Condition of Adrenergic Innervation Apparatus of the Thyroid Gland, Blood and Lymph Vessels, and Lymph Nodes during Correction of Hypothyrosis.

We used specific histochemical fluorescence-microscopic method of visualization of catecholamines to study adrenergic innervation of the thyroid gland tissue, blood vessels of the thyroid gland, cervical lymphatic vessel and lymph nodes in rats during correction of hypothyroidism with a bioactive formulation (Vozrozhdenie Plus balm with Potentilla alba L.). In experimental hypothyroidism, adrenergic innervation of the thyroid gland and the wall of the cervical lymph node, concentrated mainly along the arterial vessels and the cervical lymphatic vessel, retained its structural formations (plexuses and varicosities), but diffusion of catecholamines outside these formations was observed. Correction with the bioactive formulation restored of the contours of the nerve plexuses and varicosities and their brighter fluorescence in the thyroid gland and cervical lymphatic vessel and node. During correction of hypothyroidism with the bioactive formulation, reorganization of regional lymphatic vessels and nodes was more pronounced than reorganization of the thyroid gland.

Myo-inositol and selenium reduce the risk of developing overt hypothyroidism in patients with autoimmune thyroiditis.

OBJECTIVE: The beneficial effects obtained by myo-inositol in association with seleno-methionine in patients affected by subclinical hypothyroidism have been recently demonstrated. Here, we evaluate the immune-modulating effect of myo-inositol in association with seleno-methionine in patients with euthyroid autoimmune thyroiditis (AT). PATIENTS AND METHODS: Twenty-one consecutive Caucasian patients with newly diagnosed euthyroid chronic AT were evaluated. All subjects were treated with myo-inositol in association with selenium (600 mg/83 mg) tablets, twice per day, for six months. A complete thyroid assessment was done before the treatment, and after six months. RESULTS: After the treatment thyroid-stimulating hormone (TSH) levels significantly declined with respect to basal values, overall in patients with an initial TSH value in the high normal range (2.1

PSMA Expression in Tumor Neovasculature Endothelial Cells of Follicular Thyroid Adenoma as Identified by Molecular Imaging Using 68Ga-PSMA Ligand PET/CT.

The prostate-specific membrane antigen (PSMA) is expressed by both prostate cancer and other neoplasms. We report the case of a 65-year-old man with castration-resistant metastatic prostate cancer who underwent Ga-PSMA ligand PET/CT for restaging of disease. Ga-PSMA ligand accumulation was noted in a thyroid lesion, suspicious for thyroid malignancy on complementary ultrasound. Subsequent resection and histopathological analysis showed follicular thyroid adenoma with PSMA expression in tumor neovasculature endothelial cells, but not in thyroid epithelial cells. It is important to be aware that both malignant and benign thyroid neoplasms may show PSMA expression to avoid misinterpretation.

Terminal or truncal ligation of the inferior thyroid artery during thyroidectomy? A prospective randomized trial.

INTRODUCTION: Thyroidectomy is a common procedure in general and endocrine surgery. The technique of ligation of inferior thyroid artery (ITA) has been invoked as a possible cause of appearance of postoperative hypocalcemia. METHODS: We performed a prospective randomized study involving 184 patients undergoing total thyroidectomy to evaluate the differences of truncal ligation versus distal ligation of ITA in terms of postoperative hypocalcemia, vocal fold palsy, voice and swallowing impairment. The patients were divided into group A (trunk ligation of ITA) and group B (terminal branches ligation of ITA). RESULTS: We evaluated postoperative PTH and calcemia (immediate, 6 and 12 months after thyroidectomy), postoperative day of discontinuation of calcium and vitamin D supplementation, voice and swallowing complaints, evaluated by mean of two specific tests available in literature, day of hospital discharge. CONCLUSION: The only significant differences between the two groups were a higher immediate postoperative calcemia and a greater number of patients discharged without calcium and vitamin-D supplementation in the group B. In conclusion, no substantial differences were found between the two groups. The choice depends on the experience of the surgeon.

Thyroid-specific changes following treatment with biological therapies in patients with rheumatic diseases.

Biological anti-rheumatic agents (BAA) may induce autoimmune phenomena. Evidence on thyroid-specific effects of these agents is relatively limited. We studied prospectively, over 3 years, 36 rheumatic patients treated with BAA (18 Infliximab and 18 Rituximab) and no prior exposure to biological therapies (group-1), with respect to their thyroid function, thyroid antibody titers, and thyroid ultrasonographic parameters, such as left inferior thyroid artery peak systolic velocity (ITA PSV), left thyroid lobe vascularity index (TL VI), and echogenicity. Twenty-eight rheumatic patients treated with disease-modifying anti-rheumatic drugs and/or glucocorticoids (group-2), 21 rheumatic patients not receiving any treatment (group-3), and 49 healthy individuals (group-4) were used for comparison. Thyroid function and autoantibody titers were not significantly altered at any stage irrespectively of the administered BAA, previously unknown autoimmune thyroid disease (AITD) status, and/or concomitant treatment with glucocorticoids. Left ITA PSV was significantly increased in group-1 patients (mean ± SD start: 25.5 ± 14.1 cm/s vs. end: 29.8 ± 11.1 cm/s, p = 0.038 and p < 0.001, respectively). Six group-1, 7 group-2, and 3 group-3 patients developed reduced thyroid echogenicity during follow-up (start: p = 0.003 and end: p < 0.001). Left ITA PSV, left TL VI, and echogenicity changes were not related to alterations in thyroid volume, thyrotropin hormone levels, and/or underlying AITD. Infliximab and Rituximab do not cause any alterations in thyroid function and/or autoimmunity, even in patients with previously undiagnosed AITD. Elevated left ITA PSV and reduced thyroid echogenicity may be early features signaling progression to AITD in patients treated with BAA.

Malignancy rate in thyroid nodules classified as Bethesda category III (AUS/FLUS).

BACKGROUND: The Bethesda System for Reporting Thyroid Cytopathology is the standard for interpreting fine needle aspiration (FNA) specimens. The "atypia of undetermined significance/follicular lesion of undetermined significance" (AUS/FLUS) category, known as Bethesda Category III, has been ascribed a malignancy risk of 5-15%, but the probability of malignancy in AUS/FLUS specimens remains unclear. Our objective was to determine the risk of malignancy in thyroid FNAs categorized as AUS/FLUS at a comprehensive cancer center. METHODS: The management of 541 AUS/FLUS thyroid nodule patients treated at Memorial Sloan-Kettering Cancer Center between 2008 and 2011 was analyzed. Clinical and radiologic features were examined as predictors for surgery. Target AUS/FLUS nodules were correlated with surgical pathology. RESULTS: Of patients with an FNA initially categorized as AUS/FLUS, 64.7% (350/541) underwent immediate surgery, 17.7% (96/541) had repeat FNA, and 17.6% (95/541) were observed. Repeat FNA cytology was unsatisfactory in 5.2% (5/96), benign in 42.7% (41/96), AUS/FLUS in 38.5% (37/96), suspicious for follicular neoplasm in 5.2% (5/96), suspicious for malignancy in 4.2% (4/96), and malignant in 4.2% (4/96). Of nodules with two consecutive AUS/FLUS diagnoses that were resected, 26.3% (5/19) were malignant. Among all index AUS/FLUS nodules (triaged to surgery, repeat FNA, or observation), malignancy was confirmed on surgical pathology in 26.6% [CI 22.4-31.3]. Among AUS/FLUS nodules triaged to surgery, the malignancy rate was 37.8% [CI 33.1-42.8]. Incidental cancers were found in 22.3% of patients. On univariate logistic regression analysis, factors associated with triage to surgery were younger patient age (p<0.0001), increasing nodule size (p<0.0001), and nodule hypervascularity (p=0.032). CONCLUSIONS: In patients presenting to a comprehensive cancer center, malignancy rates in nodules with AUS/FLUS cytology are higher than previously estimated, with 26.6-37.8% of AUS/FLUS nodules harboring cancer. These data imply that Bethesda Category III nodules in some practice settings may have a higher risk of malignancy than traditionally believed, and that guidelines recommending repeat FNA or observation merit reconsideration.

Prognostic and predictive markers in medullary thyroid carcinoma.

Unlike papillary thyroid carcinoma, medullary thyroid carcinoma is insensitive to adjuvant treatment with radioactive iodine. The clinical management of patients with advanced or metastatic disease remains challenging since no effective systemic adjuvant therapy is available. We aimed to identify markers of aggressive disease and novel drugable protein targets that would provide systemic adjuvant treatment for patients with advanced medullary thyroid carcinoma. We therefore examined morphologic features of aggressive behavior and the expression of 41 proteins involved in apoptosis, cell cycle, angiogenesis, inflammation, cell adhesion, tumor-specific markers, and WNT, SHH, and AKT pathways using tissue microarray from 23 patients with medullary thyroid carcinoma. Protein expression was determined using computerized image analysis software. Statistical analysis was carried out to correlate clinical data with the average score for each marker. Angioinvasion proved to be the most reliable predictor of disease recurrence and death. The rate of angioinvasion was 43 %. All angioinvasive medullary thyroid carcinomas had locoregional and/or distant metastasis; 60 % of angioinvasive medullary thyroid carcinomas developed distant metastasis. We identified expression of several potentially important protein targets such as COX-1/2, Bcl-2a, Gst-π, Gli-1, Gli-2, Gli-3, and Bmi-1 that may be therapeutically targeted in medullary thyroid carcinoma. More importantly, the immunohistochemical profile of SSTRs in medullary thyroid carcinoma may also have clinical relevance for the administration of peptide receptor radionuclide treatment. Successful outcome of clinical trials directed against these novel targets would provide much needed systemic adjuvant treatment for patients with advanced medullary thyroid carcinoma, and our data suggest the possibility of stratifying patients who are likely to require adjuvant therapy before their burden of disease precludes successful therapeutic effect.

Peak systolic velocity of superior thyroid artery for the differential diagnosis of thyrotoxicosis.

AIM: The differentiation of destruction-induced thyrotoxicosis and Graves' disease (GD) is of great importance for selection of proper therapy. Radioactive iodine uptake (RAIU) is the gold standard for differentiating these two conditions but its application has remained somewhat limited. Thyroid color Doppler flow sonography (CDFS) is a potential alternative of RAIU but more supporting evidence is warranted. In the present study, a standard operative procedure was developed to measure the mean peak systolic velocity of superior thyroid artery (STA-PSV) and evaluate its role in the differential diagnosis of thyrotoxicosis. METHODS: A total of 135 patients with untreated thyrotoxicosis were enrolled into one retrospective study (GD, n = 103; thyroiditis, n = 32) and another prospective study recruited 169 patients (GD, n = 118; thyroiditis, n = 51). Thirty normal controls were also enrolled. Thyroid function, anti-TSH-receptor antibody (TRAb), RAIU, CFDS of thyroid and STA-PSV were performed for each patient. Receiver operator curve (ROC) was used to evaluate the diagnostic value of STA-PSV in a retrospective study so as to seek the optimal cutoff point. Then the cutoff point value was used to validate its diagnostic value in a prospective study and in another thyrotoxicosis population. RESULTS: STA-PSV of GD was significantly higher than that of thyroiditis in both retrospective and prospective studies. The area under the ROC curve of mean STA-PSV was 0.8799 and 0.9447 in the retrospective and prospective studies respectively. If a mean STA-PSV cutoff point of 50.5 cm/s was set from the retrospective analysis for the prospective study, the sensitivity and specificity in distinguishing GD from thyroiditis were 81.04% and 96.08% respectively. Mean STA-PSV and TRAb had similar area under ROC. The coefficients of variation in STA-PSV measurement were lower than 10% for the euthyroid, thyroiditis and GD groups. CONCLUSIONS: STA-PSV is a feasible supplement alternative of RAIU for differentiating the causes of thyrotoxicosis.

Increased thyroid blood flow in the hypoechoic lesions in patients with recurrent, painful Hashimoto's thyroiditis at the time of acute exacerbation.

We report two cases with painful Hashimoto's thyroiditis, who developed recurrent fever and painful thyroid. Glucocorticoid treatment was transiently successful but tenderness in the thyroid gland and fever developed when glucocorticoid was tapered. One patient underwent total thyroidectomy uneventfully. As is well known, it is frequently difficult to make differential diagnosis between painful Hashimoto's thyroiditis and subacute thyroiditis particularly at the initial phase. Interestingly, color flow doppler sonography of patient 1 revealed an increased thyroid blood flow in the hypoechoic lesions at the time of acute exacerbation although the serum level of TSH was suppressed. In the other patient, thyroid blood flow was also increased mainly in the hypoechoic lesions when the serum level of TSH was moderately increased, and it disappeared completely after supplementation of prednisolone and L-T4. Since thyroid blood flow in subacute thyroiditis is always decreased, such an increased blood flow in the hypoechoic lesion may be one of clinical characteristics of painful Hashimoto's thyroiditis, and useful for differential diagnosis from subacute thyroiditis.

Safety of same day discharge in patients undergoing sutureless thyroidectomy: a comparison of local and general anesthesia.

BACKGROUND: The thyroid gland is one of the most vascular organs in the body and surgical resection mandates meticulous surgical technique and hemostasis. The aim of this study was to assess the safety and efficacy of the electrothermal bipolar vessel sealing system in permitting ambulatory thyroid surgery under local anesthesia. METHODS: From January 1, 2004, to December 31, 2005, 224 consecutive patients underwent thyroid surgery using the LigaSure for hemostasis. Whenever possible, local/regional anesthesia with conscious sedation was utilized during the procedure. A descriptive analysis was performed to evaluate patient characteristics and outcome measures. RESULTS: Eighty-two percent (n = 184) of all unselected patients presenting for thyroid surgery had their procedure performed under local/regional anesthesia with conscious sedation whereas 18% (n = 40) received general anesthesia. When comparing these two groups, the local anesthesia patients were more likely to be female (85% vs. 68%, p < or = 0.05) and younger (mean age = 50 vs. 61 years, p < or= 0.05). Forty percent of the local anesthesia patients underwent a total thyroidectomy compared to 58% in the general anesthesia group (p < or = 0.05). The mean duration of surgery was shorter in the local anesthesia patients (71 minutes vs. 101 minutes, p < or = 0.05) and the mean gland weight was also less (26.9 g vs. 63.9 g, p < or = 0.05). There was one hematoma in the local anesthesia group, but overall the morbidity was not different. Eighty-eight percent of the local anesthesia patients were discharged same day of surgery compared to 45% of the general anesthesia patients. CONCLUSIONS: The electrothermal bipolar vessel sealing system permits safe, same day discharge in patients undergoing thyroid surgery with a low complication rate irrespective of the type of anesthesia.

Does truncal ligation of the inferior thyroid arteries during bilateral subtotal thyroidectomy affect serum calcium levels? A prospective, randomized, controlled study.

This study was designed to investigate the effect of truncal ligation of the inferior thyroid arteries on post-thyroidectomy serum calcium levels. This prospective, randomized study was carried out in 98 patients. In group 1, bilateral inferior thyroid arteries were ligated truncally during bilateral subtotal thyroidectomy procedure, whereas in group 2, ligation was not performed. In all patients, serum ionized calcium levels were measured preoperatively and on postoperative days 1, 2, 3 and 30. There were no statistically significant differences in serum ionized calcium values between group 1 and 2 on postoperative days 1, 2, 3, and 30 (P > 0.05). Laboratory hypocalcemia was found on postoperative days 1, 2, and 3 in 9 (9.2%), 15 (15.3%), and 2 (2.0%) patients, respectively. In all patients, laboratory hypocalcemia improved until postoperative day 5. It was thought that truncal ligation of the inferior thyroid arteries during bilateral subtotal thyroidectomy had no effect on post-thyroidectomy serum calcium levels.

Truncal ligation of the inferior thyroid arteries does not affect the incidence of hypocalcaemia after thyroidectomy.

OBJECTIVE: To assess the effect of truncal ligation of the inferior thyroid arteries during bilateral subtotal thyroidectomy on the incidence of hypocalcaemia after thyroidectomy. DESIGN: Prospective non-randomised study. SETTING: Teaching hospital, Turkey. SUBJECTS: 216 patients who had bilateral subtotal thyroidectomy for non-toxic nodular goitre between 1990 and 1996. INTERVENTIONS: The trunk of the each inferior thyroid artery was simply ligated during bilateral subtotal thyroidectomy. MAIN OUTCOME MEASURES: Clinical examination, and measurement of serum calcium, ionised calcium, and inorganic phosphate concentrations before and after operation. RESULTS: Four patients (2%) had low concentrations of total and ionised calcium during the postoperative period. On physical examination three of them had spasms of the facial nerve, as seen in tetany. They were given calcium supplements orally and their laboratory results returned to reference ranges within 180 days. No patients developed permanent hypocalcaemia. CONCLUSION: Truncal ligation of the inferior thyroid arteries during bilateral subtotal thyroidectomy has no effect on the incidence of hypocalcaemia after thyroidectomy.

Transposition of the lingual thyroid: A new alternative technique.

BACKGROUND: In symptomatic lingual thyroid, surgical transposition of the gland with its vascular supply intact seems to have superior results to those obtained by surgical ablation and autotransplantation. However, the procedure should be simple, reproducible, reliable, and cause less morbidity as well as providing simple access to and evaluation of the gland postoperatively. METHODS: We present the case of a 33-year-old female with lingual thyroid who was treated by transposing the whole gland to the lateral pharyngeal wall through a lateral pharyngotomy incision. The transposed lingual thyroid was nourished by a random tongue muscle pedicle flap. RESULT: At the 5-month postoperative stage, iodine scanning reviewed the radioactivity uptake of the transposed gland. Even though the patient was not on postoperative thyroid hormone supplement, her thyroid function gradually returned to normal after initially showing hypothyroid postoperatively. CONCLUSION: This new technique for transposition of lingual thyroid is simple and reliable and should be considered as an alternative method in the management of symptomatic patients.

Parathyroid function following ligation of the inferior thyroid arteries during bilateral subtotal thyroidectomy.

A randomized controlled trial was performed to compare two techniques of bilateral subtotal thyroidectomy for non-toxic nodular goitre with regard to postoperative parathyroid function. The 50 patients in group 1 underwent ligation of the trunks of the inferior thyroid arteries. In group 2 (50 patients) the branches of these arteries were suture-ligated at the thyroid capsule. Total calcium, ionized calcium and parathyroid hormone levels were determined before operation, and 6, 24 and 72 h after surgery. Ninety-one patients were seen at follow-up 5-10 months after operation. Ten patients in group 1 and 12 in group 2 required calcium and/or vitamin D supplementation for symptomatic hypocalcaemia in the immediate postoperative period. At follow-up only one patient in each group had mild hypoparathyroidism. No statistically significant differences were found between groups regarding total calcium, ionized calcium and parathyroid hormone levels. Truncal ligation of the inferior thyroid arteries during bilateral subtotal thyroidectomy does not cause hypoparathyroidism or hypocalcaemia.

[Use of hyperbaric oxygenation in the therapy of experimental hypothyroidism]. / Primenenie giperbaricheskoi oksigenatsii v terapii éksperimental'nogo gipotireoza.

In animal experiments on rabbits the effect of hyperbaric oxygen was studied on the functional state of the myocardium, the cardiac resistance to induced peroxide lipid oxidation, the structural and functional changes in the thyroid gland and the state of microcirculation in the conditions of experimentally induced hypothyrosis. It was demonstrated that hyperbaric oxygen has a favourable effect on the state of myocardium and microcirculation.

Effect of preoperative iodine in patients with Graves' disease controlled with antithyroid drugs and thyroxine.

Thirty-four patients with Graves' disease, first rendered euthyroid with antithyroid drugs (ATD) then given supplementary thyroxine (T4), were randomly allocated to three treatment groups. In Group I ATD and T4 were stopped 10 days before partial thyroidectomy and the patients were treated with Lugol's iodine alone. In Group II the patients were treated up to the time of operation with ATD and T4 alone. In Group III ATD and T4 were continued until the day of operation, but the patients also received 10 days' treatment with Lugol's iodine. Analysis of the results showed that pre-operative iodine therapy in patients with Graves' disease, already rendered euthyroid with ATD and T4, made no difference to the vascularity of the gland, operative blood loss or thyroid follicular size. Over a third of patients in Group I, treated with Lugol's iodine alone for 10 days pre-operatively, had subnormal levels of thyroid hormones at the time of operation and this was also the Group in which the complications of partial thyroidectomy tended to occur. It is concluded that the addition of iodine preoperatively is unnecessary in the patient who is already euthyroid on ATD and T4.

Vascularization and iodide transport down regulation in rat goitre.

This study was designed to investigate, in the rat, the regulation of the amount of thyroid iodide and of its organification during the involution of an experimentally induced goitre. The goitre was obtained by drastic iodine deficiency; male Wistar rats received an iodide deficient diet for 6 months, supplemented with PTU during the last 2 months. The study was followed for 16 days after the beginning of iodide refeeding (daily iodine intake = 50 micrograms). The thyroid iodide, total thyroid organic iodine and plasma iodide, PBI and TSH concentrations were determined from day 0 to 16 and compared to their control values (rats on a normal iodide diet for 6 months). In addition, a stereological study was carried out to determine if the extent of the gland vasculature might be implicated in the regulation of the thyroid iodide content. The plasma TSH concentration was very high and constant for 8 days (2.40 +/- 0.37 and 2.45 +/- 0.43 on day 0 and 8 respectively vs 0.25 +/- 0.12 microgram/ml in control rats), whereas iodination and secretion were blocked for 4 days (0.34 +/- 0.19 and 0.5 +/- 0.1 on day 0 and 4 respectively vs 14.4 +/- 2.0 micrograms 127I/gland in control rats) (Wolff-Chaikoff effect). Thyroid iodide amount increased enormously for 2 days (2.5 +/- 0.6 and 2.45 +/- 0.55 respectively on day 1 and 2 vs 0.09 +/- 0.01 micrograms 127I/gland on day 0), then strongly decreased between 2 and 4 days (1.15 +/- 0.27 127I/gland).(ABSTRACT TRUNCATED AT 250 WORDS)

[Concentration of calcium and phosphorus in patients after thyroidectomy without ligation of the inferior thyroid arteries (author's transl)]. / Das Verhalten der Serumkalzium- und Serumphosphatwerte nach Eingriffen an der Schilddrüse ohne Ligatur der Aa. thyreoideae inferiores.

In 150 patients who underwent surgery of the thyroid gland without ligation of the inferior thyroid arteries the concentrations of calcium and phosphorus were examined and the patients checked for clinical signs of hypoparathyroidism. In 149 patients without symptoms of tetania over the first 3 postoperative days a decrease of calcium could be observed as it happens likewise after cholecystectomies. Only one patient presented an acute state of hypoparathyroidism postoperatively. In this case the decrease of calcium turned out to be very rapid. Omitting the ligation of the inferior thyroid arteries lowers the incidence of postoperative hypoparathyroidism thus meeting the demand for a functional resection.