Solitary Autonomous Thyroid Nodules Research Articles

Follicular Thyroid Carcinoma Presenting with A Hyperfunctioning Nodule in An Adolescent Girl

Background: Follicular thyroid carcinoma is rare in young patients and further diagnostic challenge is added when it presents as a hyperfunctioning thyroid nodule. Case report: We described a 14-year-old girl who presented with thyrotoxicosis and a large goitre associated with compressive symptoms. Thyroid scintigraphy demonstrated a solitary autonomous hyperfunctioning thyroid nodule. FNAC examination was not suggestive of malignancy. Thyrotoxicosis was controlled with carbimazole and a hemithyroidectomy was done. Histopathological examination revealed minimally invasive follicular thyroid carcinoma, following then, complete thyroidectomy was done. Discussion: This patient’s risk factors of malignancy were her age (young), gender (female), large nodule size, progressive growth, and compressive symptoms. This case illustrates the limitation of FNAC to ascertain malignancy in patients with large AFTN as the initial FNAC report was consistent with a benign lesion. Surgical resection without prior FNAC should be considered for cases with hyperfunctioning thyroid nodule which then would allow timely histologic analysis and accurate diagnosis. Conclusion: Autonomous functioning nodules in children and adolescents warrant careful evaluation to exclude malignancy. Our case illustrated the challenges to discriminate between malignant and benign lesions preoperatively for children and adolescents who present with AFNT.

A Patient With a Preexisting (Nontoxic, Nonautonomous) Thyroid Nodule and Concurrent Thyroiditis Mimicking a Toxic Solitary Autonomous Thyroid Nodule on 99mTcO4 Scintigraphy

A Patient With a Preexisting (Nontoxic, Nonautonomous) Thyroid Nodule and Concurrent Thyroiditis Mimicking a Toxic Solitary Autonomous Thyroid Nodule on 99mTcO4 Scintigraphy

Possibilities of nontoxic autonomous thyroid nodules treatment by percutaneous ethanol injection

According to the current principles, autonomous functional thyroid nodules are treated by surgery or by radioiodin therapy. Ultrasound guided percutaneous ethanol injection into solid tumors of the soft tissues was a starting point in attempts to treat the thyroid nodules by the same method. The aim of the study was to assess the efficiency of percutaneous injection in treating solitary, nontoxic, autonomous thyroid nodules of up to 15 mL volume. In 25 patients with solitary nontoxic autonomous thyroid nodules diagnosed by tehnetium-99m scanning as an intensive area having a complete supremacy in the paranodal tissue, an ultrasound guided percutaneous ethanol injection was applied. The procedure was carried out repeatedly once a week until the reduction in nodule size to 50% of the initial size was achieved. An average size of the nodule before curing was 9.68 +/- 5.01 mL. An average quantity of the injected ethanol was 9.52 +/- 5.08 mL, ie 1.06 +/- 0.48 mL/mg of the tissue. The regression of the nodule size in the successfully (deltavol% u -57.09 +/- 13.75%, p < 0.001) and partly successfully cured (deltavol du = -48.45 +/- 14.35%, p < 0.05) was statistically significant compared to the size before the treatment. After ceasing ethanol injection, 18 months later, a further size regression (deltavol% = -79.20 +/- 9.89%) compared to the initial one (p < 0.001) was noticed. Soon, after the procedure was finished, a statistically significant concentration increase of Thyroid Stimulating Hormone (TSH) was noticed compared to the initial values (0.18 +/- 0.16 vs 0.34 +/- 0.31 mU/L, p < 0.01). According to the given criteria, in two female patients satisfactory results were not achieved, but, a year later, in one of them the nodule was not seen by repeated scintigram. The number and frequency of side effects were insignificant. Repeated percutaneous ethanol injections into nontoxic solitary autonomous thyroid nodules result in disappearing of authonomy. The regression of the nodule size of more than 50% compared to its initial volume, as well as the increase in concentration of TSH for more than 50% are the signs of a successful treatment.

Determinants of Long-Term Outcome after Radioiodine Therapy for Solitary Autonomous Thyroid Nodules

To determine the incidence and clinical predictors of hypothyroidism in one institution after radioiodine treatment of solitary toxic nodules. We retrospectively analyzed the outcome of radioiodine therapy in 105 patients with solitary autonomous thyroid nodules treated at our institution during a 10-year period (January 1996 to December 2005; mean duration of follow-up, 53 +/- 34 months). Patients were monitored until the development of hypothyroidism, death, or the end of the study period. The cumulative incidence of hypothyroidism was determined by Kaplan-Meier life-table analysis, and predictors of hypothyroidism were determined by using a Cox regression model. The cumulative incidence of hypothyroidism was 11% at 1 year, 33% at 5 years, and 49% at 10 years. The development of hypothyroidism was not associated with age, sex, radioiodine dose, radioiodine uptake, or degree of suppression of extranodal tissue on scintiscans. The predictors of occurrence of hypothyroidism were pretreatment with antithyroid medications (P = .004; relative risk = 1.94) and positive thyroid antibody status (P = .008; relative risk = 1.84). Antibody-positive patients showed an earlier progression toward hypothyroidism than did antibody-negative patients. Hypothyroidism is a common outcome of radioiodine treatment for autonomous thyroid nodules. In this study, coexistent thyroid autoimmunity and pretreatment with antithyroid medications were significant risk factors for the development of hypothyroidism.

Changes in the thyroid technetium-99m scintigram after antithyroid and subsequent radioiodine treatment for solitary autonomous nodules.

In patients with solitary autonomous thyroid nodules, the treatment of choice is radioiodine (131I) therapy, eventually preceded by antithyroid drugs to avoid aggravation of hyperthyroidism. The aim of this study was to evaluate the scintigraphical results of 131I treatment when using antithyroid pretreatment. Twenty-four patients having a solitary autonomous thyroid nodule were studied. A technetium-99m (99mTc) pertechnetate scintigraphy was performed at the time of diagnosis, when serum thyrotropin (TSH) had been normal for about 3 months on antithyroid drug treatment, and finally when serum TSH was normalized after 131I treatment. The primary scintigram showed suppression of 99mTc pertechnetate in the paranodular thyroid tissue in all patients. The second scintigram showed normal uptake in the paranodular tissue in 22 patients and a continuing suppression of the paranodular tissue in 2 patients. The third scintigram showed a solitary adenoma in 14 patients with none or almost no uptake in the paranodular tissue, resembling the first scintigram. In 6 patients an adenoma was still present, but uptake was seen in the paranodular tissue; in 3 patients a homogenous uptake without any sign of the previous nodule, and in 1 patient very low uptake in the gland was seen. Four patients developed hypothyroidism in the follow-up period of approximately 1 year. Pretreatment with antithyroid drugs induced an increase in serum TSH, stimulating the paranodular tissue. 131I will therefore be distributed in the whole thyroid gland, and not only in the autonomous solitary nodule. After 131I treatment, we continuously found a solitary nodule with low uptake in the paranodular tissue in 20 of 24 patients.

Decreased serum IGF-I and dehydroepiandrosterone sulphate may be risk factors for the development of reduced bone mass in postmenopausal women with endogenous subclinical hyperthyroidism.

Postmenopausal women with endogenous subclinical hyperthyroidism seem to have reduced bone mass, which does not correlate with serum thyroid hormone levels. Relative insufficiencies of IGF-I and dehydroepiandrosterone sulphate (DHEAS) might be additional risk factors for low bone density in these patients. We measured IGF-I, IGF-binding protein-3 (IGFBP-3) and DHEAS levels together with bone mineral density (BMD) of the femoral neck and lumbar spine in women with an autonomously functioning thyroid nodule. Sixty-three women were classified as subclinical hyperthyroid (31 pre- and 32 postmenopausal) and 39 as overt hyperthyroid (16 pre- and 23 postmenopausal) and results were compared with data obtained from 41 age-matched euthyroid healthy women. In premenopausal women BMD was reduced only in the overt hyperthyroid group, and only in the spine, to 92% (P < 0.05). Serum IGF-I as well as IGFBP-3 were increased in the manifest hyperthyroid group, to 157% (P < 0.001) and 129% (P < 0.05) respectively, whereas DHEAS levels did not change in either premenopausal patient group. In postmenopausal women BMD was significantly reduced both in the subclinical hyperthyroid group (spine to 90% and femoral neck to 88%; P < 0.05), as well as in the hyperthyroid group (spine to 78% and femoral neck to 86%; P < 0.01). In contrast to premenopausal women, serum IGF-I and IGFBP-3 did not change in the two groups who were postmenopausal and serum DHEAS levels were reduced to 58% (P < 0.001) in both postmenopausal groups with subclinical as well as overt hyperthyroidism. In the same two groups of patients, serum IGF-I and DHEAS levels correlated with BMD (femoral neck; both r = 0.50, P < 0.05). In conclusion, women with a solitary autonomous thyroid nodule with subclinical hyperthyroidism have reduced BMD only if they are postmenopausal. This is probably due to the effect of subtle increases in thyroid hormone production together with lack of oestrogen protection of the skeleton. But additional risk factors for the development of enhanced bone loss might be a state of relative IGF-I and DHEAS insufficiency in these patients as well as in postmenopausal women with overt hyperthyroidism.

Treatment of solitary autonomous thyroid nodules by percutaneous ethanol injection: results of an Italian multicenter study. The Multicenter Study Group.

Percutaneous intranodular ethanol injection (PEI) has been proposed for the therapy of autonomously functioning thyroid nodules. In 1992, an Italian multicenter study was undertaken to confirm the usefulness and the feasibility of this procedure. The study included 429 patients: 242 (56.4%) were affected by a toxic adenoma (TA) and 187 (43.5%) by pretoxic adenoma (PTA). Free thyroid hormone levels (FT4, FT3) and thyroid stimulating hormone (TSH) were measured before and 3, 6, 12 months after the end of treatment; thyroid ultrasound and thyroid scintiscan were performed in the majority of patients before and after treatment. Patients underwent 2-12 sessions of ethanol injection under sonographic guidance (median 4). The total amount of ethanol administered per patient (1.5 mL/mL nodular volume) was 2-50 mL (mean +/- SD, 17 +/- 9 mL), and the amount per each injection was 1-8 mL (3.2 +/- 1.3 mL). The treatment was judged successful when both TSH and free thyroid hormone serum levels returned within the normal range and recovery of tracer uptake in extranodular tissue was observed at scintiscan, at any time during the follow-up period. The treatment was considered unsuccessful when no change was observed at scintiscan and/or serum TSH levels remained less than 0.4 mU/L. A successful treatment was achieved in 66.5% of patients with TA and in 83.4% of patients with PTA, when assessed after a 12-month follow-up. In all cases a reduction of the nodular size was observed. Almost all positive results were obtained in nodules whose initial volume was less than 15 mL; large nodules responded less favorably. The treatment was generally well tolerated, only transient side-effects, mainly local pain at the time of injection, were observed. Once normalization of scintigraphic image and of FT4, FT3 and TSH serum concentrations was achieved, no recurrence of hyperthyroidism nor development of hypothyroidism were observed for the length of the study. In conclusion, percutaneous ethanol injection for treatment of autonomously functioning thyroid nodules is effective and safe. Better results are obtained in patients with PTA than in patients with TA, particularly when the initial volume of the nodule is less than or equal to 15 mL. PEI may be considered as an alternative to surgery and to radioiodine for treatment of autonomously functioning thyroid nodules.

Treatment of solitary autonomous thyroid nodules by percutaneous ethanol injection: results of an Italian multicenter study. The Multicenter Study Group

Treatment of solitary autonomous thyroid nodules by percutaneous ethanol injection: results of an Italian multicenter study. The Multicenter Study Group

Treatment of autonomous thyroid nodules: safety and efficacy of sonographically guided percutaneous injection of ethanol.

We evaluated the efficacy of sonographically guided percutaneous injection of ethanol as an alternative to surgery and administration of radioiodine, which have a higher risk of complications, for treatment of autonomously functioning thyroid nodules that may develop hyperthyroidism. Sixteen patients between 23 and 67 years of age who had solitary autonomous thyroid nodules were included in the study. The nodules were detected and evaluated using physical examination, measurements of hormonal levels, sonography, and scintigraphy. Sonographically guided percutaneous injection of ethanol was repeated one to two times each week for a total of four to eight treatments. The amount of ethanol used was 0.5-9.0 ml per treatment, depending on the volume of the nodule. Patients were followed up for at least 18 months. Clinical evaluation, including laboratory tests, showed that the patients' signs and symptoms subsided and hormones returned to normal levels in all cases. Scintigrams showed that the normal thyroid tissue that was suppressed before treatment regained normal function. Sonograms showed that the volume of the nodules decreased in 13 of 16 cases. No early or late permanent complications associated with treatment were noted. Our results show that sonographically guided percutaneous injection of ethanol can be used as an alternative treatment of autonomous thyroid nodules with the aim of eliminating the possible risk factors of surgery and radioiodine. This method of treatment may be particularly desirable in patients who are poor candidates for surgery and who refuse standard treatment.

Long-term follow-up of thyroid scintigraphies after 131I therapy of solitary autonomous thyroid nodules.

The aim of the present study was to assess thyroid scintigraphies after 131I treatment of autonomous thyroid nodules with respect to evolution of the hot nodules as well as the extranodular tissue. A 99mTc pertechnetate scintigraphy was carried out 1-16 years (median 8 years) after 131I treatment of a solitary autonomous nodule in 66 patients remaining euthyroid. At the time of diagnosis, 9 of the patients were euthyroid and 57 were hyperthyroid, of whom 27 received antithyroid drug therapy prior to 131I treatment. The scintigraphies were evaluated twice by 4 specialists (3 endocrinologists and 1 specialist in nuclear medicine). There was total agreement between the 4 observers in 50 and 52% in the first and second evaluation, respectively. The interobserver variation was evaluated by means of omega coefficients and omega ranged from 0.18 to 0.76 indicating poor to substantial agreement. A solitary autonomous nodule with suppression of the extranodular thyroid tissue persisted in 50% of the patients, whereas a solitary cold nodule, homogeneous uptake or inhomogeneous uptake was found in 15, 22, and 13%, respectively. We conclude that although euthyroidism is achieved by radioiodine treatment, a hot nodule suppressing the 99mTc pertechnetate in the extranodular tissue is still found in 50% of the patients even when serum TSH has been normal for years. Antithyroid drug therapy prior to 131I treatment was more frequent in this group of patients.

Bone mineral density in patients with endogenous subclinical hyperthyroidism: Is this thyroid status a risk factor for osteoporosis?

The aim of the present study was to elucidate whether endogenous subclinical hyperthyroidism due to a solitary autonomously functioning thyroid nodule affects bone metabolism and is a risk factor for osteoporosis. In a cross-sectional study measurements of bone mineral density were performed in premenopausal and post-menopausal women. Patients were categorized into non-toxic nodular goitre (n = 32), subclinical hyperthyroid (n = 37) and toxic solitary autonomous thyroid nodule (n = 22) subgroups and the results were compared with those of sex and age-matched control reference population (n = 68). Lumbar spine and femoral neck bone mineral densities were measured by dual energy X-ray absorptiometry. Single-photon absorptiometry was applied to the measurement of bone mineral content in the midshaft of the radius. In the non-toxic nodular goitre group, bone densities for all the scanned sites did not differ from the sex and age-matched reference population. At the L2-4 scanning site a significant decrease in the bone mineral density could be observed only in the toxic nodular goitre group and this decrease was more marked in the postmenopausal (P < 0.001) than in the premenopausal females (P < 0.05). At the femoral neck and midshaft radius the mean densitometric values were slightly, but significantly, lower only in the post-menopausal subclinical hyperthyroid group compared with the reference population (P < 0.01). The bone mineral density of the femoral neck, as well as the bone mineral content of the midshaft radius, was significantly decreased in both the premenopausal and post-menopausal patients with a toxic solitary nodule. This study indicates that the bone mineral density of the lumbar spine, femoral neck and the midshaft of the radius are not significantly decreased in premenopausal patients with endogenous subclinical hyperthyroidism resulting from a solitary autonomously functioning thyroid nodule. Conversely, findings hint at the possibility that long-lasting endogenous subclinical hyperthyroidism may be a contributing factor to the development of osteoporosis in some post-menopausal women, mostly at sites where cortical bone preponderates.

Percutaneous ethanol injection treatment of autonomously functioning single thyroid nodules: Optimization of treatment and short term outcome

Twenty-five patients with solitary autonomous thyroid nodules (15 nontoxic, 10 toxic) received percutaneous ethanol injection treatment (PEIT) under sonographic guidance in 4-7 sessions (1-2 weekly). To test different doses, smaller nodules (volume less than 15 mL) were given 0.75-2.8 mL ethanol/mL nodular tissue while larger nodules received 0.5-1 mL/mL. Except for 1 patient who developed hyperpyrexia, no relevant adverse effects were observed. A slight, asymptomatic increase in serum thyroid hormone levels was observed in both groups during the treatment. Three months after treatment, a biochemical and clinical remission of hyperthyroidism was observed in 8 of 10 patients with toxic nodules. A significant increase of TSH level was seen in both groups (p less than 0.01). Significant shrinkage of volume (p less than 0.001) as well as structural alterations of nodules were consistently recorded at sonography. A linear relationship (r = 0.98; p less than 0.0001) between pretreatment volume and volume reduction was found both for large and small nodules, thus suggesting that even limited ethanol doses may be therapeutically effective. A recovery of extranodular parenchyma activity at scintiscan occurred in 16 (64%) of 25 patients. These data confirm that PEIT is effective in obtaining functional ablation and in inducing remission of hyperthyroidism. Adverse effects are infrequent. In spite of the small patient sample, a 0.5-1 mL ethanol dose per each mL of tissue appears as effective as larger doses and seems appropriate for treatment.

Compensated 131I-therapy of solitary autonomous thyroid nodules: effect on thyroid size and early hypothyroidism.

Thyroid function and thyroid gland volume, ultrasonically determined, were investigated in 27 hyperthyroid patients with solitary autonomous thyroid nodules before and during one year after 131I-treatment. Total thyroid volume decreased gradually from 40.9 +/- 3.5 ml (mean +/- SEM) before treatment to 23.9 +/- 1.8 ml (P less than 0.001) at 3 months after 131I-treatment. No further change was observed. All but two patients received only one dose of 131I, and in spite of a significant decrease also of the non-adenoma side of the gland, none became hypothyroid. We conclude that 131I-therapy has an important place in the treatment of solitary autonomous thyroid nodules since all our patients became euthyroid within 3 months, only 2 of 27 patients needed more than one dose of 131I, no cases of hypothyroidism occurred, and thyroid volume was substantially decreased.

Serum thyroglobulin in patients with autonomous thyroid nodules.

To investigate further the relationship between thyroid hormones and thyroglobulin (TG) secretion, total and free thyroid hormone levels, TSH and its response to TRH and serum TG concentrations were determined in 61 patients with solitary autonomous thyroid nodules. Thyroid function varied widely from euthyroidism to clearcut thyrotoxicosis. Serum TG levels were significantly higher in patients than in normal controls. Individually they were above the normal range (greater than 50 ng/ml) in 95% of the patients, as well as in those with normal total and/or free thyroid hormone levels. Patients with high total and/or free thyroid hormone levels had higher TG concentrations than euthyroid patients. TG concentrations were significantly correlated with FT3 values. They were higher in patients in whom TSH was unresponsive to TRH than in the responsive groups. TG was also slightly higher in patients with hot nodules than in those with warm nodules. These data seem to indicate that TG is secreted along with thyroid hormones in the absence of any stimulatory action. It also is a sensitive index of thyroid hyperfunction. Twenty patients were controlled 6 months after nodulectomy. TG levels, though significantly lower than in the preoperative state, were still higher than in normal subjects. This increase was attributed to persistent hyperthyroidism in two patients only. The observation that the increase in TSH after TRH stimulation in post-operative patients was greater than that found in normal controls led us to believe that in most cases the high TG levels after surgery are due to stimulation of the normal thyroid tissue by rebound TSH secretion.

Follow-up of solitary autonomous thyroid nodules treated with 131I.

We studied the long-term effects of 131I therapy for solitary autonomous thyroid nodules on the size of the nodule and on thyroid function. Twenty-three patients with autonomous thyroid adenomas that had been treated with 131I from 4 to 16.5 years earlier (mean, 8.5) were examined, and their thyroid function was tested. In 12 patients (54 per cent), the nodules were still palpable, and in 2 they had increased in size. Eight patients (36 per cent) had become hypothyroid. The incidence of hypothyroidism was not related to nodule size or the level of thyroid function before therapy with 131I or to the total dose of 131I that had been given. We conclude that 131I therapy for autonomous thyroid adenoma often causes hypothyroidism and in many cases does not eradicate the offending nodule.

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.

Serum triiodothyronine in solitary autonomous nodules of the thyroid.

Seventeen patients with solitary autonomous nodules of the thyroid were studied. Eight had clinical features of hyperthyroidism though in some the clinical manifestations were mild. The serum T3 concentration was elevated in all patients with hyperthyroidism but the serum T4 and free thyroxine index were within the normal range in five. All patients with hyperthyroidism subsequently responded to treatment. These findings suggest a high incidence of preferential T3 hypersecretion in hyperthyoidism associated with solitary autonomous thyroid nodule. A further nine patients with single autonomous nodules were clinically euthyroid with normal serum T3 and T4 concentrations and remained euthyroid from 6 to 24 months on serial review.

Clinical Observations on the Solitary Autonomous Thyroid Nodule

Of 54 patients with solitary autonomous thyroid nodules (SAN), only one or perhaps two manifested signs or symptoms of hyperthyroidism. Eighteen of the 54 patients had nodules that were larger than 3 cm in diameter, but only one of these patients had possible thyrotoxicosis. Forty-eight of the 54 patients were followed up for 4 to 136 months (average, 24 months). The course of the disease was completely benign, and none of these subjects developed hyperthyroidism during the follow-up. Two of the 48 patients appeared to have a SAN that underwent degeneration during the study. We think that euthyroid patients with SAN may be managed under most circumstances by periodic follow-up examinations and that they need to be subjected to surgical or radioactive iodine therapy only when and if they subsequently develop hyperthyroidism.

Clinical observations on the solitary autonomous thyroid nodule

Clinical observations on the solitary autonomous thyroid nodule

Solitary Autonomous Thyroid Nodules

A solitary autonomous thyroid nodule should be suspected when a lump that moves with swallowing is sighted or palpated in the thyroid area. Most hyperthyroid patients and a select few euthyroid patients with this disorder are given ablative therapy. In the majority of euthyroid patients, ablative therapy is withheld until hyperthyroidism develops.