Thyroid-stimulating Hormone Suppressive Therapy Research Articles

Case report: fast reversal of severe osteoporosis after correction of excessive levothyroxine treatment and long-term follow-up

SummaryThis case report describes a 38-year-old woman, who presented with bilateral femoral stress fractures and osteoporosis after years of excessive levothyroxine treatment. Her bone health was restored rapidly and long-lasting with the reduction of levothyroxine dosage. No bone-active treatment was warranted.IntroductionHyperthyroidism is a known risk factor for osteoporosis and fractures. Recent studies on patients with serum thyrotropin-suppressive therapy have not, however, indicated adverse effects on bone during long-term follow-up.MethodsThis case report describes long-term follow-up data of a clinically euthyreoid patient, who developed symptomatic osteoporosis due to excessive levothyroxine treatment.ResultsAfter correction of levothyroxine dosage, her bone mineral density (BMD) and previously elevated serum osteocalcin levels normalized rapidly and she remained free from fractures during 23 years of follow-up over menopause.ConclusionExcessive TSH suppression contributed to the secondary osteoporosis in this patient; BMD normalized after dose reduction of levothyroxine and no fractures occurred during 23 years’ follow-up. Some patients develop severe osteoporosis if they are over-substituted with levothyroxine, and decent follow-up of patients with levothyroxine supplementation is mandatory.

Preoperative serum thyroglobulin and changes in serum thyroglobulin during TSH suppression independently predict follicular thyroid carcinoma in thyroid nodules with a cytological diagnosis of follicular lesion

ABSTRACTBackground: Fine-needle aspiration biopsy (FNAB) cannot distinguish a follicular thyroid carcinoma (FTC) from a follicular adenoma in follicular lesions. We designed this study to determine whether the preoperative thyroglobulin (Tg) and change in serum Tg during thyroid-stimulating hormone (TSH) suppression can predict FTC in thyroid nodules with a cytological diagnosis of follicular lesion. Methods: Among 854 patients who underwent thyroid surgery, the 198 patients who presented with thyroid nodules with a cytological diagnosis of follicular lesion were analyzed. Predictive factors for malignancy were evaluated using multivariate logistic regression models. Subgroup analyses of patients with TSH suppression therapy by levothyroxine were also conducted. Results: Thirty-two patients (16%) had FTC, and 166 patients had confirmed benign nodules. The median preoperative serum Tg levels were significantly higher in patients with FTC compared to those with benign pathology (449 vs. 34 ng/mL, p < 0.001). The serum Tg (odds ratios (OR) 10.311, p < 0.001) and tumor volume (OR 4.500, p = 0.035) were found to be independent predictors for FTC in all patients with a cytological diagnosis of follicular lesion. Forty-eight patients received TSH suppression therapy. When we performed subgroup analyses on the patients with TSH suppression therapy, decrease less than 15% in serum Tg during TSH suppression was found to be an independent predictor of FTC (OR 13.918, p = 0.018). Conclusion: Preoperative serum Tg and changes in serum Tg during TSH suppression independently predict FTC in thyroid nodules with a cytological diagnosis of follicular lesion.

The Effect of TSH Suppression on Vertebral Trabecular Bone Scores in Patients With Differentiated Thyroid Carcinoma.

The effect of thyrotropin (TSH) suppressive therapy on trabecular bone scores (TBSs) is unclear. The aim of this study was to investigate the effect of TSH suppression on vertebral TBSs of postmenopausal women with differentiated thyroid carcinoma (DTC). We conducted a retrospective cohort study including 273 postmenopausal women with DTC who had received TSH suppressive therapy. Bone mineral density (BMD) and TBSs at the lumbar spine were analyzed using dual-energy X-ray absorptiometry (DXA). The association between the parameters of TSH suppressive therapy and bone parameters was investigated. Study subjects showed upper-normal free thyroxine levels and suppressed TSH at DXA evaluation. The mean duration of TSH suppression was 4.4 ± 2.9 years. Serum free T4 and TSH were not independently associated with lumbar spine BMD or TBS levels. Duration of TSH suppression was negatively correlated with lumbar spine TBS levels, but not with BMD. Longer duration of TSH suppression was independently associated with lower lumbar spine TBSs after adjusting for age, body mass index (BMI), and BMD. Lumbar spine TBSs were significantly lower in patients whose duration of TSH suppression was ≥5 years compared with those whose duration was <3 years after adjusting for age, BMI, and BMD. Longer duration of TSH suppression in postmenopausal DTC patients was associated with decreased vertebral bone strength by altering TBSs rather than BMD. TBSs should be considered when estimating vertebral bone fragility in postmenopausal DTC patients receiving long-term TSH suppressive therapy.

Consensus on the management of advanced radioactive iodine-refractory differentiated thyroid cancer on behalf of the Spanish Society of Endocrinology Thyroid Cancer Working Group (GTSEEN) and Spanish Rare Cancer Working Group (GETHI)

Thyroid cancer is the single most prevalent endocrine malignancy; differentiated thyroid cancer (DTC) accounts for more than 90% of all malignancies and its incidence has been rising steadily. For more patients, surgical treatment, radioactive iodine (RAI) ablation, and thyroid-stimulating hormone (TSH) suppressive therapy achieve an overall survival (OS) rate of 97.7% at 5years. Nevertheless, locoregional recurrence occurs in up to 20% and distant metastases in approximately 10% at 10years. Two-thirds of these patients will never be cured with radioactive iodine therapy and will become RAI-refractory, with a 3-year OS rate of less than 50%. Over the last decade, substantial progress has been made in the management of RAI-refractory DTC. Given the controversy in some areas, the Spanish Task Force for Thyroid Cancer on behalf of Spanish Society of Endocrinology Thyroid Cancer Working Group (GTSEEN) and the Spanish Rare Cancer Working Group (GETHI) have created a national joint task force to reach a consensus addressing the most challenging aspects of management in these patients. In this way, multidisciplinary management should be mandatory and nuclear medicine targeted therapy, novel molecular targeted agents, and combinations are currently changing the natural history of RAI-refractory DTC.

Treatment of papillary thyroid microcarcinoma

The recent development and wide application of ultrasonography and ultrasonography-guided fine needle aspiration biopsy have greatly facilitated the detection of papillary thyroid microcarcinoma (PTMC). Currently, the occurrence, development and pathological features of PTMC are not clearly understood. Therefore, no consensus on the diagnosis and treatment has been reached. Patients with PTMC are suggested to be closely observed and periodically examined with ultrasonography in some countries such as Japan, and these patients are to be operated when the tumor enlarged or new lymphatic metastasis are found. Operation is the first choice in the European and American countries, and the long-term survival rates of these patients are nearly 100%. For the PTMC patients with the risk factors such as thyroid capsule invasion, lymphatic metastasis, multi-focal lesion, higher degree of malignancy, thyroid stimulating hormone suppression therapy was given after operation, which may reduce the local recurrence rate. In China, we should hold well the limitation and choose the best way for different patients according to the personalized principle in clinical practice. Key words: Thyroid neoplasms; Carcinoma, papillary; Observation; Surgical procedures, operative; Prognosis

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.

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.

Effects of suppressive therapy of thyroid-stimulating hormone on emotion status in elderly patients

Objective To analyze the effects of suppressive therapy of thyroid-stimulating hormone(TSH) on emotion status in elderly patients undergoing resection of differentiated thyroid cancer (DTC). Methods Serum levels of free T3 (FT3), free T4 (FT4) and TSH were measured in elderly patients. 165 patients were enrolled, in whom 74 cases with DTC underwent complete resection and TSH suppressive therapy 〔completely (CSG, n=33) and partially (PSG, n=41)〕, 43 cases with nodular goiter without TSH suppressive therapy (WSG) underwent bilateral subtotal thyroidectomy and 48 cases had normal thyroid function (normal control group, NCG). Hamilton Anxiety Rating Scale (HAMA) and Hamilton Depression Rating Scale (HAMD) were used to evaluate patients' emotion status. Results There were significant differences in scores of HAMA between CSG and other three groups 〔PSG (P<0.05), WSG (P<0.01) and NCG (P<0.01)〕. However, there was no significant difference in HAMD scores among the four groups. Serum levels of TSH and FT4 were associated with the total scores of HAMA in CSG (both P<0.05). Conclusions The elderly patients in TSH completely suppressive group have more severe anxiety symptoms than the other groups, and their anxiety symptoms are correlated with thyroid dysfunction. The anxiety symptoms may be relieved by adjusting the TSH suppressive levels properly after DTC in elderly patients. Key words: Thyroid neoplasms; Thyrotropin; Anxiety; Emotional disorders

New therapies for dedifferentiated papillary thyroid cancer.

The number of thyroid cancers is increasing. Standard treatment usually includes primary surgery, thyroid-stimulating hormone suppressive therapy, and ablation of the thyroid remnant with radioactive iodine (RAI). Despite the generally good prognosis of thyroid carcinoma, about 5% of patients will develop metastatic disease, which fails to respond to RAI, exhibiting a more aggressive behavior. The lack of specific, effective and well-tolerated drugs, the scarcity of data about the association of multi-targeting drugs, and the limited role of radioiodine for dedifferentiated thyroid cancer, call for further efforts in the field of new drugs development. Rearranged during transfection (RET)/papillary thyroid carcinoma gene rearrangements, BRAF (B-RAF proto-oncogene, serine/threonine kinase) gene mutations, RAS (rat sarcoma) mutations, and vascular endothelial growth factor receptor 2 angiogenesis pathways are some of the known pathways playing a crucial role in the development of thyroid cancer. Targeted novel compounds have been demonstrated to induce clinical responses and stabilization of disease. Sorafenib has been approved for differentiated thyroid cancer refractory to RAI.

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.

3,3'-Diiodothyronine Concentrations in Hospitalized or Thyroidectomized Patients: Results from a Pilot Study

To determine if various medical conditions affect the serum concentrations of 3,3'-diiodothyronine (3,3'-T2). A total of 100 patients who were recruited from a group of inpatients and outpatients with a diverse range of medical conditions, donated a single blood sample that was assayed for thyroid hormone derivatives using liquid-chromatography tandem mass spectrometry (LC-MS/MS). The associations between 3,3'-T2 concentrations and physiologic data and medical conditions were assessed. Higher quartiles of 3,3'-T2 concentrations (quartile 1: 2.01-7.48, quartile 2: 7.74-12.4, quartile 3: 12.5-17, quartile 4: 17.9-45.8 pg/mL) were associated with decreasing occurrence of critical illness (58%, 11%, 0%, 8%), stroke (29%, 7.7%, 4%, 0%), critical care unit hospitalization (75%, 39%, 8.3 %, 12%), and inpatient status (83%, 42%, 8%, 12%) (all P<.001). The same quartiles were associated with increasing frequency of thyroidectomy (4%, 12%, 17%, 60%). In multivariate analyses, after adjustment for age and sex, inpatient status was associated with decreasing concentrations of 3,3'-T2 (46% decrease for inpatients with 95% confidence interval [CI] 32-57%, P<.0001). Thyroidectomy was associated with increasing concentrations of 3,3'-T2 (29% increase (CI 0.5-66%, P = .049). We observed associations between inpatient status and reduced 3,3'-T2 concentrations. This appears to be a global change associated with illness, rather than an association with specific medical conditions. We also observed higher 3,3'-T2 concentrations in athyreotic outpatients receiving thyroid-stimulating hormone (TSH) suppression therapy. This demonstrates that there is production of 3,3'-T2 from levothyroxine (LT4) in extrathyroidal tissues. Conversion of thyroxine (T4) to 3,3'-T2 via both triiodothyronine (T3) and reverse triiodothyronine (rT3) pathways may prevent excessive T3 concentrations in such patients.

The effect of long-term thyroid-stimulating hormone suppressive therapy on the cognitive function of elderly patients with differentiated thyroid carcinoma.

Several studies have evidenced the association between subclinical hyperthyroidism and cognitive impairment in the elderly. However, the effect of long-term TSH suppressive therapy on the cognitive function in elderly patients with differentiated thyroid carcinoma (DTC) is still unclear. Our aim was to investigate the effect of long-term TSH suppression on the cognitive function of elderly patients with DTC. A cross-sectional case-control study including 50 DTC patients aged 65 years or older (mean age 70.9 ± 5.0 y) who have received a TSH-suppressive therapy for at least 5 years and 90 control subjects matched for age, sex, education period, and depressive mood was conducted. Major Outcome Measure: Comprehensive cognitive domains were compared between the patient and control groups. The association between serum thyroid hormone concentration and cognitive function was investigated. The patient group had higher serum free T4 levels and suppressed TSH levels compared with the control group. Age, sex, education period, the Korean version of the Geriatric Depression Scale scores, and Cumulative Illness Rating Scale scores were not different between the 2 groups. All assessed neuropsychiatric tests were comparable in both groups. In the patient group, those with higher serum free T4 levels performed better on Mini-Mental State Examination and Trail Making Test A. The association between serum free T4 and Trail Making Test A was maintained after adjusting for age, education period, the Korean version of the Geriatric Depression Scale, and Cumulative Illness Rating Scale. In the control group, serum free T4 and TSH levels were not associated with any of the assessed cognitive domains. Our results demonstrated the safety of long-term TSH suppression on the cognitive function in elderly DTC patients. Furthermore, the positive correlations between serum free T4 levels and some cognitive domains suggest the potential beneficial effects of exogenous levothyroxine on the cognitive function of patients who lack endogenous thyroid hormone.

Personalization of targeted therapy in advanced thyroid cancer.

Although generally the prognosis of differentiated thyroid carcinoma (DTC) is good, approximately 5% of people are likely to develop metastases which fail to respond to radioactive iodine, and other traditional therapies, exhibiting a more aggressive behavior. Nowadays, therapy is chosen and implemented on a watch-and-wait basis for most DTC patients. Which regimen is likely to work best is decided on the basis of an individual’s clinical information, but only data referring to outcomes of groups of patients are employed. To predict the best course of therapy, an individual patient’s biologic data is rarely employed in a systematic way. Anyway, the use of not expensive individual genomic analysis could lead us to a new era of patient-specific and personalized care. Recently, key targets that are now being evaluated in the clinical setting have been evidenced in the pathogenesis of these diseases. Some of the known genetic alterations playing a crucial role in the development of thyroid cancer include B-Raf gene mutations, rearranged during transfection/ papillary thyroid carcinoma gene rearrangements, and vascular endothelial growth factor receptor-2 angiogenesis pathways. The development of targeted novel compounds able to induce clinical responses and stabilization of disease has overcome the lack of effective therapies for DTC, which are resistant to radioiodine and thyroid stimulating hormone-suppressive therapy. Interestingly, the best responses have been demonstrated in patients treated with anti-angiogenic inhibitors such as vandetanib and XL184 in medullary thyroid cancer, and sorafenib in papillary and follicular DTC.

Clinicopathological pattern of lymph node recurrence of papillary thyroid cancer. Implications for surgery

IntroductionLymph nodal involvement in papillary thyroid cancers is very common, but the role of lymph node dissection is still controversial. Surgeons are consequently divided between opposed to and in favor of routine central neck dissection associated with total thyroidectomy. MethodsClinical records of 210 patients undergoing from January 2000 to December 2006 total thyroidectomy without routine lymph node dissection were retrospectively evaluated. One hundred and ninety eight patients (94.2%) underwent radioiodine ablation as well, followed by Thyroid Stimulating Hormone suppression therapy. In patients with loco regional lymph nodal recurrence, central (VI) and ipsilateral (III–IV) lymph node dissection was performed. ResultsIncidence of permanent hypoparathyroidism (iPTH < 10 pg/ml) and permanent vocal fold paralysis were respectively 1.4% and 1.9%. After an 8-year mean follow-up, the rate of loco regional recurrence was 4.2%–9/210 patients. In these cases selective lymph node dissection was carried out without complications. DiscussionThe role of neck dissection in papillary thyroid cancer management, is still subject of research and controversial regarding routine or therapeutic indications, surgical extension, its impact on local recurrence and survival. ConclusionA low loco regional recurrence rate may be observed after total thyroidectomy without prophylactic lymph node dissection. Lymph nodal recurrences were more frequent in young male patients, sometime affected by follicular variant, in each case less than 2 cm. There is a general agreement about the extension of therapeutic lymph node dissection, while routine central neck dissection is still controversial and may be indicated in high risk patients.

Expression of thyroid stimulating hormone receptor in differentiated thyroid carcinoma and its clinical significance

To explore the expression of thyroid stimulating hormone (TSH) receptor in differentiated thyroid carcinoma and its clinical significance. Seventy-four patients with differentiated thyroid carcinoma treated in our department from January 2009 to January 2011 were selected as the observation group, and 28 patients with nodular goiter were selected as the control group. Expression of TSH receptor in the two groups were detected by immunohistochemistry. The positive rate of TSH receptor expression in the observation group was 55.4 (41/74), significantly lower than that of the control group (89.3%, 25/28), with a significant difference between the two groups (χ(2) = 10.21, P < 0.05). In the observation group, the positive rate of TSH receptor expression was 75.9% (22/29) in the stage I patients, 47.8% (11/23) in the stage II patients, 38.9%6 (7/18) in the stage III patients, and 25.0% (1/4) in the stage IV patients. Along with the increase of TNM staging, the positive rate of TSH receptor expression was decreased gradually, with a significant difference between them (χ(2) = 8.93, P < 0.05). The positive rate of TSH receptor expression was 53.8% (14/26) in the lymph node metastasis positive group and 56.3% (27/48) in the lymph node metastasis negative groups, with a non-significant difference between them (χ(2) = 0.04, P > 0.05). Expression of TSH receptors in the patients with differentiated thyroid carcinoma is quite low, and along with the increase of TNM staging, its positive rate is decreasing gradually. Testing the expression of TSH receptor may provide a basis for TSH suppression therapy after thyroid cancer surgery. This TSH suppression therapy should be personalized in order to reduce the side effects and improve their quality of life.

Use and misuse of thyroid hormone

Synthetic thyroxine has replaced animal thyroid gland extract as the preferred drug in chronic thyroid hormone replacement. Synthetic thyroxine monotherapy is used to treat overt primary and secondary hypothyroidism, and some cases of subclinical hypothyroidism. In addition, thyroid-stimulating hormone suppressive therapy with thyroxine is a component of the chronic treatment for differentiated thyroid carcinoma. Liothyronine, however, is conventionally for short-term usage, including thyroid hormone withdrawal preparation for radioactive iodine scanning and treatment of differentiated thyroid carcinoma and some cases of myxoedema coma. On very rare occasions where patients are apparently intolerant of or unresponsive to thyroxine, liothyronine may be used chronically. However, there is controversy concerning the use of alternative regimens of thyroid hormone, such as the use of thyroxine-liothyronine combination and thyroid extracts. Thyroid hormone has also been misused to promote weight loss and treat 'symptomatic' biochemically euthyroid patients. There is insufficient evidence to support the use of thyroid hormone to improve treatment response in depression and severe non-thyroidal illnesses.

Total thyroidectomy, without prophylactic central lymph node dissection, in the treatment of differentiated thyroid cancer. Clinical retrospective study on 221 cases

Total thyroidectomy (TT) is the standard of care for differentiated thyroid cancer (DTC), but still there is no consensus about the role of routine use of prophylactic central lymph node dissection. The aim of this study was to analyze our results of TT without prophylactic central lymphadenectomy in the treatment of DTC. Clinical records, between January 1998 and December 2005, of 221 patients undergoing TT, without prophylactic central lymph node dissection, were retrospectively evaluated. Two hundred and eleven patients (95.47 %) also underwent radioiodine (RAI) ablation followed by thyroid stimulating hormone (TSH) suppression therapy. In patients with loco-regional lymph nodal recurrence, lateral and central lymph node dissection was performed. The incidence of permanent hypoparathyroidism (iPTH <10 pg/ml) and permanent vocal fold paralysis were, respectively, 0.91 and 0.91 %. After a 9.6 ± 3.5 years mean follow-up, the rate of loco-regional recurrence, with positive cervical lymph nodes, was 3.16 % (7/221 patients). In these cases a lateral and central lymphadenectomy was carried out without significant complications. Our results showed that TT without prophylactic central lymph node dissection, followed by RAI ablation, was associated with low morbidity and low loco-regional recurrence rate, even if the lack of a control group treated with TT plus prophylactic central lymphadenectomy suggests caution against generalization of our assumption. Such last combined procedure could be indicated in high-risk patients, in whom loco-regional recurrence is more frequent. However, given the trend in the literature toward prophylactic lymphadenectomy and the avoidance of RAI treatment, prospective randomized trials should be conducted to better clarify this issue.

Predictive value of nodal metastases on local recurrence in the management of differentiated thyroid cancer. Retrospective clinical study

BackgroundThe significance of nodal metastases, very common in papillary thyroid cancer, and the role of lymph node dissection in the neoplasm management, are still controversial. The impact of lymph node involvement on local recurrence and long-term survival remains subject of active research. With the aim to better analyze the predictive value of lymph node involvement on recurrence and survival, we investigated the clinico-pathological patterns of local relapse following total thyroidectomy associated with lymph node dissection, for clinical nodal metastases papillary thyroid cancer, in order to identify the preferred surgical treatment.MethodsClinical records, between January 2000 and December 2006, of 69 patients undergoing total thyroidectomy associated with selective lymph node dissection for clinical nodal metastases papillary thyroid cancer, were retrospectively evaluated. Radioiodine ablation, followed by Thyroid Stimulating Hormone suppression therapy was recommended in every case. In patients with loco regional lymph nodal recurrence, a repeated lymph node dissection was carried out. The data were compared with those following total thyroidectomy not associated with lymph node dissection in 210 papillary thyroid cancer patients without lymph node involvement, at preoperative ultrasonography and intra operative inspection.ResultsIncidence of permanent hypoparathyroidism (iPTH < 10 pg/ml) and permanent monolateral vocal fold paralysis were respectively 1.4 % (1/69) and 1.4% (1/69), similar to those reported after total thyroidectomy "alone". The rate of loco regional recurrence, with positive cervical lymph nodes, following 8 year follow-up, was 34.7% (24/69), higher than that reported in patients without nodal metastases (4.2%). A repeated lymph node dissection was carried out without significant complications.ConclusionsNodal metastases are a predictor of local recurrence, and a higher rate of lymph node involvement is expected after therapeutic lymph node dissection associated with total thyroidectomy. The prognostic significance of nodal metastases on long-term survival remains unclear, and more prospective randomized trials are requested to better evaluate the benefits of different therapeutic approaches.

Thyrotropin Suppressive Therapy in Differentiated Thyroid Cancer

Thyrotropin Suppressive Therapy in Differentiated Thyroid Cancer

Grand Challenges in Cancer Endocrinology: Endocrine Related Cancers, an Expanding Concept

The term Endocrine Related Cancers classically includes a group of sex steroid responsive cancers, such as cancers of the breast, endometrium, prostate, and testis, but also other cancers such as thyroid and ovary cancers that are responsive to pitui-tary hormones (1). Based on this widely accepted concept, at least 35–40% of newly diagnosed cancers fall into this definition (2). This concept has been useful for its clinical implications, and has lead to the use of anti-estrogenic/anti-androgenic treatments for sex hormone responsive cancers, as well as to thyroid-stimulating hormone (TSH) suppressive therapy with l-thyroxine (-T4) for differentiated thyl -roid cancer. Moreover, several studies have tried to identify physiological conditions, such as early menarche, late menopause, age of first pregnancy, and number of preg-nancies, prolonged lactation, and obesity, that may all affect sex steroids availabil-ity/exposure and modulate cancer risk. Another series of studies have identified germline polymorphisms, which are linked to the modulation of cancer risk through the genetic control of serum hormone lev-els or target tissue responses (3). Finally, other studies have addressed the possi-ble effects of the exposure to exogenous sex hormones, such as estroprogestins (4) or postmenopausal estrogen replac-ing therapy (5) or endocrine disruptors (6). While all these studies have provided useful information for cancer prevention and treatment, our understanding of how genetic traits relevant to hormone action, control and interaction with physiological conditions, hormonal supplementations, and environmental factors is still limited. Another grand challenge is represented by the possibility to achieve effective and risk-free chemoprevention for subjects predisposed to individual endocrine related cancers, as exemplified by the use of tamoxifen and other agents in breast cancer predisposed subjects (6).In recent years, several studies have challenged this classical view of endocrine related cancer. We now summarize recent data, which should be taken into account to reformulate the term “endocrine related cancer” in a more expanded way.