ACTA ENDOCRINOLOGICA (BUC)

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.

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.

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.

Paget’s disease is a disorder of aging bone which occurs in the setting of accelarated bone remodelling. In the presented case we discuss the difficulties in the diagnosis of Paget’s disease in a 77 year old patient with coexisting endometrium carcinoma. The patient was initially diagnosed with metastatic bone disease due to endometrium adenocarcinoma when she was admitted to oncology clinic with pelvic pain. Bone scintigraphy with Tc99 and (18) F fluorodeoxyglucose positron emission tomography/CT revealed an increased uptake on the bone lesions which were reported as metastatic bone involvement. Although the (18) F-FDG uptake was much higher than the levels that would generally be anticipated in a case with Paget’s disease, high levels of bone turnover markers indicated further evaluation in the differential diagnosis and the definitive diagnosis of Paget’s disease was established with the pathological evaluation of bone biopsy.

The eighth JNC committee raised the target of systolic blood pressure to less than 150 mmHg for patients older than 60 years. Recently, results from a randomized controlled trial from the SPRINT Research Group have shown that among non-diabetic people with hypertension and other cardiovascular risk factors, reducing systolic blood pressure to less than 120 mmHg resulted in lower incidence of major cardiovascular events and deaths from any cause. In limited area of the human brain, insulin acts in modulation of body weight by food intake and modification of metabolism: hypothalamus (the central regulator of wholebody energy homeostasis and of food intake), prefrontal cortex (inhibitory control of eating), hippocampus (memory) and the fusiform gyrus (recognition of food, positive emotions, reward). Pregnancy, obesity, increasing age and also with some common genetic variants in the genes of IRS1, FTO, MC4R, CNR2, APOE are linked with insulin resistance in the brain.

The study comments unusual associations between thyroid and cutaneous autoimmunity: Graves-Basedow disease (GBD), vitiligo and alopecia areata (AA) starting from two cases. In the first case, a woman with systemic lupus erythematosus (SLE), data were recorded from 38 to 49 years as follows: vitiligo (at 38 ys), alopecia areata (4-6 months afterwards), SLE (after 2 ys) and then GBD (after 8 ys). After 3 years, hyperthyroidism has spontaneously vanished, but vitiligo, AA, leucothrichia, SLE, goiter and ophthalmopathy persisted. In the second case, a man, data were recorded from 26 to 70 years and the disease was associated with psoriasis. The sequence of diseases was: vitiligo (at 26 ys), AA and GBD (after 8 ys), followed by iatrogenic 131I hypothyroidism, and psoriasis (after 33 ys). Vitiligo and AA have spontaneously vanished before GBD began. These multiple immune syndrome associations bring up the question: ?Are these diseases multiple associations or a unique immune disease?? A possible point of view, related to immune network, suggests that these multiple associations represent in fact only one process, therefore they represent not many diseases, but different expressions in time (sequence) and space (organ-lesion) of the disease of the immune network.

Craniopharyngioma is part of a spectrum of suprasellar cystic neoplasms, with two distinct clinicopathological entities: most are adamantinomatous tumors occurring more\r\noften in children and young adults, and radiographically are calcified, while papillary form develops more often in adults, lacks calcification, and have a better outcome.\r\nIn this report we describe clinical, CT and MRI features, together with histopathological findings of an early recurrent papillary craniopharyngioma. Reviewing the\r\nCT and MRI findings and microscopic specimens of both the initial and the recurred craniopharyngioma, we identified the rapid relapse of the solid tumoral component and\r\ncorrelate it with low-grade basal cell dysplasia of the epithelial component that evolves from small patchy foci to more extensive areas in length and width. While low-grade basal cell dysplasia is not clearly malignant, once the pathologist sees these cellular changes in a papillary cranyopharyngioma, he must note them in his report as basal cell dysplasia could be the cause of an early tumoral recurrence. Although low-grade basal cell dysplasia in\r\nsquamo-papillary craniopharyngioma is uncommon, when such a diagnosis is established, the radiologist must pay attention to MRI characteristic findings of the solid part (maximum diameters, enhancing aspects, shape, and location) and compare them with those from the previous data.

Sustained exposure to high serum insulin-like growth factor (IGF-1) levels is likely to play a role in the development of the thyroid tumor in acromegaly; however, there is no report that indicate a promoting effect on the secretion of hormones by the thyroid tumor. We report a case of acromegaly in a seventy-one-year-old female with primary subclinical hyperthyroidism. Autoantibodies including\r\nanti-thyroglobulin antibody, anti-thyroid peroxidase antibody and thyroid stimulating hormone (TSH) receptor antibody were all negative. Ultrasonography of the thyroid\r\ndemonstrated a solid adenoma in the left thyroid lobe and Technetium-99m thyroid scintigraphy showed a high level of\r\naccumulation into the same lesion, indicating that toxic nodular goiter (TNG) was the cause of hyperthyroidism. Despite serum thyroid hormones remaining at normal levels,\r\nserum TSH levels went on decreasing gradually until transsphenoidal surgery to treat a growth hormone (GH) secreting pituitary adenoma. Interestingly, as IGF-I\r\nand GH levels normalized after operation, the serum TSH level increased and finally reached the normal level without\r\nintervention to the thyroid. Additionally, accumulation of Technetium-99m seen with thyroid scintigraphy slightly decreased. The evidence obtained from this case may\r\nsuggest a novel mechanism whereby excessive secretion of thyroid hormones from TNG in an acromegalic patient is\r\nregulated by IGF-I.