A Simplified Ultrasonographic Score for the Prediction of Cytologically Suspicious Thyroid Nodules.

PURPOSE: The major aim of ultrasound (US)-based risk stratification systems is to reduce unnecessary thyroid biopsies without losing the ability to recognize nodules with clinically significant malignancy. Each of the classic suspicious features of a thyroid nodule detected on US scan (hypoechoic pattern, microcalcifications, irregular margin, taller than wide shape, irregular vascularization) is significantly independently associated with the probability of malignancy, but none of them has good diagnostic accuracy. Thus, we evaluated the predictive value of a binary score simply based on the combination of these US features, regardless of the specific predictive value of each US feature, against the outcome of suspected malignancy at cytological diagnosis (TIR3 to TIR5 categories by SIAPEC-IAP [TIR+]). MATERIALS AND METHODS: 1009 thyroid nodules from 1081 patients were considered. The US features of suspicion of all nodules were categorized in 5 binary scores (U1 to U5), each including from 1 to 5 of those features. RESULTS: U2 (at least 2 US suspicious features) was the most balanced predictor of TIR+ (PPV 0.48, NPV 0.93, LR+ 3.05 and LR- 0.24). Weighting the predictivity of the single features did not improve the estimate. Using U2 as the criterion to send nodules to FNAC would have reduced the number of biopsies by 60 % (604 patients) and the false negatives would have only accounted for 41 cases out of 237 TIR+ (17 %) with 39 cases of TIR3 and 2 cases of TIR4, including only 6 malignant nodules on histological examination. U2 performed much better than the ATA recommendations for detecting those nodules, resulting in TIR+ at cytology. CONCLUSION: This simple and reproducible sonographic score based on 2 US features of suspicion of malignancy has quite a good performance with respect to identifying thyroid lesions categorized by cytology as medium-high risk of malignancy and could allow us to reduce cytology costs for low-risk nodules.

Long-term effectiveness of ultrasound-guided laser ablation of hyperfunctioning parathyroid adenomas: present and future perspectives.

OBJECTIVE: Although surgery is the first-choice treatment of primary hyperparathyroidism (pHPT), some patients present with contraindications or refuse surgery. Data from alternative nonsurgical therapies are inconclusive. To study the long-term efficacy of laser ablation in the treatment of pHPT, we retrospectively reviewed six cases of laser-treated patients. MATERIALS AND METHODS: Six patients with pHPT were treated with laser ablation using a flat-tip technique. Energy was administered by means of one optic fiber placed into the parathyroid adenoma through a 21-gauge Chiba needle connected to a neodymium:yttrium-aluminum-garnet laser. The mean (± SD) delivered energy for all patients was 2.067 ± 1440 J (range, 1000-4200 J). Treatment was fractionated in two (n = 2 patients) or in three (n = 1 patient) ultrasound-guided sessions. Patients' serum parathyroid hormone (PTH) and calcium levels were checked periodically, with neck ultrasound performed. The mean duration of follow-up was 54 ± 34 months (range, 12-84 months). RESULTS: Two months after laser ablation, serum PTH and calcium levels decreased in six and five patients, respectively. At the last follow-up examination, serum PTH and calcium levels were above the normal range in six and three patients, respectively. Three patients underwent surgery for persistent pHPT. Laser ablation therapy was safe and without permanent side effects. One patient reported transient dysphonia. CONCLUSION: Laser ablation produces a transient reduction of serum PTH and calcium levels but not a lasting resolution of hyperparathyroidism. Laser cannot be proposed as the definitive therapy of pHPT. Thus, studies aiming to identify therapeutic algorithms specific for parathyroid glands are needed to verify the utility of laser ablation in pHPT.

Preoperative charcoal suspension tattoo for the detection of differentiated thyroid cancer recurrence.

Recurrent differentiated thyroid carcinoma can easily be detected by means of ultrasound (US) and thyroglobulin, and often requires further surgical intervention. Revision surgery is often a technical challenge with significant risk of complications, considering the altered anatomy, with a possibility of leaving behind residual neoplasm. Preoperative US-guided tattooing localization has been introduced to reduce and prevent these potential problems during revision surgery. Encouraging results have been reported in the literature. Under US guidance, the lesion is identified and 0.5-2 ml of colloidal charcoal is injected in its proximity using a 23 gauge needle. The extraction is accompanied by injection at constant pressure of charcoal in order to leave a trace of pigment along the path of the needle till the skin. From April 2008 to January 2016 we performed revision surgery in 27 patients for lymph-nodes metastasis in differentiated thyroid cancer, using the technique of preoperative charcoal tattoo localization. Our previous study on the first group of 13 patients published in 2012, reported the preliminary results in terms of success rate and complications. The tolerance of charcoal injection was good for all patients and the procedure was demonstrated to be useful, contributing to the removal of metastatic lesion in 93% of procedures. We have registered minor surgical complications during revision in the central compartment of the neck: Transitory hypoparathyroidism in 2 cases (11%) and transitory vocal cord paresis in 3 cases (16%). Based on these results, preoperative charcoal tattoo localization in revision surgery of the neck for differentiated thyroid cancer recurrence can be considered a safe technique, easy to perform, with low-costs and useful during surgical procedures, providing a significant reduction of iatrogenic damage and risks.

Assessing the risk of false-negative fine-needle aspiration cytology and of incidental cancer in nodular goiter.

OBJECTIVE: In cases of multinodular goiter with negative cytologic result, reasonable management options include surgical treatment, simple follow-up, or more recently introduced conservative therapies such as laser or radiofrequency ablation, and recombinant human thyroid-stimulating hormone-augmented radioiodine. For patients who are eligible for follow-up or nonsurgical treatments, the possibility that they may have an undiagnosed malignancy (false-negative [FN]-fine-needle aspiration cytology [FNAC] result or incidental thyroid cancer [ITC]) should be considered. The aim of our study was to assess the risk of malignancy in patients known to have presumably benign thyroid disease. METHODS: Surgical series of patients who underwent total thyroidectomy for benign disease between 2000 and 2010 at two Italian centers were reviewed. Patients with any preoperative suspicion of malignancy were excluded. RESULTS: Histologic examination revealed that 84 of 970 (8.6%) thyroidectomized patients had malignancy (5% ITC and 3.6% FN-FNAC), with 89.8% of ITCs having a diameter <10 mm, and 65.7% of FN-FNAC cancers having a diameter >30 mm. Sixty-seven thyroid malignancy patients (79.8%) had stage I disease (American Joint Committee on Cancer criteria). The risk of FN-FNAC increases with increasing size of the nodule, while the risk of ITC increases as nodule size decreases. CONCLUSION: The risk of malignancy in presumably benign thyroid disease cannot be overlooked, but can be minimized through skillfully performed ultrasonography (US) examination and FNAC. Once a patient with multinodular goiter is referred for follow-up or nonsurgical therapy, careful US surveillance is mandatory.

Thyrotropin values in patients with micropapillary thyroid cancer versus benign nodular disease.

OBJECTIVE: Studies published in the last few years suggest that increased thyroid-stimulating hormone (TSH) values are associated with increased risk of thyroid cancer and/or a more advanced stage of malignancy. The aim of this study was to explore the hypothesis that TSH may be a risk factor for thyroid cancer initiation, which was tested by comparing TSH concentrations in patients with incidental micro papillary cancer (mPTC) and controls with a negative histologic exam. METHODS: Patients were retrospectively selected from medical records from 3 district hospitals. Patients with biochemical/histologic evidence of autoimmunity, thyroid function-interfering drugs, and autonomously functioning areas, were excluded. TSH values of 41 patients with an incidental mPTC were then compared with a sex- and age-matched group of patients who had a negative histologic exam at a 4:1 ratio (164 patients). RESULTS: TSH was not significantly different in the mPTC group compared to the controls (1.1 ± 0.7 vs. 1.3 ± 1.0 mIU/L). After adjustment for age and gender, TSH levels were still not found to be significantly different between groups. In the mPTC group, TSH levels were not found to be a significant predictor of tumor size after adjusting for age and gender (ß = 0.035, SE = 0.73, P = .844). CONCLUSIONS: On the basis of these results, the hypothesis that TSH is involved in de novo oncogenesis of PTC is not supported.

Pathological findings of thyroid nodules after percutaneous laser ablation : a series of 22 cases with cyto-histological correlation.

Ultrasound (US)-guided percutaneous laser ablation (LA) of benign thyroid nodules may be a potential alternative to surgery in patients with compressive symptoms, at high surgical risk, or in patients who refuse to undergo surgery. We evaluated the morphological effects of LA procedure on 22 patients and compared the cytological findings before and after LA with the histological features on surgical specimens. Twenty-two (4.9%; 19 women, three men, mean age 53.2 years) out of 452 patients treated with LA for benign thyroid nodules in our Hospital underwent surgery after LA procedure, either because nodule regrowth (treatment failure, n = 17) or indeterminate cytology (Thy3) after LA (n = 5). Morphological findings varied according to the time between LA and surgical intervention. Within 2 months, the area was occasionally cavitated and filled in with dark amorphous material. The inflammatory response was abundant and composed of neutrophils, lymphocytes, and macrophages. After 18 months or more since LA, the expected laser-induced histologic changes in thyroid morphology consisted of a well-defined area surrounded by a fibrous capsule and filled in by amorphous material. No significant pathologic features were found in the thyroid tissue adjacent to the treated area. Histological evaluation of thyroid tissues after LA shows that thermal damage is restricted to the ablated area, with no involvement of the nearby parenchyma. Our long-term histopathological findings indicate that LA treatment of benign thyroid nodules is safe, and patients undergoing LA may also be followed up by fine needle aspiration.

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.

The nutritional control of ghrelin secretion in humans: the effects of enteral vs. parenteral nutrition.

BACKGROUND: The nutritional control of ghrelin has not been fully clarified yet. Particularly, the influence of aminoacids and lipids is controversial and, moreover, whether the intraluminal gastric contact with nutrients is required or if the modulatory action of nutrients on ghrelin secretion is mediated by insulin is still matter of debate. AIM OF THE STUDY: To clarify the role of nutrients in the control of ghrelin secretion evaluating the effects of intravenous and oral lipids and aminoacids compared with glucose and fructose load in healthy subjects. METHODS: A total of 6 healthy overnight-fasted volunteers underwent the following testing sessions: (a) iv arginine (ARG, 0.5 g/kg); (b) oral protein load (PRO, 50 g); (c) iv lipid-heparin infusion (Li He, Intralipid 10% 250 ml); (d) oral fat load (OIL, soy oil 40 g); (e) oral glucose load (OGL, 100 g); (f) oral fructose load (OFL, 100 g); (g) iv saline (SAL, 3 ml); (h) oral water load (WL, 200 ml). Total ghrelin, insulin, and glucose were assayed every 15 min from 0 up to +180 min. RESULTS: WL and SAL did not modify insulin, glucose and ghrelin. ARG induced a prompt but transient increase (P < 0.05) of insulin and glucose (P < 0.01), without modifying ghrelin secretion. PRO induced a mild but sustained increase of insulin secretion (P < 0.05) without affecting glucose and ghrelin. Li-He progressively increased circulating glucose (P < 0.01) without modifying insulin and ghrelin secretion. No significant variations in circulating glucose, insulin, and ghrelin occurred after OIL. OGL significantly (P < 0.01) increased insulin and glucose levels and progressively decreased (P < 0.05) ghrelin levels. OFL induced a mild (P < 0.05) increase of insulin without modifying glucose levels. Similarly, OFL was followed by a milder decrease (P < 0.05) of ghrelin levels. CONCLUSIONS: Differently from carbohydrates and independently from their modulatory effect on insulin secretion and glucose levels, both lipids and aminoacids play a negligible role in the acute control of ghrelin secretion either after acute enteral and parenteral administration.

Ghrelin does not mediate the somatotroph and corticotroph responses to the stimulatory effect of glucagon or insulin-induced hypoglycaemia in humans.

OBJECTIVE: Acylated ghrelin, a gastric peptide, possesses a potent GH- but also significant ACTH/cortisol-releasing activity mediated by the activation of GH secretagogue receptors (GHS-R) at the hypothalamus-pituitary level. The physiological role of ghrelin in the control of somatotroph and corticotroph function is, however, largely unclear. Glucagon is known to induce a clear increase of GH, ACTH and cortisol levels in humans, at least after intramuscular administration. In fact, glucagon is considered to be a classical alternative to insulin-induced hypoglycaemia (ITT) for the combined evaluation of the function of GH and the hypothalamus-pituitary-adrenal (HPA) axis. We aimed to clarify whether ghrelin mediate the GH and corticotroph responses to intramuscular glucagon or ITT, which has recently been reported able to induce a surprising ghrelin decrease. SUBJECTS: To this aim we enrolled six normal young male subjects [age (mean +/- SD): 29.0 +/- 8.0 years, body mass index (BMI) 21.9 +/- 2.5 kg/m(2)]. DESIGN AND MEASUREMENTS: In all the subjects we studied ghrelin, GH, ACTH, cortisol and glucose levels after glucagon (GLU; 0.017 mg/kg intramuscularly), ITT (0.1 IU/kg insulin intravenously) or saline administration. RESULTS: Saline infusion was not followed by any significant variation in ghrelin, GH and glucose levels while ACTH and cortisol showed the expected spontaneous morning trend toward a decrease. GLU administration increased (P < 0.01) circulating GH, ACTH and cortisol as well as insulin and glucose levels. ITT induced an obvious increase (P < 0.01) of GH, ACTH and cortisol levels. The ITT-induced increases in GH and ACTH, but not cortisol, levels were higher (P < 0.01) than those after GLU. Circulating ghrelin levels were not modified by GLU. On the other hand, ghrelin levels underwent a transient reduction (P < 0.01) after insulin-induced hypoglycaemia. CONCLUSIONS: Ghrelin does not mediate the GH and ACTH responses to glucagon or to the ITT. In fact, ghrelin levels are not modified at all by glucagon and transiently decrease during the ITT. These findings support the assumption that ghrelin does not play a major role in the physiological control of somatotroph and corticotroph function.

Ghrelin secretion is inhibited by glucose load and insulin-induced hypoglycaemia but unaffected by glucagon and arginine in humans.

OBJECTIVE: Circulating ghrelin levels are increased by fasting and decreased by feeding, glucose load, insulin and somatostatin. Whether hyperglycaemia and insulin directly inhibit ghrelin secretion still remains matter of debate. The aim of the present study was therefore to investigate further the regulatory effects of glucose and insulin on ghrelin secretion. DESIGN AND SUBJECTS: We studied the effects of glucose [oral glucose tolerance test (OGTT) 100 g orally], insulin-induced hypoglycaemia [ITT, 0.1 IU/kg insulin intravenously (i.v.)], glucagon (1 mg i.v.), arginine (0.5 mg/kg i.v.) and saline on ghrelin, GH, insulin, glucose and glucagon levels in six normal subjects. MEASUREMENTS: In all the sessions, blood samples were collected every 15 min from 0 up to + 120 min. Ghrelin, GH, insulin, glucagon and glucose levels were assayed at each time point. RESULTS: OGTT increased (P < 0.01) glucose and insulin while decreasing (P < 0.01) GH and ghrelin levels. ITT increased (P < 0.01) GH but decreased (P < 0.01) ghrelin levels. Glucagon increased (P < 0.01) glucose and insulin without modifying GH and ghrelin. Arginine increased (P < 0.01) GH, insulin, glucagon and glucose (P < 0.05) but did not affect ghrelin secretion. CONCLUSIONS: Ghrelin secretion in humans is inhibited by OGTT-induced hyperglycaemia and ITT but not by glucagon and arginine, two substances able to increase insulin and glucose levels. These findings question the assumption that glucose and insulin directly regulate ghrelin secretion. On the other hand, ghrelin secretion is not associated with the GH response to ITT or arginine, indicating that the somatotroph response to these stimuli is unlikely to be mediated by ghrelin.