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.

Frontal QRS - T angle is associated with severity and prognosis of acute pulmonary embolism.

INTRODUCTION: The pathological effects of acute pulmonary embolism (APE) on the right ventricle are one of the most important determinants of mortality in patients with APE. Frontal QRS-T angle (fQRSTa) predicts ventricular pathology and poor prognosis in many different cardiovascular diseases. In this study, we investigated whether there is a significant relationship between fQRSTa and APE severity. MATERIAL AND METHODS: A total of 309 patients were included in this retrospective study. The severity of APE was classified as massive (high risk), submassive (intermediate risk), or nonmassive (low risk). fQRSTa calculated from standard ECGs. RESULTS: fQRSTa was significantly higher in massive APE patients (p < 0.001). fQRSTa was also found to be significantly higher in the in-hospital mortality group (p < 0.001). fQRSTa was an independent risk factor for the development of massive APE (odds ratio:1.033; 95% CI: 1.012-1.052; p < 0.001). CONCLUSION: Our study showed that increased fQRSTa predicts high-risk APE patients and mortality in APE patients.

Entinostat-Bortezomib Hybrids against Multiple Myeloma.

Although proteasome inhibitors have emerged as the therapeutic backbone of multiple myeloma treatment, patients often relapse and become drug refractory. The combination between proteasome and histone deacetylase inhibitors has shown to be more efficient compared to monotherapy by enhancing the anti-myeloma activity and improving the patient's lifetime expectancy. Hybrid molecules, combining two drugs/pharmacophores in a single molecular entity, offer improved effectiveness by modulating more than one target and circumventing differences in the pharmacokinetic and pharmacodynamic profiles, which are the main disadvantages of combination therapy. Therefore, eleven histone deacetylase-proteasome inhibitor hybrids were synthesized, combining pharmacophores of entinostat and bortezomib. Compound 3 displayed the strongest antiproliferative activity with an IC50 value of 9.5 nM in the multiple myeloma cells RPMI 8226, 157.7 nM in the same cell line resistant to bortezomib, and 13.1 nM in a 3D spheroid model containing multiple myeloma and mesenchymal stem cells. Moreover, the compound inhibited 33% of histone deacetylase activity when RPMI 8226 cells were treated for 8 h at 10 µM. It also inhibited the proteasome activity with an IC50 value of 23.6 nM.

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.

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.

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.

Morning exercise affects the absorption of oral levothyroxine: a single center pilot study.

PURPOSE: Levothyroxine (LT4) is the first-line hormone replacement therapy for hypothyroidism. Several factors which have an influence on oral LT4 absorption have been previously described; however, the influence of exercise on oral LT4 absorption has not been reported, yet. It was aimed to investigate the possible effect of morning exercise, right after LT4 ingestion, on the absorption of LT4 tablets in this study. PATIENTS AND METHODS: Patients with primary hypothyroidism who fulfilled the inclusion criteria were offered to participate in a 6-week morning exercise programme and those who agreed to participate were enrolled in our study. Patients were required to have a walk for 30 min with a regular speed right after taking their daily LT4 treatments and start having breakfast the first hour after LT4 intake. Pre- and post-exercise TSH levels were recorded and TSH percentage change was calculated. RESULTS: All patients had decreased TSH levels after the exercise programme. There was a significant decrease in TSH levels (p < 0.001). A significant positive correlation between TSH percentage change and daily dose of LT4 per kg of body weight was also shown. CONCLUSIONS: This is the first study which demonstrates the significant positive effect of morning exercise on the absorption of LT4 tablets. In addition to that, it was also found that as the daily dose of LT4 increases, the percentage decrease of TSH level becomes greater.

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.

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.

A reference center study in thyrotropin-secreting pituitary adenomas: clinicopathological, therapeutic and long-term follow-up outcomes.

PURPOSE: This study aims to analyze the clinicopathological features, diagnostic steps, and therapeutic results of TSHomas and to reveal the effective factors on remission. METHODS: The clinical, radiological, and pathological features and surgical and endocrinological results of 41 TSHoma cases followed between 2005 and 2022 were retrospectively analyzed. The factors affecting the surgical cure were investigated by comparing the groups with and without remission. RESULTS: A total of 41 patients (23 male,18 female) were included in the study and the mean age was 42 (31.5-49). Palpitation and headache were the most common complaints. The time from the onset of symptoms to diagnosis was 8 (3-20) months. There were 8 patients with a preoperative clinical and biochemical diagnosis of TSH + GH co-secretion. In the TRH stimulation test, a blunted TSH response was obtained in 18 patients (90.0%). Complete suppression could not be obtained in any of the patients who underwent the T3 suppression test. The median maximum tumor diameter was 19.0 mm (6.8-41). There was microadenoma in 4 (9.8%) patients and macroadenoma in 37 patients (92.8%). Remission was achieved in 31 (75.6%) of 40 patients who underwent endoscopic transsphenoidal surgery (eTSS). The Ki-67 labeling index was 2% (1.00-4.00) in the entire patient group. Preoperative use of antithyroid drugs appears to be significantly associated with surgical cure. CONCLUSION: Diagnosis of TSHoma is still full of challenges and dynamic tests remain important. Recognition and good management of inappropriate TSH secretion states affect subsequent surgical outcomes.

Undescribed polyether ionophores from Streptomyces cacaoi and their antibacterial and antiproliferative activities.

Polyether ionophores represent a large group of naturally occurring compounds mainly produced by Streptomyces species. With previously proven varieties of bioactivity including antibacterial, antifungal, antiparasitic, antiviral and anti-tumor effects, the discovery of undescribed polyethers leading to development of efficient therapeutics has become important. As part of our research on polyether-rich Streptomyces cacaoi, we previously performed modification studies on fermentation conditions to induce synthesis of specialized metabolites. Here, we report four undescribed and nine known polyether compounds from S. cacaoi grown in optimized conditions. Antimicrobial activity assays revealed that four compounds, including the undescribed (6), showed strong inhibitory effects over both Bacillus subtilis and methicillin-resistant Staphylococcus aureus (MRSA) growth. Additionally, K41-A and its C15-demethoxy derivative exhibited significant cytotoxicity. These results signified that selectivity of C15-demethoxy K41-A towards cancer cells was higher than K41-A, which prompted us to conduct mechanistic experiments. These studies showed that this uninvestigated compound acts as a multitarget compound by inhibiting autophagic flux, inducing reactive oxygen species formation, abolishing proteasome activity, and stimulating ER stress. Consequently, the optimized fermentation conditions of S. cacaoi led to the isolation of undescribed and known polyethers displaying promising activities.

Comparison between somatostatin analog injections.

OBJECTIVE: Long-acting depot formulations of somatostatin analogs, i.e., octreotide and lanreotide, are the first-line medical therapies for patients with acromegaly to whom surgery/radiotherapy cannot be performed or who have inadequate response. In this study, we aimed to evaluate the short-term local and systemic adverse reactions developed after the somatostatin analogs injections in the patients with acromegaly, in order to compare the side effects of somatostatin analogs injections. METHODS: Patients diagnosed with acromegaly who were referred to our endocrinology clinic for monthly somatostatin analogs injections were questionnaired. Wong-Baker Faces Pain Rating Scale was used to evaluate the injection-site pain at the time of injection. The existence of leg pain, nausea, diarrhea, and abdominal pain following the previous injection was also investigated during the next injection. RESULTS: A total of 49 patients were included in the study. The statistical difference could not be shown between the injection-site pain, anorexia, and leg pain frequencies of the groups, while the frequency of gastrointestinal disturbances, i.e., diarrhea and abdominal pain, was significantly lower in the octreotide group (p<0.001 and p=0.015, respectively). CONCLUSIONS: This is the first prospective study that compared the severity of the injection-site pain by using a scoring scale, following the long-acting somatostatin analogs injections. We have shown that there was no significant association of the injection-site pain severity with the somatostatin analogs regimen nor the dose differences within each somatostatin analogs treatment.

Xanthomatous Hypophysitis Secondary to a Ruptured Rathke's Cleft Cyst: A Case Report.

Hypophysitis (HP) is a rare disease which develops secondary to chronic or acute inflammation of the pituitary gland and may cause symptoms related to pituitary dysfunction and mass compression. Lymphocytic HP is the most common subtype of primary HP, while xanthomatous HP (XHP) is considered the rarest form, with 35 reported cases, to date. A 35-year-old woman was initially admitted to a Gynecology clinic with a 2-year history of amenorrhea and headache. She was started on cabergoline 0.5 mg twice a week for macroprolactinoma. Due to persistent amenorrhea with low gonadotropins, she was referred to our Endocrinology clinic. Her pituitary function profile revealed panhypopituitarism and a 13×11×12 mm sized sellar mass with diffuse enhancement which sustained toward the infundibulum and dura was observed on the gadolinium-enhanced pituitary MRI. The patient underwent an endoscopic endonasal transsphenoidal approach for tumor resection and thick yellowish fluid draining from the lesion was observed. The histopathological diagnosis was reported as a rupture of an Rathke's cleft cyst and an XHP. The surgery did not improve the symptoms/pituitary functions, however, headache recovered immediately after the first dose of high dose methylprednisolone treatment. The inflammatory process in a xanthomatous lesion may actually be a secondary response to mucous fluid content release from a ruptured cyst, thus recommended to classify XHP as secondary hypophysitis. Since the differentiation of XHP from other pituitary tumors may be challenging preoperatively, surgery is the major diagnostic tool and also, the most recommended therapeutic option.

COVID-19, Anxiety, and Hopelessness: Quality of Life Among Healthcare Workers in Turkey.

The aim of the study is to investigate the effects of intense anxiety and hopelessness experienced by healthcare workers during the pandemic on their quality of life. This cross-sectional, online questionnaire-based study was conducted between August 31, 2020 and October 31, 2020, with 729 healthcare workers in Turkey. The study showed that hopelessness, the weekly working time, fatigue, and the workload of healthcare workers negatively affected their quality of life, those who found the pandemic measures inadequate had a lower quality of life and higher hopelessness levels, and those who needed knowledge on various issues to improve their skills had lower quality of life and higher levels of anxiety and hopelessness. Increasing the measures to make healthcare workers feel competent and ready during the COVID-19 pandemic and meet their information needs to improve their skills will reduce their anxiety and hopelessness and improve their quality of life. Identifying the factors affecting anxiety, hopelessness, and quality of life will help achieve sustainable success in the delivery of health services and promote employee health and safety.