Autoimmune thyroiditis with transient thyrotoxicosis: comparison between painful thyroiditis and painless thyroiditis

Clinical and laboratory findings and long-term outcomes in 8 patients (7 women) with autoimmune thyroiditis (AT), aged 34-59 years, who had a painful tender goiter and a transient thyrotoxicosis with a low thyroid radioactive iodine uptake (RAIU), were compared with those in 15 patients (13 women) with painless thyroiditis (PT), aged 23-69 years. Six painful AT and 6 PT patients had a history of prior awareness of goiter. All patients with painful AT had a moderate or marked elevation of erythrocyte sedimentation rate and a positive result for C-reactive protein, while only 3 PT patients (group B) did. There were no significant differences between the mean age, duration of symptoms, white blood cell count, serum triiodothyronine (T3) and thyroxine (T4) concentrations, serum T3/T4 ratio and duration of thyrotoxicosis after the initial examination and prevalences of positive results for antithyroglobulin and -microsomal antibodies in the two diseases. Two of 8 painful AT patients showed a histologically chronic fibrous variant and 6 others showed chronic lymphocytic thyroiditis. All PT patients examined also showed lymphocytic thyroiditis. Two and 5 painful AT patients developed transient and persistent hypothyroidism, respectively, while 8 [7 in group A (normal ESR), 1 in group B] and 3 PT patients (1 in group A, 2 in group B) did, respectively. The mean serum thyroid-stimulating hormone level in the hypothyroid phase in painful AT patients was higher than that in PT patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Congenital iodide organification defect accompanied by a large nodular goiter: a case report

A girl who had a nontoxic diffuse goiter with a congenital organification defect of iodide was first seen at the age of 8 years, and since then she has been followed up for a long period. The nodularity of the thyroid gland had gradually progressed, because of intermittent failure of ingestion of thyroid hormone preparation which was followed by excess TSH secretion. 18 years later, a nodular goiter developed and the patient underwent subtotal thyroidectomy. In order to prevent the development of nodular change in the thyroid gland in this disorder, supplemental thyroid hormone medication should be started as soon as the diagnosis is confirmed, and the therapy should be carried out regularly.     

Evaluation of the timing to reduce the initial dose of antithyroid drugs in patients with Graves' disease.

The present study was undertaken to evaluate whether the normalization of the serum TSH level in a supersensitive assay during the initial treatment with antithyroid drugs (ATD) is a useful indicator for the reduction of the initial dose of ATD in 50 patients with hyperthyroidism due to Graves' disease. The initial dose of ATD was continued until the achievement of the euthyroid state, and was then reduced either before the serum TSH level was in the normal range in 9 of 29 patients treated with methimazole (MMI) (group MMI-1) and 8 of 21 treated with propylthiouracil (PTU) (PTU-1), or after the serum TSH level was in/above the normal range in 20 of 29 treated with MMI (MMI-2) and 13 of 21 treated with PTU (PTU-2). Although there were no significant differences in age, sex, thyroid function, prevalence of autoantibodies, goiter size, duration of the disease or the initial and modified doses of ATD, the mean durations of the administration of the initial dose of ATD in MMI-2 and PTU-2 were significantly longer than those in MMI-1 and PTU-1, respectively. As a result, 4 (44%) in group MMI-1, 20 (100%) in MMI-2, 2 (25%) in PTU-1 and 7 (54%) in PTU-2 developed low free T4 levels, and 1 (11%) in MMI-1, 15 (75%) in MMI-2 and 3 (23%) in PTU-2 developed low free T3 levels. Serum TSH levels increased over the normal range in 3 (33%) in MMI-1, 18 (90%) in MMI-2 and 5 (39%) in PTU-2.(ABSTRACT TRUNCATED AT 250 WORDS)     

Transient thyrotoxicosis associated with infarction of a large thyroid adenoma

We report a 46-year-old male patient with a transient thyrotoxicosis that seems to have been caused by hemorrhagic infarction of a cold thyroid nodule. The serum level of triiodothyronine was markedly but transiently elevated, while the serum thyroxine level remained within the normal range. The resected nodule, measuring 8 x 7 x 5 cm, showed extensive degeneration and necrosis with viable follicles left only at the margin of the nodule. A transient thyrotoxicosis due to acute hemorrhagic infarction of autonomously functioning thyroid nodules has already been reported. This case showed that the phenomenon could occur even in cold thyroid nodules. Its implications were discussed in relation to the high incidence of impaired TSH response to TRH in patients with nodular goiter.     

Clinical course of IgG4-related hypophysitis presenting with focal seizure and relapsing lymphocytic hypophysitis

Coexisting of Graves’ disease and functioning struma ovarii is a rare condition. Although the histology of struma ovarii predominantly composed of thyrocytes, the majority of the patients did not have thyrotoxicosis. The mechanism underlying the functioning status of the tumor is still unclear but the presence of thyroid stimulating hormone receptor (TSHR) is thought to play a role. Here we describe the patient presentation and report the TSHR expression of the tumor. A 56-year old Asian woman presented with long standing thyrotoxicosis for 23 years. She was diagnosed with Graves’ disease and thyroid nodules. She had bilateral exophthalmos and had high titer of plasma TSHR antibody. Total thyroidectomy was performed and the histologic findings confirmed the clinical diagnosis. The patient had persistent thyrotoxicosis postoperatively. Thyroid uptake demonstrated the adequacy of the thyroid surgery and the whole body scan confirmed the presence of functioning thyroid tissue at pelvic area. The surgery was scheduled and the patient had hypothyroidism after the surgery. The pathological diagnosis was struma ovarii at right ovary. We performed TSHR staining in both the patient’s struma ovarii and in 3 cases of non-functioning struma ovarii. The staining results were all positive and the intensity of the TSHR staining of functioning struma ovarii was the same as that in other cases of non-functioning tumors, suggesting that the determinant of functioning struma ovarii might be the presence of TSHR stimuli rather than the intensity of the TSHR in the ovarian tissue. In patients with Graves’ disease with persistent or recurrent thyrotoxicosis after adequate ablative treatment, the possibility of ectopic thyroid hormone production should be considered. TSHR expression is found in patients with functioning and non-functioning struma ovarii and cannot solely be used to determine the functioning status of the tumor.     

Review of Oral Cholecystographic Agents for the Management of Hyperthyroidism

ObjectiveAlthough the use of oral cholecystographic agents (OCAs) had declined due to limited availability, there is literature to suggest it is an effective medication for thyrotoxicosis in appropriate clinical situations.MethodsThe authors performed a PubMed search and systematically reviewed all the English written case reports, original studies and reviews from 1953 to 2012. Additional information was supplemented from available online pharmacologic databases.ResultsThe off-label use of OCAs was reviewed for the management of neonatal and adult Graves’ disease, subacute thyroiditis, amiodarone-induced thyroiditis (AIT), exogenous hyperthyroidism, toxic multinodular goiter (TMNG), thyrotropinoma, thyrotoxicosis during pregnancy, rapid pre-operative control of hyperthyroidism, and thyroid storm. Adverse effects were also reviewed.ConclusionOCAs generally are effective agents in treating thyrotoxicosis in the etiologies reviewed. OCAs are clinically relevant in patients who require rapid control, such as in the pre-operative state or patient who cannot tolerate a thyrotoxicosis state. OCA may also be beneficial in situations where other anti-thyroidal medication would be hazardous or ineffective, such as thionamide allergy or exogenous thyrotoxicosis. Given concern for long-term relapse, OCAs should be considered a short-term bridge to definitive therapy. OCAs are limited in TMNG and should be second line after glucocorticoids in AIT II. OCAs do not preclude the use of radioactive iodine, which can be performed one week after OCA therapy. (Endocr Pract. 2014;20:1084-1092)     

Concomitant association of thyroid sarcoidosis and Graves' disease

OBJECTIVE: Graves' disease (GD) with sarcoid involvement of the thyroid gland has rarely been reported. METHOD: We report a case of GD with thyroid sarcoidosis in a 28-year-old woman. Thyroid function was assessed by triiodothyronine (T(3)), thyroxine (T(4)), thyroid-stimulating hormone (TSH) and TSH receptor antibodies (TSH-R Ab). Thyroid scintigraphy, ultrasound and fine-needle aspiration biopsy were performed. The patient underwent surgery. RESULT: The patient had a nodular goiter. Serum T(3), T(4) and TSH-R Ab levels were elevated with suppressed TSH level. Scintigraphy showed diffuse activity as seen in GD, and ultrasound revealed that parenchyma was heterogenous. Sarcoidosis was discovered on routine chest X-ray. Although no sarcoid involvement was found on specimen, the thyroid gland showed non-caseating granulomas on histology. CONCLUSION: Since sarcoid involvement of the thyroid gland can cause hypofunction, we report the uncommon infiltration of sarcoidosis with hyperthyroidism.     

Thyroid cancer in patients with hyperthyroidism

Thyroid cancer can be associated with thyrotoxicosis caused by Graves' disease, toxic multinodular goiter, or autonomously functioning thyroid adenoma. The objective of this study was to summarize current evidence regarding the association of thyroid cancer and hyperthyroidism, particularly with respect to the type of hyperthyroidism found in some patients, and whether this affects the outcome of the patient. A PubMed search was performed up to August 2011. Articles were identified using combinations of the following keywords/phrases: thyroid cancer, papillary thyroid cancer, follicular thyroid cancer, medullary thyroid cancer, anaplastic thyroid cancer, hyperthyroidism, Graves' disease, auto-nomous adenoma, toxic thyroid nodule, and toxic multinodular goiter. Original research papers, case reports, and review articles were included. We concluded that the incidence, as well as the prognosis of thyroid cancer associated with hyperthyroidism is a matter of debate. It seems that Graves' disease is associated with larger, multifocal, and potentially more aggressive thyroid cancer than single hot nodules or multinodular toxic goiter. Patients with Graves' and thyroid nodules are at higher risk to develop thyroid cancer compared to patients with diffuse goiter. Every suspicious nodule associated with hyperthyroidism should be evaluated carefully.     

The molecular basis of complete complement C4A and C4B deficiencies in a systemic lupus erythematosus patient with homozygous C4A and C4B mutant genes

The disease course of a complete C4-deficient patient in the U.S. was followed for 18 years. The patient experienced multiple episodes of infection, and he was diagnosed with systemic lupus erythematosus at age 9 years. The disease progressed to WHO class III mild lupus nephritis and to fatal CNS vasculitis at age 23 years. Immunochemical experiments showed that the patient and his sibling had complete absence of C4A and C4B proteins and were negative for the Rodgers and Chido blood group Ags. Segregation and definitive RFLP analyses demonstrated that the patient and his sibling inherited two identical haplotypes, HLA A2 B12 DR6, each of which carries a defective long C4A gene and a defective short C4B gene. PCR and DNA sequencing revealed that the mutant C4A contained a 2-bp insertion in exon 29 at the sequence for codon 1213. The identical mutation was absent in the mutant C4B. The C4B mutant gene was selectively amplified by long range PCR, and its 41 exons were completely sequenced. The C4B mutant had a novel single C nucleotide deletion at the sequence for codon 522 in exon 13, leading to frame-shift mutation and premature termination. Thus, a multiplex PCR is designed by which known mutations in C4A and C4B can be elucidated conveniently. Among the 28 individuals reported with complete C4 deficiency, 75-96% of the subjects (dependent on the inclusion criteria) were afflicted with autoimmune or immune complex disorders. Hence, complete C4 deficiency is one of the most penetrant genetic risk factors for human systemic lupus erythematosus.     

Sleepwalking Associated with Hyperthyroidism

ObjectiveTo report several cases of hyperthyroidism in patients presenting with the unusual symptom of sleepwalking and to discuss the possible pathophysiologic basis for this novel association.MethodsAfter encountering and reporting the first case of new-onset somnambulism in a patient presenting with thyrotoxicosis at our institution, we routinely inquired about the sleep history of patients with thyrotox-icosis, questioning both the patients and family members when applicable. Those patients who actually had sleepwalking episodes coinciding with the onset of thyrotoxi-cosis underwent close follow-up, and the relationship between the sleepwalking and the results of thyroid function tests was analyzed. In addition, we reviewed the literature on psychiatric disorders and sleep problems, and the pathophysiologic rationale for a cause-and-effect relationship is discussed.ResultsWe collected 8 cases of patients with new-onset sleepwalking episodes that coincided with the start of thyrotoxicosis. The disappearance of the sleepwalking with successful achievement of euthyroidism supports a cause-and-effect relationship. This hypothesis is further supported by the absence of a family history, the adult onset, and the relapse of sleepwalking in 2 of the patients when their thyrotoxicosis became poorly controlled as a result of noncompliance with medications and its subsequent disappearance with reachievement of euthyroidism. Of note, such a presentation was seen only in patients with thyrotoxicosis caused by diffuse toxic goiter or Graves’ disease and never in patients with other causes of thyro-toxicosis.ConclusionNew-onset sleepwalking could be caused by thyrotoxicosis or, more specifically, by thyrotoxicosis resulting from diffuse toxic goiter. The mechanism is hypothesized to be related to the combination of prolongation of non-rapid eye movement sleep and the associated fatigue. Specific inquiry about this unusual presentation of thyrotoxicosis is encouraged, and more studies are needed to confirm and evaluate its extent. (Endocr Pract. 2005;11:5-10)     

SUBSTERNAL GOITER AND PULMONARY EMPHYSEMA

Pulmonary emphysema is not an infrequent complication of tracheal compression due to goiter.In many cases the goiter is in the mediastinum and therefore overlooked.Among 13 patients with this combination of disease, chronic cough, dyspnea and wheezing were the chief respiratory symptoms. Ten of the 13 patients also had hyperthyroidism; in eight of the ten the disease was of the “masked” variety and both the thyrotoxicosis and the mediastinal mass were overlooked.Early recognition and surgical removal of substernal goiter may prevent or retard otherwise irreversible and progressive tracheobronchopulmonary disease.Medical management of such cases with thiouracil preparations may lessen the toxic symptoms but probably will not affect the mechanical compression of the trachea.     

Amiodarone: a common source of iodine-induced thyrotoxicosis

Amiodarone, a iodine-rich drug widely used in the treatment of tachyarrhythmias, represents one of the most common sources of iodine-induced thyrotoxicosis. The data concerning 58 patients with amiodarone-iodine-induced thyrotoxicosis (AIIT) were analyzed in the present study. Prevalence of AIIT was higher in males than in females (M/F = 1.23/l). Thyrotoxicosis occurred either during treatment with or at various intervals after withdrawal of amiodarone. AIIT developed not only in patients with underlying thyroid disorders, but also in subjects with apparently normal thyroid gland. Classical symptoms of thyrotoxicosis were often lacking, the main clinical feature being a worsening of cardiac disorders. Biochemical diagnosis of AIIT was established by the finding of elevated serum total and free triiodothyronine levels, since elevated serum total and free thyroxine could be found also in euthyroid amiodarone-treated subjects. Twenty-four-hour thyroid radioiodine uptake was very low or undetectable in AIIT patients with apparently normal thyroid glands, while it was inappropriately elevated in patients with underlying thyroid disorders, despite iodine contamination. The role of autoimmune phenomena in the pathogenesis of AIIT appeared to be limited, because circulating thyroid autoantibodies were undetectable in AIIT patients without underlying thyroid disorders or with nodular goiter. Conversely, humoral features of thyroid autoimmunity were mostly found in AIIT patients with diffuse goiter. Treatment of AIIT appeared to be a difficult challenge. Among the 11 patients given no treatment, thyrotoxicosis spontaneously subsided in the 5 patients with apparently normal thyroid gland, whereas the 6 patients with nodular or diffuse goiter were still hyperthyroid 6-9 months after discontinuation of the drug. The administration of high doses (40 mg/day) of methimazole alone proved to be ineffective in most (14/16) patients given this treatment. Twenty-seven patients were treated by methimazole combined with potassium perchlorate (1 g/day). With one exception, euthyroidism was restored within 15-90 days in all cases with underlying thyroid abnormalities, and within 6-55 days in subjects with apparently normal thyroid gland. Thus, the combined treatment appears to be the most effective one, but, due to the potential toxicity of potassium perchlorate, it should be reserved to patients with severe thyrotoxicosis and should be carefully monitored.     

Pituitary resistance to thyroid hormone--a case report

Pituitary resistance to thyroid hormone is a very rare cause of hyperthyroidism. It is characterized by normal, or elevated TSH concentration with high concentration of T3 and T4. Here, we present a case of a 24-year-old woman who suffered from mild thyrotoxicosis and diffuse goiter for several years. She had elevated fT3 and fT4 with slightly elevated TSH concentration. Pituitary adenoma was excluded as magnetic resonance imaging showed normal pituitary gland, alpha subunit was within normal range and TSH concentration increased after TRH administration. Sonography revealed normoechogenic, slightly enlarged thyroid gland. Previously, she was given thiamazole, but without any significant amelioration. Thus, the diagnosis of the syndrome of pituitary resistance to thyroid hormone was established. The patient was given bromocriptine at a dose of 10 mg per day. After 2 months of treatment she achieved a state of constant euthyrosis and following next few months thyroid volume diminished.     

Incidental thyroid carcinoma in thyrotoxic patients treated by surgery

BACKGROUND AND AIMS: Thyroid malignancy detected incidentally in patients who are operated for thyrotoxicosis has been reported at different rates. The aim of this study was to investigate the rate of incidental thyroid carcinoma in thyrotoxic patients managed with surgery in our institution. METHODS: Of the 375 thyrotoxic patients who had thyroid surgery between the years of 1997-2004, 70.7% were females and 29.3% were males. Among thyrotoxic patients 65.3% (n=245) had toxic multinodular goiter (TMG), 16.8% (n=63) had toxic adenoma (TA) and 17.9% (n=67) had Graves' disease. RESULTS: Twenty-six (6.9%) of all thyrotoxic patients had thyroid carcinoma. Eighteen (7.3%) of TMG, 4 (6.3%) of TA and 4 (6%) of Graves' disease patients had thyroid carcinoma. Histologic examination revealed 18 papillary (9 microscopic), 5 follicular, 2 hurthle cell and 1 anaplastic carcinoma. CONCLUSION: In our study, incidental thyroid carcinoma was found in 6.9% of subjects with thyrotoxicosis. Papillary thyroid microcarcinomas constituted 34.6% (26/9) of these newly diagnosed thyroid carcinomas. The incidence of thyroid carcinoma was not higher in subjects with Graves' disease compared to TMG and TA. The rate of incidental thyroid carcinoma in subjects with thyrotoxicosis treated with surgery was similar to previous studies reported from different countries.     

Papillary carcinoma of the thyroid arising from dyshormonogenetic goiter

A case of thyroid papillary carcinoma associated with dyshormonogenetic goiter is reported. The patient, a 35-year-old male, has been on thyroid hormone therapy since the age of three because of familial dyshormonogenetic goiter. He developed a distinct tumor in the right lobe, which was suggestive of carcinoma upon physical as well as ultrasonographic examination. Total thyroidectomy was performed, since a frozen section disclosed a focus of papillary carcinoma and the possibility of future development of further malignancy in any remaining thyroid tissue was considered. The patient is currently well with complete thyroid hormone supplementation one and a half years after the operation.     

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy presenting with severe keratopathy in an Egyptian patient with a homozygous R139X mutation

OBJECTIVE: To report a patient with an unusual presentation of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) and severe keratopathy. CASE HISTORY: An Egyptian male sustained an injury to the left eye at 13 years of age and was found to have corneal damage which was attributed to the injury. Subsequently, however, he continued to have sore eyes with photophobia. A year later he became weak with pigmentation and episodes of collapse, and investigation showed that he had Addison's disease together with mucocutaneous candidiasis. At 15 years of age he developed carpo-pedal spasm and was found to have hypoparathyroidism with intracranial calcification. At 20 years of age the ophthalmic diagnosis was revised to keratopathy by which time the patient had corneal opacity and problems with visual acuity, especially in the right eye. Investigation at 22 years of age showed that he was homozygous for an R139X mutation in the gene encoding the AIRE protein, a mutation which to date has only been found in Sardinian patients. CONCLUSIONS: Keratopathy can be an early and severe manifestation of APECED, requiring expert ophthalmic care. Its presence should prompt a search for other components of APECED, some of which are life-threatening.     

Evidence of Endemic Goiter and Iodine Deficiency in a Mountainous Area of Haiti

ObjectiveTo investigate reports of iodine-deficiency disorder in a specific area of Haiti.MethodsIn March 2008, this cross-sectional study was performed in an area 15 miles northeast of Jacmel, Haiti, within the Chaîne de la Selle Mountains. Before arrival of the study team, an announcement was made throughout local villages soliciting volunteers to meet at a central location. Of those who arrived, participants were selected in an attempt to sample individuals from all age groups, regardless of goiter status. After providing verbal informed consent, each participant was photographed and assigned a number to be used to protect privacy. An examiner performed palpation of the thyroid gland on each participant in accordance with World Health Organization criteria. Results of palpation were classified into 3 grades: grade 0, the thyroid gland was not palpable; grade 1, the thyroid gland was palpable but not visible; and grade 2, the thyroid gland was palpable and visible while the patient was in a normal position. Casual urine samples were collected from each participant and analyzed spectrophotometrically for urinary iodine concentration.ResultsEighty-eight individuals aged 2 to 72 years participated in the study. Median urinary iodine concentration was 39 μg/L. Of the 88 participants, 82 (93%) were iodine deficient (18 [20%] were severely deficient), and 45 (51%) had goiter on physical examination, including 27 with grade 1 goiters and 18 with grade 2 goiters.ConclusionsWe have documented iodine deficiency with associated endemic goiter in this previously uninvestigated Haitian population, for which world health agencies currently lack definitive data. These data have potential implications for both the local area and the country as a whole where further evaluation and treatment are needed for persons at high risk for iodine-deficiency disorder. (Endocr Pract. 2009;15:298-301)     

Arterial hypertension associated with hyper and hypothyroidism]

45 patients with hyper and hypothyroidism in the time 1989-1990 were observed. The Graves' disease was diagnosed in 29 and rather in the younger patients, but 16 had the toxic nodular goiter and those were elderly. In 27 the hypertension was secondary (symptomatic) and after the successful treatment of the hyperthyroidism was completely controlled. In 14 cases the hypertension was primary (essential) and the application of the hypotensive drugs was also necessary. Among 4 patients with primary hypothyroidism and associated hypertension and coronary insufficiency the early treatment by the thyroid preparation was successful: the blood pressure was lowered and the coronary insufficiency was improved; but if the replacement therapy was stopped and the hypothyroidism was relapsed, the blood pressure was increases and the coronary insufficiency was aggravated. Conclusions: 1. The secondary (symptomatic) hypertension associated with the hyperthyroidism may be controlled by successful treatment of the thyrotoxicosis, but the primary (essential) must be treated by the hypotensive drugs also. 2. The early treatment of the hypothyroidism may control the associated hypertension and the coronary insufficiency. 3. Graves' disease is associated mostly with symptomatic hypertension, in nodular toxic goiter in most of the cases the essential hypertension was established.     

Serum free triiodothyronine to free thyroxine ratio enables early prediction of the outcome of antithyroid drug therapy in patients with Graves' hyperthyroidism.

This study scrutinizes the correlation between serum free triiodothyronine (FT3) to free thyroxine (FT4) ratios and the eventual outcome of antithyroid drug (ATD) therapy in patients with Graves' disease. Forty-four patients with Graves' thyrotoxicosis were treated with methylmercaptoimidazole (methimazole). During the follow-up, 16 patients relapsed in the short period of one to five months after cessation of the drug (relapse group), and 28 patients remained in remission when checked at 12 to 20 months after treatment (remission group). Serum FT3 to FT4 ratios [(pg/ml/ng/dl) x 10] were less than 55 throughout ATD therapy in 27 of the 28 remission patients whereas the ratios of the relapse group exceeded 55 from the early phase of methimazole treatment in 10 of 16 patients. In eight of these 10 patients the increased ratios were detected within three months of therapy (1 month, 3 patients; 2 months, 4 patients; 3 months, 1 patient). The ratios for the remaining two patients rose above 55 at the fifth and sixth months. There was no statistical difference between the remission and relapse groups in the FT3 to FT4 ratios either before nor at the completion of the treatment. However, a clear difference could be measured at a point during the therapy. Those in whom this difference was pronounced later underwent relapse.(ABSTRACT TRUNCATED AT 250 WORDS)     

How often should patients be reviewed after treatment with iodine-131 for thyrotoxicosis?

Six to 18 years after treatment with iodine-131 for thyrotoxicosis 69 euthyroid patients with raised serum thyrotrophin (TSH) concentrations (mean 25.0 +/- SE 2.0 mU/l) and 61 with normal concentrations (mean 4.0 +/- 0.2 mU/l) were included in a prospective five-year follow-up study beginning in 1972. During this period 13 patients from the original group with raised serum TSH concentrations became hypothyroid. In contrast it was five years before hypothyroidism developed in a single patient from the group with normal serum TSH concentrations in 1972, although raised concentrations were recorded in 19 of these patients during the study.