Medium and Long-Term Data from a Series of 96 Endoscopic Transsphenoidal Surgeries for Cushing Disease.

OBJECTIVE: Postoperative data on Cushing's disease (CD) are equivocal in the literature. These discrepancies may be attributed to different series with different criteria for remission and variable follow-up durations. Additional data from experienced centers may address these discrepancies. In this study, we present the results obtained from 96 endoscopic transsphenoidal surgeries (ETSSs) for CD conducted in a well-experienced center. METHODS: Pre- and postoperative data of 96 ETSS in 87 patients with CD were included. All cases were handled by the same neurosurgical team between 2014 and 2022. We obtained data on remission status 3-6 months postoperatively (medium-term) and during the latest follow-up (long-term). Additionally, magnetic resonance imaging (MRI) and pathology results were obtained for each case. RESULTS: The mean follow-up duration was 39.5±3.2 months. Medium and long-term remission rates were 77% and 82%, respectively. When only first-time operations were considered, the medium- and long-term remission rates were 78% and 82%, respectively. The recurrence rate in this series was 2.5%. Patients who showed remission between 3-6 months had higher longterm remission rates than did those without initial remission. Tumors >2 cm and extended tumor invasion of the cavernous sinus (Knosp 4) were associated with lower postoperative remission rates. CONCLUSION: Adenoma size and the presence/absence of cavernous sinus invasion on preopera-tive MRI may predict long-term postoperative remission. A tumor size of 2 cm may be a supporting criterion for predicting remission in Knosp 4 tumors. Further studies with larger patient populations are necessary to support this finding.

The significance of forearm bone mineral density evaluation in determining surgical indications in primary hyperparathyroidism.

PURPOSE: Forearm osteoporosis is a well-known complication of primary hyperparathyroidism (PHPT). However, measuring forearm bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) at the distal radius is often neglected in clinical practice despite the fact that osteoporosis at any site is a criterion indicating surgery. We aimed to evaluate the importance and priority of forearm BMD and to determine its association with biochemical parameters. MATERIAL AND METHODS: Three hundred fourteen patients (272 females, 42 males) with PHPT who had BMD measurements at 3 sites were recruited for this retrospective study. The effect on surgical indications of osteoporosis only in the forearm was evaluated. Group 1 (n=151) with forearm osteoporosis and group 2 (n=163) without were compared in terms of biochemical and clinical parameters. RESULTS: In the overall study population, 165 of the 314 patients had osteoporosis in at least 1 site. Twenty seven percent (n=86/314) had osteoporosis only in the forearm, while the other 2 sites (lumbar spine and femoral neck) were normal or osteopenic. Surgery was indicated based on osteoporosis only in the forearm in 10% of patients (n=30/314). Corrected calcium and parathyroid hormone levels were significantly higher in group 1 than group 2 (p=0.001 and p<0.001, respectively) and were also negatively correlated with distal radius BMD, T-score and Z-score in the whole study group. CONCLUSION: Including the distal radius in BMD measurement increased the number of patients diagnosed with osteoporosis and for whom surgery was indicated. Calcium and PTH were also more frequently elevated in patients with forearm osteoporosis. These results show that distal radius BMD is relevant to the management of PHPT.

The effect of COVID-19 process on patients with endocrinological disease in a pandemic hospital: What happened to the others?

Objective: To evaluate the effects of the pandemic process on those with an endocrinological disease that will require close follow-up from the last visit before the pandemic. Materials and Methods: Patients of 3,903 with thyroid, calcium-bone metabolism, adrenal gland, pituitary diseases, and neuroendocrine tumor (NET) were retrospectively scanned. The remaining 855 (656 females and 199 males) patients with active disease or who still needed multidisciplinary approaches were included. The number of patients who continued the disease-related medical procedures and could complete these procedures on time in the pandemic period was determined, and medical deprivation rate (MDR) was calculated. Results: The prepandemic period of our patients with thyroid disease (n = 594), calcium-bone metabolism disorder (n = 130), adrenal disease (n = 85), pituitary disease, and NET (n = 46) had MDRs of 85%, 56%, 81%, and 89%, respectively. For each subgroup of patients, the lowest MDR (67%) was in medullary thyroid carcinoma, the highest MDR (89%) was in differentiated thyroid carcinoma; the lowest MDR (6%) was in osteoporosis, the highest MDR (100%) was in the active Paget's disease; the lowest MDR (0%) was in primary adrenocortical insufficiency, the highest MDR (100%) was in hyperfunctional adrenal adenomas; the lowest MDR (81%) was in pituitary nonfunctional adenomas, and the highest MDR (100%) was in Cushing's disease, active prolactinoma, TSHoma, and NET, respectively. Conclusion: This study showed that not only those who had COVID-19 but also those who had medical deprivation due to their current endocrinological disease were not to be underestimated during the pandemic period.

Insulin-Like Growth Factor-I Might be a Predictor for Severe Non-Alcoholic Fatty Liver Disease in Morbidly Obese Patients.

The aim of the study was to compare the IGF-1 levels, metabolic and clinical parameters among the ultrasonographically classified non-alcoholic fatty liver disease (NAFLD) groups and determine the factors that may predict the NAFLD severity in patients with morbid obesity. This study was conducted on 316 morbidly obese patients (250 F/66 M). The data of patients before and 1st-year after bariatric surgery were recorded. According to the ultrasonographically NAFLD screening, patients with normal hepatic features were classified as Group 1(n=57), with mild and moderate NAFLD were classified as Group 2(n=219), and with severe NAFLD were classified as Group 3(n=40). IGF-1 standard deviation scores (SDSIGF1) were calculated according to age and gender. Parameters that could predict the presence and severity of NAFLD were evaluated. IGF-1 levels were significantly associated with Group 3 than Group 1(p=0.037), and the significance remained between the same groups when IGF-1 levels were standardized as SDSIGF1(p=0.036). Decreased levels of SDSIGF1 explained 5% of severe NAFLD than the normal group (p=0.036). Liver Diameter, FPG, ALT, AST, and GGT were also found as significant predictors for severe NAFLD. There were significant differences between pre-and postop values in all groups (p<0.001). This study showed that IGF-1 might be considered a sgnificant predictor of severe NAFLD in morbidly obese patients. It is crucial in clinical practice to determine predictive factors of NAFLD that could support the diagnosis accompanied by non-invasive imaging methods.

Dry eye disease in patients with metabolic syndrome.

OBJECTIVES: To evaluate dry eye disease (DED) in patients with metabolic syndrome (MetS) and compare with healthy individuals. METHODS: The study was conducted in the Ophthalmology and Endocrinology Department of Bagcilar Education and Research Hospital, a tertiary care center in Istanbul, Turkey, between January and December 2015. In this prospective case-controlled study, dry eye disease tests were performed on 44 patients with MetS and 43 healthy controls. TearLab Osmolarity System, which is a lab-on-a-chip technology, was used to measure tear osmolarity. McMonnies & Ho symptoms questionnaire along with Schirmer I test and tear film break-up time (TFBUT) test were also performed. Statistical evaluation was performed by students' independent test. RESULTS: There was no statistically significant difference in tear osmolarity, TFBUT, and McMonnies and Ho questionnaire scores between MetS and normal group. However, Schirmer I test was significantly higher in MetS group (14.8±9.4mm versus 20.4±9.4, p=0.007). In women subgroup, tear osmolarity was significantly higher in MetS group compared  to the normal group and over the cut-off score 308 mOsm/L (309.4±13.1 mOsm/L versus 301.2±8.7mOsm/L, p=0.012). CONCLUSION: Patients with MetS present with lower tear volumes and a higher incidence of lacrimal gland hypofunction than age-matched controls. Especially women with MetS have higher tear osmolarities, which disrupt the normal functioning of the ocular surface and cause inflammation. Clinicians should be aware of higher DED incidence in patients with MetS for early treatment to prevent serious ocular complications.

Effects of Vitamin D treatment on thyroid autoimmunity.

BACKGROUND: Vitamin D was shown to be related to autoimmune thyroid diseases (AITDs) in the previous studies. We aimed to investigate the relationship between Vitamin D and thyroid autoimmunity. MATERIALS AND METHODS: Eighty-two patients, diagnosed with AITD by the endocrinology outpatient clinic, were included in this prospective study. All of the patients had both AITD and Vitamin D deficiency, defined as serum values <20 ng/mL. They were randomly assigned into two groups. The first group included 46 patients and the second one included 36 patients. The first group was treated with Vitamin D for 1 month at 1000 IU/day. The second group served as the control group and was not treated with Vitamin D replacement. Serum thyroid-stimulating hormone, free T4 (fT4), thyroid peroxidase antibody (TPO-Ab), thyroglobulin antibody (TgAb), and Vitamin D levels were measured at the initiation of the study and again at 1 month in all patients. RESULTS: Two groups were similar with regard to age, sex, and type of thyroid disease. Whereas TPO-Ab (before; 278.3 ± 218.4 IU/ml and after; 267.9 ± 200.7 IU/ml) and TgAb (before; 331.9 ± 268.1 IU/ml and after; 275.4 ± 187.3 IU/ml) levels were significantly decreased by the Vitamin D replacement therapy in group 1 (P = 0.02, P = 0.03, respectively), the evaluated parameters in the control group did not significantly change (P = 0.869, P = 0.530, respectively). In addition, thyroid function tests did not significantly change with Vitamin D replacement in two groups. CONCLUSION: Vitamin D deficiency may contribute to the pathogenesis of AITDs. Since supplementation of the Vitamin D decreased thyroid antibody titers in this study in Vitamin D deficient subjects, in the future Vitamin D may become a part of AITDs' treatment, especially in those with Vitamin D insufficiency. Further clinical and experimental studies are required to understand the effect of Vitamin D on AITD.

The relation of mean platelet volume with microalbuminuria and glomerular filtration rate in obese individuals without other metabolic risk factors: the role of platelets on renal functions.

INTRODUCTION: Mean platelet volume (MPV) is an indirect indicator of platelet activity that plays a major role in the pathogenesis of endothelial injury. Obese individuals have higher microalbuminuria which is the initial step of renal endothelial injury. We aimed to analyze the relation of microalbuminuria and MPV in obese individuals without metabolic risk factors. METHODS: A total of 290 obese individuals (body mass index (BMI)>30 kg/m2) without an accompanying chronic disorder, and 204 nonobese healthy subjects were enrolled into the study. All participants underwent physical examination. Biochemical, hemogram, and hormonal parameters along with urine albumin analysis were performed. Glomerular filtration rate (GFR) was measured by Cockcroft-Gault (GFRC&G), modification of diet in renal disease (MDRD). The BMI was calculated as weight/height2 (kg/m2). Logistic regression analysis was used to analyze relation of variables. RESULTS: The patient group consisted of 171 (59%) female (mean age: 37.15±8.05 years) and 119 (41%) male (mean age 38.98±10.68 years) obese individuals. 130 (63.7%) age matched female (mean age 36.18±8.26 years) and 74 (36.3%) age matched male (mean age 36.49±10.25 years) controls were assigned to the control group. There was a significant difference between groups with regard to BMI, spot microalbuminuria, spot urine microalbuminuria/creatinine ratio but not with to MPV and spot urine creatinine (p: 0.01, 0.004, 0.002; respectively). GFR measured by MDRD and Cockcroft-Gault formula were significantly higher in the obese group (p<0.001 for both). Correlation analysis revealed a significant correlation between BMI and spot urine microalbuminuria, spot urine microalbuminuria/creatinine ratio, GFR (Cockcroft-Gault Formula), Homeostasis Model Assessment of Insulin resistance (HOMA-IR), insulin, C-peptide, diastolic blood pressure, glucose, uric acid, total cholesterol, low density lipoprotein (LDL)-cholesterol, c-reactive protein (CRP), thyroid stimulating hormone (TSH), leukocyte count, platelet count. MPV was inversely and significantly correlated with spot urine creatinine, systolic blood pressure, triglyceride, C-peptide, and platelet count. Mean urea, creatinine, uric acid, triglyceride, total cholesterol, LDL-cholesterol, insulin, C-peptide, HOMA-IR were significantly higher in obese male individuals while obese female individuals had higher levels of mean high density lipoprotein (HDL), CRP, TSH, platelet count, spot urine microalbumin/creatinine rate, and GFR measured by MDRD. CONCLUSIONS: Obese individuals have higher microalbuminuria and nonsignificantly elevated MPV, however, urine albumin loss is independent of MPV.

Increased genome instability and oxidative DNA damage and their association with IGF-1 levels in patients with active acromegaly.

OBJECTIVE: The objectives of this study were to assess cytokinesis-block micronucleus cytome (CBMN Cyt) assay parameters and also oxidative DNA damage in patients with active acromegaly and controls and to assess the relationship between age, serum insulin-like growth factor 1 (IGF-1) levels, pituitary adenoma diameters, 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels and CBMN Cyt assay parameters in patients with active acromegaly. DESIGN: The study population included 30 patients with active acromegaly and 30 age- and sex-matched healthy controls. CBMN Cyt assay parameters in peripheral blood lymphocytes of patients with active acromegaly and controls were evaluated and plasma 8-OHdG levels were measured. RESULTS: Frequencies of micronucleus (MN), nucleoplasmic bridges (NPBs) and nuclear buds (NBUDs) in lymphocytes of patients with acromegaly were found to be significantly higher than those in controls (p<0.001, p<0.001, p<0.001, respectively). The frequencies of apoptotic and necrotic cells in lymphocytes of patients with acromegaly were found to be significantly higher than those in controls (p<0.001 and p<0.001 respectively). No statistically significant differences in the number of cells in metaphase, the number of bi-nucleated cells (M2), the number of tri-nucleated cells (M3), the number of tetra-nucleated cells (M4) and nuclear division index (NDI) values were observed between patients and controls (p>0.05). Plasma 8-OHdG (ng/ml) levels in patients with acromegaly were found to be significantly higher than those in controls (p<0.005). MN frequency in the lymphocytes of patients with acromegaly increased with elevated serum IGF-1 levels (p<0.05), whereas the number of NPBs and the frequency of apoptotic cells decreased with elevated serum IGF-1 levels (p<0.01 and p<0.05 respectively). CONCLUSIONS: Both the increase in chromosomal/oxidative DNA damage and the positive association between MN frequency and serum IGF-1 levels may predict an increased risk of malignancy in acromegalic patients. Long-term follow-up of patients with acromegaly will be necessary to establish the degree of cancer risk in this population.

Obstructive sleep apnoea syndrome is associated with relative hypocortisolemia and decreased hypothalamo-pituitary-adrenal axis response to 1 and 250µg ACTH and glucagon stimulation tests.

OBJECTIVE: The investigations regarding the effect of obstructive sleep apnoea syndrome (OSAS) on hypothalamo-pituitary-adrenal (HPA) axis revealed conflicting results. We aimed to evaluate the effects of OSAS on HPA-axis with dynamic tests. METHODS: This study was carried out on 26 patients with OSAS and 15 subjects without OSAS which, were defined according to the International Classification of Sleep Disorders. Patients were enrolled from either Endocrinology outpatient clinic or Neurology Sleep Center. Participants for the control group were included from the patients admitting to Endocrinology Department with the complaint of obesity or volunteers from hospital staff. All the participants were evaluated by polysomnography (PSG) and dynamic tests of HPA axis (dexamethasone suppression test, 1 and 250µg ACTH and glucagon stimulation tests). RESULTS: Serum basal and peak cortisol levels were found to be lower in OSAS patients when compared to the control group during 1µg ACTH and glucagon stimulation tests. When the area under curve (AUC) of cortisol responses to dynamic stimulation tests were calculated according to trapezoid formula, patients with OSAS were found to have lower values compared to control group. AUC responses of all three dynamic stimulation tests were found to be negatively correlated with AHI. CONCLUSION: OSAS is associated with relative hypocortisolemia in the morning with reduced responses to 1 and 250µg ACTH and glucagon stimulation tests.

Acromegaly is associated with decreased skin transepidermal water loss and temperature, and increased skin pH and sebum secretion partially reversible after treatment.

BACKGROUND: Acromegaly is characterized by an acquired progressive somatic disfigurement, mainly involving the face and extremities, besides many other organ involvement. Wet and oily skin was described in acromegaly patients and it was attributed to hyperhidrosis and increased sebum production but this suggestion has not been evaluated with reliable methods. OBJECTIVE: The aim of this study was to examine the skin parameters of patients with acromegaly using measurements of skin hydration, sebum content, transepidermal water loss, pH and temperature and particularly the effects of 12 months of treatment on these parameters. METHODS: 52 patients with acromegaly and 24 healthy control subjects were included in this two blinded prospective study. Skin properties were measured on forehead and forearm by Corneometer CM825, Sebumeter SM810, Tewameter TM210 and Phmeter PH900 as non-invasive reliable measuring methods. Serum GH, IGF-1 and all measurements of skin properties on forehead and forearm were repeated at the end of the 3, and 6 months of therapy in 20 cases. Patients were treated with appropriate replacement therapy for deficient pituitary hormones. RESULTS: The sebum content and pH of the skin of acromegalic patients were significantly higher and transepidermal water loss and skin temperature were found to be significantly lower in acromegalic patients when compared to the control group both on forehead and forearm. GH and IGF-1 levels were positively correlated with sebum levels and negatively correlated with skin temperature on both forehead and forearm. The sebum levels of the patients were significantly decreased both on forehead and forearm at 3rd and 6th months of treatment. CONCLUSION: The present study demonstrated increased sebum secretion, decreased transepidermal water loss, alkali and hypothermic skin surface in patients with acromegaly by reliable methods for the first time. These data suggest that GH and/or IGF-I may have a modulatory role on several skin characteristics which can be at least partially reversible with treatment.

Investigation of insulin resistance in patients with normocalcemic primary hyperparathyroidism.

While derangements in glucose metabolism in patients with primary hyperparathyroidism are well-defined, this issue is not investigated in patients with normocalcemic primary hyperparathyroidism (NPHPT). The aim of this study was to investigate the presence of insulin resistance in patients with NPHPT. Eighteen patients with NPHPT (two males and 16 females) and 18 healthy volunteers were enrolled into the study. Secondary causes of parathyroid hormone elevations were excluded in all patients. Blood samples were obtained for the measurement of serum calcium, phosphate, alkaline phosphatase (ALP), albumin, creatinine, glucose, and serum lipid levels. Glucose and insulin responses to oral glucose tolerance test (OGTT) were obtained. Homeostasis model assessment (HOMA-IR) was also used as an indice of insulin resistance. Patients and control subjects had similar age, body mass index, and sex distribution. Although within normal limits, serum calcium and ALP levels were higher in patients than in the control subjects. None of the patients and the control subjects had diabetes mellitus, while eight patients and six control subjects had impaired glucose tolerance. Insulin responses to OGTT and HOMA-IR were not significantly different among the patient and control subjects. In addition, both groups have similar serum lipid levels. Patients with NPHPT do not exhibit insulin resistance and glucose intolerance. Since so little is known about this form of disease, subjects should be monitored regularly for the metabolic aspects of the disease as well as the progression of their disease.

Evaluation of coagulation and fibrinolytic parameters in adult onset GH deficiency and the effects of GH replacement therapy: a placebo controlled study.

OBJECTIVE: Increased cardiovascular mortality/morbidity observed in patients with hypopituitarism is ascribed to growth hormone deficiency (GHD) because of its unfavorable cardiovascular risk profile. Abnormalities in the coagulation system may also contribute to increased cardiovascular morbidity/mortality. To get a better insight into the role of hemostasis in GHD we assessed several hemostatic markers at baseline and after 6 months of GH replacement therapy (GHRT). DESIGN-PATIENTS: Nineteen patients with adult onset GHD were enrolled (twelve patients into the treatment and seven patients into the placebo group) into the study. Platelet count, collagen/epinephrine closure time, collagen/ADP closure time, fibrinogen, prothrombin time (PT), activated partial thromboplastin time (aPTT), antithrombin III (AT III), protein C activity, protein S activity, lupus anticoagulant, antiphospholipid antibody immunoglobulin M, and antiphospholipid antibody immunoglobulin G were measured at baseline and 6 months after treatment. RESULTS: The investigated parameters in the groups were similar at baseline except for low protein S (PS) activity. Protein S deficiency was observed in three of the patients in the GH treatment group at baseline, however the PS activity values normalized following GHRT. AT III and protein C activities decreased when compared to baseline values in the treatment group but not in the placebo group. CONCLUSIONS: We observed protein S deficiency more frequent than seen in the general population and normalization of protein S activity and decreases, in other natural anticoagulants following GHRT. Further studies are required to understand the impact of these changes in cardiovascular morbidity and mortality in this patient population.

Micronucleus evaluation in mitogen-stimulated lymphocytes of patients with acromegaly.

Acromegaly is a syndrome characterized by a sustained elevation of circulating growth hormone and insulin-like growth factor-1 (IGF-1). Insulin-like growth factor-1 is a potent mitogen and has a role in the transformation of normal cells to malignant cells. This study aims to evaluate the spontaneous micronucleus (MN) frequency by using the cytokinesis-block MN assay to determine genetic damage in the lymphocytes of patients with acromegaly. The study was carried out in 20 patients who had active acromegaly and in 20 age- and sex-matched healthy controls. The MN values were measured in binucleated cells obtained from mitogen-stimulated lymphocytes of patients and control subjects. The distribution of binucleated cells with 1, 2, 3, or more MNs was also measured. We found significantly higher MN frequency values in the lymphocytes of acromegalic patients than in those of the control subjects (2.23 ± 0.68 vs 1.03 ± 0.54, P = .001). The MN frequency increased with increasing IGF-1 levels of acromegalic patients (P = .036, R = 0.47). We observed that the number of binucleated cells with 2 MNs was higher for the majority of patients with acromegaly than for control subjects. Furthermore, the receiver operating characteristic curve (area under the curve = 0.914, P < .0001) was calculated to assess the discriminative power of the MN frequency. Our results indicate that increased MN frequency in the lymphocytes of patients with acromegaly may reflect genomic instability and this increased MN frequency may be associated with elevated levels of circulating growth hormone and IGF-1.

Inspiratory muscle strength is correlated with carnitine levels in type 2 diabetes.

INTRODUCTION: Plasma carnitine insufficiency has been known to cause muscle weakness. Carnitine levels and pulmonary functions were lower in patients with diabetes. PATIENTS AND METHODS: To determine whether pulmonary functions are correlated with carnitine levels in patients with type 2 diabetes. In this study, we evaluated pulmonary functions and carnitine concentrations in 49 patients with type 2 diabetes and 34 healthy controls. RESULTS: Carnitine levels were lower in type 2 diabetes group than control group (52.56 +/- 12.38 and 78.96 +/- 10.66 hmol/mL, respectively, p < 0.0001). Pulmonary functions were not significantly different between groups. Carnitine levels were not correlated with age, duration of diabetes, fasting blood glucose levels, and glycemic control (HbA1c%) in patients with type 2 diabetes. However, carnitine levels in patient group were correlated with % forced vital capacity (FVC%) (r = 0.35, p = 0.016), % forced expiratory volume in 1 s (FEV1%) (r = 0.318, p= 0.029), FEV1/FVC (r= 0.302, p= 0.039), inspiratory muscle strength (PImax) (r = 0.407, p = 0.023), and PImax% (r = 0.423, p= 0.018). CONCLUSION: This study suggests that low carnitine levels may be associated with lower PImax and PImax% in type 2 diabetes.