ACTA ENDOCRINOLOGICA (BUC)

Context. Immunoassays are vulnerable to occasional analytical errors despite their sensitivity and specificity. Adrenocorticotropic hormone (ACTH) is among hormones which are vulnerable to assay interference. Objective. In this case report, we aimed to present a case of ACTH interference in a patient with subclinical hypercortisolism. Case report. We present a case of subclinical hypercortisolism with unexpectedly elevated levels of ACTH in whom interference was shown by different biochemical methods. It is important for the clinician to keep in mind the possibility of interference when clinical and laboratory results are discordant. The communication between the clinician and laboratory staff is important while interpreting results. This case report shows that ACTH interference should be considered in patients with subclinical hypercortisolism who have unexpectedly high levels of adrenocorticotropic hormone.

Context. Propylthiouracil (PTU) could cause lupus or vasculitis-like hypersensitivities thus interfering with some other concomitant diseases. Objective. Clinicians must be aware of the side effects of medications, particularly after their introduction and long-term use. Some clinical manifestations may be similar to well-known drug side effects or hypersensitivity. Every unusual clinical scenario related to drug use must be evaluated individually and thoroughly. Subjects and Methods. Hands and feet skin changes were observed several days after PTU administration in a male patient with severe diffuse toxic goitre. A complete blood count, biochemistry analyses, thyroid function tests and antibodies, and immunology analyses were performed. Results. As the skin changes were distributed regionally, liver function tests were normal, and there were no signs of clinical deterioration, it was decided to continue PTU treatment and monitor the patient. The initial maculopapular rash quickly turned vesicular, then scaly. After two weeks, the skin changes were wholly restored, with no scarring. Hand, Foot, and Mouth disease (HFMD) was diagnosed after a thorough epidemiological survey and clinical workout. Conclusions. Our case study demonstrates that skin changes associated with HFMD may resemble those associated with PTU-induced vasculitis.

Background. Polycystic ovarian syndrome (PCOS) involves various changes within folliculogenesis. Aside from its systemic action, metformin seems to exert a local direct effect independent of insulinemia. The IGF system appears to be an important local target for metformin although the evidence we possess is circumstantial. Objective. The aim of this study was to evaluate the impact of metformin on insulin growth factor (IGF) system proteins and steroids production in PCOS patients and to analyze potential involvement in oocyte quality. Material and methods. This prospective study was performed on 86 in vitro fertilization (IVF) patients who were categorized into three groups as follows: Group 1 formed of PCOS patients who received metformin (n=27); Group 2 with PCOS patients who did not receive metformin (n=29) and Group 3 with controls (n=30). Interventions. Interventions included controlled ovarian stimulation for IVF and metformin (at least 16 weeks prior to the time of ovarian puncture). Main Outcome Measures.Follicular fluid analysis was performed using radioimmunoassay with specific kits (estradiol, testosterone, progesterone, IGF I, IGF II, IGF binding protein 1 - IGFBP1, IGFBP2, IGFBP3, IGFBP4). Results. Important differences were measured for the three types of steroids among the three studied groups (PCOS treated, PCOS not treated, controls) estradiol (538 vs. 466 vs. 688 ng/mL p < 0.0001), testosterone (6.7 vs. 7.6 vs. 5.1 ng/mL p<0.01), progesterone (8899 vs. 7878 vs. 9755 pg/mL p<0.0001) while for IGF system proteins important differences were noted only regarding IGFBP1 (114 vs. 107 vs. 121 p<0.002) IGFBP2 (263 vs. 268 vs. 252 ng/mL p<0.04), and IGFBP4 (128 vs. 138 vs. 118 p<0001). Correlations were also established between fertilization rate and estradiol (R: 0.53 p<0.5), testosterone (R: -0.39 p<0.05), IGFBP1 (R: 0.48 p< 0.05), IGFBP4 (R: 0.39, p<0.05). Conclusions. Patients with PCOS and hyperinsulinemia have the greatest benefit from metformin treatment. However, metformin action surpasses correction of systemic differences having a direct action at the level of follicular structures. Alteration of IGF system proteins does not concern only hyperinsulinic patients and can be partially amended by metformin administration.

Previous studies have correlated the expression of PAR proteins with breast cancer invasiveness. The scope of this study was to evaluate the expression of PAR-1 in human breast cancer specimens and investigate possible correlations with tumor size, grade and lymph node status, as well as covariations with estrogen and progesterone receptors, c-erbB-2 protein and lysosomal protease Cathepsin D. Formalin-fixed paraffin-embedded sections of 75 mastectomy specimens deriving from patients with primary breast carcinomas were implemented. Expression of PAR-1 was detected employing immunohistochemical assays utilizing a goat polyclonal PAR-1 antibody. The granular pattern of cytoplasmic immunoreaction was considered indicative for the protein?s expression. Statistical assessment was performed using SPSS 13.0 statistical package, Pearson?s correlation, &#967;2 and Fisher?s exact test. Expression of PAR-1 protein had a statistically significant correlation (p<0.001) with tumor grade, while in invasive tumors a similar relationship (p<0.001) was documented between PAR-1 expression and presence of positive axillary lymph nodes. However, PAR-1 expression did not exhibit a significant correlation with tumor size or with the expression of ER, PR, c-erbB-2, or Cathepsin D molecules. PAR-1 possesses a role in tumor invasion and contributes to the metastatic potential of certain types of breast carcinomas. The disassociation between expression of PAR-1 and that of the ER, PR, c-erbB-2, or Cathepsin D might imply participation in alternative pathways of malignant transformation and tumor progression.

experience regarding the first 24 patients diagnosed with refractory secondary and/ or tertiary hyperparathyroidism (HPT) who underwent subtotal parathyroidectomy (sPTx) in our clinic between 2010 and 2012. Methods. Data were retrospectively retrieved from a prospectively maintained database. We included patients diagnosed with refractory secondary and/or tertiary HPT who underwent sPTx; we excluded patients who underwent total parathyroidectomy (tPTx) and patients followed-up for less than six months. Results. We analyzed 24 patients,16 women (66.7%) and 8 men (33.3%) who were evaluated in a prospective manner in a short (1-6 months)/ medium (6-18 months) term follow up. Preoperative intact parathyroid hormone level (iPTH) was characterized by a median of 2131 pg/ mL (range: 1141-10000); in the first month after surgery the median iPTH level was 28 pg/mL (range: 3-1263). We found a statistically significant difference (p<0.01: Student test) in calcium level between preoperative values and values in the first month after surgery. Postoperative serum phosphorus (nv: 2.7-4.5 mg/dL) normalized in 19 patients (79.16%) and serum alkaline phosphatase values decreased significantly in the interval 2-6 months postoperative versus preoperative levels (p-0.002). We tried to establish a correlation between preoperative alkaline phosphatase (Alk Phos) and postoperative calcium level in the first month postoperatively. The overall clinical response to sPtx was good and we did not encounter postoperative mortality in our series. Conclusion. We believe that subtotal parathyroidectomy is feasible, safe and effective for patients with refractory secondary and tertiary hyperparathyroidism.

Objectives. Maternal antibodies in cases of chronic autoimmune thyroiditis may be transferred to the baby via the transplacental route, leading to transient hyperthyroidism or hypothyroidism. The development of hyperthyroidism in one sibling and hypothyroidism in the other, however, is an extremely rare condition. We present two siblings, one with transient neonatal hyperthyroidism and the other with transient neonatal hypothyroidism, born to a euthyroid mother who was being treated for Hashimoto's thyroiditis. Case Presentation. Case 1: A term male baby was evaluated due to tachycardia, high fT4 and low TSH. Following a diagnosis of Neonatal thyrotoxicosis, the patient was started on methimazole and propranolol treatments. The doses were gradually reduced and methimazole was stopped in the 5th month of treatment. Case 2: A male baby was referred with elevated TSH identified in the neonatal screening program, with TSH >100 mIU/L and fT4 7.5 pmol/l (N: 12-22) found in a venous blood sample. The patient was started on 50 μg/day LT4, which was gradually decreased and stopped when the baby was 5.5 months old. Conclusion. It should be kept in mind that antibodies may change character in mothers with autoimmune thyroiditis, and may cause different clinical pictures in babies in different pregnancies.

Introduction. Disorders of sexual development can present isolated or as a part of complex genetic syndromes. Case presentation. A newborn with ambiguous genitalia and prenatally diagnosed brain malformations was referred to our hospital. Prenatal ultrasound examination and MRI showed lissencephaly and absence of the corpus callosum. At admission, physical examination revealed microphallus, hypospadia and complete fusion of labioscrotal folds with nonpalpable gonads, normal blood pressure and serum biochemistry. Cortisol level was normal (201 nmol/L), testosterone elevated (14.4 nmol/L), FSH 0.1 IU/L, LH 0.7 IU/L, estradiol 241 pmol/L. Seizures were noted on the 2nd day and the child was started on anticonvulsives. When 17-OHP level results came back elevated (200 nmol/L), ACTH test was performed and the child was started on hydrocortisone and fludrocortisone treatment. Congenital adrenal hyperplasia became unlikely when karyotype result showed normal male karyotype (46, XY, SRY+) with no Mullerian structures seen on ultrasonographic exam. As association of ambiguous genitalia and lissencephaly strongly suggested a mutual genetic background, diagnosis of X-linked lissencephaly with ambiguous genitalia (X-LAG) became apparent. Conclusions. The presented case highlights the importance of looking at the whole clinical picture instead of separate isolated findings with emphasis on patient-centered approach guided by clinical findings and patient history.

Aim. The epidemic of metabolic syndrome increases worldwide and correlates with elevation in serum uric acid and marked increase in total fructose intake. Fructose raises uric acid and the latter inhibits nitric oxide bioavailability. We\r\nhypothesized that fructose-induced hyperuricemia may have a pathogenic role in metabolic syndrome and treatment of\r\nhyperuricemia or increased nitric oxide may improve it.\r\nMethods. Two experiments were performed. Male Sprague-Dawley rats were fed a control diet or a high fructose diet to\r\ninduce metabolic syndrome. The latter received either sodium nitrate or allopurinol for 10 weeks starting with the 1st day of fructose to evaluate the preventive role of the drugs or after 4 weeks to evaluate their therapeutic role.\r\nResults. A high-fructose diet was associated with hyperuricemia, hypertension, dyslipidemia, insulin resistance, decreased tissue nitrite and increased adiposity index. Sodium nitrate or allopurinol was able to reverse these features in the preventive study better than the therapeutic study.\r\nConclusion. Fructose may have a major role in the epidemic of metabolic syndrome and obesity due to its ability to raise uric acid. Either sodium nitrate or allopurinol can\r\nprevent this pathological condition by different mechanisms of action.

Background. Thyroid hormone resistance (RTH) is defined as a decrease in response to thyroid hormones in the target tissue. Most patients present with nonspecific findings. In this article, we aimed to represent a 22-yearold female patient who presented with palpitation, fatigue, and heat intolerance. She was thought to have thyroid hormone resistance and her genetic examination revealed NM_001128177.1 (THRβ): c.1034G > A (p.Gly345Asp) pathogenic variation in the THRβ gene. Case report. A 22-year-old female patient presented with complaints of fatigue, heat intolerance and palpitations. She was taking Propranolol twice daily at admission. Her family history revealed hypothyroidism in her grandmother. Her physical examination results were as follows: height 160 cm, weight 65 kg, body mass index 25.4kg/m2, body temperature 36.5˚C, respiratory rate 18/min, heart rate 86 beats/min, blood pressure 120/80 mmHg. Her palms were sweaty. The heart sounds were normal, and no heart murmur was auscultated. The laboratory results were TSH: 5.31uU/mL, fT3: 6.83 pg/mL, and fT4: 2.43 ng/dL. THRβ gene mutation analysis was requested for our patient whose clinical history and laboratory results were compatible with thyroid hormone resistance. The pathogenic variation NM_001128177.1(THRβ):c.1034G>A (p.Gly345Asp) was detected after analysis. Conclusion. A diagnosis of RTH requires high clinical suspicion and a genetic mutation analysis should be requested in the case of clinical suspicion. In this way, unnecessary anti-thyroid treatment can be prevented.

Context. Pancreatic neuroendocrine tumours (PanNETs) are rare pancreatic neoplasms. PanNETs can be treated by multimodal approach including surgery, locoregional and systemic therapy. Objective. The aim of the present study is to evaluate predictive factors of overall survival in patients with PanNETs surgically treated at a single center. Subjects and methods. The study group consisted of 120 patients with PanNETs who had undergone surgery at the Center of Digestive Diseases and Liver Transplantation of Fundeni Clinical Institute, Bucharest, Romania. Surgical resection of the primary tumor was performed in 110 patients. Results. Tumor size > 2 cm (p=0.048) (90% CI) lymph node involvement (p=0.048), ENET grade (p<0.001), distant metastases (p<0.001), Ki 67 index (<2%, 2-5%, 5-10%, 10-20%, >20%) (p<0.001) were identified as significant prognostic factors for OS on univariate analysis. Using multivariate Cox proportional regression model we found that distant metastases and Ki 67 index were independent risk factors for the survival outcome. Conclusions. Surgery with curative intent should be considered in all cases if clinically appropriate and technically feasible. High grade (Ki67 index ≥10%) tumours were associated with a 2- fold increase in risk of death as compared to those with a Ki67 <10%