Treatment of Toxic Multinodular Goiter: Comparison of Radioiodine and Long-Term Methimazole Treatment.

Background: This study aimed to compare the effectiveness and safety of long-term methimazole (MMI) and radioiodine (RAI) in the treatment of toxic multinodular goiter (TMNG). Methods: In this randomized, parallel-group trial, 130 consecutive and untreated patients with TMNG, aged <60 years, were enrolled and randomized to either long-term MMI or RAI treatment. Both groups of patients were followed for 60-100 months, with median durations of 72 and 84 months in the MMI and RAI groups, respectively. Results: In the MMI and RAI groups, 12 and 11 patients, respectively, were excluded because of side effects, choosing other modes of treatment and not returning for follow-up; 53 and 54 patients, respectively, completed the study for 60-100 months. In the MMI group, two patients (3.8%) experienced subclinical hypothyroidism, and 51 (96.2%) remained euthyroid until the end of study. The dosage of MMI to maintain euthyroidism was 6.3 ± 2.0, 4.5 ± 0.9, and 4.1 ± 1.0 mg daily during the first, third, and fifth years of continuous MMI treatment. One patient had elevated liver enzymes, and three developed skin reactions during the first three months, but no adverse effects from MMI occurred from 4 to 100 months of therapy. In the RAI group, 22 (41%) became hypothyroid, 12 (22%) had persistence or recurrence of hyperthyroidism, and 20 (37%) became euthyroid after 16.7 ± 2.7 mCi 131I. Conclusion: Long-term, low-dose MMI treatment for 60-100 months is a safe and effective method for treatment of TMNG, and is not inferior to RAI treatment.

Increased Cardiovascular Mortality and Morbidity in Patients Treated for Toxic Nodular Goiter Compared to Graves' Disease and Nontoxic Goiter.

BACKGROUND: Previous research has suggested an increased risk of death and cardiovascular disease in patients treated for hyperthyroidism. However, studies on this subject are heterogeneous, often based on old data, or have not considered the impact that treatment for hyperthyroidism might have on cardiovascular risk. It is also unclear whether long-term prognosis differs between Graves' disease and toxic nodular goiter. The aim of this study was to use a very large cohort built on recent data to assess whether improvements in cardiovascular care might have changed the prognosis over time. The study also investigated the impact of different etiologies of hyperthyroidism. METHODS: This was an observational register study for the period 1976-2012, with subjects followed for a median period of 18.4 years. Study patients were Stockholm residents treated for Graves' disease or toxic nodular goiter with either radioactive iodine or surgery (N = 12,239). This group was compared to Stockholm residents treated for nontoxic goiter (N = 3685), with adjustments made for age, sex, comorbidities, and time of treatment. Comparisons were also made to the general population of Stockholm. Outcomes were assessed in terms of all-cause and cardiovascular mortality as well as cardiovascular morbidity. RESULTS: The hazard ratios (HR) for all-cause mortality and for cardiovascular mortality were 1.27 [confidence interval (CI) 1.20-1.35] and 1.29 [CI 1.17-1.42], respectively, for hyperthyroid patients compared to those with nontoxic goiter. For cardiovascular morbidity, the HR was 1.12 [CI 1.06-1.18]. Patients aged ≥45 years who were treated for toxic nodular goiter were generally at greater risk than others, and those included from the year 1990 and onwards were at greater risk than those included earlier. Increased all-cause mortality, as well as cardiovascular mortality and morbidity, were also seen in comparisons with the general population. CONCLUSIONS: This is the first large study to indicate that the long-term risk of death and cardiovascular disease in hyperthyroid subjects is due to the hyperthyroidism itself and not an effect of confounding introduced by its treatment. Much of the excess risk is confined to individuals treated for toxic nodular goiter. Despite advances in cardiovascular care during recent decades, hyperthyroidism is still a diagnosis associated with increased cardiovascular morbidity and mortality.

Recombinant human thyrotropin stimulated 131I treatment for multinodular goiter.

The aim of the study was to investigate the effects of rhTSH stimulation before 131I treatment in patients with MNG. METHODS: Sources included the Cochrane Library, MEDLINE, EMBASE, and SCOPUS database (all until January 2016). Randomized controlled trials (RCTs) that assessed the efficacy of rhTSH-stimulated 131I treatment compared to placebo or 131I treatment alone were collected. Two authors performed the data extraction independently. RESULTS: Six RCTs involving 294 patients with MNG were included in this review. Altogether 168 patients were randomized to rhTSH-stimulated 131I therapy, and 126 to either placebo and 131I or 131I alone. rhTSH-stimulated 131I vs placebo and 131I or 131I alone for MNG showed no statistically significant difference in quality of life and all-cause mortality. rhTSH- (at a dose of 0.03 mg and above) stimulated 131I treatment for MNG showed significant benefits in thyroid volume reduction. 131I treatment with rhTSH stimulation at high doses (0.03 mg, 0.1 mg, 0.3 mg and 0.45 mg) for MNG caused significantly higher adverse effects and hypothyroidism. CONCLUSIONS: The overall results indicated that using rhTSH at high doses of 0.03-0.45 mg before 131I therapy resulted in a greater TVR than 131I therapy alone for patients with non-toxic MNG. However, an increased incidence of adverse effects and hypothyroidism was observed in patients receiving high-dose of rhTSH pretreatment than in patients who received low-dose rhTSH pretreatment. Therefore, a dose of 0.03 mg rhTSH pretreatment before 131I therapy may be more potent than 131I alone in treating patients with non-toxic MNG who either had a contraindication for or declined surgery.

Graves' disease and toxic nodular goiter are both associated with increased mortality but differ with respect to the cause of death: a Danish population-based register study.

BACKGROUND: Hyperthyroidism has been associated with increased all-cause mortality. Whether the underlying cause of hyperthyroidism influences this association is unclear. Our objectives were to explore whether mortality risk and cause of death differ between Graves' disease (GD) and toxic nodular goiter (TNG). METHODS: This is an observational cohort study, using record-linkage data from nationwide Danish health registers. A total of 1291 subjects with GD and 861 with TNG, treated in a hospital setting, were identified and followed for a mean period of 11 years. Cases were matched 1:4 with nonhyperthyroid controls with respect to age and sex. The hazard ratio (HR) for mortality was calculated using Cox regression analyses. All analyses were adjusted for comorbidity using the Charlson score. RESULTS: Both GD (HR=1.42 [95% confidence interval (CI) 1.25-1.60]) and TNG (HR=1.22 [CI 1.07-1.40]) were associated with increased all-cause mortality. After stratification for the cause of death, GD was associated with increased mortality due to cardiovascular diseases (HR=1.49 [CI 1.25-1.77]) and lung diseases (HR=1.91 [CI 1.37-2.65]), whereas TNG was associated with increased cancer mortality (HR=1.36 [CI 1.06-1.75]). When analyzing mortality in GD using TNG individuals as controls, there was no significant difference in all-cause mortality between GD and TNG. However, GD was clearly associated with a higher cardiovascular mortality (HR=1.39 [CI 1.10-1.76]) compared to TNG. CONCLUSION: Both GD and TNG, treated in a hospital setting, are associated with increased all-cause mortality. The causes of death differ between the two phenotypes, with cardiovascular mortality being significantly higher in GD.

Medullary thyroid carcinoma with nodular goiter carries an excellent prognosis.

BACKGROUND: In our institution, patients with medullary thyroid carcinoma (MTC) concurrent with nodular goiter (NG) have a nearly 100% survival rate, but the reasons and characteristics are unclear. METHODS: Eighty patients with MTC who underwent surgery in our center between 1971 and 2011 were reviewed. RESULTS: A total of 21 MTC/NG and 59 MTC only patients were identified. The stage of the two groups had no significant difference (P = 0.13). The MTC/NG group had lower preoperative serum calcitonin (CT) levels (914.7 ng/L vs. 1162.6 ng/L, P = 0.003), lower postoperative serum CT levels (371.4 ng/L vs. 582.5 ng/L, P < 0.001), lower carcinoembryonic antigen levels (18.3 ng/ml vs. 130.5 ng/ml, P < 0.001), a lower propensity toward lymph node metastasis (40.0% vs. 66.7%, P = 0.07), and a lower proportion of multifocality (19.1% vs. 42.4%, P = 0.06), capsular invasion (9.5% vs. 25.4%, P = 0.21), and vascular invasion (4.8% vs. 10.1%, P = 0.67). The mean tumor diameter of the two groups was similar (20.3 mm vs. 22.1 mm, P = 0.6). Overall 15-year survival in MTC/NG versus MTC only groups was 100% versus 57.0% (P = 0.03). CONCLUSIONS: MTC with NG is an indolent disease and has an excellent prognosis. The only independent predictor of survival was the TNM stage of disease.

Uncovering a rare but critical complication following thyroid surgery: an audit across the UK and Ireland.

OBJECTIVE: Serious wound infection after thyroidectomy is uncommon, but actual incidence is not well documented in the literature. In the past a patient in our unit died secondary to fulminant streptococcal sepsis after thyroidectomy for benign disease. This prompted us to audit experience of serious wound infection among British Association of Endocrine Surgery (BAES) members. DESIGN: A questionnaire was posted to BAES members inquiring about experience of major wound infection following cervicotomy, incidence of minor wound infection, and prophylactic and therapeutic antibiotic usage. MAIN OUTCOME: Eight respondents experienced a case of fulminant wound infection after cervicotomy (8% total respondents). Five patients died and, in 6 patients, cases of streptococci were cultured. Then, 9% of respondents used prophylactic antibiotics routinely, 16% sometimes and 75% never. The most commonly used antibiotic was augmentin, and the most common reasons for use among those with a selective policy were re-operative cases (38%) and immunocompromised patients (38%). Also, 40% of respondents experienced major wound infection requiring intravenous antibiotics or surgical drainage. The most common choices of antibiotic used before sensitivities were obtained were augmentin (43%) and flucloxacillin (35%). CONCLUSIONS: Although rare, fulminant streptococcal wound infection after cervicotomy does occasionally occur and carries a high mortality.

Amiodarone-induced thyrotoxicosis: left ventricular dysfunction is associated with increased mortality.

OBJECTIVE: Amiodarone-induced thyrotoxicosis (AIT) is a challenging management problem, since patients treated with amiodarone invariably have underlying heart disease. Consequently, thyrotoxicosis can significantly contribute to increased morbidity and mortality. The aim of this study was to compare the clinical outcome and hormone profiles of patients with AIT (n = 60) with those with Graves' thyrotoxicosis (n = 49) and toxic multinodular goitre (MNG, n = 40). DESIGN: A retrospective study of patients with AIT in a single institution was conducted. METHODS: Data from patients with AIT over 12 years were collected. RESULTS: Mean TSH levels were significantly suppressed in all three groups. However, there was no intergroup significant difference. Free thyroxine (T4) levels were significantly higher in AIT (45.6 +/- 3.5 pmol/l) and Graves' disease (44.6 +/- 4.0 pmol/l) compared with toxic MNG (31.5 +/- 5.1 pmol/l, P < 0.05). In contrast, free triiodothyronine (T3) levels were only significantly higher in Graves' disease (14.7 +/- 1.5 pmol/l, P = 0.002) compared with AIT (8.6 +/- 0.7 pmol/l) and toxic MNG (7.4 +/- 0.5 pmol/l). Six deaths occurred in the patients with AIT (10.0%, P < 0.01) and no deaths occurred in the other groups. Amiodarone treatment (P = 0.002) was the most significant predictor of death, whereas free T4, free T3 and age did not affect outcome. Within the amiodarone-treated group severe left ventricular dysfunction (P = 0.0001) was significantly associated with death. CONCLUSIONS: (i) AIT differs from other forms of thyrotoxicosis, and (ii) severe left ventricular dysfunction is associated with increased mortality in AIT.

Surgical treatment of multinodular goiter in young patients.

The objectives of this study were to analyse the results of surgical treatment of multinodular goiter (MG) in a population with under 30 yr of age; (2) to determine the incidence and evolution of related thyroid carcinomas; and (3) to evaluate the rate of relapse. Eighty-one patients operated for MG and under 30 yr of age were analyzed. The control group used consisted of 510 patients between 30 and 60 yr of age, operated on for MG. Cervical surgery for thyroidectomy was performed in all patients. The main outcome measures were postoperative morbidity and mortality; related thyroid carcinoma (number, type and evolution); remission of symptoms; and relapse of goiter. There were neither cases of hypoparathyroidism nor definitive recurrent lesions. In patients with symptoms, there was total remission of these. Although more than half were treated on suspicion of malignancy, only 9% were related to a carcinoma and most were papillary microcarcinomas. The average follow-up was 124 +/- 68 mo. Of the 48 patients with partial surgery, 40% had relapse (n=19). After 5 yr, the rates of relapse were 11% for the Dunhill technique, 20% for bilateral subtotal thyroidectomy, 17% for hemithyroidectomy, and 50% for unilateral subtotal hemithyroidectomy. These rates increased by 25%, 50%, 44%, and 60% respectively, after 10 yr, and up to 33%, 50%, 62%, and 70% after 15 yr; 89% of the cases of relapse were operated on-there were two hypoparathyroidisms and two recurrent lesions, one of the cases of recurrent lesion becoming definitive. MG in young people is mainly treated because of the suspicion of malignancy, although this occurs in less than 10% of cases. Surgery can be carried out with a low rate of morbidity, although the results are only definitive with total thyroidectomy, with a high level of relapse when partial techniques are used given that these are patients with long life expectancy.

Thyroid disease and increased cardiovascular risk.

The effects of thyroid dysfunction are thought to be reversible on restoration of euthyroidism, but postmortem and epidemiologic data suggest that subclinical or treated thyroid disease is associated with increased vascular risk. In order to determine the extent of this risk, and to explore whether the nature and/or treatment of thyroid disease are critical in this relationship, we used medical record linkage to match patients with treated thyroid disease of various etiologies with routinely collected national inpatient and daycase hospital discharge records and death records, and assessed the number of hospitalizations from cardiovascular or cerebrovascular disease or death in patients with thyroid disease and control patients. Patients treated for Graves' disease had more hospitalizations from cardiovascular disease than controls (relative risk, 1.42; 95% confidence interval, 1.20 to 1.67; p < 0.001). Toxic multinodular goiter was also associated with significantly higher rates of cardiovascular disease (relative risk, 1.50; 95% confidence interval, 1.11 to 2.02; p = 0.008). Patients with Hashimoto's thyroiditis aged over 50 years had a threefold increase in cardiovascular admissions compared to controls (23.5% and 6.5%, respectively; 95% confidence interval for difference, 6.0% to 27.9%; p = 0.003). Thus, different forms of thyroid disease were associated with increased long-term vascular risk despite restoration of euthyroidism. The mechanisms that mediate this risk are unclear but may not involve thyroid hormone abnormality.

Total thyroidectomy for multinodular goiter in the elderly.

BACKGROUND: Total thyroidectomy for multinodular goiter (MNG) is increasingly being performed for the elderly population and yet their perioperative and long-term outcomes remain unclear. METHODS: A total of 279 patients who underwent total thyroidectomy for MNG in a university-based hospital during a 9-year period were analyzed according to their age at the time of operation. RESULTS: The duration of operation (P=.023), intraoperative blood loss (P=.030), weight of resected thyroid glands (P<.001) and proportion of retrosternal goiter (P<.001) were significantly greater in the elderly group (>/=70 years) (n = 55), but the incidence of surgically related complications, including recurrent laryngeal nerve palsy and hypoparathyroidism, was similar. Postoperative pneumonia occurred more frequently in the elderly group (P=.034). The number of comorbidities tended to correlate with the length of hospital stay and long-term survival in elderly patients. CONCLUSIONS: Total thyroidectomy for MNG in elderly patients had a similar perioperative outcome as their younger counterparts, but their long-term outcome is likely to be influenced by the number of comorbidities.

Current treatment of nodular goiter with hyperthyroidism (Plummer's disease): surgery versus radioiodine.

BACKGROUND: First described 9 decades ago by H. S. Plummer, thyroidectomy and radioiodine remain the 2 therapeutic modalities for toxic nodular goiter. The aim of this study was to determine its optimal treatment. METHODS: The presentation, operative treatment, pathology, and clinical course of 362 consecutive patients treated at our institution for Plummer's disease from 1990 to 1999 were retrospectively reviewed. RESULTS: Three hundred forty-six patients (63 men and 283 women) were treated surgically (181, 53%), with radioiodine (RAI, 157, 45%), or a combination of both (8, 2%). Mean age was 62 years (surgical, 55 years; RAI, 69 years). Nearly half were symptomatic, 51 (15%) with airway or swallowing compromise and 110 (32%) with cardiac complications. The estimated goiter size was larger (60 g or greater) in surgical (72 patients, 38%) than medically treated (45 patients, 29%) patients. RAI treatment dose averaged 28 mCi; 10 patients (6%) required a second treatment, and 8 patients failed treatment and required subsequent thyroidectomy. Types of thyroidectomy included total (29 patients, 16%), near-total (47 patients, 26%), bilateral subtotal (46 patients, 25%), and unilateral (58 patients, 32%). One month after treatment, hyperthyroidism had resolved in 96% of the surgical patients but only 6% of the RAI patients (mean time to resolution, 5.4 months). Only 55 (38%) of the RAI patients' goiters reduced in size. Recurrent laryngeal nerve paralysis and hypoparathyroidism each occurred in 3 (2%) patients. CONCLUSIONS: Surgical treatment results in rapid, reliable resolution of hyperthyroidism and removal of the nodular goiter with low morbidity and no mortality. RAI is also safe and effective, usually requiring a single dose, but the results are delayed and it usually fails to resolve a goiter.

[Surgical treatment of thyroid nodules. The immediate results after different thyroidectomy methods]. / Tratamentul chirurgical al nodulilor tiroidieni. Rezultate imediate dupa diferite tipuri de tiroidectomie.

The extension of the resection for thyroid nodules depends both on nodules' nature and immediate or late postoperative complications risks. This clinical study analyzed the immediate complications appeared after partial thyroidectomy comparatively with those developed after total thyroidectomy. We studied 1411 patients operated in two clinics (from Romania and from France) which have two different attitudes concerning the width of the resection. Paralysis of recurrent laryngeal nerve occurred in 1.0% of patients with partial thyroidectomy and 3.0% of patients with total thyroidectomy, while only one patient (0.6%) developed permanent hypoparathyroidism after total thyroidectomy. In conclusion, total thyroidectomy can be performed by experimented surgeons with a recurrent or parathyroid injury risk similar to partial thyroidectomy. However, the surgeon should take into account the patient survey capacity and the discomfort produced by life substitutive treatment.

Morbidity and mortality after thyroidectomy.

To assess the morbidity and mortality of thyroid operations, Professional Activity Study records of the Commission on Professional and Hospital Activities, representing an estimated one-third of all thyroidectomies performed in the United States in 1970, were reviewed. The mortality after a thyroid operation for nontoxic goiter was 0.02 per cent for patients less than the age of 50 years but increased with age to 0.66 per cent for those 70 years and older. No in-hospital deaths followed thyroidectomy for malignant goiter in 766 patients less than 40 years of age. Thyroidectomy for diffuse toxic goiter had a mortality fivefold greater than did operations for a benign nontoxic goiter. Total thyroidectomy was used for the treatment of nontoxic, nonmalignant goiter for one in 12 patients and resulted in greater morbidity than did partial or subtotal thyroidectomy. Rational choice of operation for the treatment of goiter for individual patients should be based upon knowledge of the specific risks of surgical treatment, which vary greatly depending upon the age of the patient, whether or not the goiter is toxic or nontoxic and whether or not subtotal or total thyroidectomy is performed.