ACTA ENDOCRINOLOGICA (BUC)

Context. Thyroid hormones have metabolic effects such as relationship between hypothyroidism and atherosclerosis. Objective. Evaluate the effects of hypothyroidism on Non-Alcoholic Fatty Liver Disease and atherosclerosis by using AIP, APRI score, FIB-4 indices. Material and Methods. 1370 patients with hypothyroidism who applied to the Endocrinology and Metabolism outpatient clinic between 01.01.2017-30.12.2021 were included the study. Pregnants, patients with a history of thyroid carcinoma, cardiovascular and liver diseases were excluded. TSH, fT4, Anti TPO, Anti TG, thrombocyte, ALT, AST, HDL, Triglyceride values of the cases were analyzed and atherogenic index of plasma (AIP), AST to Platelet Ratio Index (APRI) and Fibrosis-4 (FIB-4) indices were calculated. Results. 1170 (85.4%) of the cases were female.The age of those who had high risk of AIP was found to be higher than those with low and moderate risk (p=0.001; p=0.003; p<0.01). The ages of those who had low-risk FIB-4 Index were found to be lower than those with moderate risk and high risk (p=0.001; p=0.001; p<0.01). A positive relationship was detected between APRI and FIB-4 (r=0.681; p=0.001; p<0.01).AIP increased as TSH increased in hypothyroid patients. No significant correlations were detected between TSH, APRI, and the FIB-4 Index. No significant differences were detected between AIP, APRI, FIB-4, and thyroid autoantibodies. Conclusion. In hypothyroid patients, the AIP index increased with age and the increase in TSH. A strong relationship was detected between AIP and TSH . For this reason, we think that keeping TSH within the normal range with regular follow-ups and treatment in patients with hypothyroidism will reduce the risk of atherosclerosis.

Background. Malignant melanoma is the most aggressive form of skin cancer with a rapidly increasing incidence rate. In contrast to other tumors, the role of sex steroid hormones\r\nin the initiation and progression of melanoma remains unclear.\r\nObjective. To assess the interaction between the content and composition of gangliosides and sex steroid hormones 17&#946;-\r\nestradiol (E2) and testosterone (T) in malignant melanoma.\r\nPatients and methods. The analysis included 45 melanoma patients (age 28-86; 14 men, 15 non -pregnant women in mid\r\nfollicular phase and 16 postmenopausal women) and 46 healthy controls. Serum levels of gangliosides (GM1-3, GD1a,b,2,3, GT1b, GQ1b), estradiol, testosterone measured in serum by chromatographic and immunochemiluminescence methods were correlated with sex and age.\r\nResults. Steroid hormones levels showed no differences between groups (p>0.05), while total gangliosides in normal\r\nserum were significantly lower than total ganglioside concentrations determined in melanoma samples (18.63 ? 3.17 mg/dL versus 74.82 ? 34.56 mg/dL) (p<0.05). There were no differences related to sex or age within groups regarding total gangliosides levels. Gangliosides pattern in\r\nmelanoma patients compared to control showed lower GM3, higher GD3, lower GM3/GD3 ratio, increased GD2 levels, and\r\nno significant variation of GM1, GM2, GD1a, GT1b gangliosides. There is a positive correlation between estradiol levels and total gangliosides concentration both in non-pregnant premenopausal and postmenopausal melanoma patients. GM3 is negatively correlated with estradiol levels in melanoma group, GT1b and O-Acetyl GD3 concentrations are positively correlated with estradiol levels in women with melanoma. Testosterone levels showed no significant\r\ncorrelation with the content and pattern of gangliosides in melanoma patients.\r\nConclusions. The correlations between content and composition of gangliosides and estradiol in melanoma suggest a possible role of these molecules in melanoma behavior.

Acromegaly is associated with increased mortality and decreased life expectancy. Cardiovascular disease is the principal cause of premature mortality in patients with acromegaly, accounting for about 60% of deaths. GH and/or IGF-I exert direct cardiac effects: enhance cardiac contractility, stimulate cardiomyocyte growth, influence calcium influx in cardiomyocytes. Cardiac remodelling is influenced by hypertension and insulin resistance. Among cardiovascular risk factors arterial hypertension, reported in 35% of patients with acromegaly, ranks among most important negative prognostic factors for mortality. Hypertension plays significant role in the development of cardiac hypertrophy, especially in older acromegalic patients and diastolic blood pressure is best predictive factor for cardiac hypertrophy. Therefore, early and aggressive hypertension treatment is essential for prognosis in acromegaly. Other important risk factors are: valvular defects, arrhythmias, endothelial dysfunction, heart failure, lipid abnormalities and coronary artery disease. Numerous studies suggest that patients with acromegaly are under threat of arrhythmias, especially those with structural heart abnormalities. Congestive heart failure as end-stage acromegalic cardiomyopathy occurs usually in older patients, with long-term uncontrolled disease and other cardiovascular and metabolic complications. Relation between acromegaly and coronary artery disease is controversial as it seems to be connected rather with classical cardiovascular risk factors than GH and IGF-1 overexpresion.

The appearance and normal development of the anterior pituitary gland requires several signalling molecules and specific transcription factors. Gene mutations of these\r\npituitary transcription factors may lead to different degrees of combined pituitary hormone deficiency (CPHD) associated or not with morphological changes of the hypothalamicpituitary region. We present the first Romanian case of progressive CPHD in two brothers from a consanguineous family. Clinical, hormonal and MRI follow-up were performed during 20 years. Growth hormone deficiency was certified at the age of 5, respectively 3 years, followed by gonadotropin deficiency diagnosed at the age of 21, respectively 19 years, and by central hypothyroidism diagnosed at the age of 23, respectively 21 years.\r\nSubstitutive treatment rhGH was commenced, followed by testosterone and later thyroxin, in adequate doses. Adrenal function was normal during the follow-up. MRI revealed\r\nanterior pituitary hypoplasia in both siblings, with a partially empty sella in the younger brother and a thick midline septum in the sphenoid sinus in both siblings, which was not described in previous reports. The progressive CPHD suggested a PROP 1 deficiency, which was confirmed by genetic analysis. The c.301-302delAG homozygous mutation in the PROP 1 gene was identified, resulting in a complete loss of promoter binding and\r\ntranscriptional activation of the mutant protein.

Objective. Mean platelet volume (MPV) and platelet function analysis have been studied before in acromegaly, but the effect of treatment on both parameters has not been evaluated. We aimed to investigate MPV and platelet function analysis in acromegalic patients after sixmonths of treatment. Methods. Forty patients with active acromegaly and 36 healthy subjects were included in the study. Plasma glucose and lipids, fibrinogen, GH, IGF-1 levels, MPV and platelet function analysis were measured. All patients with acromegaly were re-evaluated six months after treatment. Results. Fasting blood glucose (FBG), GH, IGF- 1, fibrinogen levels and MPV values were significantly higher in acromegalic group compared with the control. Platelet function was enhanced significantly (pcol-ADP: 0.002, pcolepinephrine: 0.002). After 6 months of treatment FBG, serum GH, IGF-1, fibrinogen and MPV decreased and collagen/ADP- and collagen/epinephrine-closure times (CT) were increased. Acromegalic patients that were in remission with long-acting SSA after surgery had significantly higher fibrinogen levels and MPV and decreased collagen/ epinephrine-CT with respect to the controls (pfibrinogen: 0.001, pMPV: 0.026, pcol-epinephrine: 0.037). Conclusion. Acromegaly was associated with increased MPV and enhanced platelet activity. Although growth hormone hypersecretion was controlled by surgery and medical treatment, these parameters did not improve – indicating a still increased risk for cardiovascular events.

Background. Indication, type of surgery and choice of surgical approach for adrenal masses continues to be a subject of debate between surgeons. The aim of this study was to report our data and experience with adrenal surgery. Subjects and Methods. We performed a retrospective study on 297 patients diagnosed with adrenal masses and operated in our center between 2002 and 2011. Gender, age, surgical approach, operating time, hospital stay, histology report and complications were analyzed. Results. From a total of 297 patients who underwent adrenalectomies, 82 were performed by laparoscopic approach and 215 in a classical open approach. The most common indication for surgery was pheochromocytoma (50.2% in unilateral and 50% in bilateral adrenal masses) summing 149 patients for both types of surgery. The risk of malignancy was significantly correlated with tumor size and the cut off value of 5cm had 92.5% specificity and 74.6% sensitivity. Patients in laparoscopic group were younger (mean 44.13 years), had shorter operating times (mean 122.7 min), shorter hospital stays (mean 6.8 days), and less complications (1.7 %) compared to open adrenalectomy. Conversion rate to open procedure was 2.4 %. Conclusion. Although many adrenal masses are now excised by laparoscopic techniques, the number of procedures was still low in our center because of high surgical complexity of our cases and high institutional costs. Moreover, we should consider that the best adrenal surgery approach remains open surgical excision for larger masses and malignant conditions.

Introduction. The determination of phenylalanine (Phe) and tyrosine (Tyr) levels in blood plasma is very important not only in early diagnostic, but also in monitoring the treatment of phenylketonuria (PKU). Purpose. We present a simple, sensitive and accurate procedure to determine simultaneously the plasma concentrations of Phe and Tyr. Procedure. The measurement involves two steps: a) separation of plasma (from blood prelevated on heparin), isolation and preparation of a concentrated solution of amino acids (by ion-exchange column chromatography on Dowex- 50X8), and b) determination of Phe and Tyr concentrations in the solution of amino acids by HPLC (using a Dionex Ultimate 3000 instrument equipped with a diode array detector). The analytical column was a Thermo Scientific Acclaim 120, C18, 5 μm Analitic (4.6 x 250 mm), coupled with an Acclaim C18 guard column. The values of Phe and Tyr concentrations in plasma of several patients were calculated using a calibration curve made with standards of Phe (1834.4 μmol/L in deionized water) and Tyr (600 μmol/L in deionized water). Concentrations as low as 24 μmol/dL of Phe and 15 μmol/dL of Tyr could be determined. Conclusion. The whole procedure presented here is relatively simple, rather inexpensive, however very sensitive and accurate. Consequently, it is very adequate for confirming the diagnosis of PKU in patients with neonatal hyperphenylalaninemia, as well as for monitoring the plasma concentrations of Phe and Tyr in patients with PKU.

Context. Both human immunodeficiency virus (HIV) infection and hepatitis C virus (HCV) infection represent systemic diseases that may develop metabolic complications, thus HIV/HCV coinfection metabolic changes need to be depicted. Objective. We aimed to evaluate the body composition changes in patients with either HIV and HCV monoinfections or HIV/HCV coinfection. Methods. 123 young men divided into three groups: 41 with HIV/HCV coinfection, 42 with HIV-monoinfection, and 40 with HCV-monoinfection were evaluated for total and regional bone and soft tissue body composition assessments using a Dual-energy X-ray absorptiometry (DXA) and were compared with 40 healthy men with age and body mass index similar to the study groups. To detect sarcopenia, we calculated the appendicular limbs’ lean mass index (ALMI), for obesity, we used the percent of body fat, and for lipodystrophy, we calculated the trunk/limbs index. Results. HIV/HCV coinfection is associated with a significant higher bone demineralization in all regions of interest compared to HCV or HIV monoinfections and to controls. The prevalence of bone demineralization in HIV/ HCV patients was 31.7%, more frequently at lumbar spine. Fat mass and lean mass were significantly lower in HIV/ HCV-coinfected patients than in controls. Lipodystrophy was found in similar percentages in all three evaluated groups (80.4% in HIV/HCV, 92.5% in HIV, and 95% in the HCV group). Sarcopenia was higher in HIV/HCV group (43.9%) and important in HCV-monoinfection group (30%). Conclusions. HIV/HCV-coinfected patients had the highest prevalence of bone demineralization, fat mass, and lean mass loss, compared to controls and to HIV and HCV monoinfections.

Introduction. We aimed to investigate Cardiotrophin-1 (CT-1) levels along with other markers of cardiovascular disease and the association of androgen levels with these parameters in both lean and overweight or obese PCOS patients. Material and Methods. The study included 90 overweight or obese PCOS patients with metabolic syndrome (MS) and 80 lean PCOS patients without MS. The control group consisted of 140 healthy females. Anthropometric measurements, plasma glucose, insulin, lipid and hormone profile, homocysteine, hs-CRP, CT-1 levels and carotid-IMT were evaluated in all study subjects. Results. Fasting insulin, HOMA values were significantly higher in obese PCOS patients. Total testosteron levels were higher in both PCOS groups with respect to both controls. Serum homocysteine, hs-CRP, CT-1 and carotid- IMT values were significantly higher in both PCOS groups compared to controls (p=0.001, pCIMT: 0.005). CT-1 was positively correlated with insulin, HOMA, total testosterone, homocysteine, hs-CRP and carotid IMT. After multiple regression analysis, CT-1 was significantly positively correlated with total testosterone, hs-CRP and carotid IMT. Conclusions. CT-1 was associated with other cardiovascular risk markers and its use as a cardiovascular risk marker might be suggested. Cardiovascular risk was increased even in lean PCOS patients without MS and it might be associated with elevated androgen levels.

Context. Although, many studies have been made on the clinical course of autoimmune thyroiditis, this study focused on women and the factors effecting the natural course such as Selenium. Objective. The study aimed to determine Hashimoto’s thyroiditis (HT) clinical course in adults and the factors that could affect it. Design. The study was in a retrospective manner between 2010-2018. Subjects and Methods. 101 patients with HT were followed for 60.7±32.7 months. Biochemical and ultrasonographic data were collected. We investigated whether the age at diagnosis, family history, smoking habits, levothyroxine replacement therapy, and serum selenium (Se) levels influenced the disease course. Results. No relationship was observed between age and thyroid functions, thyroid volumes (TV), and autoantibody (Ab) levels at diagnosis. Ab levels were irrelevant with TV, echogenicity, and nodularity at diagnosis. However, initial TSH levels were significantly associated with anti-TPO levels (p=0.028, r=0.218). In the untreated group, thyroid functions seemed to be stable. TV decreased significantly in both treated and untreated patients (p<0.001). The decrease in TV was significantly higher in the treatment group (p=0.002). In euthyroid and subclinical hypothyroid patients, levothyroxine therapy did not affect the decrease in TV. Ab levels remained stable in untreated patients, but anti-TPO levels significantly decreased in treated patients (p<0.001). Smoking seemed to increase only anti-Tg levels (p=0.009). Family history was not associated with any of the studied parameters. Serum Se level was negatively correlated only with thyroid echostructure and only in treated patients. TV showed a “Gaussian distribution” in all patients at the diagnosis and at the end, independent of levothyroxine treatment. Conclusions. Most euthyroid patients remained euthyroid during five years of follow-up. The decrease in TV was significantly prominent with LT4 treatment. Importantly, TV followed a normal distribution instead of the bimodal distribution that is classically described.