Outcomes of surgery and radioiodine treatment for neck recurrence in papillary thyroid cancer.

PURPOSE: Persistent/recurrent disease in the neck is frequent in patients with papillary thyroid cancer (PTC). The goal of this study was to evaluate the efficacy of the reoperation and radioiodine (RAI) treatment for persistent/recurrent disease after the initial treatment. METHODS: A total of 30 patients (13 M/17 F) with PTC were enrolled in this study. All had been submitted to total thyroidectomy for PTC and subsequently to reoperation for local persistent/recurrent disease. All had received RAI, before and/or after reoperation. The mean age at initial thyroidectomy and cancer diagnosis was 41.4±15.2 years. Initial T status was T1 in 22 cases (73.3%), T2 in 4 cases (13.3%) and T3 in 4 cases (13.3%). Initial N status was N0 in 2 cases (6.6%), N1 in 15 cases (50%) and Nx in 13 cases (43.3%). RESULTS: Reoperation reduced the mean stimulated thyroglobulin (stimTg) serum concentration from 76.1±165.5 ng/mL to 20.1±28.8 ng/mL, p=0.002. The RAI treatment provided to 19 patients after reoperation reduced further the stimTg values from 28.6±32.4 ng/mL after reoperation, to 11.3±20.4 ng/mL, p=0.003. According to the dynamic risk stratification after the reoperation 7 patients (23.3%) had excellent response, 4 (13.3%) had biochemically incomplete response, 9 (30.0%) had indeterminate response and 10 (33.3%) had still structural incomplete response. CONCLUSION: Surgery for local persistent/recurrent disease in papillary thyroid carcinoma reduces tumor burden, improves the biochemical and structural disease. Administration of therapeutic RAI after lymph node resections appears to further improve biochemical disease.

Thyroid ultrasonographic charasteristics and Bethesda results after FNAB.

PURPOSE: Thyroid nodular disease (TND) is a frequent clinical problem and the major concern is the probability of malignancy in a solitary nodule or in one or more nodules of a multinodular goiter. For this purpose, neck ultrasound and fine needle aspiration biopsy (FNAB) under ultrasound guidance have been established as the initial investigation of choice. METHODS: A total of 1113 patients (210 male/903 female) underwent FNABs for the same number of thyroid nodules. Correlated were the demographic profile (age and gender) and sonographic features of these nodules with the FNAB outcome. The Bethesda system (B) for reporting thyroid cytopathology was used. RESULTS: Out of total 1113 cases, 255 (22.9%) were characterised as nondiagnostic (B1), 780 (70.1%) were diagnosed as benign (B2), 35 (3.1%) were diagnosed as B3 (atypia/ follicular lesion of undetermined significance), 10 (0.9%) were diagnosed as B4 (follicular neoplasm or suspicious for follicular neoplasm), while 13 (1.2%) cases were categorized as B5 (suspicious for malignancy) and 20 (1.8%) as B6 (malignant). When comparing the sonographic features of nodules with benign cytology (category B2) vs those of nodules with cytology category B3-6, irregular shape and ill-defined margins of the nodule, and microcalcifications and the hypoechogenicity increased significantly the possibility for a B3-B6 cytology result (p<0.05). Finally, there was no association of gender and age with the (B) category results. CONCLUSION: The aforementioned sonographic findings decrease the possibility for a benign cytology result according to the Bethesda classification system. Key words: Bethesda classification system, fine needle aspiration biopsy, thyroid nodules, thyroid ultrasound.

Biochemical Effects of Levothyroxine Withdrawal in Patients with Differentiated Thyroid Cancer.

BACKGROUND: Patients with differentiated thyroid carcinoma (DTC) are submitted to withdrawal of levothyroxine (LT4) aftter thyroidectomy, in order to undergo radiodine ((131)I) treatment. PATIENTS AND METHODS: A total of 345 patients with a history of DTC were enrolled in the study. Their biochemical profile and serum free triiodothyronine (FT3), free thyroxine (FT4) and thyrotropin (TSH) levels were measured during withdrawal of LT4 treatment, and several months after restarting LT4. RESULTS: During withdrawal, the intra-individual percentage increase in total cholesterol, low density lipoprotein-cholesterol, very low density lipoprotein-cholesterol and triglycerides was of the order of 60-80% and that for high density lipoprotein-cholesterol 30%. Creatinine increased by 30%, whereas Na and K levels decreased by 1%. The increase for creatine phosphate kinase was around 200-300%, for aspartate aminotransferase and alanine aminotransferase 50-80%, for γ-glutamyl transpeptidase 10-20%, and for lactate dehydrogenase 25%. Glucose decreased by 1-4%. CONCLUSION: Short-term, acute hypothyroidism in patients with DTC induces significant alterations in several biochemical parameters. The presence of other deteriorating diseases should be considered before submitting these patients to LT4 withdrawal.

Primary thyroid lymphoma: The two ends of the spectrum.

We describe two different cases of prinary thyroid lymphoma (PTL). PTL is a rare malignancy. Nevertheless, it frequently presents diagnostic and therapeutic challenges. The first patient, a 79-year-old female, presented with a large, painless thyroid mass accompanied by severe obstructive symptoms of the upper respiratory and gastrointestinal track. The second patient (67-year-old female) presented with nodular goiter. Thyroidectomy - performed on the first patient for alleviation of obstructive symptoms - revealed the presence of a diffuse large B-cell lymphoma. Although she was administered standard chemotherapy she deceased four months later. In the second patient, primary thyroid lymphoma was an incidental finding following thyroidectomy performed for nodular goiter. These two cases illustrate the variable course of PTL, the possibility of which should be kept into consideration in clinical practice.

Association of Basal and Calcium-stimulated Calcitonin Levels with Pathological Findings After Total Thyroidectomy.

BACKGROUND/AIM: Medullary thyroid carcinoma (MTC) originates from thyroid C-cells and is a calcitonin-secreting tumor. Calcitonin is also elevated in C-cell hyperplasia (CCH). The objective of the study was to determine the optimal basal (bCT) and peak stimulated calcitonin (psCT) cut-off value for differentiating MTC from CCH, and to examine the histological findings of thyroidectomy in patients with maximum psCT >100 pg/ml. PATIENTS AND METHODS: Fifty-five patients had a maximum calcium-psCT >100 pg/ml and underwent total thyroidectomy. RESULTS: A total of 20 patients were diagnosed with MTC and the remaining 35 with CCH. A bCT level >17.4 pg/ml and psCT level >452 pg/ml demonstrated the best sensitivity and positive predictive value for differenting MTC from CCH. CONCLUSION: The overlap of calcitonin levels between MTC and CCH reduces the accuracy of the calcium stimulation test. Remarkably, an appreciable number of patients with psCT levels >100 pg/ml harbor differentiated thyroid carcinoma of follicular origin.

Seasonal variation of serum vitamin D among Greek female patients with osteoporosis.

BACKGROUND/AIM: Vitamin D (vitD) levels are positively associated with bone health and seasonality affects serum vit D. The aim of the study was to investigate the degree of seasonal variation on 25-hydroxyvitamin D (25(OH)D) serum levels in a population-based cohort of post-menopausal women with osteoporosis. PATIENTS AND METHODS: Serum levels of 25(OH)D were assessed in 596 patients (mean age=65.3 years; standard deviation (SD)=9.4) in different time points over a period of 2.5 years. RESULTS: The minimum 25(OH)D serum levels were observed in March (13.4±9.5 ng/ml) and the maximum levels in August, September and October (29.1±16.1, 28.9±12 and 28.4±8.9 ng/ml, respectively). The prevalence of vitD deficiency, insufficiency and sufficiency in March was 76.5, 15.7 and 7.8%, respectively. On the contrary, the highest prevalence of vitD sufficiency was observed in August, September and October (38.1%, 45.3% and 46.5%, respectively). CONCLUSION: Seasonal variations should be considered when measuring for 25(OH)D serum levels and treating vitD deficiency.

Markers of bone metabolism in eugonadal female patients with beta-thalassemia major.

Osteoprotegerin (OPG) and receptor activator of NF-kappaB ligand (RANKL) have been recently implicated in the pathogenesis of various types of osteoporosis. The aim of this study was to investigate bone turnover in eugonadal female patients with this disease and characterize the possible role of the OPG/RANKL system in thalassemia-related bone loss. Markers of bone turnover and bone mineral density (BMD) were measured in 16 eugonadal young females with beta-thalassemia major and 18 age- and sex-matched healthy controls. Bone turnover was significantly increased in thalassemic patients compared to controls but OPG was significantly higher in healthy subjects. BMD values negatively correlated with urine markers of bone resorption but not with OPG/sRANKL system.

Circulating osteoprotegerin and receptor activator of NF-kappaB ligand system in patients with beta-thalassemia major.

Osteoporosis represents an important cause of morbidity in patients with beta-thalassemia major, and its etiology is multifactorial. Thus, the aim of this study was to characterize the possible role of the osteoprotegerin (OPG) and receptor activator of the NF-kappaB ligand (RANKL) system in thalassemia-related bone loss. Serum concentrations of OPG, soluble RANKL (s-RANKL), markers of bone turnover, and lumbar spine bone mineral density (BMD) were measured in random samples of males (n = 29; mean age +/- SEM, 24.26 +/- 1.29 years; range, 13-41 years) and females (n = 31; age, 24.59 +/- 0.95 years; range, 12-34 years) with beta-thalassemia major and in 30 healthy age-, height-, and weight-matched subjects. Thalassemic patients had significantly lower levels of OPG compared with controls (2.54 +/- 0.12 vs. 3.25 +/- 0.122, respectively; P < 0.05) and higher, albeit not statistically significantly, serum levels of s-RANKL (0.350 +/- 0.03 vs. 0.295 +/- 0.046, respectively; P < 0.05). s-RANKL correlated negatively with age (r = -0.3, P < 0.05), and OPG correlated positively with the duration of the interval between the onset of transfusions and chelation therapy (r = 0.52, P < 0.001). Regarding markers of bone metabolism, plasma values of osteocalcin correlated positively with s-RANKL (r = 0.40, P < 0.05) and negatively with OPG/s-RANKL ratio (r = -0.55, P < 0.01). In multiple regression analysis only cross-linked N-teleopeptide of type I collagen (NTX) significantly accounted for BMD. Although the OPG/RANKL system may have some clinical usefulness as a marker of bone turnover in beta-thalassemia, conventional markers of bone turnover more accurately represent changes in the BMD of these patients.

Medical treatment of acromegaly: comorbidities and their reversibility by somatostatin analogs.

Relief of symptoms can be achieved following surgery for growth hormone (GH)-secreting adenomas, as well as after pharmacological therapy with somatostatin analogs. Recently, long-acting somatostatin analog depot formulations, octreotide LAR and lanreotide SR have become available. Somatostatin analogs control GH/insulin-like growth factor (IGF)-1 excess, induce tumor shrinkage in a high proportion of patients, improve symptoms of acromegaly with relatively limited side effects and are successfully administered in patients not suitable for surgery. Furthermore, preoperative somatostatin analogs have been suggested to improve outcome for tumors with limited invasiveness, while surgical tumor debulking in cases that are, at least partially, somatostatin resistant, increases the achievement of normal IGF-1 levels by postoperative somatostatin analog treatment. Effective control of hypertension, as well as diabetes, is mandatory in order to reduce the increased vascular morbidity/mortality. Control of GH/IGF-1 excess generally improves glucose metabolism. Somatostatin analogs improve insulin sensitivity, exerting, however, a concomitant direct inhibitory effect on insulin secretion, with a net balance leaning towards a deterioration in glucose homeostasis. As a result, oral insulin secretagogues (and/or insulin) should probably be preferred to insulin sensitizers in acromegalic patients developing diabetes while on somatostatin analogs. Nevertheless, glucose tolerance remains normal in most of the nondiabetic acromegalic patients, while diabetic acromegalic patients on insulin are at risk for hypoglycemia during initiation of somatostatin analog therapy. Although successful management of acromegaly has been associated with improvement in morphological and functional parameters of cardiomyopathy, limited and conflicting information is available regarding the effect on blood pressure control. Contradictory results have also been reported regarding sleep hypopnea or apnea in treated acromegalic patients. As acromegalic skeletal abnormalities are rather irreversible, apneic episodes may persist after normalization of hormonal levels. Aggressive therapy, including surgery, pharmacological treatment and, in some cases, pituitary irradiation, aiming at normalization of IGF-1 levels, is required for arthropathy management. Some improvement in pain, crepitus and range of motion has been observed after treatment with somatostatin analogs. Information on the impact of disease control, either by surgery or somatostatin analog treatment, on gonadal function is limited. Finally, the link between the hormonal/biochemical and the psychiatric/psychological features of acromegaly, as well as a potential basis for positive effects of somatostatin analog therapy remain unclear.

Hypoparathyroidism in transfusion-dependent patients with beta-thalassemia.

Hypoparathyroidism is thought to be a rare consequence of iron overload seen in beta-thalassemic transfused patients. This study was conducted to determine the prevalence of hypoparathyroidism in a large number of beta-thalassemic patients, and its potential correlation with the presence of other endocrinopathies caused by iron overload. Serum and urine biochemical parameters were measured in 243 thalassemic patients (136 females and 107 males) in order to determine the prevalence of hypoparathyroidism and evaluate bone turnover. The patients were divided into two groups according to the presence of hypoparathyroidism. We compared the prevalence of other endocrinopathies and disease complications in the two groups. Hypoparathyroidism was detected in 13.5% of the patients (33 subjects; 17 males and 16 females). Serum-intact parathyroid hormone, and total and ionized calcium were significantly lower, while phosphorus was significantly higher in thalassemic patients with hypoparathyroidism. The reduction in BMD was more prominent in normal thalassemic patients (Z score = -2.246 +/- 0.97) compared with those with hypoparathyroidism (Z score = -1.975 +/- 0.89), although the difference was not statistically significant. Disturbed glucose metabolism was more common in patients with hypoparathyroidism (P < 0.05). In addition, heart dysfunction was statistically more frequent in this group (odds ratio = 2.51, P < 0.05). Hypoparathyroidism is a not infrequently observed complication in thalassemic patients. Since the concentration of ferritin is not a valuable tool in the prediction of the development of hypoparathyroidism, parathyroid function should be tested periodically, particularly when other iron overload-associated complications occur.

Evaluation of bone mineral density of the lumbar spine in patients with beta-thalassemia major with dual-energy x-ray absorptiometry and quantitative computed tomography: a comparison study.

Osteoporosis is a common, multifactorial cause of morbidity in patients with beta-thalassemia. The present study was performed to compare bone mineral density (BMD) results in the lumbar spine of thalassemic patients measured by both dual-energy x-ray absorptiometry (DEXA) and quantitative computed tomography (QCT), and to determine their correlations with the markers of bone turnover. BMD was measured in the lumbar spine of 13 regularly transfused patients with beta-thalassemia major by both DEXA and QCT. Blood and urine samples were obtained for the determination of biochemical and hormonal profiles. Both T-scores and Z-scores were higher when measured by QCT (T-score = -0.41 +/- 1.31, Z-score = -0.56 +/- 1.08, mean +/- SD) compared with the values given by DEXA (T-score = -2.57 +/- 0.88, Z-score = -2.32 +/- 1.11, P = 0.0005). In comparison to DEXA, QCT T-scores were more closely correlated with age (r = -0.19 vs. r = -0.70, P = 0.0068). Strong negative correlation was found between QCT values and age (r = -0.67, P = 0.01). In comparison to DEXA T-scores, QCT T-scores were more closely correlated with osteocalcin, urine N-telopeptide cross-links of type I collagen, and deoxypyridinoline, but without statistical significance. DEXA T-scores were better correlated only with urine C-terminal telopeptides of type I collagen, but again without statistical significance. These results imply that the two methods cannot be used interchangeably in assessing BMD in thalassemic patients. However, which one of these two techniques more precisely determines the overall strength of vertebrae in patients with beta-thalassemia remains to be investigated.

Endocrine pancreatic insufficiency in chronic pancreatitis.

Chronic pancreatitis (CP) is considered to be a rare cause of diabetes mellitus. However, in both the developed and developing world, there is an increasing number of patients suffering from pancreatitis probably due to lifestyle changes, which is partially associated with both social factors and the poor health status of immigrants. Owing to these circumstances, CP has evolved with one of the possible causes of diabetes in a selected group of patients and should be included in the differential diagnosis of diabetes. Several studies have shown that the long-term rate of diabetic complications in patients with CP and insulin-dependent diabetes is similar to that in patients with type 1 diabetes of equal duration. The hypothesis that early diagnosis of CP should result in better prognosis is not validated and may complicate the issue, since the risk of diabetes has been shown to increase significantly only once pancreatic calcification has developed. Accumulative evidence suggests that the risk of diabetes is not influenced by elective pancreatic surgical procedures other than distal pancreatectomy. The lack of contemporary data points to the urgent need for large prospective studies in order to accurately evaluate the special characteristics of disorders in glucose homeostasis in patients with CP.