Roberto Valcavi

Complications of Central Neck Dissection in Patients with Papillary Thyroid Carcinoma: Results of a Study on 1087 Patients and Review of the Literature

BACKGROUND Prophylactic central neck dissection (CND) has been proposed in the treatment of patients affected by papillary thyroid carcinoma (PTC) with clinically negative neck lymph nodes. The procedure allows pathologic staging of lymph nodes of the central compartment and treatment of the micrometastases. Nevertheless, the morbidity that its routine use adds to the total thyroidectomy must be taken into account. The aim of this study was to characterize the morbidity that CND adds to the total thyroidectomy. METHODS This was a retrospective study of 1087 patients with PTC and clinically negative neck lymph nodes. Patients were divided into three study groups: Group A, total thyroidectomy; Group B, total thyroidectomy and ipsilateral CND; Group C, total thyroidectomy and bilateral CND. Primary endpoints of the study were evaluated by comparing the rates of transient and permanent recurrent laryngeal nerve (RLN) injury and hypoparathyroidism in the three study groups. RESULTS Analysis of data showed no significant differences in the rate of transient (Group A: 3.6%, Group B: 3.9%, and Group C: 5.5%; p=0.404) and permanent (Group A: 1%, Group B: 0.5%, and Group C: 2.3%; p=0.099) RLN injury between the three study groups. Both ipsilateral CND and bilateral CND were associated with a higher rate of transient hypoparathyroidism (Group: A 27.7%, Group B: 36.1%, and Group C: 51.9%; p=0.014; odds ratio [OR]: 1.477; 95% confidence interval [CI]: 1.091-2.001; p<0.001; OR: 2.827; 95% CI: 2.065-3.870, respectively). Bilateral CND had a higher rate of permanent hypoparathyroidism (Group A: 6.3%, Group B: 7%, and Group C: 16.2%; p<0.001; OR: 2.860; 95% CI: 1.725-4.743). CONCLUSIONS The increased rates of transient and permanent hypoparathyroidism in our series suggest a critical review of indications for the routine use of prophylactic CND for PTC. Prophylactic CND ipsilateral to the tumor associated with total thyroidectomy may represent an effective strategy for reducing the rate of permanent hypoparathyroidism. Concomitant completion contralateral paratracheal lymph node neck dissection should be performed in presence of lymph node metastasis on intraoperative frozen-section pathology. This approach limits the use of bilateral CND to patients with intraoperative pathological findings of lymph node metastases.

Prognostic Factors Affecting Neck Lymph Node Recurrence and Distant Metastasis in Papillary Microcarcinoma of the Thyroid: Results of a Study in 445 Patients

BACKGROUND The management of thyroid papillary microcarcinoma (PMC) is controversial. Total thyroidectomy, thyroid lobectomy/isthmectomy, and even no treatment have been proposed. We investigated the clinical course and prognostic factors for disease recurrence and distant metastasis in 445 patients with PMC. METHODS Data from 445 patients diagnosed with PMC in the period from 1978 to 2003 were reviewed and analyzed. Total thyroidectomy was performed in 404 patients and loboisthmusectomy in 41. Neck dissection took place in 226 patients (49.7%), with 166 of only the central compartment and 60 of both the central and lateral compartments. Radioiodine ((131)I) ablation treatment was given to 389 patients. RESULTS Median tumor size was 7 mm (range 1-10 mm). PMC was multifocal in 156 cases (35%) and bilateral in 60 cases (13.5%). Extrathyroidal tumor extension (pT3) and neck lymph node metastasis (pN1) were present in 133 (30%) and 182 (40.9%) patients, respectively. Capsular invasion without extrathyroidal tumor extension was observed in 39 (8.7%) patients. Mean follow-up was 5.3 (range 1-26) years. Seventeen (3.8%) patients had recurrence or persistence of disease: neck recurrence (NR) in 12 (2.7%), distant metastasis (DM) in four (0.9%), NR + DM in one (0.2%). One patient (0.2%) died of the disease. Capsular invasion, extrathyroidal tumor extension (pT3), and neck lymph node metastasis at presentation (pN1) were the only independent risk factors for NR and/or DM occurrence (p < 0.05). Patients not showing these features, who were treated with loboisthmusectomy only, never experienced disease recurrence. CONCLUSION Total thyroidectomy seems advisable in PMC with extrathyroidal extension and neck lymph node metastasis at presentation. Capsular invasion without extrathyroidal extension may suggest aggressive tumor behavior and require radical treatment.

Thyroid nodule guidelines: agreement, disagreement and need for future research

This article reviews agreement, disagreement and need for future research of the thyroid nodule guidelines published by the British Thyroid Association, National Cancer Institute, American Thyroid Association and the joint, transatlantic effort of three large societies, the American Society of Clinical Endocrinologists, Associazione Medici Endocrinologi and the European Thyroid Association, published in 2010. Consensus exists for most topics in the various guidelines. A few areas of disagreement, such as the use of scintigraphy, are mostly due to differences in disease prevalence in different countries. Most of the discordance, for example, on the use of calcitonin screening or fine-needle aspiration cytology classification, could probably be resolved by further expert discussions, as the basis is the same published evidence. Importantly, owing to a current lack of evidence in many areas, clinically very relevant areas of uncertainty need to be addressed by further research. This situation applies, for instance, to better definition of ultrasound malignancy criteria and the evaluation of emerging new diagnostic and therapeutic techniques, including molecular markers. For clinicians who advise individual patients, these areas of uncertainty can currently only be resolved by sound management on the basis of clinical judgment, experience and patient preference.

Percutaneous Laser Ablation of Cold Benign Thyroid Nodules: A 3-Year Follow-Up Study in 122 Patients

BACKGROUND Percutaneous laser ablation (PLA) is a proposed therapeutic procedure for the management of benign thyroid nodules. However, long-term results are unknown. The aim of this study was to evaluate retrospectively the safety and effects of PLA treatment in patients with benign nonfunctioning thyroid nodules in a 3-year follow-up. METHODS One hundred twenty-two patients (95 women and 27 men; age 52.2 ± 12.3 years) with benign cold thyroid solitary nodules or a dominant nodule within a normo-functioning multinodular goiter (volume range: 2.6-86.4 mL) underwent thermal Nd:YAG laser ablation of thyroid nodular tissue by 1-4 optical fibers positioned into the tissue by 21-gauge needles under ultrasound real-time assistance. The setting was an interventional suite and outpatient endocrine clinics in a community hospital in Italy. Nodule volume, ablation volume, side effects, serum thyroid-stimulating hormone (TSH), free triiodothyronine, free thyroxine (fT4), thyroglobulin (Tg), anti-Tg, anti-thyroperoxidase antibodies, symptoms, and cosmetic signs were recorded. RESULTS Data are mean ± standard deviation. Energy delivered was 8522  ± 5365 J with an output power of 3.1 ± 0.5 W. Three years after PLA, nodule volume decreased from 23.1 ± 21.3 to 12.5 ± 18.8 mL (-47.8%  ± 33.1% of initial volume, p ≤ 0.001). At day 1, TSH and fT4 values significantly changed (time 0 vs. day 1: TSH = 1.16  ± 1.06 vs. 0.62 ± 0.81 μU/mL, p ≤ 0.001; fT4 = 11.68 ± 1.88 vs. 13.20 ± 3.32 pg/mL, p ≤ 0.01) and normalized within 1 month. No change in free triiodothyronine, thyroperoxidase antibodies, and Tg antibodies values was observed. Symptoms improved in 89 patients (73.0%), were unchanged in 28 (22.9%), and worsened in 5 (4.1%). Cosmetic signs improved in 87 patients (71.3%), were unchanged in 29 (23.8%), and worsened in 6 (4.9%). In 11 patients (9%), nodules regrew above baseline. Two patients (1.6%) experienced delayed (12-24 hours) laryngeal dysfunction with vocal cord motility recovery after 6-10 weeks. Two patients (1.6%) became hypothyroid and two patients (1.6%) hyperthyroid after PLA. CONCLUSIONS After 3 years, the PLA technique achieved shrinkage of about 50% of the initial volume in a wide size range of benign cold thyroid nodules, with an improvement in local symptoms and signs. Side effects and failures were few although not negligible. PLA may be a new option for the management of benign cold thyroid nodules. Long-term controlled studies are required to establish the eligibility of patients for routine PLA.

Thermal ablation for benign thyroid nodules: radiofrequency and laser.

Although ethanol ablation has been successfully used to treat cystic thyroid nodules, this procedure is less effective when the thyroid nodules are solid. Radiofrequency (RF) ablation, a newer procedure used to treat malignant liver tumors, has been valuable in the treatment of benign thyroid nodules regardless of the extent of the solid component. This article reviews the basic physics, techniques, applications, results, and complications of thyroid RF ablation, in comparison to laser ablation.

Ultrasound-guided percutaneous ethanol injection therapy in thyroid cystic nodules.

OBJECTIVE To provide an overview of ultrasound (US)-guided percutaneous ethanol injection (PEI) therapy for thyroid cystic nodules and discuss the practical and technical details. METHODS We present preliminary data of a controlled randomized study involving 281 patients (221 women and 60 men; 18 to 85 years old) with benign thyroid cystic nodules. Study inclusion criteria were local discomfort or cosmetic damage, cystic volume more than 2 mL, 50% or more fluid component, benignity as confirmed by cytologic specimen obtained by US-guided fine-needle aspiration biopsy (FNAB), and euthyroidism. Exclusion criteria were inadequate, suspicious, or positive FNAB cytology, high serum calcitonin, and contralateral laryngeal cord palsy. By random assignment, 138 patients underwent simple cyst evacuation, and 143 underwent cyst evacuation plus PEI by a skilled operator using a US-guided technique. The amount of ethanol injected was 50 to 70% of the cystic fluid extracted. RESULTS Before treatment, the mean (+/-SD) nodule volume was 19.0 +/- 19.0 mL versus 20.0 +/- 13.4 mL in the PEI versus the simple evacuation group (no significant difference). After 1 year, volumes were 5.5 +/- 11.7 mL versus 16.4 +/- 13.7 mL (P<0.001), with a median 85.6% versus 7.3% reduction, respectively (P<0.001), of the initial volume. The median nodule volume reduction after PEI was 88.8% and 65.8% in empty body and mixed thyroid cysts, respectively. Compressive and cosmetic symptoms disappeared in 74.8% and 80.0% of patients treated with PEI versus 24.4% and 37.4% of patients treated with simple evacuation, respectively (P<0.001). Side effects were minor. CONCLUSION These data provide definitive evidence that PEI is a safe and effective treatment for thyroid cystic nodules. Unicameral thyroid cysts are the most suitable candidate nodules for PEI.

Challenges in neck ultrasonography: lymphadenopathy and parathyroid glands.

OBJECTIVE To assess the performance of neck ultrasonography (US) in the detection of lymph node lesions metastatic from differentiated thyroid carcinoma (DTC) and the detection of parathyroid adenomas. METHODS Neck US was performed in 667 patients with DTC (173 men and 494 women; mean age, 47.7 years). In cases of suspicious neck nodes, US-guided fine-needle aspiration biopsy (US-FNAB) plus measurement of thyroglobulin in the needle washouts (FNAB-Tg) was done. In addition, 75 patients with primary hyperparathyroidism (pHPT) (15 men and 60 women; mean age, 56 years) underwent neck US and sestamibi scintiscanning for localization of parathyroid adenoma. For confirmation of US findings, US-FNAB plus measurement of parathyroid hormone in the needle washouts (FNAB-PTH) was performed. FNAB-PTH was also measured in 129 suspected parathyroid adenomas incidentally detected in a series of 4,129 patients undergoing neck US examination for thyroid disease. RESULTS The presence of DTC metastatic lesions was confirmed in 46 of 95 patients with suspicious neck nodes. US sensitivity and specificity were 82.1% and 91.2%, respectively. The positive predictive value (PPV) of US-FNAB + FNAB-Tg was 94.7%. In the 75 patients with pHPT, US followed by US-FNAB + FNAB-PTH showed a higher PPV (97.5%) in comparison with sestamibi scintiscanning (83.7%) in the detection of parathyroid adenoma. A parathyroid adenoma was also incidentally detected in 0.62% of the 4,129 patients undergoing neck US for thyroid disease. CONCLUSION US accurately detects DTC neck metastatic lesions and localizes parathyroid adenomas. Moreover, neck US may lead to discovery of parathyroid incidentalomas.

Melatonin stimulates growth hormone secretion through pathways other than the growth hormone‐releasing hormone

OBJECTIVE There is evidence that melatonin plays a role in the regulation of GH secretion. The aim of this study was to investigate the neuroendocrine mechanisms by which melatonin modulates GH secretion. Thus we assessed the effect of oral melatonin on the GH responses to GHRH administration and compared the effects of melatonin with those of pyridostigmine, a cholinergic agonist drug which is likely to suppress hypothalamic somatostatin release.

Detection and diagnosis of parathyroid incidentalomas during thyroid sonography.

The aim of our study was to evaluate the incidence of incidentally found parathyroid adenomas (incidentalomas) in patients undergoing sonography of the neck for thyroid disease.

Influence of hyperthyroidism on growth hormone secretion

OBJECTIVE Hyperthyroidism is associated with altered GH secretion. Whether this is due to changes of somatotroph responsiveness or reflects an alteration in negative feedback signals at the hypothalamic level is unknown. We therefore performed a series of studies to shed some light onto this issue.