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Introduction: Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer mortality worldwide. Recent animal studies suggest that thyroid hormone treatment improves HCC prognosis. The aim of this study was to describe the association between thyroid disease and HCC prognosis in humans. Methods: We performed a nationwide cohort study including all persons with an HCC diagnosis from 2000 to 2018. Patients’ age, sex, HCC treatment, and diagnoses of thyrotoxicosis, nontoxic goiter, and myxedema were obtained from Danish national healthcare registries. We used regression models to examine the association between thyroid disease and mortality hazard and restricted mean survival time after HCC diagnosis, adjusting for confounding by sex and age. Results: We included 4,812 patients with HCC and 107 patients with thyroid disease. Median follow-up time was 5 months (total 5,985 person-years). The adjusted mortality hazard ratio was 0.68 (95% CI: 0.47–0.96) for thyrotoxicosis and 0.60 (95% CI: 0.41–0.88) for nontoxic goiter. The restricted mean survival time during the 5 years following HCC diagnosis was 6.8 months (95% CI: 1.1–12.6) longer for HCC patients with thyrotoxicosis than for patients without thyroid disease, and it was 6.9 months (95% CI: 0.9–12.9) longer for HCC patients with nontoxic goiter than for patients without thyroid disease. Conclusions: In this large nationwide cohort study, thyrotoxicosis and nontoxic goiter were associated with prolonged HCC survival.

Nodular formations of the thyroid gland are quite a widespread pathology. The prevalence of nodular goiter in the population is present in 50–70% of the total population. Basically, thyroid nodes are benign and aren’t a direct threat to human life. Laser-induced thermotherapy is one of the minimally invasive methods of treatment. The main idea of laser-induced thermotherapy is to heat the thyroid nodule by laser radiation with a wavelength of 805–1060 nm to a temperature of 41–46°С. In this case, the results of treatment by laser-induced thermotherapy (LITT) in 7 patients with nontoxic goiter were studied. There were no complications after the procedure. The technique of LITT showed high efficiency as a treatment of nontoxic goiter, because in many cases there was a decrease in the size of the thyroid node by 71.6 ± 16.8%. The introduction of LITT to the clinical practice and inclusion it into guidelines of nodular non-toxic goiter treatment can give to patient opportunity to treat nodes without surgical operations.

Previous research has suggested an increased risk of death and cardiovascular disease in patients treated for hyperthyroidism. However, studies on this subject are heterogeneous, often based on old data, or have not considered the impact that treatment for hyperthyroidism might have on cardiovascular risk. It is also unclear whether long-term prognosis differs between Graves' disease and toxic nodular goiter. The aim of this study was to use a very large cohort built on recent data to assess whether improvements in cardiovascular care might have changed the prognosis over time. The study also investigated the impact of different etiologies of hyperthyroidism.This was an observational register study for the period 1976-2012, with subjects followed for a median period of 18.4 years. Study patients were Stockholm residents treated for Graves' disease or toxic nodular goiter with either radioactive iodine or surgery (N = 12,239). This group was compared to Stockholm residents treated for nontoxic goiter (N = 3685), with adjustments made for age, sex, comorbidities, and time of treatment. Comparisons were also made to the general population of Stockholm. Outcomes were assessed in terms of all-cause and cardiovascular mortality as well as cardiovascular morbidity.The hazard ratios (HR) for all-cause mortality and for cardiovascular mortality were 1.27 [confidence interval (CI) 1.20-1.35] and 1.29 [CI 1.17-1.42], respectively, for hyperthyroid patients compared to those with nontoxic goiter. For cardiovascular morbidity, the HR was 1.12 [CI 1.06-1.18]. Patients aged ≥45 years who were treated for toxic nodular goiter were generally at greater risk than others, and those included from the year 1990 and onwards were at greater risk than those included earlier. Increased all-cause mortality, as well as cardiovascular mortality and morbidity, were also seen in comparisons with the general population.This is the first large study to indicate that the long-term risk of death and cardiovascular disease in hyperthyroid subjects is due to the hyperthyroidism itself and not an effect of confounding introduced by its treatment. Much of the excess risk is confined to individuals treated for toxic nodular goiter. Despite advances in cardiovascular care during recent decades, hyperthyroidism is still a diagnosis associated with increased cardiovascular morbidity and mortality.

Objective: To determine the status of thyroid system in girls with secondary amenorrhea (SA).Patients and methods. The study included 82 girls in the age 14-17 years with SA (main group). The control group consisted of 78 girls of the same age with a normal volume of the thyroid gland (TG), harmonious physical development and normal menstrual function. Ultrasound examination and examination of the thyroid gland state are included in the study.Results. The results of visual palpation and ultrasound examination of the thyroid gland state revealed the presence of thyropathies in more than half of patients with SA: diffuse nontoxic goiter of 1-2 (9.8%), autoimmune thyroiditis (12.2%), nodular goiter (3.6%) and thyroid hypoplasia (17.1%).Conclusions a significant number of girls with SA have thyroid dysfunction due to various changes in TTH and free fractions of thyroid hormones independently on the presence of the thyroid pathology.Key words: girls, thyroid gland, thyroid status, secondary amenorrhea.

The objective of the research was to assess the thyroid status of children with diffuse nontoxic goiter and its effect on dental pathology depending on age.Materials and methods. Clinical observation of 226 children at the age of 12-15 years was conducted. To analyze their thyroid status, serum levels of total thyroxine, free thyroxine, total triiodothyronine, and thyroid stimulating hormone were determined using enzyme immunoassay. The following thyroid indices were calculated for the integral estimation of the functional state of the pituitary-thyroid system: the peripheral inversion index (total triiodothyronine/total thyroxine), the integral index (total triiodothyronine + total thyroxine/thyroid stimulating hormone) and the indices of thyroid stimulating hormone/total triiodothyronine and thyroid stimulating hormone/total thyroxine. Their dental status was determined by means of standard indices recommended by the World Health Organization.Conclusions. In children with euthyroid enlargement of the thyroid gland, there were detected changes in the thyroid status within the reference range. According to the direction of changes in the most indices, dysthyroidism is characterized by the reduced thyroid function that can affect metabolic processes in the body, including the dentofacial system, as evidenced by significantly worse indices of the intensity of damage to hard dental tissues and periodontal tissues in children with diffuse nontoxic goiter.

In this work, based on the research of treatment results of 646 patients that were operated for nodular and multinodular nontoxic goiter in Hospital St. Elizabeth endocrinology center, in the period from 1997 to 2013, an analysis of the malignant tumor frequency in patients with follicular thyroid tumors who underwent surgical treatment for the nodular goiter was performed. In this group gender and age characteristics of patients with follicular thyroid tumors were identified, and also an evaluation of surgical treatment safety in patients operated for follicular thyroid tumors was performed.

BACKGROUND AND PURPOSE: Patient-reported outcomes have become important endpoints in comparative effectiveness research and in patient-centered health care. Valid patient-reported outcome measures detect and respond to clinically relevant changes. The purpose of this study was to evaluate responsiveness of the thyroid-related quality of life (QoL) instrument ThyPRO in patients undergoing relevant clinical treatments for benign thyroid diseases and to compare it with responsiveness of the generic SF-36 Health Survey.METHODS: A sample of 435 patients undergoing treatment completed the ThyPRO and SF-36 Health Survey (Version 2) at baseline and 6 months after treatment initiation. Responsiveness was evaluated in three thyroid patient groups: patients with hyperthyroidism (n = 66) and hypothyroidism (n = 84) rendered euthyroid after medical therapy, and patients with a clinically detectable nontoxic goiter treated with surgery or radioactive iodine and remaining euthyroid (n = 62). Changes in QoL were evaluated in terms of effect size and compared to the changes predicted by clinical experts. The responsiveness of equivalent scales from ThyPRO and SF-36 Health Survey were compared with the relative validity index.RESULTS: The ThyPRO demonstrated good responsiveness across the whole range of QoL aspects in patients with hyper- and hypothyroidism. Responsiveness to treatment of nontoxic goiter was also demonstrated for physical and mental symptoms and overall QoL, but not for impact on social life or cosmetic complaints, in contrast to clinicians' predictions. For all comparable scales except one, the ThyPRO was more responsive to treatment than the SF-36 Health Survey.CONCLUSIONS: The ThyPRO was responsive to treatment across the range of benign thyroid diseases. We suggest implementing this measurement instrument as a patient-reported outcome in clinical studies and in clinical management.

Background: Thyroid diseases are the commonest endocrine disorders worldwide and India is no exception. Goiter may be generalized or localized, toxic or nontoxic. The present study is being carried out in a government notified endemic area to study the etiology and surgical management with postoperative complications in patients with nontoxic goiter.Methods: A observational study was carried out at a tertiary care academic hospital. Patients with a clinically diagnosed nontoxic goiter with normal T3, T4 and TSH values were included in the study. The study subjects underwent relevant investigations and surgical intervention. The outcome factors were histopathology of the surgically removed gland and postoperative complications.Results: A total of 67 patients of nontoxic goiter were enrolled. The mean age of the patients was 33.3±11.1 years with female preponderance. The mean duration of the thyroid swelling was 2+/- 2 years. Hemithyroidectomy was most common surgery (68.7%) carried out. A majority (88%) of resected thyroid specimens were benign histopathologically as colloid goiter. An intergroup analysis was carried out between metabolic, autoimmune and neoplastic etiologies. Neoplastic etiology was significantly associated with smooth surface and hard consistency of the gland. Autoimmune goiter had significantly less than 12 months duration and painful. The postoperative complications observed were hypothyroidism (22.4%), hypoparathyroidism (10.5%), RLN palsy (6%) and SSI (3%). Conclusions: Benign pathology was commonly seen with nontoxic goiter. Hypothyroidism and Hypoparathyroidism were the most frequent postoperative complications.

We studied the effect of suppressive therapy with graded doses of thyroxine (T4) on serum levels of T4, 3,5,3′-triiodothyronine (T3) and 3,3′,5′-triiodothyronine (rT3) in patients with diffuse, nontoxic goiter. For comparison and in order to elucidate the degree of suppression of the pituitary thyroid axis by T3 the effect of suppressive therapy with T3 was studied in the same type of patients. We found that T4 in serum rose significantly to a constant level during T4 treatment (0.10, 0.15 and 0.20 mg/day). Dose-related rises in T4 were only seen after 3 months of treatment. T3 and rT3 only changed minimally. The T4/T3 ratio rose to a constant level during the initial 3 months of treatment. T3/rT3 ratio remained unchanged. No dose-related differences in T3/rT4 and T3/rT3 ratio were observed. Treatment with T3 in doses of 0.06 mg per day caused a significant but slow fall in T4 and rT3 to hypothyroid levels while T3 only rose slightly. The T4/T3 ratio dropped significantly during T3 therapy.

SUMMARY. In children with euthyroiden largement of the thyroid gland there are changes of the thyroid status within referential meanings. According to the direction of changes of the most indices thyroid dysfunction is characterized by hypo function of the thyroid gland that can affect on metabolic processes in the child’s organism, and the dento-alveolar system in particular. Its evidence is reliably worse indices of the intensity of affliction of the hard dental tissues and periodontal tissues in children suffering from diffuse nontoxic goiter. Key words: сhildren, diffuse nontoxic goiter, dental diseases. Отримано 13.10.2015

Nodular goiter is caused by excessive replication of thyroid epithelial cell with formation of new follicles. The clinical presentation of patients with nontoxic multinodular goiter is variable and depends on the volume and location of the thyroid. In this chapter some principles of diagnosis and management of nontoxic multinodular goiter are briefly discussed. Furthermore some typical images of patients with nontoxic multinodular goiter are showed.

The influence of clinically apparent thyroid dysfunction on cardiovascular system is indisputable. However, until now there is no clarity weather hypothyroidism, particularly its subclinical form, influences the coronary heart disease (CRT)) course. 102 patients with CRT) who have no thyroid dysfunction and who have nontoxic colloid nodular goiter were included in the present study. Subclinical decrease of thyroid function was revealed in 24 patients (23 % of events). Used methods included 24-hour electrocardiography and blood pressure (BP) monitoring, determination of plasma thyroid hormones and thyrotropin, ultrasound imaging of thyroid gland. The results showed that all groups of patients with CRD independently of thyroid function have a silent myocardial ischemia prevailed over painful myocardial ischemia as in frequency and as in duration. Diastolic BP and heart rate meanings were in a reverse dependence on thyroid hormone plasma levels that was more evidential in patients with subclinical thyroid dysfunction.

Previous studies, mostly performed in iodine-deficient areas, have suggested that the administration of iodine to patients with endemic goiter may be associated with the development of thyroid autoantibodies (ThAbs); however, this has not been a consistent finding. In this study, we evaluated the effect of iodine on thyroid function and on the development of indices of autoimmunity (ThAbs and lymphocytic infiltration) in an iodine replete area.Iodized oil (1 mL) was administered intramuscularly to 40 euthyroid patients with nontoxic goiter, adequate iodine intake, and absent or normal levels of ThAbs. Blood and urinary samples were taken at time 0, 3, 6, and 12 months after iodine administration. Thyroid volume was evaluated and fine-needle aspiration (FNA) was performed at 0, 6, and 12 months.Seven patients developed abnormal levels of ThAbs at some time between 3 and 12 months after iodine administration (p = 0.017). Mean anti-thyroglobulin (Tg) antibody levels increased at 6 months without reaching abnormal levels, but did not reach statistical significance (p = 0.062). Lymphocytic infiltration was detected in FNA smears in 10 cases before and in 27 cases after treatment (p = 0.0003). Triiodothyronine (T3) decreased at 12 months of follow-up, while thyroxine (T4) and thyrotropin (TSH) levels did not change significantly. A decrease in the mean levels of thyroglobulin as well as a small reduction in goiter size was observed at 6 and 12 months.The administration of iodized oil to patients with small nontoxic goiter in an iodine-replete area was accompanied by the development of abnormal levels of ThAbs in some cases and by an increase in thyroid lymphocytic infiltration.

Objective: The objective of the study was to evaluate the long-term outcome of recombinant human TSH (rhTSH)-augmented radioiodine ((131)I) therapy for benign multinodular nontoxic goiter. Patients and Methods: Between 2002 and 2005, 86 patients with a multinodular nontoxic goiter were treated with (131)I in two randomized, double-blind, placebo-controlled trials. (131)I-therapy was preceded by 0.3 mg rhTSH (n = 42) or placebo (n = 44). In 2009, 80 patients completed a follow-up (FU) visit, including determination of thyroid volume, thyroid function, and patient satisfaction by a visual analog scale. Results: In both groups, thyroid volume was further reduced from 1 yr to final FU (71 months). The mean goiter volume reductions obtained at 1 yr and final FU [59.2 ± 2.4% (sem) and 69.7 ± 3.1%, respectively] in the rhTSH group were significantly greater than those obtained in the (131)I-alone group (43.2 ± 3.7 and 56.2 ± 3.6%, respectively, P = 0.001 and P = 0.006), corresponding to a gain of 24% at final FU. At last FU the mean reduction in compression visual analog scale score was significantly greater in patients receiving rhTSH (P = 0.049). Additional therapy (thyroid surgery or (131)I) was required more often in the placebo group (nine of 44) compared with the rhTSH group (two of 42) (P = 0.05). The prevalence of hypothyroidism at 1 yr [9 and 43% in the placebo and rhTSH groups, respectively (P

Substernal goiter is usually defined as a goiter in which the thyroid mass has descended the plane of the thoracic inlet or if more than 50% of the thyroid mass is located below the thoracic inlet. Substernal goiters may be asymptomatic or may present with symptoms caused by compression of adjacent organs. Acute respiratory failure is rare in cases of substernal goiter. In cases of symptomatic substernal goiter the treatment is surgical by thyroidectomy. We present a rare case of a giant substernal nontoxic goiter which caused acute respiratory failure which was treated by urgent thyroidectomy through a T-incision.

Background Total thyroidectomy for treatment of Graves’ disease is controversial and much of the debate centers on the concern for complications. The purpose of this study was to evaluate the morbidity of total thyroidectomy for Graves’ disease and determine if it is different than for patients with nontoxic nodular goiter. Methods The rates of life threatening neck hematoma, recurrent laryngeal nerve (RLN) injury, transient hypocalcemia, and hypoparathyroidism were determined for consecutive patients with Graves’ disease treated with total thyroidectomy from 1996 to 2010. Results were compared with patients who underwent total thyroidectomy for nontoxic nodular goiter during the same period, matched for the weight of the excised thyroid gland. Results Total thyroidectomy was performed in 111 patients with Graves’ disease (group I) and 283 patients with nontoxic nodular goiter (group II). Parathyroid autotransplantation was performed in 31(28%) patients in group I and 98 (35%) patients in group II ( P = NS). Comparative analysis of morbidity revealed no significant difference in neck hematoma, 0(0%) (I) versus 3(1%) (II); permanent RLN injury, 0(0%) (I) versus 2(1%) (II); and permanent hypoparathyroidism in 1(1%) (I) versus 1 (0.4%) (II) ( P = NS). Transient hypocalcemia was more common in patients with Graves’ disease, 80(72%) (I) versus 170 (60%) (II) ( P Conclusions Total thyroidectomy can be performed with low morbidity in patients with Graves’ disease; only transient hypocalcemia occurred more often than in patients with nodular goiter. Total thyroidectomy should be presented as a therapeutic option for all patients with Graves’ disease.

To test the hypothesis that during the natural history of sporadic nontoxic goiter (SNG), a diffuse goiter precedes a multinodular goiter with gradual development of autonomous thyroid function. A cross-sectional survey of 102 consecutive patients with SNG (seven male, 95 female) was performed. Thyroid volume was measured by ultrasonography, and plasma thyroid-stimulating hormone (TSH) by a sensitive assay (TSH immunoradiometric assay). Patients with a multinodular goiter were older and had a larger thyroid volume than patients with a diffuse or uninodular goiter. Plasma free thyroxine (T4) and total triiodothyronine (T3) were higher and plasma TSH was lower in patients than in normal subjects. Free T4 was higher in the subgroup of patients with a multinodular goiter and a decreased TSH response to thyrotropin-releasing hormone. Plasma TSH (y, in mU/L) was negatively related to thyroid volume (x, in mL): y = 8.2x-0.667 (r = 0.578, p less than 0.001). Thyroid volume (y, in mL) was positively related to age (x, in years): y = -21.8 + 2.0x (r = 0.455, p less than 0.001); and to duration of goiter (x, in years): y = 40.6 + 2.1x (r = 0.505, p less than 0.001). The annual increase in thyroid volume was calculated at 4.5%. The data suggest a continuous growth of SNG and provide support for the concept of increasing thyroid nodularity and autonomy of thyroid function--related to increasing thyroid volume--during the natural history of this disorder

The ultrasonic picture and volume of the thyroid, concentrations of intrathyroid stable iodine, total amount of stable iodine, scintigraphy of the organ, blood concentrations of basal TTH, fгее T4 and T3, antibodies to thyroglobulin, and microsomal fraction were studied in 77 patients (69 women and 8 men) with diffuse nontoxic goiter and 37 controls (18 women and 19 men) aged 18 to 50 without enlargement or signs of impairment of the function of the thyroid. Diffuse nontoxic goiter was found to be associated with increase of the thyroid volume, concentrations of intrathyroid stable iodine and total amount of stable iodine, and TTH, and a decreased concentration of T4. A deficit of intrathyroid stable iodine and of T3 in the blood was revealed in 20% of women with antibodies to thyroglobulin and microsomal fraction in the blood, in comparison with patients who had no antibodies to thyroglobulin and microsomal fraction. A reduced concentration of intrathyroid stable iodine in control women was attended by the presence of antibodies to thyroglobulin and/or microsomal fraction and indirect ultrasonic signs of autoimmune pathology of the thyroid. These results permit a conclusion that iodine measurements directly in the thyroid using noninvasive x-ray fluorescent analysis is a sensitive and informative additional method for the diagnosis of thyroid abnormalities.

The results of treatment of 86 patients - the indigenous inhabitants of the northern region of Saudi Arabia with newly diagnosed diffuse nontoxic goiter. Peculiarities of diagnostics, treatment and therapy of diffuse toxic goiter in this ethnic group were studied. We revealed the prevalence of goiter grade II and III. Treatment, that was most effective in reducing the volume of the thyroid, was a combination of potassium iodide (150-200 mg daily) and L-thyroxine in individually selected dose. This treatment resulted in a reduction in the size of 34% of goiter. Potassium iodide monotherapy did not result in a statistically significant reduction in the volume of the thyroid gland.

Symptoms of tracheal-esophageal compression are often related to a large nontoxic goiter. The aim of the present study was to evaluate to what degree upper airway obstruction, as measured by flow volume loops, FIF50% and FEF50%/FIF50% (Forced Expiratory Flow at 50% of the vital capacity/ Forced Inspiratory Flow at 50% of the vital capacity) exists in nontoxic multinodular goiter, and whether changes occur after 131I-treatment. Thirteen patients with large multinodular nontoxic goiters were evaluated by estimation of FIF50%, FEF50%/FIF50% ratio and a graphic plot of the flow volume loop curve before and three, six and 12 months after treatment with 131I. FIF50% increased over 12 months from median 1.79 l/sec (range 1.46-3.02) to 2.84 l/sec (1.13-5.69) (p = 0.01). A progressive increase was seen over time (p = 0.001, trend analysis). The FEF50%/FIF50% ratio decreased from in 1.45 (0.32-2.26) to 1.03 (0.43-2.13) 12 months after treatment (p0.001). A progressive decrease was seen over time (p = 0.001, trend analysis). By visual evaluation 11 had a flow volume loop curve typical for an upper airway obstruction and in 9 patients the FEF50%/FIF50% ratio was1.2. In conclusion we found that upper airway obstruction is present in patients with multinodular nontoxic goiter, and seems to be reduced after 131I-treatment. Flow volume loop curves and measurement of FEF50% and FIF50% are important estimates for upper airway obstruction in these patients.

Thyroid hormone has been used to reduce the size of sporadic nontoxic goiter since 1894. Noncontrolled clinical studies suggest that about two thirds of goiters respond to therapy, and a recent randomized clinical trial confirms the efficacy of suppressive therapy for sporadic nontoxic goiter. Efficacy is at least partly correlated with suppression of pituitary TSH production, response is usually evident by 3 months, relapse occurs when therapy is withdrawn, and nodular goiters may be less responsive than diffuse goiters. Some, but not all, series suggest that postoperative use of thyroid hormone suppressive therapy prevents recurrence of benign goiter. Three recent randomized trials suggest that thyroid hormone administered for 6 months to 3 years does not reduce the size of solitary thyroid nodules. About one third of nodules regressed in both treatment and placebo groups. Long-term studies are needed to define the effects of thyroid hormone suppressive therapy on the growth of goitrous lesions based on their underlying pathophysiology.

In a double-blind study, 114 patients with clinically benign nontoxic goiter were treated either with liothyronine (T3), 50 μg/day, or thyroxine (T4), 200 μg/day. After 12 weeks of therapy, patients whose goiters decreased in size were continued on the same therapy for an additional 16 weeks. Those who did not respond were randomly divided into two groups: in one group the same dose of the same medication was continued, and in the other twice the dose of their original medication was given. By the end of 28 weeks, 40 of 54 patients treated with T3 and 29 of 59 patients treated with T4 showed a significant decrease in goiter size. The difference in effectiveness of the two agents was statistically significant (p T3 produced a uniform and consistent depression of radioiodine uptake and circulating hormonal iodine levels, and was effective shrinking both small and large thyroid nodules, whether or not radioiodine uptake was reduced to hypothyroid levels. T4 uniformly increased circulating hormonal iodine levels. However, in T4-treated patients who responded with regression of thyroid nodules, suppression of radioiodine uptake was substantially greater than in those who did not respond.

The effect of suppressive treatment with thyroid hormones on thyroidal iodothyronines and T4/T3 ratio in nodular and paranodular tissues was investigated in 12 patients with nont

Surgical treatment can be justified already for nontoxic goiter stage I (WHO) because of tracheal stenosis. Surgery for “cosmetic” reasons may be adequate, if treatment with thyroid hormones is neither successful nor promising. Diagnostic (histologic) or prophylactic reasons are today the most frequent causes for surgery, in order to detect or avoid thyroid malignancies. — Iodine prophylaxis is advocated in the Federal Republic of Germany, where iodine deficiency and endemic goiter (15 %) are still prevalent.

Human thyroid blood flow rate (TBF) was measured during operations by electromagnetic flowmetry in 75 euthyroid patients with normal thyroid tissue, nodular goiter, or solitary adenoma, and in 22 hyperthyroid patients with diffuse or nodular goiter. Blood flow rate was measured in one to four of the thyroid arteries. No difference in blood flow rate was seen between the left and right lobes. The slight difference found between the inferior and superior arteries was not significant. In each subject, total TBF was calculated as 4 times the mean of the recorded blood flow in the single arteries. The total TBF was 31 (9-109) ml/min (inner 95 percentile range) in euthyroid patients, similar in all 3 groups. This is less than in most earlier reports. The relative TBF was 1.2 (0.4-3.8) ml/min/g thyroid tissue in normal thyroid tissue and 0.6 (0.1-3.7) ml/min/g in nontoxic nodular goiter (p less than 0.01). Patients with hyperthyroidism had a higher total TBF 54 (15-197) ml/Min (p less than 0.001), despite preoperative treatment giving euthyroidism, Similar TBF rates were found in 3 hyperthyroid patients given propranolol preoperatively. Electromagnetic flowmetry is applicable to study thyroid blood flow rate. Human TBF shows considerable interindividual variations, which must be kept in mind when studying directly the rate of thyroid hormone secretion from arteriovenous gradients.

400 μg TRH given intravenously to normal subjects produced a peak serum TSH within 20 or 30 min. TSH levels were significantly increased as early as 10 min. after the injection. An oral dose of 10 mg of TRH gave a slower and more sustained response in normal subjects. The magnitude of the TSH response was directly related to the basal serum TSH level and inversely proportional to the basal concentration of blood thyroxine. No alteration in the normal pattern of TSH response was observed in patients with euthyroid nontoxic goiters. The data obtained from the normal subjects indicate that the magnitude of the pituitary response to TRH is closely related to the level of the circulating thyroid hormones. Thus, in patients with thyroid pathology the significance of the TSH response curve to TRH must be interpreted after taking into account the level of circulating thyroid hormones. This is particulary important before drawing conclusions concerning any primary defect of the hypothalamo-pituitary system in thyroid pathology.

The 24-hour thyroidal uptake of radioiodine (I131) was determined in control subjects and hyperthyroid patients before and after administration of either 500 mg. of thiourea or 4 Gm. of potassium thiocyanate. Thiourea abolished I131 uptake in 21 normal controls and in 2 patients with nontoxic goiter, whereas the mean uptake value in the hyperthyroid group (8 patients) was above 20 per cent. Potassium thiocyanate reduced the uptake values below 10 per cent in 18 euthyroid controls and 7 patients with nontoxic goiter, whereas in 15 hyperthyroid patients the values were significantly higher. The inhibitory effect of thiocyanate appeared to vary directly with the serum concentration of the ion in both the hyperthyroid and control groups. This difference in response to thiocyanate or thiourea may be a useful means to distinguish between normal subjects and patients with hyperthyroidism.

There is a conflict of evidence concerning the alterations of nondiffusible plasma magnesium in disorders of the thyroid gland. In this investigation it was found in 12 normal individuals, 9 patients with hyperthyroidism, 10 with myxedema, 6 with nontoxic goiter, and 14 patients with miscellaneous diseases, that the nondiffusible plasma magnesium was relatively constant in a wide range of conditions and was not altered even in patients with marked thyroid dysfunction.

ABNORMAL iodoproteins have been found in the serum and thyroid glands of patients with various thyroid diseases: thyroiditis1 2 3; thyroid cancer4 , 5; exophthalmic goiter (Graves's disease)6; and occasionally nontoxic goiter.7 8 9 10 These iodoproteins are in general butanol insoluble and resemble albumin in their solubility and electrophoretic mobility. The production of large amounts of iodoprotein may contribute to the genesis of nontoxic goiter by diverting iodide into metabolically inactive material. In recent years several enzymatic defects in thyroid-hormone synthesis have been recognized as contributing to the development of nontoxic goiter: iodide-trapping defect; oxidase defect; deiodinase deficiency; coupling defect; and an abnormality . . .

A family in which nontoxic goiter was known to occur in 5 generations is reported. Goiters which appeared in early teens were present in 4 of 5 members of the propositus's generation. Their firmness, nodularity and calcification were unique in our experience of familial goiter. Investigations failed to identify any of the recognized thyroid dyshormonogenetic abnormalities. In vivo 131I tracer studies showed a pattern of increased thyroid iodine avidity and rapid turnover. Analyses of the thyroid glands of 3 of the family showed no characteristic abnormality.

The thiocyanate suppression test, as described in the present paper, has proved to be a useful diagnostic assay in patients in whom the thyroidal radioiodine uptake or the clinical findings are equivocal. Thiocyanate, administered during 2 days by mouth at a total dose of 3 g, caused a sharp decrease in the 24-hr I131 uptake in 9 euthyroid patients and in 28 subjects with nontoxic diffuse goiter or nontoxic nodular goiter. No value exceeded 20%. In contrast, no value under 20% was obtained in 17 patients with thyrotoxicosis following thiocyanate administration.

Three groups of patients with nontoxic goiter were treated with T4 and studied serially. The first group (54 cases) was treated with 50 μg/day for the first month, 100 μ/day for the second, 150 μg/day for the third, and 200 μg/day for the fourth. The 4- and 24-h thyroidal 131I uptake, serum T4, resin T3 uptake, and serum TSH before and 30 min after the iv injection of 200 μg TRH were measured before and after each treatment period. The TRH response was suppressed with smaller doses of T4 than the 131I uptake. Using as the criterion for TSH suppression a completely absent TRH response and as the criterion for 131I suppression a 24-h 131I uptake of ≦5% of the administered dose, the proportion of patients showing a suppression by the TRH and the 131I tests respectively, were: with 50 μg/day, 28.5% for TRH and 0% for 131I uptake; with 100 μg/day, 70% for TRH and 7.5% for 131I uptake; with 150 μg/day, 87.5% for TRH and 22.5% for 131I uptake; and with 200 μg/day, 100% for TRH and 54.2% for 131I uptake. All diff...

Thyroglobulin (Tg) levels were found to be elevated in 30 to 35 patients with euthyroid sporadic goiter and in 15 of 37 patients with euthyroid endemic goiter. The elevated Tg levels in the goitrous patients did not correlate with either goiter size, TSH levels, or urinary iodine excretion, but did correlate with the triiodothyronine to thyroxine ratio. It was concluded, therefore, that in both sporadic and endemic euthyroid goiters, factors other than goiter size and TSH, such as hypoiodination of Tg may be responsible for the elevated Tg secretion.

The effect of suppresive treatment with thyroid hormones on thyroidal iodothyronines and T4/T3 ratio in nodular and paranodular tissues was investigated in 12 patients with nontoxic goiter. Results were compared to those from 11 nontreated patients. Continous thyroid hormone administration produced a significant increase in thyroidal T4 and T4/T3 ratio in nodular tissues while T3 remained unchanged. In paranodular tissues a significant rise of T4/T3 ratio, an insignificant increase in T4 and a decrease in T3 were observed following the administration of thyroid hormones. The results are very similar to those obtained in paranodular tissues of autonomously functioning thyroid nodule, and are probably a consequence of suppressed TSH secretion, as TSH predominantly stimulates the synthesis of T3 and/or throidal T4 monodeiodination.

Os autores estudam o comportamento da tireóide em um grupo de 304 pacientes com miastenia grave, constatando 15 casos de tireopatias, sendo 9 de hipertireoidismo, um de hipotireoidismo e 5 de bócio sem alterações da função tireoidiana. Nenhum paciente era proveniente de região de bócio endêmico e não havia bócio familiar. A tireotoxicose, que foi a disfunção mais frequente, foi estudada quanto a sua prevalência em pacientes miastênicos, quanto a sua influência sobre os sintomas da miastenia grave e quanto à época do seu aparecimento. In a group of 304 myasthenic patients 15 cases with thyropathies were reported: nine with hiperthyroidism, one with hypothyroidism and five with nontoxic goiter. Four patients presented diffuse simple goiter and one a multinodular goiter with normal thyroid function. No patient came from an endemic goiter region, not even familial goiter. The prevalence and influence of hyperthyroidism on myasthenic symptomatology were studied. Our findings suggest that there is no clinical correlation between both myasthenia symptomatology and thyroid dysfunction, neither significant influence on myasthenic symptoms when the endocrine disorders improve.

Twenty-five patients with nontoxic nodular goiters and six with toxic goiter were studied prior to subtotal thyroidectomy, with closely spaced blood sampling up to three weeks after surgery, and approximately one year after surgery. Serum thyroglobulin (Tg) was measured by a previously described radioimmunological method. The mean serum Tg was elevated in patients with nontoxic nodular and toxic goiters compared to sex and age matched control groups with pronounced increases during surgery. The disappearance curves of Tg in both groups had two exponentials, an initial steep slope with a half-life of 4.0 +/- 1.8 (SD) h in nontoxic goiter and 4.5 +/- 3.2 h in toxic goiter. This was followed by a more shallow slope with a half-life of 3.6 +/- 1.1 days in nontoxic goiter and 3.4 +/- 0.8 h in toxic goiter, the breaking point between the slopes lying approximately at 48-72 h. There was no significant difference between the half-life of Tg in patients with toxic or nontoxic goiters, respectively. There was a weak correlation between the weight of the removed thyroid tissue and the maximally obtained Tg concentration at the time of surgery, but no correlation with the levels before operation. Serum Tg was significantly lower three weeks after operation and approximately one year after surgery. In conclusion, different forms of the Tg molecules seem to be removed at different rates, independent on the type of goiter.

In 16 patients with nontoxic goiter T3 was given orally, 20 μg daily for the first month, 40 μg for the second and 60 μg for the third. Before and at the end of each month the basal serum TSH levels and the 30 min response to 200 μg TRH iv were measured. The difference was calculated as δ TSH. Serum T4, T3 resin uptake, and T3 were measured at the beginning and at the end of treatment. The results were compared to those obtained in 2 groups of 18 and 54 patients, respectively, treated with increasing doses of oral T4. In the patients treated with exogenous T3 there was a rise of serum T3 from 2.02 ± 0.06 to 3.48 ± 0.08 nmol/l, and whileon 60 μg/day all had serum T3 levels well within the hyperthyroid range. However, the TRH test became negative in only 62.5% of them. On the contrary, in the groups treated with T4 the TRH test was promptly suppressed completely, and ATSH became 0 with 100 μg of T4 daily in virtually all cases. It is concluded that although 60 μg of T3 are more than the daily maintainance dose and result in hyperthyroid serum T3 levels, the pituitary-thyroid axis is not completely suppressed, probably because pituitary TSH secretion is regulated by the intrapituitary conversion of T4 to T3 and not by serum T3 levels. Hence, if one wants to suppress the pituitary TSH release, as in the treatment of nontoxic goiter, T4 and not T3 is the drug of choice: it is selectively converted to T3 in the pituitary, where it produces higher T3 levels and so more complete suppression of the TSH release, without unduly high serum T3 levels and thyrotoxic manifestations from the peripheral tissues.

The intrathyroidal stable iodine (ITI) determined in 776 patients chosen at random. Ninety % of these patients presented with nontoxic goiter. Curve-filtering analysis techniques showed a seasonal variation in ITI: an acrophase was found in April/May, a nadir in September/October. The possible relationship of this seasonal variation with the intake of iodine or alimentary antithyroid substances are discussed, as well as possible relationship with variation in chronic TSH stimulation related to ambient temperature.

This article discusses the diagnostic and therapeutic measures the authors have used during the past 5 years to treat 861 patients from an endemic goiter area with various thyroid disorders. The similarities and differences between these patients, with nontoxic goiter, toxic goiter, and thyroid cancer, were compared with those seen in patients with thyroid problems who live in iodine-rich areas.

During 30 yr of iodine prophylaxis endemic goiter in school children had disappeared in the Savonlinna area which has been the location of continuous surveillance in the East of Finland. In adults goiter is still found to some extent especially in older people. The iodine intake has increased from about 50 to 300 micrograms per day during these yr and the thyroidal uptake of radioactive iodine has decreased from over 60% to between 20 and 30%. However, there is a significant difference in this regard between nongoitrous individuals and goiter patients. In the present study comprising only goiter patients it was found that the thyroidal uptake was significantly higher in the group of patients with a subnormal response to TRH. These patients also had larger goiters and more palpable thyroid nodules than those with a normal response to TRH. The mean age was significantly higher (60.3 yr) as compared to that in the group which had a TSH-response to TRH of greater than 20 mU/l, smaller glands and less thyroid nodules (45.1 yr). The data fit well with the reports on increasing autonomy with increasing age in nontoxic goiter.

Up to the present, 4 methods applicable to study of the electrical properties of skin have been proposed for the diagnosis of thyroid diseases: constant-current resistance, capacitance with audio-frequency current, impedance angle, and impedance. However, accurate correlation of these parameters with the histologic structure of the skin has not been possible. In this study, the initial capacity of the skin to resist a constant current was measured by a new electrical method in 75 untreated subjects with suspected thyroid disease. It was found that: 1) the correlation coefficient between the initial capacity and the basal metabolic rate was 0.90 in 19 males and 0.74 in 56 females, and between the initial capacity and the 24-hour thyroidal I131 uptake was 0.88 in 13 males and 0.61 in 33 females; 2) the initial capacity was normal or higher in 15 hyperthyroid patients and the lower than normal in 5 hypothyroid patients, whereas in 17 euthyroid subjects with nontoxic goiter and in 17 subjects with nonthyroid ...

A quantitative study of the dynamic aspects of thyroid secretion has been carried out in patients with sporadic nontoxic goiter living in Belgium. There is a functional heterogeneity of thyroid tissue, that is, the existence of a rapidly utilizable and renewable iodine pool alongside one or more glandular pools with a slow turnover. Only part of the iodine stored in the thyroid is effectively utilized. In the patients studied here, the true secretory activity falls within normal limits.

Different parameters of intrathyroidal iodine metabolism have been investigated in 27 sporadic nontoxic goiters, and compared with similar observations carried out in normal thyroid glands. In nontoxic goiters, the marked drop in 127I concentration is found to be linked with a similar fall in the iodination level of the thyroglobulin, the average value being .06% compared with .23% in normal glands. The percentage distribution of the iodoaminoacids in the glands shows a significant decrease in the amount of iodine present as DIT and T4. In each sample, the ratio DIT*/MIT*+DIT* decreases as a function of the drop in the iodine concentration of the tissue; the 2 parameters also show marked modifications in different samples taken from the same glands. The T4-127I percentage is about normal in some goiters, but appears noticeably lower when the iodination level of the thyroglobulin falls under .1%. An almost parallel modification occurs in the T4/DIT ratio. The relative specific activities of the di...

In 9 cases of sporadic goiter, a study was made of the soluble proteins of thyroid glands obtained at operation. All the patients were euthyroid. A tracer dose of radioiodine I131 was given before the operation. Similar investigations were performed on histologically “normal” tissue (from 5 patients, thyroidectomized because of localized carcinoma of the thyroid). In both normal and goitrous tissues, thyroglobulin was the only iodoprotein present. In the goitrous glands, the general characteristics of this protein were normal, but its iodinated amino acids content was altered: an average MI131T/DI131T ratio of 2.58 was observed (below 1 in normal tissue), together with a very low content of iodothyronines. These observations seem to indicate that the iodination of MIT into DIT and the synthesis of the iodothyronines are decreased. These facts suggest that hormone synthesis is less active. Nevertheless, the thyroid secretion—as shown by the level of protein-bound iodine—still appears to be sufficient, owin...

In patients suffering from nontoxic goiter, TSH metabolic clearance and production rates are not higher than in normal subjects living in the same environment. Goiter maintenance is therefore not explained by an increased TSH secretion rate. Normal Belgian subjects living with a relatively iodine-deficient intake have a high TSH production rate, as compared to the values reported in the USA.

A 20-year-old man with stridor and dyspnea from goitrous tracheal compression was treated with large doses of thyroid hormone derivatives and had complete regression of symptoms and goiter with restoration of the tracheal lumen. Surgery was not necessary. This "suppressive" medical approach has a sound physiologic basis and should be considered in the management of nontoxic goiter.

Nontoxic goiter, a compensatory phenomenon, reflects a defect in the synthesis of thyroxine. The compensation is not always complete and hypothyroidism sometimes coexists with goiter. Two hundred thirty-four such patients were observed during a 13-year period. The frequency of the signs and symptoms were tabulated. Both the PBI and 24-hour 131I uptake by the thyroid were carried out in 200 patients. The most common symptoms were fatigue, paresthesias, intolerance to cold and dry skin; the most common signs were dry skin and the appearance of hypothyroidism. The most frequently encountered combinations of the laboratory tests were a low PBI and normal uptake, and a low PBI and low uptake. Treatment with thyroid relieved the individual symptoms and signs in 78 to 98 per cent. Eighty per cent of the goiters decreased in size or disappeared during treatment. The syndrome recurred in 88 per cent of patients in whom treatment was interrupted. The study also confirmed earlier findings that hypothyroidism accompanies about 15 per cent of nontoxic enlargements of the thyroid.

Summary A family of six Negro children,four of whom had goiters, has been described. The goitrous children were found to have a defect in organic binding of iodine, as shown by the release of thyroidal radioiodine after the administration of potassium thiocyanate. Of great interest was the fact that these children have remained euthyroid as determined by clinical and laboratory observations. Studies of thyroid metabolism have been presented and the histopathology of a thyroid biopsy from one of the children has been described. It was concluded that this familyof goitrous children clearly demonstrated examples of “simple” nontoxic goiter due to an intrinsic metabolic defect in thyroxine synthesis.

The syndrome of iodide-induced hyperthyroidism (Jodbasedow) is not common and has been reported to occur in patients with iodine-deficient goiter after iodide replenishment. As part of a larger study to assess the effects of iodide administration on thyroid hormone synthesis in normal subjects and in patients with various underlying disorders of the thyroid, iodides (5 drops of a saturated solution of potassium iodide) were administered to eight patients with nontoxic goiter residing in Boston, an area of iodine sufficiency. Hyperthyroidism developed during and after iodide administration in four of the eight — an unexpectedly high frequency. This finding suggests that the homeostatic mechanism controlling thyroid hormone synthesis and release in these patients is not functioning normally. We recommend that large doses of iodides not be administered to patients with nontoxic goiter.