ACTA ENDOCRINOLOGICA (BUC)

The discovery of thyrotropin releasing hormone (TRH) in 1969 was the definitive step in decoding the hypothalamic-pituitary thyroid (HPT) axis, thereby opening up the era of neuroendocrinology, while it also revolutionized the diagnostic and therapeutic approach to patients with thyroid diseases. TRH, produced in the hypothalamus, is the central regulator of the HPT. It functions via neurons originating in the paraventricular nucleus (PVN), which integrates multiple neuronal and humoral signals and resets the HPT axis according to variations of external and internal environmental conditions. The TRH activates TSH in the pituitary that stimulates the secretion of thyroxine from thyroid which, in turn, exerts a negative feedback on TSH and TRH secretion. However, various factors are involved in the regulation of the HPT axis. Leptin has both indirect and direct effects on TRH regulation, the former by regulating agouti-related peptide (AGRP) in the arcuate nucleus (ARN) that antagonizes the α-MSH stimulatory activity on pro-TRH gene expression in the PVN, and the latter by stimulating hypothalamic TRH expression, TRH transcription via stimulation of proconvertase 1 and 2 expression, which lead to enhanced processing of pro-TRH into TRH. The interplay of TRH with leptin and the recently reported influence of ghrelin on the HPT axis can alter the setpoint of the axis. The polyphenol resveratrol, as recently observed, exerts an anxiolytic and antidepressant activity in subclinical hypothyroid (SCH) rats. Resveratrol, by decreasing both TSH and TRH mRNA expression, regulates the HPT axis, while in parallel it regulates the Wnt/β-catenin pathway in the hippocampus. These findings open up possibilities for the therapeutic use of resveratrol as coadjuvant, especially in overt and SCH states marked by anxiety and depression. The clinician should be aware of clinical changes that can invalidate the normal regulation of the HPT axis, the most commonly observed being medications and comorbidities.

Vertebrate nonapeptide neurohormones constitute an evolutionarily conserved family, involved in vital functions, such as hydro-osmotic balance regulation, reproduction and social behaviour. Two human members of this family are known, vasopressin (AVP) and oxytocin (OXT), with their highly homologous genes closely located on Chr 20p13. Presence of vasotocin (AVT) in man has been suggested, but remains controversial, and genetic evidence is lacking. AVT activity could be explained by the presence of a third distinct gene for AVT or an RNA-processing mechanism involving products of AVP and/or OXT genes. To test the first hypothesis, we developed bioinformatics and experimental approaches using genomic DNA and fetal tissues mRNAs. Family-specific primers for AVT and neurophysin were designed based on CODEHOP strategy and used in our experiments. Results of bioinformatics and genomic DNA experiments (family-specific and Alu step-out PCR) suggest there is no evidence for an AVT gene in the genome. RNA-based techniques 3?-RACE and Family-Specific Domain Restriction Fragment RTPCR provided evidence for new transcript species that could code for AVT. Further experiments will be needed to characterize them. We discuss potential mechanisms of AVT mRNA generation based on AVP and OXT mRNAs, by alternative splicing, heterologous transsplicing or RNA-editing. While all methods we developed proved feasible, current results suggest there is no AVT gene in the genome, but specific mRNAs could be present in fetal tissues. Their full characterization may potentially allow identification of vasotocin mRNA and shed light on a subject of fundamental scientific interest.

Background. Adiponectin, vaspin and leptin are only a few of these numerous adipocytokines. Little is known about the behavior of adipocytokines and how adipose tissue metabolism is affected in this Type 1 DM model. In this study we investigated the serum levels of adiponectin, leptin, vaspin in streptozotocin(STZ) induced diabetic rats. Material and methods. Twelve Spraque Dawley albino rats were included in the study. The animals were divided into two groups. The first group was diabetic (D) (n: 6) and 60mg / kg STZ was administered intraperitoneally (i.p.) to these rats. The second group was the non-diabetic control (ND) group (n: 6). All the animals were euthanized by cervical dislocation. Quantification of vaspin, Adiponectin, leptin in serum was performed using the ELISA kit. Results. Adiponectin, vaspin levels of diabetic group were found to be statistically lower than of control group (p<0.05). Leptin levels were significantly higher in the diabetic group (P<0.05). Conclusion. There is a need for new researches that can explain the relationship between Vaspin, Leptin and Adiponectin and Type 1 diabetes. New studies in this area will open new horizons for the identification of new biomarkers in the diagnosis and treatment of Type 1 diabetes.

Objectives. The purpose of this study was to evaluate the association between the follicle-stimulating hormone (FSH) receptor (c.-29G>A) and FSH beta chain (c.- 280G>T) polymorphisms and endometriosis in Romanian women. Material and methods. We performed the polymorphic analysis of the FSH receptor gene and FSH beta chain in 44 patients with endometriosis and 34 controls. Genomic DNA was obtained from peripheral blood and polymorphisms were investigated using restriction fragment length polymorphism analysis (RFLP). Results. There were no significant differences in genotype frequencies of FSH receptor gene between endometriosis patients and controls. For the heterozygous type of the FSH receptor polymorphism (c.-29G>A) we did not find a significant difference in its frequency between patients with minimal/mild and moderate/severe endometriosis (p = 0.136). Also, the FSH beta chain (c.- 280G> T) polymorphism frequency was not significantly associated with the severity of endometriosis (p = 0.966). Conclusions. FSH receptor and FSH beta chain polymorphisms do not seem to influence the severity of endometriosis, but they could be correlated with female infertility (primary or secondary), therefore further studies are required to debate this topic.

Objective. We aimed to investigate the potential relationship between plasma alarin levels and type 2 diabetes mellitus (T2DM). Patients and Method. We included 154 participants, divided into four groups in a cross-sectional study design. The first group includes patients with T2DM without complications (n=30), the second group patients with T2DM with microvascular complications (T2DMnoC n=32), the third group patients with T2DM with macrovascular complications, T2DM-MV (n=32) and the last group is the healthy control group (n=60). Results. In our study 94 patients were diabetic; 47 females and 47 males. The control group consists of 60 people, 30 women and 30 men. It was found that these had a significant (p>0.05) variation in serum alarin levels among the T2DM (T2DM-noC=3.1±0.7 ng/mL T2DMmV=2.8±0.4 ng/mL, T2DM-MV= 3.6±0.4 ng/mL) versus control group (15.6±2.6). We failed to find a significant variation of serum alarin levels (p>0.05) between T2DM subgroups. Serum alarin levels were significantly higher among control patients (p<0.05). There was no difference between diabetic sub-groups. Conclusion. We concluded that serum alarin levels in patients with T2DM are lower than in normal people. Further studies are needed to investigate the possible prognostic value of alarin in clinical practice in T2DM.

Background. Abnormal thyroid function is accepted to be associated with disordered production of hormones released by adipose tissue. Objective. We aimed to investigate the relationship between thyroid functions and adipocytokines as leptin and visfatin and Angiopoietin-like Protein 3 (ANGPTL), a secretory protein that affects adipocity in patients with thyroid dysfunction. Methods. Twenty-seven patients with hyperthyroidism, 27 patients with hypothyroidism and 31 euthyroid subjects as control group were selected. Serum TSH, fT3, fT4, fasting glucose, lipid profile, ANGPTL, visfatin, leptin, insulin levels were determined. Results. ANGPTL and visfatin were significiantly different in hypothyroid group when compared to other groups. (p<0.0167) ANGPTL was positively correlated with TSH and leptin. Leptin was correlated with insulin and ANGPTL positively. Visfatin, positively correlated with TSH, total cholesterol, LDL-C and negatively correlated with fT3 and fT4. Conclusion. Serum ANGPTL may be increased because of lipid abnormalities in hypothyroid patients. Visfatin is thought as a partly mediator to the effect of hyper/ hypothyroidism on several metabolic parameters. We suggest that the release of Visfatin is regulated by thyroid hormones. The effect of thyroid dysfunction on production and release of adipocytokine is not yet clarified.

Objective. The mechanisms underlying the development of diabetic neuropathic pain (NeP) are still unknown. The aim of the study was to evaluate painful diabetic neuropathy in Type II diabetic patients with Leeds Assessment of Neuropathic Symptoms and Signs Scale (LANSS), thermal and vibratory Quantitative Sensory Testing (QST) and, EMG supported Diabetic Neuropathy Score (DNS) and to evaluate the differences in patients with and without neuropathic pain. Methods. Eighty three Type II diabetic patients (26 males, 57 females) were investigated. Patients with pain were assessed by the LANSS pain scale and a score of ≥12 was classified as NeP. All patients underwent nerve conduction studies (NCS) to obtain EMG supported diabetic neuropathy score (DNS). Cold and warm sensation thresholds and cold pain and heat pain thresholds were obtained for evaluation of A-delta and C type fibers. Vibratory perception thresholds were recorded for evaluation of thickly myelinated fibers. Results. The percentage of NeP (LANSS score ≥12) was 15.7 %. QST revealed significantly lower cold detection, higher warm detection and higher heat pain thresholds at the feet in patients with NeP compared with patients without NeP. Although small fiber dysfunction has been revealed in all patients with NeP, the percentages of the presence of small fiber neuropathy and EMG supported diabetic neuropathy were not significantly different among patients with NeP and without NeP. Conclusions. We concluded that QST is a useful and a noninvasive tool to detect small fiber dysfunction in Type II diabetic patients. QST revealed increased severity of small fiber dysfunction in patients with NeP. Although small fiber neuropathy has been revealed in all Type II diabetic patients with neuropathic pain the absence of pain does not predict preserved small fiber function.

Objective. We aimed to determine the risk of hypercalcemia in a geriatric population with very high dose levels of 25-hydroxy-vitamin D (25(OH)D). Patients and Method. This study was designed as a retrospective, cross-sectional two-center study for examining the elderly patients with very high 25(OH)D levels (>88ng/mL) between January 2014 and December 2019. After recruitment, subgroup analyses of the patients were performed based on their calcium and vitamin D levels. Results. A total of 81.101 elderly patients, who had been evaluated for their vitamin D levels, were screened. Of the 458 (0.6%) elderly patients with 25(OH)D>88 ng/ mL according to our criteria, 217 patients with complete data were accepted into our study. The median 25(OH)D level was 103.7ng/mL (min-max:88.2-275.9). Most of the elderly patients (86.6%) with very high 25(OH)D levels were normocalcemic. When patients with hypercalcemia were compared with normocalcemic group, no difference was observed in the levels of 25(OH)D, intact parathormone (iPTH), phosphorus, alkaline phosphatase (ALP), and their age. However, the PTH suppression rate was significantly higher in hypercalcemic group (p=0.005). Conclusion. The elderly patients with very high 25(OH)D levels would appear to be mostly normocalcemic whereas life-threatening hypercalcemia would also occur. Treatment and follow-up planning should be done according to the clinical guideline recommendations.

Context. Management of neuroendocrine tumors is highly dynamic, in both diagnosis and treatment. Objective. Surgical resection with lymph node approach offers excellent 5-years survival. Design. Between 2008 and 2011 we operated with radical intent 326 lung cancers. Patients and Methods. Cases without lymph node approach were excluded. We found 38 neuroendocrine malignancies: 12 typical carcinoids, 3 atypical carcinoids, 4 large cell neuroendocrine carcinomas (LCNEC) and 10 small-cell lung cancers (SCLC). Limits of the study are: variable lymphadenectomy technique; absence of PET - CT and EBUS-TBNA (EndoBronchial UltraSound - TransBronchial Needle Aspiration) for staging; incomplete data for disease-free survival. Results. We performed 13 pneumonectomies, 22 lobectomies and 3 non-anatomical resections. There were 5 bronchoplasties. The 5-year survival difference between NSCLC (non-small-cell lung cancer - 42.9%) and SCLC (40.53% - one of the best from the literature) is not statistically significant (p=0.4780). Five-years survival was 100% for typical and atypical carcinoids – the best published. We found lymph node metastasis in 2 typical carcinoids, in 2 atypical carcinoids and in 6 SCLCs. Conclusions. For typical and atypical carcinoids, radical resection with lymphadenectomy offers 100% 5-years survival. Early-stage SCLC may benefit from radical resection; lymph node dissection is mandatory because of the well-known precocious lymphatic dissemination.

Ectopic lingual thyroid is a rare developmental abnormality caused by aberrant embryogenesis during thyroid migration. Even though, most patients are asymptomatic, uncommonly the mass can be enlarged and cause dysphagia, dyspnea, upper airway obstruction, dysphonia, hypothyroidism. We report a very rare case of ectopic lingual thyroid presenting with massive hematemesis.