ACTA ENDOCRINOLOGICA (BUC)

Background Supplementation of Lcarnitine is associated with improvement in some abnormalities present in hemodialysis (HD) patients. Objective. The study aim was to analyze the effect of oral L-carnitine supplementation on endothelial dysfunction (ED), oxidative stress (OS), inflammation and anemia in HD patients. Design. A prospective, longitudinal and observational study was performed in a single dialysis unit. Subjects and methods.We studied 31 HD patients: 21 patients formed the Lcarnitine supplementation group (group 1) and 10 entered the control group (group 2). At baseline and after 3 months of L-carnitine supplementation (500mg/day) we determined endothelial-dependent flow-mediated vasodilatation (FMD) and nitroglycerin induced endothelium independent vasodilatation, involving ultrasonographic brachial artery measurements, serum visfatin, malondialdehyde, body mass index, systolic blood pressure, diastolic blood pressure, interdialytic body weight gain, C-reactive protein, albumin, cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, ferritin, transferrin saturation, hemoglobin, erythropoietin dose, calcium (Ca), phosphorus (P), parathormone and Kt/V . Results. In group 1, FMD (8.9 (4.5-12.5) to 10.6 (6.7-18), p=0.04) and Ca (8.4±0.6 to 8.8±0.5 mg/dL, p<0.001) significantly increased after L-carnitine supplementation, while visfatin (1.0 (0.2-1.3) to 0.4 (0-0.9) pg/mL, p=0.03), malondialdehyde (2.8 (2.4- 3.2) to 1.3 (1.2-1.5) nmol/mL, p<0.001) and P (5.6±1.3 to 5.0±1.2 mg/dL, p=0.005) significantly decreased. Albumin increased significantly in both groups (3.9±0.3 to 4.2±0.3 mg/dL, p<0.001 in group 1 and 3.7±0.3 to 4.0±0.3 mg/dL, p=0.02 in group 2). There were no other significant variations of the studied parameters. Conclusions. L-carnitine supplementation reduces ED, visfatin levels and markers of OS, but has no effect on inflammation, nutrition and anemia in HD patients.

Aims. Earlier studies suggested that patients with nonfunctioning pituitary adenoma (NFPA) experience premature mortality, mostly from vascular diseases. The present study aims to identify risk factors associated with mortality in patients with NFPA. Methods. All consecutive patients admitted to a tertiary neuroendocrinology center for pituitary adenoma during 2001-2010 were screened. Only those with a final diagnostic of NFPA were retained. All 196 NFPA subjects (57.7% males, mean age 52.7±0.9 years) were followed-up for allcause mortality until December 31, 2011 (1298 person-years of follow-up). PAMCOMP software was used to calculate standardized mortality ratio (SMR), using the corresponding general population as reference. Cox regression analysis evaluated the independent hazards for mortality. Results. There were 26 deaths among 196 patients as compared to 20 expected. Standard Mortality Ratio (SMR) was 1.2 (95% Confidence interval (CI) 0.83-1.86). Females had a doubled mortality ratio: SMR 2.03 (95%CI 1.01-3.64), but males had a mortality ratio similar with general population: SMR 0.87 (95%CI 0.48-1.44). More patients with hypopituitarism for at least one axis deceased (22/156, 14.10%), as compared with patients without pituitary failure (1/22 patient deceased –2.07%), p=0.03. Prednison replacement for corticotrophin insufficiency (HR 1.46 (95%CI 1.12-1.90)) was correlated to mortality in females, but not in males, and mortality rose progressively with prednison dose (log rank: p=0.01). In males, last known maximal pituitary tumour diameter (HR 1.04 (95%CI 1.001-1.08) and age at baseline (HR 1.1 (95%CI 1.05-1.1) were modestly related to mortality. Conclusions. Females with nonfunctioning pituitary adenomas and hypopituitarism had a reduced life expectancy as compared with general population, possibly related to glucocorticoid substitution or a more severe pituitary insufficiency.

Calciphylaxis, also known as calcific uremic arteriolopathy (CUA), is usually observed in women and it is a serious complication of hyperparathyroidism secondary to chronic renal failure. CUA is characterized by ischemic tissue loss secondary to progressive vascular degeneration. Although it is rare, it may end up with sepsis and organ failure and can be fatal. Its pathogenesis is not fully understood, but it is thought that it occurs secondary to increased calcification activators such as oxidized LDL, TNF- α, calcitriol, fibronectin, collagen-I, and TGF-1α. The most effective treatment is managing underlying pathology and decreasing serum calcium and phosphorus levels. In this report, we aimed to present an end stage renal failure case with coexisting hyperparathyroidism, hyperthyroidism and calciphylaxis in whom cutaneous manifestations were healed 6 months after parathyroidectomy.

Context. With the widespread use of neck ultrasound, parathyroid incidentaloma (PI) emerges as an additional opportunity for incidental detection of primary hyperparathyroidism (PHPT). Objective and design. This study aimed to investigate PHPT cases detected by PI and to compare them with other PHPT patients. A retrospective analysis of newly diagnosed PHPT patients between 2014 and 2020 was conducted in our hospital. Subjects and methods. The cohort of 124 subjects was divided in two groups: 22 (17.7%) PHPT patients detected by PI (PI PHPT group) and the rest of 102 PHPT patients (non-PI PHPT group). Overall, 21 PIs were discovered on ultrasound and one was found during thyroid surgery. Clinical features, work-up and management of two study groups were compared. Results. The PI PHPT group had lower ionized calcium at diagnosis (p=0.034), lower peak serum calcium during follow-up (p<0.01), less fractures (p=0.022) and was less likely to meet the international criteria for parathyroidectomy (p<0.01). Positive sestamibi scan (p=0.022) and confirmed concordant localization in at least two different parathyroid imaging techniques (p=0.033) were more likely in the PI PHPT group. The frequency of surgical management did not differ between groups. Conclusions. PHPT detected by PI is clinically relevant and mostly comparable to PHPT in other patients with some features that correspond more often to a mild disease. Higher rate of positive preoperative localization in PHPT detected by PI might encourage parathyroidectomy even without the international criteria met.

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.

Background. Growth hormone (GH) therapy is widely used for pediatric growth disorders, with short-acting (Saizen) and long-acting (Jintropin) formulations available. This study assesses height, weight, and bone age outcomes in children treated with Jintropin, Saizen, or a combination of both. Methods. This retrospective cohort study (N=108) compared Jintropin (n=31), Saizen (n=50), and Combination Therapy (n=27). To control for baseline heterogeneity (age, puberty) and repeated measures, analyses used ANCOVA and LMM. Post-hoc comparisons used Bonferroni correction. Safety was evaluated by ΔBA/ΔCA ratio. Results. Following multivariable LMM adjustment, the estimated marginal means for annualized GV were 9.30 cm/year (95% CI: 8.46–10.15) for Jintropin, 8.55 cm/year (95% CI: 7.90–9.20) for Saizen, and 9.56 cm/year (95% CI: 8.77–10.34) for Combination Therapy. Adjusted pairwise comparisons showed no significant efficacy differences between groups (Jintropin vs. Saizen: p=0.501; Combination vs. Saizen: p=0.160). Skeletal safety was confirmed across cohorts (ΔBA/ΔCA: 0.34, 0.46, 0.68), indicating no premature epiphyseal fusion. Conclusion. Long-acting Jintropin monotherapy provides growth outcomes comparable and non-inferior to daily Saizen, offering a convenient, effective alternative that reduces injection burden. The non-standard combination of long- and short-acting GH showed no statistically superior benefits, suggesting such complex regimens are unnecessary in clinical practice.

Background. Idiopathic hypercalciuria is a risk factor for nephrolithiasis. Both renal stones and hypercalciuria are associated with lower bone mineral density (BMD), but the relationship between these modifications is not completely understood. Aims. To evaluate some metabolic particularities possibly related to relapsing nephrolithiasis (RN) in young male patients. Methods. We performed a crosssectional study including a group of 30 young male patients with RN and a group of 30 healthy, age and BMI (body mass index) matched controls (CTR). We evaluated calcium and phosphate metabolism, bone remodeling markers alkaline phosphatase (AP) and osteocalcin in serum and 24-hour urine samples, and lumbar and hip BMD. Results. We observed higher values of serum calcium (P<0.05) and 24 hour urinary calcium (P<0.001) in the RN group. Parathyroid hormone (PTH) and AP were also higher in the RN group (P<0.01), whereas serum 25OH-D3 was lower (P<0.01). BMD, T and Z scores were lower in the RN group in both the lumbar (P<0.01) and hip (P<0.05) regions. Conclusions. Young male patients with hypercalciuric RN have lower BMD and higher bone turnover. Higher PTH levels related to vitamin D deficiency may contribute to bone demineralization in certain cases.

Objective. Highly active antiretroviral therapy (HAART) is involved in the potential pathogenic mechanisms linking thyroid autoimmunity with immune restoration. The objective is to emphasize the emergence of autoimmune thyroid disease in a HIV patient long period after restoration of immune competence, unlinked to the immune reconstitution inflammatory syndrome (IRIS) occurring shortly after HAART initiation. We report a case of acute autoimmune thyroiditis with thyrotoxicosis in a patient with stage C3 HIV infection, who had been under HAART for more than 7 years. From the beginning there was a good immune response to the regimen, due to a good adherence and compliance (over 90%). Nine months after HAART initiation the viral load was undetectable (under 34 copies/μL) and the CD4 count reached 645 cells/mm3 (within normal range) after one year of treatment. Eight years after HAART initiation, based on clinical and laboratory findings, autoimmune thyroiditis was diagnosed. At this time immune competence with a normal CD4 count and a CD4/CD8 ratio over 1 was achieved. The chronic inflammation status of an HIV infection is the reason that autoimmunity appears outside the IRIS period. Treatment was initiated with antithyroid drugs. Thyroid function should be monitored periodically in HIV patients undergoing HAART. Future observations must be made for HIV related thyroid disorders using new classifications and studies with a larger number of patients.

Background: The solitary benign thyroid nodules represent one of the most common\r\nabnormalities affecting the thyroid gland. The appearance of solitary thyroid nodules is\r\nvariable and all the patients should be assessed as soon as possible in order to establish the\r\nbenign nature of the lesion and to rule-out malignancy.\r\nThe aim of the present study is to show the histological changes that appear during\r\nevolution of benign solitary thyroid nodules and rapid growing rate along 6 years, in 71\r\npatients (65 women and 6 men).\r\nMethods: All cases were evaluated by clinical, ultrasound, biochemical (at every 6\r\nmonths) and FNA (initially and repeated between 10 months and 4 years afterwards); 26 out\r\nof 71 presented, along evolution, an increase of thyroid nodule (24 women and 2 men) from\r\n1.77 cm diameter (1.4-2 cm) to more than 2.5 cm (2.5-4.3 cm), therefore a radical surgical\r\nattitude was performed.\r\nResults: Histological postsurgery data showed degenerative changes in all cases, with\r\nrepetitive nodular hemorrhage (26 cases), sclerohyalinisation of the interfollicular stroma (4\r\ncases), cholesteatoma (5 cases) and inflammatory infiltrate (8 cases).\r\nIn conclusion, the significant growth of a benign solitary nodule is determined by\r\nrepetitive hemorrhages in the thyroid tissue. The associated sclerosis induces changes in the\r\nnodular firmness and might trigger the thyroid surgery.

Abstract Objective. The aim of the present study is to evaluate the effects of methimazole (MTZ) and propylthiouracil (PTU) treatments on osteopontin (OPN) and oxidative stress in Graves’ disease (GD). Material and Methods. The study included 60 cases with GD in hyperthyroid state and taking no antithyroid treatment, and 30 healthy volunteers. GD patients were randomly separated into two groups; 30 of them took PTU, and the other 30 took MTZ treatments. Blood samples were taken from the patients with GD before the treatment, and three months after the treatment was begun, when they were in the euthyroid state; blood samples of the healthy control subjects were also taken at these times. Results. TAS and OSI levels before treatment were significantly higher in the GD group, when compared to the control group (p<0.001, for each). GD subjects taking PTU treatment had significantly higher TAS levels (p=0.001), and significantly lower TOS and OSI levels (p=0.008 and p=0.001, respectively). TAS levels significantly decreased in the patients taking MTZ treatment (p=0.029), but TOS and OSI levels did not change significantly (p>0.05). Pretreatment OPN levels were significantly higher in GD patients, when compared to the control group (p=0.014). OPN level significantly decreased in the GD group taking PTU treatment; however OPN levels in the group taking MTZ treatment did not change significantly when compared to the pretreatment value. Conclusion. PTU treatment is more effective in decreasing OPN and oxidative stress in GD patients, when compared to the MTZ treatment.