ACTA ENDOCRINOLOGICA (BUC)

In the past years a high interest has been observed for understanding the early stages of type 1 diabetes. That interest has been stimulated by the failures of the various “preventive” approaches of the autoimmune mechanism operating in this phenotype, carried out in young diabetic patients, soon (several months) after the clinical onset of the disease. Unfortunately, the recent Statement of three scientific organisations from the USA proposed a reconsideration of the well-known classical stages, not going backward to know better the true early onset of the autoimmunity, but refining only the second part of the classical stages which are closer to the clinical onset of diabetes (when the β-cell mass/function is about 70% already irreversibly lost). In opposition with the above mentioned initiative, our effort has been devoted to the detection of earlier stages of diabetes which silently operate before the detection of the first islet autoantibodies (mainly proinsulin/insulin antibodies) which strangely was omitted in the new mentioned reclassification of preclinical stages of type 1 diabetes.

Context. Advanced skin cancers have high mortality and morbidity, and early detection is crucial for prognosis. Information regarding the patterns of skin self-examination and tumor early detection in the Central and Eastern Europe is scarce. Objective. Analyze the gender differences in the practices and attitudes related to skin cancer early detection of skin cancer patients in Romania. Methods. Prospective questionnaire- based survey of patients with confirmed diagnosis of skin cancer, registered in a university reference center for dermatooncology between 2011-2012. Results. 122 skin cancer patients completed the survey (response rate 72%). Female skin cancer patients reported lower level of education and likelihood to receive a medical full skin examination. Women were more likely to check their own skin and to detect suspicious lesions on themselves and their partners than men. They delayed longer the presentation to a physician after noticing a suspicious lesion (11.4 months vs. 6.4 months median). 90.76% of all skin cancer patients were not warned by any doctor about their skin cancer risk; 30% of them never check their skin. Conclusions. Women tend to be more concerned about their skin than men, but receive less medical attention and delay longer the diagnosis. Our study also signaled an urgent need of improving the patients and physicians education for skin cancer early detection in Romania.

This study evaluates the differences of radiotherapy in patients with pituitary tumors, in relation to gonadotropin immunoreactivit.\r\nDesign. It is a longitudinal, retrospective study of 117 patients submitted to pituitary surgery and high voltage radiotherapy. The excised tumors were 70 non-functioning adenomas (NFA) and 47 GH-secreting adenomas producing active acromegaly (ACM). They were evaluated before and after pituitary surgery, before radiotherapy as baseline, then at 3 different intervals at 0 - 2, 2 - 5 and > 5 years after baseline.\r\nMethods and patients. Computer tomography was used for measuring the tumor size and specific immunoassays were used for FSH, LH and nadir GH during 75 g oral glucose load. Immunohistochemistry (IHC) was performed with avidin-biotine method. High voltage conformational radiotherapy used a linear accelerator of 10 meV, with a 50 Gy on target tumor. For statistics, student&#8217; t test was used. Data before surgery (tumor volume and hormonal sexretion) were available in 70 unselected patients (31 NFA and 39 ACM from the above group). Postsurgery we defined following groups: NFA-A1 exposed to radiotherapy (n=21) and NFA-C1 unexposed to radiotherapy (n=22); ACM-A2 exposed to radiotherapy (n=20) and ACM-C2 unexposed to radiotherapy (n=10).\r\nResults. Immunohistochemistry for NFA showed 27 immunopositive for FSH or/and LH (GD+) and 40 immunonegative for FSH and LH (GD-), 3 undetermined, while for ACM were 12 GD+, 33 GD-, 2 undetermined. Immunohistochemistry data on defined groups was as follows: NFA-A1 (n=21: 12 GD+, 9 GD-) and NFA-C1 (n=22: 6 GD+, 16 GD-); ACM-A2 (n=20: 4 GD+, 16 GD-) and ACM-C2 (n=10: 3 GD+, 7 GD-). In patients with NFA presented before therapy, there are not significant differences of tumor sizes or of the levels of FSH/LH between GD+ and GD- adenomas. In ACM, before any therapy, the GD+ patients showed a significantly higher FSH levels (20.7+11.4 U/L, n=6) than GD- patients (FSH 6.6+1.6 U/L, n=22, p< 0.05) and a nonsignificant lower serum GH levels (15.1+3.5 ng/mL, n=8 versus 33.5+8.9 ng/mL, n=30 p=0.06), although the tumor size was similar between the two groups. Radiotherapy upon NFA: GD+ adenomas did not decrease their volume after radiotherapy (cranio-caudal diameter 1.63+0.79 cm, before and 1.54+0.68 cm at 2 - 5 years post-radiotherapy n=6, p= NS), in contrast with GD- tumors in which a slightly, but significant decrement in volume could be demonstrated (from 2.79+0.53 cm to 2.43+0.31 cm at 2 - 5 years, n=5, p= 0.01). Radiotherapy in ACM resulted in a decrement of serum GH level and tumor size, as compared with the control group without radiotherapy. The effect was maximal at the interval of 2-5 years. The ACM, GD- tend to respond better to radiotherapy, (i.e. GH levels decreased from 15.1+5.4 to 6.6+2.4 ng/ml at 2-5 years, p=0.05), while in patients with ACM, GD+ the GH level did not show a significant decrease (serum GH was 7.3+3.3 ng/ml before and 5.1+4 ng/mL at 2-5 years post-radiotherapy, p = NS). The CC diameter of GD- decreased from 1.1+0.3 to 0.7+0.2 at 2-5 years, p=.059, while in GD+: from 1.64+0.4 to 1.2+0.3 ng/mL at 2-5 years, p = NS.\r\nConclusion. Pituitary adenomas, both NFA and ACM that contain gonadotropin immunoreactive cells tend to be more radioresistant than those without gonadotroph cells.

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Objective. Type 2 diabetes mellitus (T2DM) is a major health problem worldwide. Earlier studies have reported that pancreatic fat content (PFC) and liver fat content (LFC) are risk factors for T2DM. The aim of the present study was to demonstrate the relationship between PFC, LFC and T2DM. Methods. A total of 70 T2DM subjects and 30 nondiabetic volunteers who underwent Dixon-based magnetic resonance imaging (MRI) method at Yixing People’s Hospital between December 2018 to December 2020 were included in the study. The three-point Dixon (3p-Dixon) method was used to measure the fat content in the pancreas and liver. Clinical indices including gender, age, body mass index (BMI), total cholesterol, triglyceride, glucose and C peptide levels were collected. The association between PFC, LFC, and OGTT-derived parameters was examined by Pearson and Spearman correlation analyses. Results. T2DM subjects had higher PFC and LFC than those measured in the non-diabetic subjects (p <0.05). PFC and LFC were associated positively with OGTT-derived parameters such as insulin secretion, insulin resistance, and early- and late-phase insulin secretion in the male T2DM subjects(p <0.05), but not in the non-diabetic and female T2DM subjects. The relationship between PFC and OGTTderived parameters was also more obvious than that for LFC in overweight and obese male patients with T2DM whose BMI was >24 kg/m2. Conclusion. PFC and LFC were both associated with β-cell dysfunction and insulin resistance in males with T2DM. The relationship between PFC and β-cell dysfunction and insulin resistance was more obvious than that observed for LFC in overweight and obese male T2DM patients. More attention should therefore be paid to PFC in clinical settings.

Context. Regulatory T cells (Tregs) have critical roles in preventing autoimmune diseases such as Hashimoto’s thyroiditis (HT). Forkhead box P3 (Foxp3), the master transcription factor of Tregs, plays a pivotal role in Treg function. Objective. Herein, we investigated the association of two single nucleotide polymorphisms (SNPs) of the Foxp3 gene with HT development. Methods and study design. A total of 129 HT patients and 127 healthy subjects were genotyped for rs3761548 (-3279 A/C) and rs3761549 (-2383 C/T) in the Foxp3 gene, using polymerase chain reaction-restriction fragment length polymorphism. Results. Genotypic and allelic distribution of rs3761548 SNP showed a significant association with HT. The CC genotype was observed in 37.2% of patients versus 22.1% of the controls [P<0.008, odds ratio (OR): 2.1; 95% confidence interval (CI): 1.2-3.6] and the AC genotype in 41.1% of patients compared to 54.3% of the controls (P<0.025, OR: 2.1; CI: 1.2-3.6). In addition, higher frequency of C allele in patients compared to controls (P=0.05, OR: 1.4; 95% CI: 0.9-2) suggested that patients with the CC genotype and C allele had increased susceptibility to HT. There were significantly higher serum levels of anti-thyroid peroxidase (ATPO) antibody in patients with the rs3761548 CC genotype (1156±163 IU/mL) compared to the other genotypes (≈582-656 IU/mL; P<0.004). We observed a greater frequency of the AC genotype in patients who had decreased ATPO antibody levels (P=0.02). Conclusions. The association of the rs3761548 SNP with risk of HT and its influence on ATPO antibody levels suggested an important role for Foxp3 in the biology and pathogenesis of HT.

Aim: We aimed to assess the final outcome of combined therapeutic approaches in patients with macroprolactinomas that were resistant to dopamine agonists (DA).\r\nPatients: Records of patients with macroprolactinoma hospitalized in the Institute of Endocrinology, Bucharest, between 1978-2005, were reviewed. There were 29 eligible patients resistant to DA therapy (8 men and 21 women), out of 119 patients with macroprolactinomas (24.4%); age at diagnosis of the resistant patients ranged between 16-59 years (31.9 ? 2.4 years), with mean prolactin (PRL) levels 2,110.2 ? 656.6 ng/mL (range 42-16,000 ng/mL). The mean maximal tumor diameter was 2.7 ? 0.2 cm (range 1-6.8 cm).\r\nMethods: Rapid fluoroimmunoassay using Europium was used for hormonal levels; computed tomography imaging and/or MRI were used to assess tumor size. Study design: The resistance to DA drugs was evaluated using initial criteria: the lack of prolactinoma response to current daily dose of Bromocriptine (BRC) 7.5 mg/day or to Cabergoline (CAB) up to 2 mg/week for at least 6 months (step 1) or final criteria: the lack of response to high BRC doses (30 mg/day) or CAB doses between 2.5-4 mg/week for at least 6 months (step 2). The lack of response was considered if PRL levels remained above the upper normal limit (20 ng/mL) and the tumor mass size decreased by less than 50%. All resistant cases at step 1 received thereafter maximal medical therapy with DA drugs, according to step 2. Thereafter, resistant macroprolactinomas after step 2 were submitted to step 3 - high voltage radiotherapy ? surgery. Serum PRL levels and tumor size were finally evaluated 110 ? 26.5 months later (range: 6-381).\r\nResults: Outcome of medical therapy with DA (n=29): Overall, 7 out of 29 resistant macroprolactinomas (24.1%) were successfully treated by increasing BRC dose (n=5) or changing BRC to CAB (n=2). But 22/119 (18.5%) patients remained resistant to DA drugs independent of dose, duration or type of drug used. 14 patients failed to normalize PRL levels despite CAB treatment in doses up to 7 mg/week. Outcome of radiotherapy alone or combined with surgery (n=15): PRL normalization was achieved in 4 patients out of the only 7 assessed at least at 18 months after radiotherapy. Withdrawal of DA therapy revealed 2 cured cases, both after radiotherapy and surgery. Outcome of surgery: Only one patient normalized PRL levels after surgery, but she soon relapsed. Apparently, only one case of acquired resistance to DA drugs was revealed. We found that 15.1% (18/119) of the patients with macroprolactinoma did not finally normalize their serum PRL even after combined therapy approaches (DA + radiotherapy ? surgery), after 79 ? 17.4 months (range 6 to 206 months) treatment total duration and 45.4 ? 19 months (range 3 to 206 months) after radical therapies, respectively.\r\nConclusion: In summary, the resistance was successfully treated in 38% cases (11 out of 29).

Objective. Although bariatric surgery including gastrectomy has recently emerged as a useful treatment for type 2 DM with obesity, it is not clear whether gastrectomy itself can have beneficial effects on glucose metabolism. Therefore, in this study, we investigated changes in blood glucose in patients with and without diabetes who underwent gastrectomy. Methods. From Jan 2010 to May 2014, 77 patients with diabetes and 77 patients without diabetes who underwent gastrectomy at Chonbuk National University Hospital, South Korea, were included. We compared fasting plasma glucose levels and HbA1c value before and after gastric surgery. Results. After gastrectomy, 59 patients (38.3%) showed reduced fasting plasma glucose levels at the 1 year point, and 80 patients (51.9%) exhibited reduced fasting plasma glucose at 3 years, irrespective of their diabetes status. Among 77 patients with diabetes, decreased fasting plasma glucose was observed in 22 (28.6%) and 46 patients (59.7%) 1 and 3 years after gastrectomy, respectively. In patients who exhibited reduced fasting plasma glucose after gastrectomy, the degree of reduced glucose was as follows: 56.4±48.5 vs 23.2±16.1 mg/dL after 1 year, 58.3±52.3 vs 18.4±13.7 mg/dL after 3 years, in DM and non-DM patient respectively. Conclusions. Although there was a significant drop in mean fasting glucose after gastrectomy, not all patients experienced a drop in fasting glucose. Gastrectomy did not show a consistent association with glucose reduction in patients with and without diabetes, and in about half of the patients, fasting plasma glucose levels increased after gastrectomy. Therefore, bariatric surgery including gastrectomy needs to be performed with care in diabetes, and glucose monitoring including oral glucose tolerance tests should be done for assessing or prediction of the glucose state after gastric surgery in non-DM patients.

The aim of this study is to analyze and identify the main predictors that may indicate multifocal growth of PTC. Materials and methods. The main and control groups included patients with the category of malignant multifocal process T1-3mN0Mx (n=109) and unifocal T1- T3N0Mx (n=50) respectively, who underwent thyroidectomy with lymphadenectomy. Ultrasound characteristics of the nodes, tissue changes of the thyroid gland were taken into account. Results. Fibrous changes can be considered as one of the risk factors of the presence of additional PTC lesion. Discussion. There is no unambiguity in the definition of predictors of multifocal PTC growth. Conclusions. No clear predictors of multifocal PTC have been identified. It is advisable to improve the quality of ultrasound, to focus on single-focus PTC in patients with fibrinous changes in the thyroid gland at normal levels of TSH.

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