Clinical features of generalized lipodystrophy in Turkey: A cohort analysis.

AIM: To describe the Turkish generalized lipodystrophy (GL) cohort with the frequency of each complication and the death rate during the period of the follow-up. METHODS: This study reports on 72 patients with GL (47 families) registered at different centres in Turkey that cover all regions of the country. The mean ± SD follow-up was 86 ± 78 months. RESULTS: The Kaplan-Meier estimate of the median time to diagnosis of diabetes and/or prediabetes was 16 years. Hyperglycaemia was not controlled in 37 of 45 patients (82.2%) with diabetes. Hypertriglyceridaemia developed in 65 patients (90.3%). The Kaplan-Meier estimate of the median time to diagnosis of hypertriglyceridaemia was 14 years. Hypertriglyceridaemia was severe (≥ 500 mg/dl) in 38 patients (52.8%). Seven (9.7%) patients suffered from pancreatitis. The Kaplan-Meier estimate of the median time to diagnosis of hepatic steatosis was 15 years. Liver disease progressed to cirrhosis in nine patients (12.5%). Liver disease was more severe in congenital lipodystrophy type 2 (CGL2). Proteinuric chronic kidney disease (CKD) developed in 32 patients (44.4%) and cardiac disease in 23 patients (31.9%). Kaplan-Meier estimates of the median time to diagnosis of CKD and cardiac disease were 25 and 45 years, respectively. Females appeared to have a more severe metabolic disease, with an earlier onset of metabolic abnormalities. Ten patients died during the follow-up period. Causes of death were end-stage renal disease, sepsis (because of recurrent intestinal perforations, coronavirus disease, diabetic foot infection and following coronary artery bypass graft surgery), myocardial infarction, heart failure because of dilated cardiomyopathy, stroke, liver complications and angiosarcoma. CONCLUSIONS: Standard treatment approaches have only a limited impact and do not prevent the development of severe metabolic abnormalities and early onset of organ complications in GL.

Low Bone Density and High Sclerostin in Non-Functioning Pituitary Adenoma.

PURPOSE: Sclerostin reduces bone formation by inhibiting the Wnt signaling pathway in bone tissue. This study evaluated the serum sclerostin level in non-functioning pituitary adenoma (NFPA) patients and analyzed its relationship with bone metabolism. METHOD: The data of the patients who applied to the Dicle University Endocrinology, diagnosed with non-functioning pituitary adenoma, and the control group consisting of healthy individuals were included in the study. Serum sclerostin levels and DXA analysis parameters were evaluated and compared with healthy control groups. RESULTS: The study consisted of 39 patients (F / M: 27/12) with NFPA (patient group) and 43 control groups (F / M: 26/17). There was no difference in terms of gender, age, height, weight and serum calcium, phosphorus, creatinine, 25-OH vitamin D, parathyroid hormone levels. Serum sclerostin levels (32.31 ± 1.53 ng / ml) in the patient group was found to be significantly higher than the control group (22.45 ± 8.9 ng / ml) (p < 0.001). BMD (Patients groups vs control group); total lumbar BMD (0.951-1.56 gr / cm2) (p < 0.001), femoral neck BMD (0.752-1.15 g / cm2) (p < 0.001), femoral total BMD (0.995- 1.63 gr / cm2) (p < 0.001), were found to be statistically significantly lower. CONCLUSION: This study provides the first evidence that serum sclerostin levels were increased in non-functioning pituitary adenomas, which showed that bone parameters were negatively affected.

Assesment of attainment of recommended TSH levels and levothyroxine compliance in differentiated thyroid cancer patients.

OBJECTIVE: Thyroid-stimulating hormone (TSH) suppression treatment can induce signs and symptoms of hyperthyroidism and hypothyroidism due to inappropriate treatment or poor compliance to the treatment. The current study aimed to investigate TSH levels, frequency of being on target TSH, adherence to levothyroxine (LT4) suppression treatment in differentiated thyroid cancer (DTC) patients after surgery in a multicentric setting. DESIGN AND PATIENTS: This multicentric cross-sectional study was conducted at 21 medical centres from 12 cities in Turkey. DTC patients followed at least one year in the same center included in the study. Clinical data, serum TSH, free thyroxine (FT4), thyroglobulin (Tg) and anti-Tg levels were recorded during the most recent visit. Body mass index, systolic and diastolic blood pressures, pulse rate were measured. LT4 doses were recorded and doses per kilogram of bodyweight were calculated. Pill ingestion habits recorded and adherence to the therapy were evaluated using the Morisky Medication Adherence Scale and categorized as good, moderate or poor compliant based on their scores. Risk stratification forpredicting the disease persistance and/or reccurence was assessed using the American Joint Committee on Cancer-7th edition thyroid cancer staging calculator. TSH serum concentrations were classified as severe suppression (TSH < 0.01 mU/L), moderate suppression (TSH: 0.01-0.1 mU/L), mild suppression (TSHL 0.1-0.5 mU/L), euthyroid (TSH: 0.5-4 mU/L) and hypothyroid (TSH > 4 mU/L). TSH levels can also be classified as on being on target, under the target, or beyond over the target, according to the American Thyroid Association recommendations. RESULTS: A group of 1125 patients (F/M: 941/184, 50.7 ± 11.7 years) were included in the study. The mean LT4 daily dosage was 132.4 ± 39.6 mcg/day. TSH levels showed severe suppression in 99 (%8.8) patients, moderate suppression in 277 (%24.6) patients and mild suppression in 315 (%28) patients and euthyroid range in 332 (%29.5) patients and hypothyroid range in 97 (8.6%). TSH levels were in target in 29.2% of the patients 20.4% of the patients were undertreated, 50.4% overtreated. The daily LT4 dose and LT4 dose/kg were significantly higher in the severe suppression group (p < .001, p < .001). According to the Morisky scale, 564 patients (50.1%) were good compliant, 368 patients (32.7%) were moderate compliant, and 193 patients (17.1%) were noncompliant. Patients with poor compliance need a higher dose of LT4 compared to the good compliance group (p < .001). TSH levels of patients with good compliance were 0.67 ± 1.96 mU/L and TSH with poor compliance was 2.74 ± 7.47 mU/L (p < .001). TSH levels were similar in patients on fixed and alternating dosages. CONCLUSION: In 29.2% of the DTC patients, serum TSH levels were at target levels. Remaining of the study group have TSH levels under or over treatment range, exposing the patient to medication side effects. Majorty of the study group 82.8% have good or moderate adherence to LT4 therapy. Reaching TSH targets requires simplified and applicable guidelines and following the guideline recommendations.

Identifying Clinical Characteristics of Hypoparathyroidism in Turkey: HIPOPARATURK-NET Study.

Hypoparathyroidism is an orphan disease with ill-defined epidemiology that is subject to geographic variability. We conducted this study to assess the demographics, etiologic distribution, treatment patterns and complication frequency of patients with chronic hypoparathyroidism in Turkey. This is a retrospective, cross-sectional database study, with collaboration of 30 endocrinology centers located in 20 cities across seven geographical regions of Turkey. A total of 830 adults (mean age 49.6 ± 13.5 years; female 81.2%) with hypoparathyroidism (mean duration 9.7 ± 9.0 years) were included in the final analysis. Hypoparathyroidism was predominantly surgery-induced (n = 686, 82.6%). The insulting surgeries was carried out mostly due to benign causes in postsurgical group (SG) (n = 504, 73.5%) while patients in nonsurgical group (NSG) was most frequently classified as idiopathic (n = 103, 71.5%). The treatment was highly dependent on calcium salts (n = 771, 92.9%), calcitriol (n = 786, 94.7%) and to a lower extent cholecalciferol use (n = 635, 76.5%) while the rate of parathyroid hormone (n = 2, 0.2%) use was low. Serum calcium levels were most frequently kept in the normal range (sCa 8.5-10.5 mg/dL, n = 383, 46.1%) which might be higher than desired for this patient group. NSG had a lower mean plasma PTH concentration (6.42 ± 5.53 vs. 9.09 ± 7.08 ng/l, p < 0.0001), higher daily intake of elementary calcium (2038 ± 1214 vs. 1846 ± 1355 mg/day, p = 0.0193) and calcitriol (0.78 ± 0.39 vs. 0.69 ± 0.38 mcg/day, p = 0.0057), a higher rate of chronic renal disease (9.7% vs. 3.6%, p = 0.0017), epilepsy (6.3% vs. 1.6%, p = 0.0009), intracranial calcifications (11.8% vs. 7.3%, p < 0.0001) and cataracts (22.2% vs. 13.7%, p = 0.0096) compared to SG. In conclusion, postsurgical hypoparathyroidism is the dominant etiology of hypoparathyroidism in Turkey while the nonsurgical patients have a higher disease burden with greater need for medications and increased risk of complications than the postsurgical patients.

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.

Clinical predictors of incipient vertebral fractures and bone mineral density in kidney transplant patients.

PURPOSE: Kidney transplant recipients are prone to metabolic bone diseases and consequent fractures. This study aimed to evaluate the incidence of incipient vertebral fractures, osteopenia, osteoporosis, and the clinical factors associated with incipient vertebral fractures in a group of kidney transplant patients. METHODS: Two hundred sixty-four patients (F/M 124/140, 45.3 ± 13 years) who had undergone kidney transplantation in tertiary care centers were included. Vertebral fractures were assessed semiquantitatively using conventional thoracolumbar lateral radiography in 202 of the patients. RESULTS: Vertebral fractures were observed in 56.4% (n = 114) of the study group. The frequency of osteoporosis was 20.0% (53 of 264 patients), and osteopenia was 35.6% (94 of 264 patients). Bone mineral density (BMD) levels were in the normal range in 40.3% (n = 46) of the subjects with vertebral fractures. It was in the osteoporotic range in 20.1% (n = 23) and the osteopenic range in 40.3% (n = 46). Vertebral fractures were associated with age, duration of hemodialysis, BMI, and femoral neck Z score (R2 37.8%, p = 0.027). CONCLUSION: As incipient vertebral fractures can be observed in patients with normal BMD levels in kidney transplant recipients, conventional X-ray screening for vertebral fractures may be beneficial for a proper therapy decision of metabolic bone disease in kidney transplant recipients.

Quantitative Evaluation of Pupil Responses in Patients with Prolactinomas Being Treated with Dopamine Agonists.

The aim of this study was to determine whether the dopamine agonist (DA) drug cabergoline used in the treatment of prolactinoma causes autonomic dysfunction by measuring static and dynamic pupillary responses. The study included 25 eyes from 25 patients who were receiving DA for the treatment of prolactinoma and 25 eyes from 25 healthy individuals. Static and dynamic pupillary responses were measured by automatic quantitative pupillometry. The scotopic pupillary diameter was found to be significantly higher in patients receiving DA medication compared with the control group, while pupil contraction time and pupillary dilatation latency were significantly lower. DA drug use changes static and dynamic pupillary responses, probably by increasing sympathetic tone. Pupillometry can be used as a non-invasive method to provide information about changes in the autonomic nervous system in patients receiving such drug therapy.

The effectiveness of automatic pupillometry as a screening method to detect diabetic autonomic neuropathy.

PURPOSE: This study aimed to compare static and dynamic pupil responses of diabetic patients with and without nonproliferative diabetic retinopathy (DR) and normal healthy individuals under different lighting conditions via quantitative automated pupillometry. METHODS: Forty patients with DM with nonproliferative DR (group 1), 40 patients with DM without DR (group 2), and 40 healthy controls (group 3) underwent a complete ophthalmologic examination. Static pupillometry [scotopic pupil diameter (PD), mesopic PD, low photopic PD, and high photopic PD] and dynamic pupillometry (resting PD, contraction amplitude, latency, duration, velocity of contraction, dilatation latency, and duration and velocity at rest) were measured via automatic quantitative pupillometry. RESULTS: Analysis of variance revealed that scotopic PD [F(2, 117) = 6.42; p = 0.02], mesopic PD [F(2, 117) = 3.20; p = 0.04], and low photopic PD [F(2, 117) = 4.86; p = 0.009] were significantly different among the groups. Scotopic PD and low photopic PD were significantly lower in group 1 than in group 2 (p = 0.03 and p = 0.03, respectively). Meanwhile, the resting diameter, velocity of pupil contraction, and velocity of pupil dilatation were found to be significantly lower (p = 0.02, p = 0.01, and p = 0.008, respectively), and the duration of pupil contraction was significantly higher in group 1 than in group 3 (p = 0.03). CONCLUSION: Both DM patients with and without nonproliferative DR exhibited pupillary involvement. Automated pupillometry may be an easily applicable, noninvasive screening option for reducing mortality and morbidity rates associated with diabetic autonomic neuropathy.

Importance of Parathyroid Hormone Needle Aspiration Washout in Adenoma Localization in Primary Hyperparathyroidism.

BACKGROUND Primary hyperparathyroidism is an endocrine disease characterized by excessive secretion of parathyroid hormone and hypercalcemia. Although scintigraphy is commonly used for pre-operative localization, it does not always localize the parathyroid lesion. In such patients, ultrasonography can visualize the suspected lesion and needle washout sample for parathyroid hormone titer can be used to confirm parathyroid tissue. The aim of this study was to investigate the accuracy of the parathyroid hormone needle aspiration washout method in detecting the localization of parathyroid adenoma. MATERIAL AND METHODS Patients with primary hyperparathyroidism who underwent surgery between 2010 and 2017 at the Dicle University Medical Faculty Hospital were retrospectively evaluated using medical records. Patients undergoing parathyroid hormone needle aspiration washout were performed in the suspected lesion were included in the study. Accompanied by ultrasonography, the suspected area was penetrated with needle, and negative aspiration was performed. Pre-operative scintigraphic data of patients were evaluated. Patients with positive scintigraphy, negative scintigraphy or patients who did not undergo scintigraphy were included in our study. Demographic data were presented as continuous data means ± standard deviation. Categorical variables were presented as frequency and percentage. RESULTS Forty-nine patients (female/male, 40/9) who underwent parathyroid hormone needle aspiration washout were included in the study. Parathyroid hormone washout result was positive in 47 patients (47/49) and negative in 2 patients (2/49), sensitivity/positive predictive value (PPV) 95.91%. Twenty-six patients who had negative/suspicious scintigraphic results were diagnosed using the parathyroid hormone needle aspiration washout method (24/26, 92.3% accuracy). Parathyroid hormone needle aspiration washout without scintigraphy was performed in 13 patients (13/13, 100% accuracy). CONCLUSIONS Parathyroid adenoma localization can be easily done using parathyroid hormone needle aspiration washout in centers experienced in adenoma localization in primary hyperparathyroidism cases in which scintigraphic results are negative or scintigraphy cannot be performed. We believe that primary parathyroid hormone needle aspiration washout can be a new localization method for adenoma localization.

Are There Differences in the Management of Acute Pancreatitis Cases Due to Severe Hypertriglyceridemia in Pregnant Women?

BACKGROUND The aim of this study was to determine the prognosis of severe disease and treatment approaches of both normal and pregnant, especially in patients with severe pancreatitis due to hypertriglyceridemia. MATERIAL AND METHODS We included 30 patients (20 females and 10 males) in this study whose follow-ups and treatments were performed after a diagnosis of hypertriglyceridemia-induced acute pancreatitis between January 2011 and May 2017. Patient personal information, such as age, sex, pre-treatment and post-treatment triglyceride levels, receipt of anti-hyperlipidemic treatments or plasmapheresis, and family history, were collected from hospital records and patient files. Patients with severe pancreatitis history, score, and prognosis were included to increase the value of our study. Mild and moderate cases were excluded. RESULTS The mean age of the patients was 35±6 years. Twenty-four patients (80%) received an anti-hyperlipidemic treatment before their pancreatitis attacks. Plasmapheresis was performed on 8 patients before their pancreatitis attacks. Eighteen patients (60%) had a family history suggesting familial hypertriglyceridemia. Twelve patients (40%) were pregnant. CONCLUSIONS The treatment of hypertriglyceridemia-induced acute pancreatitis was mostly confined to supportive, palliative treatments. However, plasmapheresis is a possible treatment option and should be used in the early stages of this disease. The response to medical treatment and support treatment was better in pregnant patients than in the other patient group, and pregnant patients did not require plasmapheresis.

Association of clinical and laboratory parameters with ambulatory arterial stiffness index in acromegaly patients.

OBJECTIVE: In this study, we determined the relationship between the ambulatory arterial stiffness index (AASI) and clinical and laboratory parameters in patients with acromegaly. METHODS: Sixty-five patients with acromegaly, who visited to Dicle University Medical Faculty Department of Endocrinology (33 females and 32 males), were included in this study. The study control group consisted of 65 subjects. Demographic and clinical data were recorded. Laboratory data (complete blood count, blood urea nitrogen, creatinine, electrolytes, albumin, lipid profile, growth hormone [GH], insulin-like growth factor-1, and the 75-g oral glucose tolerance test) performed over the last year were evaluated. The AASI was obtained from 24-hour ambulatory blood pressure monitoring records of all patients. This study was completed in 15 months from 2013 to 2015. RESULTS: Twelve patients (18.4%) had diabetes and 21 patients (32%) had hypertension. The mean AASI value was 0.41 ± 0.14. The mean AASI value in the control group was 0.25 ± 0.09. Growth hormone (GH) levels were positively correlated with the AASI values. AASI values tended to be higher in hypertensive subjects than that in normotensive individuals. CONCLUSIONS: Our results show that the AASI value increased in patients with acromegaly, independent of the increase in blood pressure. The AASI was strongly dependent on the degree of the GH increase in patients with acromegaly and may have an important role predicting cardiovascular risk in patients with acromegaly.

Retina ganglion cell/inner plexiform layer and peripapillary nerve fiber layer thickness in patients with acromegaly.

Increased secretion of growth hormone and insulin-like growth factor-1 in acromegaly has various effects on multiple organs. However, the ocular effects of acromegaly have yet to be investigated in detail. The aim of the present study was to compare retina ganglion cell/inner plexiform layer (GCIPL) and peripapillary nerve fiber layer thickness (pRNFL) between patients with acromegaly and healthy control subjects using spectral domain optical coherence tomography (SD-OCT). This cross-sectional, comparative study included 18 patients with acromegaly and 20 control subjects. All participants underwent SD-OCT to measure pRNFL (in the seven peripapillary areas), GCIPL (in the nine ETDRS areas), and central macular thickness (CMT). Visual field (VF) examinations were performed using a Humphrey field analyzer in acromegalic patients. Measurements were compared between patients with acromegaly and control subjects. A total of 33 eyes of 18 patients with acromegaly and 40 eyes of 20 control subjects met the inclusion criteria of the present study. The overall calculated average pRNFL thickness was significantly lower in patients with acromegaly than in control subjects (P = 0.01), with pRNFL thickness significantly lower in the temporal superior and temporal inferior quadrants. Contrary to our expectations, pRNFL thickness in the nasal quadrant was similar between acromegalic and control subjects. The mean overall pRNFL thickness and superonasal, nasal, inferonasal, and inferotemporal quadrant pRNFL thicknesses were found to correlate with the mean deviation (MD) according to Spearman's correlation. However, other quadrants were not correlated with VF sensitivity. No significant difference in CMT values was observed (P = 0.6). GCIPL thickness was significantly lower in all quadrants of the inner and outer macula, except for central and inferior outer quadrants, in the acromegaly group than that in the control group (P < 0.05). GCIPL thicknesses of the inferior inner and outer macula quadrants were found to correlate with MD, whereas no correlation was observed between other quadrants and VF sensitivity. We demonstrated that GCIPL thickness decreased in patients with acromegaly compared with that in control subjects. However, the nasal quadrant pRNFL thickness was similar in acromegaly, in contrast to our expectations. SD-OCT may have utility in the assessment of the effects of acromegaly on retinal structures.

Disease-free survival and the prognostic factors affecting disease-free survival in patients with medullary thyroid carcinoma: a multicenter cohort study.

PURPOSE: Despite several factors that may have been associated with poor disease-free survival (DFS) in patients with medullary thyroid carcinoma (MTC), only a few studies have evaluated the prognostic factors affecting DFS in MTC patients. Therefore, this study evaluated the prognostic factors affecting DFS, in a large number of patients with MTC. METHODS: Patients treated for MTC were retrospectively analyzed. Patients were stratified as having persistent/recurrent disease and no evidence of disease (NOD) at the last follow-up. The factors affecting DFS after the initial therapy and during the follow-up period were investigated. RESULTS: This study comprised 257 patients [females 160 (62.3%), hereditary disease 48 (18.7%), with a mean follow-up time of 66.8 ± 48.5 months]. Persistent/recurrent disease and NOD were observed in 131 (51%) and 126 (49%) patients, respectively. In multivariate analysis, age > 55 (HR: 1.65, p = 0.033), distant metastasis (HR: 2.41, p = 0.035), CTN doubling time (HR: 2.7, p = 0.031), and stage III vs. stage II disease (HR 3.02, p = 0.048) were independent predictors of persistent/recurrent disease. Although 9 (8%) patients with an excellent response after the initial therapy experienced a structural recurrence, the absence of an excellent response was the strongest predictor of persistent/recurrent disease (HR: 5.74, p < 0.001). CONCLUSIONS: The absence of an excellent response after initial therapy is the strongest predictor of a worse DFS. However, a significant proportion of patients who achieve an excellent response could experience a structural recurrence. Therefore, careful follow-up of patients, including those achieving an excellent response is essential.

Does oxidative status affect serum sclerostin levels in patients with type 2 diabetes mellitus?

INTRODUCTION: Sclerostin is a glycoprotein known as a negative regulator of bone formation, predominantly expressed by mature  osteocytes. There is no causative evidence information on the role of sclerostin in the pathogenesis of type 2 diabetes mellitus (T2DM) in humans. AIM: This study aimed to investigate the relationship between serum sclerostin levels and oxidative status and biochemical parameters in T2DM patients and healthy people. MATERIALS AND METHODS: This cross-sectional study, conducted in a clinical trial center, included 45 subjects with T2DM and 45 subjects as controls. RESULTS: Serum sclerostin, total oxidative status (TOS), albumin, and ferritin levels were significantly higher in T2DM patients than in the control group (p<0.05). Total antioxidant status (TAS) was significantly higher in the control group (p<0.05). There was a weak positive correlation between sclerostin and TOS (r=0.23, p=0.03) and a weak negative correlation between sclerostin and TAS (r=-0.28, p=0.03). CONCLUSIONS: We have demonstrated that serum sclerostin levels increase in patients with T2DM and that the increased sclerostin levels are associated with oxidative stress.

A National Multicenter Study of Leptin and Leptin Receptor Deficiency and Systematic Review.

CONTEXT: Homozygous leptin (LEP) and leptin receptor (LEPR) variants lead to childhood-onset obesity. OBJECTIVE: To present new cases with LEP and LEPR deficiency, report the long-term follow-up of previously described patients, and to define, based on all reported cases in literature, genotype-phenotype relationships. METHODS: Our cohort included 18 patients (LEP = 11, LEPR = 7), 8 of whom had been previously reported. A systematic literature review was conducted in July 2022. Forty-two of 47 studies on LEP/LEPR were selected. RESULTS: Of 10 new cases, 2 novel pathogenic variants were identified in LEP (c.16delC) and LEPR (c.40 + 5G > C). Eleven patients with LEP deficiency received metreleptin, 4 of whom had been treated for over 20 years. One patient developed loss of efficacy associated with neutralizing antibody development. Of 152 patients, including 134 cases from the literature review in addition to our cases, frameshift variants were the most common (48%) in LEP and missense variants (35%) in LEPR. Patients with LEP deficiency were diagnosed at a younger age [3 (9) vs 7 (13) years, P = .02] and had a higher median body mass index (BMI) SD score [3.1 (2) vs 2.8 (1) kg/m2, P = 0.02], which was more closely associated with frameshift variants (P = .02). Patients with LEP deficiency were more likely to have hyperinsulinemia (P = .02). CONCLUSION: Frameshift variants were more common in patients with LEP deficiency whereas missense variants were more common in LEPR deficiency. Patients with LEP deficiency were identified at younger ages, had higher BMI SD scores, and had higher rates of hyperinsulinemia than patients with LEPR deficiency. Eleven patients benefitted from long-term metreleptin, with 1 losing efficacy due to neutralizing antibodies.

Evaluation of Ocular Hypoperfusion in Patients with Acromegaly by Using Optical Coherence Tomography Angiography.

PURPOSE: This study aimed to evaluate the retinal blood vessel parameters and the foveal avascular zone (FAZ) area using optical coherence tomography angiography (OCTA) in patients with acromegaly in comparison with healthy controls. METHODS: A total of 45 patients with acromegaly and 45 healthy controls were included in this study. In all patients, the vessel density (VD) of the deep and superficial macular vascular networks and the foveal avascular zone (FAZ) were measured using OCTA. The correlation of insulin-like growth factor 1 (IGF-1) level and disease duration with deep macular VD and FAZ values was analyzed. All parameters were registered. Results were assessed and compared between the two groups. RESULTS: Deep macular plexus VD values were lower in patients with acromegaly compared to the control group. No significant differences in VD values in the superficial segment, except for that in the inferior parafovea (P = .01) were found between the two groups. Furthermore, patients with acromegaly showed enlargement in the superficial (P = .30) and deep FAZ areas (P < .001). IGF-1 level and disease duration showed a significant negative correlation with the deep whole image (R = -0.216, P = .041, R = -0.339, P = .001, respectively), deep parafovea (R = -0.271, P = .01; R = -0.372, P < .001, respectively), deep parafovea superior hemi (R = -0.342, P = .001; R = -0.350, P = .001, respectively), deep parafovea temporal (R = -0.224, P = .034; R = -0.234, P = .026, respectively), deep parafovea nasal (R = -0.320, P = .002; R = -0.361, P < .001, respectively), and deep parafovea superior VD values (R = -0.293, P = .005; R = -0.307, P = .003, respectively) and a significant positive correlation with the deep FAZ area values (R = 0.244, P = .02; R = 0.329, P = .002, respectively). CONCLUSION: VD values in the deep macular capillary plexus were lower in patients with acromegaly, and the superficial and deep FAZ area enlarged. Patients with acromegaly may have an increased risk of developing ocular vascular complications. OCTA can be used to evaluate retinal blood VD in patients with acromegaly.

Evaluation of Peripapillary Microcirculation in Patients with Acromegaly.

OBJECTIVES: The aim of this study was to evaluate the radial peripapillary capillary (RPC) and the optic nerve head (ONH) perfusion of patients with acromegaly using optical coherence tomography angiography (OCTA). METHODS: Twenty-four eyes of 24 acromegaly patients comprised the study group and 24 eyes of 24 healthy individuals were used as a control group. The ONH and RPC vascular density (VD) was measured for each patient using OCTA. The insulin-like growth factor 1 (IGF-1) levels were also recorded and compared. RESULTS: The VD of the inferior nasal ONH and nasal RPC was significantly lower in the acromegaly group than in the control group (p=0.047 and p=0.001, respectively). There was a significant negative correlation between the VD of the superior nasal ONH and the IGF-1 level (r=-0.283, p=0.038). CONCLUSION: The ONH and RPC VD values measured using OCTA were segmentally different in the acromegaly group compared with those of the control group. This method of non-invasive quantitative analysis of retinal perfusion using OCTA may be useful for future studies involving patients with acromegaly.

Biochemical characteristics and calcium and PTH levels of patients with high normal and elevated serum 25(OH)D levels in Turkey: DeVIT-TOX survey.

Vitamin D intake over the recommended dose is usually associated with high serum 25(OH)D levels and generally not associated with symptoms of hypercalcemia. High doses of cholecalciferol need to be avoided to protect against vitamin D toxicity and related complications. Strict adherence to the clinical guidelines for treating vitamin D deficiency can ensure safe and effective treatment. PURPOSE: We observed a tendency to use high doses of cholecalciferol for vitamin D deficiency treatment or vitamin D supplementation. We aimed to determine the biochemical characteristics of patients with high normal and elevated serum 25(OH)D levels. METHODS: An online invitation was sent to all tertiary endocrinology clinics in Turkey to complete an online retrospective survey (DeVIT-TOX Survey) for patients diagnosed with high serum 25(OH)D levels (> 88 ng/mL) between January 2019 and December 2019. The patients were evaluated according to the presence of signs and symptoms of hypercalcemia and doses of vitamin D intake, evaluated into the following three groups according to their 25(OH)D levels: group 1, > 150 ng/mL; group 2, 149-100 ng/mL; and group 3, 99-88 ng/mL. RESULTS: A total of 253 patients were included in the final analysis (female/male: 215/38; mean age, 51.5 ± 15.6 years). The average serum 25(OH)D level was 119.9 ± 33 (range, 88-455) ng/mL, and the average serum calcium level was 9.8 ± 0.7 (range, 8.1-13.1) mg/dL. Most (n = 201; 75.4%) patients were asymptomatic despite having high serum 25(OH)D and calcium levels. The serum 25(OH)D level was significantly higher in the symptomatic groups than in the asymptomatic groups (138.6 ± 64 ng/mL vs. 117.7 ± 31 ng/mL, p < 0.05). The most common cause (73.5%) associated with high serum 25(OH)D levels was the inappropriate prescription of a high dose of oral vitamin D (600.000-1.500.000 IU) for treating vitamin D deficiency/insufficiency in a short time (1-3 months). The cut-off value of 25 (OH) D level in patients with hypercalcemia was found to be 89 ng/mL [median 116.5 (89-216)]. CONCLUSIONS: High dose of vitamin D intake is associated with a high serum 25 OH D level, without symptoms of hypercalcemia. Inappropriate prescription of vitamin D is the primary cause for elevated 25(OH) D levels and related hypercalcemia. Hypercalcemia may not be observed in every patient at very high 25(OH) D levels. Adherence to the recommendation of guidelines is essential to ensure safe and effective treatment of vitamin D deficiency.

Increased Serum Sclerostin Levels in Patients With Active Acromegaly.

CONTEXT: Bone mineral density is normal in acromegalic patients and the cause of increased fracture risk that characterizes active acromegaly is unknown. OBJECTIVE: This study compared serum sclerostin levels between patients with active acromegaly and healthy individuals. DESIGN, SETTING, AND PARTICIPANTS: The serum sclerostin levels of patients with active acromegaly were compared with those of healthy volunteers in a cross-sectional study. The mean age of the 30 acromegaly patients (male/female: 14/16) was 47.26 ±â€…12.52 years (range, 18-64 years) and that of the healthy volunteers (male/female: 17/13) was 44.56 ±â€…10.74 years (range, 19-62 years). IGF-1 and GH levels were measured using an electrochemiluminescence method, and serum sclerostin levels using an ELISA. The Mann-Whitney U test was used to compare sclerostin levels between the 2 groups. The correlations of sclerostin level with IGF-1 and GH were determined using Spearman's test. RESULTS: The 2 groups did not differ in age or sex (P > 0.05). The median GH and IGF-1 levels in the patient group were 2.49 ng/mL (range, 0.22-70.00 ng/mL) (interquartile range [IQR], 1.3-4.52) and 338.5 ng/mL (range, 147-911 ng/mL) (IQR, 250-426), respectively. The median GH and IGF-1 levels in the control group were 0.95 ng/mL (range, 0.3-2.3) and 144 ng/mL (range, 98-198), respectively. The median sclerostin level was 29.95 ng/mL (range, 7.5-78.1 ng/mL) (IQR, 14.37-37.47) in the acromegaly group and 22.44 ng/mL (range, 8.45-36.44 ng/mL) (IQR, 13.71-27.52) in the control group (P < 0.05). There was a moderate positive correlation between the sclerostin and IGF-1 levels (rho = 0.54; P < 0.01), and between the sclerostin and GH levels (rho = 0.41; P < 0.05). CONCLUSIONS: High sclerostin levels may contribute to the increased fracture risk seen in patients with acromegaly.

Mental status and physical activity in patients with homozygous familial hypercholesterolemia: A subgroup analysis of a nationwide survey (A-HIT1 registry).

BACKGROUND: Homozygous familial hypercholesterolemia (HoFH) is a rare, life-threatening disease due to high serum low-density lipoprotein (LDL) cholesterol levels. LDL cholesterol-lowering interventions are fundamental for patients with HoFH. OBJECTIVE: It was aimed to investigate the association between the mental status of patients with HoFH and healthy lifestyle behaviors. METHODS: This subgroup analysis of the A-HIT1 population included the data of patients aged ≥18 years with a clinical diagnosis of HoFH undergoing therapeutic LDL apheresis. Besides the demographic and clinical characteristics of patients, healthy lifestyle behaviors were assessed, and psychiatric symptoms were screened by Symptom Check List (SCL-90-R). RESULTS: The highest percentage for pathology was observed in dimensions of obsessive-compulsive, somatization, interpersonal sensitivity, and depression in SCL-90-R. Patients with any cardiovascular condition have more psychiatric symptoms in different fields of SCL-90-R. The outcomes of the correlative analysis indicated that lower the age of the first coronary event better the psychiatric status, probably denoting a better adaptation to disease and its treatment. Among 68 patients, 36 patients were not exercising regularly. Patients with regular physical activity had significantly lower scores in most dimensions of SCL-90-R and there was no association between regular physical activity and other investigated variables. The strongest predictor of regular exercising was global severity index of SCL-90-R. CONCLUSION: In the HoFH population, there was a high prevalence of mental disturbances. Better psychiatric status was associated with regular exercising. Therefore, assessing the mental status of patients with HoFH and referring patients in need, to a psychiatrist, may improve the outcome of patients.