Endemic goiter: clinical picture and evolution

The goiter is the most frequent clinical manifestation of the nutritional deficiency of iodine. If present in more than 5% of the general population or more than 10% of the children in school of a defined geographic area, goiter is defined endemic. Endemic goiter is an adaptive disease produced by the persistent stimulation of the thyroid gland as consequence of the thyrotropin increased secretion due to the iodine deficiency. If iodine deficiency is severe or persistent, other manifestations can be observed in the clinical picture of the iodine deficiency disorders (IDD), such as cretinism. In general goiter is not associated to other manifestations during the initial state of the disease, but nodular and toxic evolution are frequent complication of long standing disease.     

Interactions of vitamin A and iodine deficiencies: effects on the pituitary-thyroid axis

Vitamin A (VA) deficiency (VAD) and the iodine deficiency disorders (IDD) affect > 30% of the global population and these deficiencies often coexist in vulnerable groups. VAD has multiple effects on the pituitary-thyroid axis; VA status modulates thyroid gland metabolism, peripheral metabolism of thyroid hormone, and production of thyrotropin (TSH) by the pituitary. Findings from Africa children indicate that VAD in severely-IDD-affected children increases TSH stimulation and thyroid size, and reduces risk for hypothyroidism. In children with VAD, the higher TSH concentrations in the face of higher circulating total thyroxine suggest central resistance to normal TSH suppression by thyroid hormone. In IDD- and VAD-affected children receiving iodized salt, concurrent VA supplementation improves iodine efficacy. Recent VA and iodine depletion studies in rats indicate moderate VAD alone has no measurable effect on the pituitary-thyroid axis; however, concurrent iodine deficiency (ID) and VAD produce more severe primary hypothyroidism than ID alone. Repletion studies in VA- and iodine-deficient animals suggest: 1) primary hypothyroidism in animals with concurrent moderate VAD and ID does not reduce the efficacy of high doses of oral VA; 2) VAD does not reduce the efficacy of dietary iodine to correct pituitary-thyroid axis dysfunction due to iodine deficiency; and 3) given alone, without iodine repletion, high-dose VA supplementation in combined VAD and ID may reduce thyroid hyperstimulation and reduce risk for goiter.     

Iodine deficiency and iodine prophylaxis experience in Sicily

Twenty years ago we described an area of goiter endemia in North-Eastern Sicily. In this area endemic goiter was associated to a variable degree of iodine deficiency and, in some places, also to an increased thiocyanate urine excretion. Our studies have demonstrated a strict relationship between iodine deficiency and congenital hypothyroidism (both permanent and transient), an increased prevalence of autonomously functioning thyroid nodules and an increased prevalence of thyroid cancer (follicular and anaplastic histotypes). A number of cases of endemic cretinism have also been described. An active iodine prophylaxis program has been carried in the town of Troina in the years 1979-87, by iodinating the municipal water supply. This intervention caused the disappearance of goiter in schoolchildren in only five years. In the last 20 years the prevalence of goiter has decreased in all endemic areas probably because of the "silent prophylaxis", due to improved socio-economic conditions and industrial food consumption. Today the persistence of endemic goiter confirms the inadequacy of the silent iodine prophylaxis and the need to immediately introduce an active iodine prophylaxis in Sicily.     

Transient congenital hypothyroidism: physiopathology and clinica

The fetus and the newborn are more sensitive than adults to a reduced environmental iodine supply, and in iodine-deficient areas, transient neonatal hypothyroidism is frequently observed. This transient thyroid failure may be associated with neonatal goiter and elevated serum thyroglobulin levels at birth. Borderline elevated neonatal serum TSH concentrations frequently occur in newborns in iodine deficient areas, and result in a higher recalling rate at the screening for congenital hypothyroidism. Minor defects in mental performances and neurological development are observed in children living in areas of mild to moderate iodine deficiency, and result from the concomitant effects of iodine deficiency in the mother during pregnancy and transient neonatal hypothyroidism. Endemic cretinism is the severe and irreversible neurological consequence of iodine deficiency during fetal and neonatal life. Iodine prophylaxis is highly effective in preventing the development of iodine deficiency disorders including transient neonatal hypothyroidism. Since iodine prophylaxis in Italy is inadequate, variable degrees of iodine deficiency are still present all-over the country, and are responsible of a higher incidence of transient neonatal hypothyroidism or hyperthyrotropinemia.     

Appropriate iodine nutrition in Iran: 20 years of success

Iodine is a trace element in the human body, its only known function is the synthesis of thyroid hormones. Effects of iodine deficiency, termed iodine deficiency disorders (IDD), include endemic goiter, hypothyroidism, cretinism, decreased fertility rate, increased infant mortality and mental retardation. 2.2 billion people worldwide are at risk for IDD. Of these, 30-70% have goiter and 1-10% have cretinism. Two decades ago the I.R. Iran was among the countries most severely affected by iodine deficiency, but during the last two decades has made much progress in the development of universal salt iodization strategies and IDD prevention, and since 1996 meets all WHO/UNICEF/ICCIDD criteria for the sustainable elimination of iodine deficiency.     

Serum TSH, FT3, and FT4 levels in inhabitants of an endemic goiter area in China supplied iodized salt for twenty-five years

The thyroid function and TSH concentration of villagers in an endemic goiter area in China where iodized salt had been supplied for twenty-five years were surveyed. We found that the serum FT3 and TSH (IRMA) levels of villagers were higher and the FT4 levels was lower than those of the controls, which suggested that the inhabitants of the endemic goiter area had subclinical hypothyroidism based on the ultrasensitive method for TSH assay. Therefore, we suggest that the best biochemical techniques for monitoring the iodized salt prophylaxis program and the physiological response of villagers to iodine are measurements of serum TSH level and FT4 level periodically.     

Cognitive and motor functions of iodine-deficient but euthyroid children in Bangladesh do not benefit from iodized poppy seed oil (Lipiodol)

Iodine supplementation before pregnancy in iodine-deficient women prevents cretinism and neuromotor deficits in their offspring. It is unclear whether iodine supplementation benefits cognitive function in iodine-deficient school-aged children. We therefore conducted a double-blind, randomized, controlled trial of the effects of iodized poppy seed oil (Lipiodol) on cognitive and motor function and weight gain of iodine-deficient school children. The study was conducted with 305 children in grades 1 and 2 from 10 primary schools in two iodine-deficient areas in Bangladesh. The children were stratified by school and grade and randomly assigned to receive 400 mg of oral Lipiodol or a placebo. All children were given a battery of cognitive and motor function tests and had their weights, serum thyroxine (T4) and thyroid-stimulating hormone (TSH) and urinary iodine levels measured before and 4 mo after the intervention. On enrollment, both groups were moderately iodine deficient (median urinary iodine values: placebo group = 3.3 micromol/L, n = 148; iodine group = 3.1 micromol/L, n = 152; goiter prevalence in both groups >95%). However, their T4 and TSH levels were within the normal range. After 4 mo, there was a significant treatment effect on urinary iodine levels (P < 0.0001), but the levels of the treated group were still below normal (median = 7.9 micromol/L). No significant differences were found in T4 and TSH levels, weight gain, cognitive or motor function. The findings suggest that Lipiodol supplementation in moderately iodine-deficient children with normal T4 levels is unlikely to benefit their cognitive function. However, it remains possible that other iodine preparations may have benefits.     

Vitamin A supplementation in iodine-deficient African children decreases thyrotropin stimulation of the thyroid and reduces the goiter rate

BACKGROUND: Vitamin A (VA) deficiency (VAD) and iodine deficiency (ID) often coexist in children in Africa. VAD may affect thyroid function and the response to iodine prophylaxis. OBJECTIVE: The aim was to investigate the effects of supplementation with iodine or VA alone, and in combination, in children with concurrent VAD and ID. DESIGN: A 6-mo randomized, double-blind, 2 x 2 intervention trial was conducted in 5-14 y-old South African children (n = 404), who, on average, had mild-to-moderate VAD and ID. At baseline and after 3 mo, children received 1) iodine (191 mg I as oral iodized oil) + placebo (IS group), 2) VA (200000 IU VA as retinyl palmitate) + placebo (VAS group), 3) both iodine and VA (IS+VAS group), or 4) placebo. At baseline, 3 mo, and 6 mo, urinary iodine (UI), thyroid volume, thyrotropin (thyroid-stimulating hormone; TSH), total thyroxine (TT(4)), thyroglobulin, serum retinol (SR), and retinol-binding protein (RBP) were measured. RESULTS: SR and RBP increased significantly with VA supplementation (P < 0.05). For UI, SR, and RBP, there were no significant treatment interactions between iodine and vitamin A. The 3-factor and all three 2-factor interactions were significant for thyroid volume, TSH, and thyroglobulin (P < 0.001), whereas none of these interactions were significant for TT(4). There was a clear effect of VAS without IS on TSH, thyroglobulin, and thyroid volume; all 3 variables decreased significantly (P < 0.05). CONCLUSIONS: Iodine prophylaxis is effective in controlling ID in areas of poor vitamin A status. VA supplements are effective in treating VAD in areas of mild ID and have an additional benefit-through suppression of the pituitary TSHbeta gene, VAS can decrease excess TSH stimulation of the thyroid and thereby reduce the risk of goiter and its sequelae.     

On goiters and the stupidity which in some countries accompanies them. Endeavours of Vincenzo Malacarne, from Saluzzo

Two hundred years ago, V. Malacarne, pathologist and surgeon, published a booklet entitled "Su i gozzi e sulla stupidità che in alcuni paesi gli accompagna". Malacarne was born at Saluzzo, a town at the foot of the Cottian Alps, in Western Piedmont. Goiter and endemic cretinism were prevalent at the time (1789) in the countryside. In 1940-45 goiter epidemics spread through these still endemic regions. On the basis of his own observations on autoptic material, he suggested that the main cause of cretinism was brain damage due to impeding of the blood circulation by the neck swelling, and invited the pathologists of the Po and Aosta valleys to send him the head and the neck of these goitrous idiots for his researches. Today, too, we believe the thyroid and the brain to contain crucial factors of cretinism and assume that iodine deficiency is the main cause of the disease. Yet we do not know either the factor which damages and prevents in the myxoedematous cretin postnatal thyroid growth, or the pathogenesis of deaf-mutism, spastic paraplegia and severe mental deficiency of the neurological, non-hypothyroid cretin. While these questions remain unanswered, ample evidence has been gathered during the last two centuries regarding the practical importance of iodine prophylaxis to prevent these scourges, today referred to as "iodine deficiency disorders".     

Efficacy and safety of iodine prophylaxis

Iodine deficiency and iodine deficiency disorders (IDD) are still present in developing countries as well as in some European areas. It is well known that iodine deficiency correction prevents endemic goiter and other IDD. Iodized oil has been shown to reduce goiter prevalence and cretinism in African countries. In countries where iodine prophylaxis is performed since many years (USA, Switzerland, Scandinavian countries) IDD are dramatically reduced. One example of the efficacy of iodine prophylaxis through iodized salt was reported in a Tuscan village were urinary iodine excretion increased from 47 micrograms/l in 1981 to 130 micrograms/l in 1991. Goiter prevalence in schoolchildren dropped from 60% in 1981 to 8.1% in 1991. In the same children neuropsychological performances were evaluated showing a reduction of motor response to perceptive stimuli assessed by measurement of reaction times in children born before the beginning of iodine prophylaxis. Iodine prophylaxis has no side effects, although a transitory increase of hyperthyroidism has been reported in the past and recently in African countries. A reevaluation by the experts of the International Council for the Control of Iodine Deficiency Disorders (ICCIDD) has pointed out that this phenomenon is not relevant with respect to the efficacy of iodine prophylaxis. In conclusion, universal iodine prophylaxis prevents endemic goiter and other IDD, without side effects.     

The role of iodine in the evolution of thyroid disease in Greece: from endemic goiter to thyroid autoimmunity

The thyroid gland is dependent on dietary iodine for the production of thyroid hormones, normal iodine requirement being about 150-200 microg/day. Long-term deficiency in iodine intake is associated with the development of goiter. When the prevalence of goiter in a population rises above 5-10%, the problem is considered endemic. Greece is a country with a recent history of moderate iodine deficiency, endemic goiter being prevalent in the 1960s in inhabitants of mountainous regions. Despite recognition of the problem, an iodine prophylaxis program was never officially implemented. Instead, "silent iodine prophylaxis" took place during the 1980s and 1990s with Greece's improvement in socioeconomic conditions. This resulted in the elimination of iodine deficiency and a parallel decrease in the prevalence of goiter among schoolchildren in formerly iodine deficient areas. However, the transition from iodine deficiency to iodine sufficiency or excess was followed by the emergence of autoimmune thyroiditis, especially among young girls, indicating that exposure to excess iodine may trigger thyroid autoimmunity. Thus, the modification of an environmental factor, ie dietary iodine, over the last 40 years in Greece has been associated with changes in the phenotypic expression of thyroid disease from endemic goiter to goiter associated with autoimmune thyroiditis.     

The role of prevention in decreasing endocrine pathology

Time course of changes in the incidence of thyroid diseases and their association with other noncontagious chronic diseases (NCCD) have been evaluated among therapeutic patients hospitalized at Research Center for Clinical and Experimental Medicine of Siberian Division of Russian Academy of Medical Sciences in 1983-1995. The incidence of thyroid diseases was low in 1983, when prevention of iodine-deficiency diseases was a state program. In 1989, when iodine deficiency prevention was reduced, the incidence of cases with enlarged gland and its dysfunction has drastically increased. In 1995, when the system of population protection from endemic goiter virtually ceased to function, the incidence of thyroid diseases increased, including such serious diseases as diffuse toxic goiter, nodular goiter, primary hypothyrosis, and autoimmune thyroiditis; the number of patients in whom thyroid diseases were concomitant with other NCCD increased. These results demonstrate the principal significance of the preventive trend in public health.     

Subclinical prenatal iodine deficiency negatively affects infant development in Northern China

Although mild-to-moderate levels of iodine deficiency (ID) have been associated with poor cognitive outcomes in children, little is known about subclinical prenatal ID and infant development. In this study, the association between elevated cord blood thyroid stimulating hormone (TSH, thyrotropin) and infant development was examined in Northern China. Three groups of infants with elevated cord blood TSH were compared with infants with normal TSH levels on an information processing task at 7 mo, and in cognitive and motor developmental assessments at 13 mo. Infants with elevated TSH had poorer information processing skills and lower scores on the cognitive development index. There were no differences in motor abilities. Relationships between socioenvironmental factors and iodine status were assessed. Infants from more rural settings and those whose mothers had completed fewer years of schooling and had lower paying occupations had higher cord blood TSH levels. A regression analysis indicated that maternal education was predictive of cognitive performance among infants with elevated TSH but not control infants. The findings suggest that subclinical prenatal ID has negative effects on infant development and that, in some instances, maternal education may ameliorate these effects.     

某市中小学教师职业紧张及甲状腺异常情况调查

  目的  探讨珠三角某市中小学教师职业紧张现状及甲状腺异常情况，提高教师健康水平。
  方法  选择2019年1月—12月在珠三角某三甲医院进行健康检查的618名中小学教师作为研究对象，收集其基本信息和职业紧张状况，测定其血清中甲状腺功能指标，运用彩色多普勒超声检查其甲状腺，二元logistic回归分析探索甲状腺肿大的危险因素。
  结果  研究对象教龄5~30年，平均（9.83 ±2.09）年。职业紧张发生率为26.21%（162/618），其中:轻度职业紧张者102名（占62.96%），中度职业紧张者37名（占22.84%），重度职业紧张者23名（占14.20%）。研究对象职业紧张任务总得分高于国内常模[（167.51 ±22.36）分vs.（162.89 ±27.04）分，P < 0.05）]；个体应对资源总得分低于国内常模[（124.16 ±16.08）分vs.（128.23 ±17.73）分，P < 0.01]。中度职业紧张组、重度职业紧张组的促甲状腺素（thyroid stimulating hormone，TSH）水平低于非职业紧张组和轻度职业紧张组，而游离甲状腺素（FT4）水平高于非职业紧张组和轻度职业紧张组，差异均有统计学意义（P < 0.05）。logistic回归分析结果显示:TSH水平降低，游离三碘甲状腺原氨酸（FT3）、FT4水平升高，教龄增加，职业紧张是中小学教师甲状腺肿大的危险因素（P < 0.05）。
  结论  职业紧张可能增加中小学教师甲状腺功能异常和肿大的发生风险，因此应加强定期体检，提高其健康水平。
     

彩超对结节性甲状腺肿的诊断与鉴别

目的分析结节性甲状腺肿声像图特征，探讨超声结节性甲状腺肿与甲状腺瘤及甲状腺癌的鉴别诊断价值。方法分析比较68例结节性甲状腺肿与60例甲状腺瘤、21例甲状腺癌的二维及彩色多普勒超声声像图。结果68例结节性甲状腺肿与60例甲状腺瘤、21例甲状腺癌比较，甲状腺大小、结节大小、结节内回声及周围回声差异无统计学意义（P〉0．05）；而结节边缘晕环及结节内部和周边血流信号差异有统计学意义（P〈0．05）。结论结节性甲状腺肿较易误诊为甲状腺癌，结节边缘晕环及结节内部和周边血流信号可鉴别诊断，为临床治疗提供一定的帮助。     

The problem of exogenous subclinical hyperthyroidism

Over the past two decades a plethora of publications and clinical practice data have established that subclinical thyroid dysfunction is a common condition occurring much more frequently than the overt expression of thyroid disease. Subclinical hypothyroidism is considered to be the most common of these entities. However, far more common and relatively less studied is exogenous sublinical hyperthyroidism (SubHyper) caused by L-thyroxine (T4) administration to thyroidectomized or hypothyroid patients or patients with simple or nodular goiter. Despite iodination, simple goiter is still prevalent and single or multiple nodules are now detected by ultrasound screening in 25-30% of adults, who are accordingly frequently given long-term T4 treatment. Approximately half of European Endocrinologists administer T4 permanently to patients with the above entities with the aim of suppressing TSH levels. Furthermore, in the USA the Colorado Study demonstrated that 40% of patients receiving thyroid hormones had abnormal [corrected] TSH levels (i.e. lower than 0.3 or higher than 5.1 mU/L); of these, 0.9% had hyperthyroidism and 20.7% subclinical hyperthyroidism [corrected] These facts render exogenous SubHyper an everyday problem for the endocrinologist. Exogenous SubHyper differs in many aspects from endogenous, its principal difference being that it is an iatrogenic thyroid disorder induced by the endocrinologist. The management of exogenous SubHyper relies on appropriate adjustment of T4 dosage taking into consideration a) individual requirements in T4, sex, age and the presence of cardiovascular disease or other co-morbidity, b) the recognition that small changes in serum FT4 have a logarithmic effect on TSH, c) the variability of FT4-TSH interactions between individuals, d) the instability of T4 preparations and its bioavailability, and e) the values of serum FT4 and FT3 that accompany a suppressed TSH. This last parameter is of importance since it is the free thyroid hormones values in the serum that generate and reflect the thyroid metabolic state of the organism rather than the degree of TSH suppression.     

甲状腺次全切术结合海藻玉壶汤治疗结节性甲状腺肿患者的效果观察

目的探讨甲状腺次全切术结合海藻玉壶汤治疗结节性甲状腺肿的临床疗效。方法 80例结节性甲状腺肿患者随机分为两组各40例,观察组给予甲状腺次全切术结合海藻玉壶汤治疗,对照组给予甲状腺次全切除术治疗,比较两组的治疗效果。结果观察组的治疗总有效率显著高于对照组(97.50%vs. 82.50%, P<0.05)。治疗后,观察组的TSH、FT3、FT4水平均显著优于对照组(P<0.05)。术后半年,观察组的复发率显著低于对照组(0.00%vs. 12.50%, P<0.05)。结论甲状腺次全切术结合海藻玉壶汤治疗结节性甲状腺肿具有显著的临床疗效,可改善甲状腺激素水平,降低复发率。     

结节性甲状腺肿合并甲状腺微小癌的临床诊断及治疗

目的研究结节性甲状腺肿合并甲状腺微小癌的临床特征、诊断与治疗方法。方法回顾性分析本院收治的78例结节性甲状腺肿合并甲状腺微小癌的临床资料。结果术前彩超检查准确率为26.92%;术中冰冻切片检查准确率为74.36%;与确诊结果比较均具有统计学显著差异性(P<0.01)。结论结节性甲状腺肿合并甲状腺微小癌的术前诊断难度较高,因此应结合临床表现适当扩大手术适应证,并充分结合术中实际情况给予个性化手术治疗。     

59例结节性甲状腺肿合并甲状腺癌的临床诊治体会

目的：探讨结节性甲状腺肿合并甲状腺癌的治疗原则与措施,研究二者之间可能存在的联系。方法：回顾分析本院5年间接受手术治疗的结节性甲状腺肿合并甲状腺癌的59例患者的临床资料,分析病例的临床及病理特点。结果：59例接受手术治疗的结节性甲状腺肿合并甲状腺癌患者,其中乳头状癌28例;滤泡癌12例;乳头状癌合并滤泡癌10例;髓样癌7例;未分化癌2例。所有患者经过1-7年的随访,有4例复发。结论：结节性甲状腺肿与甲状腺癌有着密切的关系,其中以甲状腺乳头状癌最为常见,对于术前难以诊断的微小癌,可以借助术中快速冰冻病理提高甲状腺癌的检出率,选择合理的手术方式和手术范围可以提高甲状腺癌的疗效。     

Administration of iodized oil during pregnancy: a summary of the published evidence.

This brief review of the available studies confirms that the administration of iodized oil before or during pregnancy prevents endemic cretinism and brain damage by correcting iodine deficiency and thyroid function in pregnant women, fetuses, neonates, infants and children. The potential benefits derived from using iodized oil immediately before or during pregnancy greatly outweigh the potential risks in areas of moderate and severe prevalence of iodine-deficiency disorders, where iodized salt is not yet available.