ACTA ENDOCRINOLOGICA (BUC)

We present a 18 year old phenotypic female patient who presented for primary amenorrhea. Pelvic ultrasound revealed a hypoplastic uterus and CT scan showed a hypoplastic right gonad and a left gonadal tumor with extrapelvic location. Karyotype was 46XY. Hormonal assessment indicated hypergonadotropic hypogonadism: FSH was 39.69 mUI/ml, estradiol was 28.07 pg/ml, testosterone was 0.17 ng/ml. DHEA level was high – 21 ng/ml. Gonadectomy was performed at 15 years and histologic examination diagnosed left gonadoblastoma and right teratoma in a dysgenetic gonad. The patient had a good postoperatory evolution. Menses were induced with estrogenic and then estroprogestogenic treatment. Plastic breast surgery was performed at 18 years. Establishing the genotypic sex in patients with primary amenorrhea represents a crucial step knowing that intersex disorders bearing Y chromosomal material have a high risk for gonadoblastoma and germ cell tumors.

Based on epidemiological, clinic, biochemical and hormonal data (both personal and\r\ninternational), our personal view is that natural history of autoimmune type 1 diabetes could\r\ninclude the following stages: 1) The presence of a complex genetic predisposition towards ?\r\ncell autoimmunity (possibly “latent” until death); 2) The “initiation” of autoimmunity in\r\nsubjects carrying a defect in the post-translational processing of pre-proinsulin/ proinsulin/\r\ninsulin, manifested precociously as increased proinsulin-to-insulin ratio; 3) Stimulation by the\r\nincreased proinsulin of the plasmacytoid dendritic cell clones capable to capture the natural\r\nantigens (proinsulin/insulin, Glutamic Acid Decarboxylase, etc.) from the pancreatic beta\r\ncells; 4) Activation of the process generating reactive T cell clones (Teffs) in the detriment of\r\nprotective immuno-regulatory T cell clones (Tregs), triggering the anti-beta cell attack,\r\nexpressed as autoimmune insulitis and/or the presence of circulating anti beta cell antibodies;\r\n5) The onset of the beta cell apoptosis process mediated by pro-inflammatory cytokines (IFN\r\n?, TNF ?, IL6) or by the direct contact between Teffs and the beta cells; 6) Identification of\r\nthe first secretory beta cell defects (the loss of the first phase insulin response followed by the\r\nprogressive decrease of the area under the insulin curve and the progressive increase of the\r\narea under the blood glucose curve) while fasting glycemia is still normal; 7) The progressive\r\nloss of the beta cell mass. All these processes take place during the pre-hyperglycemic stage\r\nof diabetes, with a higher or lower speed depending on the genetic background. The overt\r\nclinical stage of diabetes, marked by the presence of hyperglycemia, occurs rather late, when\r\nmore than 90% of the beta cell function/mass is irreversibly lost.

Context. Despite CT being generally used in thymic pathology, in the case of regions with the same tissue density, only functional radioisotopic imaging can hint towards malignity. Objectives. To assess the usefulness of 99mTc MIBI scintigraphy for diagnosis and treatment planning in thymoma, in relation with the radiotracer uptake mechanism. Patients and methods. 99mTc MIBI thymic scans for 19 patients diagnosed with thymic disorders were assessed using tumor uptake ratio (UR). Specimens of thymectomies were examined and cytological assessments were correlated with the UR. Results. The UR of all surgical patients was higher than 1.2, with a 1.5 cutoff between lymphoid hyperplasia and thymoma. The UR values were correlated with the histopathologic diagnosis (Pearson correlation 0.91, significant at p<0.01). The highest UR was 3.24, found in the case of an AB thymoma where the rate lymphocytes/ epithelial cells (L/E) was 1.6. In B1 thymoma UR was 1.14 and L/E was 2.46. Conclusion. Phenotype differences between thymoma types correlate with 99mTc MIBI cellular uptake: lower rate L/E corresponds to higher UR, higher malignity potential and invasiveness. A thymic 99mTc MIBI UR higher than 1.5, corresponding to a CT tumoral image, is suggestive for a thymoma, requiring surgical treatment first.

Context and objective. The new insights in the pathogenesis of osteoarthritis (OA) reveal the implications of adipocytokines. This study aims to analyze the correlations between the serum value of adiponectin and the clinical rehabilitation effects in patients diagnosed with knee OA, admitted and treated in the complex balneal resort of Techirghiol lake. Subjects and methods. The prospective randomized clinical study included 23 patients in the study group, diagnosed with knee OA according to ACR criteria, and a matching control group of 23 subjects. Serum level of adiponectin (using ELISA technique), uric acid, triglycerides, cholesterol, HDLcholesterol and clinical response using a visual analog scale (VAS) were evaluated in all patients on their admission day and after 10 days of balneal treatment. Control group benefited from the same procedures except for cold mud therapy and mineral water baths. Results. Plasma adiponectin levels (23.73±6.44 ng/dL) were statistically higher (p<0.05) in the study group compared to the control group (18.15±6.49 ng/dL). The mean VAS in both groups was decreased (p<0.005) compared to the initial moment. Conclusions. Cold peloidotherapy combined with physical therapy and balneal factors induces serum adiponectin elevation and improves knee pain in OA. Therapeutic properties of Techirghiol mud still need further research.

The pathogenesis of type 1 diabetes became a history longer and longer. There are 40 years since the immunogenetic theory of type 1 diabetes has been launched. Near this anniversary a challenge of this theory was recently published. We give here our interpretation of primary cause of type 1 diabetes which must be connected with the pathogenesis of other phenotypes of diabetes which has a main similar mechanism: the β-cell dysfunction.

Introduction. In the community, hypoglycemic coma is commonly caused by therapies for diabetes mellitus, or excessive alcohol consumption. Little information is available on the causes and outcome of hypoglycemic coma in non-diabetic patients. Patients and Methods. We retrospectively surveyed adult patients admitted to a regional emergency hospital with hypoglycemic coma in a 18-years period, identifying 80 admissions of 79 patients. 72 cases (91.14%) presented hypoglycemic coma induced by anti-diabetic medications in attempted suicide. The others had hypoglycemic coma induced by deliberate selfpoisoning with other drugs influencing glucose metabolism, sometimes associated with excessive consumption of alcohol. Results. A history of psychiatric illness was present in 15 patients (19%), and 2 cases (2.53%) had chronic alcoholism. Neurological manifestations of hypoglycemia were the principal reason for admission, observed in all patients, and 15 patients (19%) had precipitated convulsions. Although some patients received treatment for hypoglycemia before admission, hypoglycemia recurred in 12 cases (15.19%) in hospital. Morbidity included ventricular arrhythmias (8.86%), non-cardiogenic acute pulmonary edema (1.26%), and transient neurological disturbances, in 2 elderly patients. Two cases died following admission, but death was not the direct result of hypoglycemia. Therapeutic measures consisted in antidote therapy, toxin removal, and supportive therapy. Conclusion. Though drug-induced hypoglycemic coma is rarely encountered in medical practice (2.44% in our study), management of these patients represents a challenging task in every practitioner.

No inheritance of early-onset female-related type 2 diabetes was reported within Chinese families. In this study, we aim to describe the inheritance pattern of type 2 diabetes in a 3-generation family and identify the gene responsible for type 2 diabetes. Genome-wide multipoint parametric linkage analysis revealed a maximum multipoint logarithm of odds (lod) score of 2.1 for a locus being associated with type 2 diabetes in this family on chromosome 20p11.2-12 between 23.5~30.8cM. Type 2 diabetes may be transmitted as an autosomal dominant trait with a high female-related penetrance in this family. Here we describe the first genetic locus for type 2 diabetes at chromosome 20p11.2-12. This region contains 8 known or predicted genes (PLCB1, PLCB4, LAMP5, PAK7, ANKEF1, SNAP25, SLX4IP, and JAG1). Gene SNAP25 which linked to energy or glucose homeostasis associated phenotypes may play a role in the development of type 2 diabetes in this family.

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A 62 years old woman was diagnosed with multinodular toxic goiter and primary hyperparathyroidism/ left parathyroid adenoma by hormonal assessment, ultrasound and nuclear thyroid/parathyroid scans. Cervical ultrasound illustrated a multinodular aspect of the thyroid with solid nodules and cystic-component nodules; the larger one represented a multinodular complex with necrosis areas in the left thyroid lobe, ACR TI-RADS score 4 (moderately suspicious). Functional nuclear imaging was performed for accurate differential diagnosis between thyroid vs. parathyroid localization, between cold vs. hot nodules, and eventually, for guiding the choice of a subsequent Fine- Needle Aspiration Biopsy (FNAB). Scans described an early intense 99mTc-sestaMIBI uptake with no 99mTc-pertechnetate uptake in the left thyroid lobe larger nodule. Due to the suspicion of malignancy for this nodule, we performed an additional scan (1 hour before the classical 2 hours parathyroid delayed scan). The intense uptake persists in both delayed scans suggesting no malignant phenotype and which was confirmed after surgery by benign histology. In conclusion, using a 99mTc-sestaMIBI personalized protocol, related to the radiotracer cellular uptake mechanisms: 1 hour scan (supplementary image, corresponding to the maximum uptake pattern of 99mTc-sestaMIBI for cancer cells) and 2 hours scan (for parathyroid washout evaluation) may avoid unnecessary extensive thyroid surgery.

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