ACTA ENDOCRINOLOGICA (BUC)

Objective: The goal of this research is to investigate whether melatonin, a circadian informant, is implicated in idiopathic oligospermia in men.\r\nSubjects and methods: 12 men (mean age 30.5 yr) with normal sexual function diagnosed with idiopathic oligospermia and 8 healthy men were included. In urine 6-sulfatoxymelatonin (aMT6s), a reliable index of melatonin secretion and gonadotropins, LH and FSH were assayed. In plasma LH, FSH, DHEA-S, 17-OH progesterone, testosterone, free testosterone, SHBG were measured at 08:00.\r\nResults: As expected, in the infertile group reproductive hormones were within normal limits but persisted low testosterone and high gonadotropins. Estimated bioavailable testosterone also showed a significant decrease (p=0.03). Evaluation of individual differences in circadian production of both melatonin and gonadotropins exhibited substantial changes in their secretion pattern from the phase shifts to loss of rhythm for aMT6s. The reduced amplitudes (p=0.04) of aMT6s were associated with a longer duration of melatonin secretion (p< 0.001) as estimated from onset/offset time and a reduced ratio between night- and daytime; the mean 24h amount of aMT6s tended to decrease at significant limit (p=0.05); no significant correlation between aMT6s and gonadotropins was observed compared with the control group. The amplitudes of gonadotropins were lower while their mean 24 h amount showed a moderate increase.\r\nConclusions: The present findings suggest that the significant increase in the duration of melatonin secretion may contribute to the imbalance of reproductive hormones that affect spermatogenesis; aMT6s, urinary metabolite of melatonin may be a sensitive predictor in circadian disorders of reproductive axis.

Objective. Estrogen receptor alpha (ESR1) polymorphisms (XbaI and PvuII) and vitamin D receptor (VDR) polymorphisms (FokI, BsmI, ApaI and TaqI) are the most frequently studied regarding the correlations with the infertility in males, but the results are controversial. The purpose of this study is to evaluate possible correlations between hormonal markers, VDR and ESR1 genotypes and semen analysis, in order to bring new data for a better understanding of male infertility. Subjects and Methods. 42 infertile men and 28 controls were enrolled. The polymorphisms of VDR gene (ApaI, TaqI, BsmI and FokI) and ESR1 (XbaI and PvuII) were performed by PCR-RFLP, along with hormonal markers. Results. An important correlation between PvuII polymorphism and infertility status was revealed. A significant difference between control and infertility group regarding the presence of BsmI (A>G) and ApaI (G>T) polymorphisms was observed in infertile group, prolactin and DHEA were found to correlate significantly statistic with BsmI GG genotype, whereas ApaI AA genotype correlates with prolactin and SHBG levels. Conclusions. By a multivariate analysis, we demonstrated a cumulative effect of some genetic variants in the hormonal status of infertile patients. Therefore, we show that specific genetic variants of ESR1 and VDR genes may jointly influence human spermatogenesis.

Context. Studies investigating the association between serum IGF-1, and thyroid nodule, ovarian or thyroid volume in polycystic ovarian syndrome (PCOS) are limited. Objective. We aimed to analyze the association between serum IGF-1 level, and ovarian or thyroid volume, or thyroid nodule in PCOS. Design. The study was performed between June 2017 and August 2019 as prospective design. Subjects and Methods. Adult females with newonset PCOS were included. The patients having comorbid illness, or using medication were excluded. Basic tests, thyroid and ovarian sonography were performed. The patients were grouped according to thyroid nodule(absent/ present) and ovarian volume (<10mL/≥10mL). We planned to find a positive association between IGF-1, and thyroid nodule, thyroid or ovarian volume in PCOS. Results. Of total 118 patients, 11(9%) had thyroid nodule. The patients with thyroid nodule had a higher ovarian volume (p=0.006). No correlation was found between GH or IGF-1, and thyroid or ovarian volume. IGF-1 was not a predictor for thyroid nodule or higher ovarian volume. Thyroid nodule was a significant predictor for higher ovarian volume. Conclusion. Our study is the first to analyze the association between IGF-1 and thyroid nodule in PCOS. We found that thyroid nodule was associated with thyroid and ovarian volume, but IGF-1 was not associated with thyroid nodule, thyroid or ovarian volume.

Introduction. Symptoms related to hypersecretion of hormones in patients with pituitary adenomas do not always correlate with immunohistochemical staining results. Objective. To evaluate the relationship between the pituitary adenomas hormone immunoexpressions and endocrine presentations. Patients and methods. The clinical status and immunoexpression of 72 patients who underwent transsphenoidal surgery for pituitary adenomas were analyzed. Results. Macroadenomas were diagnosed in 51 cases (70.84%), while microadenomas were found in 21 cases (29.16%). The 72 adenoma specimens were divided into 22 monohormonal, 21 plurihormonal, 21 immunonegative and 8 unreliable specimens. The positive immunohistochemical staining results occurred as follows: prolactin and growth hormone 25% each, adrenocorticotropic hormone 13.89%, thyroid-stimulating hormone 5.56%, leuteinizing hormone and follicle-stimulating hormone 12.5%, glycoprotein hormone alpha-subunit 22.22%. Statistically significant relationships between the immunohistochemical presentation and the preoperative diagnosis were found for prolactin and hyperprolactinemia, growth hormone and acromegaly and adrenocorticotropic hormone and Cushing’s syndrome. Conclusions. The lack of full concordance between the clinical presentations and immunohistochemical staining was mainly a result of the presence of nonfunctioning adenomas, plurihormonal adenomas and unreliable specimens. The morphometric method introduced in this study, utilizing the immunoexpression index, provided a very precise evaluation of pituitary adenomas pathology.

Background. In vitro studies of the changes about osteoblastogenesis and adipogenesis potential of BMSCs were not clear. As it is the critical pathway for osteogenic differentiation and bone formation, whether or not Wnt/β- catenin signalling is involved in the changes of osteogenic and adipogenic potential of BMSCs and participates in bone content decrease of ovariectomized (OVX)osteoporosis rats has been rarely reported. Material/Methods. BMSCs from femurs of ovariectomzed rats were isolated and cultured in vitro. The proliferation potential of BMSCs was analysed by CCK-8 assays . Osteoblastic and adipogenic differentiation potential of the BMSCs was assessed by ALP activity assay, Alizarin red S staining, Oil red O staining and RT-PCR analysis. Results. The results demonstrated that BMSCs from bilateral ovariectomization rats were endowed with lower proliferation and osteoblastic differentiation potential but higher adipogenic potential than the control group in vitro. In addition, β-catenin was found to have been decreased in OVX BMSCs, indicating that Wnt/β-catenin signalling pathways were suppressed in OVX BMSCs . Conclusions. Results suggested that changes in the Wnt canonical signalling pathway may be related to imbalances of osteogenic and adipogenic potential of BMSCs, and this may be an important factor related to bone content decrease in ovariectomized osteoporosis rats.

Introduction: Obesity, a disease whose morphological background has as main problem the “dysfunctional” adipocyte, continues to raise scientific interest for the completion of the existing data and the verification of the hypothetic ones. Material and method: We determined insulinemia and glycemia within the oral glucose tolerance test (OGTT), and we analyzed the relation between the fat mass and cortisolemia in a group of 50 obese patients aged between 4 months –18 years. In 19 obese patients, between 5 ½ -17 ½ years old, we determined the basal leptin and resistin serum levels, comparatively to a control group of 19 normal weight children. In 14 obese and 10 normal weight controls, we determined the number of androgenic and estrogenic adipocyte receptors, which we correlated with the degree of obesity, the Tanner stage and respectively the testosterone, progesterone and estradiol serum levels. We studied the cellularity, morphohistochemical and ultrastructural features of the adipose tissue in 42 obese and 20 normal weight controls. Leptin and resistin were determined by ELISA. The measurement of the fat mass was done by bioelectric impedance. For the study of the adipose tissue we took 1g of tissue from the retro-trochanterian area. We identified the estrogenic (ER) and androgenic (AR) receptors by LSAB2 technique. We interpreted the data statistically by the linear regression analysis and variance test “t” for two unequal parameters using Microsoft Excel 2002. Results: A positive correlation was demonstrated between glycemias and insulinemias for the entire group (r=0.927, p=0.002), as well as between cortisolemia and fat mass excess (r=0.917; p=0.001). Serum leptin levels were significantly high in the obese (mean values: 81.07 ng/ml) comparatively to normal weight individuals (mean values: 4.17 ng/ml). Resistin serum levels did not show significant differences between the obese and normal weight individuals. We cannot talk about the existence of any correlation between resistin and leptin.

Purpose. Vitamin D insufficiency and age related cataract (ARC) are public health problems. We evaluated serum vitamin D levels in ARC patients. Method. A prospective hospital-based crosssectional study was designed to measure the vitamin D status of patients with ARC. Patients have grouped either presence of any type of posterior subcapsular cataract (PSC) (group 1) or ARC without the PSC component (Group 2). After full ophthalmologic consideration, patients over 40 years of age with no history of ocular trauma, multivitamin supplement ingestion, chronic renal failure, thyroidectomy, parathyroidectomy, skin cancer, and cigarette smoking were included in the study. Results. Totally, 79 subjects of which 26 (32.9%) subjects in group 1 and 53 (67.1%) subjects in group 2 were included in the study. Group 1 had mean vitamin D levels of 17.31±13.30 ng/mL. Vitamin D levels in Group 2 were 13.34±7.87 ng/mL. Group 1 did not show vitamin D insufficiency (P = 0.31; one-sample t-test). However, Group 2 showed a statistically significantly lower vitamin D level compared to the insufficiency level of 20ng/mL (P= 0.00; one-sample t-test). Conclusion. Vitamin D may have an important function in lens metabolism. Vitamin D deficiency and cataract development need further extensive researches.

A certain degree of insulin resistance in patients with Gaucher disease type 1 (GD) under enzyme replacement therapy (ERT) was reported. Data on insulin sensitivity in treatment naïve patients are inconsistent. Objective. To analyse prospectively changes in parameters of insulin resistance under ERT and to estimate when they occur. Design. prospective, controlled study; three years follow-up. Patients and methods. 12 treatment naïve patients with GD type 1 (M/W 8/4), 29.5±12.9 years, without overweight, diagnosed enzymatically and by genotyping, without previous diabetes mellitus. Patients were evaluated before and every 6 months up to 3 years under ERT and compared at baseline and after 3 years with matched healthy controls. Fasting-glucose (FG), - insulin (FI), C-peptide, HOMA-IR, IRI, HOMA-B, blood count, hepatic and splenic volume, chitotriosidase, severity score index di Rocco (SSI) were assessed. Results. Baseline glycemic parameters did not differ from controls. FG increased from baseline after two years of ERT (+16.4%,p<0.010), FI (+40.3%,p=0.030), HOMA-IR (+61.2%,p=0.007) and IRI (+9.1%,p=0.010) after 18 months, HOMA-B after 2.5 years (+51%, p=0.015. After 3 years of ERT patients were more insulin resistant compared to controls (p<0.001): FG (96.0±6.2 vs. 73.2±6.4 mg/dL), FI (11.2±2.4 vs. 5.6±1.3 μU/L), HOMA-IR (2.7±0.6 vs. 1.0+0.3), IRI (3.02±0.10 vs. 2.62±0.13). FG, FI, HOMAIR, IRI, HOMA-B correlated with disease severity markers. Conclusions. This is the first controlled study which evaluates prospectively insulin resistance in GD patients, finding significant differences compared to baseline starting with 18 months ERT.

The coexistence of Cushing’s syndrome (CS) and pregnancy is uncommon due to the suppression of gonadotropin secretion in CS. Adrenocorticotropic hormone (ACTH) dependent CS in pregnancy is less frequent than adrenal causes. The diagnosis of CS during pregnancy is difficult since physiological changes in the hypothalamopituitary- adrenal axis may cause dynamic tests to be misinterpreted. Radiological imaging is limited. We report the case of a 27-year old woman with Cushing’s disease (CD) diagnosed in the 5th-week of pregnancy. The mild symptoms of hypercortisolism did not lead to serious complications for the mother or the fetus, so insulin was the only treatment used. The pregnancy was completed without any complications, and at 38 weeks of gestation a healthy female infant was delivered vaginally. Complications, such as hypocortisolemia and hypoglycemia, were not observed in the infant. Postpartum tests were consistent with CD. Contrast-enhanced pituitary magnetic resonance imaging revealed a microadenoma which was removed with transsphenoidal surgery. Histopathology revealed a pituitary adenoma with positive immunohistochemical staining for ACTH. Biochemical remission required prednisolone treatment, but the insulin requirement decreased significantly over time. As a conclusion, CD with mild features can be well tolerated during pregnancy, but the mother and the fetus must be monitored closely.

An 81-year-old woman presented with a history of essential hypertension for eight years and an asymptomatic multinodular goiter that had been incidentally discovered on neck ultrasonography two years ago and an-isohypoechoic mass lesion located adjacent to the right lobe inferior pole of the thyroid gland. Parathyroid adenoma or lymphadenopathy were the differential diagnosis. After two years, the endocrine surgeon decided to operate her multinodular goiter and her probably benign lesion. Intraoperatively, the blood pressure and pulse rate increased markedly and intravenous antihypertensive treatment was administered. She was discharged after blood pressure control. A 2 mm micromedullary thyroid carcinoma with C-cell hyperplasia located on the left lobe of the thyroid was detected. The aforementioned mass lesion was also reported as typical cervical paraganglioma. Because of concomitant medullary thyroid carcinoma with C-cell hyperplasia and paraganglioma the patient was subjected to genetic counseling and molecular testing for hereditary cancer syndromes. A variation of the succinate dehydrogenase gene D (SDHD) NM_003002.3: c.325C> T (Gln109Term) has been reported as the disease-causing mutation. Herein we present a case diagnosed for neck paraganglioma and medullary thyroid carcinoma after an intraoperative hypertensive crisis.