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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.

TODAY interest centers predominantly in the experimental studies which are adding to our knowledge of the physiology of the thyroid and the therapy of its diseases, yet practical problems still arise in the management of these conditions, especially as they are related to surgery of the gland. To the surgeon falls the lot of making important practical decisions about treatment, which are modified by the knowledge being acquired from laboratory and clinical studies. Nontoxic goiter is a very common disease. Partial thyroidectomy for this condition is one of the operations most frequently performed. It is because it is so important for a doctor to be able to determine with discrimination and accuracy those patients who should be subjected to surgery that a discussion of this matter is thought to be worthwhile. The removal of goiters which produce or threaten tracheal obstruction, or those which are large and unsightly, presents technical problems only. There is no question about the indication for surgery i...

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 . . .

Thyroidal clearance rate measurements were made in 55 patients from 1 to 6 yr after receiving 131iodine therapy for thyrotoxicosis or nontoxic goiter. A regression of clearance rate on years after therapy was calculated for each patient. The slope of this regression line was taken as a measure of the long-term effect of therapy. The intercept of the line at zero yr (i.e., the time when the last therapy dose was administered) was used as a measure of the initial effect of therapy. The initial effect was found to correlate with estimated gram rads and millicuries retained at the first therapy dose. There was no correlation with goiter type. The longterm effect was correlated with me retained at the first dose. When this rate of fall of clearance rate was compared with the clearance rates obtained after therapy, a fall of 25% per annum was observed irrespective of thyroidal status before therapy. This was a 30-fold increase over the natural fall due to aging.

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.

A Comparative Study of Emotional Factors in the Etiology of Toxic and Nontoxic Goiter. Dr. Joseph M. Lubart. Since no reports have appeared in the literature concerning emotional factors in the etiology of nontoxic goiter, whereas much has appeared concerning toxic goiter, the author has undertaken a study in which such factors have been compared and contrasted between 18 cases of nontoxic and 14 cases of toxic goiter. The results are as follows: 1. Disturbed family patterns were universally present in both groups. 2. Typical basic neurotic fears were present and equal in both groups. 3. Every patient in both groups presented neurotic character disorders. 4. Compulsive character traits were more marked in the toxic group. 5. Catastrophic dreams were present in both groups. 6. Denial of dependence was more marked in the toxic group. 7. Toxic persons showed more drive toward advancement and performance, but the mechanism often involved

A rare syndrome composed of blepharochalasis, double lip, and nontoxic goiter was first described by Ascher in 1920. Many of the cases reported since that time are not representative of the complete form of the syndrome. A case of the complete syndrome in a 17-year-old girl is reported.

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.

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.

Measured thyroidal radiosensitivity factors were found to depend on goiter size but not on sex, thyroidal status (hyperthyroid or euthyroid), type of goiter (diffuse or nodular) or value of uptake rate. A method of radioiodine therapy for thyrotoxicosis is outlined which is predicted to yield a myxedema rate of about 2 per cent, with 60 per cent of the patients requiring only one dose, 30 per cent two doses, and 10 per cent three or more doses. The average time required to achieve a permanently euthyroid uptake rate is about ten weeks. Later than three years after completion of therapy there seems to be a slight fall in the uptake rate beyond that expected on account of the patient's aging.

An extensive literature concerning the relationship between nontoxic goiter and thyroid cancer has accumulated during the past 25 yr. Considerable diversity of opinion still exists, however, concerning selection of appropriate therapy for patients with thyroid nodules. The controversial nature of this important medical problem is perpetuated by the lack of precise knowledge of the natural history of thyroid cancers and by the limited reports concerning the ability of any particular method of therapy to alter the usually benign course of most thyroid cancers. In the absence of sufficient reliable scientific data upon which to make therapeutic decisions, most investigators have based their recommendations upon analysis of available epidemiologic information derived from large series of patients. In this presentation, these general conclusions will be reviewed and examined to provide the practicing physician with sufficient empiric information upon which to organize his own thinking concerning management of patients with thyroid nodules.

The amount of thyroid iodine was determined in vivo by x-ray spectrophotometry in 19 cases of thyrotoxicosis, 15 nontoxic goiters and 18 controls. The mean iodine values for the 3 groups were 12.5, 20.4 and 12.9 mg, respectively, but large individual variations were found. The radioiodine uptake test was also performed on all the subjects, and their PBI values were determined. The results obtained for cases of nontoxic goiter show that, on an average, there is an increase in both the thyroid uptake of radioiodine and the stored iodine. Although the causes of these changes remain obscure, it seems likely that there is an increased demand for iodine in nontoxic goiter. In thyrotoxic subjects the specific activity of radioiodine 7 days after the administration of radioiodine was considerably higher in the plasma than in the thyroid. In the metabolism of thyroid iodine occurring in thyrotoxicosis, there appears to be an important pathologic change whereby the iodine taken up from the blood stream and synthesi...

Bei 16 Patienten mit blander Struma kam es bereits nach 4-wochentlicher Behandlung mit taglich nur 200 µg Kaliumjodid zu einer Normalisierung des zuvor erhohten T3/T4-Quotienten. Die TSH-Spiegel zeigten unter dieser Kaliumjodidbehandlung dagegen keine mesbaren Veranderungen. Die Schilddruse besitzt demnach offensichtlich auch beim Menschen die Fahigkeit, die Synthese und Sekretion der beiden Schilddrusenhormone T3 und T4 unabhangig vom TSH der jeweiligen Jodzufuhr anzupassen (sog. Autoregulation der jeweiligen Jodzufuhr anzupassen (sog. Autoregulation der Schilddruse).

Lymphocytes from peripheral blood of patients with various thyroid diseases and of healthy volunteers were tested for blast transformation reaction by human thyroglobulin, thyroid extract, adrenal extract, phytohemagglutinin (PHA) and staphylococcal nitrate (SF). The subjects comprised 9 patients with Hashimoto's disease, 12 hypothyroids, 8 with nontoxic goiter, 10 thyrotoxics, and 15 healthy controls. Lymphocytes from 6 of the patients with Hashimoto's disease were specifically stimulated to transform by human thyroglobulin or thyroid extract, while, among the other groups tested, only one patient with nontoxic goiter demonstrated a significant specific stimulation. It is suggested that the specific blast transformation may be caused by auto-immunization to thyroid antigens.

Increased concentrations of immunoglobulin M have been found in the circulation of approximately half of patients with either endemic or sporadic nontoxic goiter. Blood was obtained from patients in several iodine-deficient goitrous areas; the patients with sporadic goiter resided in or about New York City. Concentrations of immunoglobulins G, A, and D were normal. Blood for control purposes was taken from patients residing in cities near the goiter areas where there was no iodine deficiency, and in New York City. Most of these samples came from hospitalized patients without known thyroid disease and were collected at random. Chi-square values for the difference between the number of goitrous patients with elevated concentrations of immunoglobulin M and those in the control patients were highly significant statistically.

Administration of 75 μg of sodium liothyronine per day for 12 weeks resulted in a measurable decrease in the size of nontoxic goiters in about half of 46 patients. No nodules disappeared during these short courses of thyroid-suppressive therapy; in most cases, decrease in goiter size was relatively slow, and measurable changes were often not observed until after 8 weeks of therapy. Suppression of thyroidal iodine uptake or of endogenous hormone secretion was not necessary in order to obtain reductions in goiter size. This suggests the possibility that treatment of goiter with thyroid hormones could be reduced to a simple routine by using moderate doses for all patients and by omitting iodine uptake studies and determinations of protein-bound iodine.

An extended study of the basal metabolism in its relation to the clinical features of toxic goiter 1 has been in progress in this clinic since June, 1914. As a by-product of this work there has been collected a considerable amount of data on patients with clinically nontoxic goiter and on patients without frank hyperthyroidism or hypothyroidism, but in whom the possibility of one of these conditions was suspected, and also on patients with a variety of pathologic states not including the thyroid. Since the use of the basal metabolism determination as a test of thyroid function has come into rather wide use in the last two or three years, it has seemed to us advisable to place these data on record. A large amount of data on normal persons, which, as regards the thyroid problem, serves as normal control data, has been secured by Benedict of his associates. 2 Our own

The relationship between blood pressure and hyperthyroidism is significant if some views of the present day are true. It is common knowledge that there is an increased pulse pressure in hyperthyroidism. Statements have been made that if this were continued over a sufficient time, cardiovascular changes and permanent arterial hypertension might ensue. Furthermore, it is the belief of some writers that the nontoxic adenomatous goiter can lead to similar changes over a period of years. There has been no adequate survey, as far as I am aware, to show that either active hyperthyroidism or prolonged but slight over-activity of the thyroid in otherwise clinically nontoxic goiter leads to permanent cardiovascular degeneration, hypertension or cardiac enlargement. In observing patients who have been operated on for toxic goiter, one frequently finds the blood pressure higher after operation than before, although the basal metabolic rate is normal and the patient is clinically free

For several decades writers in this country and abroad have reported the coincident finding of glycosuria in some cases of hyperthyroidism. Joslin and Lahey,1in their recent study of 500 cases of disease of the thyroid, reported the occurrence of glycosuria in 38.6 per cent of 228 cases of primary hyperthyroidism and in 27.7 per cent of 83 cases of adenomatous goiter with secondary hyperthyroidism, as compared with only 14.8 per cent in 189 cases of nontoxic goiter and 13.6 per cent of patients without diabetes or any disease of the thyroid gland. In a series of 100 dextrose tolerance tests which I2did in 82 cases of hyperthyroidism and 10 cases of colloid goiter, there was a fasting glycosuria in 19 per cent. In table 1 are given the reports of various authors as to the incidence of glycosuria in cases of hyperthyroidism. When chemical analyses of

In December, 1930, Mason, Hunt and I 1 published observations on the blood cholesterol in hyperthyroidism and hypothyroidism. The results of forty-seven determinations of the blood cholesterol in patients with toxic goiter were reported, and it was definitely shown that low values were found in severe cases, although there appeared to be no individual reciprocal relationship between the elevation of the basal metabolic rate and the lowering of the blood cholesterol. The present study was begun on a larger group of patients to determine whether our impression that the degree of clinical toxicity is reflected more accurately in the lowering of the blood cholesterol than by the basal metabolic rate is correct. Furthermore, the behavior of the blood cholesterol as the result of the various therapeutic procedures warranted further study. METHOD OF STUDY The cases studied were unselected, specimens of the blood having been taken as a routine in all

Reports from various centers indicate that Hashimoto thyroiditis is increasing in frequency. 9,15,17 There are two schools of thought regarding its treatment, and willingness to use medical treatment depends on confidence in the accuracy of the diagnosis. We have undertaken a study of 1,000 consecutive operations done for nontoxic goiter in an attempt to determine (1) the degree of diagnostic accuracy in current surgical practice; (2) the indications or contraindications for surgical treatment of thyroiditis, and (3) how increasing knowledge of the natural history of Hashimoto thyroiditis may alter some current methods of management. The series of operations was obtained from the files of the U.C.L.A. Medical Center and from two accredited private hospitals near the Medical Center, St. John's and Santa Monica hospitals. All cases of toxic diffuse goiter have been excluded from this study because the ubiquitous lymphoid accumulations accompanying Graves' disease are interpreted by some pathologists as

This monograph on thyroidology has been prepared by two German internists with the collaboration of two Austrian surgeons and two Swiss pathologists. According to the principal authors' foreword, they have intended primarily to assemble the results of clinical and experimental studies since 1955 rather than to present a comprehensive treatise; much of the data are derived from their ten years of experience at the clinic and polyclinic in Dusseldorf (a city of 700,000). They need not be so modest. The experience which they cite is impressive: 3,000 cases of nontoxic goiter, 644 cases of thyrotoxicosis, etc. The information and opinions are consistent with those prevailing in the United States; it is well organized and clearly stated in text and tables. Each chapter, and in some instances subsection, has a bibliography in which the world literature is well represented and up-to-date. Minor points that are not fully discussed are supported with

THE PURPOSE of this report is to describe the occurrence of Hashimoto's thyroiditis in a mother and her three daughters, two of whom are monovular twins. All of these cases became symptomatic over a two-year period. The familial incidence of struma lymphomatosa was first reported in 1959.1Subsequent reports appeared in 1960,21961,31962,4,51963,6and 1964.7 It is well known that various thyroid diseases such as hypothyroidism, hyperthyroidism, and nodular, nontoxic goiter may arise in members of the same family.8,9Hashimoto's thyroiditis may be transmitted on a genetic basis.6,8Evidence has also been presented suggesting genetic predisposition to thyroid autoimmunity.3,6,8Hung and Winship6report a case of a mother and daughter with Hashimoto's thyroiditis with serologic and histologic confirmation. Irvine et al3report struma lymphomatosa in both members of two pairs of monovular twins. Zarno and Guerra7

The ability of skilled physicians to estimate cancer risk in nontoxic goiter was determined by reviewing 235 evaluations of patients referred as thyroid cancer suspects and comparing the diagnostic impressions with the subsequent clinical and histological findings. Of 202 patients classified as "benign" on clinical evaluation, 2% proved to have thyroid cancer. In contrast, 28% of those classified as "suspected of cancer" and 53% of those classified as "probably cancer" did indeed have malignant goiters. Furthermore, although only 63 patients with "benign" goiters were subjected to early thyroidectomy, these included all 4 with thyroid cancer so far identified in this group. These figures indicate that patients with goiter can be divided quite successfully into low and high cancer-risk groups and that preoperative selection is justified.

Excerpt Nontoxic goiter, a compensatory phenomenon, reflects a defect in the synthesis of thyroxine. The deficiency stimulates secretion of thyroid-stimulating hormone, enlargement of the thyroid e...