Long-term follow-up of patients with residual thyroid autonomy after surgical treatment of Plummer's disease.

Residual autonomously functioning tissue after surgical treatment of Plummer's disease was previously shown to be present in 18 of 87 patients; no clear symptoms were found in these cases. In the present study the results are presented of a second follow-up study in 15 of these 18 patients, an average of 12.2 years after the operation (or 5.8 years after the previous study). Overt hyperthyroidism was found in one case, minor (scintigraphic and/or biochemical) signs of progression in nine others. It is concluded that clinical recurrence may eventually develop in some operated patients, but rarely within ten years.

Thyroglossal cysts in patients over 30 years of age.

8 patients over 30 years of age with a thyroglossal cyst, who had not been operated on before and who underwent excision of the cyst by a Sistrunk procedure, are described. In 8 additional patients, a wait-and-see policy was adopted. Follow-up data of these 16 patients are reported 1.5-14 years after their last visit to the hospital. There were no recurrences in the group of treated patients. In the group of untreated patients, the cyst remained unchanged in 1, decreased in size in 3 and disappeared completely in the remaining 4 patients. The present study indicates that removal of a thyroglossal cyst in patients over 30 years of age is not obligatory.

Long-term follow-up in untreated Plummer's disease (autonomous goiter).

Plummer's disease presents a spectrum of forms and its evolution is often slow. Longitudinal studies have been limited both in number of patients and duration of follow-up. In order to answer the question of whether euthyroid patients with no local symptoms should be treated prophylactically, 70 patients were reexamined 5.2-21.8 years (average, 8.9) after Plummer's disease had been diagnosed. Data are included on four others who developed symptoms that indicated treatment within five years. Gross (clinically relevant) changes were seen in 24 cases. Of these, 16 were progressive, including 12 where hyperthyroidism developed. Gross regressive changes included two cases with complete remission. Minor changes (28 cases) were about as often regressive as progressive. Most patients with a solitary autonomous nodule showed either gross changes or no change, whereas minor changes prevailed in multifocal autonomy. All eight male patients had a solitary nodule, 28 of 66 females had multifocal autonomy. Gross changes were seen in nine of 12 patients under 40 years at presentation, more often than in those over 49 years; seven of these changes were progressive. Six short case reports illustrate the great diversity in evolution. It is concluded that treatment seems wise in teenagers and in elderly patients with borderline (biochemical) hyperthyroidism but others generally may be left untreated, as long as they have few or no complaints.

Lingual thyroid. A clinical and postmortem study.

3 patients with lingual thyroid are reported. In addition, 5 patients are described with hypothyroidism in whom functioning thyroid tissue was only present at the base of the tongue without any noticeable swelling. In a postmortem study of 120 tongues, not a single case of lingual thyroid was encountered. The preponderance of females among cases of congenital hypothyroidism and/or lingual thyroid is discussed.

Autoimmunity and the pathogenesis of localized thyroid autonomy (Plummer's disease).

The pathogenesis of Plummer's disease (localized thyroid autonomy) is incompletely known. It has been shown that a normal thyroid follicle can harbour cells with widely different properties, and hyperactive follicles may arise from cells with both high replicating and hormonogenic potencies under the influence of chronic mild stimulation. We now find thyroid growth-stimulating immunoglobulins (TGI) to be present in low or intermediate titre in the serum of 7 of 9 patients with Plummer's disease. Haemagglutinating antibodies against thyroid microsomal antigen were present in low titre in two of these as well as in three of 21 other patients with this disorder. Two of the patients had a suppressible goitre in addition to the autonomous nodule. One of these is described in more detail. The possibility is discussed that autoimmunity may play a pathogenic role in Plummer's disease. TGI, in relatively low titres as found here, could exert the chronic mild stimulation supposed to be the prime event in the generation of hyperactive follicles. Whether autonomy is intrinsically present in these follicles or triggered by stimulation, remains to be established. Hyperthyroidism supervenes only when the mass of autonomous cells surpasses a certain limit. It appears that these patients with Plummer's disease should be included in the multidimensional spectrum of autoimmune thyroid disease.

Long-term follow-up after iodine-131 treatment for Plummer's disease (autonomous goiter).

A follow-up study is presented in 88 patients treated with I-131 for Plummer's disease (localized autonomous thyroid function, either multifocal or as a solitary nodule) one to 17 years before the present study. Studies included clinical examination, scintigraphy, and function tests. One patient was hypothyroid, seven were marginally hyperthyroid, and five still received low dose antithyroid drugs. Of 75 euthyroid patients, the thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH) was absent in 16 (generally with scintigraphic evidence of autonomous function), subnormal in 20, and normal in 39. A single autonomous nodule prior to treatment was found relatively frequently in males and in patients with a normal TRH test at follow-up. Most goiters had become smaller and one third of all solitary nodules could not be detected anymore. Autonomous function at follow-up was probably due to residual rather than recurrent disease in most, if not all, cases. It is concluded that I-131 therapy is at least as satisfactory as partial thyroidectomy in the treatment of Plummer's disease; lifelong follow-up was not found to be necessary.

Is partial thyroidectomy definitive treatment for Plummer's disease (autonomous goiter)?

Plummer's disease is a thyroid disorder in which both autonomously functioning and normal tissue is present in the gland. Surgery and I-131 therapy are generally regarded as equally effective for definitive treatment. However, since progression of the disease is very slow, postoperative recurrences should become evident only after many years. We reexamined 87 patients thyroidectomized for Plummer's disease one to 15 (average 7.1) years before the present study. Studies included clinical examination, scintigraphy, and a TRH test. No patient was overly hyperthyroid; one had biochemical hyperthyroidism and another had mechanical complaints. Localized autonomous function was considered present in 18 patients (21%); the TRH test result was abnormal in 10 of these. Postoperative autonomy was found more frequently in males. The scans suggested residual rather than recurrent autonomy in nearly all cases. It is concluded that the presence of residual autonomously functioning thyroid tissue after surgery for Plummer's disease is common and recurrent hyperthyroidism may eventually develop in some of the patients. This knowledge may in some cases turn the scale towards I-131 treatment.

Value of the free triiodothyronine index in the diagnosis of hyperthyroidism.

Normalized T4 (T4N), total T3, T3 resin sponge uptake (T3U) and the response of TSH to TRH were determined in 264 patients sent for diagnosis of thyroid function. Many of these patients were diagnostic problem cases. Those with disease or medication known to invalidate the TRH test, but not those with abnormal thyroid hormone binding capacity in serum, were excluded. A free T3 index (FT3 index) was calculated as the product of total T3 and T3U. The FT3 index tended to decline with increasing age, the mean value being significantly higher in the youngest patients (12-20-years-old) than in the older age groups. In the diagnosis of hyperthyroidism, the FT3 index was superior not only to T4N but also to total T3, particularly in the presence of elevated hormone binding capacity (relatively low T3U). It is anticipated that the FT3 index will be most useful as a routine test for hyperthyroidism, especially in several (though not all) instances where the TRH test is invalidated.

Evaluation of cold areas on the thyroid scan with 99mTc-bleomycin.

The value of 99mTc-bleomycin scintigraphy in the evaluation of cold areas on a 99mTc-pertechnetate scan was investigated in 35 patients. A histological diagnosis was obtained in 31 patients. Only one of the six malignant lesions was considered as positive and two as doubtful. Of the remaining 25 patients with non-toxic colloid goitre, one was clearly positive and four were doubtful. These results indicate that 99mTc-bleomycin scintigraphy is not a valuable procedure in the further evaluation of patients with cold lesions.

On the natural history of Plummer's disease.

Plummer's disease (autonomous goiter) presents a spectrum of forms, raging from solitary autonomous thyroid nodules to numerous small autonomous areas, and from unequivocal to servere hyperthyroidism. Progression is often very slow, but data on long-term follow up are scare, contradictory and limited to solitary nodules. We re-examined 58 untreated patients on one or more occasions. Follow-up time ranged from 1 to 12 years (average 4 years). There were gross clinical or scintigraphic changes in 13 patients. Three included six euthyroidal patients who became (mildly) hyperthyroid, one with a change from single to numerous "hot spots," and one in which the radionuclide disappeared in one of two separate autonomous areas. Minor changes were seen in 14 patients. Changes occurred irrespective of the scintigraphic pattern. In contrast, progression was very rapid in two of 300 other patients with the disease, leading to fatal thyrotoxic crisis withing three months in one. In another patient, transient hyperthyroidism was documented after excessive iodine administration. It is concluded that patients may be left untreated as long as serious complaints and clinical suspicion of associated malignancy are absent.