Recurrent Cushing's Disease in Adults: Predictors and Long-Term Follow-Up.

Cushing's disease (CD) is characterized by endogenous hypercortisolism that is associated with increased mortality and morbidity. Due to high recurrence rates in CD, the determination of high-risk patients is of paramount importance. In this study, we aimed to determine recurrence rates and clinical, laboratory, and histological predictors of recurrence in a high volume single-center. This retrospective study included 273 CD patients operated in a single pituitary center between 1997 and 2020. The patients with early postoperative remission were further grouped according to recurrence status (recurrent and sustained remission groups). Demographic, radiologic, laboratory, pathologic, and follow-up clinical data of the patients were analyzed and compared between groups. The recurrence rate was 9.6% in the first 5 years; however, the overall recurrence rate was 14.2% in this study. Higher preoperative basal ACTH levels were significantly correlated with CD recurrence even with ACTH levels adjusted for tumor size, Ki-67 levels, and tumoral invasion. Recurrence rates were significantly higher in patients with ACTH levels higher than 55 pg/ml, tumor diameter>9.5 mm, and if adrenal axis recovery was before 6 months. The severity of hypercortisolism, morbidities, and demographic factors except age were not predictive factors of recurrence. Based on our study data, younger age at diagnosis, a diagnosis of osteoporosis, higher preoperative ACTH levels, larger tumor size, invasive behavior, higher Ki 67 index, and early recovery of the adrenal axis during the postoperative period attracted attention as potential predictors of recurrent disease.

The acromegaly treatment satisfaction questionnaire (Acro-TSQ): turkish adaptation, validity, and reliability study.

PURPOSE: The patient-reported outcome becomes important to evaluate the situation perceived by the patients and to develop new strategies. This study aims to adapt the Acromegaly Treatment Satisfaction Questionnaire (Acro-TSQ), which was specially developed for patients with acromegaly, into Turkish by conducting a validity and reliability study. METHODS: After the translation and back-translation process, Acro-TSQ was filled in by face-to-face interviews with 136 patients diagnosed with acromegaly and currently receiving somatostatin analogue injection therapy. Internal consistency, content validity, construct validity, and reliability of the scale were determined. RESULTS: Acro-TSQ had a six-factor structure and explained 77.2% of the total variance in the variable. The Cronbach alpha value calculated for internal reliability showed high internal consistency (Cronbach's alpha = 0.870). Factor loads of all items were found to be between 0.567 and 0.958. As a result of EFA analysis, one item fell into a different factor in the Turkish version of the Acro-TSQ, different from its original form. CFA analysis shows that acceptable fit values are obtained for fit indices. CONCLUSION: The Acro-TSQ, a patient-reported outcome tool, shows good internal consistency, and good reliability, suggesting it is an appropriate assessment tool for patients with acromegaly in the Turkish population.

The Importance of DHEA-S Levels in Cushing's Syndrome; Is There a Cut-off Value in the Differential Diagnosis?

The purpose of this study was to determine possible cut-off levels of basal DHEA-S percentile rank in the differential diagnosis of patients with Cushing's syndrome (CS) with ACTH levels in the gray zone and normal DHEA-S levels. In this retrospective study including 623 pathologically confirmed CS, the DHEA-S percentile rank was calculated in 389 patients with DHEA-S levels within reference interval. The patients were classified as group 1 (n=265 Cushing's disease; CD), group 2 (n=104 adrenal CS) and group 3 (n=20 ectopic ACTH syndrome).ROC-curve analyses were used to calculate the optimal cut-off level of DHEA-S percentile rank in the reference interval in the differential diagnosis of CS, and the effectiveness of this cut-off level in the identification of the accurate etiology of CS was assessed in patients who were in gray zone according to their ACTH levels. The DHEA-S percentile rank in the reference interval were significantly lower in group 2 compared to the other two groups (p<0.001), while group 1 and group 3 had similar levels. The optimal cut-off level of DHEA-S percentile rank in the reference interval providing differential diagnosis between group 1 and group 2 was calculated as 19.5th percentile (80.8% sensitivity, 81.5% specificity) and the level demonstrated the accurate etiology in 100% of CD and 76% of adrenal CS patients who were in the gray zone. This study showed that the cut-off value of DHEA-S level less than 20% of the reference interval could be used for differential diagnosis of CD and adrenal CS with high sensitivity and specificity, and it should be taken into the initial evaluation.

The association of bone mineral density Z-score with the early postoperative remission and characteristics of bone mineral loss in patients with Cushing's disease: a retrospective study.

AIM: To investigate the association of bone mineral density (BMD) Z-scores with early-postoperative remission rate and clinical parameters in patients with Cushing's disease (CD). METHODS: We retrospectively evaluated the records of patients diagnosed with CD. After the exclusion of 230 patients, 87 CD patients were finally enrolled. BMD was determined by dual-energy x-ray absorptiometry (DXA) at the lumbar spine 1-4 (L1-4) and left femur. Early-postoperative remission was defined as a morning cortisol concentration on the first day after surgery of less than 5 µg/dL. The diagnosis of BMD "below the expected range for age" was defined as a Z-score≤-2.00 standard deviations. RESULTS: DXA results were not significantly associated with early postoperative remission. They also did not significantly differ between eugonadal and menopausal groups. Preoperative morning cortisol significantly negatively but weakly correlated with Z-score of the total femur, while preoperative adrenocorticotropic hormone/cortisol ratio positively but weakly correlated with DXA results of L1-4. CONCLUSION: The severity of bone loss was not significantly related to the failure of transsphenoidal surgery for Cushing's disease.

Association of ultrasonographically determined anatomical location of Bethesda 3 thyroid nodules with differentiated thyroid cancer.

BACKGROUND: The size of a thyroid nodule and certain sonographic features, such as marked hypoechogenicity, microcalcifications, taller-than-wide shape, microlobulated, or irregular margins, indicate the greater malignancy risk. The frequency of the atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) category among cytology reports from thyroid fine-needle aspirations ranges from 0.8% to 28%, whereas the risk of malignancy of these nodules varies from 6% to 97%. This retrospective analysis investigated whether the preoperative ultrasonographic location of Bethesda 3 thyroid nodules is a predictive risk factor for differentiated thyroid cancer (DTC). METHODS: A total of 387 patients who underwent total thyroidectomy for a nodule with AUS/FLUS cytology and diagnosed with a DTC at five tertiary referral centers between 2010 and 2020 were retrospectively analyzed. The location of the thyroid nodule with AUS/FLUS cytology was categorized into two groups: one group was composed of the isthmus, upper lobe, middle lobe, and lower lobe, whereas the latter consisted of right lobe, left lobe, and isthmus. RESULTS: DTC was diagnosed in 40.6% (n = 157) of the operated nodules. Multiple logistic regression analysis has revealed that hypoechogenicity of the nodule (odds ratio [OR] = 2.929, p < 0.001) was the only independent predictive factor for the malignancy of the nodules with AUS/FLUS, whereas the location of the nodule, age, and sex were not significantly independent risk factors. Multifocality and contralateral benign nodules were independent predictive factors for multicentricity (OR = 3.5, p = 0.002; OR = 5.5, p = 0.001, respectively). CONCLUSION: As the first study investigating the association between a Bethesda 3 nodule location and the risk of malignancy by evaluating postoperative cytology reports, the results showed that nodule location with AUS/FLUS on fine-needle aspiration biopsy was not a predictive risk factor for the diagnosis of DTC.

Differentiation of insulinoma from accessory spleen by 99mTc-labelled heat-denaturated red blood cell scintigraphy: case report.

BACKGROUND: Neuroendocrine tumors (NETs) are rare tumors harboring overexpression of somatostatin receptors (SSTRs) on their cell membrane. Because some organs, such as the spleen, adrenal glands and liver, physiologically express SSTR, it might be challenging to distinguish some pancreatic NETs located in the pancreatic tail from the accessory spleen next to the splenic hilum. In this manuscript, we report a case with hypoglycemia attack and 2 different masses displayed by Gallium 68-tetraazacyclododecane tetraacetic acid-octreotate (68Ga-DOTATATE) positron emission tomography/computed tomography (PET/CT). CASE PRESENTATION: A 63-year-old woman presented to the hospital with confusion and profuse sweating. Biochemical diagnosis of insulinoma was established. 68Ga-DOTATATE PET/CT revealed two masses with increased tracer uptake located adjacent to the splenic hilum and inferior pole of the spleen which were initially reported as two separate accessory spleens. Then, 99mTc-labelled heat-denaturated red blood cell (99mTc-HDRBC) scintigraphy-single-photon emission computed tomography (SPECT)/CT was performed to distinguish a NET in the pancreatic tail from accessory spleen at the splenic hilum. Enhanced tracer uptake remained in the inferior pole of spleen, but not in the splenic hilum. The lesions were suggestive of insulinoma in the pancreatic tail and an accessory spleen adjacent to the inferior pole of the spleen. CONCLUSION: Approximately 10% of the population have an accessory spleen which can show similar imaging characteristics with pancreatic NETs, especially if located in the pancreatic tail. In our presented case, 99mTc-HDRBC scintigraphy-SPECT/CT is a useful nuclear medicine method to differentiate a NET in the pancreatic tail from accessory spleen at the splenic hilum which may avoid unnecessary surgeries in the presence of enhanced tracer uptake or vice versa.

Proteomic analysis of thyroid tissue reveals enhanced catabolic activity in Graves' disease compared to toxic multinodular goitre.

Graves' disease (GD) and toxic multinodular goitre (TMNG) are the most common thyroid diseases which mainly lead to thyrotoxicosis, however, the underlying mechanism of distinct clinical presentations remains unclear. Protein extracts from the thyroid tissue specimens of the patients with GD and TMNG were subjected to Difference Gel Electrophoresis (DIGE). Differentially regulated protein spots were determined by image analysis, and the spots displaying statistically significant differences were identified by Matrix-Assisted Laser Desorption Ionization Time of Flight Mass Spectrometer (MALDI-TOF) followed by MASCOT search. Western blot analysis was used to verify changes occurring at the protein levels. The identified proteins were classified based on their functions in metabolic pathways using bioinformatics algorithms. Fifteen proteins showed significant alterations in abundance between the two disease groups. Bioinformatic analysis revealed the differentially regulated proteins were particularly related to catabolism, oxidative stress and especially energy utilization pathways, including glycolysis, proteolysis, ketone body catabolism and other energy metabolism-related pathways. SIGNIFICANCE OF THE STUDY: Previously, GD has been the subject of many studies that performed the proteomics approaches in the orbital tissue samples or tear. This is one of the very few studies that investigate the changes in the proteome of thyroid tissue in GD. We demonstrated mainly the upregulation of catabolic activity-related proteins in patients with GD compared to TMNG. Although it remains to be elucidated, some of these proteins can be used as markers for GD or have a role in the pathogenesis of the disease. Our study contributes the increasing data over time by providing new biomarker candidates for GD.

Infiltration of thyroid papillary cancer tissue with myeloid leukemic cells: a case report.

BACKGROUND: Extramedullary leukemia, also known as myeloid sarcoma, is a rare form of acute myeloid leukemia and often accompanies bone marrow involvement. Myeloid infiltration of the thyroid gland is extremely rare. Here, a unique case in which thyroid cancer tissue was infiltrated with myeloid cells is presented. CASE PRESENTATION: We present a case of thyroid papillary cancer infiltrated by blastic cells and bilateral breast and axillary myeloid sarcoma in a 30-year-old Caucasian female patient with a history of osteosarcoma and MDS-RAEB2. The patient firstly received 6 cycles of chemotherapy for osteosarcoma, and allogeneic hematopoietic stem cell transplantation was performed after anthracycline-based chemotherapy due to MDS-RAEB2. The patient remained in remission on follow-up in terms of both osteosarcoma and MDS-RAEB2. Malignant features (Bethesda VI) were observed in the fine needle aspiration biopsy performed from a newly developed firm, fixed thyroid nodule approximately 4-5 cm in length in the left thyroid lobe. Because of the Bethesda VI thyroid nodule, the patient underwent total thyroidectomy. In the pathological evaluation, CD34-, CD117-, MPO-, and HLA-DR-positive blastic cells which infiltrated into follicular variant papillary thyroid carcinoma were detected. In the evaluation performed due to blastic cell infiltration, multiple lesions showing increased 18-fluorodeoxyglucose activity in bilateral breast and axillae were detected. Myeloid sarcoma was found as a result of tru-cut biopsy from these lesions. A fungal cystic lesion was detected in the frontal region of the patient who developed altered consciousness after the second cycle of treatment of myeloid sarcoma. During her follow-up in the intensive care unit, she died of cranial septic embolism and acute infarction. CONCLUSIONS: Here, we present a very interesting case that is the first. A staged approach to diagnosis with methods including immunohistochemical staining, radiological imaging methods, and cytogenetic and molecular analyses can help make the definitive diagnosis.

The association between insulin-like growth factor 1 levels within reference range and early postoperative remission rate in patients with Cushing's disease.

INTRODUCTION: The relationship between growth hormone (GH)/insulin-like growth factor 1 (IGF-1) and glucocorticoids (GC) was examined in various studies. Long-term GC treatment was shown to decrease GH concentration and, interestingly, to increase IGF-1 concentration. We performed a retrospective study in order to examine how preoperative IGF-1 concentrations vary within the reference range and if tertiles of age- and sex-adjusted normal IGF-1 are predictive for early postoperative remission in the patients with Cushing's Disease (CD). PATIENTS AND METHODS: Patients diagnosed with CD were retrospectively evaluated. After the exclusion of 67 patients, a final cohort of 250 CD patients were included. Age- and sex-adjusted normal IGF-1 levels were divided into tertiles (T1, T2 and T3). Early postoperative remission was defined as a nadir morning cortisol concentration measured within the first 3 consecutive days following surgery of less than 5 µg/dL (138 nmol/L). RESULTS: Early postoperative remission rate was the lowest in T1 and highest in T3; 49.1% (n = 28) versus 77.3% (n = 75), p = .001, respectively. Binary logistic regression analysis showed the remission rate in T3 was three times higher than that in T1 (p = .003). Cortisol and ACTH concentration were significantly higher and GH concentrations were significantly lower in T1 compared to those in the other two tertiles. CONCLUSIONS: As the first study evaluating the correlation between early postoperative remission rate in patients with CD and the tertiles of normal age- and sex-adjusted IGF-1 levels, we have shown that higher IGF-1 levels could predict better outcome in CD.

Solid variant of papillary thyroid carcinoma: An analysis of 28 cases with current literature.

INTRODUCTION: Solid variant papillary thyroid cancer (SVPTC) is a rare variant of papillary thyroid carcinoma (PTC) and its prognostic value is still unclear. Therefore, we re-evaluate the histopathological and clinicopathological features of 28 patients with SVPTC in the light of current literature. MATERIAL-METHODS: Of the 1308 cases were previously diagnosed with PTC and 28 (2,1%) of them which had been diagnosed with SVPTC were re-evaluated retrospectively. RESULTS: Of the 28 patients with SVPTC, 85.7% were female, mean age was 45.18 years and mean tumor diameter was 2.96 cm. Microscopically; tumors had a solid growth pattern amounting to at least 50.0% of the tumor volume. In all cases the tumor cells had characteristic nuclear features of conventional PTC. 11 patients had multifocal tumors, extrathyroidal extension was present in 4 patients and vascular invasion was observed in 7 cases. Regional lymph node metastases were noted in 2 (7.1%) cases at the time of diagnosis. One patient died because of locally advanced disease. Another patient is alive with lung metastases after 48 months from the initial surgery. There was no evidence of local recurrence in other patient. CONCLUSIONS: SVPTC is a rare variant of PTC that should be considered in the differential diagnosis of tumors which show a solid/trabecular growth pattern in the thyroid. It has poor prognostic features such as widespread angioinvasion, extrathyroidal extention, lymph node metastasis, and distant organ metastasis. Multicenter studies involving large number of cases are needed to reveal the prognostic significance of SVPTC, with standardized diagnostic criteria.

The coexistence of infundibular pituicytoma and Cushing's disease due to pituitary adenoma: A case report.

OBJECTIVES: Pituicytomas are rare, solid, well-circumscribed, low grade (grade I), non-neuroendocrine, and noninfiltrative tumors of the neurohypophysis or infundibulum, which appear in the sellar/suprasellar regions. Herein, we present a case with Cushing's disease (CD) caused by an ACTH-secreting pituitary adenoma in association with an infundibular pituicytoma. Subject and Results. A 37-year-old male patient presented to the hospital with a six-month history of blurry vision. Physical examination demonstrated plethora, excessive sweating, weight gain, moon facies, and acne. Basal serum cortisol and ACTH levels were 16 µg/dl and 32 pg/ml, respectively. The results of screening tests were suggestive of Cushing syndrome. It was also 1.97 µg/dl following 8 mg dexamethasone suppression test which was consistent with CD. Pituitary MR imaging revealed a single lesion measuring 6x6.5 mm on the pituitary stalk. Infundibular mass excision and pituitary exploration by extended endoscopic endonasal approach were applied. On immunohistochemistry, strong diffuse immunolabeling for both S100 and TTF-1 was noted for the cells of infundibular mass, diagnosed as pituicytoma. Because the developed panhypopituitarism postoperatively, patient was discharged with daily desmopressin, levothyroxine, hydrocortisone, and intramuscular testosterone, once a month. CONCLUSIONS: Pituicytoma is an uncommon noninvasive tumor of the sellar and suprasellar regions. In this case report, we described a patient with Cushing's disease to whom MRI displayed only an infundibular well-circumscribed lesion, but not any pituitary adenoma. Despite the absence of any sellar lesion, awareness of other undetected possible lesion and exploring hypophysis during the transsphenoidal surgery is mandatory for the correct diagnosis.

Thyroid autoimmunity: is really associated with papillary thyroid carcinoma?

The incidence of thyroid cancer has been greatly increasing. Several studies aimed to investigate biomarkers for prediction of thyroid cancer. Some of these studies have suggested that thyroid autoantibodies (TAb) could be used as predictors of thyroid cancer risk, but the correlation between TAb and PTC is still a matter of debate. The aim of this study is to evaluate thyroid autoimmunity and TAbs in patients with PTC and benign multinodular goiter (MNG) to investigate if TAbs and autoimmune thyroid disease (ATD) could predict thyroid malignancy. A total of 577 patients with thyroid papillary carcinoma (PTC) and 293 patients with benign MNG disease were enrolled postoperatively. Demographic features, thyroglobulin (TgAb) and thyroid peroxidase antibodies (TPOAb) and histologic outcome of the patients were evaluated. The prevalence of ATD and TgAb or TPOAb measurements was not statistically different in PTC and MNG groups. However, tumors were significantly smaller and tumor capsule invasion was seen less frequently in patients with PTC and ATD than without ATD. Patients without ATD had more advanced stage (TNM stage III/IV) tumors than with ATD. Only one of the 11 patients with distant organ metastasis had ATD. The present study demonstrated that the prevalence of ATD diagnosed even with histology or TAb positivity was not different in patients with PTC and MNG. However, having ATD might be associated with a better prognosis in PTC patients.

Histologic outcome of thyroid nodules with repeated diagnosis of atypia in thyroid fine-needle aspiration biopsy.

AIM: We hypothesized that the estimated risk of malignancy for atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) is higher than anticipated in Bethesda system. Therefore, we analyzed the actual malignancy risk of repeated AUS/FLUS diagnosis of thyroid fine-needle aspiration biopsies (FNAB). MATERIALS & METHODS: We reported retrospective analyzes of 112 cases with repeated AUS/FLUS diagnosis among 10,769 thyroid FNABs. The histologic follow-up were evaluated in the study. RESULTS: 112 cases with a repeated diagnosis of AUS/FLUS, histologic follow-up revealed 56 (50%) benign, 46 (41%) malignant and ten (9%) well-differentiated tumors of uncertain malignant potential outcome. CONCLUSION: The malignancy risk of AUS/FLUS category in thyroid FNABs was higher than anticipated in Bethesda system. Therefore, the management strategy of AUS/FLUS should be revised.

Latent polyglandular autoimmune syndrome type 2 case diagnosed during a shock manifestation.

There are many types of polyglandular autoimmune syndrome (PAS). PAS type 2 is the most common type among adults. For PAS type 2 (PAS-2) diagnosis, detection of Addison's disease with autoimmune thyroid disease and/or type 1 diabetes mellitus are required. Premature ovarian insufficiency, pernicious anemia, vitiligo, alopecia, myasthenia gravis, celiac disease and autoimmune diabetes insipidus may be comorbidities of this condition. Contrary to the common belief, latent PAS is more common than the manifest forms. Here, we present a PAS-2 case diagnosed via adrenal crisis. At the time of diagnosis, the case was observed to have thyroid, adrenal and ovarian involvement. Therefore, PAS-2 and possible immunologic disorders were discussed.

A Method for Diabetic Wound Specific Insole Design, Manufacturing and Biomechanical Validation for Better Recovery.

Muscle disorders may cause a change in plantar pressures by the misalignment on the foot during gait phases. Therefore, corns or calluses develop at the plantar regions, and diabetic foot ulcers follow for severe cases although it can be prevented and even treated by podiatric approaches with patient specific therapeutic insole and footwear. Although the importance of a threshold value of 200 kPa in peek plantar pressure reduction has been highlighted as a gold standard to prevent re-ulceration in diabetic foot, it may not be possible to ensure this pressure reduction for each patient. In this study, 3 types of ethylene-vinyl acetate have been utilized to optimize the off-loading performance for pre-determined early-stage diabetic foot ulcer scenarios by means of baropodometric plantar pressure analyses and finite element method for each gait phase. The total cost of the manufacturing for this study was reduced down to $10.26 and was performed in 24.6 minutes. In addition, the offloaded pressure was increased by 2.3 times while the volume of the off-loading geometry was increased 8.12 times based on the utilized foam polymer. Consequently, improved off-loading was obtained and a standard was proposed for the first time to calculate the off-loading performance before manufacturing of the therapeutic insole model to ensure a better recovery period.

N-Nitrosomorpholine-induced oncocytic transformation in rat endocrine organs.

BACKGROUND: N-Nitrosomorpholine (NMO) is one of the most common N-nitroso compounds. An oncocytic transformation has been demonstrated in renal tubules of NMO-treated rats. In our study, we aimed to investigate the potential transformation of oncocytic cells in 6 endocrine organs, i.e., thyroid, adrenal and pituitary glands, pancreas, testis, and bone, of NMO-exposed rats. METHODS: Thirty male rats were born and raised. Fifteen of them were given a single dose of 320 mg NMO per kg body weight, dissolved in drinking water, by a gavage tube. At the end of 52 weeks, the animals in both series were killed. Right after the killing, 6 different endocrine organs (hypophysis, thyroid, pancreas, adrenal gland, bone [femur], and testicles) of each animal were excised. RESULTS: There was no evidence of oncocytic cell development in the control group. In contrast, oncocytes were observed in 8 out of 13 NMO-treated rats: 2 in the adrenal sections, 1 in the thyroid sections, 3 in the pituitary sections, and 2 in the pancreas sections. Thesticle and bone sections were completely normal. CONCLUSIONS: We showed that NMO induced an oncocytic change in pancreas, thyroid, pituitary, and adrenal glands. To date, no identified specific environmental risk factors that lead to an oncocytic transformation in endocrine glands have been reported previously. Given the increasing prevalence of endocrine-disrupting chemicals in the environment, personal care products, manufactured goods, and food sources, there is a need to advance our understanding of the pathological mechanisms underlying oncocytosis in endocrine organs.

Brentuximab vedotin-associated diabetic ketoacidosis: a case report.

Background: Diabetic ketoacidosis (DKA) is a life-threatening complication of diabetes mellitus (DM). It is characterized by hyperglycemia, metabolic acidosis, and ketonemia. Fortunately, drug-induced hyperglycemias are usually mild and not life-threatening. However, rarely some cases may present with ketoacidosis. In this case report, we aimed to present a brentuximab vedotin (BV) associated with DKA. Case presentation: A 23-year-old Caucasian man presented with abdominal pain, nausea, and vomiting for 1-2 weeks. The patient had a previous diagnosis of Hodgkin's lymphoma and primer hypothyroidism. He is using levothyroxine 150 µg per day and received BV treatment for Hodgkin lymphoma (HL) 10 days ago. No steroid treatment was administered for premedication before BV. Except for obesity, all system examinations are normal. There were no signs of any infection. Laboratory data revealed hyperglycemia, metabolic acidosis, and ketonemia. The patient was admitted to the service with a diagnosis of DKA. After the patient was admitted to our clinic, insulin treatment and hydration started immediately. Despite the insulin infusion reaching 1700 units per day, the patient's diabetic ketoacidosis extended to 1 week. Anti-insulin, anti-glutamic acid decarboxylase, and islet cell autoantibodies were negative, which were checked to exclude type 1 DM. Fasting C-peptide was 28 ng/mL (normal range, 0.9-7.1 ng/mL). With all these, the diabetic ketoacidosis status of the patient was evaluated as a BV side effect. Conclusion: This patient is a rare case of BV-associated DKA. It is very important to know this relationship since BV treatment has turned into a standard treatment for relapsed Hodgkin lymphoma. Our case highlights that this diagnosis should be kept in mind as a complication of each dose of BV administration.

Clinicopathological Features of Insulinoma: A Single Tertiary Center Experience.

Insulinoma is a rare pancreatic neuroendocrine tumor with an incidence of 1-4 cases per million. Here we present our 10 years of experience in 13 cases of insulinoma. We retrospectively reviewed all insulinoma patients diagnosed and treated between 2012 and 2022. Clinical and pathological features, diagnostic methods, and follow-up results of insulinoma patients were discussed. A total of 13 patients were included in this study (7 men, and 6 women). The mean age at the time of diagnosis was 58 (36.5-70.5) years. There is only one patient diagnosed with MEN-1 syndrome. The mean time from the onset of symptoms to the diagnosis was 15 (7-27.5) months. In the prolonged fasting test, symptomatic hypoglycemia occurred in all patients within 48 h. The median size of lesions was 15 (12-24) mm, and 46.2% of these lesions were isolated in the pancreatic tail. Ga-68 DOTATATE PET/CT detected lesions with 100% accuracy. Three patients met the criteria for malignant insulinoma. Octreotide LAR was given to 1 patient with metastatic disease and 1 patient who did not accept surgery. The metastatic patient received 8 cycles of Lu treatment and died after 51 months of follow-up. The diagnosis of insulinoma can be challenging. The 48-h fasting test period provided sufficient information for the diagnosis of insulinoma. Ga-68 DOTATATE PET/CT may be an alternative in cases where cross-sectional imaging cannot localize the pancreatic lesion.

The effects of exenatide and insulin glargine treatments on bone turnover markers and bone mineral density in postmenopausal patients with type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) related bone fracture. The effects of glucagon-like peptide-1 receptor analogs for the treatment of T2DM on bone are controversial in human studies. This study aimed to compare the effects of GLP-1 receptor analogs exenatide and insulin glargine treatment on bone turnover marker levels and bone mineral density (BMD) in postmenopausal female patients with T2DM. Thirty female patients with T2DM who were naive to insulin and incretin-based treatments, with spontaneous postmenopause, were randomized to exenatide or insulin glargine arms and were followed up for 24 weeks. BMD was evaluated using dual-energy X-ray absorptiometry and bone turnover markers by serum enzyme-linked immunosorbent assay. The body mass index significantly decreased in the exenatide group compared to the glargine group (P < .001). Receptor activator of nuclear factor kappa-B (RANK) and RANK ligand (RANKL) levels were significantly decreased with exenatide treatment (P = .009 and P = .015, respectively). Osteoprotegerin (OPG) level significantly increased with exenatide treatment (P = .02). OPG, RANK, RANKL levels did not change with insulin glargine treatment. No statistically significant difference was found between the pre- and posttreatment BMD, alkaline phosphatase, bone-specific alkaline phosphatase, and type 1 crosslinked N-telopeptide levels in both treatment arms. Despite significant weight loss with exenatide treatment, BMD did not decrease, OPG increased, and the resorption markers of RANK and RANKL decreased, which may reflect early antiresorptive effects of exenatide via the OPG/RANK/RANKL pathway.

A Significant Association between Parathyroid Adenoma Volume and Bone Mineral Loss at Distal Forearm.

INTRODUCTION: The cortical bone is the most severely affected site in patients with primary hyperparathyroidism (PHPT) and thus, a low bone mineral density (BMD) is predominantly observed in distal forearm. Several studies have investigated potential associations between the weight of the gland and bone mineral loss. In this study, we wanted to investigate the relationship between parathyroid adenoma (PTA) volume and bone mineral loss. METHODS: All patients with a diagnosis of PHPT who were operated at our hospital, and with a histologically proven single PTA were retrospectively analyzed. Z-scores were used as the main variable in our analysis to eliminate the effects of age, sex and gonadal status on BMD. RESULTS: Total of 153 patients who met the inclusion criteria were eligible for the study. A significant negative correlation between the PTA volume and z-score for distal third of the radius (DR) (p = 0.006, r = -0.297) was shown. The cut-off value of gland volume for predicting cortical bone mineral loss was 9043.2 mm3. There was also a significant negative correlation between the 24-hour urine calcium and z-scores for lumbar vertebrae and total hip. A significant negative correlation was found between preoperative 25-hydroxy vitamin D levels and the PTA weight. CONCLUSIONS: As the first study that evaluated any possible association between the volume of a parathyroid adenoma and bone mineral loss in patients with PHPT, we found a significant negative correlation between DR z-scores and resected gland volume. Since the volume of a PTA can also be determined by a preoperative US, our findings may be helpful during the preoperative evaluation of a patient with a preliminary diagnosis of PHPT.