ACTA ENDOCRINOLOGICA (BUC)

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.

Hypothyroidism is a frequently diagnosed endocrine disorder that has characteristic\r\nclinical signs and symptoms. The frequency of myopathy in hypothyroidism ranges from 30 to\r\n80%. The major symptoms related are: weakness, muscular cramps and myalgia. The\r\npseudohypertrophic form is called Hoffman's syndrome and is quite rare, reassign diagnosis\r\ndifficulties both to endocrinologists and neurologists. The pathogenesis of this form of\r\nmyopathy is still unclear. We report the case of two patients, daughter and father with\r\npseudohypertrophic myopathy and hypothyroidism by Hashimoto's thyroiditis. The two were\r\npreviously treated for hyperthyroidism: first by antithyroid drugs and secondary by surgery (the\r\ndaughter) and radioiodine (the father). Both developed iatrogenic hypothyroidism that vas\r\ntreated by thyroxin replacement therapy. The muscular symptoms: progressive proximal\r\nweakness, muscle hypertrophy accompanied by stiffness, spontaneous muscular pain, muscular\r\ncramps and fatigue during mild exercise have developed during the year before admittance. In\r\nboth patients Hashimoto's thyroiditis was revealed by the high level of TPO antibodies and the\r\nthyroid appearance in sonography. Hormonal dosages confirmed hypothyroidism. Elevated\r\nvalues of CPK and electromyography established the diagnosis of thyroid myopathy. Muscular\r\nsymptoms were improved but not remitted by the thyroxin replacement therapy in adequate\r\ndoses, but CPK normalized. It is the first time that a familial case of Hoffmann syndrome is\r\ndescribed, suggesting a genetic susceptibility to the development of the syndrome.

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.

Niemann-Pick disease (NPD), is a rare autosomal recessive lysosomal storage disorder. Niemann-Pick A and B are caused by homozygous or compound heterozygous mutations in the sphingomyelin phosphodiesterase-1 (SMPD1) gene on chromosome 11p15. Type B is panethnic, although its frequency is increased in Turkish, Arabic and North African populations. Clinical features vary significantly among patients. It is a rare condition and information about its management an outcome during pregnancy and labor is limited. Both maternal mortality and morbidity due to severe postpartum hemorrhage has been reported. We represent a case of successful pregnancy outcome in patient with NPD type B. Type of mutations in SMPD 1 gene and severity of disease before pregnancy can predict the prognosis of pregnancy.

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.

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.

OBJECTIVE: To report an unusual cause of respiratory failure in a 33-year old Caucasian woman, diagnosed at 26 years with pulmonary lymphangioleiomyomatosis (LAM) and treated with gonadoliberin analogs (aGnRH) four years.\r\nMETHODS: The respiratory failure was diagnosed on functional tests (spirometry, oxymetry, diffusing capacity of carbon monoxide). High resolution chest computed tomographic (HRCT) scan and open lung biopsy with specific immunohistochemistry certified the diagnosis.\r\nRESULTS: The diagnosis of pulmonary LAM was established after one year on chest HRCT and lung biopsy which revealed the proliferation of smooth muscle of pulmonary vessels, positive for actin, desmin, vimentin, estrogen- and progesterone- receptors. Spirometry revealed mixed obstructive and restrictive dysfunction. A correlation between worsening of dyspnea and estradiol peaks occurred during three gestation periods. Despite a short treatment with medroxyprogesterone 10 mg/day and tamoxifen (20 mg/day), the patient?s symptoms and pulmonary function tests worsened. aGnRH treatment improved both symptoms and pulmonary function tests during the first year and was associated with a slow decline in pulmonary function tests and stabilization of the cystic lesions during the following 3 years. The patient did not develop LAM-complications such as: pneumothorax, chylothorax, or hemoptysis.\r\nCONCLUSION: Treatment with aGnRH is effective in slowing the evolution of pulmonary LAM.

Introduction. Hypogonadotropic hypogonadism is an endocrine disease with a major effect on bone tissue turnover leading to bone demineralization and secondary osteoporosis. Case report. A 42 year old man underwent a total left hip joint arthroplasty for a left aseptic femoral head necrosis with an unsatisfactory evolution because of pain, marked functional deficit, limping and instability sensation in the operated lower limb. Five years before the patient was diagnosed with hypogonadotropic hypogonadism presenting gynecomastia, gynoid fat distribution, eunuchoidal skeletal proportions, reduced facial hair, a Tanner III stage of the external genital development, without erectile dysfunction. The unsatisfactory post-operative result was secondary to an aseptic mechanical degradation due to bone mineral loss (secondary osteoporosis) and also application of undersized non-cemented implant. Standard biological analyses did not show modification, the inflammatory tests were negative. The DXA examination, after a period of 2 years without treatment, showed a decrease of bone mineral density and confirms the diagnosis of secondary osteopenia. It was made the decision of surgical intervention and replacement of the uncemented femoral component with a cemented one. After the surgery, the therapy with bisphosphonates, calcium, vitamin D3 and testosterone is reinitiated. Discussion. The clinical outcome of biointegration of a non-cemented prosthesis depends in first of all of the biological status of the patient, with normal BMD, normal calcium and D vitamin levels. The secondary osteoporosis with local aseptic inflammation on the surface of the prosthesis and bone contact led to mechanical failure which maked necessary the revision surgery, in order to replace the prosthesis with a cemented one. Conclusions. In our case the presence of hypogonadotropic hypogonadism with secondary osteoporosis, represents a contraindication for non-cemented total hip joint arthroplasty, due to major risk of loosening.