The lateralization accuracy of inferior petrosal sinus sampling in Cushing's disease: experiences of a tertiary center.

BACKGROUND: The purpose of this study is to determine the accuracy of bilateral inferior petrosal sinus sampling (IPSS) in lateralization and to investigate variables associated with accurate IPSS lateralization prediction. METHODS: Initially, data from 55 patients who underwent IPSS in our institution were reviewed retrospectively. IPSS lateralization and pituitary magnetic resonance imaging (MRI) results of these patients were compared with postoperative follow-up and immunohistochemical data to calculate the positive predictive values (PPVs) for IPSS and MRI. Variables likely to be associated with the accurate prediction of IPSS lateralization were analyzed. RESULTS: Twenty-seven patients (85.2% female, mean age of 38.5 ± 13.1 years) were enrolled in the study. With IPSS, interpetrosal ratios were found to be ≥ 1.4 in 26 (96.2%) cases, and this ratio correctly predicted adenoma localization for 18 patients (PPV: 69.2%). For 16 (59.2%) patients, right lateralization was detected, while left lateralization was detected for 10 (37%) patients. Right-sided IPSS lateralization was associated with enhanced accuracy (p = 0.026). No masses were detected in the MRI images of 10 (37%) patients, while microadenoma of ≤ 6 mm was detected for 17 (63%) patients. MRI results (when positive) correctly identified adenoma localization for 14 of the patients with lateralization accuracy higher than that of IPSS (PPV: 82.3% vs. 69.2%). DISCUSSION: IPSS is a valuable procedure in detecting tumor lateralization, especially in patients with Cushing's disease who have negative pituitary MRI results. However, since lateralization has a limited reliability, the pituitary gland should be comprehensively evaluated by taking into account the MRI findings (if positive) as well as data on the side of IPSS lateralization.

Prevalence of Papillary Thyroid Carcinoma is Significantly Higher in Graves Disease with Synchronous Thyroid Nodules.

OBJECTIVE: The association between autoimmunity-related tissue injury and thyroid cancer development remains an area of interest. Evidence suggests that patients with Graves disease (GD) may have an elevated risk for differentiated thyroid cancer. Multicenter studies are needed to gain insight into the correlates of papillary thyroid carcinoma (PTC) identified in this particular group of patients. This study aimed to investigate the prevalence of PTC and synchronous thyroid nodules in thyroidectomy specimens from GD patients in an endemic goiter region. MATERIAL AND METHODS: A retrospective review of institutional pathology records at two tertiary care centers identified 237 surgically treated patients with GD. Patients were categorized as having nodular Graves disease (N-GD) if synchronous nodular thyroid was identified by ultrasonography, while those without synchronous thyroid nodules were categorized as non-nodular or simple Graves disease (S-GD). The prevalence of PTC, histopathological correlates, and demographic characteristics were recorded and compared between groups N-GD and S-GD. RESULTS: One hundred thirty-one and 106 patients were assigned to N-GD and S-GD, respectively. The mean age was significantly higher in N-GD (mean 45.52 years) compared to S-GD (mean 35.18 years) (p < 0.001). The overall frequency of PTC was 36.3% (86/237) in the entire cohort. PTC was identified in 48.1% (63/131) of N-GD and 21.7% (23/106) of S-GD (p < 0.001). Subcentimeter tumors constituted the majority of cases in both groups (76.2% in N-GD and 82.6% in S-GD) (p > 0.05). The group of S-GD was enriched in BRAF-like PTCs, whereas N-GD had equal distribution for RAS- and BRAF-like tumors. CONCLUSION: This study underscores that the majority of PTCs encountered in GD were enriched in low-risk subcentimeter PTCs with a prevalence that varies depending on the presence of underlying nodular thyroid tissue.

Granulation Patterns of Functional Corticotroph Tumors Correlate with Tumor Size, Proliferative Activity, T2 Intensity-to-White Matter Ratio, and Postsurgical Early Biochemical Remission.

Unlike somatotroph tumors, the data on correlates of tumor granulation patterns in functional TPIT lineage pituitary neuroendocrine tumors (corticotroph tumors) have been less uniformly documented in most clinical series. This study evaluated characteristics of 41 well-characterized functional corticotroph tumors consisting of 28 densely granulated corticotroph tumors (DGCTs) and 13 sparsely granulated corticotroph tumors (SGCTs) with respect to preoperative clinical and radiological findings, tumor proliferative activity (including mitotic count and Ki-67 labeling index), and postoperative early biochemical remission rates. The median (interquartile range (IQR)) tumor size was significantly larger in the SGCT group [16.00 (16.00) mm in SGCT vs 8.5 (9.75) mm in DGCT, p = 0.049]. T2-weighted signal intensity and T2 intensity (quantitative) did not yield statistical significance based on tumor granulation; however, the T2 intensity-to-white matter ratio was significantly higher in SGCTs (p = 0.049). The median (IQR) Ki-67 labeling index was 2.00% (IQR 1.00%) in the DGCT group and 4.00% (IQR 7.00%) in the SGCT group (p = 0.043). The mitotic count per 2 mm2 was higher in the SGCT group (p = 0.001). In the multivariate analysis, the sparse granulation pattern (SGCT) remained an independent predictor of a lower probability of early biochemical remission irrespective of the tumor size and proliferative activity (p = 0.012). The current study further supports the impact of tumor granulation pattern as a biologic variable and warrants the detailed histological subtyping of functional corticotroph tumors as indicated in the WHO classification of pituitary neuroendocrine tumors. More importantly, the assessment of the quantitative T2 intensity-to-white matter ratio may serve as a preoperative radiological harbinger of SGCTs.

Diabetes is an independent predictor of severe acute pancreatitis.

We aimed to determine the effect of diabetes mellitus (DM) on the severity of acute pancreatitis (AP) and whether diabetes is a predictor of severe acute pancreatitis (SAP). A total of 181 patients diagnosed with a first attack of AP in our hospital were retrospectively evaluated. AP severity was evaluated and compared between diabetic and non-diabetic patients. Independent factors predicting SAP were identified with a binary logistic regression model. Of the 164 patients [108 (65.9%) women, 56 (34.1%) men] enrolled in the study, 35 patients (21.3%) had been diagnosed with DM, while 129 (78.7%) did not have DM. SAP, necrotizing pancreatitis, and local complications were observed to be more common among diabetic patients compared to non-diabetic patients (all P < 0.001), while the incidences of systemic complications and transient or persistent organ failure were similar between the groups. The incidences of DM and cancer were higher in the SAP group (P < 0.001 and P = 0.033, respectively). The presence of DM (OR: 3.246, 95% CI: 1.278-8.244, P = 0.013), high (≥3) Ranson score (OR: 3.529, 95% CI: 1.342-9.280, P = 0.011), and high maximum C-reactive protein level (OR: 1.005, 95% CI: 1.001-1.010, P = 0.046) were independent risk factors predicting SAP. DM is both a risk factor for SAP and an independent predictor of SAP. Evaluation of the presence of DM at the time of diagnosis can help predict SAP in a considerably early phase.

Cancer prevalence and cancer screening in patients with acromegaly: a single center experience.

PURPOSE: To investigate the prevalence of cancer in patients with acromegaly and the variables associated with malignant and premalignant lesions detected by cancer screening. METHODS: The data of 214 patients diagnosed with acromegaly in our institution were evaluated retrospectively. Prevalence of cancer was compared with national rates to estimate standardized incidence ratios (SIRs). The relationships of malignant and premalignant lesions detected by cancer screening with demographic, clinical, and radiological variables were also analyzed. RESULTS: Cancer was detected in 24 (13.4%) of 179 patients enrolled in the study. Compared to the general population, the incidence of all malignancies was increased in both women and men with acromegaly (SIR: 4.78, 95% CI: 2.43-8.53, p = 0.002 and SIR: 8.97, 95% CI: 5.51-14.7, p < 0.001, respectively). The most common cancers were thyroid, colorectal, breast, kidney, gastric, and testicular cancer, respectively. Duration of disease was the only independent risk factor for the development of cancer (OR: 1.007, 95% CI: 1.002-1.011, p = 0.002). Malignant/premalignant lesions were detected in 21.5% of the patients with a colonoscopy scanning procedure and in 20.8% with an esophagogastroduodenoscopy procedure, and current age was found to be higher among the patients with malignant/premalignant lesions (p = 0.023 and p = 0.003, respectively). Breast cancer was detected in 3.7% of screening tests performed with mammography. CONCLUSION: In this study, it was shown that the prevalence of cancer increases with acromegaly and this increase is associated with disease duration. Considering the increase in the number of premalignant lesions, the scope of cancer screening recommendations in the guidelines should be expanded to ensure early diagnosis.

Efficacy of preoperative therapeutic plasma exchange in patients with hyperthyroidism and factors affecting the number of sessions.

PURPOSE: Achieving preoperative euthyroidism in patients with hyperthyroidism for whom antithyroid drugs (ATDs) cannot be used for treatment is a serious clinical problem. We aimed to evaluate the effectiveness of therapeutic plasma exchange (TPE) in hyperthyroid patients scheduled for surgery and predictive factors for a high number of TPE sessions. METHODS: We retrospectively analyzed the data of 21 patients with hyperthyroidism who were treated with TPE for preoperative euthyroidism in our institution. Pre- and post-TPE thyroid function tests were compared to assess efficacy. Binary logistic regression analysis was applied to determine predictors of patients requiring a high number of TPE sessions. RESULTS: All patients (20 patients with Graves' disease and 1 patient with toxic multinodular goiter; 12 women and 9 men; mean age 35.71 ± 12.38 years) had severe hyperthyroidism before TPE. The changes before and after TPE in fT3, fT4, and TSH levels were statistically significant (p < 0.001, p < 0.001, p = 0.002, respectively). The median number of TPE sessions was 8 (range: 1-24). Levels of fT3 before TPE were significantly higher in patients for whom higher numbers of TPE sessions were required (≥8) (OR: 1.427, 95% CI: 1.038-1.961, p = 0.028). Receiver operating characteristic curve analysis revealed an optimum cut-off value of 12.8 pg/ml for fT3 before TPE (91% sensitivity, 80% specificity, area under the curve: 0.927). CONCLUSION: TPE should be considered as an effective alternative treatment option that can be used to rapidly achieve euthyroidism before surgery when ATDs cannot be used. Pre-TPE fT3 levels of >12.8 pg/ml may be an independent factor predicting the need for higher numbers of TPE sessions (≥8).

Age, GH/IGF-1 levels, tumor volume, T2 hypointensity, and tumor subtype rather than proliferation and invasion are all reliable predictors of biochemical response to somatostatin analogue therapy in patients with acromegaly: A clinicopathological study.

PURPOSE: To determine whether biochemical responses to long-acting forms of first-generation somatostatin analogue (SSA) therapy in patients with acromegaly could be predicted from baseline and postoperative hormone concentrations, and tumor radiological and histopathological characteristics. METHODS: A total of 68 patients with acromegaly for whom postoperative SSA therapy was started were categorized according to their responses to treatment (SSA-responders vs. non-responders). The patients were compared based on their demographic characteristics, hormone levels, magnetic resonance imaging (MRI), and histopathological findings. Receiver-operating-characteristic (ROC) curves were constructed using the predictive factors that were significant in the univariate analysis to determinate the optimal cut-off values. RESULTS: The SSA-responders were significantly older (p = 0.041). Lower GH at diagnosis (p = 0.036), the postoperative 1st-week GH level (p = 0.027), baseline GH, insulin-like growth factor-1 (IGF-1) and IGF-1% upper limit of normal (ULN) (p = 0.001, p = 0.006, p = 0.023, respectively) were associated with biochemical response. T2-hypointensity and lower tumor volume were more common in the SSA-responders (p = 0.018, p = 0.03, respectively). Compared to sparsely granulated somatotroph tumors, densely granulated somatotroph tumors and other PitNETs causing GH excess including mammosomatotroph and mixed somatotroph and lactotroph tumors were more likely to respond to SSA therapy (p = 0.026, p = 0.03, respectively). The cut-off values generated by ROC curve analysis were GH at diagnosis of ≤8.8 ng/mL, GH at baseline of ≤2.69 ng/mL, IGF-1 at baseline ≤461.5 ng/mL, IGF-1% ULN at baseline ≤180.4%, and tumor volume of ≤1.11 cm3 (all p < 0.05). There were no differences between the groups in terms of tumor invasiveness, proliferative activity (mitotic count per 2 mm2 and Ki-67 labeling index) and quantitative analyses of T2-weighted MRI. CONCLUSION: This study underscores that advanced age, low baseline GH and IGF-1 at diagnosis, low tumor volume, densely granulated tumor subtype, and T2 hypointensity may help predict biochemical response to SSA therapy in cases of acromegaly. These variables should be assessed with utmost attention for all patients prior to SSA treatment. In cases of possible resistance to SSA therapy, therapeutic activity should be monitored more closely and other therapies should be administered immediately in the event of poor response.

Clinicopathological variables that correlate with sestamibi positivity in uniglandular parathyroid disease: a retrospective analysis of 378 parathyroid adenomas.

PURPOSE: Technetium-99 m sestamibi parathyroid scintigraphy (MIBI scan) has been used to localize abnormal glands in patients with primary hyperparathyroidism to guide parathyroidectomy. This series aimed to identify the biochemical and histopathological correlates of MIBI scan findings in patients with parathyroid adenoma. METHODS: A total of 378 patients with histologically and biochemically proven parathyroid adenoma were included. The results of MIBI scan, histopathological (gland volume and weight, oxyphil cell ratio), biochemical (blood and 24 h urine calcium, creatinine, glomerular filtration rate, parathormone, alkaline phosphate, and vitamin D3) variables were recorded. A positive uptake on the MIBI scan referred to a localized adenoma. Among histological variables, a cutoff of 30% was applied to define parathyroid adenomas with low (≤ 30%) and high (> 30%) oxyphil cell content. Statistical analyses were performed to assess the relationship among variables. RESULTS: MIBI scan localized the adenoma in 306 patients. Parathyroid gland volume and weight, and oxyphil ratio were significantly higher in the MIBI scan-positive group. Among the biochemical variables, only PTH was found to be significantly increased in the MIBI scan-positive group. Binary logistic regression models identified statistically significant cutoffs for the gland volume (1700 mm3), gland weight (1.3 g) and PTH levels (170 pg/mL) that can be used to predict the MIBI scan positivity. CONCLUSION: In addition to PTH levels, this series underscored the impact of cellular composition along with the parathyroid gland volume and weight, both of which correlate with sestamibi positivity in patients with benign uniglandular parathyroid disease.