Comparative effects of desiccated thyroid gland and sodium salt of L-thyroxine in the treatment of hypothyroidism

The studies comparing the actions of dried thyroid gland (Thyroideum-Polfa) with L-thyroxine sodium (L-T4) were carried out in 20 female patients with hypothyroidism, including 19 patients with the primary hypothyroidism and 1 patient with hypothyroidism secondary to pituitary deficiency. Administration of the dried thyroid gland did not normalize blood serum T4 an TSH in any patient. Normal serum T4 or even slightly increased was achieved in all patients treated with L-T4. Serum TSH was normalized in 17 patients with the primary hypothyroidism. The following conclusions have been drawn: 1. Dried thyroid gland (Thyroideum-Polfa) is ineffective in the treatment of hypothyroidism. 2. Serum TSH remains elevated despite normal serum T3 in cases of the primary hypothyroidism with decreased serum T4 levels. 3. Sodium salt of L-thyroxine should be used for the treatment of hypothyroidism. 1-Triiodothyronine sodium may be used as an adjuvant therapy.     

Optimum replacement dose of thyroid hormone assessed by highly sensitive TSH determination in patients with congenital hypothyroidism

Serum thyroid hormone concentrations were measured in 100 samples from 25 patients with congenital hypothyroidism who were clinically well while receiving L-T4 therapy. Thyroxine concentrations were significantly higher than those of controls (p less than 0.01), while triiodothyronine was not significantly different. These samples were divided into four groups according to serum thyroid stimulating hormone concentrations as measured by highly sensitive immunoradiometric assay (IRMA-TSH). Serum thyroid hormone concentrations were compared among groups. The replacement dose of L-T4 and serum thyroid hormone in groups with undetectable IRMA-TSH were significantly higher than those in groups with normal or increased IRMA-TSH. These results show that serum thyroxine concentrations increase in most patients with congenital hypothyroidism on L-T4 therapy. Therefore, thyroxine concentrations above normal are not necessarily of clinical significance if IRMA-TSH is detectable. Undetectable IRMA-TSH might indicate the necessity for a reduction in the L-T4 replacement dose in patients with congenital hypothyroidism.     

Selenium concentrations in the human thyroid gland

Recently, we found that prediagnostic serum selenium concentration was significantly lower for cases developing thyroid cancer (n=43) than for controls. We assumed that redistribution of serum selenium into the affected tissue took place in the prediagnostic period. The present study was carried out to determine the physiological concentration of selenium in the thyroid, since very few data are available in the literature. The concentrations of selenium in the thyroid (n=45) and liver samples from Norwegians who had died because of acute illness or accidents were determined by hydride generation atomic absorption spectrometry. The mean selenium concentration was found to be 0.72±0.44 μg/g in the thyroid and 0.45±0.11 μg/g in the liver tissue. The surprisingly high concentration of selenium in apparently normal thyroids indicates that selenium has important functions in this organ. The remarkably broad range, together with the observation that no significant correlation exists between thyroid and liver concentrations, suggest that factors other than the selenium status are important determinants for the selenium concentration in the thyroid gland. This observation is consistent with our hypothesis that in carcinogenesis, prediagnostic processes influence the serum-/thyroid-ratio of selenium.     

Grades of Hypothyroidism

Seventy-nine patients with hypothyroidism and autoimmune thyroid disease were studied, and allotted to one of four categories on the basis of clinical and biochemical features. Firstly, patients with overt hypothyroidism had obvious clinical features of hypothyroidism and abnormal results from routine tests of thyroid function. Secondly, those with mild hypothyroidism, however, had minor and non-specific symptoms, but the routine measurements of circulating thyroid hormone concentration generally lay within the normal range, although they were significantly lower than those seen in subclinical hypothyroidism or in normal subjects. The serum concentration of thyroid-stimulating hormone (TSH) was raised in this group and their symptoms resolve with treatment. Thirdly, patients with subclinical hypothyroidism were asymptomatic, had a raised serum TSH concentration, but all other measurements of thyroid function are indistinguishable from those recorded in people with autoimmune thyroid disease without disturbance of thyroid function and in normal subjects. Lastly, subjects with circulating thyroid antibodies, normal indices of thyroid function, and a normal serum TSH concentration were indistinguishable biochemically from normal subjects.Thus hypothyroidism is a graded phenomenon, the most valuable features for defining the individual grade being the clinical manifestations, the serum TSH concentration, and the presence of circulating antibodies to thyroid tissue.     

Selenium concentrations in the human thyroid gland.

Recently, we found that prediagnostic serum selenium concentration was significantly lower for cases developing thyroid cancer (n = 43) than for controls. We assumed that redistribution of serum selenium into the affected tissue took place in the prediagnostic period. The present study was carried out to determine the physiological concentration of selenium in the thyroid, since very few data are available in the literature. The concentrations of selenium in the thyroid (n = 45) and liver samples from Norwegians who had died because of acute illness or accidents were determined by hydride generation atomic absorption spectrometry. The mean selenium concentration was found to be 0.72 +/- 0.44 microgram/g in the thyroid and 0.45 +/- 0.11 microgram/g in the liver tissue. The surprisingly high concentration of selenium in apparently normal thyroids indicates that selenium has important functions in this organ. The remarkably broad range, together with the observation that no significant correlation exists between thyroid and liver concentrations, suggest that factors other than the selenium status are important determinants for the selenium concentration in the thyroid gland. This observation is consistent with our hypothesis that in carcinogenesis, prediagnostic processes influence the serum-/thyroid-ratio of selenium.     

Serum cyclic 3',5'-nucleotide phosphodiesterase in patients with various thyroid disorders

Previous observations that cyclic 3',5'-nucleotide phosphodiesterase activity exists in mammalian sera including human serum prompted us to investigate the phosphodiesterase levels in sera of patients with various thyroid disorders. Both serum cyclic AMP phosphodiesterase (cAMP-PDE) and cyclic GMP phosphodiesterase (cGMP-PDE) activities measured in a low substrate concentration were elevated 3-fold in subacute thyroiditis and slightly in hyperthyroidism, compared to the normal. Slight decreases of these enzyme activities were observed in primary hypothyroidism. PDE activities were positively correlated with the value of T3-RSU and serum thyroid hormone levels in hyper- and hypothyroidism. Altered enzyme activities returned to normal during the course of recovery. Identical results were obtained when plasma was tested. These results suggest that serum PDE activities may be partly related to the thyroid function.     

Prediction of Hypothyroidism after Partial Thyroidectomy for Thyrotoxicosis

Hypothyroidism is one of the major complications after thyroidectomy for thyrotoxicosis, but the factors responsible are not well defined. In an attempt to define these factors 278 patients operated on in 1965-9 were studied in detail. The overall incidence of hypothyroidism was 49%. The high incidence of hypothyroidism during 1965-6 led to a policy of leaving larger remnants in the later years of the study, and it became apparent that the most important aetiological factor in postoperative hypothyroidism was small remnant size. There seemed to be an association between the incidence of hypothyroidism and the presence of antithyroglobulin antibodies, but this association was not statistically significant. The data suggested that blood group O might be more common and blood group A less common in hypothyroid patients. The incidence of hypothyroidism seemed to be uninfluenced by the age or sex of the patient, the size of the gland, or the amount and duration of preoperative antithyroid drug therapy.Though a reasonable prediction of the incidence of hypothyroidism can be made for a group of patients on the basis of remnant size, the fate of the individual can be predicted only within very wide limits. An indication of the future status of the individual patient at one year and subsequently does, however, seem possible from serum protein-bound iodine estimations at one and four months after operation. Hypothyroidism developing later than one year after operation has not been observed in this series. The ability to assess thyroid status early after surgery is of some merit in the long-term supervision of the postoperative thyrotoxic patient, and in this respect surgical treatment seems to have some advantage over radioiodine therapy.     

Relevance of increased serum thyroxine concentrations associated with normal serum triiodothyronine values in hypothyroid patients receiving thyroxine: a case for "tissue thyrotoxicosis".

Fifteen patients receiving standard thyroxine replacement therapy (100-200 micrograms daily) for primary hypothyroidism and who had persistently raised free thyroxine concentrations in their serum were investigated to see whether the dose being given was too high. In addition to the usual thyroid hormone assays systolic time intervals (which indicate left ventricular contractility) were calculated as accurate reflectors of tissue thyroid activity. All patients showed the expected increased free and total thyroxine concentrations; but mean total and free concentrations of triiodothyronine were normal, while reverse triiodothyronine values were raised. Mean systolic time intervals were significantly reduced as compared with normal and fell within the thyrotoxic range. Seven patients subsequently had their doses of thyroxine reduced by 50 micrograms daily and were reinvestigated one month later. All showed significant falls in circulating thyroxine and triiodothyronine concentrations and an increase in mean systolic time intervals to the normal range. In patients receiving thyroxine replacement therapy for primary hypothyroidism a raised serum thyroxine concentration may indicate tissue thyrotoxicosis and should prompt a reduction of the thyroxine dose.     

Disappearance of blocking type thyrotropin binding inhibitor immunoglobulin (TBII) during thyroid and steroid medication in a patient with autoimmune thyroiditis

A 55 year-old female had suffered from 3 consecutive diseases for a year. The diseases were ulcerative colitis, primary hypothyroidism and idiopathic thrombocytopenic purpura, and had been treated with L-thyroxine (50 micrograms daily) and betamethasone (0.5 to 1.5 mg daily). On examination, the thyroid gland was not palpable at all, thyroid 99 mTc pertechnetate uptake was 0%, and an echogram revealed the existence of an atrophic gland. Thyrotropin binding inhibitor immunoglobulin (TBII) in the serum was elevated to 58.0% and her IgG almost completely inhibited the in vitro cAMP increase due to bTSH. After 5 months TBII turned out to be negative and the inhibitory IgG activity was reduced significantly. The thyroid gland also became visible scintigraphically. Thyroid medication was then stopped. Four months after the cessation of thyroxine, she felt quite well and her thyroid functions remained within the normal ranges. Antibody to Yersinia enterocolitica was positive at a low titer (X20) in the early stages, but elevated reciprocally with the fall in TBII and finally reached X320. In conclusion, evidence of the disappearance of blocking type TBII from the serum was demonstrated for the first time. Steroid might have caused some favorable effects, and this clinical report indicates the possibility that remission of hypothyroidism due to blocking type TBII can be expected.     

Monitoring of treatment for hypothyroidism with L-thyroxine]

The study was aimed at the evaluation of treatment of hypothyroidism with L-thyroxine administration monitored by the determination of T3 and T4 concentrations. The investigations were carried out in a group of 57 patients with hypothyroidism including 37 patients with autoimmune etiology of hypothyroidism, 12 patients after strumectomy and 8 patients after treatment with 131J. The administration of L-thyroxine at a dose of 2 micrograms/kg/day effectively eradicated all symptoms of the disease and led to the normalization of blood serum T3 and T4 values in the majority of patients with autoimmune hypothyroidism. So the majority of women required the daily dose of L-thyroxine of 100-150 micrograms, and the majority of men 125-175 micrograms. Lower dosage of L-thyroxine (50-100 micrograms daily) was required to attain euthyroid state in some patients with postoperative or postradiation hypothyroidism. Monitoring of the therapy by the determination of blood serum T3 and T4 concentrations greatly facilitated the proper choice of the therapeutic dose of L-thyroxine as the return of the thyroid hormone concentrations to normal usually brought about the complete remission of symptoms of the disease. The exception from this rule was only in the case of patients with arterial hypertension and coronary disease in whom, because of the side-effects, lower dosage of L-thyroxine (usually 50 micrograms daily) must have been applied to attain the optimal improvement. The treatment with L-thyroxine caused much less side-effects as compared to the therapy using the dessicated thyroid preparations (Thyroideum).     

Blocking activity to action of thyroid stimulating hormone in serum from patients with primary hypothyroidism.

Spontaneous primary hypothyroidism in adults is usually associated with autoimmune thyroiditis. The hypothesis that hypothyroidism may result from the presence in serum of a factor that blocks stimulation of the thyroid by thyroid stimulating hormone was examined. Serum samples were collected from 28 patients with recently diagnosed primary hypothyroidism. After removal of endogenous thyroid stimulating hormone the effect of the serum on secretion of triiodothyronine induced by thyroid stimulating hormone or thyroid stimulating antibodies was examined in thyroid slices incubated in vitro. Serum samples from six of the patients demonstrated significant blocking of the stimulation by bovine thyroid stimulating hormone. Inhibition of the stimulatory action of thyroid stimulating antibodies was also exhibited by serum samples with blocking activity. It is concluded that in some patients with primary hypothyroidism a serum factor, which is probably an IgG, exists that can block the thyroid response to thyroid stimulating hormone and thyroid stimulating antibodies; it may represent an important mechanism in the pathogenesis of hypothyroidism.     

Diagnosing amyloid goitre with thyroid aspiration biopsy

OBJECTIVE: The aim of the study was to evaluate the value of fine needle aspiration biopsy of the thyroid as a tool for diagnosing amyloid goitre and assess how amyloidosis affects thyroid tissue and thyroid function. METHODS: Clinical and laboratory evaluation of 50 patients with secondary systemic amyloidosis was done, and goitre was found in 38 of them. All 38 patients underwent thyroid aspiration biopsy. Tissue samples were stained with haematoxylin and eosin, May-Grünwald-Giemsa, crystal violet and Congo red. RESULTS: Of the 38 cases of amyloid goitre, 10 showed euthyroid sick syndrome, two showed primary hyperthyroidism, two showed hypothyroidism and one showed subacute thyroiditis. The serum levels of thyroid hormones and thyroid-stimulating hormone were normal in the remaining patients. Thirty-five of the 38 patients (92%) showed amyloidosis after thyroid aspiration. One of these patients had papillary carcinoma in addition to amyloid goitre. Ten patients underwent subtotal thyroidectomy, and one patient underwent total thyroidectomy after aspiration. Microscopic evaluation revealed that the thyroid parenchyma in all patients was largely replaced with amyloid and adipose tissue. CONCLUSION: Fine needle aspiration of the thyroid is a valuable and sensitive method for diagnosing amyloid goitre, especially because it is a safe and easily performed procedure. Further, amyloid goitre has no significant influence on thyroid function even when it causes extensive parenchyma replacement.     

Na-K-dependent ATPase in red cells and thyroid status

The Relationship between ouabain-sensitive ATPase (Na-K ATPase) activity in erythrocytes and the thyroid status was studied in 36 patients with Graves' disease and 58 patients receiving L-thyroxine (T4) replacement therapy. Forty normal children served as control. Total ATPase activity in 4 untreated hypothyroid patients was significantly reduced (11.0 +/- 4.6 vs 17.3 +/- 4.1 micrograms-P/h/mg-protein, P less than 0.01), and Na-K ATPase was undetectable, both of which were normalized after 4 weeks of L-T4 therapy. Na-K ATPase in hyperthyroid patients was also decreased (0.9 +/- 0.8 vs. 4.0 +/- 2.7, P less than 0.01), but was gradually normalized after 3 months of euthyroid state. Clinically euthyroid children treated with L-T4 were divided into 2 groups with regard to Na-K ATPase activity, normal and low. Analysis of the possible factors producing this difference revealed that, in primary hypothyroidism, the factor appeared to be the endogenous T4 level, while in patients with dwarfism, the secretory capacity of TSH or TSH-releasing hormone (TRH) was contributory. Thus Na-K ATPase activity in red cells remains within the normal range after L-T4 replacement in the presence of a severe degree of primary hypothyroidism or in association with secondary or tertiary hypothyroidism. Other factors such as the L-T4 dose, duration of the therapy, serum T4 and T3 concentrations, were not significantly different in the two groups. These results indicate that (1) Na-K ATPase in red cells is decreased in hyper- or hypothyroid state, (2) restoration of normal activity requires 1-3 months of euthyroid period, and (3) it is a sensitive index of peripheral thyroid status over the preceding few months.     

Cardiac performance and coenzyme Q10 in thyroid disorders

To investigate the relationship between serum levels of Coenzyme Q10 and cardiac performance in thyroid disorders, we studied the cardiac performance and assessed serum levels of thyroid hormones and Coenzyme Q10 in 20 patients with hyperthyroidism, 5 patients with hypothyroidism and 10 normal subjects. A significant inverse correlation between thyroid hormones and Coenzyme Q10 levels was found by performing partial correlation analysis. Because low serum levels of Coenzyme Q10 were found in thyrotoxic patients and congestive heart failure may occur as a result of severe hyperthyroidism, 120 mg of Coenzyme Q10 was administered daily for one week to 12 hyperthyroid patients and the change in cardiac performance was assessed. Further augmentation of cardiac performance was found in hyperthyroid hearts, which were already augmented, after the administration of Coenzyme Q10. It appears, therefore, that the Coenzyme Q10 dose actually has a therapeutic value for congestive heart failure induced by severe thyrotoxicosis.     

Scintigraphic imaging of paediatric thyroid dysfunction

Imaging of thyroid dysfunction is safe and clinically relevant in children. In congenital hypothyroidism (CH), thyroid imaging permits a precise characterization of the aetiology, which is important for genetic counselling and clinical management. CH may be due to thyroid dysgenesis (ectopia, hypoplasia and athyrosis) or occurs in eutopic glands. In the latter, hypothyroidism may be either transient, especially after iodine overload, or due to permanent autosomal recessive dyshormonogenesis. Thyroid scintigraphy (TS) with either 99mTcO4 or 123I will identify ectopic thyroid tissue, which is the commonest cause of CH. However, recent reports favour the use of 123I, which enhances the accuracy of the aetiological classification. In cases of eutopic thyroid, the measurement of 123I uptake before and after perchlorate administration evaluates the organification process. At all ages, colour Doppler ultrasound scanning (CDU) is helpful in assessing thyroid volume, in identifying nodules and in characterizing tissue vascularization. TS and CDU images of most paediatric thyroid dysfunctions are presented.     

Optimization of 131I ablation in patients with differentiated thyroid carcinoma: comparison of early outcomes of treatment with 100 mCi versus 60 mCi

INTRODUCTION: The aim of this study was to compare the early outcomes between two groups of patients with differentiated thyroid carcinoma (DTC) who received 60 or 100 mCi of (131)I for remnant ablation. MATERIAL AND METHODS: 224 DTC patients with primary tumor > 1 cm of diameter or multifocal were randomised into prospective clinical trial. Patients with extrathyroideal extension of primary tumor and nodal metastases or M1 were not enrolled. 99 patients received 60 mCi, and 125--100 mCi of radioiodine as the first ablative dose. RESULTS: The effectiveness of thyroid ablation was evaluated after one year, during endogenous TSH (thyroid stimulating hormone) stimulation, and after two years during Lthyroxine therapy. Whole body scintigraphy (WBS) was performed under thyroxine withdrawal and thyroglobulin serum level was assessed. Distant micrometastases were detected in 9.8% of patients by post-therapy WBS, 11 patients in group A treated with 60 mCi and 11 in group B treated with 100 mCi. In other patients no symptoms of persistent disease were detected. At one year follow up full remission was diagnosed in 176 patients: 76 in group A and 100 in group B. The remaining ones, 13.3% and 11.2% respectively, received the second course of (131)I for remnant ablation. There were no statistically significant differences in Tg (thyroglobulin) serum level either 12 or 24 months after 131I treatment. CONCLUSIONS: Our evaluation of early efficacy of adjuvant radioiodine treatment in low risk DTC patients shows no differences between two radioiodine activities - 60 and 100 mCi in relation to thyroid ablation. Thus, the activity of 60 mCi is recommended.     

Therapeutic exploration of betulinic acid in chemically induced hypothyroidism

Hypothyroidism is a chronic condition characterized by abnormally low thyroid hormone production. The decreased serum level (>5.1 mIU/l) of thyroid-stimulating hormone (TSH) in blood indicates hypothyroidism. The study was an attempt to access the effect of betulinic acid on chemically induced hypothyroidism in female albino rats. Betulinic acid is a naturally occurring pentacyclic triterpenoid, which has antiretroviral, antimalarial, and anti-inflammatory properties, as well as anticancer potential, by inhibiting topoisomerase. Hypothyroidism was induced in female albino rats using propylthiouracil (PTU) at a dose of 60 μg/kg body weight orally for 1 month. Induction of hypothyroidism was confirmed by increased TSH level. At the end of second month, blood was collected, centrifuged and serum was analyzed for TSH, T3, and T4 level and protocol was terminated by killing of animals. The animals exposed to PTU were treated with pure standard drug thyroxine at a dose of 10 μg/kg of body weight by oral route and the test drug betulinic acid 20 mg/kg by oral route through force feeding in their respective groups. Treatment was carried out for a period of 2 months. Group with PTU-induced hypothyroidism showed an elevation in serum TSH and reduction level, which was restored by the betulinic acid in treated female albino rats. Betulinic acid also reduced the damage caused in the thyroid tissues by PTU, thus minimizing the symptoms of hypothyroidism. Histopathological examinations of the thyroid tissue showed changes in the thyrocytes of PTU-treated group while thyroxine group showed normal thyroid follicles cell architecture and the group treated with betulinic acid also showed marked improvement in the follicles integrity which shows that betulinic acid has some protective activity. This study shows that the betulinic acid has thyroid-enhancing potential by lowering down the TSH levels and reducing the damage caused in the thyroid tissues, thus minimizing the symptoms of hypothyroidism when used anaphylactically in rats.     

Serum fructosamine in assessment of diabetic control and relation to thyroid function

Measurement of serum fructosamine using a Roche kit is a simple and reliable method for the estimation of glycated serum proteins. The value of serum fructosamine can be affected by hyperglycemia in diabetics and an abnormal turnover rate of serum protein in patients with thyroid dysfunction. We measured the serum fructosamine level in 18 normal control subjects, 71 diabetics (8 IDDM, 63 NIDDM) and 46 non-diabetic untreated patients with thyroid dysfunction (28 hyperthyroidism, 18 hypothyroidism). The serum fructosamine level was significantly increased in the diabetics compared with the normal control subjects (3.84 +/- 0.15 mmol/l vs 2.58 +/- 0.08; mean +/- SE, P less than 0.01). The serum fructosamine level in the diabetics was positively correlated with the fasting plasma glucose and HbAlc level, showing the highest correlation with fasting plasma glucose at 2 weeks before and with the HbAlc level at 2 weeks after serum fructosamine measurement. In the patients with thyroid dysfunction, the serum fructosamine level in hyperthyroidism (2.08 +/- 0.03 mmol/l) and hypothyroidism (3.11 +/- 0.07 mmol/l) were significantly lower (P less than 0.001) and higher (P less than 0.001) than the normal control subjects (2.58 +/- 0.08 mmol/l), respectively. Furthermore, the serum fructosamine level in these patients was negatively correlated with the level of serum thyroid hormones such as T3 (P less than 0.001) and T4 (P less than 0.001). It is concluded that measurement of serum fructosamine is clinically useful for the evaluation of shorter-term glycemic control in diabetics, but its level for diabetic patients with thyroid dysfunction must be cautiously interpreted.     

Radioimmunoassay for calcitonin gene-related peptide and its measurement in sera of patients with thyroid disease.

To investigate serum levels of calcitonin gene-related peptide (CGRP), we developed a sensitive radioimmunoassay (RIA). RIA for CGRP in serum can present some problems: the serum may degradate the tracer during incubation and suppress the antigen-antibody reaction. We avoided these problems by using aprotinin and CGRP-free serum instead of a buffer for the standard curve. We detected serum CGRP in all 39 healthy subjects when CGRP-free serum was not used for the standard curve, but 34 of these subjects had serum CGRP levels below the detection limit (less than 80 pmol/l) when CGRP-free serum was used for the standard curve. We defined the normal range for serum CGRP as below 100.8 pmol/l, which was the maximum level found in the healthy subjects. We studied serum levels of this peptide in patients with thyroid diseases, because the thyroid may be one origin of circulating CGRP. Four of 10 patients with medullary thyroid carcinoma had elevated serum levels of CGRP. Seven of 24 patients with subacute thyroiditis had elevated serum levels of CGRP, but at least one year after clinical recovery, CGRP was undetectable in all. Seven of the 37 patients with hypothyroidism had elevated serum levels of CGRP. None of the patients with hyperthyroidism, adenomatous goiter, thyroid adenoma, or thyroid carcinoma had elevated serum CGRP levels. It is necessary to use a standard curve obtained by the addition of aprotinin and CGRP-free serum to the assay standards to measure serum CGRP levels. Some patients with subacute thyroiditis, hypothyroidism, or medullary thyroid carcinoma had elevated serum CGRP levels.     

Acute thyroid dysfunction (thyroiditis) after therapy with interleukin-2.

Interleukin-2 (IL-2) is frequently incorporated in antineoplastic therapy: While the effect of interferon on the thyroid has been extensively studied the impact of other cytokines on thyroid function is less well understood. We monitored the thyroid function in six patients who received IL-2 in combination with tumor necrosis factor-alpha (TNF) or alpha-Interferon (alpha IFN). Hyperthyroxinemia with suppressed TSH developed within the first four weeks of IL-2 administration; during this phase, there was no technetium or iodine uptake by the thyroid gland. During the following few weeks, serum thyroxine decreased and serum TSH rose, consistent with the development of primary hypothyroidism; during this phase, thyroidal isotope incorporation was normal. All hypothyroid patients received thyroxine replacement therapy upon documentation of hypothyroidism; in several cases thyroxine was successfully discontinued after 2-3 months. None of the patients had detectable antithyroidal antibodies and none experienced thyroid-related pain, although two patients developed thyroid enlargement. We conclude that IL-2 administration is associated with the development of transient, subacute, painless thyroiditis. The frequency and severity of this complication requires further elucidation through systematic, prospective study.