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Graves’ Disease: What Is the Role and Timing of Surgery?
Abstract
The surgical treatment of Graves’ disease classically was limited to a small subset of patients with contraindications to medical therapy or radioactive iodine or who presented with severe ophthalmopathy, complications of severe acute thyrotoxicosis, or concurrent thyroid nodules. With the introduction of endocrine surgery fellowship training and improving surgical outcomes, total thyroidectomy is now becoming more widely used as first-line therapy for Graves’ disease. This chapter will describe the evolving role of surgery for Graves’ disease, highlight circumstances where thyroidectomy is definitively the treatment of choice, and discuss controversies in the perioperative management of these patients.
Background:
Our goal was to elucidate the differences in degree of technical difficulty of thyroidectomy in patients with autoimmune thyroid diseases.
Methods:
Charts of adult patients who had undergone thyroidectomy were reviewed. Patients with Hashimoto's Thyroiditis (HT) or Graves' Disease (GD) were individually compared to a control group of patients with early stage malignancy or goiter.
Results:
The HT (n = 65) group was significantly more likely to have friable (P = .001) and fibrotic (P < .001) thyroids, longer operative times (P = .02), and a 22-modifier (P = .005). The GD (n = 169) group was significantly more likely to have friable (P < .001), vascular (P < .001), fibrotic (P = .038), and heavy (P = .002) thyroids, longer operative times (P = .03), increased length of stay (P = .01) and a 22-modifier (P = .01).
Conclusion:
Our experience at an institution with a high-volume thyroid practice demonstrates that patients with autoimmune thyroid disease have consistent qualitative changes of the thyroid and significantly increased operative times and surgical difficulty.
Background: Patients with Graves' disease (GD) have disturbances in calcium regulation with manifestations such as postoperative hypocalcemia. We have investigated the thyroid as well as the parathyroid function in detail.
Intraoperative nerve monitoring (IONM) aimed at reducing the injuries of recurrent laryngeal nerve during thyroidectomy is controversial. We conducted a meta-analysis to assess the incidence of nerve injuries with or without IONM. Studies published from January 1994 to February 2012 in English language on humans were identified. Heterogeneity of studies was checked by the Higgins test. Summary estimates of predictive values of injury were made using the Mantel-Haenszel test based on the fixed-effects model. Publication bias was assessed by a funnel plot and Egger's method. Eight articles were selected accounting a total of 5257 nerves at risk. IONM revealed a significant impact in preventing transient injuries (positive predictive value = 5% [95% CI: 2-8], negative = 96% [95% CI: 91-100], relative risk = 0.73 [95% CI: 0.54-0.98], p = 0.035), whereas they failed to demonstrate effect on permanent injuries (positive predictive value = 2% [95% CI: 0.6-3.8], negative 99% [95% CI: 97-100], relative risk = 0.73 [95% CI: 0.44-1.23], p = 0.235). This meta-analysis demonstrated the merit of IONM in preventing transient injury during thyroidectomy. No advantage was found in permanent injuries.
Background
Persistent or recurrent hyperthyroidism after treatment with radioactive iodine (RAI) is common and many patiedlxnts require either additional doses or surgery before they are cured. The purpose of this study was to identify patterns and predictors of failure of RAI in patients with hyperthyroidism.
Methods
We conducted a retrospective review of patients treated with RAI from 2007 to 2010. Failure of RAI was defined as receipt of additional dose(s) and/or total thyroidectomy. Using a Cox proportional hazards model, we conducted univariate analysis to identify factors associated with failure of RAI. A final multivariate model was then constructed with significant (p
Graves' ophthalmopathy (GO) is an autoimmune disorder of the orbit that is clinically relevant in 25-50% of patients with Graves' disease and 2% of patients with chronic thyroiditis. The age-adjusted annual incidence of clinically relevant GO is 16 per 100,000 population in women and 2.9 in men. At the onset of ophthalmopathy, 80-90% of patients have hyperthyroidism, with the rest having euthyroidism or hypothyroidism. The natural history of GO consists of two phases: an active inflammatory phase and a static phase. Anti-inflammatory therapy is indicated for the first phase of GO. Approximately 5% of patients experience late reactivation of GO. Asians appear to have less severe manifestations, with milder orbital edema, proptosis and muscle restriction. Genetic, anatomic and environmental factors influence the development of GO. Aging, thyroid dysfunction, thyroid stimulating hormone (TSH) receptor antibodies, smoking and radioiodine treatment for hyperthyroidism also influence the development and course of GO.
Total thyroidectomy (TT) is the preferred operative approach to Graves' disease. Current guidelines of the American Thyroid Association call for the administration of potassium iodide (KI) and achievement of euthyroid state before operation. Small numbers and a mixture of operative approaches spanning several decades hinder previous operative series. We present the outcomes for TT at a single high-volume center.
A retrospective cohort study was conducted on 165 patients undergoing TT for Graves' disease from July 2007 to May 2012.
Mean age was 43 years (range, 17-78), and 128 patients (78%) were female. A total of 95% of patients were on methimazole or propylthiouracil, and 42% remained hyperthyroid at time of TT. Only 3 (2%) patients received KI. Mean operative time was 132 minutes (range, 59-271). Mean gland size and blood loss were 41 g (range, 8-180) and 55 mL (range, 10-1050), respectively. No patient developed thyroid storm. Median follow-up was 7.5 months. Temporary and permanent hypocalcemia developed in 51 (31%) and 2 patients (1.2%), respectively. Temporary and permanent recurrent laryngeal nerve paresis occurred in 12 (7%) and one (0.6%) patient, respectively. Sixty-one (37%) patients experienced at least one complication. On multivariate analysis, patient age younger than 45 years (odds ratio 2.93, 95% confidence interval 1.39-6.19) and obesity (odds ratio 2.11, 95% confidence interval 1.00-4.43) were associated with the occurrence of complications.
This high-volume surgeon experience demonstrates no appreciable detriment to patient outcomes when recommendations of the American Thyroid Association for routine use of KI and euthyroid state before thyroidectomy are not met. Transient hypocalcemia and hoarseness are frequent complications of TT for Graves' disease, resolving within 6 months in most patients. Age younger than 45 years and obesity are risk factors for postoperative complications.
Hyperthyroidism has been linked with different morbidities, like atrial fibrillation, stroke and diabetes mellitus. However, our knowledge regarding the extent and temporal relation between hyperthyroidism and other diseases is fragmented. Here, we aimed at evaluating various morbidities before and after the diagnosis of hyperthyroidism.
Observational cohort study. From nationwide Danish health registers 2631 hyperthyroid singletons and 375 twin pairs discordant for hyperthyroidism were identified and followed for an average of 6 years (range 0-13). Data on the occurrence of cardiovascular diseases, lung diseases, diabetes mellitus, rheumatic diseases and malignant diseases was obtained by person-to-person record linkage with the National Danish Patient Register and/or the Danish National Prescription Registry (lung diseases and diabetes mellitus). Logistic and Cox regression models were used to assess the risk of morbidity before and after the diagnosis of hyperthyroidism, respectively. All Cox regression analyses were adjusted for the degree of co-morbidity preceding the diagnosis of hyperthyroidism, using the Charlson score.
Hyperthyroid individuals had a significantly higher risk of being diagnosed with cardiovascular diseases (odds ratio (OR) 1.65; 95% confidence interval (CI): 1.45-1.87), lung diseases (OR 1.53; 95% CI: 1.29-1.60), and diabetes mellitus (OR 1.43, 95% CI: 1.20-1.72), but not with malignant diseases (OR 1.16, 95% CI: 0.99-1.36) prior to the diagnosis of hyperthyroidism. After the diagnosis of hyperthyroidism, subjects had a significantly higher risk of being diagnosed with cardiovascular diseases (hazard ratio (HR) 1.34; 95% CI: 1.15-1.56), lung diseases (HR 1.28; 95% CI: 1.10-1.49), and diabetes mellitus (HR 1.46; 95% CI: 1.16-1.84), but not with rheumatic diseases (HR 1.39, 95% CI: 0.92-2.09) or malignant diseases (HR 1.18, 95% CI 0.97-1.42).
We demonstrate a significantly increased burden of morbidity, both before and after the diagnosis of hyperthyroidism.
Context:
More than two decades have passed since members from the American Thyroid Association (ATA), European Thyroid Association, and Japan Thyroid Association were surveyed on management practices for patients with hyperthyroidism due to Graves' disease (GD).
Objective:
We sought to document current practices in the management of GD and compare these results both to those documented in earlier surveys and to practice recommendations made in the 2011 ATA/American Association of Clinical Endocrinologists (AACE) hyperthyroidism practice guidelines. Lastly, we sought to examine differences in GD management among international members of U.S.-based endocrine societies.
Methods:
Members of The Endocrine Society (TES), ATA, and AACE were invited to participate in a web-based survey dealing with testing, treatment preference, and modulating factors in patients with GD.
Results:
A total of 730 respondents participated in the survey, 696 of whom completed all sections. Respondents included 641 TES members, 330 AACE members, and 157 ATA members. The preferred mode of therapy in uncomplicated GD was antithyroid drugs (ATDs) by 53.9% of respondents, radioactive iodine (RAI) therapy by 45.0%, and thyroid surgery in 0.7%. Compared with 1991, fewer U.S. (59.7 vs. 69%) and European (13.3% vs. 25%) respondents would use RAI therapy. Methimazole and carbimazole were the preferred ATDs, with only 2.7% of respondents selecting propylthiouracil. Patients with Graves' ophthalmopathy were treated with ATDs (62.9%) or surgery (18.5%) and less frequently with RAI plus corticosteroids (16.9%) or RAI alone (1.9%).
Conclusions:
Striking changes have occurred in the management of GD over the past two decades, with a shift away from RAI and toward ATDs in patients with uncomplicated GD. Apparent international differences persist but should be interpreted with caution. Current practices diverge in some areas from recently published guidelines; these differences should be assessed serially to determine the impact of the guidelines on future clinical practice.
Background:
The management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists for Graves' disease (GD) include any of the following modalities: (131)I therapy, antithyroid medication, or thyroidectomy. No in-depth analysis has been performed comparing the treatment options, even though a single treatment option seems to be universally accepted.
Methods:
A systematic review of the literature was performed to examine contemporary literature between 2001 and 2011 evaluating the management options of GD. We compiled retrospective and prospective studies analyzing surgery and radioactive iodine. Outcomes of interest included postoperative hypothyroidism, euthyroidism, and persistent or recurrent hyperthyroidism without supplementation. Success was defined as postoperative euthyroidism or hypothyroidism. Failure was defined as persistent or recurrent hyperthyroidism.
Results:
Of the 14,245 patients, 4,546 underwent surgery [3,158 patients had subtotal thyroidectomy (STT) and 1,388 had total thyroidectomy (TT)] and 9,699 had radioactive iodine. The radioactive iodine group consisted of 2,383 patients receiving 1-10 mCi, 1,558 patients receiving 11-15 mCi, 516 patients receiving >15 mCi, and 5,242 patients receiving an unspecified amount. Surgery was found to be 3.44 times more likely to be successful than radioactive iodine (p < 0.001). STT and TT were found to be 2.33 and 94.45 times more likely to be successful than radioactive iodine (p < 0.001), respectively.
Conclusions:
On the basis of the outcomes analyzed, surgery appears to be the most successful in the management of GD, with TT being the preferred surgical option.
Thyroid storm (TS) is life threatening. Its incidence is poorly defined, few series are available, and population-based diagnostic criteria have not been established. We surveyed TS in Japan, defined its characteristics, and formulated diagnostic criteria, FINAL-CRITERIA1 and FINAL-CRITERIA2, for two grades of TS, TS1, and TS2 respectively.
We first developed diagnostic criteria based on 99 patients in the literature and 7 of our patients (LIT-CRITERIA1 for TS1 and LIT-CRITERIA2 for TS2). Thyrotoxicosis was a prerequisite for TS1 and TS2 as well as for combinations of the central nervous system manifestations, fever, tachycardia, congestive heart failure (CHF), and gastrointestinal (GI)/hepatic disturbances. We then conducted initial and follow-up surveys from 2004 through 2008, targeting all hospitals in Japan, with an eight-layered random extraction selection process to obtain and verify information on patients who met LIT-CRITERIA1 and LIT-CRITERIA2.
We identified 282 patients with TS1 and 74 patients with TS2. Based on these data and information from the Ministry of Health, Labor, and Welfare of Japan, we estimated the incidence of TS in hospitalized patients in Japan to be 0.20 per 100,000 per year. Serum-free thyroxine and free triiodothyroine concentrations were similar among patients with TS in the literature, Japanese patients with TS1 or TS2, and a group of patients with thyrotoxicosis without TS (Tox-NoTS). The mortality rate was 11.0% in TS1, 9.5% in TS2, and 0% in Tox-NoTS patients. Multiple organ failure was the most common cause of death in TS1 and TS2, followed by CHF, respiratory failure, arrhythmia, disseminated intravascular coagulation, GI perforation, hypoxic brain syndrome, and sepsis. Glasgow Coma Scale results and blood urea nitrogen (BUN) were associated with irreversible damages in 22 survivors. The only change in our final diagnostic criteria for TS as compared with our initial criteria related to serum bilirubin concentration >3 mg/dL.
TS is still a life-threatening disorder with more than 10% mortality in Japan. We present newly formulated diagnostic criteria for TS and clarify its clinical features, prognosis, and incidence based on nationwide surveys in Japan. This information will help diagnose TS and in understanding the factors contributing to mortality and irreversible complications.
To characterise potential fear of radiation exposure in a normal population of individuals who have volunteered to care for a radioactive family member or friend after outpatient radioimmunotherapy (RIT) treatment for cancer, and obtain their knowing and willing acceptance of the risk.
Over 750 carers of 300 patients confined to their homes for 1 week following outpatient iodine-131 rituximab RIT of lymphoma were interviewed by a nuclear medicine physicist according to a multi-visit integrated protocol designed to minimise radiation exposure, define risk and gain informed consent.
Median radiation exposure of carers was 0.49 mSv (range 0.01-3.7 mSv) which is below the Western Australian regulatory limit of 5 mSv for consenting adult carers of radioactive patients. After signing a declaration of consent, only 2 carers of 750 abrogated their responsibility and none of those who carried out their duties expressed residual concerns at the end of the exit interview with respect to their radiation exposure.
Fear of radiation exposure in a normal population may be characterised as a normal emotional response. In the special case of carers of radioactive patients, this fear may be successfully managed by rational, authoritative and empathic explanation to define the risk and gain willing acceptance within the context of domiciliary patient care.
Although antithyroid drug (ATD)-induced hematopoietic damage is a significant concern, it has not been comprehensively investigated.
Our objective was to describe the clinical features of ATD-induced hematopoietic damage.
This was a retrospective cohort study in Tokyo, Japan.
Between January 1983 and December 2002, 50,385 patients at Ito Hospital were diagnosed with Graves' disease. We retrospectively reviewed their medical, pathological, and laboratory records between January 1983 and December 2010.
Incidence and clinical features of ATD-induced agranulocytosis and pancytopenia were evaluated.
Of 55 patients with documented hematopoietic damage, 50 had agranulocytosis and 5 had pancytopenia. All of them received ATD, either methimazole (n = 51) or propylthiouracil (n = 4). Median intervals between initiation of ATD therapy and the onset of agranulocytosis and pancytopenia were 69 d (range, 11-233 d) and 41 d (range, 32-97 d), respectively. Either anemia or thrombocytopenia was also documented in seven of the 50 patients with agranulocytosis. Agranulocytosis was the first manifestation of hematopoietic damage in four of the five patents with pancytopenia. Hematopoietic damage recovered with supportive measures including granulocyte colony-stimulating factor (n = 37), steroids (n = 10), and other supportive measures (n = 8) in 54 patients, whereas the remaining patient died of complications from infection. This study failed to identify the risk factors for ATD-induced hematopoietic damage.
This study showed that ATD cause hematopoietic changes, which are occasionally severe and potentially fatal. The pathogenesis of agranulocytosis and pancytopenia might overlap, and additional studies are warranted to clarify this and to establish an optimal treatment strategy.
Radiation safety is an essential component in the treatment of patients with thyroid diseases by ¹³¹I. The American Thyroid Association created a task force to develop recommendations that would inform medical professionals about attainment of radiation safety for patients, family members, and the public. The task force was constituted so as to obtain advice, experience, and methods from relevant medical specialties and disciplines.
Reviews of Nuclear Regulatory Commission regulations and International Commission on Radiological Protection [corrected] recommendations formed the basic structure of the recommendations. Members of the task force contributed both ideas and methods that are used at their respective institutions to aid groups responsible for treatments and that instruct patients and caregivers in the attainment of radiation safety. There are insufficient data on long-term outcomes to create evidence-based guidelines.
The information was used to compile delineations of radiation safety. Factors and situations that govern implementation of safety practices are cited and discussed. Examples of the development of tables to ascertain the number of hours or days (24-hour cycles) of radiation precaution appropriate for individual patients treated with ¹³¹I for hyperthyroidism and thyroid cancer have been provided. Reminders in the form of a checklist are presented to assist in assessing patients while taking into account individual circumstances that would bear on radiation safety. Information is presented to supplement the treating physician's advice to patients and caregivers on precautions to be adopted within and outside the home.
Recommendations, complying with Nuclear Regulatory Commission regulations and consistent with guidelines promulgated by the National Council on Radiation Protection and Measurement (NCRP-155), can help physicians and patients maintain radiation safety after treatment with ¹³¹I of patients with thyroid diseases. Both treating physicians and patients must be informed if radiation safety, an integral part of therapy with ¹³¹I, is to be attained. Based on current regulations and understanding of radiation exposures, recommendations have been made to guide physicians and patients in safe practices after treatment with radioactive iodine.
Appropriate scale validity and internal consistency reliability have recently been documented for the new thyroid-specific quality of life (QoL) patient-reported outcome (PRO) measure for benign thyroid disorders, the ThyPRO. However, before clinical use, clinical validity and test-retest reliability should be evaluated.
To investigate clinical ('known-groups') validity and test-retest reliability of the Danish version of the ThyPRO.
For each of the 13 ThyPRO scales, we defined groups expected to have high versus low scores ('known-groups'). The clinical validity (known-groups validity) was evaluated by whether the ThyPRO scales could detect expected differences in a cross-sectional study of 907 thyroid patients. Test-retest reliability was evaluated by intra-class correlations of two responses to the ThyPRO 2 weeks apart in a subsample of 87 stable patients.
On all 13 ThyPRO scales, we found substantial and significant differences between the groups expected to have high versus low scores. Test-retest reliability was above 0.70 (range 0.77-0.89) for all scales, which is usually considered necessary for comparisons among patient groups, but below 0.90, which is the usual threshold for use in individual patients.
We found support for the clinical validity of the new thyroid-specific QoL questionnaire, ThyPRO, and evidence of good test-retest reliability. The questionnaire is now ready for use in clinical studies of patients with thyroid diseases.
Background
Definitive treatment of Graves’ disease includes radioactive iodine (RAI) and thyroidectomy, but utilization varies. We hypothesize that, in addition to clinical reasons, there are socioeconomic factors that influence whether a patient undergoes thyroidectomy or RAI.
Methods
Patients treated for Graves’ disease between August 2007 and September 2013 at our university hospital were included. A comparative analysis of clinical and socioeconomic factors was completed.
Results
Of 427 patients, 300 (70 %) underwent RAI, whereas 127 (30 %) underwent surgery. Multiple factors were associated with surgery: younger age (mean 36 vs. 41 years, p
Background
Hypocalcemia occurs after total thyroidectomy (TT) for Graves disease via parathyroid injury and/or from increased bone turnover. Current management is to supplement calcium after surgery. This study evaluates the impact of preoperative calcium supplementation on hypocalcemia after Graves TT.
Methods
A prospective study of patients with Graves disease undergoing TT was performed. Patients with Graves disease managed over a 9-month period took 1 g of calcium carbonate (CC) three times a day for 2 weeks before TT. Those managed the previous year without supplementation served as historic controls. Age-, gender-, and thyroid weight-matched, non-Graves TT patients were procedure controls. Patient demographics, postoperative laboratory values, complaints, and medications were reviewed. Parathyroid hormone (PTH)-based postoperative protocols dictated postoperative CC and calcitriol use.
Results
Forty-five patients with Graves disease were treated with CC before TT, and 38 patients with Graves disease were not. Forty control subjects without Graves disease were identified. Age, gender, and thyroid weight were comparable. Preoperative calcium and PTH levels were equivalent. PTH values immediately after surgery, at postoperative day 1, and at 2-week follow-up were equivalent. Postoperative use of scheduled CC (p = 0.10) and calcitriol (p = 0.60) was similar. Postoperatively, patients with untreated Graves disease had lower serum calcium levels than pretreated patients with Graves disease or control subjects without Graves disease (8.3 mg/dL vs. 8.6 vs. 8.6, p = 0.05). Complaints of numbness and tingling were more common in nontreated Graves disease (26 %) than in pretreated Graves disease (9 %) or in control subjects without Graves disease (10 %, p
Graves' disease (GD) is the most common cause of hyperthyroidism in iodine-sufficient areas. Radioactive iodine I treatment (RIT), as the 1st therapeutic option, is widely accepted by doctors and patients. The aim of this study was to investigate factors influencing the success rate of calculated RIT in GD.
Thyroid function outcome (hyperthyroidism or euthyroidism/hypothyroidism) was verified retrospectively at least 1 year after RIT and was compared with presenting clinical characteristics and pre-RIT parameters in 167 patients with GD treated with I-iodide in the authors' institute.
After RIT, 83 patients (49.7%) became euthyroid, 64 patients (38.3%) became hypothyroid and 20 (12.0%) remained hyperthyroid. Multiple logistic regression analyses demonstrated that there was no statistically significant association between RIT outcomes and sex, age, history of GD, previous antithyroid drug treatment, thyroid hormone levels, thyroid gland mass or radioactive iodine I dosage. The only variables associated with the success rate were the course of disease over 6 months (odds ratio, 3.70; confidence interval, 1.75-7.17; P = 0.014) and 2-hour radioactive iodine uptake (RAIU) >58.5% (odds ratio, 4.08; confidence interval, 2.03-7.83; P = 0.005).
Our study has shown that a calculated approach for the treatment of GD was effective, but high failure rates were observed in patients presenting higher 2-hour RAIU, particularly those with 2-hour RAIU of more than 58.5%.
A Thyroidectomy Difficulty Scale (TDS) was previously developed that identified more difficult operations, which correlated with longer operative times and higher complication rates. The purpose of this study was to identify preoperative variables predictive of a more difficult thyroidectomy using the TDS.
A four item, 20-point TDS, was used to score the difficulty of thyroid operations. Patient and disease factors were recorded for each patient. Difficult thyroidectomy and non-difficult thyroidectomy (NDT) patients were compared. A final multivariate logistic regression model was constructed with significant (P < 0.05) variables from a univariate analysis.
A total of 189 patients were scored using TDS. Of them, 69 (36.5%) suffered from hyperthyroidism, 42 (22.2%) from Hashimotos, 34 (18.0%) from thyroid cancer, and 36 (19.0%) from multinodular goiter. Among hyperthyroid patients, the DT group had a greater number preoperatively treated with Lugols potassium iodide (81.6% DT versus 58.1% NDT, P = 0.032), presence of ophthalmopathy (31.6% DT versus 9.7% NDT, P = 0.028), and presence of (>4 IU/mL) antithyroglobulin antibodies (34.2% DT versus 12.9% NDT, P = 0.05). Using multivariate analysis, hyperthyroidism (odds ratio [OR], 4.35, 95% confidence interval [CI], 1.23-15.36, P = 0.02), presence of antithyroglobulin antibody (OR, 3.51, 95% CI, 1.28-9.66, P = 0.015), and high (>150 ng/mL) thyroglobulin (OR, 2.61, 95% CI, 1.06-6.42, P = 0.037) were independently associated with DT.
Using TDS, we demonstrated that a diagnosis of hyperthyroidism, preoperative elevation of serum thyroglobulin, and antithyroglobulin antibodies are associated with DT. This tool can assist surgeons in counseling patients regarding personalized operative risk and improve OR scheduling.
The objective of this study was to compare the results of total thyroidectomy (TT) for hyperthyroidism secondary to Graves' disease (GD) with TT for other benign thyroid diseases to determine if TT should be considered more often as first-line therapy for GD. Seven hundred eighty patients underwent TT for benign disease: 203 for GD, 56 for other hyperthyroidisms, and 521 for other benign diseases from March 1, 2003, to December 31, 2009. The perioperative results of these three groups were compared for demographics, blood loss, operative time, complications, and hospitalization. There were no significant differences among the three groups except the patients with GD were more likely to be younger (42 vs 56 vs 57 years; P < 0.001), have more blood loss (154 vs 99 vs 110 mL; P = 0.05), and were more likely to develop permanent hypoparathyroidism (1.0 vs 1.8 vs 0%; P = 0.03) when compared with other causes of hyperthyroidism and other benign thyroid diseases. Permanent recurrent laryngeal nerve injury did not occur in the GD group (0 vs 0 vs 0.4% nerves at risk; P = 0.69) with transient recurrent laryngeal nerve injury occurring in 1.7 versus 2.7 versus 3.1 per cent nerves at risk (P = 0.35). The lack of a euthyroid state preoperatively had no influence on surgical outcomes or complications. Eighty percent of the TTs for GD were done as same-day outpatient procedures. TT offers a safe, low-risk, and rapid cure for GD to justifiably be considered as a reasonable first-line therapy in selected patients with Graves' hyperthyroidism.
Previous studies suggest that patients with hyperthyroidism remain at an increased risk of cardiovascular morbidity even after restoring euthyroidism. The mechanisms of the increased risk and its dependency on the different treatment modalities of hyperthyroidism remain unclear. The aim of this long-term follow-up study was to compare the rate of hospitalizations for cardiovascular causes and the mortality in hyperthyroid patients treated surgically with an age- and gender-matched reference population.
A population-based cohort study was conducted among 4334 hyperthyroid patients (median age 46 years) treated with thyroidectomy in 1986-2007 in Finland and among 12 991 reference subjects. Firstly, the hospitalizations due to cardiovascular diseases (CVD) were analysed until thyroidectomy. Secondly, the hazard ratios for any new hospitalization due to CVDs after the thyroidectomy were calculated in Cox regression analysis adjusted with the prevalent CVDs at the time of thyroidectomy.
The risk of hospitalization due to all CVDs started to increase already 5 years before the thyroidectomy, and by the time of the operation, it was 50% higher in the hyperthyroid patients compared to the controls (P < 0·001). After the thyroidectomy, the hospitalizations due to all CVDs (HR 1·15), hypertension (HR 1·23), heart failure (HR 1·17) and valvular diseases or cardiomyopathies (HR 1·55) remained more frequent among the patients than among the controls for 20 years after thyroidectomy. The increased morbidity was not clearly related to the aetiology of hyperthyroidism. Despite the increased CVD morbidity among the patients, there was no difference in cardiovascular mortality.
The present study shows that hyperthyroidism increases the risk of hospitalization due to CVDs and the risk is sustained up to two decades after effective surgical treatment. However, there was no excess CVD mortality in the middle-aged patient cohort studied.
Radioactive iodine (RAI) therapy is preferred in the treatment of hyperthyroidism because of its effectiveness, noninvasiveness, and low costs. I has been detected in extrathyroidal tissues, such as in gastric mucosa, salivary glands, and lacrimal glands. To the best of our knowledge, there is no publication concerning the effects of RAI therapy for hyperthyroidism on tear production. In the present study, we evaluated whether or not the lacrimal glands are affected after RAI therapy when compared with pretreatment period.
The Schirmer and tear break-up time (TBUT) tests were used to assess 32 eyes of 16 patients with conditions that were diagnosed as hyperthyroidism before and at 3 and 6 months after RAI treatment. In addition, pretreatment values of patients were compared with that of controls. It was evaluated whether or not a correlation exists between the results and the dose or iodine uptake values.
There was no significant difference between pretreatment values of Schirmer and TBUT tests obtained in the patient group and those of the control group (P > 0.05). In the patient group, there was a significant difference between the posttreatment and pretreatment values (P < 0.05). There was a positive correlation between uptake values obtained at 24 hours and the values obtained by TBUT and Schirmer tests on both eyes at 3 and 6 months. At 6 months, the uptake value at 24 hours was 28.83 ± 60 for both eyes in patients with TBUT test values less than 10, whereas it was 39.25 ± 7.88 for the right eye and 39.00 ± 6.85 for the left eyes in patients with TBUT test values greater than 10. The difference was statistically significant (P < 0.05).
In our study, we concluded that the decrease in mucin and aqueous production occurs due to affected lacrimal glands by RAI therapy; however, this effect is not dose dependent.
Thyroid hormones are essential for the normal development of the fetal brain, while hyperthyroidism in adults is associated with mood symptoms and reduced quality of life. We aimed to investigate the association and temporal relation between hyperthyroidism and psychiatric morbidity.
Register-based nation-wide cohort study.
Data on hyperthyroidism and psychiatric morbidity was obtained by record linkage of the National Danish Patient Registry and the Danish National Prescription Registry. A total of 2631 hyperthyroid individuals were identified and matched 1:4 with non-hyperthyroid controls and followed for a mean of 6 years (range 0-13). Logistic and Cox regression models were used to assess the risk of psychiatric morbidity before and after the diagnosis of hyperthyroidism, respectively.
Prior to the diagnosis of hyperthyroidism, such individuals had an increased prevalence of hospitalization with psychiatric diagnoses (Odds ratio, OR 1.33; 95 CI: 0.98-1.80) and increased prevalence of treatment with antipsychotics (OR 1.17; 95% CI: 1.00-1.38), antidepressants (OR 1.13; 95% CI: 1.01-1.27) or anxiolytics (OR 1.28; 95% CI: 1.16-1.42). After the diagnosis of hyperthyroidism, there was a higher risk of hospitalization with psychiatric diagnoses (Hazard ratio, HR 1.51, 95% CI: 1.11-2.05), and an increased risk of being treated with antipsychotics (HR 1.46; 95% CI: 1.20-1.79), antidepressants (HR 1.54; 95% CI: 1.36-1.74), or anxiolytics (HR 1.47; 95% CI: 1.27-1.69).
Hyperthyroid individuals have an increased risk of hospitalization with psychiatric diagnoses and being treated with antipsychotics, antidepressants, and anxiolytics, both before and after the diagnosis of hyperthyroidism.
This study aimed to evaluate the effects of indications for thyroidectomy on patient outcomes and to examine the impact of surgical volume on these outcomes.
The nationwide inpatient sample was used to identify all patients who underwent total thyroidectomy (TT) between 2000 and 2009. We examined the effects of surgeon volume and hospital characteristics on predicting patient outcomes. Univariate and multivariate analyses were used to examine the effects of the indication for surgical care on postoperative outcomes.
Overall, 46,261 procedures were identified. Patients with Graves disease had the highest postoperative complications (17.5%) compared to patients undergoing TT for other benign (13.9%) and malignant (13.2%) thyroid disease (P < .001). After stratification by surgeon volume, Graves disease was found to be a significant predictor of postoperative complications in surgeries performed by low- and intermediate-volume surgeons (P < .05). However, Graves disease was not a significant predictor of postoperative complications when performed by high volume surgeons (P = .81). Hospital volume had an inconsistent and marginal protective effect on postoperative outcomes.
Surgery for Graves disease is associated with a higher risk for complications when performed by less experienced surgeons. This finding should prompt recommendations for increasing surgical specialization and referrals to high-volume surgeons in the management of Graves disease.
Our aim was to perform a meta-analysis of high-quality published trials, randomized and observational, comparing total thyroidectomy (TT) and bilateral subtotal thyroidectomy (ST) for Graves' disease.
All studies published from 1970 to August 2012 were identified. All randomized controlled trials (RCTs) were included. Selection of high-quality, nonrandomized comparative studies (NRCTs) was based on a validated tool (Methodological Index for Nonrandomized Studies). Recurrent hyperthyroidism during follow-up, progression of ophthalmopathy, postoperative temporary and permanent hypoparathyroidism, and permanent recurrent laryngeal nerve (RLN) palsy were compared using odds ratios (ORs).
Twenty-three studies were included (4 RCTs and 19 NRCTs) compromising 3,242 patients (1,665 TT, 1,577 ST). TT was associated with a decrease in recurrent hyperthyroidism (P < .00001; OR, 0.10; 95% confidence interval [CI], 0.06-0.18), but with an increase in both temporary (P < .00001; OR, 2.70; 95% CI, 2.04-3.56) and permanent hypoparathyroidism (P = .005; OR, 2.91; 95% CI, 1.59-5.32). Progression of ophthalmopathy (P = .76; OR, 0.90; 95% CI, 0.48-1.71) and permanent RLN palsy (P = .82; OR, 0.91; 95% CI, 0.41-2.02) were similar.
TT offers a better chance of cure of hyperthyroidism than bilateral ST and can be accomplished safely with only a small increase in temporary and permanent hypoparathyroidism.
Potassium iodide (KI) has traditionally been used to reduce gland vascularity and diminish blood loss in patients undergoing thyroidectomy for Graves disease (GD). Current American Thyroid Association (ATA) guidelines (Recommendation 22) call for its routine administration in GD but avoidance in toxic multinodular goiter (TMNG).
A retrospective review (July 2008-May 2012) of perioperative data was performed on 162 patients undergoing total thyroidectomy without preoperative KI and compared to 102 patients with TMNG. Statistical analysis included Student's t test, χ (2) test, and multivariate linear regression.
Compared to TMNG patients, GD patients had a lower mean age (42.7 vs. 49.6 years, p < 0.001) and were less likely to be obese (37 vs. 54 %, p = 0.047). No patients were provided KI in preparation. GD patients did not differ significantly from TMNG patients with respect to mean estimated blood loss (55.4 vs. 51.5 mL, p = 0.773) or mean operative time (131.5 vs. 122.6 min, p = 0.084). GD patients had a lower rate of transient hypocalcemia (31 vs. 49 %, p = 0.004), but the two groups did not statistically differ in rates of prolonged hypocalcemia, temporary recurrent laryngeal nerve (RLN) palsy, prolonged RLN paralysis, or hematoma formation.
Although current ATA recommendations for the management of GD call for routine use of KI before thyroidectomy, this large series demonstrates no appreciable detriment to patient outcomes when this goal is not met.
This brief review describes the history of Graves’ disease, starting with the original descriptions by Parry, Graves and von Basedow. The true aetiology of the disorder was uncovered in the 1950s and 1960s, based on the search for a novel thyroid stimulator which turned out to be an immunoglobulin G autoantibody. Assays for these thyroid stimulatory antibodies have been continually refined and their epitopes on the thyroid stimulating hormone receptor are increasingly well characterized. We also understand far more about the genetic and environmental susceptibility factors that predispose to disease, and even thyroid-associated ophthalmopathy has now been better defined as primarily a T-cell-mediated disease resulting from cytokine stimulation of orbital fibroblasts. These advances should improve treatment options for Graves’ disease in the foreseeable future.
Context:
Several treatment options are available for Graves' disease (GD), including antithyroid drugs (ATDs), radioactive iodine (RAI), and thyroidectomy.
Objective:
The primary outcome was to determine the relapse rates of various treatment options. The secondary outcome was to present data regarding adverse effects of ATDs.
Data sources:
We searched multiple databases through March 2012.
Study selection:
Eligible studies were randomized clinical trials and comparative cohort studies in adults that included 2 or more treatment options for GD.
Data extraction:
Two reviewers independently selected studies, appraised study quality, extracted outcome data, and determined adverse effect profiles.
Data synthesis:
We found 8 studies with 1402 patients from 5 continents. Mean follow-up duration in months was: ATDs, 57; RAI, 64; and surgery, 59. Studies were at moderate to high risk of bias. Network meta-analysis suggested higher relapse rates with ATDs (52.7%; 352 of 667) than RAI (15%, 46 of 304) (odds ratio = 6.25; 95% confidence interval, 2.40-16.67) and with ATDs than surgery (10%; 39 of 387) (odds ratio = 9.09; 95% confidence interval, 4.65-19.23). There was no significant difference in relapse between RAI and surgery. Examination of 31 cohort studies identified adverse effects of ATDs in 692 of 5136 (13%) patients. These were more common with methimazole, mainly owing to dermatological complications, whereas hepatic effects were more common with propylthiouracil use.
Conclusion:
We confirm the relatively high relapse rate of ATD therapy in comparison with RAI or surgery, along with a significant side effect profile for these drugs. These data can inform discussion between physicians and patients regarding the choice of therapy for GD. The limited quality of the evidence in the literature underlines the need for future randomized clinical trials in this area.
Fifty endocrine surgery (ES) fellows have completed their training since the American Association of Endocrine Surgeons initiated a formal match process in 2007. This study was designed to better understand the job prospects of current and future endocrine surgeons and to evaluate the evolution of ES practices nationwide.
Three surveys were conducted of former fellows, surgery department chairs, and surgery recruiters.
Of former fellows, 90% are working in academic centers and 10% in private practice. Average number of job interviews was 3.1 and job offers was 2.2. Eighty-eight percent have a practice that attends to≥50% ES cases, and 45% practice entirely ES. Ninety-eight percent are satisfied with their job. Subjectively, 57% believe that there are not enough job opportunities for young endocrine surgeons, and 50% believe that there are too many ES fellowships. Department chair survey showed that the average number of endocrine surgeons in their department increased from 1.3 to 2.2 in the past decade. A recognized ES section exists in 49% of centers, and 39% of chairs feel that they will need to recruit another endocrine surgeon in the next 2 years. Only 3 of 10 recruiters were familiar with ES, and all had<5 of their hiring institutions asking for endocrine surgeons.
To date, there have been adequate job opportunities to sustain currently trained endocrine surgeons. This contrasts with their subjective belief of limited job prospects. This information can guide the optimal number of fellowship positions and alerts the American Association of Endocrine Surgeons to the opportunity to promote the creation of formal ES sections.
Background
Conducting total thyroidectomy (TT) or subtotal thyroidectomy (ST) in patients with Graves' disease remains controversial. We performed a meta-analysis based on the published randomized controlled trials to evaluate the complications of TT vs ST. Methods
We searched multiple electronic databases for prospective, randomized, controlled trials related to safety and effectiveness of TT vs ST. Relative risk (RR) was estimated with 95% confidence interval (CI) based on an intention-to-treat analysis. We considered the following outcomes: recurrent hyperthyroidism, ophthalmopathy progression, temporary and permanent hypoparathyroidism, temporary and permanent recurrent laryngeal nerve palsy (RLNP) and post-operative bleeding. ResultsFour trials with 674 patients (342 with TT, 332 with ST) were analysed. Although the overall rates of ophthalmopathy progression were similar between TT and ST (RR 092, 95% CI=050-171; P=080), TT was associated with a significant reduction in recurrent hyperthyroidism (RR 014, 95% CI=005-041; P<001). The pooled RR of post-operative bleeding for TT was similar to that for ST (RR 032, 95% CI=005-196; P=022). However, comparing with ST, the RR of temporary hypoparathyroidism was significantly higher for TT (RR 266, 95% CI=189-373; P<001). There was no significant difference in permanent hypoparathyroidism (RR 230, 95% CI=078-676; P=013), temporary (RR 108, 95% CI=047-248; P=085) and permanent RLNP (RR 154, 95% CI=041-573; P=052) between the two groups. Conclusions
With regard to ophthalmopathy progression, post-operative bleeding, permanent hypoparathyroidism, temporary and permanent RLNP, TT is consistent with ST in patients with Graves' disease. However, TT is associated with a reduced incidence of recurrent hyperthyroidism and results in an increase in temporary hypoparathyroidism. Therefore, TT should be proposed for the treatment of Graves' disease.
Background:
Staged thyroidectomy has been recommended when loss of the signal from intraoperative nerve monitoring is observed after first-side dissection of the recurrent laryngeal nerve. There is no high-quality evidence supporting this recommendation. In addition, it is not clear whether signal loss predicts postoperative vocal cord paralysis.
Methods:
This was a prospective observational study of consecutive adult patients undergoing neuromonitored total thyroidectomy for either malignancy or multinodular goitre. The prevalence of first-side loss of signal was recorded. Surgery was completed, and vagus and laryngeal nerves on the first side were rechecked at the end of the procedure.
Results:
Two-hundred and ninety patients were included. Loss of signal on the first side was noted in 16 procedures (5.5 per cent). Thyroidectomy was completed and, at retesting, 15 of 16 initially silent nerves recovered an electromyographic signal with a mean(s.d.) amplitude of 132(26) mcV. Mean time to recovery was 20.2 (range 10-35) min. In no patient was the signal lost on the opposite side. Only three of 15 nerves with a recovered signal were associated with transient vocal cord dysfunction.
Conclusion:
After loss of signal of the recurrent laryngeal nerve dissected initially, there was a 90 per cent chance of intraoperative signal recovery. In this setting, judicious bilateral thyroidectomy can be performed without risk of bilateral recurrent nerve paresis.
Background:
Current postoperative thyroid replacement dosing is weight based, with adjustments made after thyroid-stimulating hormone values. This method can lead to considerable delays in achieving euthyroidism and often fails to accurately dose over- and underweight patients. Our aim was to develop an accurate dosing method that uses patient body mass index (BMI) data.
Study design:
A retrospective review of a prospectively collected thyroid database was performed. We selected adult patients undergoing thyroidectomy, with benign pathology, who achieved euthyroidism on thyroid hormone supplementation. Body mass index and euthyroid dose were plotted and regression was used to fit curves to the data. Statistical analysis was performed using STATA 10.1 software (Stata Corp).
Results:
One hundred twenty-two patients met inclusion criteria. At initial follow-up, only 39 patients were euthyroid (32%). Fifty-three percent of patients with BMI >30 kg/m(2) were overdosed, and 46% of patients with BMI <25 kg/m(2) were underdosed. The line of best fit demonstrated an overall quadratic relationship between BMI and euthyroid dose. A linear relationship best described the data up to a BMI of 50. Beyond that, the line approached 1.1 μg/kg. A regression equation was derived for calculating initial levothyroxine dose (μg/kg/d = -0.018 × BMI + 2.13 [F statistic = 52.7, root mean square error of 0.24]).
Conclusions:
The current standard of weight-based thyroid replacement fails to appropriately dose underweight and overweight patients. Body mass index can be used to more accurately dose thyroid hormone using a simple formula.
Background:
Conventional intraoperative nerve monitoring, predicated on intermittent stimulation, can predict recurrent laryngeal nerve (RLN) palsy only after the damage has been done.
Methods:
Fifty-two patients (52 nerves at risk) who underwent continuous intraoperative nerve monitoring (CIONM) for thyroid surgery via vagus nerve stimulation had their electromyographic (EMG) tracings recorded and correlated with surgical maneuvers and postoperative RLN function.
Results:
There was 1 imminent loss of signal (LOS) with intraoperative signal recovery and there were 4 losses of signal with corresponding unilateral transient RLN palsy. When EMG amplitude decreased >50% and EMG latency increased >10%, LOS and postoperative RLN palsy were noted in 4 of 8 patients (50%) who had multiple combined events. In 9 of 13 patients (70%) who developed adverse EMG changes, modification of the causative surgical maneuver resulted in recovery of those EMG changes and aversion of impending RLN palsy.
Conclusion:
CIONM reliably signaled impending nerve injury, enabling immediate corrective action.
To bring to the attention of healthcare professionals the additional information on propylthiouracil (PTU)-related hepatotoxicity, based on a reanalysis of medical files reported to the Food and Drug Administration (1982-2008) for acute liver failure in PTU-treated hyperthyroid patients, and propose recommendations for the clinical use of PTU. Thirteen files of PTU-related severe liver adverse effects were analyzed for the pediatric population, seventeen for nonpregnant adults and two for pregnant women.
The recent findings showed that the daily PTU dose administered was high in the children, with a mean of 300 mg/day for an average 10-year-old individual. With regard to treatment duration, PTU administration lasted for at least 4 months in 75% of pediatric cases. Similarly, in a majority of adult cases (64%), PTU-induced liver injury occurred after a relatively long treatment period (4 months to >1 year).
PTU should not be used in children, in whom methimazole (MMI) represents the logical alternative. In adults, PTU should be restricted to those rare patients with Graves' disease for whom no better alternative can be offered and in patients with thyroid storm. For the special circumstance of pregnancy, PTU is the preferred choice during early gestation; switching back to MMI during later gestational stages remains a matter of clinical judgment. It is unknown whether liver function tests monitoring is worthwhile to prevent life-threatening, PTU-related hepatotoxicity.
The optimal treatment for pediatric Graves' disease (GD) is controversial. Antithyroid drugs are often used initially, but they are associated with a high failure rate. Therefore alternative therapies have become important. In the present study, we analyze our institution's experience regarding the safety and efficacy of thyroid surgery among pediatric patients with GD.
This is a retrospective chart review of 27 pediatric patients (age ≤ 18 years) with GD who underwent thyroid surgery between 1991 and 2009 at a single academic Institution. We recorded preoperative, intraoperative, and short-term postoperative data.
All 27 patients were initially treated with thionamides. The high rate of hyperthyroidism relapse after discontinuation of medical treatment, age < 5 years, adverse reaction to medical therapy, severe ophthalmopathy, and patient preference justified the final decision to proceed with surgery as definitive therapy. All patients underwent total thyroidectomy. We had no mortality; surgical complications were rare: 4 (14.8 %) cases of transient hypocalcemia, 1 (3.7 %) of permanent hypocalcemia, 3 (11.1 %) of transient RLN neuropraxia, and 2 (7 %) of keloid scar. No bleeding, permanent RLN palsy or relapse hyperthyroidism were reported.
Surgical therapy for pediatric GD performed by experienced thyroid surgeons is a safe, definitive and cost-effective treatment.
The objective of this study was to determine whether health care disparities exist in management of Graves' disease.
Patients treated for Graves' disease from 1999 to 2009 were divided into medical and surgical treatment groups. A comparative analysis of age, sex, race, health insurance, and income was completed. Address and/or zip code were geocoded and median income was determined from census data.
A total of 634 patients were treated for Graves' disease; 535 (84%) medically and 99 (16%) surgically. Mean age (40 ± 15 vs 43 ± 11 y), percentage of women (84% vs 91%), and racial distribution were similar in the 2 groups (P > .05). In the surgical group, median income was lower ($31,530 vs $34,404; P = .07) and 52% of patients were uninsured compared with 30% of patients treated medically (P < .0001).
A disproportionate number of uninsured patients underwent thyroidectomy for Graves' disease. Social and economic factors may have a role in determining definitive therapy for Graves' disease.
The increasing complexity in the management of surgical disorders of the thyroid, parathyroid, adrenal glands, and neuroendocrine pancreas tumors have led to the emergence of endocrine surgery as a surgical subspecialty. Studies showing the relationship between hospital/surgeon volume and patient outcomes highlight the importance of advanced postgraduate training in this field.
Thyrotoxicosis has multiple etiologies, manifestations, and potential therapies. Appropriate treatment requires an accurate diagnosis and is influenced by coexisting medical conditions and patient preference. This article describes evidence-based clinical guidelines for the management of thyrotoxicosis that would be useful to generalist and subspeciality physicians and others providing care for patients with this condition.
The development of these guidelines was commissioned by the American Thyroid Association in association with the American Association of Clinical Endocrinologists. The American Thyroid Association and American Association of Clinical Endocrinologists assembled a task force of expert clinicians who authored this report. The task force examined relevant literature using a systematic PubMed search supplemented with additional published materials. An evidence-based medicine approach that incorporated the knowledge and experience of the panel was used to develop the text and a series of specific recommendations. The strength of the recommendations and the quality of evidence supporting each was rated according to the approach recommended by the Grading of Recommendations, Assessment, Development, and Evaluation Group.
Clinical topics addressed include the initial evaluation and management of thyrotoxicosis; management of Graves' hyperthyroidism using radioactive iodine, antithyroid drugs, or surgery; management of toxic multinodular goiter or toxic adenoma using radioactive iodine or surgery; Graves' disease in children, adolescents, or pregnant patients; subclinical hyperthyroidism; hyperthyroidism in patients with Graves' ophthalmopathy; and management of other miscellaneous causes of thyrotoxicosis.
One hundred evidence-based recommendations were developed to aid in the care of patients with thyrotoxicosis and to share what the task force believes is current, rational, and optimal medical practice.
Although thyroidectomy for Graves' disease (GD) is well established, surgical indications remain less well defined. This study aimed to evaluate the changes in surgical indication, type of resection, and surgical outcomes at a single institution.
A total of 346 patients who underwent thyroidectomy for GD were divided into 2 time periods: period 1 (1995-2001) and period 2 (2002-2008). Their surgical indication, type of resection, and surgical outcomes were compared.
Patients in the earlier period were significantly younger, suffered more previous relapses, and were on a longer duration of antithyroid drugs before surgery. Graves' ophthalmopathy and refusal for radioactive iodine were the indications that changed significantly between the 2 periods. Total/near-total thyroidectomy was performed more commonly and resulted in a higher temporary hypoparathyroidism rate in the latter period (P < .001).
Over the study period, significant changes in surgical indication, type of resection, and surgical outcomes were noted. Graves' ophthalmopathy became one of the most common surgical indications. Total thyroidectomy became the preferred surgery but that resulted in a higher temporary hypoparathyroidism rate.
No consensus exists on optimal treatment for Graves' disease once anti-thyroid medication fails to induce remission. Total thyroidectomy is a more cost-effective treatment than radioactive iodine or life-long anti-thyroid medication, but hypocalcaemia is an important complication, leading to longer hospital admissions and increased prescription costs. This study aimed to compare the relative risk of hypocalcaemia requiring medical treatment for patients with Graves' disease.
Prospective cohort study of patients undergoing total thyroidectomy for Graves' disease and for multinodular goitre, calculating serum calcium levels 24-hours post-operatively and prescription rates.
Mean corrected calcium concentrations 24 hours post-operatively were 2.05 mmol/l for Graves' disease patients and 2.14 mmol/l for multinodular goitre patients (p = 0.003). Biochemical hypocalcaemia developed in 92 per cent (n = 34) of Graves' disease patients and 71 per cent (n = 43) of multinodular goitre patients (p = 0.012). Graves' disease patients were more likely to be prescribed calcium supplementation pre-discharge (p = 0.037).
Total thyroidectomy for Graves' disease carries an increased risk of hypocalcaemia at 24 hours, and of calcium supplementation pre-discharge. Graves' disease patients should be informed of the increased risk of hypocalcaemia associated with total thyroidectomy, and this risk must be factored into future cost-effectiveness analysis.
Total thyroidectomy for treatment of Graves' disease is controversial and much of the debate centers on the concern for complications. The purpose of this study was to evaluate the morbidity of total thyroidectomy for Graves' disease and determine if it is different than for patients with nontoxic nodular goiter.
The rates of life threatening neck hematoma, recurrent laryngeal nerve (RLN) injury, transient hypocalcemia, and hypoparathyroidism were determined for consecutive patients with Graves' disease treated with total thyroidectomy from 1996 to 2010. Results were compared with patients who underwent total thyroidectomy for nontoxic nodular goiter during the same period, matched for the weight of the excised thyroid gland.
Total thyroidectomy was performed in 111 patients with Graves' disease (group I) and 283 patients with nontoxic nodular goiter (group II). Parathyroid autotransplantation was performed in 31(28%) patients in group I and 98 (35%) patients in group II (P = NS). Comparative analysis of morbidity revealed no significant difference in neck hematoma, 0(0%) (I) versus 3(1%) (II); permanent RLN injury, 0(0%) (I) versus 2(1%) (II); and permanent hypoparathyroidism in 1(1%) (I) versus 1 (0.4%) (II) (P = NS). Transient hypocalcemia was more common in patients with Graves' disease, 80(72%) (I) versus 170 (60%) (II) (P < 0.05), but not when matched for thyroid weight.
Total thyroidectomy can be performed with low morbidity in patients with Graves' disease; only transient hypocalcemia occurred more often than in patients with nodular goiter. Total thyroidectomy should be presented as a therapeutic option for all patients with Graves' disease.
Thyroidectomy as a first line treatment for Graves' disease is rarely utilized in the US. The purpose of this study was to analyze the safety and efficacy of thyroid surgery among patients with Graves' disease.
Fifty-six patients with Graves' disease underwent thyroid surgery between May 1994 and May 2008 at a single academic institution. Preoperative, intraoperative, and postoperative variables were analyzed.
A total of 58 surgeries were performed: 55.1% (n = 32) total thyroidectomy, 41.3% (n = 24) subtotal/lobectomy, 3.4% (n = 2) completion thyroidectomy. The average gland weight was 47.3 ± 10.8 gm, with 70% weighing > 30 gm. Reasons for having thyroid surgery were persistent disease despite medical therapy (46.6%), patient preference (24.1%), multinodular goiter/cold nodules (20.3%), failed RAI (radioactive iodine) treatment (16%), and opthalmopathy (12.1%). Of those patients that failed prior RAI therapy, the only factor that was predictive of failure was disease severity, as demonstrated by a markedly elevated initial free-T4 value (11.8 ± 4.5 ng/dL, P = 0.04). Transient symptomatic hypocalcemia occurred in 10.7% (n = 6) of patients, and one patient (1.8%) had symptomatic hypocalcemia lasting > 6 mo. There were no permanent recurrent laryngeal nerve injuries. There was no difference in overall complication rates between patients based on surgical procedure (subtotal versus total thyroidectomy), preoperative RAI treatment, or gland size. Recurrences occurred in 6% of the subtotal thyroidectomy group and 0% of the total thyroidectomy group (P = 0.008).
Thyroidectomy for patients with Graves' disease can be performed with very low complication rates and when a total thyroidectomy is performed, there is almost no risk of recurrence.
A 37-year-old woman presented with palpitations, tremulousness, shortness of breath, and a 9-kg (20-lb) weight loss, and received a diagnosis of Graves' hyperthyroidism. At the time of diagnosis, she had mild proptosis, no diplopia, and no signs of eye inflammation. Her thyroid gland was two times the normal size and non-nodular. Her initial serum triiodothyronine (T(3)) concentration was 655 ng per deciliter (9.2 nmol per liter), and her free thyroxine (T(4)) concentration was 5.7 ng per deciliter (73 pmol per liter). She was treated with methimazole for a year, and her thyroid tests became normal. She discontinued the methimazole 10 weeks before the current presentation with recurrent palpitations and tremulousness. Her serum T(3) concentration is 345 ng per deciliter (5.4 nmol per liter), and her free T(4) concentration is 2.8 ng per deciliter (36.0 pmol per liter). The patient does not smoke. She has a 3-year-old daughter and wishes to become pregnant again. Her endocrinologist recommends radioiodine ablation of her thyroid.
This study was undertaken to determine the presence of thyroid autoantibodies and associated pregnancy complications from 49 pregnant women with thyroid disease. There were 31 (63%) women with Graves' disease (GD) and 18 (37%) with primary hypothyroidism (PHT). A total of 26 (53.1%) women, 19 (61%) with GD and seven (39%) with PHT, had positive antibodies. Six had thyroid peroxidase antibodies (TPO), one with thyroglobulin antibody (TG) and eight had TSH receptor antibodies (TR). Two had a mixture of antibodies involving TG/TPO (one GD vs one PHT), four with TG/TPO/TR (all had GD) and five with TPO/TR (four with GD vs one with PHT). There were associations in women with positive thyroid antibodies and pre-eclampsia (15.4%), abruptio placenta (4%), caesarean deliveries (31%), postpartum thyroiditis (19.2%) and abnormal neonatal thyroid function (15.4%). Women with positive thyroid antibodies in pregnancy need close care during and after pregnancy, as they can develop complications affecting both mother and fetus.
Graves' disease (GD) is the most common cause of thyrotoxicosis in children and adolescents. Caused by immunologic stimulation of the thyroid-stimulating hormone receptor, lasting remission occurs in only a minority of pediatric patients with GD, including children treated with antithyroid drugs (ATDs) for many years. Thus the majority of pediatric patients with GD will need thyroidectomy or treatment with radioactive iodine (RAI; (131)I).
When ATDs are used in children, only methimazole should be used. Propylthiouracil is associated with an unacceptable risk of severe liver injury in children and should never be used as first-line therapy. If remission (defined as normal thyroid function off ATDs) is not achieved after 1 or 2 years of ATD therapy, (131)I or surgery may be considered, with the choice influenced by the age of the individual. When (131)I is used, administered doses should be >150 μCi/g of thyroid tissue. When surgery is performed, near total or total thyroidectomy is recommended.
Choosing a treatment approach for childhood GD is often a difficult and highly personal decision. Discussion of the advantages and risks of each therapeutic option is essential to help the patient and family select a treatment option.
Autoimmunity against the thyrotropin receptor (TSH-R) is a key pathogenic element in Graves' disease (GD) and the autoimmune aberration may be modified by antithyroid treatment. An association between radioactive iodine (RAI) therapy for GD and the development or worsening of Graves' orbitopathy (GO) is widely quoted. RAI-associated leakage of thyroid antigen(s) leads to an increased production of TSH-R antibodies that may initiate the eye injury.
RAI therapy leads to prolonged worsening of autoimmunity against the TSH-R, and the number of patients entering remission of TSH-R autoimmunity is considerably lower than with other antithyroid therapies. Scientific evidence has indicated that RAI treatment for GD is associated with increased risk of occurrence or progression of GO compared with antithyroid drugs (ATD) and thyroid surgery. The risks of developing new GO or worsening of preexisting GO is around 20% after RAI and around 5% after ATD. The risk of developing severe GO after RAI is around 7%. Smoking, high levels of pretreatment serum triiodothyronine, and post-RAI hypothyroidism are associated with increased risk of GO, whereas a high TSH-R autoantibody titer is an independent risk factor for the progression of GO. In patients with mild preexisting GO, steroid prophylaxis is effective in preventing deterioration of GO. Also, routine use of prophylactic oral steroids with RAI therapy should be considered in GD patients without overt GO, but even more so in those at higher risks of eye complications such as smokers, old men, and those with severe hyperthyroidism or high TSH-R antibody titers.
In contrast to ATD, remission of TSH-R autoimmunity after RAI therapy is less common, and RAI for GD is associated with definite increased risk of GO. Oral steroids are beneficial for patients with preexisting GO, particularly smokers.
In the United States, Graves' disease is most commonly treated with radioiodine, yet thyroidectomy remains an important option for correcting hyperthyroidism. In many countries, limited access to thyroid hormone makes subtotal thyroidectomy the procedure of choice. In the United States, where levothyroxine is widely available, we hypothesized that total (TT) or near-total thyroidectomy (NT) is superior to subtotal thyroidectomy (ST) for long-term control of Graves' disease.
A retrospective review of patients who underwent ST, NT, or TT for Graves' disease between 1990 and 2008 was conducted. Differences in rates of disease recurrence were assessed by analysis of variance (ANOVA). Rates of parathyroid autotransplantation, complications, gland weight, and final pathology were determined.
A total of 136 patients with Graves' disease were treated with thyroidectomy. Average age was 36.4 +/- 11.3 years (range: 16-81 years) and 88% were female. From 1990 to 1994, 10 patients underwent ST and 6 had NT. Since then, all patients have undergone TT (n = 120). There was a significantly higher rate of recurrence for ST (30%) compared to NT (0%; P = 0.15) and TT (0%; P < 0.0001). Parathyroid autotransplantation was performed in 36 (26.5%) patients, only 2 of whom underwent ST or NT. Transient postoperative hypocalcemia was more common after TT (P = 0.04). No patient in any group had permanent hypoparathyroidism. Two TT pts had transient recurrent laryngeal nerve palsy.
Subtotal thyroidectomy resulted in 30% long-term failure to correct Graves' hyperthyroidism. We saw no recurrences and no increase in postoperative complications in the TT group. We feel that TT is safe and superior to ST for management of Graves' disease in the United States.
To address terminology and other issues related to thyroid fine-needle aspiration (FNA), the National Cancer Institute (NCI) hosted The NCI Thyroid FNA State of the Science Conference. The conclusions regarding terminology and morphologic criteria from the NCI meeting led to the Bethesda Thyroid Atlas Project and form the framework for the Bethesda System for Reporting Thyroid Cytopathology.
Participants of the Atlas Project were selected from among the committee members of the NCI FNA State of the Science Conference and other participants at the live conference. The terminology framework was based on a literature search of English language publications dating back to 1995 using PubMed as the search engine; online forum discussions ( http://thyroidfna.cancer.gov/forums/default.aspx ); and formal interdisciplinary discussions held on October 22 and 23, 2007, in Bethesda, MD.
For clarity of communication, the Bethesda System for Reporting Thyroid Cytopathology recommends that each report begin with one of the six general diagnostic categories. Each of the categories has an implied cancer risk that links it to an appropriate clinical management guideline.
The project participants hope that the adoption of this framework will facilitate communication among cytopathologists, endocrinologists, surgeons, and radiologists; facilitate cytologic-histologic correlation for thyroid diseases; facilitate research into the understanding of thyroid diseases; and allow easy and reliable sharing of data from different laboratories for national and international collaborative studies.
First-line treatment for Graves disease is frequently 18 months of antithyroid medication (ATM). Controversy exists concerning the next best line of treatment for patients who have failed to achieve euthyroidism; options include lifelong ATM, radioactive iodine (RAI), or total thyroidectomy (TT). We aim to determine the most cost-effective option.
We performed a cost-effectiveness analysis comparing these different strategies. Treatment efficacy and complication data were derived from a literature review. Costs were examined from a health-care system perspective using actual Medicare reimbursement rates to an urban university hospital. Outcomes were measured in quality-adjusted life-years (QALY). Costs and effectiveness were converted to present values; all key variables were subjected to sensitivity analysis.
TT was the most cost-effective strategy, resulting in a gain of 1.32 QALYs compared with RAI (at an additional cost of 9,594 US dollars) and an incremental cost-effectiveness ratio of 7,240 US dollars/QALY. RAI was the least costly option at 23,600 US dollars but also provided the least QALY (25.08 QALY). Once the cost of TT exceeds 19,300 US dollars, the incremental cost-effectiveness ratio of lifelong ATM and TT reverse and lifelong ATM becomes the more cost-effective strategy at 15,000US dollars/QALY.
This is the first formal cost-effectiveness study in the US of the optimal treatment for patients with Graves disease who fail to achieve euthyroidism after 18 months of ATM. Our findings demonstrate that TT is more cost effective than RAI or lifelong ATM in these patients; this continues until the cost of TT becomes > 19,300 US dollars.
Autoimmune thyroid diseases (AITDs), including Graves' disease (GD) and Hashimoto's thyroiditis (HT) are prevalent autoimmune diseases, affecting up to 5% of the general population. Autoimmune thyroid diseases arise due to complex interactions between environmental and genetic factors. Significant progress has been made in our understanding of the genetic and environmental triggers contributing to AITD. However, the interactions between genes and environment are yet to be defined. Among the major AITD susceptibility genes that have been identified and characterized is the HLA-DR gene locus, as well as non-MHC genes including the CTLA-4, CD40, PTPN22, thyroglobulin, and TSH receptor genes. The major environmental triggers of AITD include iodine, medications, infection, smoking, and possibly stress. Recent data on the genetic predisposition to AITD lead to novel putative mechanisms by which the genetic-environmental interactions may lead to the development of thyroid autoimmunity.