ACTA ENDOCRINOLOGICA (BUC)

Context. Anti-Mullerian hormone (AMH) assay is becoming the best indicator of successful IVF treatment response to fertility drugs and could be a useful marker of embryo implantation potential. Various protocols are being used for controlled ovarian stimulation (COS), but there is an uncertainty regarding the implementation of the best protocol for endometriosis patients and also little evidence is available concerning the clinical value of AMH levels in endometriosis. Objective. This study aimed to evaluate the prognostic value of serum AMH levels for pregnancy in COS using GnRH-agonist(GnRH-a) and GnRHantagonist( GnRH-ant) protocols in endometriosis patients. Design. This is a cross-sectional study between March 2012 and November 2015. Subjects and Methods. Data were collected from 249 COS cycles of endometriosis patients, including 129 cycles with GnRH-a and 120 cycles with GnRH-ant. Patients in each group were classified into three subgroups based on their serum AMH levels. The outcomes of ICSI program were evaluated. Results. The ROC curve analysis showed that embryo and oocyte counts and AMH were equally predictive for pregnancy, as demonstrated by a similar area under the curve (AUC) of 0.69, 0.66 and 0.64, respectively. The sensitivity and specificity for prediction of positive pregnancy were 70.91% and 67.01% for embryo counts, 70.91% and 67.53% for oocyte counts at the cutoff values of 5 and 7, respectively, and 83.64% and 52.58% for AMH levels at the cutoff values of 1.3ng/mL. Conclusions. This study demonstrates that AMH as a single test has substantial accuracy in the prediction of pregnancy using the GnRH antagonist protocol for patients with endometriosis. In other words, AMH assay prior to ovarian stimulation initiation guides the clinicians to choose the antagonist stimulation protocol for the patients with two extreme AMH levels. AMH levels can be used to individualize control ovarian stimulation in endometriosis patients.

Context. It is a challenge to determine the origin of Cushing syndrome (CS), especially in patients with low-normal adrenocorticotropic hormone (ACTH) concentrations. Objective. To evaluate the reliability of the corticotropin-releasing hormone (CRH) stimulation test in patients with CS whose origin of disease was not clearly identified using ACTH values, the high-dose dexamethasone suppression test (HDDST), and imaging in a single tertiary referral center. Design and Methods. Twenty-one patients with CS who were admitted to the endocrinology-metabolism clinic between 2004 and 2016 whose ACTH concentrations were 5-20 pg/mL and needed CRH stimulation test were retrospectively assessed. Results. Nine out of 21 patients were diagnosed as having Cushing’s disease (CD) and 12/21 had adrenal CS. The CRH stimulation test had a sensitivity and specificity of 100% and 8%, and positive and negative predictive values of 100% and 45% according to the current diagnostic criteria, respectively. An increase in ACTH ≥115% at 15 minutes and cortisol ≥86% at 60 minutes after CRH were associated with the highest likelihood ratio. The sensitivity and specificity of ACTH was 67% and 83% (AUC=0.75±0.12, 95% CI: [0.5-0.9]; p=0.03), and for cortisol it was 75% and 78% (AUC=0.71±0.15, 95% CI: [0.5-0.9]; p=0.03). Cortisol suppression of more than 64% from basal level in the HDDST suggested CD with the highest likelihood ratio. When these cut-off values were used together, both tests were negative in the patients with CD. Conclusion. The CRH stimulation test has low specificity to localize CS in patients with ACTH concentrations of 5-20 pg/mL according to the current diagnostic criteria. Different diagnostic criteria may be used in the CRH stimulation test and also in the HDDST in this group of patients.

Background. The transport of gametes and embryos is facilitated by motile cilia lining the inside of the fallopian tube. Progesterone regulates ciliary beat frequency (CBF) through multiple types of progesterone receptors in the fallopian tube. Membrane progesterone receptors beta and gamma (mPRβ and mPRγ) are both expressed in the ciliated cell lining of the fallopian tubes of humans. This study aimed at exploring the mRNA expression of mPRβ and mPRγ in the fallopian tubes of women with ectopic pregnancy. Materials and Methods. In this Case control study, a quantitative reverse transcriptase polymerase chain reaction was performed to determine the mRNA expression of mPRβ and mPRγ in the fallopian tubes obtained from 12 women with ectopic pregnancies, 12 women with normal pregnancies, and 12 healthy nonpregnant women in the luteal phase of their menstrual cycle. Results. It was indicated that mPRβ and mPRγ were expressed in the fallopian tube of the three groups of participants. However, the expression of mPRβ and mPRγ mRNA in the fallopian tube of women with ectopic pregnancy was not significantly different from that of the nonpregnant and normal pregnant women. Conclusion. These results suggest that mPRs might play no role in etiology of ectopic pregnancies associated with disturbed progesterone signalling.

abdominal cystic lesions should include investigation of cystic pheochromocytomas. To date only a few cases of purely cystic pheochromocytoma have been reported in the English literature. Aim. To present the management in four cases of silent pheochromocytomas patients who presented with pure or partially cystic abdominal lesions with benign (n:3) and malignant characteristics (nonspecific neuroendocrine tumor) (n:1) in histological evaluation. Results. Resection of the tumor is considered the primary treatment option in the management of pheochromocytoma, and preoperative preparation with alpha and beta antagonists is crucial in order to avoid precipitation of hypertensive crisis during surgical procedures. The absence of clinical symptoms and lack of typical radiological features may complicate the diagnosis of pheochromocytoma resulting with increased mortality and morbidity during surgery. Conclusion. Asymptomatic pheochromocytomas are rare and they are responsible for approximately 5% of adrenal incidentalomas. These lesions may be referred to surgery as clinically nonfunctional adrenal adenomas.

Background and aim. Antithyroid drugs are first treatment for Graves hyperthyroidism worldwide. Although remission can be achieved in approximately 40-50% of patients in 12-18 months with antithyroid drugs, this period can be extended up to 24 months. We aimed to evaluate the effect of individual clinical/biochemical variables and GREAT score in predicting response to antithyroid drug in Graves disease. Material and methods. This is a retrospective single-center study including 99 patients with the first episode of Graves disease treated for at least 18 months. The patients were classified into two groups as those who responded to antithyroid medication at 18-24 months (group 1) and those who did not respond at 24 months and continued with low-dose antithyroid medication (group 2). Results. Medical treatment response was obtained in 38 (38.3%) of the patients at 18 months, and in 19 (19.1%) patients at 24 months. Long-term medical treatment (>24 months) was given to the remaining 43 patients due to the lack of response to medical treatment. Thyroid volume and free T4 levels were higher in those followed up with longterm antithyroid drugs, and orbitopathy was more common in this group. Median anti TPO value was significantly higher in group 1 when compared to group 2 (593 U/l and 191.6 U/l respectively). More patients were classified as GREAT class 3 in group 2 when compared to group 1 (46.5% and 12,5% respectively). We analyzed the Thyroperoxidase Antibody(anti TPO) titers, which we divided into three levels, according to groups 1 and 2. Post-hoc Chi-Square analysis revealed that falling into the highest anti TPO category was significantly associated with response to medical therapy in 24 months (p <0.05). Conclusion. According to our study, GREAT score and anti TPO Ab titers at presentation may help predict response to ATD in Graves disease

Objective. We aimed to determine the risk of hypercalcemia in a geriatric population with very high dose levels of 25-hydroxy-vitamin D (25(OH)D). Patients and Method. This study was designed as a retrospective, cross-sectional two-center study for examining the elderly patients with very high 25(OH)D levels (>88ng/mL) between January 2014 and December 2019. After recruitment, subgroup analyses of the patients were performed based on their calcium and vitamin D levels. Results. A total of 81.101 elderly patients, who had been evaluated for their vitamin D levels, were screened. Of the 458 (0.6%) elderly patients with 25(OH)D>88 ng/ mL according to our criteria, 217 patients with complete data were accepted into our study. The median 25(OH)D level was 103.7ng/mL (min-max:88.2-275.9). Most of the elderly patients (86.6%) with very high 25(OH)D levels were normocalcemic. When patients with hypercalcemia were compared with normocalcemic group, no difference was observed in the levels of 25(OH)D, intact parathormone (iPTH), phosphorus, alkaline phosphatase (ALP), and their age. However, the PTH suppression rate was significantly higher in hypercalcemic group (p=0.005). Conclusion. The elderly patients with very high 25(OH)D levels would appear to be mostly normocalcemic whereas life-threatening hypercalcemia would also occur. Treatment and follow-up planning should be done according to the clinical guideline recommendations.

Objective. To evaluate circulating FFAs in relation to glucose and insulin metabolism and to different fat compartments in men with and without diabetes. Patients and Methods. Thirtythree men with uncomplicated type 2 diabetes mellitus (T2DM) and 28 controls underwent an oral fat load and were studied at baseline and for 5 hours postprandially for serum FFAs, glucose and insulin. Abdominal fat distribution and gluteal fat accumulation were evaluated by anthropometrics and axial MRI images. Insulin resistance and sensitivity were estimated by HOMA and Matsuda index respectively. Results. Fasting and postprandial FFAs were higher in diabetics (p=0.007) despite similar fat accumulation and distribution between groups. Postprandial FFAs correlated positively with postprandial glucose, and fasting and postprandial insulin levels (p< 0.05) in controls, and with fasting and postprandial insulin levels (p< 0.05 and p < 0.01 respectively) in diabetics. Postprandial FFAs were positively correlated to HOMA (p<0.01) and negatively to Matsuda index (p<0.05), and positively to total visceral and retroperitoneal fat,the strongest association observed at L2- L3 (p<0.05 and p<0.001 respectively) in diabetics. Conclusions. Diabetics have higher serum FFAs, despite similar levels of adiposity and fat distribution. Interestingly, postprandial FFAs correlate strongly and positively with total visceral fat, underlying the importance of visceral fat in metabolic abnormalities in diabetes.

Chronic transfusion regimen and chelating therapy has dramatically improved the life expectancy of thalassemic patients. The aim of this study was to assess the prevalence of endocrine disturbances in patients with beta-thalassemia major. Subjects were 64 patients with a mean age of 19.45 ? 6.82 years found in haematological care at the National Institute of Transfusional Haematology. All the patients were evaluated clinically and biologically. LH, FSH, estradiol, testosterone, TSH, free T4, insulin were measured by chemiluminescence; mean ferritin value was used to assess iron overload. Fifty one patients (79.68%) -27 male and 24 female in our group were at pubertal or adult age. Eleven boys (40.74%) had delayed puberty, 10 (37%) arrested puberty and 4 (14.8%) had reached complete sexual maturation. In the female group, 6 (25%) had delayed puberty, 4 (16.66%) arrested puberty and 14 (58.32%) reached full sexual development. Half of both the male and female patients with complete sexual maturation had hypogonadotropic hypogonadism at the evaluation moment. Moreover, 34 (53.12%) of our patients had pathological short stature, 11 (17.18%) primary hypothyroidism, 5 (7.8%) hypoparathyroidism, 3 (4.68%) diabetes mellitus and 6 (9.37%) insulin resistance. We found a significantly higher mean ferritin value in patients with endocrine disturbances of any type compared to subjects without endocrinopathies. In conclusion, our data showed that hypogonadism and short stature were the most frequently found endocrine disturbances. Early form of hypogonadism had a major clinical impact on sexual development and final height. These results suggest that early endocrine evaluation and treatment are necessary in order to improve the quality of life of these patients.

Background. This study aimed to assess fractal dimension (FD) and the radiomorphometric indexes on the digital panoramic radiography (DPR) of patient with primary hypothyroidism receiving levothyroxine sodium replacement therapy. Methods. A total of 115 subjects were included in this cross sectional retrospective study. According to the results of the thyroid function tests, the subjects were divided into two groups as primary hypothyroidism (levothyroxine sodium replacement therapy given), (n = 57) and the healthy control group (n = 58). The fractal dimension (FD), panoramic mandibular index (PMI), mandibular cortical width (MCW), gonial index (GI) and mandibular cortical index (MCI) values of all patients were calculated on DPRs. The statistical analysis of all data was performed with SPSS version 22. Results. The distributions of age and gender in the primary hypothroidism group were similar to control group (p = 0.19 and p = 0.62, respectively). The two groups did not differ statistically significantly in terms of FD, PMI, MCW, GI, and MCI. Conclusion. We determined that mandibular cortical and trabecular bone structure did not significantly differ between healthy individuals and patients receiving drug replacement theraphy due to hypothyroidism, but our results should be further supported with the investigation of clinical parameters.

Objective. To compare two chromatographic methodologies for determination of plasma phenylalanine (Phe) and their usefulness for diagnosing hyperphenylalaninemia (HPA) and phenylketonuria (PKU). Methods. The plasma amino acids were isolated and concentrated from blood collected from infants with HPA detected by newborn screening. The plasma Phe was determined in parallel by HPLC and by image-densitometry of 2D-TLC plates. Results. Typical examples of 2D-TLC plates and HPLC chromatograms from infants with HPA and PKU are presented and evaluated. The Phe spot was visible on 2D - TLC plates at Phe concentrations higher than 300 μmol/L. The standard calibration curve traced after imagedensitometry of the Phe spot presented high dispersion of values at each concentration of Phe, high SD values, the equation of the curve having a low R-squared value (0.862). In contrast, the standard calibration curve obtained by HPLC shows linearity on the range of concentrations from 100 - 16,000 μmol/L, extremely small SD values, the equation of the curve has a very high R-squared value (0.999). Conclusions. The HPLC methodology is appropriate to confirm HPA detected by newborn or selective screening of PKU. The 2D - TLC methodology is adequate to detect patients with severe PKU.