Association between vitamin D concentration and levels of sex hormones in an elderly Polish population with different genotypes of VDR polymorphisms (rs10735810, rs1544410, rs7975232, rs731236).

BACKGROUND: Vitamin D co-regulates the synthesis of sex hormones in part by interaction with its nuclear receptor. The aim of this study was to determine whether there is an association of vitamin D concentration vs the level of sex hormones in elderly Polish individuals with different genotypes of the vitamin D receptor (VDR) gene. MATERIALS AND METHODS: Rs10735810, rs1544410, rs7975232, and rs731236 polymorphisms of VDR, the serum sex hormone level, free estrogen index (FEI) and free androgen index (FAI) as well as vitamin D, were evaluated in 766 persons (362 women and 404 men) selected from 5695 Polish population, aged 65-90years from the PolSenior survey. RESULTS: We observed that women with GG (rs731236), TT (rs7975232), BB (rs1544410) and FF (rs10735810) genotypes were characterized by a significant correlation between vitamin D vs testosterone concentration and FAI value. We found a significant correlation between testosterone level and FAI vs vitamin D concentration in men with heterozygote AG in the rs731236 polymorphism and in the GG (rs7975232), the BB (rs1544410), and the Ff (rs10735810) genotypes. CONCLUSION: In elderly selected Polish population with different genotypes of VDR polymorphisms, a statistically significant relationship between vitamin D concentration vs testosterone level was observed.

Interrelation between genotypes of the vitamin D receptor gene and serum sex hormone concentrations in the Polish elderly population: the PolSenior study.

AIM: Vitamin D co-regulates the synthesis of sex hormones. Therefore, the aim of this study was to determine whether the presence of certain genotypes of the vitamin D receptor gene (VDR) is associated with the serum levels of sex hormones in the elderly Polish population. MATERIALS AND METHODS: The rs10735810, rs1544410, rs7975232, and rs731236 polymorphisms of VDR, the serum levels of testosterone and estradiol, as well as free estrogen index (FEI) and free androgen index (FAI) were evaluated in 360 women and 400 men aged 65-90years selected from 5695 respondents of the PolSenior survey. RESULTS: Only the rs1544410 VDR polymorphism was associated with the serum levels of sex hormones. The prevalence of rs1544410 genotypes was 38% BB, 46% Bb, and 16% bb in women and 41% BB, 44% Bb, and 15% bb in men. In women the frequency of the B allele was p=0.61 and b allele q=0.39, while in men it was p=0.63 and q=0.37, respectively. We found significant differences in the serum testosterone level (p<0.0004) and FAI (p<0.0015) between the rs1544410 genotypes in women but not in men. Higher mean testosterone level and higher mean FAI were observed in women with a rare bb genotype in comparison to a common BB genotype. CONCLUSION: We hypothesize that in women the increase in VDR expression associated with a rare genotype of the rs1544410 polymorphism of this gene may be associated with an increase in testosterone and FAI levels.

The reference values of sex hormones and SHBG serum levels in subjects over 65 years old - The PolSenior Study.

INTRODUCTION: Over the last decade, average life expectancy has continuously increased. There has been no data on normal sex hormone (SH) levels in a Polish elderly population. In this study, we assessed SH in the PolSenior cohort to determine normal reference ranges in relation to gender, age, and cardiovascular disease risk factors (CVDRFs). MATERIAL AND METHODS: The study was performed with 4,352 participants (2,168 men and 2,088 women), aged from 55 to over 90 years, stratified in five-year age groups. Pre-elderly subjects (55-59 years of age) served as the reference group. We assessed total testosterone (TT), estradiol (TE2) and DHEA-S (by RIA) SHBG and FSH (by IRMA) and calculated free androgen and free estrogen indices (FAI and FEI). Percentage body fat (%BF) was measured by bioelectric impedance analysis. The CVDRFs assessment included blood pressure and biochemical (blood glucose, high-density lipoproteins, triglycerides) and anthropometric (waist circumference) components of the metabolic syndrome. RESULTS: TT was low in 19.9%, normal in 78.2%, and high in 1.8% of men. TE2 was low in 94.6% of women. Age and CVDRFs significantly influenced values of SHBG, FSH, TT, FAI, FEI, and DHEA-S in men, while in women values of FSH, TT and TE2 did not change. BMI and %BF affected SH regardless of the age groups and CVDRFs. CONCLUSIONS: Our findings suggest that the reference ranges stratified by the five-year age bands seem more accurate than those given for the overall population over 60 years of age. The clinical relevance of these reference ranges increases when they are considered in relation to CVDRFs, BMI and %BF.

Thyroid dysfunction and thyroid autoimmunity in a large unselected population of elderly subjects in Poland - the 'PolSenior' multicentre crossover study.

INTRODUCTION: Data on the thyroid function of a randomly chosen elderly population was collected during a multicentre study performed in Poland (PolSenior) in 2007-2010. MATERIAL AND METHODS: The population of 4,190 participants under study was divided into six age subgroups of > 65 to > 90 years of age and a younger group aged between 55 and 59 years. Assessment of thyroid function was based on hormonal measurements. RESULTS: Concentrations of both TSH and fT(4) were significantly higher in females than in males. No differences in TSH and fT(4) concentrations between different age groups were found. Thyroid dysfunction was revealed in more than 10% of participants, hypothyroidism in 7.95%, and hyperthyroidism in 2.95%. Both types of dysfunction were more prevalent in women, and in more than 80% both dysfunctions were subclinical. In 1,542 participants, concentrations of TPOAb were measured. Increased TPOAb was revealed in 19% of the cohort and the prevalence of thyroid autoimmunity was higher in women and also more often found in participants with hypothyroidism. CONCLUSIONS: Cross sectional survey revealed thyroid dysfunctions in over 10% of non selected elderly population. No age related differences were found in TSH concentrations, TPOAb positivity and prevalence of thyroid dysfunctions.

[Does type 2 diabetes predispose to osteoporotic bone fractures?]. / Czy cukrzyca typu 2 predysponuje do osteoporotycznych zlaman kosci?

Chronic complications of diabetes are associated mainly with changes in major and small arterial vessels as well as in peripheral and autonomic fibers of the nervous system. For years it has been suggested that DM2 does not predispose to osteoporosis because bone mineral density (BMD) in DM2 patients is commonly normal or even increased. However, results of recent large cross-sectional studies have indicated that patients with DM2 have significantly increased risk of bone fractures, predominantly hip fractures (by 70%). Results of these studies suggest that the increased risk of fractures in DM2 is independent of BMD. In this group of patients is frequently associated the loss of vision caused by diabetic eye disease, peripheral neuropathy, arterial hypertension, orthostatic hypotonia (caused by autonomic neuropathy or/and by concomitant antihypertensive treatment), and ischemic disease of the brain, heart and lower extremities--conditions that predispose to falls. There are no specific methods of prophylaxis and treatment of osteoporosis associated with diabetes; therefore they should be based on widely accepted principles as in non-diabetic populations. It seems that in DM2 patients the most purposeful strategy could be the popularization of healthy attitudes aiming the elimination of unfavorable dietetic and environmental factors, such as low physical activity, smoking, and low vitamin D intake, as well as education against falls.

[Endocrine tumors of the stomach and duodenum (including gastrinoma) - management guidelines (recommended by the Polish Network of Neuroendocrine Tumors)]. / Guzy endokrynne zoladka i dwunastnicy z uwzglednieniem gastrinoma ( zasady postepowania rekomendowane przez Polska Siec Guzów Neuroendokrynnych).

The neuroendocrine tumors of the stomach and duodenum constitute only minority of neoplasms in this localisation. However due to their clinical behaviour and/or hormonal syndromes they pose diagnostic and therapeutic challenge. They display distinct phenotypes, regarding their pathogenesis, pathology and clinical course. Herein we present Polish guidelines for biochemical, pathological and localisation diagnosis, and discuss therapeutic approaches, considering endoscopic and surgical treatment, pharmacological and radionuclide therapy.

Consensus statement of the Polish Society for Endocrinology: presurgical somatostatin analogs therapy in acromegaly.

Consensus statement of the Polish Society for Endocrinology, regarding presurgical somatostatin analogs in acromegaly has been presented. It is suggested to administer depot somatostatin analog (Octreotide LAR at the dose 20 mg and then 30 mg or equivalent doses of Lanreotide Autogel 90/120 mg every 4 weeks) in order to normalize or suppress to a maximal extent GH and IGF-1 concentrations. The period of therapy in case of microadenoma would be at least 3 months (targets: biochemical improvement, reduced risk of disease's complications, perioperative risk reduction, inhibition of tumor growth). The period of therapy in case of macroadenoma would be at least 6 months, until maximal possible reduction of GH and IGF-1 concentrations (targets: tumor shrinkage, biochemical improvement, reduced risk of disease's complications, perioperative risk reduction). Using an uniform approach in a group, as numerous as possible, of treated patients would allow objective evaluation of long-term efficacy of the treatment.

[Consensus of the Polish Society of Endocrinology. Presurgical somatostatin analogs therapy in acromegaly]. / Konsensus Polskiego Towarzystwa Endokrynologicznego. Przygotowanie analogami somatostatyny do leczenia operacyjnego akromegalii.

Consensus statement of the Polish Society of Endocrinology, regarding presurgical somatostatin analogs in acromegaly has been presented. It is suggested to administer depot somatostatin analog (Octreotide LAR at the dose 20 mg and then 30 mg or equivalent doses of Lanreotide Autogel 90/120 mg every 4 weeks) in order to normalize or suppress to a maximal extent GH and IGF-1 concentrations. The period of therapy in case of microadenoma would be at least 3 months (targets: biochemical improvement, reduced risk of disease's complications, perioperative risk reduction, inhibition of tumor growth). The period of therapy in case of macroadenoma would be at least 6 months, until maximal possible reduction of GH and IGF-1 concentrations (targets: tumor shrinkage, biochemical improvement, reduced risk of disease's complications, perioperative risk reduction). Using an uniform approach in a group, as numerous as possible, of treated patients would allow objective evaluation of long-term efficacy of the treatment.

[Preproghrelin gene, ghrelin receptor and metabolic syndrome]. / Gen preproghreliny i receptor ghreliny a zespól metaboliczny.

Obesity is a multi-gene syndrome, expression of which is modulated not only by environmental factors but above all by a number of modified genes interacting with each other. Among candidate genes related to obesity phenotype is ghrelin gene. Ghrelin plays a significant role in feeding regulation and is the strongest stimulator of growth hormone secretion. Ghrelin acts by GHS1a receptor (growth hormone secretagogue receptor). Mutations in preproghrelin and ghrelin gene or ghrelin receptor gene could be responsible for low ghrelin levels observed in obese individuals. Among identificated mutations, two Arg51 Gln and Leu72Met are most often described and change amino-acid sequence of ghrelin (Arg51Gln) and preproghrelin (Leu72Met). Although no direct relationship between Arg51Gln mutation and obesity phenotype was found, it had been shown that carriers of Arg51Gln mutation had significantly decreased plasma ghrelin levels. Furthermore 51Gln allele carriers had higher prevalence of type 2 diabetes mellitus and hypertension than non-carriers. Met 72 carrier status is associated with higher serum IGF-1 levels and seems to be a protective factor against fat accumulation and cardiovascular complications of obesity. No evidence of relationship between ghrelin receptor gene polymorphisms and body mass regulation was found, however, until now there is no study on relationships between these polymorphisms and metabolic complications of obesity. The presence of genetic variants in ghrelin or GHS receptor gene could be responsible for impaired GH secretion in visceral type obesity and development of metabolic syndrome in some of obese subjects. On the other hand, some mutations in preproghrelin gene could be protective against metabolic syndrome.

[Magnetic resonance imaging and soluble forms of adhesion molecules: sICAM and sVCAM in assessing the activity of thyroid orbitopathy]. / Magnetyczny rezonans jadrowy oraz stezenia rozpuszczalnych form molekul adhezyjnych: sICAM-1 i sVCAM-1 w ocenie aktywnosci orbitopatii tarczycowej.

The aim of this study is to compare two different diagnostic methods (magnetic resonance imaging (MRI) and soluble forms of adhesion molecules: ICAM-1 and VCAM-1 measurement) in assessment of the activity of thyroid orbitopathy (TO) in patients with Graves' disease. 21 patients with infiltrative TO were treated with modified method by Bartalena et al. MRI scans and the measurement of soluble forms of ICAM-1 and VCAM-1 were performed before treatment, after methylprednisolone pulses along with radiotherapy of the retroorbital spaces and after the end of prednisone treatment. MRI scans did not reveal active stage of the disease in 4/21 patients with infiltrative TO, despite elevated levels of sICAM-1 and sVCAM-1. Patients both with active stage of the disease and with the results of MRJ scans revealing fibrotic changes in muscles responded well to therapy parallel with a significant decrease in levels of sICAM-1 and sVCAM-1. Levels of sVCAM-1 increased slightly under prednisone treatment despite improvement of clinical picture of TO, a significant decrease in sICAM-1 levels and in the number of muscles with active inflammatory process on MRI scans. In conclusion, serum levels of ICAM-1 seem to be more sensitive marker than MRI in assessment of the activity of TO. Concentrations of sVCAM-1 do not correspond with the clinical picture of the disease and the results of MRJ during treatment of TO.

[Effectiveness of treatment for thyroid orbitopathy in patients hospitalized at the Endocrinology Department of Pomeranian Medical University]. / Ocena skutecznosci leczenia orbitopatii tarczycowej w materiale Kliniki Endokrynologii PAM w Szczecinie.

UNLABELLED: The aim of the present study is the assessment of efficacy of systemic corticosteroid treatment combined with orbital radiotherapy in patients with thyroid ophthalmopathy. MATERIAL: 101 patients hospitalized in the Endocrinology Department of the Pomeranian Medical University in the years 1999-2002. METHODS: During first stage of treatment 3 to 6-7 intravenous pulses of methylprednisolone (SoluMedrol Pharmacia & Upjohn) in a dose of 1.0 g/day in consecutive 3 days were administered in combination with radiotherapy of the retroorbital spaces. Ten daily doses of 200 cGy using X-ray to each retroorbital space were given between the 2-nd to 4-th SoluMedrol pulse. Prednisone (Encorton Polfa) at an initial dose of 60 mg/day was used during the second stage of therapy. RESULTS: Donaldson's ophthalmopathy index scored for each eye separately decreased significantly after both stages of treatment (right eye: 6.35 (before treatment); 2.25 (after first stage), 1.2 (after second stage), p<0.05; left eye: 6.1 (before treatment); 2.1 (after first stage); 1.15 (after second stage), p<0.05). The clinical picture of Graves ophthalmopahty after the end of therapy in most of patients was significantly improved. Persistent diplopia was found in 16/101 patients. Two of them were referred for surgical correction of abnormal eyeball fixation, the rest were using prismatic glasses. Until now, no recurrence of thyroid eye disease in treated patients was observed. CONCLUSIONS: Combined therapy is an effective method of treatment of Graves' ophtahlmopathy in terms of both rapid regression of inflammatory changes in orbital soft tissues and in prevention of recurrence of the disease.

[Complications during systemic corticosteroid therapy combined with orbital radiotherapy in patients with graves orbitopathy]. / Powiklania skojarzonego leczenia orbitopatii tarczycowej glikokortykosteroidami i napromienianiem tkanek pozagalkowych.

OBJECTIVE: An assessment of complications during systemic corticosteroid therapy combined with orbital radiotherapy in patients with thyroid eye disease. MATERIAL: 101 patients including 86 women and 15 men hospitalized in the Endocrinology Department of Pomeranian Medical Academy in 1999-2002. METHODS: During the first stage of therapy, methylprednisolone in a daily dose of 1.0 g was administered intravenously for the following 3 days. The number of methylprednisolone pulses ranged from 3 up to 6-7. Orbital radiotherapy was usually performed between 2 and 4 pulse. Ten daily doses of 200 cGy were given in 2 weeks. After the series of methylprednisone and orbital radiotherapy had been finished, patients were treated with prednisone (Encorton, Polfa) given orally with an initial dose of 60 mg/day. RESULTS: During the first stage of therapy carbohydrate metabolism disturbances were observed in 27 patients. Cardio-vascular complications were noted in 8 patients. Four patients complained of digestive tract dysfunction. Acute psychosis was diagnosed in 3 patients. Twelve patients developed infectious diseases. During prednisone administration, 1 case of bacterial pneumonia, 1 purulent meningitis and 1 schizophrenia onset were observed. In prolonged ophthalmologic follow-up 3/101 patients with cataract needed surgical treatment.

Growth hormone, IGF-1, insulin, SHBG, and estradiol levels in girls before menarche.

The timing of pubertal changes depends on the concerted function of the hypothalamic - pituitary - ovarian and other endocrine systems. The somatotropin system and insulin play important roles during the growth and maturation of girls. Our clinical observations have enabled us to determine and implement criteria that split the pre-menarcheal period into three phases with distinct features associated with rising levels of estrogens (pre-estrogenization, onset of estrogenization and full estrogenization). The aim of this work was to determine levels of growth hormone, insulin - like growth factor 1 (IGF-1), sex hormone binding globulins (SHBG), insulin, and estradiol in relation to somatic features in girls during subsequent phases of estrogenization. This prospective study was done in 45 healthy girls. Every three months, we recorded weight, height, BMI, maturation of tertiary sex features, estrogen-related changes in hymen, sonographic dimensions of ovaries and uterus and serum levels of growth hormone, IGF-1, SHBG, insulin, and estradiol. Onset of estrogenization was accompanied by reduction of body mass and slowing down of growth associated with declining levels of growth hormone. These changes were followed by weight gain, pubertal acceleration of growth, rising levels of growth hormone, IGF-1, insulin, and estradiol, and falling levels of SHBG.