A rare case of poorly differentiated mixed neuroendocrine-nonneuroendocrine tumor of the caecum with long term survival: A case report.

A 59-year-old woman presented with flushing attacks accompanied by tachycardia and hypotension, which lasted approximately 30 to 60 minutes, underwent 18 years ago a gastrointestinal tumor resection. The histologic examination revealed a poorly differentiated mixed neuroendocrine/adenocarcinoma located in the caecum with regional metastases. Postoperatively, the patient received combined chemotherapy of 5-fluorouracil with interferon for six months and since has remained asymptomatic. Her examination revealed positivity for chromogranin A (CgA) and a-Fetoprotein (aFP) (580 ng/24 h, normal range 27-94, and 10 IU/mL, normal range 0-6, respectively). Urinary 5-hydroxy indole acetic acid excretion was remarkably high (41.8 mg/24 h, normal range 2-10 mg/24 h). An abdominal Magnetic Resonance Imaging scan revealed multiple focal loci in the liver whose histological examination revealed a carcinoid tumor confirmed by an Octreoscan. Additional uptake was noted on the right shoulder and the right sternum-clavicle joint confirmed by Tc-99m MDP scan. The patient received somatostatin analogue therapy followed by long-acting release octreotide analogue therapy (30 mg/month) showing a partial improvement of relevant biomarkers. Two years later, carcinoid syndrome symptoms reappeared and due to the tumors expression of somatostatin receptors the patient received peptide receptor radionuclide therapy with 177Lu-DOTATATE that resulted in both clinical and biochemical improvements.

Prevalence and geographic variation of abdominal obesity in 7- and 9-year-old children in Greece; World Health Organization Childhood Obesity Surveillance Initiative 2010.

BACKGROUND: In children, abdominal obesity is a better predictor of the presence of cardiovascular risk factors than body mass index (BMI)-defined obesity. We aimed to evaluate the prevalence of abdominal obesity in the Greek pediatric population and to assess the impact of residence on the prevalence of both BMI-defined and abdominal obesity. METHODS: In the context of the Childhood Obesity Surveillance Initiative of the World Health Organization (WHO) Regional Office for Europe, a national representative sample of 7.0-7.9 and 9.0-9.9-year-old children was evaluated (n = 2,531 and 2,700, respectively). Overweight and obesity according to BMI were estimated using both the WHO and International Obesity Task Force cut-off points. Abdominal obesity was defined as waist circumference/height ratio >0.5. RESULTS: The prevalence of abdominal obesity did not differ between 7-year-old boys and girls (25.2 and 25.3%, respectively; p = NS). Among 9-year-old children, abdominal obesity was more prevalent in boys than in girls (33.2 and 28.2%, respectively; p = 0.005). Among normal weight and overweight children, the prevalence of abdominal obesity was 1.6-6.8 and 21.8-49.1%, respectively. The prevalence of abdominal and BMI-defined obesity did not differ between children living in the mainland, in Crete and in other islands except in 7-year-old girls, where the prevalence of BMI-defined obesity was highest in those living in Crete, intermediate in those living in other islands and lowest in those living in the mainland. In 9-year-old boys and in 7- and 9-year-old girls, the prevalence of abdominal obesity was highest in children living in Athens and lowest in children living in Thessaloniki, whereas children living in other cities and in villages showed intermediate rates. The prevalence of abdominal obesity in 7-year-old boys and the prevalence of BMI-defined obesity did not differ between children living in cities and villages. CONCLUSIONS: The prevalence of pediatric abdominal obesity in Greece is among the highest worldwide. Boys and children living in the capital are at higher risk for becoming obese. Given that abdominal obesity is more prevalent than BMI-defined obesity and appears to be more sensitive in identifying cardiovascular risk, measurement of waist circumference might have to be incorporated in the screening for childhood obesity.

Patients with Hashimoto's thyroiditis present higher immune response to COVID-19 mRNA vaccine compared to normal individuals.

AIM: To evaluate the response (titers of anti-COVID-19 antibodies) to COVID-19 mRNA vaccine of patients with Hashimoto's thyroiditis and normal individuals. PATIENTS AND METHODS: Twenty-four patients with Hashimoto's thyroiditis and 51 normal individuals were studied after the third dose of the vaccine. RESULTS: Patients with Hashimoto's thyroiditis showed significantly higher immune response after the third dose of the COVID-19 mRNA vaccine compared with normal individuals (p = 0.020). After elimination of the four smokers with Hashimoto's thyroiditis, the immune response between the remaining 20 non-smoking patients compared with the response of the 23 non-smoking normal individuals was not different (p = 0.564). There was a significant positive correlation of the anti-COVID-19 antibodies with BMI (p = 0.029) but not with waist circumference in the patients with Hashimoto's thyroiditis (p = 0.054). Similar correlations were not found in normal individuals. Waist circumference could be considered as representative of visceral adipose tissue. In obese normal individuals (BMI ≥ 30), anti-COVID-19 antibodies were not different from those in lean normal individuals (BMI < 25). In obese patients with Hashimoto's thyroiditis, anti-COVID-19 antibodies were significantly higher compared to those in lean patients (p = 0.013). Median anti-COVID-19 antibody titer in obese patients with Hashimoto's thyroiditis was also significantly higher compared to that in obese normal individuals (p = 0.009). CONCLUSIONS: Patients with Hashimoto's thyroiditis show significantly higher immune response after the third dose of the COVID-19 mRNA vaccine compared with normal individuals. Obese patients with Hashimoto's thyroiditis show additionally a significantly higher immune response compared with lean patients.

Anthropometric indicators of insulin resistance.

During recent years, there have been numerous published reports associating increased circumferences of certain regions of the human body with insulin resistance or increased risk of cardiovascular disease. In the present review, we summarize the findings and conclusions of some of these publications.

The effects of recombinant human TSH on bone turnover in patients after thyroidectomy.

Thyrotropin receptors are expressed in several extrathyroidal tissues including bone. We investigated whether the increase of thyroid-stimulating hormone (TSH) levels, under stable thyroid hormone levels, affects the bone markers. Thirty-two postmenopausal women, with papillary thyroid carcinoma, previously treated with near-total thyroidectomy and I131 remnant ablation underwent routine evaluation for residual disease by using injections of recombinant human TSH (rhTSH) without withdrawal from thyroxine therapy. Changes in TSH levels and various serum and urine markers of bone metabolism were followed before and 1, 2, 5, and 7 days after the rhTSH injections. A transient, significant decrease in serum calcium and urinary excretion of C- and N-terminal telopeptides of type I collagen was observed after the injections of rhTSH. Serum parathyroid hormone (PTH) started to rise along with TSH, but a significant increase of PTH was only reached on Day 5 when the TSH concentration had fallen more than 80% of the peak value. Bone alkaline phosphatase and osteocalcin did not show any significant change over time. There was no significant correlation between TSH concentration and the various parameters we measured. The study provides evidence that rhTSH produces a transient inhibition of bone resorption, as well as an attenuation of osteoblast response in spite of the PTH activation. Additional studies are needed to resolve the mechanisms by which TSH alters the response of the bone cells.

Excessive Leukocytosis Leading to a Diagnosis of Aggressive Thyroid Anaplastic Carcinoma: A Case Report and Relevant Review.

INTRODUCTION: Leukocytosis and particularly neutrophilia are usually caused by acute infection, inflammation, and myeloproliferative neoplasms. However, leukocytosis can also occur in patients with malignancy either due to bone marrow metastases or in the context of a paraneoplastic syndrome. CASE PRESENTATION: An 86-year-old female was admitted to our hospital due to marked leukocytosis (white blood cells [WBC] >40,000/µL), neutrophilia, and monocytosis. She was afebrile and reported hoarseness and mild difficulty swallowing. Upon physical examination, lung auscultation revealed inspiratory wheezing and a non-tender mass was observed in the anterior midline of the neck. Blasts and immature WBC were not found, and polymerase chain reaction for the detection of BCR/ABL gene was negative. A mass (5.4 cm in diameter) of abnormal parenchymal composition with calcifications occupying the right lobe, was seen on thyroid ultrasound. Cytology, after fine-needle aspiration, showed an anaplastic thyroid carcinoma (ATC). The cervical and chest computed tomography scan revealed a low-density lesion with calcifications that shifts and presses the trachea and multiple lung nodular lesions bilaterally. Since the case was inoperable and the airway was severely obstructed, a DUMON stent was placed. Biopsy of specimens from the trachea lesion revealed a tumor with significant atypical cells and focal squamoid features. The patient's WBC increased to 72,470/µL. Additionally, interleukin-6 (IL-6) was markedly elevated (20.2 pg/mL). The patient passed away due to respiratory arrest 55 days after her initial admission. DISCUSSION: Excessive leukocytosis in a patient, having excluded infectious disease and myelodysplastic syndrome, could represent a manifestation of a paraneoplastic syndrome due to various cytokines secretion from the tumor. In our case, ATC synthesized and secreted IL-6, which seems to be the cause of severe leukocytosis.

Normalization of thyroid hormone levels in patients with either hyper- or hypothyroidism results in a profound change of atrial natriuretic peptide (ANP) levels.

Atrial Natriuretic Peptide (ANP) is a hormone produced by cardiac atrial myocytes. Thyroid hormones may affect its release. The aim of this study was to analyze the effect of hyper and hypothyroidism on the secretion of ANP and its relationship with the changes of the renin-angiotensin-aldosterone system. Plasma ANP concentration as well as plasma renin activity (PRA) and aldosterone (ALDO) were measured in 21 patients with hyperthyroidism, 12 patients with hypothyroidism and 29 normal controls. Moreover, in 5 hyperthyroid and 8 hypothyroid patients hormones measurements were performed at diagnosis and 15, 30, 45 and 60 days after starting the appropriate therapy. Statistical analysis was performed employing the Wilcoxon two sample test to compare the ANP levels in normal and hyper or hypothyroid patients while the pairwise comparisons were evaluated using the Spermans rank correlation. Partial correlation and regression models were used to examine the joint effects of multiple predictors on ANP. ANP levels were significantly higher in hyperthyroid (mean+/-SEM, 17+/-1.7 pmol/L, +/-<0.001) and lower in hypothyroid patients (6.18+/-1.14 pmol/L, p<0.01) compared to normals (10.35+/-0.59 pmol/L). In the hyperthyroid patients following treatment with antithyroid drugs plasma ANP levels reached normal values after 15 days and remained stable thereafter. In the hypothyroid patients, ANP levels increased gradually following initiation of treatment with thyroxine, reaching values comparable to controls at day 45. PRA was significantly higher only in hyperthyroid patients compared to controls. ALDO concentrations were not different in all groups studied. No correlation was found between plasma ANP levels and T3, T4, TSH, PRA and ALDO levels in the individual groups, while a positive correlation for T3 (r=0.610, p<0.01), T4 (r=0.653, p<0.01) and pulse rate (r=0.704, p<0.01) and negative correlation with TSH (r=-0.519, p<0.01) was found when all groups were pooled together. In conclusion, our data indicate that thyroid hormones affect positively ANP secretion from cardiac myocytes. This effect may be, at least in part, indirect via hemodynamic alterations.

An Average Body Circumference Can Be a Substitute for Body Mass Index in Women.

Introduction. Significant correlations between BMI and some body circumferences have been previously reported. In this study we investigated if the average of the sum of eight body circumferences can be a substitute for BMI. Patients and Methods. BMI and eight body circumferences (neck, waist, hip, arm, forearm, wrist, thigh, and ankle) were measured in 193 apparently healthy women aged 20-83, and within a wide range of BMI. Women with BMI ≤ 24.9 were designated as normal, with BMI 25-29.9 as overweight and with BMI ≥ 30 as obese. The relationship of the average body circumference (ABC) of the sum of the eight circumferences, and of each individual circumference with BMI, was evaluated. Results. ABC had the strongest correlation with BMI (r = 0.95, P < 0.001) among all the circumferences tested. Hip circumference had the strongest correlation with BMI (r = 0.89, P < 0.001) among the circumferences of individual body sites. Receiver-Operator Characteristic analysis showed that women with ABC > 44.0 cm could be recognized as having BMI ≥ 25 with sensitivity 90.2% and specificity 88.5%, while women with ABC > 47.1 cm could be diagnosed as having BMI ≥ 30 with sensitivity 92.2% and specificity 91.5%. Conclusion. An average body circumference strongly correlated with BMI in women and can serve as a surrogate of BMI.

Hemodynamic markers and subclinical atherosclerosis in postmenopausal women with primary hyperparathyroidism.

CONTEXT: Recent evidence suggests that primary hyperparathyroidism (pHPT) is linked with hypertension and subclinical atherosclerosis. These associations have not been examined in postmenopausal women, in whom cardiovascular risk steeply rises after menopausal transition. OBJECTIVE: The objective of the study was to assess whether pHPT is associated with hemodynamic markers and subclinical atherosclerosis in postmenopausal women under a cross-sectional case-control design. METHODS: One hundred two postmenopausal women with pHPT and 102 women matched 1:1 for age and menopausal status were consecutively recruited. In all patients, flow-mediated dilatation, carotid-femoral pulse wave velocity, reflected waves, aortic blood pressures (BP), intima-media thickness, and the presence of plaques in the carotid and common femoral arteries were measured. RESULTS: Women with pHPT had higher aortic and peripheral BP (P < .05 for all), but no correlation was observed with subclinical atherosclerosis. After adjusting for possible confounders, pHPT was an independent determinant of peripheral and aortic diastolic BP (P < .05 for all). The association with systolic BP was lost after adjusting for C-reactive protein. Further adjustment for PTH and 25-hydroxyvitamin D levels revealed that PTH but not 25-hydroxyvitamin D was an independent determinant of all BP parameters. Both peripheral and aortic BP increased across PTH tertiles as compared with the control group, but this association lost significance after adjustment for C-reactive protein. CONCLUSIONS: These results suggest that pHPT may increase peripheral and aortic BP through PTH and inflammatory-mediated mechanisms. A direct impact of the disease on the arterial wall cannot be implicated despite the large number of markers of subclinical atherosclerosis measured in this study.

The pluses and minuses of bariatric surgery for morbid obesity: An endocrinological perspective.

Obesity both in adults and children has emerged as a worldwide epidemic. Obesity is associated with an increased risk of a number of comorbidities including type 2 diabetes mellitus, hypertension, dyslipidemia, obstructive sleep apnea, certain types of cancer, degenerative joint disease, non-alcoholic fatty liver disease, reflux esophagitis, stroke, coronary heart disease, venous stasis ulcers, cholelithiasis, erectile dysfunction and polycystic ovary syndrome. It is now generally accepted that bariatric surgery procedures induce long-term weight loss and offer resolution or dramatic improvement in numerous comorbidities of obesity, including type 2 diabetes mellitus, hypertension and dyslipidemia. These effects mainly arise from endocrine changes resulting from the gastrointestinal surgical procedures. The aim of this short review was to evaluate the pros and cons of bariatric surgery for morbid obesity seen from the perspective of a practicing endocrinologist.

Metastatic papillary thyroid carcinoma to the maxilla: case report and literature review.

Metastatic tumors to the oral cavity are uncommon and a thyroid origin is considered exceedingly rare. A case of metastatic papillary thyroid carcinoma (PTC) presenting as a painful swelling in the right posterior maxilla of a 63-year-old male is reported here. The patient had been diagnosed with PTC 2 years ago and treated with thyroidectomy and radioactive iodine treatment. Radiographically, the metastatic lesion presented as a poorly-defined radiolucent lesion around an impacted maxillary third molar in the right maxilla. Histopathologic examination revealed features of PTC which was immunohistochemically positive for pancytokeratin, keratin 19 and thyroglobulin. Imaging studies revealed the presence of residual maxillary and neck disease as well as additional metastatic lesions in the sternum, ribs, and left tibia. A thorough review of the English language literature revealed only 36 previously published cases of thyroid cancer metastases to the oral cavity, the demographic and clinicopathologic features of which are summarized.

Detection of prostate cancer by sialic acid level in patients with non-diagnostic levels of prostate-specific antigen.

INTRODUCTION: Ideally, there will be reproducible markers easily and non-invasively available to test for malignancy, or alternative procedures when there is no accurate marker available. For prostate cancer, one of the most common cancers in men, levels of prostate-specific antigen (PSA) lack specificity and sensitivity for the determination of malignancy when they fall within a range of values termed the 'grey zone'. OBJECTIVE: To examine the predictive value of sialic acid in prostate neoplasms. STUDY DESIGN: In our study of diagnostic accuracy we recruited 70 men complaining of urinary symptoms who presented in the urology department as outpatients or inpatients. All patients were checked with biopsy and pathology in order to relate benign and malignant lesions of the prostate to levels of sialic acid, a member of a family of acetylated products of neuraminic acid, which has so far proved to be a very sensitive and accurate marker of malignancy. RESULTS: The sialic acid level was found to be elevated in patients with prostate cancer (mean 75.06±10.4 mg/dl) and reduced in patients with benign prostate hyperplasia (mean 57.086±8.7 mg/dl) (p<0.01); it had a sensitivity of 86% and specificity of 84% in diagnosing malignancy. CONCLUSION: Sialic acid can be used as an adjunct in predicting prostate malignancy when PSA values fall in the grey zone.

Hyperinsulinemia during oral glucose tolerance test and high normal serum cortisol are associated with increased secretion of calcitonin in normal subjects.

OBJECTIVE: Previous studies showed that insulin stimulated directly calcitonin (Ct) secretion in the pig thyroid, while dexamethasone stimulated the production of Ct and Ct mRNA in medullary thyroid carcinoma (MTC) cell lines. The objective of this study was to investigate if hyperinsulinemia during the oral glucose tolerance test (GTT) stimulates Ct secretion in normal subjects as well as to examine the relationship between serum cortisol and Ct. DESIGN: In 26 normal subjects (9 men and 17 women) with detectable basal serum Ct, aged 22-70 yr [51.5±14.6 (mean±SD), median 55.5], we measured serum or plasma Ct, cortisol, ACTH, insulin, and blood glucose before (0 min) and at 30, 60, 90, and 120 min after ingestion of 75 g glucose. RESULTS: During GTT mean serum cortisol increased slightly by 9.3% at 30 min, whereas mean serum insulin increased 9.4-fold, reaching a peak value at 60 min. Median serum Ct increased by 51% (p<0.001) in normal subjects (by 27% in men, p=0.004, and by 44% in women, p<0.001) at 30 min and remained significantly higher thereafter (up to 120 min) when compared to median baseline level. Regression analysis showed that basal serum cortisol, but not basal serum insulin, was correlated with basal serum Ct (p=0.01). Peak concentrations of Ct were also correlated with peak concentrations of cortisol at 30 min (p<0.001) but not at later time points. Serum insulin was correlated with serum Ct at the serum insulin peak level (60 min), and at later time points (90 and 120 min) (p=0.001). Multiple and simple regression analysis showed that calcitonin-AUC (Area Under Curve) values correlated with insulin-AUC (p=0.003), and also with cortisol-AUC (p=0.02) values, the standardized effect of insulin-AUC on Calcitonin-AUC being greater than that of cortisol-AUC. CONCLUSIONS: These findings suggest that acute hyperinsulinemia during GTT is very likely associated with increased Ct secretion in normal subjects. Serum cortisol within the physiological range was also correlated with serum Ct under basal conditions, as well as during GTT.

Changes in risk factors and Tumor Node Metastasis stage of sporadic medullary thyroid carcinoma over 41 years, before and after the routine measurements of serum calcitonin.

The measurement of serum calcitonin (CT) in all thyroid nodules for the detection of medullary thyroid carcinoma (MTC) is controversial. We compare several prognostic factors, Tumor Node Metastasis (TNM) stage, and survival in sporadic MTC patients operated on before and after the use of routine measurements of serum CT in combination with thyroid ultrasonography (US). Thirty-seven patients had been operated on between 1969 and 1989 (group I), before the use of routine measurements of serum CT and the routine use of thyroid US, and 39 (group II) had been operated on between 1990 and 2009, after the introduction of routine use of serum CT and thyroid US. There were no between-group differences concerning age and sex. Group I had larger tumors at the time of operation (P < .001) and higher postoperative serum CT levels (P < .001). Cervical lymph node and distant metastases were found more frequently in group I in comparison with group II. The cases with TNM stage I were significantly higher in group II than in group I, in contrast with the cases with TNM stage IV that were significantly higher in group I. Univariate analysis revealed a significantly higher 15-year survival rate in group II than in group I (P = .002). The postoperative CT levels were positively correlated with tumor size (P < .001). During the last 2 decades, the diagnosis of sporadic MTC at an earlier stage has been made possible by the routine use of serum CT in combination with thyroid US. The significant increase of the 15-year survival rate shows better outcome in these patients.