Successful Treatment of Infertility in a Patient with Probable 17 Hydroxylase Deficiency and Particularities of Association with Adrenal Autoimmunity-A Case Report and Review of the Literature.

Congenital adrenal hyperplasia (CAH) due to 17-hydroxylase deficiency (17OHD) is a rare disease accounting for less than 1% of cases of CAH. In female patients, fertility is severely affected mainly due to constantly increased progesterone affecting endometrium receptivity and implantation. The optimal treatment for infertility in these patients is not clearly established, with only a few recent case reports of successful pregnancies available in the literature. Hereby, we present the case of an infertile female patient with 17OHD who obtained pregnancy through an in vitro fertilization (IVF) freeze-all strategy and particularities of association with adrenal autoimmunity. A 32-year-old infertile female patient was referred for infertility evaluation and treatment. She had normal sex development and menstrual history with oligomenorrhea alternating with normal menstrual cycles. During the evaluation, a reduced ovarian reserve and obstruction of the left fallopian tube were identified, and IVF treatment was recommended. During a controlled ovarian stimulation for IVF, increased values of serum progesterone were observed; thus, all the embryos were frozen and additional tests were performed. Increased values of 17-hydroxyprogesteron, 11-deoxycorticosteron, and adrenocorticotropic hormones in association with low basal and stimulated serum cortisol, testosterone, androstenedione, and dehydroepiandrosterone sulfate were found, supporting the presence of 17OHD. She started treatment with oral hydrocortisone given at 20 mg/day but, because follicular phase serum progesterone remained high, hydrocortisone was replaced by an oral dexamethasone treatment of 0.5 mg/day, followed by the normalization of serum progesterone. A thawed blastocyst was transferred after preparation with oral estradiol at 6 mg/day and intravaginal progesterone at 600 mg/day under continuous suppression of endogenous progesterone production with a gonadotropin-releasing hormone agonist and oral dexamethasone. The patient became pregnant and delivered two healthy girls at term. One year after delivery, the presence of 21-hydroxylase antibodies was detected, which might explain the particularities of adrenal steroids in our patient. Our case report demonstrates that a patient with 17OHD can become pregnant through IVF and the transfer of thawed embryos in a subsequent cycle under continuous suppression of adrenal and ovarian progesterone production.

Prolactin Relationship with Fertility and In Vitro Fertilization Outcomes-A Review of the Literature.

Hyperprolactinemia is a known cause of amenorrhea and infertility. However, there is an increasing body of evidence suggesting that prolactin is involved in multiple physiological aspects of normal reproduction. Thus, the present paper aims to review the current literature regarding the relationship between serum prolactin level and in vitro fertilization (IVF)/intracytoplasmic sperm injection outcome and the role of dopamine agonists treatment in IVF success. Moreover, the mechanisms by which prolactin may exert its role in fertility and infertility were summarized. Although not all studies agree, the available evidence suggests that higher prolactin levels in follicular fluid are associated with increased oocytes competence, but also with positive effects on corpus luteum formation and survival, endometrial receptivity, blastocyst implantation potential and survival of low-motile sperm. Transient hyperprolactinemia found in IVF cycles was reported in most of the studies not to be related to IVF outcome, although a few reports suggested that it may be associated with higher implantation and pregnancy rates, and better-cumulated pregnancy outcomes. Administration of dopamine agonists for hyperprolactinemia preceding IVF treatment does not seem to negatively impact the IVF results, while treatment of transient hyperprolactinemia during IVF might be beneficial in terms of fertilization rates and conception rates. Due to limited available evidence, future studies are necessary to clarify the optimal level of circulating prolactin in patients performing IVF and the role of dopamine agonist treatment.

An Approach to Traumatic Brain Injury-Related Hypopituitarism: Overcoming the Pediatric Challenges.

Traumatic brain injury (TBI)-related hypopituitarism is a rare polymorphic complication of brain injury, with very little data, particularly concerning children and teenagers. This is a comprehensive review of the literature regarding this pathology, starting from a new pediatric case. The research was conducted on PubMed and included publications from the last 22 years. We identified nine original studies on the pediatric population (two case reports and seven studies; only four of these seven were prospective studies). TBI-related hypopituitarism is associated with isolated hormonal deficits ranging from 22.5% to 86% and multiple hormonal deficiencies from 5.9% to 50% in the studied pediatric population. Growth hormone (GH) deficiency is most often found, including the form with late occurrence after TBI; it was described as persistent in half of the studies. Thyroid-stimulating hormone (TSH) deficiency is identified as a distant complication following TBI; in all three studies, we identified this complication was found to be permanent. Adrenocorticotropic hormone (ACTH) deficiency did not relate to a certain type of brain trauma, and it was transient in reported cases. Hyperprolactinemia was the most frequent hormonal finding, also occurring late after injury. Central diabetes insipidus was encountered early post-TBI, typically with a transient pattern and did not relate to a particular type of injury. TBI-related hypopituitarism, although rare in children, should be taken into consideration even after a long time since the trauma. A multidisciplinary approach is needed if the patient is to safely overcome any acute condition.

The response to growth hormone treatment in a child with short stature, growth hormone deficiency and autosomal dominant cutis laxa type 3 - case report.

OBJECTIVES: The aetiology of short stature in cutis laxa (CL) syndromes is largely unknown. Herein, we report a case with autosomal dominant CL type 3 (ADCL3) with severe short stature and growth hormone (GH) deficiency. CASE PRESENTATION: A male patient with a genetically confirmed diagnosis of ADCL3 was referred for endocrinological evaluation of short stature at the age of 3.4 years. The examination revealed severe proportional short stature (-4.14 standard deviations (SD) score for height) in a patient born small for gestational age (birth weight 2080 g, -2.46 SD, birth length 41 cm, -4.22 SD). Assessment of GH reserve with two clonidine stimulation tests (0.15 mg/m2) with peak GH values of 8.07 ng/mL and 2.98 ng/mL, respectively, were indicative of GH deficiency. Also, the MRI examination revealed a small size pituitary. Thus, the treatment with somatropin was started. The height deficit significantly improved (from -4.14 SD to -1.48 SD) without side effects during the follow-up of 4.5 years. CONCLUSIONS: With this report, the GH deficiency as a possible cause of short stature in ADCL3 and the response to somatropin administration were reported for the first time in the literature.

The ratio of exogenous Luteinizing hormone to Follicle stimulating hormone administered for controlled ovarian stimulation is associated with oocytes' number and competence.

We performed a retrospective study aiming to study the relationship between the ratio of the exogenous luteinizing hormone to follicle stimulating hormone (LH/FSH) administrated for controlled ovarian stimulation (COS) and the number and competence of the oocytes retrieved for in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). Eight hundred sixty-eight consecutive infertile patients (mean age 34.54 ± 4.01 years, mean anti-Müllerian hormone (AMH) 2.94 ± 2.07 ng/ml) treated with long agonist protocol and a mixed gonadotropin protocol (human menopausal gonadotropin in association with recombinant FSH (recFSH)) who performed IVF/ICSI between January 2013 and February 2016, were included. Patients with severe male factor were excluded. LH/FSH was calculated based on total doses of the two gonadotropins. We found, after adjustment for confounders, a positive relationship between LH/FSH and the retrieved oocytes' (ß = 0.229, P<0.0001) and zygotes' number (ß = 0.144, P<0.0001) in the entire study group and in subgroups according to age (<35 and ≥35 years) and ovarian reserve (AMH < 1.1 and ≥ 1.1 ng/ml). The fertilization rate was positively associated with LH/FSH in patients with LH/FSH in the lowest three quartiles (below 0.77) (ß = 0.096, P=0.034). However, patients in the fourth quartile of LH/FSH had a lower fertilization rate as compared with patients in quartiles 1-3 which, after adjustment for covariates, was only marginally negatively related with LH/FSH (ß = -0.108, P=0.05). In conclusion, our results suggest that the adequate LH/FSH administrated during COS can improve the oocytes' and zygotes' number in IVF/ICSI cycles, but also the fertilization rate when a certain proportion of LH/FSH is not exceeded.

An ICET-A survey on occult and emerging endocrine complications in patients with ß-thalassemia major: Conclusions and recommendations.

In adult thalassemia major (TM) patients, a number of occult and emerging endocrine complications, such as: central hypothyroidism (CH), thyroid cancer, latent hypocortisolism, and growth hormone deficiency (GHD) have emerged and been reported. As the early detection of these complications is essential for appropriate treatment and follow-up, the International Network of Clinicians for Endocrinopathies in Thalassemia and Adolescent Medicine (ICET-A) promoted a survey on these complications in adult TM patients, among physicians (pediatricians, hematologists and endocrinologists) caring for TM patients in different countries. The data reported by 15 countries are presented.The commonest endocrine complications registered in 3.114 TM adults are CH and GHD (4.6 % and 3.0 %, respectively), followed by latent hypocortisolism (1.2%). In 13 patients (0.41%) a cytological papillary or follicular thyroid carcinoma was diagnosed in 11 and 2 patients, respectively, and a lobectomy or thyroidectomy was carried out. Of 202 TM patients below the age of 18 years, the  reported endocrine complications were: GHD in 4.5%, latent hypocortisolism in 4.4% and central hypothyrodisim in 0.5%. Transition phase was an area of interest for many clinicians, especially as patients with complex chronic health conditions are responding to new treatments extending their lifespan beyond imagination.. In conclusion, our survey provides a better understanding of  physicians' current clinical practices and beliefs in the detection, prevention and treatment of some endocrine complications prevailing in adult TM patients. Regular surveillance, early diagnosis, treatment and follow-up in a multi-disciplinary specialized setting are recommended.

The relationship between anti-Müllerian hormone serum level and body mass index in a large cohort of infertile patients.

PURPOSE: To evaluate the relationship between serum Anti-Müllerian hormone (AMH) level and body mass index (BMI) in infertile patients. METHODS: Medical records of patients with infertility evaluated between January 2013 and February 2018 in the Reproductive Medicine Department of a private hospital were reviewed. Patients with the following criteria were excluded from the study: polycystic ovary syndrome, primary ovarian insufficiency, AMH values > 10 ng/mL, current oral contraceptive users and previous ovarian surgery or endometriosis, and anovulation of other causes, except decreased ovarian reserve. RESULTS: A total of 2204 infertile patients were included (mean age 34.58 ± 4.3 years, mean BMI 22.35 ± 3.6 kg/m2, and mean serum AMH 2.44 ± 2.17 ng/ml). In the entire group of patients, serum AMH level was positively correlated with BMI after adjustment for age (beta = 0.059, p < 0.005). When the association between serum AMH level and BMI was analysed in subgroups of patients, after adjustment for age, we found a positive correlation between the two parameters in patients ≤ 35 years old (< 0.05), of normal weight (p < 0.05) and with normal ovarian reserve (p < 0.05). After adjustment for age, BMI ≥ 25 kg/m2 was significantly associated with higher AMH values in comparison to normal weight patients. CONCLUSIONS: In infertile patients, AMH is positively correlated with BMI, especially in patients younger than 35 years, of normal weight and with normal ovarian reserve. Moreover, the presence of mild excess adiposity seems to be associated with higher AMH values. Our data contradict the previous studies showing a negative impact of excess adiposity on AMH serum levels.

Is growth hormone administration essential for in vitro fertilization treatment of female patients with growth hormone deficiency?

Available evidence suggests that the fertility of growth hormone deficient female patients could be decreased, although the responsible mechanisms are unknown. Taking into account the multiple effects of growth hormone on reproduction suggested by experimental and clinical studies in women without growth hormone deficiency, the growth hormone deficit by itself could contribute to infertility in these patients. However, the necessity of growth hormone administration and the profile of the infertile patients with growth hormone deficiency who would benefit from treatment are largely unknown. Growth hormone effects on oocyte quality is one of the possible mechanisms through which growth hormone could be involved in fertility of these patients. However, this hypothesis was not tested in patients with adequately diagnosed growth hormone deficiency. We present the case of a 29-year-old female patient with growth hormone deficiency and tubal infertility who was referred for in vitro fertilization treatment. The couple underwent two conventional in vitro fertilization procedures: the first one, without growth hormone treatment and, because no pregnancy was achieved, the second one after growth hormone (somatropinum) administration for 3 months. Although the number of the retrieved oocytes was the same, the quality of the oocytes was improved and their ability to evolve into good quality embryos after fertilization was increased after growth hormone administration. Consequently, the pregnancy was obtained after the second in vitro fertilization treatment and patient gave birth to a healthy boy. In conclusion, our case report suggests that adequate levels of growth hormone are essential for an adequate competence of the oocytes in infertile patients with growth hormone deficiency. Therefore, growth hormone administration should be taken into consideration for patients with this deficiency in order to optimize the results of infertility treatment. Abbreviations: GH: growth hormone; GHD: growth hormone deficiency; HCG: human chorionic gonadotropin; IVF: in vitro fertilization; IGF: insulin like growth factor.

Cardiovascular risk assessment in osteoporotic patients using osteoprotegerin as a reliable predictive biochemical marker.

Osteoprotegerin (OPG), a member of the tumour necrosis factor receptor (TNFR) superfamily of proteins known to be involved in a large number of biological systems, plays a pivotal role in bone remodelling. In addition to the roles of OPG in bone metabolism, it has been reported to be associated with a high cardiovascular risk in patients with metabolic syndrome. In most cases, the exact functions of OPG remain to be established; however, the widespread expression of OPG suggests that this molecule may have multiple biological activities, mainly in the cardiometabolic environment. The aim of this study was to evaluate the value of OPG as a predictive marker for cardiovascular and metabolic risk in osteoporotic patients. The study group comprised patients with osteoporosis, in order to evaluate the association between OPG serum levels and cardiovascular pathology. Our results revealed significant correlations between classical biochemical bone and metabolic parameters, such as osteocalcin and parathyroid hormone with lipid and glucose biomarkers, sustaining the crosstalk between calcium and bone parameters and cardiovascular risk. The OPG serum level proved to have a significant and independent predictive value for metabolic syndrome (MetS) as a cardiovascular risk standard in osteoporotic patients. The OPG serum levels were increased in patients with MetS as a protective response against the atherosclerotic lesions. The serum levels of 25­hydroxy vitamin D had significant and independent predictive value for cardiovascular and metabolic risk in our subjects, sustaining the active role of vitamin D beyond the area of bone metabolism.

Review and Recommendations on Management of Adult Female Thalassemia Patients with Hypogonadism based on Literature Review and Experience of ICET-A Network Specialists.

BACKGROUND: Multi-transfused thalassemia major (TM) patients frequently develop severe endocrine complications, mainly due to iron overload, anemia, and chronic liver disease, which require prompt diagnosis, treatment and follow-up by specialists. The most common endocrine complication documented is hypogonadotropic hypogonadism which increases with age and associated comorbidities. It is thus important for physicians to have a clear understanding of the pathophysiology and management of this disorder. Also to be aware of the side effects, contraindications and monitoring of sex steroid therapy. In this paper, practical ICET-A recommendations for the management of hypogonadism in adult females with TM are addressed. METHODS: In March 2015, the Coordinator of the International Network of Clinicians for Endocrinopathies in Thalassemia and Adolescent Medicine (ICET-A) conducted a two-step survey to assess the attitudes and practices of doctors in the ICET-A network taking care of adult female TM patients with hypogonadism. They were clinically characterized by the absence of pubertal development or discontinuation or regression of the maturation of secondary sex characteristics, and biochemically by persistent low FSH, LH and estradiol levels. Recently a supplementary survey on adult female hypogonadism in TM was undertaken within the ICET-A network. RESULTS: The completed questionnaires were returned by 16 of 27 specialists (59.2%) following 590 female TM patients over the age of 18 years; 315 patients (53.3%) had hypogonadism, and only 245 (74.6%) were on hormone replacement therapy (HRT). Contraceptive oral pills (COC) were the first treatment choice in 11 centers (68.7%). A wide range of COCs was used with different progestin contents. In general, the patients' compliance to treatment was reported as good in 81.2 % of centers. The frequency of required tests for follow-up HRT, in addition to the regular check-up for thalassemia, was variable in the participating centers. CONCLUSIONS: Doctors taking care of TM patients should have sound knowledge of the pathophysiology of hypogonadism in adult females with TM. They should know the potential effects of HRT including advantages and disadvantages of estrogen and progestins. Moreover, they should keep in consideration the emotional needs of these patients dreaming of attaining a full pubertal development.

Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy in acromegalic patient with severe headache.

A 68-year-old female patient was admitted in our clinic with severe frontal bilateral headache, dizziness, depression and cognitive decline in the context of a previously diagnosed acromegaly. She also had high blood pressure, dyslipidemia, secondary diabetes mellitus. Acromegaly was caused by a growth hormone (GH) secreting-pituitary macroadenoma, so a transsphenoidal surgery was performed. The postoperative magnetic resonance imaging (MRI) scan revealed a 20÷22÷25 mm pituitary mass remnant and medical therapy with somatostatin analogues (SSAs) was started. After nine months of treatment with SSAs, she continued having severe headache, the blood pressure was well controlled, but GH secretion was only partially controlled with insulin-like growth factor-1 (IGF-1) level still above the normal value. The MRI scan showed the same pituitary tumor remnant with supra- and parasellar right extension and also multiple fronto-temporo-parietal subcortical lesions that could suggest in the clinical context cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). According to a pregenetic screening tool, the Pescini Scale, the patient had a 19 points score, which is highly suggestive for CADASIL, an inherited cerebrovascular disease due to mutations of the Notch3 gene at the chromosome locus 19p13. In the absence of genetic testing, an alternate way to prove small vessels disease, the skin biopsy, was performed. Electron microscopy showed granular osmiophilic material (GOM) surrounding the vascular smooth muscle cells on that are pathognomonic for the disease. Our report underscores the importance of repeated investigations even in patients with apparently obvious explanations of their condition since they may have multiple diseases with the same presenting clinical signs.

The ICET-A Survey on Current Criteria Used by Clinicians for the Assessment of Central Adrenal Insufficiency in Thalassemia: Analysis of Results and Recommendations.

BACKGROUND: In March 2015, the International Network of Clinicians for Endocrinopathies in Thalassemia and Adolescent Medicine (ICET-A) implemented a two-step survey on central adrenal insufficiency (CAI) assessment in TM patients and after analysis of the collected data, recommendations for the assessment of hypothalamic-pituitary- adrenal (HPA) axis in clinical practice were defined. METHODS: To ascertain the current practice for assessment of CAI in thalassemia, the Coordinator of ICET-A sent two questionnaires by email: i) The first to evaluate the current interpretation of basal serum cortisol level (first step) and ii) The second to assess the current usage of ACTH test and the variability in practice" (second step). Based on the surveys the core ICET-A group prepared the recommendations for the assessment of suspected CAI in thalassemia (third step). RESULTS: A total of 19 thalassemologists/endocrinologists have participated in the first survey and 35 specialists participated in the second step questionnaire. The study demonstrated a considerable variability in almost all aspects of relevant current criteria used for the diagnosis of CAI. An ROC analysis using peak value > 20 µg/dl (> 550 nmol/L), after ACTH stimulation test, was performed with the aim of identifying the optimal basal serum cortisol cut-off. The optimal threshold that maximizes sensitivity plus specificity for morning basal cortisol against peak post-ACTH value >20 µg/dl (>550 nmol/L) was 10 µg/dl (275 nmol/L). Furthermore, the values associated with the highest negative predictive value (NPV) and highest, positive predictive value (PPV) were 4.20 (115 nmol/L) and 18.45 µg/dl (510 nmol/L), respectively. Surprisingly, 20 specialists in thalassemia working in blood bank, thalassemia centres (day hospital), internal medicine, hematology and onco-hematology had poor knowledge and experience in testing for CAI and stopped filling the questionnaire after the second question. In contrast, 9 endocrinologists (8 pediatricians) and 6 hematologists working in collaboration with endocrinologists completed the questionnaire. CONCLUSIONS: While waiting for more extensive adequately powered and targeted studies, physicians should adopt an acceptable policy for accurate assessment of HPA in TM patients. Regular surveillance, early diagnosis, treatment and follow-up in a multi-disciplinary specialized setting are also recommended. The ICET-A recommendations are reported in order to facilitate for interested physicians the approach to a successful assessment of adrenal function in thalassemia.

Is prolactin the missing link in adipose tissue dysfunction of polycystic ovary syndrome patients?

The aims of the study were to evaluate whether adiposity was among the determinants of circulating prolactin levels and to determine whether serum prolactin independently predicted metabolic abnormalities in patients with polycystic ovary syndrome (PCOS). A total of 322 PCOS patients with normal serum prolactin levels were recruited between January 2007 and January 2014. Anthropometric, metabolic, and hormonal parameters were measured in all of the patients. HOMA-IR was calculated as an index of insulin resistance. Serum prolactin was negatively correlated with age (p < 0.0001), all the adiposity indices [body mass index p < 0.0001; waist circumference p < 0.0001; waist-hip ratio (WHR) p < 0.0001], visceral adiposity index (VAI, p = 0.043), fasting insulinemia (p = 0.002), and HOMA-IR (p = 0.002), and was positively correlated with serum adiponectin (p = 0.034), but not with circulating androgens or serum leptin levels. Serum adiponectin, but not HOMA-IR or fasting insulinemia, was independently associated with serum prolactin after adjustment for age, leptin, and anthropometrical adiposity parameters. Of the adiposity parameters, only WHR and VAI were independent predictors of serum prolactin after adjustment for adiponectin. Circulating prolactin was also negatively correlated with fasting glycemia (only in patients with normal glucose metabolism, p = 0.037) and was inversely correlated with the presence of metabolic syndrome (p < 0.001), but this association was not maintained after adjustment for possible confounders. In PCOS patients, serum prolactin level was related to adipose tissue quantity and function, and adiponectin was a possible mediator of this relationship. Low serum prolactin levels were associated with an unfavorable metabolic profile, but this association seemed to be due to the complex interplay among prolactin, adiposity, and insulin resistance rather than to a direct metabolic effect of prolactin.

Leading Nursing Into the Future: Development of a Strategic Nursing Platform on a System Level.

Leading and orchestrating the mission-essential work of 47 diverse hospitals toward a common vision with a supporting strategy is a challenge for any health care system. Trinity Health embraced this challenge while reorganizing the pivotal role of nursing in designing the future of health care delivery. This article outlines the roadmap utilized to create a common nursing platform to drive strategy aligned to future viability, strength, and growth across a system.

Obesity and eating behaviors in school children and adolescents -data from a cross sectional study from Bucharest, Romania.

BACKGROUND: Epidemiological data on obesity prevalence are scarce in Romanian population. Consequently, the aim of our study was to evaluate the prevalence of obesity and unhealthy behaviors among school children and adolescents from Bucharest, Romania. METHODS: Cross-sectional study, 866 participants (53.2% girls, 46.8% boys, age range 6-18 years), selected by systematic sampling with probability-proportionate-to-size from all Bucharest's schools. MEASUREMENTS: height, weight and a questionnaire to collect information about life style and eating behavior. Nutritional status was established based on World Health Organization recommendations (WHO), International Obesity Task Force (IOTF), Center for Diseases Control (USA-CDC) cut off values and local standards, respective. RESULTS: The prevalence of overweight (including obese) and obesity alone based on different standards, was 31.6% and 11.4% (WHO), 24.6% and 6.2% respectively (IOTF), 25.2% and 10% (USA-CDC), 22.3% and 12.5% (local standards). When using local standards (weight only based), the obese subjects proportion among overweight children raised questions regarding the appropriateness of these standards. Overweight (including obese) prevalence was significantly higher among the boys versus girls: 36.2% vs. 27.6%, ( OR 1.5; 95% CI 1.12-2.03; p value = 0.006) and among the 6-10.9 years vs. 11-17.9 age group, (40.7% vs 26.6%). Almost all the participants (95%) reported at list one unhealthy eating behavior but no significant relationship was found with overweight or obesity only. CONCLUSIONS: This first epidemiological study of obesity prevalence in school children and adolescents showed that 11.4% of Bucharest's children and adolescents were obese by WHO classification, 6.1% by IOTF cut off values and 10% by CDC classification. Younger children and the boys were more affected no matter which standard we used. In spite of unsignificant relationship to the adiposity status, our data showed a high prevalence of unhealthy eating behaviors reported by the participants. Particular aspects of the overweight versus obesity prevalence, after applying local standards, suggests that international recognized algorithms should be used for constant epidemiological evaluation instead of establishing local criteria.

Biochemical hyperandrogenism is associated with metabolic syndrome independently of adiposity and insulin resistance in Romanian polycystic ovary syndrome patients.

The aim of the study was to determine whether Romanian polycystic ovary syndrome (PCOS) patients have an increased prevalence of metabolic syndrome (MetS) and to study the involvement of adiposity, insulin resistance and hyperandrogenism in the pathogenesis of MetS in PCOS. A total of 398 PCOS patients and 126 controls were evaluated between January 2006 and December 2012. MetS was defined by National Cholesterol Education Program, Adult Treatment Panel III criteria. Principal component analysis (PCA) was used to analyze the correlations among variables of interest by grouping them in few components, and principal component (PCs) scores were saved and used as independent variables in logistic regression. The prevalence of MetS was higher among patients with PCOS (20.4 %) than in controls (11.1 %, p < 0.05). In PCOS patients, PCA extracted three PCs from the analyzed variables. First PC aggregated variables related to adiposity and insulin resistance, with factor loadings showing strong relationship between these parameters. The second PC included markers of hyperandrogenemia and was best represented by free androgen index (FAI) which correlated strongly and exclusively with this PC. The third component was best represented by hirsutism. Logistic regression analysis revealed that in PCOS patients, the first and the second PCs were independently associated with MetS, whereas the third component was not. Romanian PCOS patients have an increased risk for MetS; adiposity, insulin resistance and hyperandrogenemia, but not hirsutism, are independent predictors of MetS presence. Our data also suggest that insulin resistance is only secondary to increased adiposity and FAI is a good marker of biochemical hyperandrogenism with little influences from the metabolic component.

Risk factors associated with hypogonadism in ß-thalassemia major patients: predictors for a frequent complication of a rare disease.

BACKGROUND: ß-Thalassemia major (BTM) is a rare disease that challenges clinicians because of the high prevalence of complications despite progress in the development of new therapeutic methods. The aim of this study was to identify clinical and hematological parameters associated with hypogonadism, the most frequent iron overload-related complication found in Romanian patients. METHODS: Patients with BTM were evaluated in the Endocrinology Department of Elias Hospital between February 2004 and December 2013. Only patients who provided written informed consent were included in the study. A complete physical and hormonal evaluation was performed on all patients, and data regarding treatment of the hematological disease were collected. RESULTS: Of the evaluable patients, 85 were included in the study (median age, 21[10] years; range, 13-36 years). We found that 30.6% of the study participants (26 of 85) had normal gonadal status, 54.1% (46 of 85) had early forms of hypogonadism (delayed or arrested puberty), and 15.3% (n = 13) developed hypogonadism after complete sexual maturation. Patients with any form of hypogonadism were older (median age 22 vs 16.5 years, P = 0.047), had significantly lower average hemoglobin levels (P = 0.003), and had higher levels of serum ferritin (P = 0.006) versus patients without hypogonadism. Patients with delayed puberty were associated with increased average serum ferritin levels (P = 0.007), decreased hemoglobin levels (P = 0.001), and increased age at initiation of iron chelation therapy (P < 0.01). We found no significant differences between patients with early forms of hypogonadism and those with hypogonadism after complete sexual maturation, with respect to the analyzed parameters. Patients with adult hypogonadism were significantly older (median age 26 vs 16.5 years, P = 0.007) and tended to have higher serum ferritin levels (P = 0.056) compared with patients without hypogonadism. CONCLUSION: Our data show that hypogonadism is highly prevalent among Romanian patients with BTM, its presence being associated with higher iron overload and lower hemoglobin values. The late start of iron chelation therapy was particularly associated with pubertal abnormalities.

The clinical value of human leukocyte antigen HLA-DRB1 subtypes associated to Graves' disease in Romanian population.

The aim of this study was to identify the primary susceptibility HLA-DRB1 alleles associated with GD in Romanian population and to seek whether specific HLA-DRB1 haplotypes are associated with differences in the clinical presentation of GD at diagnosis. Molecular typing of HLA-DRB1 alleles was performed in 77 Romanian Caucasian GD patients and 445 racially matched controls. In GD patients, age, presence of eye disease, goiter grade, autoantibody status and titer, TSH, FT4, FT3, TT3 levels were recorded at diagnosis. The allelic frequencies of HLA-DRB1*03 (41.55% vs. 17.75%, p < 0.0001, χ(2) = 20.81) and DRB1*11 (42.85% vs. 30.56%, p = 0.045, χ(2) = 3.98)were higher, whereas those of HLA-DRB1*01(3.89% vs. 16.40%, p = 0.007, χ(2) = 7.281) and DRB1*15 (10.38% vs. 21.34%, p = 0.038, χ(2) = 4.309)were lower in GD patients than in controls. FT4/TT3 ratio (p = 0.015) and anti-thyroglobulin antibodies (p = 0.024) were higher in *03/11 patients compared to *X/X, *11/Z, *03/Y patients (where X is any other allele than *03 and *11, Y is any other allele than *11, Z is any other allele than *03). In conclusion, HLA-DRB1*03 and DRB1*11 may be the primary susceptibility HLA-DRB1 alleles associated with GD in Romanian population, whereas HLA-DRB1*01 and DRB1*15 seem to be protective. At diagnosis, HLA-DRB1*03/11 GD patients had higher FT4/TT3 ratio and anti-thyroglobulin antibody levels.

Thyroid autoimmunity in 72 children with type 1 diabetes mellitus: relationship with pancreatic autoimmunity and child growth.

The aim of this study was to assess the association between pancreatic and thyroid autoimmunity (TA) and determine impact of thyroid antibodies on statural growth. Seventy-two children with type 1 diabetes mellitus (TIDM) and no clinical evidence of thyroid disorders were evaluated: glycated haemoglobin (A1c), thyroid peroxidase antibodies (TPOAb), glutamic acid decarboxylase antibody (GADA), tyrosine phosphatase antibodies (IA2A), and thyroid-stimulating hormone (TSH). The score of standard deviation for height (SDS) was calculated. There were 72 patients, 38 (52.7%) boys and 34 (47.2%) girls, with a mean age of 10.89 +/- 4.26 years and a mean duration of T1DM of 3.41 +/- 2.56 years. TPOAb were present in 23.6% of patients; 12.5% of subjects were positive for GADA and 41.6% for IA2A. Patients with TA had more prevalent GADA and IA2A (23.5% vs. 9%, p < 0.001, and 58.8% vs. 36.3%, p < 0.001, respectively). A1c was higher in patients with TA (9.7% +/- 2.05% vs. 8.6% +/- 2.11%, p = 0.05). TA was associated with lower SDS (0.26 vs. 0.98, p = 0.043). TSH was higher in patients with TA (3.39 vs. 2.15 microU/mL, p < 0.05). Logistic regression analysis revealed that a negative SDS for height was independently associated with duration of diabetes (p = 0.049) and TSH (p = 0.027) but not with birth weight, A1c, and TPOAb. In conclusion, TA was found in 23.6% TIDM children. Patients with TA had significantly higher prevalence of GADA and IA2A and significantly higher A1c vs. patients without TA. Our data suggest significant association between TA and height in children with T1DM. SDS was independently associated with diabetes duration and TSH.

FTO gene associates to metabolic syndrome in women with polycystic ovary syndrome.

The FTO (Fat mass and obesity associated) locus has recently been associated with obesity and type 2 diabetes (T2D) in humans. To understand the role of the FTO gene in polycystic ovary syndrome (PCOS) we genotyped single nucleotide polymorphism (SNP) rs1421085 (C/T) in women with PCOS (n=207) and controls (n=100) from a Central European population. The homozygous C/C genotype showed increased prevalence in PCOS patients either obese or with metabolic syndrome (MetS) compared to lean PCOS patients or controls (27.6%, 38.9%, 22.3%, and 16.3%, respectively). In logistic regression, this genotype strongly associated with MetS (P<0.0001, OR 3.2, 95% CI 1.8-5.7) and impaired fasting glucose (IFG) with P<0.0007, OR 7.7, 95% CI 2.1-28.6, independently of BMI or age, and to AUC(gluc) during OGTT (P<0.0001, alpha=0.99), indicating an influential role of the FTO gene in the glucose intolerance component of MetS.