risk is increased in hyperthyroidism and hypothyroidism. Thyroid surgery seems associated with a decreased fracture risk in hyperthyroid patients.

Every patient operated for nodular goiter by a partial surgery is exposed to recurrence. In order to verify this idea, the authors followed 36 patients operated on for nodulargoiterat least 10 years ago. A clinical examination for all the patients and echographic study for 24 of them allowed the detection of recurrence and the evaluation of survival and recurrence without any opotherapy. It seemed that clinical recurrence is observed in 16.65% of cases whereas echographic study revealed recurrence in 50% of patients examined. Only two patients were reoperated on. The predictive factors of the recurrence are geographic endemic origin and ethny, partial surgery and vesicular goiters. With 66.65% of survival without recurrence at 18 years without opotherapy, the authors argue about the utility of such treatment.

Toxic nodular goiter (TNG) is the most frequent cause of thyrotoxicosis in the elderly, specially in iodine deficient areas. Epidemiological studies have shown that in iodine deficient areas (Jutland) the incidence of hyperthyroidism is significantly higher with respect to areas with normal iodine intake (Iceland) and it is due to TNG. A careful epidemiological study recently carried out in Pescopagano, in southern Italy, an area characterized by a mild to moderate iodine deficiency, indicates that, in its natural history, nodular goiter contributes to the development of functional autonomy and eventually hyperthyroidism. Somatic activating mutations of the TSH receptor are involved in the pathogenesis of TNG. It is supposed that the prolonged iodine deficiency associated with chronic TSH stimulation increases the replication of follicular thyroid cells, and favor the appearance and expression of mutations of the TSH receptor gene. The clinical signs are usually more subtle than those observed in Graves' disease: a long phase of subclinical hyperthyroidism (normal circulating thyroid hormones and undetectable TSH levels) can precede the appearance of the symptoms. Cardiac symptoms are most frequent, (arrhythmia and atrial fibrillation). Thyroid scintigraphy in toxic multinodular goiter shows an uneven distribution of the radionuclide with multiple hyperfunctioning nodules and cold nodules. Thyroid US shows goiter with inhomogeneous solid nodules often with ill-defined borders. The treatment with antithyroid drug does not allow a permanent remission of hyperthyroidism, but its use is indicated to achieve euthyroidism before the definitive treatment. The definitive treatment is radioiodine or thyroidectomy.

Thyroid nodules were assessed by ultrasound in 3 621 presumably healthy free-living French subjects participating in the SU.VI.MAX cohort (2 160 females aged 35-60 years and 1 461 males aged 45-60 years). Urinary iodine was measured in all participants in random morning urine samples. Nodular thyroid structures ranging from 3 mm to 57 mm in diameter were found in 14.5% of the population, without significant differences between regions in the different age and sex groups. Single nodules and multiple lesions were found in, respectively, 9.7% and 3.1% of the subjects. In females, nodules increased from 12.9% to 19.2% between 35-45 years and 45-60 years, respectively (p<0.001). Thyroid nodularity was more frequent among women aged 45-60 years than among men of those ages (19.2% vs. 11.0%, p=0.001). Descriptive data provided by ultrasound differentiated the nodules into solid (43.4%), cystic (38.4%), and mixed solid-cystic (18.2%). Most solid thyroid nodules, 76.1%, were hypoechoic, while 16.6% were iso-, and 7.3% were hyperechoic. The median of iodine concentrations (n=3 276) was 8.0 microgram/100 ml, with 19.4% of the samples being<5 microgram/100 ml. Median iodine concentrations displayed wide regional variations, with values significantly higher in residents of western regions than among those living in the eastern areas (p<0.001), independently of age and sex. No relationship was found between prevalence of nodular thyroid structure and the state of borderline iodine status observed in France.

Objective: To study the annual incidence of thyroid diseases before and after the increase of iodized salt intake., Method: A total of 26,010 persons were examined from mid August to the end of December in 1999., Results: 1. Three hundred and ten patients of thyroid diseases were identified from 1990 to July 1999. One hundred and eighty-three patients were diagnosed after iodine supplementation. 2. The constitution of thyroid diseases had changed significantly regarding the increase of hyperthyroidism, simple goiter and thyroid nodule. 3. Fifty-five patients with hyperthyroidism including 39 patients (70.91%) receiving iodine supplementation were diagnosed. The average annual incidence of hyperthyroidism after iodine supplementation was 36.87 per 100,000, a three-time increase as compared with that before iodine supplementation. The incidence of hyperthyroidism began to show a significant rise in 1996. The year with highest annual incidence was 1997, remaining at high level after supplying iodized salt. Since then the annual relative risk for hyperthyroidism had been increasing., Conclusion: The number of patients with thyroid diseases showed a significant increase after mass iodine supplement. At the same time, the spectrum of thyroid diseases had also changed. Iodized salt intake and the incidence of hyperthyroidism showed a significant correlation. However, the typical model of the change of disease patterns incidence needs further study.

In black Africa, and particularly in Togo, management of thyreotoxicosis is not simple. The intervention of several specialists and effective patient collaboration is needed. In a majority of cases, the patient's apprehensions, financial problems, and taboos prevent correct management. We report 30 cases of thyreotoxicosis in 82 patients with thyroid disease seen over a 5-year period in the Internal Medicine and Cardiology Department of the Lomé teaching hospitals. Graves' disease was the most frequent (83.33%), followed by multinodular goiter (10%) and toxic nodule (6.67%). Diagnosis was strictly clinical in 53.33% of the cases. The main complication was cardiothyreosis in 46.67% of the patients. Drug treatment was used. Short-term results (4 - 6 weeks) was favorable in 96.67% of the cases. A percentage (65.41%) were lost to follow-up after discharge. The main impairment encountered for the management of thyreotoxicosis was financial and economical difficulties not specific to the disease. Other problems included the lack of diagnostic and therapeutic means and insufficient cooperation between the surgeon, the cardiologist and the endocrinologist.

Background: The association of hyperparathyroidism (HPT) with thyroid disease has long been known, but the mechanisms underlying such an association have not yet been clarified., Objective: To elucidate the main factors determining this combination of endocrine diseases, in a retrospective multicenter study., Methods: We retrospectively reviewed all patients referred for parathyroid scintigraphy in the period 1990-1999. A total of 487 patients in the age range 17-65 years were selected for the analysis (339 women and 148 men); group A included 241 patients with primary and group B 246 patients with secondary HPT., Results: A total of 124/241 patients in group A (51.5%), but only 92/246 patients in group B (38.2%) had thyroid disorders (notably nodular goiter) associated with HPT (P=0.0035). Thyroid disorders were evenly distributed throughout the entire 17-65 years age range in group A, but 17-40-year-old patients in group B had significantly fewer thyroid disorders than the older patients of the same group (15.5% compared with 43.3%, P<0.002), as expected in a general population. In patients with primary HPT there was no difference in the prevalence of thyroid disease between women and men, whereas the ratio of women to men in secondary HPT patients with thyroid disease was about 3:1., Conclusions: These results demonstrate an increased prevalence of nodular goiter in patients with primary rather than secondary HPT, and are consistent with a possible role of increased endogenous calcium concentrations (a hallmark of primary, but not of secondary, HPT) as a goitrogenic factor in patients with HPT.

Aim: Selective and critical presentation of the present exploring methods concerning surgical thyroid diseases and accomplishing a pre-surgical diagnosis as accurate as possible. Depending of the diagnosis--choosing the most appropriate surgical strategy according to the newest concepts in thyroid pathology., Materials and Method: Clinical-statistic study, carried out retrospectively over 1,108 patients having various surgical thyroid maladies hospitalized in 1980-1999 period. There have been operated 1,058 cases. Demographic structure as regards sex, F/M was 9.07/0.93 for goiters, whereas for thyroid cancer it was 3/1., Results: Nodular goiters are the most frequent (77.31%), with a pathology benign majority (91.30%). The fundamental problem is the pre-surgical establish malign lesions that require a complex therapeutic protocol comparing to benign nodules. Benign lesions 91.30%, carcinomas 5.48%, others 3.21%. All types of thyroidectomies have been made: T.ST 69.37%, T.T for benign and malign lesions 7.65% and other procedures. Thyroid specific morbidity is 4.25%, whereas unspecific is 8.69%. The 0.08% mortality (1 case), virtually null, place the result between the best of the kind., Conclusions: Pre-surgical diagnosis, as accurate as possible, based on the clinic exam using the vacuum punction with a fine needle, finally confirmed by the paraffin exam, provided the choice of an optimal surgical strategy, followed by an appropriate post-surgical protocol. Total thyroidectomy is the preferred procedure is most of the thyroid cancer forms and in benign diseases is highly recommended (multi-nodular goiters, hyperthyroid, Basedow disease, cancer).

Thirty-four hyperthyroid patients selected on preset criteria for radioiodine therapy were given low dose radioiodine-131 (I-131) in the Nuclear Medicine Unit of the Tikur Anbessa Hospital as a preferential alternative to repeat or protracted administration of antithyroid drugs, or surgery. The dose chosen was 85 uCi per gram of thyroid tissue based on the 24 hour uptake of a test dose of I-131. The age range of the patients was 18 to 68 years, female to male ratio was 7.5:1 and 80% of the females were in the reproductive age group. Twenty-five patients had multinodular goiter, four had persistent hyperthyroidism after surgery, and five had recurrent Graves' disease. Estimated thyroid gland weight was from 3.5 to 51.4 grams and the amount of I-131 administered was from 0.2 to 4.9 mCi. Only 11 of the 34 patents became euthyroid after a single dose of I-131, 14 required one or more repeat doses and only six of those became euthyroid making a total of 17 (50%) responders. The low dose regimen we used in this study, though economical in a situation of limited I-131 supply, resulted in a high failure rate of 50%. This shows the need to formulate a better dosage scheme that can benefit the majority of patients by optimizing the prospects of the resolution of hyperthyroidism with a single dose of radioiodine.

Recent studies have raised doubts about the efficacy of the postoperative use of levothyroxine (LT4) suppressive doses in patients who underwent thyroid surgery for multinodular goiter. The purpose of this retrospective study was to examine the efficacy of different doses of LT4 in preventing postsurgical recurrences of simple multinodular goiter and to identify a marker that could be useful in discriminating patients with a higher risk of developing recurrence. Two hundred thirty-two patients (57 male, 175 female) operated for nontoxic multinodular goiter were divided into two groups: (I) patients with normal postsurgery thyrotropin (TSH) levels (0.25 to 4.5 mU/L) and (II) patients with elevated postsurgery TSH levels (>4.5 mU/L). All patients were subjected to replacement (1.3 microg LT4/kg/day) or suppressive (1.7 microg LT4/kg/day) doses of LT4, and they were followed for a median period of 6 years (range 2 to 12). No statistical difference was found for sex, age, and postsurgery serum TSH between patients submitted to suppressive and replacement therapy. The ultrasound (US) detection of new postsurgery nodules of at least 0.5 cm maximum diameter was considered a recurrence of disease and was found in 10% of the cases studied. Patients with normal postsurgery serum TSH showed a high recurrence rate (30.4%) when submitted to lower daily doses of LT4. In patients with elevated postsurgery serum TSH, the rate of nodular goiter recurrence did not vary with different types of LT4 therapy. In conclusion, our results suggest that the postsurgical serum TSH is useful for prediction of nodular goiter recurrence, as it reflects the amount of residual functioning thyroid tissue in the cervical area. It may also be indicative of patients who might benefit from LT4 suppressive therapy.

From 1949 through 1989 nuclear weapons testing carried out by the former Soviet Union at the Semipalatinsk Nuclear Test Site (SNTS) resulted in local fallout affecting the residents of Semipalatinsk, Ust-Kamenogorsk and Pavlodar regions of Kazakstan. To investigate the possible relationship between radiation exposure and thyroid gland abnormalities, we conducted a case review of pathological findings of 7271 urban and rural patients who underwent surgery from 1966-96. Of the 7271 patients, 761 (10.5%) were men, and 6510 (89.5%) were women. The age of the patients varied from 15 to 90 years. Overall, a diagnosis of adenomatous goiter (most frequently multinodular) was found in 1683 patients (63.4%) of Semipalatinsk region, in 2032 patients (68.6%) of Ust-Kamenogorsk region and in 1142 patients (69.0%) of Pavlodar region. In the period 1982-96, as compared before, there was a noticeable increase in the number of cases of Hashimoto's thyroiditis and thyroid cancer. Among histological forms of thyroid cancer, papillary (48.1%) and follicular (33.1%) predominated in the Semipalatinsk region. In later periods (1987-96), an increased frequency of abnormal cases occurred among patients less than 40 years of age, with the highest proportion among patients below 20 in Semipalatinsk and Ust-Kamenogorsk regions of Kazakstan. Given the positive findings of a significant cancer-period interaction, and a significant trend for the proportion of cancer to increase over time, we recommend more detailed and etiologic studies of thyroid disease among populations exposed to radiation fallout from the SNTS in comparison to non-exposed population.

Seasonal variations in the frequency of thyrotoxicosis are known for a long time. Both, variations in the temperature and in the iodine supplementation are believed to affect the incidence of the diagnosis of hyperthyroidism. Seasonal variation of the incidence of hyperthyroidism was investigated before and after increase of salt iodination in 1990/1991. In the period from January 1987 to December 1995 hyperthyroidism was diagnosed for the first time on 4711 patients in our department. This population was subdivided according to etiology (Graves' disease, autonomous nodular goiter) and grade of hyperthyroidism (preclinical or clinical form). The so formed groups were divided according to the month of diagnosis into further 12 subgroups. Significant differences in month to month variation were found in the patients suffering from Graves' disease and autonomous nodular goiter with preclinical hyperthyroidism after increased iodine supplementation. The peak incidence of the diagnosis occurred in June, July, and August. Our results indicate that improved iodine supplementation may be the main cause of seasonal variations in the incidence of thyrotoxicosis.

Although thyroid carcinoma is more common in the adult population, the risk of a nodule being malignant is greater in children. The aim of our present investigation was to ascertain the percentage of malignancy in nodular goiter observed in patients from the Lower Silesia region in the last 12 years. The examination included 60 children (12 boys and 48 girls) treated in our clinic from 1987 to June 1998. Age varied from 7 to 18 years (mean 14.8 +/- 2.4), most of them in the age group between 13 and 18 years. The following investigations were performed: TSH, T3, T4, thyroid ultrasonography, fine needle aspiration biopsy and Tc99 scintigraphy of the thyroid. Most of the patients were euthyroid; two children demonstrated pressure symptoms. All the patients were treated by operation. Histological examinations revealed the following: nodular goiter in 19 patients, cystic nodular goiter in 5, follicular adenoma in 20, fetal adenoma in 3, nodular goiter and follicular adenoma in 6, papillary carcinoma in 6, and follicular carcinoma in 1 patient. We concluded that an increased incidence of thyroid cancer has been noted in children with nodular goiter in Lower Silesia during the last 12 years. Thyroid cancer was observed mostly in patients with single nodules and was associated with a high risk of malignancy.

Aims and Background: The aim of this study was to analyze the frequency of coexisting hyperthyroidism and thyroid malignancy in endemic goiter areas and review the current literature on the subject., Methods: During the period January 1984 to June 1998, 1853 patients were examined for hyperthyroidism at the Spedali Civili Hospital of Brescia, Italy; 512 (27.6%) subjects underwent surgery. Of these patients 108 (21%) had Graves' disease, 251 (49%) multinodular toxic goiter (MTG) and 153 (30%) uninodular toxic goiter (UTG)., Results: Malignancy was found in 24 (4.7%) patients: 19 females and 5 males with a mean age of 52.2 years (range, 21-76 years). The frequency of cancer in Graves' disease was 6.4%, 5 females and 2 males; in MTG 3.9%, 2 females and 8 males, and in UTG 4.4%, 7 females and 1 male., Conclusions: Our data confirm previous reports on the frequency of thyroid cancer in hyperthyroidism. This association is more relevant than previously suspected. The frequent coexistence of hyperthyroidism and neoplasia, demonstrated by our study and the most recent literature, underlines the importance of studying and excluding the possibility of neoplastic degeneration by means of a systematic approach.

We investigated thyroid abnormality in Mauritania by carrying out a prospective ultrasound study of 171 patients. One hundred and thirty four patients underwent thyroid hormone determination (T3, T4 and TSH) and 123 had complementary plain film X rays of the chest and neck. These ultrasound examinations accounted for 3.8% of all ultrasound examinations performed over the study period. Thyroid abnormalities were more frequent in young adults aged 20 to 40 years (67.4%) and in women (83%) in Mauritania. Thyroid diseases affected people from savanna and mountain regions in particular. Diffuse goiters were the most frequent problem (76.3%) and most were multinodular or heterogeneous forms with necrosis or hemorrhage. One case of homogeneous diffuse goiter was found to be an infiltrating vesicular adenocarcinoma with metastatic adenopathy. Nodular goiters were mostly cystic, with septation (51.9%) and could be mistaken for hydatid cysts, which are endemic to the region. Further study of these aspects of thyroid diseases in Mauritania are required.

Primary hyperparathyroidism (HPT) and thyroid disease are both relatively common diseases, which can coexist in the same patient. However, mere coincidence does not seem to be a satisfactory explanation for this association. Some factors like prior exposure to radiation may play a role in the association. The aim of this study was to determine the frequency of thyroid disease associated with HPT in 54 consecutive patients who underwent parathyroidectomy in our center from January 1990 to December 1997. Twenty-eight (52%) patients had thyroid disease associated to HPT. The patients had a mean age of 61+/-13 yr; they were predominantly postmenopausal women. Thyroid disease was detected preoperatively in 20 (71%) patients and during the surgical procedure in 8 (29%). Two patients had previous radiation exposure; one of them with papillary carcinoma of the thyroid. Two patients had hypothyroidism. UItrasonography was performed in the majority of patients in their preoperative evaluation. A multinodular goiter was seen to be the most frequent finding (76%). In addition to parathyroidectomy, 23 (82%) patients were also thyroidectomized. In conclusion, patients with HPT showed a high prevalence of thyroid disease, especially in postmenopausal women. Unsuspected thyroid lesions were found with sufficient frequency to warrant careful preoperative and intraoperative evaluation of both glands, in order to obviate reoperation. In experienced hands, combined surgery can be safely performed. Cervical ultrasonography is useful in the preoperative detection of nodular thyroid disease in these patients.

We carefully assessed thyroid status and goiter by ultrasound in 1411 subjects virtually representing the entire resident population of Pescopagano, an iodine-deficient village of Southern Italy. Median urinary iodine excretion was 55 microg/L. The prevalence of goiter was 16.0% in children and 59.8% in adults. Thyroid nodularity was 0.5% in children and progressively increased with age to 28.5% in the 56- to 65-yr-old group. The prevalence of present or past hyperthyroidism was 2.9%, including 9 cases with toxic diffuse goiter and 20 with toxic nodular goiter. Functional autonomy was rare in children, progressively increased with age up to 15.4% in the elderly, and was related to nodular goiter. The prevalences of overt and subclinical hypothyroidism in the adults were 0.2% and 3.8%, respectively. Serum autoantibodies to thyroglobulin and thyroperoxidase were detected in 12.6% of the entire population. The prevalence of diffuse autoimmune thyroiditis was 3.5%, being very low in children. Thyroid cancer was found in only 1 case. In conclusion, in the present survey of an iodine-deficient community, a progressive increase with age of goiter prevalence, thyroid nodularity, and functional autonomy was observed. Hyperthyroidism was twice as high as that reported in iodine-sufficient areas, mainly due to an increased frequency of toxic nodular goiter. Although low titer serum thyroid antibodies were relatively frequent, the prevalences of both overt and subclinical autoimmune hypothyroidism were not different from those observed in iodine-sufficient areas.

Objective: To investigate the prevalence of nodular goiter and thyroid dysfunction in uremic patients undergoing hemodialysis (HD) and peritoneal dialysis., Design: Cross-sectional study., Setting: Single dialysis unit and outpatient clinic., Patients: The study included 221 patients [143 HD and 78 continuous ambulatory peritoneal dialysis (CAPD) patients] along with 135 consecutively selected outpatients as controls., Main Outcome Measures: Ultrasonography was used to detect patients' thyroid function and nodular goiter., Results: Nodular goiter was detected in 54.8% of the uremic patients and in 21.5% of the controls. Uremic patients had higher prevalence of thyroid dysfunction, which included reduced serum concentration of total T3, total T4, and free T4, and increased serum level of TSH. Hypothyroidism was also observed more frequently in uremic patients than in the control group (5.4% vs 0.7%, p < 0.05). Nodular goiter was more frequently found in females than in males (63.5% vs 48%, p < 0.05). Moreover, the prevalence of nodular goiter increased with age (p < 0.02) in uremic patients. Hemodialysis patients had a higher frequency of reduced total T3 level (46.9% vs 29.5%, p < 0.02). However, CAPD patients had lower T4 levels (6.23+/-1.82 microg/dL vs 7.15+/-1.99 microg/dL, p < 0.05)., Conclusion: Because of the high incidence of hypothyroidism and nodular goiter in uremic patients, screening of thyroid function and goiter detection with ultrasound should be considered in evaluation of end-stage renal disease patients.

Thyroid reoperations can be technically difficult and associated with an increased risk of complications. To determine the indications for reoperations and the risk of postoperative complications with these procedures, records of 362 patients undergoing thyroidectomy by a single surgeon (R.A.P.) were reviewed. Thirty-two patients had a reoperation. The group consists of 21 women and 11 men with an average age of 55 years (range, 31-79). Twenty-four patients had 1 prior operation, and 8 patients had 2 or more. We performed 4 of the initial operations, and 28 were done by surgeons at other centers. Fourteen reoperations were done for symptomatic multinodular goiter (MNG), and 5 because of a change in the histologic diagnosis from benign to cancerous. The remainder were for further treatment of malignancy. The most common operation was completion thyroidectomy (31). In 3 patients, either unilateral or bilateral modified radical neck exploration was performed. One patient required median sternotomy. One subtotal thyroidectomy was also performed. Recurrent laryngeal nerve injury occurred in 2 patients. It resolved in 1 patient but was permanent in another, who had 3 operations for MNG. One of the 2 patients with preoperative unilateral vocal cord paralysis had return of function after removal of a substernal goiter. The other had a permanent nerve injury from the original surgery. Three patients had postoperative hypocalcemia (calcium <8.0 mg/dL). This resolved in all patients within 1 to 6 months. One patient who had a third operation for MNG had postoperative hemorrhage necessitating tracheostomy for airway control. Another patient developed a seroma that resolved within 2 months. We conclude that reoperations are indicated for both benign and malignant thyroid disease. Because they carry a higher risk of complications, every effort should be made to avoid them by performing definitive initial treatment.

Solitary toxic adenoma and toxic multinodular goiter are very common forms of thyrotoxicosis around the world. Advances in molecular biology and genetics have led to new insights into the pathogenesis of these disorders. Current theories on autonomy in the thyroid are discussed in this article. The therapeutic roles of surgery, radioiodine ablation, and percutaneous ethanol administration also are reviewed.

From November 1991 to December 1996, 158 patients of whom 137 were Gabonese were examined at the Hospital Center of Libreville (department of internal medicine "B") for a thyroid disorder. The retrospective analysis of their files showed a large majority of women (94.2%) and the main diseases were euthyroidgoiter (54.7%), Graves'disease(13.1%), hypothyroidism (8.8%), thyroiditis (6.6%), toxic multinodular goiter (6.6%) while about 10% of goiters remained unclassified.

With the purpose of studying effects of a complex of factors of Chernobyl Atomic Power Plant breakdown on evolution of nodular goiter, an analysis was carried out of clinical and laboratory evaluation of 6572 individuals (3549 men and 3023 women) who had taken part in the elimination of aftermath of Chernobyl accident, with regard to sex, dose and length of time during which the above individuals were exposed to radiation. Duration of exposure did not appear to affect nodular goiter rates either in men (7.92% in liquidators of "iodine" period and 8.19% among those of "noniodine" period of irradiation, or women (17.31% and 24.66% respectively). Results of studies made 5-7 years after the Chernobyl accident did not show relationship between incidence rate of nodular goiter and dose of radioactive irradiation received.

Background: Surgical treatment is the first option for patients with obstructive multinodular goiter. The extent of the resection and the use of postoperative hormonal therapy are, on the other hand, still under debate., Objective: To analyze the results of surgical treatment in 101 patient with multinodular goiter seen from 1980 to 1995., Materials and Methods: The clinical/pathologic charts of all patients were reviewed with emphasis to the clinical diagnosis, extent of resection, final histology, type and number of complications, and long-term follow-up. The mean follow-up was three years (range 0.5-12)., Results: Ten males and 91 females with a mean age of 46 years were included. Surgery was recommended for a nodule suspicious of malignancy in 60 patients, for airway compression in 33, and for cosmetic reasons in eight. Unilateral lobectomy was performed in 30, bilateral subtotal thyroidectomy in 55 and total thyroidectomy in 16. Postoperative hormone therapy was administrated to 83 patients. Surgical complications occurred in six patients. Four developed permanent hypoparathyroidism and two vocal cord paralysis. There was no operative mortality. A final diagnosis of multinodular goiter was established in 89 whereas 12 had cancer. There were three asymptomatic recurrences in the group with benign lesions (they had undergone unilateral lobectomy followed by hormonal therapy)., Conclusion: Bilateral subtotal thyroidectomy was the best treatment for multinodular goiter in our series. This procedure had few complications and there was no recurrence of the disease.

During the period 1986-1993, 24 children with hyperthyroidism were referred to us for management. Two of them had factitious hyperthyroidism, one toxic nodular goiter and another neonatal Graves' disease. Twenty children (6M, 14F) had Graves' disease. Their age at presentation was 10.86 +/- 2.02 years and duration of symptoms ranged from 2.5 months to 7 years. Neuropsychiatric manifestations, such as hyperkinesis, irritability, excitability and behavioral problems, were the most common initial presenting symptoms (90%). Goiter of varying grades was present in 18 children. Eye involvement of mild or moderate intensity was present in 85% and cardiac involvement in 30%. Serum free thyroxine and triiodothyronine levels were high and radioactive iodine uptake was elevated. All of them received carbimazole 0.5-0.7 mg/kg in three divided doses. Seventeen responded to therapy over a period of time while three did not. On withdrawal, six of the responders relapsed. Hyperthyroidism in children is rare and when it occurs it is almost always due to Graves' disease. The prominence of neuropsychiatric symptoms, insidious onset and absence of severe infiltrative ophthalmopathy differentiates it from the adult type of disease. Prolonged medical therapy is needed to induce good continued remission.

Nodular goiter is the natural evolution of nontoxic goiter, that may be endemic, sporadic or familiar. Iodine deficiency is the cause of endemic goiter, while genetical defects, impairing the thyroid hormone biosynthetic efficiency or altering the number and/or activity of growth factor receptors, play the major role in the pathogenesis of sporadic and familiar nontoxic goiter. The prevalence of nodular goiter is directly related to the degree of iodine deficiency that is still present in several areas of the world. In iodine deficient areas such as some Italian regions, nodular goiter is present in 25-33% of the population, its frequency increasing with age. In iodine sufficient areas the prevalence of nodular goiter is comprised between 0.4 and 7.2% high in iodine deficient areas and about 4% in iodine sufficient countries, its frequency increasing with the age. Dysphagia, dyspnea and coarsening of the voice may occur for esophagous, tracheal or laryngeal nerve compression, respectively. Iodine deficiency has little if any effect on the frequency of thyroid carcinoma, while, with regard to the histological pattern, it leads to an increased ratio papillary/follicular. Thyroid function is normal in uncomplicated nontoxic goiter. However, the evolution of nodular goiter is toward the functional autonomy of nodules that may result in thyrotoxicosis. Hypothyroidism is rare and is usually the result of thyroid autoimmunity. All the cases due to iodine deficiency can be prevented by an adequate iodine prophylaxis that can be accomplished in industrialized countries by the use of sale enriched in iodine.