Thyroid-stimulating Hormone Suppression Research Articles

Well-Differentiated Thyroid Cancer: The Philippine General Hospital Experience

BackgroundWell-differentiated thyroid cancer (WDTC) is the most common form of thyroid malignancy. While it is typically associated with good prognosis, it may exhibit higher recurrence and mortality rates in selected groups, particularly Filipinos. This paper aims to describe the experience of a Philippine Hospital in managing patients with differentiated thyroid cancer.MethodsWe performed a retrospective cohort study of 723 patients with WDTC (649 papillary and 79 follicular), evaluating the clinicopathologic profiles, ultrasound features, management received, tumor recurrence, and eventual outcome over a mean follow-up period of 5 years.ResultsThe mean age at diagnosis was 44±13 years (range, 18 to 82), with a majority of cases occurring in the younger age group (<45 years). Most tumors were between 2 and 4 cm in size. The majority of papillary thyroid cancers (PTCs, 63.2%) and follicular thyroid cancers (FTCs, 54.4%) initially presented as stage 1, with a greater proportion of FTC cases (12.7% vs. 3.7%) presenting with distant metastases. Nodal metastases at presentation were more frequent among patients with PTC (29.9% vs. 7.6%). A majority of cases were treated by complete thyroidectomy, followed by radioactive iodine therapy and thyroid stimulating hormone suppression, resulting in a disease-free state. Excluding patients with distant metastases at presentation, the recurrence rates for papillary and FTC were 30.1% and 18.8%, respectively.ConclusionOverall, PTC among Filipinos was associated with a more aggressive and recurrent behavior. FTC among Filipinos appeared to behave similarly with other racial groups.

Colchicum autumnale in Patients with Goitre with Euthyroidism or Mild Hyperthyroidism: Indications for a Therapeutic Regulative Effect-Results of an Observational Study.

Introduction. Goitre with euthyroid function or with subclinical or mild hyperthyroidism due to thyroid autonomy is common. In anthroposophic medicine various thyroid disorders are treated with Colchicum autumnale (CAU). We examined the effects of CAU in patients with goitre of both functional states. Patients and methods. In an observational study, 24 patients with goitre having suppressed thyroid stimulating hormone (TSH) levels with normal or slightly elevated free thyroxine (fT4) and free triiodothyronine (fT3) (group 1, n = 12) or normal TSH, fT3, and fT4 (group 2, n = 12) were included. After 3 months and after 6 to 12 months of CAU treatment, we investigated clinical pathology using the Hyperthyroid Symptom Scale (HSS), hormone status (TSH, fT4, and fT3), and thyroidal volume (tV). Results. After treatment with CAU, in group 1 the median HSS decreased from 4.5 (2.3–11.8) to 2 (1.3–3) (p < 0.01) and fT3 decreased from 3.85 (3.5–4.78) to 3.45 (3.3–3.78) pg/mL (p < 0.05). In group 2 tV (13.9% (18.5%–6.1%)) and TSH (p < 0.01) were reduced. Linear regression for TSH and fT3 in both groups indicated a regulative therapeutic effect of CAU. Conclusions. CAU positively changed the clinical pathology of subclinical hyperthyroidism and thyroidal volume in patients with euthyroid goitre by normalization of the regulation of thyroidal hormones.

Cardiac Effects of Thyrotropin Oversuppression with Levothyroxine in Young Women with Differentiated Thyroid Cancer.

Background. We investigated the cardiac effects of TSH (thyroid-stimulating hormone) oversuppression in women with thyroidectomized differentiated thyroid cancer (DTC) during levothyroxine suppression therapy. Methods. Fourteen young female patients with DTC were enrolled. The duration of TSH-suppressive therapy was 5 to 9 years. They satisfied the following criteria: (1) a serum level of TSH < 0.1 mU/L in the intermediate-risk or TSH < 0.3 mU/L in the low-recurrence-risk group and (2) having been receiving a fixed dose of LT4 before the study. Controls matched for age, sex, and body mass index (BMI) were compared in terms of the levels of serum free T4, free T3, TSH, plasma N-terminal pro-brain natriuretic peptide (NT-pro-BNP), and cardiac functions and structures. Results. DTC patients and control subjects were well matched in heart rate and blood pressure. There were marked differences in serum TSH (P = 0.001) and free T4 (P = 0.002). However, there were no differences between the groups in serum free T3 and plasma NT-pro-BNP. Furthermore, there were nonsignificant differences in cardiac functions and structures between the groups. Conclusions. This study shows that TSH suppression therapy in women with DTC may be safe with respect to cardiac functions and structures despite intermittent oversuppression of TSH during long-term suppressive therapy. Trial Registration. This trial is registered with clinicaltrials.gov identifier NCT02645786.

2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer.

Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. Since the American Thyroid Association's (ATA's) guidelines for the management of these disorders were revised in 2009, significant scientific advances have occurred in the field. The aim of these guidelines is to inform clinicians, patients, researchers, and health policy makers on published evidence relating to the diagnosis and management of thyroid nodules and differentiated thyroid cancer. The specific clinical questions addressed in these guidelines were based on prior versions of the guidelines, stakeholder input, and input of task force members. Task force panel members were educated on knowledge synthesis methods, including electronic database searching, review and selection of relevant citations, and critical appraisal of selected studies. Published English language articles on adults were eligible for inclusion. The American College of Physicians Guideline Grading System was used for critical appraisal of evidence and grading strength of recommendations for therapeutic interventions. We developed a similarly formatted system to appraise the quality of such studies and resultant recommendations. The guideline panel had complete editorial independence from the ATA. Competing interests of guideline task force members were regularly updated, managed, and communicated to the ATA and task force members. The revised guidelines for the management of thyroid nodules include recommendations regarding initial evaluation, clinical and ultrasound criteria for fine-needle aspiration biopsy, interpretation of fine-needle aspiration biopsy results, use of molecular markers, and management of benign thyroid nodules. Recommendations regarding the initial management of thyroid cancer include those relating to screening for thyroid cancer, staging and risk assessment, surgical management, radioiodine remnant ablation and therapy, and thyrotropin suppression therapy using levothyroxine. Recommendations related to long-term management of differentiated thyroid cancer include those related to surveillance for recurrent disease using imaging and serum thyroglobulin, thyroid hormone therapy, management of recurrent and metastatic disease, consideration for clinical trials and targeted therapy, as well as directions for future research. We have developed evidence-based recommendations to inform clinical decision-making in the management of thyroid nodules and differentiated thyroid cancer. They represent, in our opinion, contemporary optimal care for patients with these disorders.

Update on the treatment of hypothyroidism.

Differentiated thyroid cancer is a malignancy that is rapidly increasing in frequency. As thyroidectomy plays a central role in the treatment of thyroid cancer, it is incumbent on physicians treating this patient group to be well versed in the intricacies of treating hypothyroidism. Treatment of hypothyroidism may be refined by careful attention to dose selection, monitoring of therapy and achievement of thyrotropin goals that are specific to the individual patient's overall clinical situation. These goals are common not only to patients with a sole diagnosis of hypothyroidism, as discussed in the recent American Thyroid Association Guidelines, but also to patients with hypothyroidism in the setting of thyroid cancer. Several recent studies have illuminated our understanding of the benefits and risks of thyrotropin suppression therapy in patients with differentiated thyroid cancer. Multiple studies of combination therapy with levothyroxine and liothyronine for treating hypothyroidism have not led to a clear conclusion about its benefits over levothyroxine monotherapy. Animal studies have advanced our understanding of the altered serum and tissue milieu that characterizes levothyroxine monotherapy. Crossing the bridge from this translational research into clinical research using sustained release triiodothyronine preparations may ultimately enhance the health of our patients. Continued refinement of our understanding of thyroid status and our ability to flawlessly implement thyroid hormone replacement is an active area of research.

Effect of Thyrotropin Suppression Therapy on Bone in Thyroid Cancer Patients.

The thyroid cancer incidence is rising. Despite current guidelines, controversy exists regarding the degree and duration of thyrotropin suppression therapy. Also, its potential skeletal effects remain a concern to physicians caring for thyroid cancer patients. We conducted a review of published data to evaluate existing studies focusing on the skeletal effects of thyrotropin suppression therapy in thyroid cancer patients. A systematic search of the PubMed, Ovid/Medline, and Cochrane Central Register of Controlled Trials databases was conducted. The retained studies were evaluated for methodological quality, and the study populations were categorized into premenopausal women, postmenopausal women, and men. Twenty-five pertinent studies were included. Seven studies were longitudinal and 18 were cross-sectional. Of the 25 included studies, 13 were assigned an excellent methodological quality score. Three of 5 longitudinal studies and 3 of 13 cross-sectional studies reported decreased bone mineral density (BMD) in premenopausal women; 2 of 4 longitudinal studies and 5 of 13 cross-sectional studies reported decreased BMD in postmenopausal women. The remaining studies showed no effect on BMD. The only longitudinal study of men showed bone mass loss; however, cross-sectional studies of men did not demonstrate a similar effect. Studies to date have yielded conflicting results on the skeletal effects of thyrotropin suppression therapy and a knowledge gap remains, especially for older adults and men. Existing data should be cautiously interpreted because of the variable quality and heterogeneity. Identifying groups at risk of adverse effects from thyrotropin suppression therapy will be instrumental to providing focused and tailored thyroid cancer treatment. The standard treatment for thyroid cancer includes total thyroidectomy with or without radioactive iodine ablation, often followed by thyrotropin suppression therapy. Despite current guidelines, controversy exists regarding the degree and duration of thyrotropin suppression therapy, and discordant results have been reported on its adverse effects on bone. The present review provides physicians with existing data on the skeletal effects of thyrotropin suppression therapy, highlighting the need for further research to identify the groups at risk of adverse skeletal effects. This knowledge will aid in developing tailored thyroid cancer treatment.

The effect of thyroid stimulating hormone suppressive therapy on bone geometry in the hip area of patients with differentiated thyroid carcinoma

Subclinical hyperthyroidism has been reported to increase the fracture risk. However, the effect of thyroid stimulating hormone (TSH) suppressive therapy on bone geometry in the hip area of patients with differentiated thyroid carcinoma (DTC) is still unclear. The aim of this study was to investigate the effect of TSH suppression on bone geometry in the hip area of pre- and postmenopausal women with DTC.We conducted a retrospective cohort study including 99 women with DTC (25 pre- and 74 postmenopausal) who had received TSH suppressive therapy for at least 3years and 297 control subjects (75 and 222, respectively) matched for sex and age. Bone mineral density (BMD) in the spine and hip area and bone geometry at the femoral neck measured by dual energy X-ray absorptiometry (DXA) were compared between patients and controls. The association between thyroid hormone and bone parameters was investigated. All analyses of bone parameters were adjusted for age, body mass index, and serum calcium levels.In premenopausal subjects, TSH suppressive therapy was not associated with poor bone parameters. In postmenopausal subjects, patients with DTC undergoing TSH suppression showed lower cross-sectional moment of inertia (CSMI), cross-sectional area, and section modulus and thinner cortical thickness at the femoral neck than those of control subjects, whereas their femoral neck BMD was comparable with controls. Total hip BMD was lower in postmenopausal patients than in controls. CSMI and section modulus at the femoral neck were independently associated with serum free T4 levels in postmenopausal patients. The difference in femoral neck bone geometry between patients and controls was only apparent in postmenopausal DTC patients with free T4 >1.79ng/dL (23.04pmol/l), and not in those with free T4 levels ≤1.79ng/dL (23.04pmol/l).TSH suppression in postmenopausal DTC patients was associated with decreased bone strength by altering bone geometry rather than BMD in the hip area, especially the femoral neck. This alteration in bone quality was observed only in patients with free T4 levels above the upper normal limit.

Clinical Usefulness of F-18 FDG PET/CT in Papillary Thyroid Cancer with Negative Radioiodine Scan and Elevated Thyroglobulin Level or Positive Anti-thyroglobulin Antibody.

Elevated thyroglobulin (Tg) levels, along with a negative radioiodine scan, present a clinical problem for the diagnosis of recurrence in papillary thyroid cancer (PTC) patients. The purpose of this study was to assess (1) the usefulness of (18)F-fluorodeoxyglucose (F-18 FDG) positron emission tomography (PET)/computed tomography (CT) for PTC patients with negative diagnostic radioiodine scan and elevated serum Tg level or positive anti-thyroglobulin antibody (TgAb), and (2) the effect of endogenous thyroid stimulating hormone (TSH) stimulation (ETS) on detecting recurrence in these circumstances. Eighty-four patients with negative diagnostic radioiodine scan and elevated serum Tg or positive TgAb under ETS were included. Correlation with clinicopathological features and recurrence, detectability of FDG PET/CT and cut-off value of serum Tg for recurrence in PTC patients with these circumstance were assessed. In addition, detectability of F-18 FDG PET/CT under ETS and suppression were compared. In Cox regression analysis, only serum Tg level was significantly associated with recurrence (P < 0.001, HR = 1.13; 95% CI, 1.061-1.208). The cut-off level of Tg was 21.5ng/mL (AUC, 0.919; P < 0.001) for discriminating the recurrence in the patients with positive PET/CT finding. The sensitivity, specificity, PPV, NPV, and accuracy of F-18 FDG PET/CT for detecting recurrence were 64%, 94%, 86%, 81%, and 83%. In the analysis of F-18 FDG PET/CT under ETS, the sensitivity, specificity, PPV, NPV and accuracy was 64%, 94%, 88%, 81% and 83%. Those under TSH suppression were 67%, 92%, 80%, 85% and 83%. F-18 FDG PET/CT, although less sensitive, showed high specificity, PPV, NPV, and accuracy and therefore can be useful for the patients with negative diagnostic radioiodine scan and elevated serum Tg or positive TgAb. In addition, FDG PET/CT under ETS does not seem to have an additive role in detecting recurrence in these patients.

The Role of Adjuvant External Beam Radiation Therapy for Papillary Thyroid Cancer Invading the Trachea: A Single-Institution Study

The Role of Adjuvant External Beam Radiation Therapy for Papillary Thyroid Cancer Invading the Trachea: A Single-Institution Study

Moans, Bones, Groans, and a Thyroid Mass

Parathyroid carcinoma accounts for less than 1 per cent of cases of primary hyperparathyroidism.1, 2 Its synchronous occurrence with thyroid carcinoma is rarer still, with only seven such patients previously reported in the literature.3, 4 We report another case, unique not only because the parathyroid carcinoma was found within the left thyroid lobe but also because of the presence of a synchronous papillary thyroid carcinoma within the contralateral thyroid lobe. The case illustrates the need for surgeons to be aware of the possibility of concomitant thyroid pathology and the potential for the synchronous occurrence of other endocrine neoplasms. Our case is a 56-year-old female who presented with hypercalcemia, complaints of pain in her left shoulder and hip and a history of recurrent kidney stones over a period of several months. One year prior to the present admission she had undergone an extensive workup for an intrathyroidal lesion located within the central aspect of the left thyroid lobe and for bilateral adrenal incidentalomas measuring 4.3 cm on the right and 1.7 cm on the left. Fine-needle aspiration biopsy of the thyroid nodule revealed parathyroid tissue. Biopsy of the larger of the two adrenal lesions was negative for malignancy. At that time she had bilateral ureteral stents placed for obstructive uropathy. She was discharged with instructions to follow up after recovery from her ureteral stenting to undergo resection of her presumed intrathyroidal parathyroid adenoma. She subsequently was readmitted because of worsening bone pain. On her subsequent presentation, physical examination her of head, neck, and cervical nodal basins were normal. Laboratory evaluations revealed hypercalcemia with a serum level of 12.2 mg/dL and a parathyroid hormone (PTH) level of 1246 pg/mL. Radiological imaging confirmed pyelocalyectasis from an obstructed stent in her left ureter and areas of osteitis fibrosa cystica in her left iliac crest and left humeral head. She was treated with intravenous saline infusion, diuresis, and cinacalcet (Sensipar™, Amgen™, Thousand Oaks, CA) to acutely control her hypercalcemia. A percutaneous nephrostomy tube was placed within the left renal pelvis and replacement of both ureteral stents were performed to relieve her recurrent obstructive uropathy. Ultrasound demonstrated two lesions in the thyroid: a solid 5.6 × 3 × 3.4 cm mass in the left lobe and a 1.4-cm hypoechoic lesion in the central aspect of the right lobe. A Single-photon emission computed tomography (SPECT-CT) study demonstrated the presence of an intrathyroidal mass within the left lobe with imaging characteristics consistent with parathyroid tissue (Fig. 1A and B). A 24-hour urine for metanephrines and vanillylmandelic acid were within normal limits. Fig. 1 SPECT-CT Scan, (A) Nuclear parathyroid imaging. (B) Tracer accumulation in left thyroid bed. She underwent total thyroidectomy and biopsy of the remaining three parathyroid glands. The right thyroid lobe contained a firm mass surrounded by a sclerotic capsule and frozen section confirmed the mass in the right lobe to be a follicular variant of papillary thyroid carcinoma. Pathology also confirmed intrathyroidal parathyroid carcinoma in the left lobe. A bilateral central compartment neck dissection was then performed. Final pathological examination confirmed the presence of both carcinomas, and demonstrated nodal metastases of papillary carcinoma to the right paratracheal lymph nodes. Intraoperative PTH determinations were obtained and demonstrated a drop from a preexcision level of 3300 pg/mL to a steady state value of 259 pg/mL at 60 minutes. The patient was scheduled to receive radioactive I131 ablation and was given levothyroxine at a dose sufficient to achieve thyroid-stimulating hormone suppression due to her nodal metastases. She underwent periodic measurements of serum calcium and PTH for follow-up of her parathyroid carcinoma. In addition, laparoscopic resection of her 4.3-cm nonfunctioning adrenal incidentaloma is planned, as is close follow-up of the contralateral smaller adrenal lesion to ensure benign biologic behavior. Parathyroid carcinoma, itself a rare tumor may be very rarely accompanied by synchronous thyroid cancer. More commonly parathyroid carcinoma may coexist with another parathyroid disease process, such as a parathyroid adenoma, hyperplasia, or a second parathyroid carcinoma.1–4 Our case of synchronous thyroid and parathyroid carcinomas is only the eighth such case reported3–4 (Table 1), and the first to coexist with bilateral adrenal incidentalomas. The spectrum of endocrine neoplasms encountered in this patient suggests the possibility that she has a genetic predilection for the development of endocrine neoplasia, albeit not the classically described syndromes of multiple endocrine neoplasia 1 or 2. Table 1 Previous Reported Cases of Synchronous Thyroid and Parathyroid Carcinoma

Management Guidelines for Children with Thyroid Nodules and Differentiated Thyroid Cancer.

Previous guidelines for the management of thyroid nodules and cancers were geared toward adults. Compared with thyroid neoplasms in adults, however, those in the pediatric population exhibit differences in pathophysiology, clinical presentation, and long-term outcomes. Furthermore, therapy that may be recommended for an adult may not be appropriate for a child who is at low risk for death but at higher risk for long-term harm from overly aggressive treatment. For these reasons, unique guidelines for children and adolescents with thyroid tumors are needed. A task force commissioned by the American Thyroid Association (ATA) developed a series of clinically relevant questions pertaining to the management of children with thyroid nodules and differentiated thyroid cancer (DTC). Using an extensive literature search, primarily focused on studies that included subjects ≤18 years of age, the task force identified and reviewed relevant articles through April 2014. Recommendations were made based upon scientific evidence and expert opinion and were graded using a modified schema from the United States Preventive Services Task Force. These inaugural guidelines provide recommendations for the evaluation and management of thyroid nodules in children and adolescents, including the role and interpretation of ultrasound, fine-needle aspiration cytology, and the management of benign nodules. Recommendations for the evaluation, treatment, and follow-up of children and adolescents with DTC are outlined and include preoperative staging, surgical management, postoperative staging, the role of radioactive iodine therapy, and goals for thyrotropin suppression. Management algorithms are proposed and separate recommendations for papillary and follicular thyroid cancers are provided. In response to our charge as an independent task force appointed by the ATA, we developed recommendations based on scientific evidence and expert opinion for the management of thyroid nodules and DTC in children and adolescents. In our opinion, these represent the current optimal care for children and adolescents with these conditions.

The Efficacy of Thyrotropin Suppression Therapy in Treatment of Differentiated Thyroid Cancer after Total Thyroidectomy

Abstract Background: The aim of this prospective study was to assess the effect of the TSH suppression on both disease-free and overall survivals in patients with nonmetastatic differentiated thyroid cancer (DTC) after total thyroidectomy. Patients &amp; Methods: One hundred and forty eight patients with pathologically proved operable differentiated thyroid carcinoma were enrolled in this prospective study. Levothyroxin (L-T4) therapy was started in doses according to treatment groups. Patients were randomly assigned to receive either postoperative TSH suppression therapy in group I (76 patients) or nonsuppression therapy in group II (72 patients). Results: During the period of follow up with a median 54 months, the disease-free survival for patients without TSH suppression therapy did not reach statistically significant difference comparing with those for patients with the suppression therapy (p=0.09). However, the difference was statistically significant for high-risk patients (p=0.04). On comparing both groups there was no statistically significant difference with regard to overall survival (p=0.17). The age of the patients more than 45 years, tumour size more than 4 cm and high-risk group were significant independent predictors for thyroid carcinoma-related relapse in univariate analysis. However, tumour size was the only significant factor in multivariate analysis. Conclusion: Suppressive treatment with L-T4 therapy in patients with differentiated thyroid carcinoma should be individualised and balanced against the adverse effects. TSH suppression is indicated in patients with high-risk disease or recurrent tumour. Normalisation of serum TSH is preferred for long-term treatment of disease-free elderly patients with DTC and comorbidities.

Well-differentiated thyroid cancer: the Philippine General Hospital experience

the clinicopathologic profiles, ultrasound features, management received, tumor recurrence, and eventual outcome over a mean follow-up period of 5 years. Results: The mean age at diagnosis was 44±13 years (range, 18 to 82), with a majority of cases occurring in the younger age group (<45 years). Most tumors were between 2 and 4 cm in size. The majority of papillary thyroid cancers (PTCs, 63.2%) and follicular thyroid cancers (FTCs, 54.4%) initially presented as stage 1, with a greater proportion of FTC cases (12.7% vs. 3.7%) presenting with distant metastases. Nodal metastases at presentation were more frequent among patients with PTC (29.9% vs. 7.6%). A majority of cases were treated by complete thyroidectomy, followed by radioactive iodine therapy and thyroid stimulating hormone suppression, resulting in a disease-free state. Excluding patients with distant metastases at presentation, the recurrence rates for papillary and FTC were 30.1% and 18.8%, respectively. Conclusion: Overall, PTC among Filipinos was associated with a more aggressive and recurrent behavior. FTC among Filipinos appeared to behave similarly with other racial groups.

Serum Thyroglobulin Measured With a Second-Generation Assay in Patients Undergoing Total Thyroidectomy Without Radioiodine Remnant Ablation: A Prospective Study

Follow-up consisting of the measurement of nonstimulated serum thyroglobulin (Tg) combined with neck ultrasonography is recommended for patients with papillary thyroid carcinoma without indication for radioiodine ablation. There is no recommendation of thyrotropin suppression during this follow-up. New-generation Tg assays have been increasingly used, but few studies involve patients submitted only to thyroidectomy and they have several limitations. The objective of this prospective study was to define expected concentrations of nonstimulated Tg measured with a second-generation assay after total thyroidectomy in the absence of tumor. Serum Tg was measured using a second-generation assay in 69 patients without tumor and serum thyrotropin between 0.5 and 2 mIU/L, 3, 6, 12, and 24 months after total thyroidectomy. All patients had undetectable anti-Tg antibodies. Serum Tg was undetectable in 44.4%, 57%, 62.5%, and 62.1% of the patients 3, 6, 12, and 24 months after thyroidectomy, respectively, and was ≤0.5 ng/mL in 60.3%, 80%, 90.6%, and 90.9% of patients. All patients had a Tg≤2 ng/mL 6 months after thyroidectomy, and 97% had a Tg≤1 ng/mL 24 months after surgery. There was no case of Tg conversion from undetectable to detectable and none of the patients presented an increase in Tg. An important decline in serum Tg occurred between 3 and 6 months after total thyroidectomy. One year after surgery, Tg was undetectable in approximately 60% of the patients and was ≤2 ng/mL in all of them.

Thyroid stimulating hormone suppression post-therapy in patients with Graves' disease: a systematic review of pathophysiology and clinical data.

Post-treatment hypothyroidism is common in Graves' disease, and clinical guidelines recommend monitoring for it; however, thyroid stimulating hormone (TSH) can remain suppressed in these patients following treatment. The objectives of this study were to explore the proposed pathophysiology behind the phenomenon of post-therapy TSH suppression and to systematically review existing clinical data on post-therapy TSH suppression in patients with Graves' disease. A systematic literature search was performed using EMBASE and PubMed databases, with several combinations of MeSH terms. Bibliography mining was also done on relevant articles to be as inclusive as possible. A total of 18 articles described possible mechanisms for post-therapy TSH suppression. Several of the studies demonstrate evidence of thyrotroph atrophy and hypothesize that this contributes to the ongoing suppression. TSH receptors have been identified in folliculo-stellate cells of the pituitary as well as astroglial cells of the hypothalamus, mediating paracrine feedback. A few studies have demonstrated inverse correlation between autoantibody titres and TSH levels, suggestive of their role in mediating ongoing TSH suppression in patients with Graves' disease. In addition, five studies were identified that provided clinical data on the duration of TSH suppression. Combined data show that 45.5% of patients recover TSH by 3 months after treatment, increasing to 69.3% by 6 months, and plateauing to 73.8% by 12 months (p>0.0001). Sub-analysis also shows that for patients who are TBII negative, 80.7% recover their TSH by 6 months compared with only 58.7% in those who are TBII positive (p= 0.003). Clinical data suggests that TSH recovery is most likely to occur within the first 6 months after treatment, with recovery plateauing at approximately 70% of patients, suggesting that reliance on this assay for monitoring can be very misleading. Furthermore, TBII positivity is associated with lower likelihood of TSH recovery. Pathophysiology behind suppressed TSH involves not only anatomical but also autoimmune mechanisms.

Guía clínica para el manejo de pacientes con carcinoma diferenciado de tiroides de bajo riesgo

Incidence of thyroid cancer is increasing in Spain and worldwide. Overall thyroid cancer survival is very high, and stratification systems to reliably identify patients with worse prognosis have been developed. However, marked differences exist between the different specialists in clinical management of low-risk patients with thyroid carcinoma. Almost half of all papillary thyroid carcinomas are microcarcinomas, and 90% are tumors < 2cm that have a particularly good prognosis. However, they are usually treated more aggressively than needed, despite the lack of adequate scientific support. Surgery remains the gold standard treatment for these tumors. However, lobectomy may be adequate in most patients, without the need for total thyroidectomy. Similarly, prophylactic lymph node dissection of the central compartment is not required in most cases. This more conservative approach prevents postoperative complications such as hypoparathyroidism or recurrent laryngeal nerve injury. Postoperative radioiodine remnant ablation and strict suppression of serum thyrotropin, although effective for the more aggressive forms of thyroid cancer, have not been shown to be beneficial for the treatment of low risk patients, and may impair their quality of life. This guideline provides recommendations from the task force on thyroid cancer of the Spanish Society of Endocrinology and Nutrition for adequate management of patients with low-risk thyroid cancer.

Diagnostic value of thyroglobulin measurement with fine-needle aspiration biopsy for lymph node metastases in patients with a history of differentiated thyroid cancer.

The aim of this study was to evaluate the diagnostic value of FNA-Tg for detecting lymph node metastases in patients with a history of differentiated thyroid cancer (DTC). A total of 58 patients with DTC diagnosis and evidence of single or multiple suspicious cervical lymph nodes were assessed. All underwent total or near-total thyroidectomy with (35 cases) or without (23 cases) radioiodine (RAI) ablation, followed by thyroid stimulating hormone (TSH) suppression therapy. A total of 68 lymph nodes were examined by ultrasound-guided fine needle aspiration (US-FNA) for both cytological examination and FNA-Tg measurement. Serum Tg and anti-thyroglobulin antibody (TgAb) levels were also measured. Diagnostic performance including sensitivity, specificity, accuracy, positive (PPV) and negative predictive value (NPV) of FNAC and FNA-Tg were calculated and compared. The Spearman's rank correlation coefficient was used to estimate the relationship between FNA-Tg and serum TgAb. The FNA-Tg levels were significantly higher with DTC metastatic lymph nodes (median 927.7 ng/mL, interquartile range 602.9 ng/mL) than non-metastatic lymph nodes (median 0.1 ng/mL, interquartile range 0.4 ng/mL) (p<0.01). Considering 1.0 ng/mL as a threshold value for FNA-Tg, the sensitivity, specificity, accuracy, PPV and NPV of FNA-Tg were 95.7%, 95.5%, 95.6%, 97.8% and 91.3%, respectively. The sensitivity and accuracy of the combination of FNAC and FNA-Tg were significantly higher than that of FNAC alone (p<0.05). The diagnostic performance of FNA-Tg was not significantly different between cases with or without RAI ablation, and the serum TgAb levels did not interfere with FNA-Tg measurements. Measurement of FNA-Tg is useful. The combination of FNAC and FNA-Tg is more sensitive and accurate for detecting lymph node metastases in patients with a history of DTC than FNAC alone. Serum TgAbs appear to be irrelevant for measurement of FNA-Tg.

Ability of the rhTSH stimulation test to predict relapse in patients with differentiated thyroid carcinoma, after long-term follow-up.

The analysis of serum thyroglobulin (Tg) following thyroid-stimulating hormone (TSH) stimulation (sTg) has been recommended in the follow-up of differentiated thyroid carcinoma (DTC) patients, however, its routine use remains controversial. The aim of the current study was to evaluate the accuracy of sTg testing following recombinant human (rh) TSH stimulation in DTC patients, with a follow-up of 12.4 years. Retrospective studies were conducted of 125 DTC patients, who underwent rhTSH stimulation testing between 1999 and 2002. The exclusion criteria were: Patients with anti-Tg antibodies, Tg levels >1 ng/ml under TSH suppression and the absence of radioactive iodine (RAI) ablation therapy following surgery. In total, 49 patients were included in the study and all had been previously treated with total or near total thyroidectomy (with or without central neck dissection) and RAI, postoperatively. The Tg functional sensitivity was 1.0 ng/ml. The follow-up for patients was performed annually. During the median follow-up of 12.4 years after the rhTSH stimulation test, nine patients exhibited recurrence (18.4%). Of the nine patients, six exhibited sTg levels >2 ng/ml (positive result) and three exhibited levels <2 ng/ml (negative result). Relapse occurred at a mean of 5.9 years following the rhTSH stimulation test. The positive predictive value and negative predictive value (NPV) of positive sTg were 50 and 91.9%, respectively, with a sensitivity of 66.6% and a specificity of 85.0%. The rhTSH-stimulated Tg levels have a high NPV, allowing the identification of the patients who are free of the tumour. These results are consistent with the previously published data; however, to the best of our knowledge, this is the study with the longest follow-up duration after rhTSH stimulation.

Weight Changes in Patients with Differentiated Thyroid Carcinoma during Postoperative Long-Term Follow-up under Thyroid Stimulating Hormone Suppression.

BackgroundThere are limited data about whether patients who receive initial treatment for differentiated thyroid cancer (DTC) gain or lose weight during long-term follow-up under thyroid stimulating hormone (TSH) suppression. This study was aimed to evaluate whether DTC patients under TSH suppression experience long-term weight gain after initial treatment. We also examined the impact of the radioactive iodine ablation therapy (RAIT) preparation method on changes of weight, comparing thyroid hormone withdrawal (THW) and recombinant human TSH (rhTSH).MethodsWe retrospectively reviewed 700 DTC patients who underwent a total thyroidectomy followed by either RAIT and levothyroxine (T4) replacement or T4 replacement alone. The control group included 350 age-matched patients with benign thyroid nodules followed during same period. Anthropometric data were measured at baseline, 1 to 2 years, and 3 to 4 years after thyroidectomy. Comparisons were made between weight and body mass index (BMI) at baseline and follow-up.ResultsSignificant gains in weight and BMI were observed 3 to 4 years after initial treatment for female DTC but not in male patients. These gains among female DTC patients were also significant compared to age-matched control. Women in the THW group gained a significant amount of weight and BMI compared to baseline, while there was no increase in weight or BMI in the rhTSH group. There were no changes in weight and BMI in men according to RAIT preparation methods.ConclusionFemale DTC patients showed significant gains in weight and BMI during long-term follow-up after initial treatment. These changes were seen only in patients who underwent THW for RAIT.

Pediatric Graves’ Disease

Graves' disease is the most common cause of hyperthyroidism in children. It is characterized by suppressed thyroid stimulating hormone and elevated thyroxine levels with varying levels of thyroid stimulating immunoglobulins; and evidence of increased iodine uptake on thyroid scan. It is a multisystem disease with interplay of genetics and environmental factors. Due to the insidious onset of symptoms, diagnosis is often delayed leading to poor growth and development. The disorder could present at any age including neonatal period due to transfer of maternal antibodies in context of maternal Graves' disease. Herein, we review the current literature for Graves' disease affecting children and adolescents.