Treatment Of Autonomous Thyroid Nodules Research Articles

Discussion on radioactive iodine treatment of hyperthyroidism and the risk of induced cancer

Iodine-131 (131I, radioiodine) has been used for over eight decades for the treatment of Graves’ disease, either as initial therapy or following failure of thionamides, as well as for the treatment of autonomous thyroid nodules. 131I treatment is simple to administer, effective, and relatively inexpensive. Recently, there has been some turmoil after a study published in JAMA Internal Medicine reported an increased risk of cancer from 131I treatment. The impact was of short duration however, as the paper received severe criticisms from many nuclear medicine physicians as well as from endocrinologists. Here we explain why that paper's conclusions are doubtful. We also review the major data on the topic of 131I therapy of hyperthyroidism and the risk of cancer.

Ultrasound-guided percutaneous ethanol injection in the treatment of autonomous thyroid nodules--a review.

Percutaneous ethanol injection therapy (PEIT) in patients with autonomously functioning thyroid nodules (AFTN) has been evaluated with respect to indication for PEIT, treatment procedure, results of therapy and side effects of this treatment. As PEIT has not been tested against the standard procedure of radioiodine treatment and surgery up to now, PEIT should be an alternative treatment for selected patients who cannot or will not be treated by radioiodine therapy or surgery. The clinical data available demonstrate that better results are obtained in patients with euthyroid AFTN or AFTN with subclinical hyperthyroidism as compared to patients with AFTN and overt hyperthyroidism, particularly in small thyroid nodules (thyroid nodular volume less than 15 ml). After PEIT significant reduction of thyroid nodular volume can be achieved (reduction 21 to 88 %). Adverse events of PEIT are few and usually mild and with special respect to transient dysphonia, strongly correlated with the technical skills of the operator. Limitations of PEIT are mainly the need of repeat ethanol injections in order to achieve a complete cure of AFTN. In conclusion, a prospective controlled randomized clinical study has to be carried out in patients with AFTN in order to define the role of PEIT in comparison to the standard therapies (radioiodine treatment, surgery), in the treatment of patients with AFTN conclusively.

Treatment of hyperfunctioning thyroid nodules by percutaneous ethanol injection.

BackgroundAutonomous thyroid nodules can be treated by a variety of methods. We assessed the efficacy of percutaneous ethanol injection in treating autonomous thyroid nodules.Methods35 patients diagnosed by technetium-99 scanning with hyperfunctioning nodules and suppressed sensitive TSH (sTSH) were given sterile ethanol injections under ultrasound guidance. 29 patients had clinical and biochemical hyperthyroidism. The other 6 had sub-clinical hyperthyroidism with suppressed sTSH levels (<0.24 μIU/ml) and normal thyroid hormone levels. Ethanol injections were performed once every 1–4 weeks. Ethanol injections were stopped when serum T3, T4 and sTSH levels had returned to normal, or else injections could no longer be performed because significant side effects. Patients were followed up at 3, 6 and, in 15 patients, 24 months after the last injection.ResultsAverage pre-treatment nodule volume [18.2 ± 12.7 ml] decreased to 5.7 ± 4.6 ml at 6 months follow-up [P < 0.001]. All patients had normal thyroid hormone levels at 3 and 6 months follow-up [P < 0.001 relative to baseline]. sTSH levels increased from 0.09 ± 0.02 μIU/ml to 0.65 ± 0.8 μIU/ml at the end of therapy [P < 0.05]. Only 3 patients had persistent sTSH suppression at 6 months post-therapy. T4 and sTSH did not change significantly between 6 months and 2 years [P > 0.05]. Ethanol injections were well tolerated by the patients, with only 2 cases of transient dysphonia.ConclusionOur findings indicate that ethanol injection is an alternative to surgery or radioactive iodine in the treatment of autonomous thyroid nodules.

Treatment of autonomous and toxic thyroid adenomas by percutaneous ultrasound-guided ethanol injection

To evaluate the feasibility and efficacy of US-guided percutaneous ethanol injection (PEI) in the treatment of autonomous and toxic thyroid adenomas. PEI was performed in 42 patients with solitary, scintigraphically "hot" nodules (n=37) or toxic nodular goiter (n=5). The nodular volume ranged from 2.5 to 38 cm3 (mean volume, 20.7+/-14.1 cm3). Ethanol was injected using a free-hand technique, usually in multiple sessions, using color and power Doppler US guidance. Treatment success was evaluated following 3-4 months after PEI by scintigraphy, hormonal status, and US findings. The procedure was technically successful in 39 patients (93%). Three patients were lost to follow-up. Minor complications were pain (all patients), subcutaneous hematoma (n=6), and transitory dysphonia (n=1). A complete cure was achieved in 22 patients (52%), and a partial cure in 10 patients (24%). In 4 cases (9%), the result was unsatisfactory since only moderate hormonal remission was observed. A satisfactory results was thus achieved in 32/42 patients (76%). Significant nodular volume reduction was observed in all cases. Better results were observed in smaller nodules and in cases of autonomous adenomas. There were no cases of recurrent hyperthyreosis. US-guided PEI is an efficient and safe method in the treatment of autonomous thyroid nodules and it enables inactivation of nodules with minimal or transitory complications.

Treatment of autonomous and toxic thyroid adenomas by percutaneous ultrasound-guided ethanol injection.

To evaluate the feasibility and efficacy of US-guided percutaneous ethanol injection (PEI) in the treatment of autonomous and toxic thyroid adenomas. PEI was performed in 42 patients with solitary, scintigraphically "hot" nodules (n=37) or toxic nodular goiter (n=5). The nodular volume ranged from 2.5 to 38 cm3 (mean volume, 20.7+/-14.1 cm3). Ethanol was injected using a free-hand technique, usually in multiple sessions, using color and power Doppler US guidance. Treatment success was evaluated following 3-4 months after PEI by scintigraphy, hormonal status, and US findings. The procedure was technically successful in 39 patients (93%). Three patients were lost to follow-up. Minor complications were pain (all patients), subcutaneous hematoma (n=6), and transitory dysphonia (n=1). A complete cure was achieved in 22 patients (52%), and a partial cure in 10 patients (24%). In 4 cases (9%), the result was unsatisfactory since only moderate hormonal remission was observed. A satisfactory results was thus achieved in 32/42 patients (76%). Significant nodular volume reduction was observed in all cases. Better results were observed in smaller nodules and in cases of autonomous adenomas. There were no cases of recurrent hyperthyreosis. US-guided PEI is an efficient and safe method in the treatment of autonomous thyroid nodules and it enables inactivation of nodules with minimal or transitory complications.

Percutaneous ethanol injection therapy in the treatment of thyroid and parathyroid diseases.

Relevant English language articles published from 1966 to 1995 regarding ethanol therapy in the treatment of thyroid and parathyroid diseases were identified through a MEDLINE search and manual searches of identified articles. The sclerosing properties of ethanol have been recognized for many years and have offered interventional possibilities in the management of various benign as well as malignant lesions. The mechanism of action of ethanol appears to be related to a direct coagulative necrosis and local partial or complete small vessel thrombosis. Ultrasound-guided percutaneous ethanol injection therapy (PEIT) is rapid and performed on an out-patient basis and has now gained wide acceptance due to the accumulating evidence of the efficacy and safety of this therapeutic tool. Yet, there is a lack of prospective, randomized clinical trials comparing PEIT with 131I therapy or surgery with regard to its effects, especially long-term ones and it should therefore still be considered an experimental procedure. In benign endocrine diseases, PEIT has shown promising results in the treatment of autonomous thyroid nodules, benign solitary cold solid as well as cystic thyroid nodules and parathyroid tumours. Its use in pretoxic and toxic thyroid nodules has been evaluated in several uncontrolled studies, all demonstrating a high success rate in spite of the large number of treatments needed. So far efficacy and cost-effectiveness seem inferior to 131I and surgery. Short-term results of PEIT in benign cystic thyroid nodules are convincing with a high cure rate, but no controlled studies with long-term results are available. Preliminary results suggest that PEIT could become an alternative to surgical excision or levothyroxine therapy in the symptomatic solid cold benign thyroid nodule. Ultrasound-guided PEIT of parathyroid tumours has proven to be a useful method in highly selected patients in whom surgery has been found non-attractive and medical treatment ineffective. However, no prospective randomized trials have been published comparing the results of PEIT in parathyroid tumours with conventional surgical and medical treatments. PEIT has never been tested against standard therapy, but seems inferior to 131I and surgery. Side-effects caused by ethanol injection are generally few and transient and are related to the injection into solid nodules rather than cysts. Ethanol injection into solid profund nodules may seriously jeopardize subsequent surgery because of perinodular fibrosis. As an experimental procedure, not yet evaluated sufficiently, it should be reserved for patients who cannot or will not undergo standard therapy. Caution in routine use is advisable.

Five-year follow-up of percutaneous ethanol injection for the treatment of hyperfunctioning thyroid nodules: a study of 117 patients.

Percutaneous ethanol injection (PEI) has been suggested as an alternative to radioiodine and surgery for the treatment of autonomous thyroid nodules (ATN). In this study we have defined the long-term efficacy and safety of PEI for the treatment of ATN, and we have attempted to optimize the clinical usefulness and improve the technical approach to PEI treatment. One hundred and seventeen patients with ATN, 26 males and 91 females, aged 48 +/- 12.9 years (mean +/- SD), were offered PEI when other established treatments were refused or contraindicated. Seventy-seven patients were affected by toxic adenoma (60 with a single nodule, 17 with a multinodular goitre); 40 patients suffered from a pretoxic single nodule. Sterile 95% ethanol was administered weekly under sonographic control by a 20-22 gauge needle without anaesthesia or pharmacological sedation. During PEI treatment, 26 toxic elderly patients were treated with methimazole and propranolol. According to hormone and scintigraphic data, three possible outcomes were identified for statistical analysis: failure (persistent suppression of extra-nodular tissue uptake, along with elevated free T4 (FT4) and free T3 (FT3) and undetectable TSH levels); partial cure (normalization of FT4 and FT3 levels, with low/ undetectable TSH levels; persistent suppression of extra-nodular uptake); complete cure (normal thyroid hormone and TSH levels; restored extra-nodular uptake). The patients were followed for up to 5 years (median 2.5). PEI therapy was well tolerated by all patients. Complete cure was achieved in all pretoxic patients and in 60 (77.9%) patients with toxic adenoma, while partial cure was observed in 7 cases (9.1%) and failure in 10 (13%). PEI treatment proved similarly effective in toxic patients with a single nodule or with multinodular goitre (87 vs 88.2%, respectively). At the end of treatment, a significant shrinkage of nodule volume was observed in all patients (P = 0.0001). Toxic patients with pretreatment volume > 40 ml (n = 8) did not show a significant difference in treatment response rate as compared to those with volume < 40 ml. Recurrence of hyperthyroidism was never observed during follow-up, independently of thyroid status before treatment. Only one patient with significant thyroid autoantibody serum levels before PEI treatment, developed sub-clinical hypothyroidism at 3 years. The administration of methimazole and/or propranolol did not modify PEI outcome. Our data confirm the efficacy and safety of percutaneous ethanol injection for the therapy of autonomous thyroid nodules. The very low incidence of hypothyroidism along with the absence of recurrence of hyperthyroidism suggests that percutaneous ethanol injection is the treatment of choice in patients with pretoxic thyroid adenoma. Percutaneous ethanol injection appears an effective alternative procedure in toxic patients with a high surgical risk even if they have large nodules, and in younger ones in whom radioiodine is contraindicated. Patients may be submitted to anti-thyroid drug and/or beta-blocker therapy if it is necessary, but this does not affect percutaneous ethanol injection treatment outcome. Finally, not only single autonomous thyroid nodules but also toxic multinodular goitre may be successfully treated by percutaneous ethanol injection.

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.

Treatment of autonomous thyroid nodules with percutaneous ethanol injection: 4-year experience.

To evaluate the long-term efficacy of treatment of autonomous thyroid nodules with percutaneous ethanol injection under ultrasound guidance. Treatment was performed in 101 patients. The mean ratio of injected ethanol volume to nodule volume was approximately 1.5; ethanol was usually administered in four to eight sessions. Complete cure was achieved in 59 patients. Partial cure was achieved in 34 patients. Eight patients had remission of thyrotoxicosis but persistence of thyroid-stimulating hormone level suppression and radionuclide uptake only in the nodule. The extent of the response was inversely proportional to the nodule volume. Marked nodule shrinkage was observed in all groups. No recurrences were observed. Transient vocal cord paresis occurred in four patients, with full recovery in all cases. This method compares favorably with both surgery and radioiodine treatment, especially when the very low prevalence of posttreatment hypothyroidism is considered.

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.

Treatment of autonomous thyroid nodules with percutaneous ethanol injection: preliminary results. Work in progress.

Eight patients with autonomous thyroid nodules 2.4-4.3 cm in diameter received percutaneous ethanol injections (PEIs) under guidance by means of ultrasound (US). Sterile ethanol at 95% was injected with a 22-gauge needle and a 7.5-MHz probe with a guide device. Each patient received one or two treatments, with 1-3 mL of alcohol (depending on the nodule size) per treatment, each week for a total of three to six injections per lesion. After a total of 36 injections in all eight patients, there were no complications. Follow-up ranged from 2 to 10 months. After therapy, symptoms subsided and hormonal levels became normal or reached the range of subclinical hypothyroidism. Scintigrams showed that the previously suppressed thyroid tissue had resumed functioning. At US, all nodules had shrunk. PEI was risk free and easy to perform. If these preliminary results are confirmed in a larger study with longer follow-up, the new treatment may become an alternative to surgical or radioiodine ablation of autonomous thyroid nodules.