ACTA ENDOCRINOLOGICA (BUC)

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.

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.

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.

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.

Context. Trabecular Bone Score (TBS) has been recently proposed as a good tool to investigate secondary osteoporosis. Objective. The aim of this study was to assess TBS from spine DXA images in patients with primary hyperparathyroidism (PHPT) and look at its correlates. Subjects and Methods. 153 patients, mean age 59.1 ± 12.1 yrs, females and males (10%), mean BMI 26.2 ± 4.8 kg/m2, mean serum calcium and PTH of 11.3 ± 1.2 mg/dL and 232 ± 329 pg/mL, respectively; 89% had osteoporosis/ osteopenia by LS DXA and 46% had renal involvement. There were 7.6% patients with vertebral fractures, 13.2% patients with nonvertebral fractures. TBS indices were derived from LS-DXA images and cutoff points used were those previously reported. Results. Mean TBS was in the partially degraded range (1.258 ± 0.115); 32% of patients had degraded microarchitecture (TBS ≤ 1.20), 51% had partially degraded microarchitecture (TBS > 1.20 and < 1.35) and 17% had normal TBS. TBS was significantly correlated with areal BMD both at the LS (r=0.544; p<0.001) and FN (r = 0.315; p < 0.001), and negatively with age (r= - 0.354; p < 0.001) and years since menopause - YSM (r = - 0.257, p = 0.005). Patients with vertebral fractures had mean values of TBS in the degraded range, significantly lower than those without vertebral fractures (1.173 ± 0.076 vs. 1.263 ± 0.115; p = 0.006). The presence of vertebral fracture was independently associated only with YSM (OR = 1.131, 95% CI = 0.032 – 0.214, p = 0.008) but not with TBS. Conclusions. In a cohort of symptomatic PHPT patients, including postmenopausal, premenopausal and male patients, we have shown that TBS was in the partially degraded range, but it was not independently associated with fractures.

Background. Gestational diabetes mellitus (GDM) is associated with high frequency of obstetric complications, such as gestosis, polyhydramnios, urogenital infection, premature birth. An increase in the number of cases of detection of GDM in pregnant women living in Kazakhstan is noted recently. Objective. This research was carried out in order to see the influence of GDM on the course of the third trimester of pregnancy, outcomes and fetal status in women of Kazakh ethnic group. Research design. Cohort observational study. Subjects and Methods. The main group of research consisted of 61 pregnant women with GDM (Meanage= 32.8±6.314), the control group included 39 pregnant women with normal glucose tolerance (Meanage=30±5.432 years). The pregnant women in both groups were examined by calculation of body mass index (BMI), determination of fasting plasma glucose and the system of hemostasis. Also, the fetal ultrasound was implemented and the uterineplacental, fetal-placental blood flow were evaluated using the Doppler mode. Results. In the main group initial BMI was equal to Mean=31.1±7.433 kg/m2; we revealed manifestation of gestational hypertension in 36.1%, 95%CI (2.52, 48.6); preeclampsia was diagnosed in 14.8% (95%CI (8; 25.7); the disorders of uteroplacental and fetoplacental blood flow recorded significantly more frequently in main group RR=6.393, 95%CI (1.581-25.840), like the diabetic fetopathy RR=5.115, 95%CI (1.240-21.033). The premature delivery, the prevalence of induction of delivery and intranatal trauma were significantly more frequent in women with GDM. Conclusions. GDM significantly worsens course of gestation.

The most common cause of hypercalcemia is parathyroid hyperplasia and carcinoma. Tuberculosis(TB) and sarcoidosis are the most common granulomatous diseases of the parathyroid. We report a case of parathyroid adenoma that can mimic many lesions. A 46-year-old woman on continuous ambulatory peritoneal dialysis (CAPD) with symptoms and signs of hypercalcemia. Laboratory findings were consistent with tertiary hyperparathyroidism. She underwent elective parathyroidectomy due to high PTH values despite effective treatment including calcimimetics and vitamin D receptor activators. Subtotal thyroidectomy and three and a half of parathyroid adenomas were removed. Histopathological examination revealed features of parathyroid adenoma with granulomatosis infection that supports tuberculosis. In order to confirm the pathological findings, the PCR study was performed on the pathology specimens. After obtaining a negative result, the treatment was stopped. We have reported a case of parathyroid adenoma that mimicking tuberculosis.

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Background. Type 1 diabetes mellitus is a common disorder which causes a variety of complications such as cognitive deficits in central nervous system. Auditory P300 event related potential is a wellestablished neurophysiologic approach in the assessment of cognitive performance. In this study, we aimed to evaluate the cognitive performance in insulin dependent diabetic patients by auditory event related potentials. Methods. In this descriptive analytical and non-interventional study, auditory P300 event related potential was measured in oddball paradigm by using two tone burst stimuli (1000 & 2000 Hz) on 25 diabetic patients and 25 age, education and sex matched healthy controls, with mean age 28.76±4.1 in patients and 29.68±3.6 in controls. Results. The mean P300 latency of the diabetic patients was significantly prolonged and the mean P300 amplitude of the diabetic patients was significantly lower when compared with that of controls at all electrode sites (p<0.01). Also there was a strong correlation between P300 latency and glucose level, HbA1c and diabetes duration (p<0.01). Conclusion. Auditory information processing is slower and the speed of information categorizing is lower in diabetic patients than in controls.

years because of their cardio-protective and renoprotective properties in diabetes. SGLT-2 inhibitors, when introduced in diabetic patients, may cause euglycemic diabetic ketoacidosis. A 55-year-old woman presented with low-grade fever, vomiting, and lethargy. She was started on dapagliflozin two years back. On workup, she was diagnosed with euglycemic diabetic ketoacidosis (EDKA) and was managed accordingly. She improved clinically while her dapagliflozin was stopped. With a literature search, we have identified 15 case reports of EDKA with dapagliflozin since 2015. There are no standard guidelines regarding the monitoring of patients for this rare but potentially morbid complication. Moreover, the exact mechanism for this is unknown. Various precipitating factors are linked with SGLT-2 inhibitors in promoting EDKA. We recommend that customary plans should comprise educating the patient about this rare complication before commencing medication, close follow-up with serial electrolyte monitoring, and discontinuing medications in the state of infection, dehydration and recent surgery and serious illness requiring hospitalization.