Serum osteoprotegerin levels, endothelial function and carotid intima-media thickness in type 2 diabetic patients.

OBJECTIVES: Osteoprotegerin (OPG), a well-known protein that inhibits osteoclast formation and activity, might also be a potential marker for identifying patients with high cardiovascular risk. This study aimed to compare OPG levels, FMD, and CIMT measurements in subjects with vs. without diabetes and investigate the association of serum osteoprotegerin level with the early atherosclerotic markers, endothelial function, and carotid intima-media thickness (CIMT) in patients with type 2 diabetes mellitus (DM2). METHODS: Forty-nine patients with DM2 (F/M: 26/23, 49.3 ± 10.0 years) and 45 healthy volunteers (F/M: 26/19, 48.3 ± 7.5 years) were included in this cross-sectional study. Serum OPG levels were measured by solid-phase enzyme-linked immunosorbent assay (ELISA). Fasting plasma glucose (FPG) and HbA1c levels were measured. CIMT was measured by B-mode ultrasound, and endothelial function was evaluated via flow-mediated dilation (FMD) of the brachial artery with Doppler ultrasonography. RESULTS: Serum OPG levels were significantly higher in patients with DM2 (617.0 ± 111.0 pg/mL) compared to controls (481.0 ± 96.0 pg/mL, p < 0.001). While CIMT in diabetic patients (0.65 + 0.13 mm) was higher than controls (0.54 ± 0.10 mm, p = 0.009), FMD measurement was lower in DM2 group (4.2% ± 3.1 mm vs. 7.6% ± 4.1 mm, p = 0.01). Univariate analysis showed that OPG was associated with the presence of diabetes (OR: 6.999, p = 0.001, R2: 15.1%) and hypertension (OR = 6.925, p = 0.001, R2: 13.2%). There was no relationship between OPG levels and CIMT or FMD. CONCLUSION: Osteoprotegerin and CIMT levels were increased, and FMD measurements were decreased in patients with DM2. No association between CIMT, FMD, and OPG measurements was observed. The presence of DM and hypertension were associated with circulating OPG levels.

A clinical and pathophysiological approach to traumatic brain injury-induced pituitary dysfunction.

PURPOSE: This review aimed to evaluate the data underlying the pathophysiology of TBI-induced hypothalamo-pituitary dysfunction. METHODS: Recent literature about the pathophysiology of TBI-induced hypothalamo-pituitary dysfunction reviewed. RESULTS: Traumatic brain injury (TBI) is a worldwide epidemic that frequently leads to death; TBI survivors tend to sustain cognitive, behavioral, psychological, social, and physical disabilities in the long term. The most common causes of TBI include road accidents, falls, assaults, sports, work and war injuries. From an endocrinological perspective, TBIs are important, because they can cause pituitary dysfunction. Although TBI-induced pituitary dysfunction was first reported a century ago, most of the studies that evaluate this disorder were published after 2000. TBI due to sports and blast injury-related pituitary dysfunction is generally underreported, due to limited recognition of the cases. CONCLUSION: The underlying pathophysiology responsible for post-TBI pituitary dysfunction is not clear. The main proposed mechanisms are vascular injury, direct traumatic injury to the pituitary gland, genetic susceptibility, autoimmunity, and transient medication effects.

Does Primary Hyperparathyroidism Have an Association with Thyroid Papillary Cancer? A Retrospective Cohort Study.

BACKGROUND: To investigate the relationship between primary hyperparathyroidism (pHPT) and papillary thyroid cancer (PTC). METHODS: The perioperative findings of 275 patients with pHPT who underwent surgery between January 2014 and December 2017 were retrospectively reviewed. Thirty-one patients were diagnosed with pHPT and PTC concurrently. Pathology results and demographic findings of these patients were compared with 186 patients who underwent thyroidectomy and diagnosed with PTC at the same time interval. RESULTS: The co-occurrence of pHPT and PTC was 11.3% (31/275). The median ages of the pHPT, pHPT + PTC, and PTC groups were 55, 57, and 50 years old, respectively (p < 0.001). The diameter of tumor was smaller in the pHPT + PTC group [median 7 mm (range 0.5-25 mm) vs. 15 mm (range 1-100 mm)], with higher rates of microcarcinomas (p < 0.001), than the patients in the PTC group. Examination of tumor morphology showed higher rates of tumor capsule invasion and multicentricity in the pHPT + PTC group than those in the isolated PTC group (p = 0.02, p = 0.04, respectively). CONCLUSION: The pHPT + PTC group had significantly smaller tumor diameter than the PTC group. This result may support the idea that pHPT leads to overdiagnosis of PTC. However, observation of high rates of tumor capsule invasion and multicentricity in the pHPT + PTC group may suggest an associative etiology with more aggressive PTC.

Dehydroepiandrosterone sulfate/free androgen index ratio predicts a favorable metabolic profile in patients with polycystic ovary syndrome.

Potential effect of hyperandrogenemia on metabolic disturbances in polycystic ovary syndrome (PCOS) has always been a matter of interest. We analyzed the records of 125 patients with PCOS and 54 age-matched healthy women. All participants underwent biochemical and hormonal assessment and a 75 g oral glucose tolerance test was performed. PCOS and control groups were comparable in terms of age. Dehydroepiandrosterone sulfate/free androgen index (DHEAS/FAI) ratio was negatively correlated with body mass index (BMI) (p < .001), fasting glucose (p = .02), area under the curve (AUC) of glucose (p = .03), AUC of insulin (p = .001), homeostasis model assessment-estimated insulin resistance (HOMA-IR) (p < .001), and triglycerides (TG) (p = .009), and positively correlated with insulin sensitivity index (ISI) (p < .001) and high-density lipoprotein cholesterol (HDL-C) (p < .001) among PCOS patients. In logistic regression analysis, higher DHEAS/FAI ratio levels were associated with lower risk of low HDL-C [RR(95%CI); 0.97(0.95-0.98); p < .001] as well as atherogenic dyslipidemia (TG/HDL-C) [RR(95%CI); 0.97(0.94-0.99); p = .035] even after adjustment for BMI in the PCOS group. Androgens, DHEAS and FAI act differently on metabolic parameters. Our results demonstrate that high DHEA-S/FAI ratio levels are associated with a more favorable metabolic profile.

Osteoporosis development and vertebral fractures after abdominal irradiation in patients with gastric cancer.

BACKGROUND: Decrease in bone mineral density, osteoporosis development, bone toxicity and resulting insufficiency fractures as late effect of radiotherapy are not well known. Osteoporosis development related to radiotherapy has not been investigated properly and insufficiency fractures are rarely reported for vertebral bones. METHODS: Ninety-seven patients with gastric adenocarcinoma were evaluated for adjuvant treatment after surgery. While 73 out of 97 patients treated with adjuvant chemoradiotherapy comprised the study group, 24 out of 97 patients with early stage disease without need of adjuvant treatment comprised the control group. Bone mineral densities (BMD) of lumbar spine and femoral neck were measured by dual energy x-ray absorptiometry after surgery, and one year later in both groups. RESULTS: There was statistically significant decline in BMDs after one year in each group itself, however the decline in BMDs of the patients in the irradiated group was more pronounced when compared with the patients in the control group; p values were 0.02 for the decline in BMDs of lumbar spine, and 0.01 for femoral neck respectively. Insufficiency fractures were observed only in the irradiated patients (7 out of 73 patients) with a cumulative incidence of 9.6%. CONCLUSIONS: Abdominal irradiation as in the adjuvant treatment of gastric cancer results in decrease in BMD and osteoporosis. Insufficiency fracture risk in the radiation exposed vertabral bones is increased. Calcium and vitamin D replacement and other measures for prevention of osteoporosis and insufficiency fractures should be considered after abdominal irradiation.

PERCUTANEOUS ETHANOL INJECTION FOR BENIGN CYSTIC AND MIXED THYROID NODULES.

OBJECTIVE: We aimed to determine the effect of percutaneous ethanol injection (PEI) on volume of cystic and mixed thyroid nodules, thyroid function tests (TFTs), antibody titers, and cytologic changes for 1 year. METHODS: Fifty-five nodules from 53 patients with cystic and mixed properties treated with PEI were included. Nodule volumes, TFTs, and thyroid autoantibodies were analyzed at baseline, 6 months, and 12 months. Fine-needle aspiration biopsy (FNAB) was performed to PEI-treated nodules in the 12th month. Thyroid nodules were classified into three groups by structural properties (purely cystic, predominantly cystic, predominantly solid). RESULTS: PEI caused a volume reduction of 80.7% at 6 months and 82.1% at 12 months, without any serious complications. PEI was repeated 1.4 ± 0.4 times with a mean total ethanol amount of 3.6 ± 3.1 mL. Volume reduction in the purely cystic nodules in the 6th and 12th months after PEI was greater than the volume reductions in predominantly cystic and predominantly solid nodules. We found that smaller nodules had greater volume reductions after PEI in the 12th month. During the study, patients remained euthyroid. Antithyroglobulin levels were decreased at 12 months. None of the FNAB results were compatible with a malignant or suspicious for malignancy cytology at the 12th month. CONCLUSION: PEI is an effective means of treatment for benign cystic and mixed thyroid nodules, without any serious side effects. We can also assume that PEI is not a trigger for autoimmunity and malignancy development over the short term. ABBREVIATIONS: anti-TG = anti-thyroglobulin; anti-TPO = anti-thyroperoxidase; AUS = atypia of unknown significance; CV = coefficient of variation; FNAB = fine-needle aspiration biopsy; fT3 = free triiodothyronine; fT4 = free thyroxine; PEI = percutaneous ethanol injection; TFT = thyroid function test; TSH = thyroid-stimulating hormone; US = ultrasonography.

Biochemical and pathologic factors affecting technetium-99m-methoxyisobutylisonitrile imaging results in patients with primary hyperparathyroidism.

OBJECTIVE: Technetium 99 m methoxyisobutylisonitrile (Tc-99m MIBI) scintigraphy represents the most commonly utilized imaging modality for the detection of the diseased gland in patients with primary hyperparathyroidism (PHPT). In this study, we aimed to identify potential biological factors with an impact on MIBI sensitivity. METHODS: A total of 147 patients with surgically confirmed parathyroid adenomas were assessed retrospectively. Data including medical history, biochemical and hormonal measurements, cervical US, Tc-99m MIBI scans as well as pathology reports were retrieved and recorded. RESULTS: Of the 147 patients, there were a total of 77, 39, and 31 cases with a positive, negative, and suspicious parathyroid adenoma on Tc-99m MIBI scan, respectively. Serum calcium (Ca), parathyroid hormone (PTH) and 25 (OH) D levels were comparable among MIBI positive and negative patients [Ca: 11.5 ± 0.9 vs 11.3 ± 0.9 mg/dL (P = 0.42); PTH: 216 (146-347) vs 194 (140-317) pg/mL (P = 0.45); 25(OH)D: 8.4 (5.7-18.2) vs 10.0 (4.7-23.3) ng/mL (P = 0.64), respectively]. P-glycoprotein (P-gp) staining was negative in both groups. Also, pathological examination of tissue preparations revealed no difference in terms of the volume of the adenomas, incidence of cystic adenomas, cell-type dominance (oxyphilic cell), percent fat, and Ki-67 ratio in MIBI positive and negative groups. The rate of hyalinization was 13% in MIBI positive and 28% in MIBI negative subjects, the difference being statistically significant (P = 0.04). CONCLUSION: Presence of hyalinization in parathyroid adenomas was found to be negatively correlated with MIBI scan results.

THE RESULTS OF PARATHYROID HORMONE ASSAY IN PARATHYROID ASPIRATES IN PRE-OPERATIVE LOCALIZATION OF PARATHYROID ADENOMAS FOR FOCUSED PARATHYROIDECTOMY IN PATIENTS WITH NEGATIVE OR SUSPICIOUS TECHNETIUM-99M-SESTAMIBI SCANS.

OBJECTIVE: This study aimed to evaluate the results of parathyroid hormone (PTH) assay in parathyroid aspirates to determine uniglandular disease by an endocrinologist-performed ultrasound (US) in patients with discordant or negative technetium-sestamibi scans and to evaluate whether this procedure increases the number of focused parathyroidectomies (FPs). METHODS: We analyzed the data of 65 patients who underwent an endocrinologist-performed US-guided parathyroid fine-needle aspiration (FNA) with PTH wash-out, retrospectively. The results of PTH wash-out procedure and the reports of parathyroid surgery and pathology were reviewed. RESULTS: Of 65 patients, 54 had positive PTH wash-out results. The median serum PTH level of patients with positive and negative PTH wash-out results was 143 (25 and 75% interquartile range [IQR], 114 to 197) versus 154 (IQR, 115 to 255) pg/mL (P = .45), and the median PTH in FNA was 3,533 (IQR, 1,481 to 3,534) versus 6.0 (IQR, 1 to 6) pg/mL (P<.001), respectively. Forty-five patients underwent surgery. Of the operated patients, 42 had positive PTH wash-out results and had successful FP. Four patients with redo surgery had positive PTH wash-out results and were successfully re-operated with FP. Of 11 patients with negative PTH wash-out results, 3 had bilateral neck exploration (BNE) surgery and 2 patients were successfully operated, while surgery was unsuccessful in 1 patient, despite BNE. CONCLUSION: Our study results suggest that endocrinologist-performed US and parathyroid FNA with PTH wash-out increases the number and success of FPs. In particular, patients with redo surgery may benefit from this procedure. ABBREVIATIONS: 4D-CT = four-dimensional computed tomography BNE = bilateral neck exploration FNA = fine-needle aspiration FNAB = fine-needle aspiration biopsy FP = focused parathyroidectomy IQR = 25 and 75% inter-quartile range PHPT = primary hyperparathyroidism PPV = positive predictive value PTH = parathyroid hormone 99mTc = technetium US = ultrasound.

Correlation of BRAF mutation and SUVmax levels in thyroid cancer patients incidentally detected in 18F-fluorodeoxyglucose positron emission tomography.

The prognostic importance of 18F-fluorodeoxyglucose avidity in primary thyroid tumor and molecular basis responsible for its mechanism has not yet been well characterized. In this study, we aimed to evaluate the correlation between the maximum standardized uptake levels and B-type Raf kinase mutation positivity in incidentally detected papillary thyroid cancer patients during 18F-fluorodeoxyglucose positron emission tomography examination. We retrospectively evaluated 6873 18F-fluorodeoxyglucose-positron emission tomography scans of consecutive subjects from a database search for tumor staging in 2014 at our hospital Nuclear Medicine Center. In total, 135 patients had focal 18F-fluorodeoxyglucose uptake in the thyroid. Of these, 76 patients had fine-needle aspiration biopsy. 18F-fluorodeoxyglucose-maximum standardized uptake of the positron emission tomography-detected nodules was recorded. B-type Raf kinase (V600E) mutation and p53 protein expression were evaluated in papillary thyroid cancer patients. The incidence of thyroid incidentaloma in 18F-fluorodeoxyglucose-maximum standardized uptake scans was 2 % (135/6873). Of the 76 patients evaluated, 41 % (n = 31) were diagnosed papillary thyroid cancer. B-type Raf kinase mutation was positive in 51 % (17/30) of the papillary thyroid cancer patients. Maximum standardized uptake levels of the nodules (≥1 cm) were significantly higher in B-type Raf kinase-mutated papillary thyroid cancer patients than in non-mutated patients [16.6 (10.4-27.9) vs. 9.7 (6.8-11.1); P = 0.007]. Correlation analysis revealed that maximum standardized uptake was significantly associated with B-type Raf kinase mutation positivity (r = 0.519; P = 0.005). Logistic regression analysis showed an association between maximum standardized uptake and B-type Raf kinase mutation positivity even after adjustment for age and gender (P = 0.01). B-type Raf kinase mutation is closely related to 18F-fluorodeoxyglucose-positron emission tomography maximum standardized uptake levels in patients with incidentally detected papillary thyroid cancer.

Voice characteristics associated with polycystic ovary syndrome.

OBJECTIVES/HYPOTHESIS: To test the assumption that voice is changed in polycystic ovary syndrome (PCOS) and identify changes that occur. STUDY DESIGN: Cross-sectional pilot study. METHODS: Thirty patients with PCOS and a control group of 22 age-matched and body mass index-matched healthy women were included. Demographic data, anthropometric measurement, serum androgens, and Voice Handicap Index-10 were determined. Transnasal fiberoptic laryngoscopy and rigid stroboscopy were performed. Supraglottic hyperfunction was assessed during fiberoptic laryngoscopy. Presence of supraglottic hyperfunction was interpreted as abnormal muscle tension pattern. Glottal closure configuration and vibratory wave characteristics were evaluated via stroboscopy. Acoustic analysis was performed with the Dr. Speech software program version 4 (Tiger DRS Inc., Seattle, WA). RESULTS: Voice complaints and acoustic parameters were similar between groups, whereas serum androgens were significantly higher in patients (P < 0.001). Laryngeal examination detected pathology in 17 (56.7%) patients and two (9.1%) controls (P < 0.001). Fiberoptic examination determined supraglottic hyperfunction in 11 patients but in only two controls (P = 0.023). In stroboscopy, incomplete glottal closure configuration and impaired vocal fold vibration were present in 10 and 11 patients, respectively, whereas only one control had glottal closure abnormality and none of the controls had abnormal vibration (P = 0.028 and P = 0.001, respectively). CONCLUSION: Abnormal muscle tension patterns and impaired vocal fold vibration are frequent among patients with PCOS; but they are not accompanied by increased vocal symptoms or deteriorated acoustic voice parameters. This may be important for professional voice users or in extensive or extraordinary voice use demands in patients with PCOS. LEVEL OF EVIDENCE: 3b. Laryngoscope, 126:2067-2072, 2016.

A case of Madelung's disease accompanied by Klinefelter's syndrome.

UNLABELLED: Madelung's disease is a rare fat metabolism disorder characterised by benign multiple symmetric, encapsulated lipomatosis. The exact cause of the disease is unknown; it may be associated with chronic alcoholism and mutations in mitochondrial DNA (A8344G), but there have been cases without these factors reported in the literature. A 29-year-old man with a 6-year history of diabetes mellitus was admitted to our hospital for poorly regulated diabetes and decreased libido. He was not an alcohol consumer. His family history was unremarkable. Physical examination revealed that he had a eunuchoid body shape. There was a symmetric excess fat accumulation in his submandibular, deltoid, nuchal, suprapubic and inguinal areas. He was diagnosed with Madelung's disease, and imaging studies supported the diagnosis. Hormonal evaluation revealed a hypergonadotropic hypogonadism. Karyotype analysis revealed a 47,XXY mutation. Genetic research showed no mitochondrial DNA mutation. Metabolic disorders, such as diabetes mellitus, hyperlipidaemia, hyperuricaemia and liver disease, endocrine gland diseases, such as hypothyroidism, and neurological diseases, such as polyneuropathy and cognitive disorders, may accompany Madelung's disease. The present study represents the first reported case of Madelung's disease accompanied by Klinefelter's syndrome. LEARNING POINTS: Madelung's disease is a rare fat metabolism disorder characterised by benign multiple symmetric and encapsulated lipid accumulation.The exact cause of the disease is unknown.Metabolic disorders, such as diabetes mellitus, hyperlipidaemia, hyperuricaemia and liver disease, endocrine gland diseases, such as hypothyroidism, and neurological diseases, such as polyneuropathy and cognitive disorders, may accompany Madelung's disease.

Case report: patient with multiple paragangliomas treated with long acting somatostatin analogue.

Paragangliomas of the head and neck are uncommon neoplasms. They are usually benign, but tend to be locally invasive. Although surgical resection remains the definitive treatment, important issues about management arise when such lesions are inoperable. Beneficial effects of octreotide treatment have already been reported in a malign paraganglioma case. Here we report a 24 year old female with familial, bilateral, multiple paraganglioma in the head and neck region, who firstly presented with pulsatile tinnitus and hearing loss in her left ear. After embolization was performed, she underwent operation twice because of the gross tumor mass. No significant change in tumor size was determined after the operations, however there were no distant metastases. Although she experienced hypertension attacks, no hormonal overproduction was found in repeated measurements. As the tumor was unresectable, new alternative therapies were sought. Octreotide scintigraphy was positive in the tumoral tissue, so we began to treat her with somatostatin analogue octreotide. After a 16 month follow up period, an improvement of the performance status, the near normalisation of attacks and stabilization of tumor growth were achieved. However, in the last three visits, she began to experience symptoms more frequently and it had been necessary to increase the octreotide dose. She is now well and being followed up. In conclusion, the beneficial effects of octreotide treatment could be quantified by clinical, tumor and scintigraphic criteria. These data suggest that octreotide can be useful in the treatment of inoperable paragangliomas.