ACTA ENDOCRINOLOGICA (BUC)

Introduction. Estrogens are known to have a neuroprotective role and to influence the permeability of the blood brain barrier (BBB). An ongoing debate exists on the changing effects of estrogens on target tissues with advancing age and at menopause and on the potential disruptive role of increasing gonadotropin levels.\r\nThe aim of the present study was to assess the permeability of the BBB for estradiol, FSH and LH in three physiological states: early follicular phase, preovulatory phase and at menopause.\r\nMethod. Hormonal levels were assessed simultaneously in the serum and cerebrospinal fluid (CSF) of 15 women at menopause (mean age 60?8 years), 16 of reproductive age in early follicular phase and 11 in preovulatory phase (mean age 31?7 years), all undergoing surgery for benign gynecologic disorders. FSH, LH and estradiol levels were assessed using chemo luminescence and are expressed as median and 10-90 percentile interval. Statistical analysis assessed the serum-CSF correlation and the CSF/serum ratio for each hormone between groups.\r\nResults. Estradiol serum levels were 26.2 pg/ml (6.4-43.5) at menopause (n=15), 58.5 pg/ml (25.7-75.9) in early follicular phase (EFP, n=16) and 221.2 pg/ml (113.7-405.5) in preovulatory phase (PREOV, n=11). CSF estradiol is 18.5 pg/ml (0.4-30.5) at menopause, 5.4 pg/ml (2.2-10.2) in EFP (p<0.001) and 17.3 pg/ml (10.3-34.6) in PREOV patients. Estradiol serum and CSF levels correlate positively in the fertile cycle (r=0.72, p<0.0001) and negatively at menopause (r=-0.88, p<0.05). The CSF/serum ratio for estradiol is 0.8 (0.01-4.4) at menopause, 0.1 (0.04-0.13) in EFP and 0.1 (0.03-0.13) in PREOV patients. FSH serum levels were 75.8 mUI/ml (35.9-129.8) at menopause, 7.7 mUI/ml (3.5-11.4) in EFP and 7.3 mUI/ml (3.1-10.7) in PREOV patients. CSF FSH is 2.7 mUI/ml (0.4- 5.9) at menopause, significantly higher than 0.7 mUI/ml (0.3-1) in EFP (p<0.001) and 0.5 mUI/ml (0.2-1) in PREOV patients (p<0.05). FSH serum and CSF levels correlate positively in the fertile cycle (r=0.8, p<0.0001) and do not correlate at menopause (p=NS). The CSF/serum ratio for FSH is 0.03 (0.01-0.1) at menopause, significantly lower than 0.09 (0.06-0.16) in EFP (p<0.001) and is 0.06 (0.03-0.13) in PREOV phase. LH serum levels were 57.4 mUI/ml (27.5-84.8) at menopause, 4.7 mUI/ml (1.7-7.1) in EFP and 5.5 mUI/ml (4.9-8.02) in PREOV phase. CSF LH is 1.6 mUI/ml (0.7-2.6) at menopause, significantly higher than 0.4 mUI/ml (0.1-1) in EFP (p<0.001) and 0.5 mUI/ml (0.2-0.9) in preovulatory phase (p<0.05). The CSF/serum ratio for LH is 0.03 (0.01-0.07) at menopause, it is significantly lower than 0.09 (0.03-0.27) in EFP (p<0.001) and is 0.07 (0.03-0.14) in preovulatory phase.\r\nConclusions. This study shows the negative correlation of serum and CSF estradiol levels at menopause reflecting the need of constant estrogen levels within the CSF despite low chronic serum levels. Simultaneously, the CSF/serum ratio for gonadotrophins is\r\nreduced significantly at menopause and the positive correlation of serum and CSF levels is lost, reflecting a protective mechanism against rising levels of FSH and LH.

In response to increasing interest of the European Commission on large-scale\r\ngenotyping for complex diseases, including variability in ethnic minorities in\r\nEurope (HEALTH-2009-4.3.3-1), at the end of 2008 we composed the\r\nHAPLOGENDIS consortium with partners from Russia and European countries. A\r\nfirst program (SICA) was proposed in cooperation with Russian Federal Agency for\r\nScience and Innovation, focusing on comparative population genetics on diseases\r\naccompanied by insulin resistance. Beside the specificity in analyzing the human\r\ngenome with SNP (single nucleotide polymorphism) and defining haplotype\r\nstructure of genes, the program rises new hypotheses which directly link\r\ncolonization of Europe at the Neolithic period from Eastern Ukraine or Anatolia\r\nwith the development of agriculture and major dietary and life style changes that\r\nmay have an impact on the genome. Although there will be many occasions to\r\nreview both genetic and clinical detailed aspects, this short note will expose some\r\nunifying ideas that joint these partners.

IGF-I (Insulin like growth factor-I) plays a definitive role in the central nervous system (CNS) by modulating neuronal regeneration and survival. The local production of IGF-I in CNS has been demonstrated, but the contribution of circulating IGF-I transported through blood-brain barrier (BBB) has been just suggested in animals. There is currently no data available concerning IGF-I transport in CNS in humans. In order to investigate the passage of IGF-I over BBB in humans we have simultaneously measured the IGF-I and GH levels in serum and CSF in 25 patients with active acromegaly. IGF-I and GH levels in CSF were lower than in serum (2.2 ? 0.24 ng/mL vs 686.6 ? 46.83 ng/mL for IGF-I and 2.13 ? 0.627 mU/l vs 58.8 ? 15.86 mU/L for GH). However, both IGF-I and GH serum levels correlated with their CSF levels (r= 0.4, p<0.05 for IGF-I and r= 0.651, p= 0.006 for GH), suggesting that BBB is permeable for both hormones. In conclusion, we demonstrate the correlation of the IGF-I levels in serum and CSF, providing indirect evidence for IGF-I passage through BBB.

Introduction: The impaired transport of leptin into the brain through a decreased permeability of the blood-brain barrier (BBB) for leptin in obesity represents one of the important mechanisms involved in leptin resistance which is characteristic in human obesity. Some pituitary tumors can increase the blood-cerebrospinal fluid barrier (BCB) permeability for peptides. BCB is a part of BBB.\r\nObjectives: The aim of our study was to search if the by-pass of BCB for pituitary hormones produced by adenomas does influence the transport of leptin into the central nervous system in obese patients.\r\nMaterials and methods: We investigated 20 males with pituitary adenomas: group A (11 patients) had cerebrospinal fluid (CSF) to serum ratio more than one for prolactin (PRL) and in some patients for growth hormone (GH) and follicle stimulating hormone (FSH), suggesting an increased permeability of BCB and a control group C (9 patients), which had CSF/serum ratio less than one for GH, PRL or FSH, suggesting an intact BCB. Both A and C groups contain subgroups of patients with obesity (body mass index, BMI>30 kg/m2) and normal body weight (BMI<25 kg/m2). In these patients we measured the CSF to serum leptin ratio in order to clinically evaluate the leptin transport into the brain. Rapid fluoroimmunoassay method with europium was used. Leptin was assayed by ELISA method.\r\nResults: The patients of group A with pituitary adenomas show a higher level of pituitary peptides, PRL and in some cases GH, FSH in CSF as compared to serum (ratio CSF/serum over 1), both in obese and non-obese. By contrast, in the same patients, there is\r\na low level of CSF leptin as compared to serum leptin (ratio CSF/serum less than 1). In the subgroup of obese patients from group A we found even less ratio of CSF to serum leptin, than in non-obese. There is a well known higher leptin concentration in the plasma of obese patients with pituitary adenomas as compared to non-obese ones (26.4?3.8ng/ml vs 12.4?3.4ng/ml, p<0.05). In the control group C, both pituitary peptides (PRL, or GH, FSH) and leptin showed a ratio CSF/serum less than 1, in all patients.\r\nConclusions: These data show a decrease in hemato-encephalic barrier permeability for leptin in obese patients through a specific mechanism, not influenced by other peptides passing through injuries of BBB produced by pituitary adenomas. It is tempting to suggest that there is a specific by-pass of BCB for pituitary peptides, in some pituitary adenomas.

Background. In the Carpathian area of Romania the Iodine Deficiency Disorders (IDD) including endemic goiter are a public health problem. Recently, the legislation imposing salt iodization was strengthened (from 10 to 20 ± 5 mg iodine/kg salt) and enlarged (universal salt iodization, USI, has been applied to bread industry since 2002). Objective. The effect of bread iodization by law upon the characteristics of goiter endemy was assessed in Arges county, Romania. Design. The characteristics of goiter endemy (as defined by WHO/ICCIDD/UNICEF) were determined in children in the years 1999 (control group C) and 2004 (study group S), two years after universal bread iodization. In the control group C there were 1,241 schoolchildren 6-14 years old, living in 5 villages and in Pitesti town. In the study group S there were 408 schoolchildren 6-12 years old, living in 7 villages and in Pitesti town. After universal bread iodization, a neonatal screening for hypothyroidism was also performed on 11,216 newborns in Arges county, between January 2003 and December 2004. The content of KIO3 in the salt was assessed both in samples collected from village shops in the years 1999 (10 samples) and 2004 (17 samples). The iodine content of drinking water in Arges county villages was assessed in 1999. Methods. Three parameters of IDD endemy were evaluated, i.e. the thyroid volume in schoolchildren by palpation or/and ultrasonography, urinary iodine by the Sandell-Kolthoff method, and neonatal blood TSH levels in dry spot by immunoassay. A questionnaire was filled in by 912 schoolchildren in 1999 and by 408 schoolchildren in 2004.

Aims: To assess if amiodarone maintains its antiarrhythmic efficacy in the presence of amiodarone-induced hyperthyroidism (AIT) and to identify the tri-iodothyronine (T3) threshold for atrial fibrillation in patients with AIT versus common hyperthyroidism.\r\nPatients and methods. Study group A consists in 49 patients (25 M/24 F) with AIT (220.83 ? 71.33 mg/day along 2.36 ? 2.25 years) and severe cardiopathies (9 valvulopathies, 40 ischaemic, dilatative and hypertensive cardiomyopathies), aged 57.87?12.63 years. Control group B consists in 51 hypothyroid (B1) or euthyroid patients (B2) treated with amiodarone (222.55 ? 68.78 mg/day along 2.67 ? 1.84 years) and also in 100 patients (23M/77F) with overt hyperthyroidism (B3), without major heart diseases, aged 52.74?12.85 years; TSH, total T3, total T4, free T4 were measured by radioimmunoassay. All were clinically, ECG and echocardiography evaluated.\r\nResults. Prevalence of arrhythmias recurrence was 59.2% (29/49 patients) in group A, significantly higher than in each control subgroups B: B1- 28% (7/25), B2- 15.45% (4/26) and B3- 20% (20/100), P< 0.001. Patients from study group A with AIT and T3 levels >250 ng/dL developed significantly more frequent atrial fibrillation (p= 0.04). However, in control group B3 with common hyperthyroidism, no T3 threshold for arrhythmias could be identified. Overall, there were no significant differences in total T3 levels with respect to the presence of atrial fibrillation in both study group A and subgroup B3 with common hyperthyroidism (p=ns).\r\nConclusion. Amiodarone antiarrhythmic efficacy is surpassed in AIT by the increased arrhythmic susceptibility of damaged myocardial tissue to minimally increased thyroid hormones levels. A tri-iodothyronine level > 250 ng/dL superimposed on preexistent proarrhythmic substrate in amiodarone-induced hyperthyroidism should be avoided.

A 51 years old woman, diagnosed 23 years ago with acromegaly and non-insulin dependent diabetes mellitus, who denied radical treatment and took bromocriptine 2.5 - 7.5 mg/day sporadically and oral antidiabetic drugs, presented with chronic headaches, acromegalic features, bilateral temporal hemianopia, hypertension, hyperglycemia. Her pituitary function was normal (random serum growth hormone 2.5 - 2.8 ng/mL). The skull X-ray showed an enlarged sella turcica, with blurred multiple contour and an &#8222;egg-shell&#8221; calcification boarding the interior sellar floor. Cranial CT scan revealed a 1.7/0.7 cm intrasellar macrocalcification with a low-density core, lying on most of the sellar floor. In addition there were partial empty sella, asymmetrical optic chiasm, multiple cerebral,\r\nvascular and pineal microcalcifications, but no visible pituitary or tumor mass. Apoplexy within a previous large pituitary growth hormone-secreting tumor, followed by resorption and peripheral calcification, may have produced this rare case of pituitary stone associated with remission of acromegaly and sequelar visual field defect.

An increased risk of non-Hodgkin?s lymphoma was found for a personal history of autoimmune conditions: rheumatoid arthritis, systemic lupus erythematosus, celiac disease, autoimmune hemolytic anemia, Crohn?s disease, psoriasis, sarcoidosis and thyroiditis. The associations may not be general but rather for specific non-Hodgkin?s lymphoma subtypes. These non-Hodgkin?s lymphoma subtypes develop during postantigen exposure stages of lymphocyte differentiation, consistent with a role of antigenic drive in autoimmunity-related lymphomagenesis. We present the case of a 30 years old mane, with simultaneous diagnosis of Graves? disease and a huge anterior mediastinal mass which was actually the mediastinal involvement of a diffuse large B-cell lymphoma stage III. The patient had also hypercalcemia, remitted after two courses of chemotherapy. The possible relationship between the two diseases and the role of parathyroid hormone related peptide PTHrP in paraneoplastic syndrome is discussed.