ACTA ENDOCRINOLOGICA (BUC)

The appearance and normal development of the anterior pituitary gland requires several signalling molecules and specific transcription factors. Gene mutations of these\r\npituitary transcription factors may lead to different degrees of combined pituitary hormone deficiency (CPHD) associated or not with morphological changes of the hypothalamicpituitary region. We present the first Romanian case of progressive CPHD in two brothers from a consanguineous family. Clinical, hormonal and MRI follow-up were performed during 20 years. Growth hormone deficiency was certified at the age of 5, respectively 3 years, followed by gonadotropin deficiency diagnosed at the age of 21, respectively 19 years, and by central hypothyroidism diagnosed at the age of 23, respectively 21 years.\r\nSubstitutive treatment rhGH was commenced, followed by testosterone and later thyroxin, in adequate doses. Adrenal function was normal during the follow-up. MRI revealed\r\nanterior pituitary hypoplasia in both siblings, with a partially empty sella in the younger brother and a thick midline septum in the sphenoid sinus in both siblings, which was not described in previous reports. The progressive CPHD suggested a PROP 1 deficiency, which was confirmed by genetic analysis. The c.301-302delAG homozygous mutation in the PROP 1 gene was identified, resulting in a complete loss of promoter binding and\r\ntranscriptional activation of the mutant protein.

controversial. Aim. This study retrospectively reviews the tumor evolution in patients with NFA macroadenomas treated with surgery and conventional RT, as compared to surgery alone. Methods. Of 107 unselected patients with operated NFA (aged 19 - 77 years), evaluated between 1977 - 2008, 71 patients were follow-up without RT (group A), while 36 patients were submitted to RT (group B). Patients submitted to radiosurgery were not included. Both groups underwent serial imaging studies with computed tomography or magnetic resonance. Tumor evolution was conventionally defined as a change of minimum 25% of diameter. Results. The surgical approach was transfrontal in 47% of patients, transsphenoidal in 43% or both in 10% of patients, similar in both study groups. In group B, 30 patients underwent highvoltage RT (mean total dose 50.5 Gy) and 6 patients low-voltage RT (mean emission dose 16,775 R). Mean follow-up after surgery in group A was 3.4 years (range 6 months - 10 years) and after RT in group B it was 6.8 years (range 2 &#8211; 24 years), p < 0.001. In group A, 16 out of 71 patients had no visible tumor remnants. In this subgroup, 2 patients (12.5%) showed tumor recurrence. Fifty-five out of 71 patients had residual tumors, 21 with extrasellar extension after surgery. In this subgroup, 21 patients (38%) showed tumor re-growth and 7 (13%) showed tumor decrease. In group B (n=36) all patients had tumor remnants after surgery with extrasellar extension in 30 patients. After RT, tumor re-growth occurred in 5 out of 36 patients (14%) as compared to subgroup A with residual tumors (p< 0.05) and tumor decrease in 14 out of 34 (41%), as compared to the same subgroup A (p < 0.01). The 5 year-tumor re-growth free survival rate of 88% in irradiated patients was significantly better than in non-irradiated patients with residual tumors (31%, log-rank test, p < 0.01, Kaplan-Meier analysis), but similar to that in patients without remnants (87.5%). Age, sex, tumor parasellar extension and size of residual tumor were not predictors of recurrency. Conclusion. Postoperative radiotherapy provides a significant improvement of local control in patients with residual NFA compared to surgery alone. It is necessary a long term follow-up due to recurrency noticed up to 8 years postsurgery. In patients without tumor remnants, a wait-and-see policy is indicated after surgery.

Context. Ghrelin is a hormone secreted primarily from stomach that can affect growth by its somatotropic and orexigenic activities. Objective. The aim of this study was to investigate the relationship of ghrelin and growth in children and adolescents with idiopathic short stature. Subjects and Methods. After thorough clinical examination, 56 subjects including 31 with normal weight and height and 25 with short stature were evaluated for fasting total (TG) and acylated (active) ghrelin (AG) levels. All the parameters of growth including growth hormone and IGF-1 levels, bone age and body mass index were also investigated. Appetite was also assessed and all the studied subjects were also divided into two groups, poor or good appetite. Results. TG and AG levels were not significantly different in the two groups. There was not any significant correlation between ghrelin and parameters of growth. On the other hand, TG concentration was significantly higher in subjects with poor appetite, but AG was not significantly different. Conclusions. The results of this study show that ghrelin is not significantly altered in idiopathic short stature. Although TG is increased in children with poor appetite its acylation is not increased concomitantly.

Objective. Mean platelet volume (MPV) and platelet function analysis have been studied before in acromegaly, but the effect of treatment on both parameters has not been evaluated. We aimed to investigate MPV and platelet function analysis in acromegalic patients after sixmonths of treatment. Methods. Forty patients with active acromegaly and 36 healthy subjects were included in the study. Plasma glucose and lipids, fibrinogen, GH, IGF-1 levels, MPV and platelet function analysis were measured. All patients with acromegaly were re-evaluated six months after treatment. Results. Fasting blood glucose (FBG), GH, IGF- 1, fibrinogen levels and MPV values were significantly higher in acromegalic group compared with the control. Platelet function was enhanced significantly (pcol-ADP: 0.002, pcolepinephrine: 0.002). After 6 months of treatment FBG, serum GH, IGF-1, fibrinogen and MPV decreased and collagen/ADP- and collagen/epinephrine-closure times (CT) were increased. Acromegalic patients that were in remission with long-acting SSA after surgery had significantly higher fibrinogen levels and MPV and decreased collagen/ epinephrine-CT with respect to the controls (pfibrinogen: 0.001, pMPV: 0.026, pcol-epinephrine: 0.037). Conclusion. Acromegaly was associated with increased MPV and enhanced platelet activity. Although growth hormone hypersecretion was controlled by surgery and medical treatment, these parameters did not improve – indicating a still increased risk for cardiovascular events.

Context. GnRHa treatment has been a standard of care in progressive early puberty (EP). Choice of the GnRHa formulation is dependent on the preference of the clinician. Objective. To compare the effects of triptorelin acetate (TA) and leuprolide acetate (LA) on anthropometry in girls with EP. Design. A descriptive observational study. Subjects and Methods. Girls diagnosed with central EP and treated with GnRHa at least for one year were included; treated with TA (n=46) and LA (n=35). First year anthropometric response and final height were evaluated. Results. The mean age at the initiation of GnRHa treatment of girls was 8.5±0.5 years. The ratio of obesity and of overweight was 7.4 and 25.9%, respectively. In both TA and LA groups, anthropometric data of the patients at initiation and at the first year of treatment were similar. Although growth velocity was similar in each group, in LA group height SDS at the first year of the treatment showed a significant decrease (p=0.045), but not in TA group (p=0.317). No significant ΔBMI was observed with treatment. The differences between FH – PAH at initiation (height gain) in TA and LA groups were 2.9±4.7 and 4.0±5.8 cm, respectively (p=.316). Height gain per treatment year was 1.7±3.0 cm. Conclusions. There was a significant decrease in height SDS at the first year of leuprolid treatment, but not in triptorelin. Although these two analogs show similar effects on treatment, a not significant but slightly better benefit in leuprolide was observed.

Pediatric chronic kidney disease (CKD) has a substantial global impact because is associated with notable morbidity. Secondary hyperparathyroidism (SPHT) frequently emerges as a complication in the early stages of renal insufficiency, it is an adaptive response to uphold mineral balance. It is a component of the chronic kidney disease-mineral and bone disorder (CKD-MBD). The development of SHPT in CKD involves multiple factors and it is important to understand them in order to properly manage it, starting with early diagnosis and continuing with proper treatment. In children with CKD and SHPT, the difficulty in case management is due to non-adherence to proper diet which makes it difficult for the pediatric nephrologist to manage the case. In this review we want to focus on new data regarding this CKD complication.

Background. The prevention of type 2 diabetes has great clinical importance. Many pharmacologic and nonpharmacologic\r\nmethods are used to prevent type 2 DM. Metformin reduces the risk of developing diabetes in insulin resistant subjects. Oxidative stress plays pivotal roles in the pathogenesis and complications of diabetes mellitus. Paraoxonase 1 has\r\nantioxidant capacity.\r\nObjective. This study was planned to assess the effects of metformin and life style changes on paraoxonase activity and\r\noxidative stress markers in premenopausal, obese, insulin resistant women.\r\nDesign.Open-pilot clinical study.\r\nSubjects and methods. Thirty-two insulin resistant, premenopausal, obese women were enrolled into this clinical\r\nstudy. These women were treated by diet + exercise + metformin (1700 mg/d) for 6-month interval. All anthropometric characteristics, serum fasting and\r\npostprandial glucose, fasting insulin, paraoxonase, arylesterase, and malondialdehyde (MDA) levels and lipid\r\nsub-fractions were measured at the commencement and the finish of the study. Homeostasis model assessment (HOMAIR)\r\nwas used to estimate insulin resistance.\r\nResults. Significantly reduced body weight, body mass index, waist circumference measurements, HOMA-IR and serum fasting\r\ninsulin, postprandial glucose, triglyceride, MDA levels and paraoxonase/high density lipoprotein cholesterol (HDL-C) ratio were observed at the end of the study compared\r\nwith initial evaluations. Conversely, there were considerable increases in serum arylesterase and HDL-C levels following the treatment. Nevertheless, the increase in serum PON-1 level was statistically insignificant.\r\nArylesterase was inversely correlated with TC, LDL-C levels and HOMA-IR.\r\nConclusions. Metformin treatment with intensive life-style modification may be appropriate management in premenopausal,\r\nobese, insulin resistant women who have increased propensity for the development of type 2 diabetes, although long-term,\r\ncontrolled studies are needed for evaluation in greater detail.

Objective. This study assesses, in patients from counties with iodine deficiency (ID) and without ID, the concentrations of thyroid hormones in newborns (cord blood) and mothers at delivery, maternal and fetal thyroid volumes (less than 24 hours before delivery) and maternal urinary iodine at delivery. Another aim of this paper is to identify the interrelations between maternal and neonatal thyroid functions in the premature and full term delivery.\r\nMethods. In this study there were 83 mothers without thyroid pathology (goitre included) aged 26.51 ? 4.88 years, range 16-38 years) and their 83 newborns immediately after delivery. Four groups were identified: group A - 13 mothers from iodine sufficient area (IS) who delivered prematurely, group B - 13 mothers from iodine deficient area (ID), who delivered prematurely, group C - 38 mothers from IS area who delivered at term and group D - 19 mothers from ID area who delivered at term. The serum concentrations of TSH, total (T)T4, free (F)T4, TT3 and FT3 were evaluated by a microparticle enzyme immunoassay (MEIA). The thyroid volumes in mothers and their fetuses were measured by ultrasonography with a high resolution equipment (Accuvix XQ).\r\nResults. The values of TSH in newborns (cord blood serum), expressed as mean ? standard deviation (SD), were significantly higher in groups from ID areas (B+D) vs. groups from IS areas (A+C) (p<0.03). TSH levels were higher in group D vs. group C (6.62 ? 4.53 mU/L vs. 5.46 ? 2.83 mU/L [p<0.03]). The values of TT4 in newborns were significantly lower in group B vs group D (8.09 ? 1.68 ?g/dl vs. 9.45 ? 2.23 ?g/dl [p<0.05]), in premature group (A+B) vs term group (C+D) [p<0.007] and in groups from ID areas (B+D) vs. IS groups (A+C) vs [p<0.01]. Thyroid volumes (TV) in fetuses from IS areas (A+C) were lower than in ID areas (B+D) (p<0.002), but TV was similar in fetuses born at term or prematurely. Serum TSH levels in newborns (71.73 ? 26.54 ?g/l) were negatively correlated with maternal urinary iodine (r = -0.827, p<0.0001). Serum TSH in newborn was not correlated with maternal TSH in any group (A-D). The TV in fetuses (1.25 ? 0.1 ml) were highly correlated with TSH in newborns (r = 0.83, p<0.001), negatively correlated with maternal urinary iodine (r = -0.81, p<0.001) and correlated with maternal TV (17.12 ? 1.82 ml) (r = 0.44, p<0.02).\r\nConclusions. The status of the thyroid hormones and thyroid volumes in the newborn was dependent on the severity of iodine deficiency and in a less proportion on prematurity. The fetus is more sensitive to iodine deficiency than the mother.

Background. Indication, type of surgery and choice of surgical approach for adrenal masses continues to be a subject of debate between surgeons. The aim of this study was to report our data and experience with adrenal surgery. Subjects and Methods. We performed a retrospective study on 297 patients diagnosed with adrenal masses and operated in our center between 2002 and 2011. Gender, age, surgical approach, operating time, hospital stay, histology report and complications were analyzed. Results. From a total of 297 patients who underwent adrenalectomies, 82 were performed by laparoscopic approach and 215 in a classical open approach. The most common indication for surgery was pheochromocytoma (50.2% in unilateral and 50% in bilateral adrenal masses) summing 149 patients for both types of surgery. The risk of malignancy was significantly correlated with tumor size and the cut off value of 5cm had 92.5% specificity and 74.6% sensitivity. Patients in laparoscopic group were younger (mean 44.13 years), had shorter operating times (mean 122.7 min), shorter hospital stays (mean 6.8 days), and less complications (1.7 %) compared to open adrenalectomy. Conversion rate to open procedure was 2.4 %. Conclusion. Although many adrenal masses are now excised by laparoscopic techniques, the number of procedures was still low in our center because of high surgical complexity of our cases and high institutional costs. Moreover, we should consider that the best adrenal surgery approach remains open surgical excision for larger masses and malignant conditions.

Debates flow in the medical and psychological field about burnout symptoms: from considering it as a distinct illness, a separate entity or correlated with physiological changes and/or job-related reaction. Seen as a form of depression, the researches are investigating the correlations between various changes in the normal human body functioning, environmental and job lever / implications. The following pages refer to the recent studies of neuroendocrine indicators involved in burnout. It is known that the endocrine system is highly interrelated with the immune and neural systems, the neuro-immuno-endocrine axis is subject to clear biphasic changes in the acute and chronic phases of a critical illness, most likely reflecting a beneficial adaptation.