ACTA ENDOCRINOLOGICA (BUC)

Introduction. Heart failure and dilated cardiomyopathy (DCM) in adults are rarely caused by hypoparathyroidism induced hypocalcemia. Case report. Female patient, 40 years old, diabetic, with previous history of thyroidectomy for Graves’ disease, was hospitalized for syncope and symptoms of heart failure. ECG revealed sinus tachycardia, long QT, negative T from V1 up to V4. Chest X-ray, cardiac ultrasound and contrast cardiac MRI confirmed dilated left chambers, severe systolic dysfunction of the left ventricle (left ventricle ejection fraction=15%) due to diffuse hypokinesia and restrictive type of diastolic dysfunction. Patient status insignificantly improved with specific heart failure depletion treatment but important signs of hypocalcemia occurred. Low levels of total and ionic serum calcium were detected (total serum calcium 3.6 mg/dL, ionic calcium=2.2 mg/dL) along with low serum levels of parathormone (10 pg/mL) and high level of phosphatemia (6.4 mg/dL). After one month of parenteral treatment with calcium and oral vitamin D, hypocalcemic signs disappeared and heart failure significantly improved. Conclusion. This rare adult condition is refractory to heart failure conventional therapy but promptly responds to restoration of normocalcemia. It is important to be aware of this pathophysiological setting, in order to treat it correctly.

Introduction. Prader-Willi syndrome (PWS) is one of the most common known genetic causes of morbidly obese, resulting in\r\ndiabetes mellitus (DM) and the management of DM in PWS is difficult. Recently, glucagon-like peptide 1 (GLP-1) receptor agonists have been introduced for the treatment of type 2 DM. Here, we report the use of liraglutide, a GLP-1 receptor agonist, in a patient with DM in PWS.\r\nCase report. A Japanese male patient was diagnosed as having PWS at the age of 1 year. He was mentally retarted and developed morbid obesity. When he was 18 years old, his\r\nweight was 79 kg and height was 152 cm (BMI 34.1 kg/m2). His HbA1c level was 6.2 % and thus DM was diagnosed. Despite\r\nseveral medications, the control of DM worsened and thus at the age of 22 years his body weight and HbA1c further increased (83 kg and 10.8%, respectively). At this time,\r\nliraglutide was initiated. His weight and BMI did not change, however his HbA1c level decreased to 7.4 % after one year treatment. He did not have any side effects of liraglutide. This case indicates that GLP-1 receptor\r\nagonists may be useful for the treatment of DM with PWS.

Introduction. Wolfram Syndrome (WS) is a rare autosomal recessively inherited disorder characterized by juvenile-onset diabetes mellitus (DM), diabetes insipidus, optic atrophy (OA), hearing loss and neurodegeneration. This report describes three cases with WS. Case report. The first case was diagnosed with DM and OA at the age of 6 and 11 years, respectively. Second patient was the sibling of the first patient, also had DM and was investigated for WS after his brothers’ diagnosis. The third patient was diagnosed with DM at the age of 5 years and developed bilateral sensorineural hearing loss and OA at the ages of 7 and 12 years, respectively. Preliminary diagnoses of all patients were confirmed by Sanger sequencing of the WFS1 gene. Two previously reported and a novel mutation were detected. While our first patient was diagnosed with attention deficit hyperactivity disorder previously described in WS patients, obsessive compulsive disorder observed in case 2, was not previously reported in WS to the best of our knowledge. Puberty delay was detected in our first patient and was diagnosed as constitutional delay of puberty and growth. Conclusion. Early diagnosis of WS can lead to early detection of associated pathologies and to decrease complications, morbidity and mortality.

The beta 3 agonists have antiobesity, thermogenetic and lipolytic properties. Starting from BRL35135 structure, a well-known beta 3 agonist, 3 new phenylethylamine derivates (A, B, C) and 2 new pyrazol derivates (D, E) were synthesized.\r\nPurpose. The aim of this study was to evaluate the effect of five new compounds derived from of BRL35135 on glycemia in normal and diabetic rats.\r\nMethods. For each experiment, test and control groups of 6, 8 or 10 male Wistar rats were used. For inducing experimental diabetes mellitus, alloxan (100 mg/kg body weight) was intravenously injected. Tested substances were intraperitoneally injected (1 or 100 mg/kg body weight) and glycemia values were measured before and at 3 hours after their administration. Control groups received propyleneglycol, the solvent of the new compounds. Glycemia values were measured with a calibrated glucometer.\r\nResults. In normal rats one of the phenylethylamine compounds (substance C) (100 mg/kg body weight) had a hypoglycemic effect comparative to control (p=0.03). In glucose tolerance test, substance E (100 mg/kg body weight) stopped the increase of glycemic values determined by glucose oral administration in the first 60 minutes comparative to control (p=0.03). In the alloxanic diabetes model, before insulin administration the substances hypoglycemic effect could not be measured with the glucometer because of very high values of glycemia. After insulin administration no significant differences between the treated and the control groups were registered. Further studies on the hypoglycemic effect of substances C and E are needed in order to establish their possible antidiabetic effect.\r\nConclusion. A phenylethylamine derivate and a pyrazol derivate of BRL35135 had a hypoglycemic effect in normal rats, but this effect could not be confirmed in rats with alloxanic diabetes.

Increased frequency of adrenal tumours and adrenal myelolipoma has been reported in patients with 21-hydroxylase deficiency (21-OHD). Adrenal myelolipoma is an uncommon, benign, biochemically non-functioning tumor and occasionally reported in association with endocrine disorders. Diagnosis of myelolipomas is based on imaging with ultrasonography, CT or MRI being effective in more than 90% of cases. We present a 34-year-old man with massive bilateral adrenal masses which was detected on computed tomography and was diagnosed as 21-hydroxylase deficiency (21-OHD) based on biochemical findings. Computerized tomography of the abdomen demonstrated bilaterally very low-density adrenal masses (16x28 mm on the right side and 91x88 and 33x30 mm on the left side) consistent with adrenal myelolipomas. Since myelolipomas are considered as benign tumors, he was not operated. Tumor size did not increase during two year follow-up periods. It is recommended to the physicians to be aware of increased frequency of benign adrenal tumors that occur frequently in patients with 21-OHD. Untreated CAH with prolonged excessive ACTH stimulation might contribute to the growth of adrenal masses. CAH should always be ruled out in incidentally detected adrenal masses to avoid unnecessary surgical procedures.

Pituitary apoplexy (PA) is a life-threatening clinical syndrome. Dopamine receptor agonists are the drugs of choice in the treatment of prolactinomas. The use of cabergoline is reported to cause an increased risk of PA, particularly in macroprolactinomas of cystic nature. In this report, we present a patient with a cystic macroprolactinoma who developed PA on the 16th week of cabergoline treatment.

Objective. This study aims to determine the frequency and prognostic significance of lactic acidosis in children with diabetic ketoacidosis (DKA) admitted to the pediatric intensive care unit. Methods. The study was carried out retrospectively by examining the patients admitted to the pediatric intensive care unit for the treatment of DKA. The ages of the patients ranged from 2 to 18 years. The patients with the following parameters were enrolled in the study: serum blood glucose>200 mg/dL, ketonuria presence, venous blood gas pH ≤7.1, bicarbonate <15. Results. A total of 56 patients were included in the study with a mean age of 111.07 ± 51.13 months. The recovery time from DKA was 16.05 ± 6.25 h in the group with low lactate level and it was 13.57 ± 8.34 h in the group with high lactate level with no statistically significant difference. There was a negative correlation between lactate levels and the recovery time from DKA. Conclusion. Lactic acidosis is common in DKA, and unlike other conditions, such as sepsis, it is not always a finding of poor prognosis that predicts the severity of the disease or mortality. We think that high lactate may even protect against possible brain edema-cerebral damage in DKA.

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Background. Molecular defects in the SHOX gene including deletions, duplications or pathogenic point mutations are responsible for well-known pathologies involving short stature as a clinical manifestation: Léri–Weill dyschondrosteosis, Langer mesomelic dysplasia, Turner syndrome or idiopathic short stature. Duplications flanking the SHOX gene (upstream or downstream of the intact SHOX gene involving conserved non-coding cis-regulatory DNA elements - CNEs) have been described but their clinical involvement is still difficult to understand. Results. We describe two cases with short stature and normal GH-IGF1 status. Multiplex ligation-dependent probe amplification (MLPA) and array comparative genomic hybridization (arrayCGH) identified in both cases heterozygous duplications involving downstream regions of SHOX gene, within CNEs (CNE8, CNE9 and CNE4, CNE5, CNE6, ECR1, CNE8, CNE9 and surrounding areas, respectively). One of the cases showed a maternally inherited duplication. Although every case has several particularities, we consider that duplications in these non-coding regions of SHOX gene may explain the short stature phenotype. Conclusion. To our knowledge, these are the first Romanian-reported cases of ISS with a large duplication of downstream SHOX enhancers CNEs region. The spectrum of phenotypic consequences and the exact mechanism of the presumed clinical expression of these genetic alterations still needs to be evaluated and described.

Context. Neuroendocrine tumors are tumors developing from primitive cells in the intestinal walls, but can also affect the lungs, liver, pancreas, ovaries. Objective. We aim to describe the clinical, imagistic and biologic aspect of neuroendocrine tumors with different localizations and present the evolution, treatment options and prognosis. Design. Four patients either with previously known neuroendocrine tumors or with newly discovered tumors were studied. Subjects and methods. The first patient was diagnosed with primary liver carcinoid with pulmonary metastases by abdominal and thoracic CT scan, liver biopsy and determination of serologic markers. The second patient was diagnosed with primary lung neuroendocrine tumor using thoracoscopy biopsy and serologic markers The third patient was diagnosed with a large gastric neuroendocrine tumor with liver and spleen metastases. using CT scan, MRI and biopsy from the abdominal mass. The fourth patient was diagnosed with primary liver carcinoid using imagistic methods (CT scan) and liver biopsy. Results. The first patient died after 4 months due to the extent of the disease and comorbidities. The second patient had a good evolution, as the tumor was diagnosed in a localized stage. The third patient had a decreased survival due to the dimensions of the primary tumor and the multiple liver metastases which later caused obstructive jaundice requiring external biliary drainage. The fourth patient has had a good evolution, the tumor masses in the liver are being kept under control using transarterial chemoembolization. Conclusion. Neuroendocrine tumors are very versatile both in location and clinical aspect. The diagnosis requires imagistic methods but it is imperative to perform biopsy of the lesions with special histologic stains in order to be sure of the diagnosis.