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Due to complex interplay between host and viral factors, pathogenesis of chronic hepatitis C (CHC) is considered a challenging issue. Infection with hepatitis C virus (HCV) is not confined only to liver but can induce disturbances in many other organs and systems. Our primary aim for this study was to evaluate biological response rates and sustained virological response (SVR) in patients diagnosed with CHC, treated with Interferon-alpha (IFN-α), Pegylated (PEG)–IFN-α2a or -α2b plus Ribavirin. The second aim of the study was the identification of predictive factors for a favorable response to antiviral therapy in patients diagnosed with CHC. We enrolled in this study 210 patients diagnosed with CHC who have accomplished all inclusion and exclusion criteria, treated with PEG–IFN plus Ribavirin. Patients’ recovery progress has been evaluated by determining: age, gender; biochemical tests: alanine aminotransferase (ALT), aspartate aminotransferase (AST); serological assays – detect anti-HCV antibody and molecular assays – detect, quantify and/or characterize hepatitis C viral load (ribonucleic acid) (HCV-RNA); liver histopathological (HP) examination. According to their response to treatment, they were classified into responders (n=145) and non-responders (n=65). Liver biopsies were histopathologically evaluated for necroinflammatory grade and fibrosis stage according to the modified Ishak and Metavir scoring systems for chronic hepatitis. Demographic, laboratory, and HP results were introduced in statistical analysis. These parameters were included in area under curve (AUC) analysis in order to estimate their degree of influence on getting early virological response (EVR) and SVR. Our study demonstrates that factors connected to treatment failure in CHC are linked to older age, high hepatitis C viral load, and impaired glucose tolerance at beginning of treatment [high fasting glucose and insulin, high homeostatic model assessment of insulin resistance (HOMA-IR) index] and also to liver histology features (high fibrosis score, liver steatosis, iron infiltration, and more or less high necroinflammatory activity). Analyzing results of our study shows that HOMA-IR index, serum insulin levels, baseline HCV-RNA, baseline mean blood glucose and HP score like Ishak fibrosis score, steatosis score and liver iron score may have a predictive value for obtaining an EVR in patients diagnosed with CHC.

Hereditary syndromes underlying neuroendocrine tumours are extremely heterogeneous and, despite the genetic background, their recognition may actually be done later in life in many cases. Our purpose is to introduce a case of neurofibromatosis type 1 – related pheocromocytoma on a patient within his six decade of life after multiple cardiovascular complications. A 53-year old male is admitted for loss of appetite with weight loss, decreased exercise tolerance, transient occipital headache, night sweats. His medical history revealed arterial hypertension, right carotid artery ischemic stroke, and a recently non-STEMI myocardial infarction diagnosed two months ago. The pathological family history illustrated mother and a brother prematurely dying of myocardial infarction (no date of skin anomalies). Clinical examination reveals café-au-lait spots, axillary freckles, skin neurofibromas and a large plexiform neurofibroma in the right thigh. Evaluation of the adrenal gland revealed highly elevated values of urinary metanephrines and normetanephrines. Computed tomography showed a left adrenal gland tumour of 31/39 mm. Thus neurofibromatosis type 1 in addition to a left pheocromocytoma was confirmed. A cardiologic examination before surgery was re-done. Given previous pathological history (cardiovascular events like stroke and nonSTEMI infarction) adrenalectomy was delayed for the moment in addition to second antiplatelet agent and the alpha blocker medication in increasing doses. The adrenal tumour removal is planned to be done as soon as cardiovascular risk is acceptable. The importance of endocrine check is seen in young patients with severe cardiovascular and neurological acute conditions that are actually caused by a hormonal excess like found in pheocromocytoma. Nevertheless, the spectrum of tumours associated with neurofibromatosis type 1 is heterogeneous and screening protocols are still a matter of debate. Delayed diagnosis worsts the overall prognosis.

TBS (Trabecular Bone Score) is the latest tool for clinicians to evaluate bone micro-architecture based on a pixel greyscale, which is provided by lumbar dual-energy X-ray absorptiometry (DXA). Its use enhances fracture prediction in addition to DXA-BMD (Bone Mineral Density). This is independent of fracture risk assessment (FRAX) and DXA results. We present a narrative review regarding the connection between TBS and Glucocorticoids (GC), either as a drug used for different conditions or as a tumor-produced endogenous excess. TBS is a better discriminator for GC-induced vertebral fractures compared to DXA-BMD. This aspect is similarly available for patients with osteoporosis diagnosed by DXA. TBS is inversely correlated with the cumulative dose of GC (systemic or inhaled), with disease duration, and positively correlated with respiratory function in patients with asthma. Low TBS values are found in females with a T-score at the hip within the osteoporosis range, with diabetes mellitus, or who use GC. Lumbar TBS is a screening tool in menopausal women with type 2 diabetes mellitus. TBS is an independent parameter that provides information regarding skeleton deterioration in diabetic patients receiving GC therapy in a manner complementary to DXA-BMD. TBS might become an essential step regarding the adrenalectomy decision in patients with adrenal incidentaloma in whom autonomous cortisol secretion might damage bone micro-architecture. TBS currently represents a standard tool of fracture risk evaluation in patients receiving GC therapy or with endogenous Cushing’s syndrome, a tool easy to be applied by different practitioners since GCs are largely used

Ganglioneuroma, a rare neural crest-derived tumor, exhibits a benign profile in contrast to other neuroblastic tumors (neuroblastoma/ganglioneuroblastoma). Ganglioneuromas can be found anywhere autonomic ganglia are located, mostly abdominal/pelvic sites followed by the adrenal glands (one-third of cases), mediastinum/thorax and cervical area. Affecting especially children more than 10 years of age, Ganglioneuroma is either asymptomatic or may cause local compressive effects; rarely inducing nonspecific abdominal complains or arterial hypertension related to oversecretion of epinephrine/norepinephrine/dopamine. Despite a good prognosis, adrenalectomy is necessary in order to rule out a malignancy. Open procedure represents the standard therapeutic option; alternatively, centers with large laparoscopic pediatric experience and good stratification protocols have reported successful procedures. High uptake of I(123)-MIBG is associated with a more severe outcome in cases with increased mitotic index. In neuroblastic tumors, neuron-specific enolase >33 ng/ml, age at diagnosis

Li-Fraumeni syndrome (LFS) is a cancer-prone, autosomal dominant syndrome caused by underlying germline gene mutations of TP53, a tumor-suppressor gene encoding the p53 protein with a major role in apoptosis, DNA repair and cell cycle regulation. Cumulative cancer incidence for LFS patients by the age of 70 years is 80-100%, mostly involving adrenocortical carcinoma, brain tumors, bone and soft tissue sarcomas, leukemia and female breast cancer from the age of 20 years. Dominant negative TP53 variant is correlated with an increased tumorigenesis risk in LFS. Sporadic TP53 mutations are related to almost half of global cancers since p53 in addition to p73 protein represent essential players in anticancer cellular protection. Epidemiological aspects concerning skin cancers, especially malignant melanoma (MM), in LFS are less clear. A low level of statistical evidence demonstrates LFS cases with pediatric MM, multiple MM, spitzoid MM, atypical presentations, mucosal and uveal MM. Retrospective cohorts indicate a higher cumulative risk than the general population by the age of 70 years for MM and basal cell carcinoma. Non-syndromic and syndromic TP53 mutations are a major pathway of metastasis, including MM. In LHS, an important level of awareness involves skin cancers despite not being a part of the typical malignancy-containing picture. Additional data are crucially needed. However, at least one dermatologic control is a step in the multidisciplinary panel of surveillance of these patients; but in cases with benign and pre-malign pigmentations, serial dermatoscopy and full body photography are recommended for early melanoma detection in order to improve the prognosis and to reduce the overall malignancy burden.

Introduction. Precocious puberty is a common endocrine disorder in pediatric patients, leading to important changes in growth patterns. Case presentation. We present the case of a patient with precocious puberty and accelerated bone maturation, evaluated in several medical centers. A 9-year-and-11-month-old female patient was evaluated for premature thelarche, adrenarche and menarche starting at the age of 7. On clinical examination, height was 143 cm, 0.9 SD above the age and sex median, with 37.91% excess weight. She also presented with acne, cervical posterior acanthosis nigricans, hirsutism and Tanner puberty development stage B3/P4. The endocrine profile showed pubertal values for FSH (Follicle-Stimulating Hormone), LH (Luteinizing Hormone) and estradiol, before and after the Diphereline test, hyperprolactinemia (of 38.6 ng/mL, normal: 2-18.9 ng/mL) and high levels of 17-OH Progesterone (of 2.60 ng/mL, normal: 0.2-0.9 ng/mL). The Synactene® test excluded 21-hydroxylase deficiency. Knee X-rays showed a tendency for premature growth plate fusion and bone age advancement of 3.1 years. Gynecological examination and pelvic ultrasound showed normal ovarian morphology and volume, according to chronological age and a 17-mm endometrium. Hypothalamic-pituitary MRI (Magnetic Resonance Imaging) excluded the presence of a local lesion. Conclusions. In the absence of therapeutic intervention, accelerated skeletal development due to precocious puberty initially leads to high stature compared to the patient’s age group, followed by premature closure of the growth plates and low final height.

This is a clinical study on 56 subjects included in normal weight (NW) group (N=17), overweight (OW) group (N=19) and grade I obese (O) group (N=20), based on BMI (Body Mass Index) values: NW group had a mean BMI of 22.2 � 2.14 kg/sqm, OW group had a BMI of 25.89 � 1.04 kg/sqm, and O group had an average BMI of 32.2 � 2.09 kg/sqm (p-value NW-OW, NW-O, respective OW-O groups was p[0.0005). The 3 groups were similar as age (p-value NW-OW groups = 0.7, between NW- O groups = 0.8, respective between OW - O group = 0.7). The circulating bone formation (osteocalcin, P1NP alkaline phosphatase) and resorption profile (CrossLaps) indicated no statistical significant difference between groups while the coefficient of regression r between each biochemical bone marker and BMI in every BMI group exceeded the value of p]0.05. All the 3 groups had a mean value of 25-hydroxycholecalciferol in deficiency ranges ([ 30 ng/mL, normal recommended values are above 30 ng/mL) without significant differences regarding BMI groups, except for obese group when compare to the other two groups. No secondary hyperparathyroidism was associated in any group despite low vitamin D levels. Based on our observation, bone turnover biochemical markers are not influenced by BMI.

Introduction. Current studies support the implication of metabolic changes associated with type 2 diabetes in altering bone metabolism, structure and resistance. Objective. We conducted a cross-sectional study on postmenopausal women aimed to analyze the differences in metabolic and bone profile in patients with and without type 2 diabetes Methods. We analyzed the metabolic and bone profile in postmenopausal women with and without type 2 diabetes (T2DM). Clinical, metabolic, hormonal parameters, along with lumbar, hip and femoral bone mineral density (BMD) and trabecular bone score (TBS) were evaluated. Results. 56 women with T2DM(63.57±8.97 years) and 83 non-T2DM (60.21±8.77 years) were included. T2DM patients presented a higher value of body mass index (BMI) and BMD vs. control group (p = 0.001; p = 0.03-lumbar level, p = 0.07-femoral neck and p = 0.001-total hip). Also, BMI correlated positively with lumbar-BMD and glycated hemoglobin (HbA1c) (r = 0.348, p = 0.01; r = 0.269, p = 0.04), correlation maintained even after age and estimated glomerular filtration rate (eGFR) adjustment (r = 0.383, p = 0.005; r = 0.237, p = 0.08). Diabetic patients recorded lower levels of 25(OH)D(p = 0.05), bone markers (p ≤ 0.05) and TBS(p = 0.07). For the entire patient group we found a negative correlation between HbA1c level and bone markers: r = -0.358, p = 0.0005-osteocalcin, r = -0.40, p = 0.0005-P1NP, r = -0.258, p = 0.005-crosslaps. Conclusions. Our results indicate the presence of altered bone microarchitecture in T2DZ patients according to the TBS score, combined with lower levels of bone markers, with a statistically significant negative correlation between HbA1c level and bone markers.

This is a narrative review focusing on neuroendocrine neoplasia (NEN) and bone status, in terms of metastases and osteoporosis/fractures. One fifth of NEN have skeletal dissemination, this affinity being regulated by intrinsic tumor factors such as the C-X-C chemokine receptor 4 (CXCR4). Bone colonization impairs the patient quality of life, representing a surrogate of reduced survival. Patients with NEN without bone metastases may exhibit low bone mineral density, perhaps carcinoid-related osteoporosis, yet not a standardized cause of osteoporosis. Case-finding strategies to address bone health in NEN with a good prognosis are lacking. Contributors to fractures in NEN subjects may include: menopausal status and advanced age, different drugs, induced hypogonadism, malnutrition, malabsorption (due to intestinal resection, carcinoid syndrome), hypovitaminosis D, impaired glucose profile (due to excessive hormones such as glucagon, somatostatinoma or use of somatostatin analogues), various corticoid regimes, and high risk of fall due to sarcopenia. Pheocromocytoma/paraganglioma involve bone through malignant forms (bone is an elective site) and potential secondary osteoporosis due to excessive hormonal content and increased sympathetic activity which is a key player of bone microarchitecture/quality as reflected by low Trabecular Bone Score. Glucocorticoid osteoporosis is related to NEN-associated ectopic Cushing syndrome. Currently, there are a lack of studies to emphasis that excessive gut-derivate serotonin in NENs with carcinoid syndrome is a specific activator of bone loss thus a contributor to carcinoid-related osteoporosis.

Glucagonoma is a hormonally active rare pancreatic neuroendocrine tumour causing an excess of glucagon. This is a narrative review based on a multidisciplinary approach of the tumour. Typically associated dermatosis is necrolytic migratory erythema (NME) which is most frequently seen at disease onset. Insulin-dependent diabetes mellitus, depression, diarrhoea, deep vein thrombosis are also identified, as parts of so-called 'D' syndrome. Early diagnosis is life saving due to potential aggressive profile and high risk of liver metastasis. NME as paraneoplastic syndrome may be present for months and even years until adequate recognition and therapy; it is remitted after successful pancreatic surgery. Thus the level of practitioners' awareness is essential. If surgery is not curative, debulking techniques may improve the clinical aspects and even the outcome in association with other procedures such as embolization of hepatic metastasis; ablation of radiofrequency type; medical therapy including chemotherapy, targeted therapy with mTOR inhibitors such as everolimus, PRRT (peptide receptor radiotherapy), and somatostatin analogues (including combinations of medical treatments). Increased awareness of the condition involves multidisciplinary practitioners.

Adults and children who were exposed to head and/or neck radiotherapy for different cancers associate a life time higher risk than general population for a heterogeneous panel of secondary conditions like thyroid nodules, cancer and radiation induced primary hypothyroidism. We introduce an adult female case who was diagnosed and treated for Hodgkin lymphoma type IIB and one year after she presented non-autoimmune thyroiditis and high TSH. Hypothyroidism was substituted for 29 years; the ultrasound pattern remained hypoechoic with a relatively small gland and also associated radiation induced lung fibrosis.

Osteoporosis and periodontal disease (PD) are two chronic diseases, characterized by bone loss, with systemic or local impact (alveolar bone). Both pathologies have a progressive evolution, leading to systemic bone loss in the case of osteoporosis and bone lysis localized in the alveolar bone in the case of periodontal disease. The present paper presents recent data from the literature on the association between periodontal disease and osteoporosis, on the role of cytokines in the bone resorption-apposition imbalance, and on how periodontal disease causes changes in serum levels of cytokines, leading to disorders in the systemic bone formation. We also found it useful, especially for rheumatologists, to outline the extent to which periodontal disease can create a systemic context favorable to the development of osteoporosis.

Background Ovarian Leydig cell tumour is a very rare steroid hormones producing mass, causing clinical and biochemical hyperandrogenism. Even if the level of evidence is based on case studies, many authors (but not all) agree that raised androgens increase the cardio-metabolic risk thus early diagnosis and treatment are necessary On the other hand, the endocrine features pointing an ovarian tumour source of testosterone do not indicate the specific histological finding which needs a post-operative conformation. Case presentation We report a case of a 60-year-old woman with a 4-year history of progressive virilisation in association with hypertension, high number of red blood cells, impaired glucose tolerance and dyslipidemia. Total testosterone was 20 times above normal with suppressed gonadotropins, inadequate for menopause. Trans-vaginal ultrasound and pelvic and abdominal computerized axial tomography imaging revealed a right ovarian solid nodule, and no evidence of alteration in the adrenal glands. Total hysterectomy and bilateral salpingo-oophorectomy were performed. Histopathology and immunohistochemistry confirmed the diagnosis of Leydig cell tumour. After surgery, androgen levels returned to normal and the doses of anti-hypertensive drugs were reduced. Conclusions The hyperandrogenic state with elevated plasma testosterone and progressive signs of virilization raises suspicion of an ovarian androgen-secreting tumor. For a postmenopausal patient with hyperandrogenism the diagnosis of Leydig cell tumour should be considered. However, the exact diagnosis is provided by post-operative histological exam. Prolonged exposure to hyperandrogenism may generate cardiovascular abnormalities and metabolic syndrome which after tumor excision and removal of the source of androgen hormones are expected to significantly improve.

A total of 55 patients were: G1 of 9 patients, G2 of 23 subjects, and G3 of 23 patients. Similar age and years since menopause was found between the groups. There was no statistical significant difference between the groups regarding these aspects: p-value G1-G2 of 0.67, p-value G1-G3 of 0.72, p-value G2-G3 of 0.47. Similar results were obtained when TSH, FT4 and anti-thyroperoxidase antibodies were analysed between the groups. No TSH-25-OHD correlation reached the statistical significance, neither FT4-25-OHD, TPO-25-OD. P-values between G1 and G2 for TSH, FT4, TPO were 0.23, 0.38, respective 0.7, between G2 and G3 were 0.19, 0.1, 0.35, between G1 and G3 were 0.48, 0.84, respective 0.75. Bone profile analyze based on 25-OHD levels did not identify any statistical significance difference between the mentioned groups (including bone turnover markers).

Introduction. Multiple myeloma represents a malignant skeleton condition, been considered the most frequent bone malignancy of primary type in people older than 70 years. Myeloma causes a particular deterioration of bone via bone loss which can be localized or diffuse. The skeletal anomalies may include osteoporosis and vertebral fractures as first sign of the condition which need to be differentiated from others types of osteoporosis. This is a case presentation. This is a 56-year old female who was diagnosed with a lumbar fracture 5 months ago and considered osteoporosis treated with alendronate. Bone pain continued in addition to hypoanabolic syndrome. Second opinion showed hypercalcemia with suppressed parathomone and high bone resorption marker CrossLaps in association with mild anaemia, highly increased ESR (erythrocyte sedimentation rate), and newly discovered renal failure, and large ostolytic lesions at computed tomography. A bone biopsy was necessary and confirmed multiple myeloma. Conclusion. Severe diagnosis like malignant bone conditions may be first diagnosed as osteoporosis.

The complications of thyroidectomy vary from hypocalcemia and recurrent laryngeal nerve lesions to injury of vocal folds, local hematoma, cysts, granuloma. Post-operative hypocalcemia has an incidence of 1.2-40%. Permanent hyoparathyroidism is registered in 3% of cases. This is a brief narrative review focusing on the levels of calcium after performing a thyroidectomy and the need of calcium supplements under these circumstances. This complication, even it seems rather harmless at first, in fact it represents an important contributor to hospitalization delay and, especially for severe forms, to poor quality of life, including the risk of life threatening episodes. Devascularisation of parathyroid glands in addition to injury or dissection causes hypoparathyroidism. Hypocalcemia risk differs with sex (females have a higher risk), lymph node dissection (it increases the risk), it differs with type of thyroidectomy (larger dissections have a higher risk; also the intervention for recurrent goitre and second intervention for post-operatory bleeding increase the risk of hypocalcemia; while Basedow disease is probably at higher risk than multinodular goitre among benign conditions) and the duration of procedure. Pre-operatory low calcium, parathormon (PTH), 25-hydroxivitamin D increases the risk. The calcium drop rate matters as well: a decrease of 1 mg/dL calcium over 12 hours after surgery is independently correlated with the risk of symptomatic hypocalcemia. Early post-operatory PTH and calcium are best predictors for the need of oral calcium supplements. Routine post-operatory calcium and vitamin D supplementation statistically significant decreases the risk of developing transitory hypocalcemia and acute complications compare to calcium alone supplements or no supplements. In cases of hypoparathyroidism calcitriol is preferred.

Introduction The Rathke cyst represents an unusual benign tumour derived from Rathke’s cleft remnants. The diagnosis is potential seen at any age. The most frequent signs are mostly mass effects as headache, visual field defects and hypopituitarism. Case presentation 30-year old female is admitted for persistent headache that was later associated with secondary amenorrhea and visual field defects for the last two years. The clinical data are consistent with high levels of serum prolactin, gonadotropes deficiency, as well as central hypothyroidism. The magnetic resonance imagery found a pituitary tumour of 2.7 centimetres with extrapituitary extension up to the optic chiasm. Surgery was performed in order to remove the tumour. The pathologic report confirmed a Rathke’s cleft cyst. Diabetes insipidus associated with panhypopituitarism was diagnosed and treated after the procedure. Close follow-up is necessary. Conclusion This case highlights the fact that headache sometimes embraces a severe neoplasia diagnosis and that the iatrogenic complications after surgery are lifelong care demanding

Introduction Cushing’s disease is a complex endocrine disorder characterized by excessive glucocorticoid secretion caused by an ACTH-secreting pituitary adenoma. Hyperandrogenism and menstrual disorders such as amenorrhea and oligomenorrhea complete the clinical picture of Cushing’s syndrome. Infertility is relatively common, involving complex pathogenetic mechanisms, which differ depending on the cause of hypercortisolism. Case presentation We present the case of a female patient diagnosed with Cushing’s disease during the investigations carried out to assess infertility. After transsphenoidal adenomectomy, the patient underwent treatment with pasireotide and dopamine agonists, achieving normalization of gonadotropin and estradiol levels. Conclusion Current guidelines recommended transsphenoidal adenomectomy as first-line therapy in an attempt to correct hypercortisolism and restore fertility in patients with Cushing’s disease. In case of relapse pasireotide and dopamine agonists can be effective in normalizing the hormonal profile

Background and aims. Acromegaly is a complex endocrine disorder caused by excessive secretion of GH, secondary to a GH secreting pituitary adenoma or a mixed pituitary adenoma secreting GH and PRL.Methods. The aim of this study was to evaluate the effects of combination therapy: dopamine agonist and somatostatin analogue on GH and IGF1 levels in a group of 30 patients with acromegaly. Cabergoline in a dose of 2 mg/week and 4 mg/week respectively was associated with Sandostatin LAR in a dose of 20 mg/month and 30 mg/months respectively. Eight patients were treated with Lanreotide 30 mg/week and Cabergoline 2 mg/week and 3 patients were treated with Bromocriptine 10 mg/day and Sandostatin LAR 30 mg/month.Results. Combination therapy: Cabergoline and Sandostatin achieved normal levels of IGF1 in 32% of the patients, better results being obtained after 12 months of treatment in the group treated with 4 mg Cabergoline/week. In 37% of cases the levels of IGF1 decreased by 50% after 12 months of treatment. In the group treated with Cabergoline and Somatuline a normal level of IGF1 was achieved in 25% of patients after 12 months of treatment. The outcome for the group treated with Sandostatin and Bromocriptine was similar to that obtained under Cabergoline 2 mg/week. There was no significant correlation between the level of GH and the type or dose of dopamine agonist used.Conclusions. In conclusion, combination therapy consisting of dopamine agonist and somatostatin analogue achieves a significant reduction of IGF1 levels in patients with mixed adenomas secreting GH and PRL. A decrease in IGF1 levels is directly correlated with the dose of Cabergoline used.

Serotonin is a brain neurotransmitter, a local gut-produced pro-kinetic agent and a platelets-released monoamine with haemostasis role. We focus on revealing the serotonin interferences with menopause mainly related to climacteric syndrome and bone health. This is a short commentary type of manuscript, centred on English language PubMed research. Serotonin is connected to the hypothalamic thresholds for temperature regulation in vasomotor symptoms that is why drugs that elevate the serotonin synaptic plaque exposure like SSRI (serotonin selective reuptake inhibitors) are indicated. Serotonin is also linked to bone field but its testing into the blood has not been unanimously found to be correlated with bone mineral density or menopausal bone remodelling markers. Conditions with age-related onset as carcinoid tumours bring a serotonin excess but not necessary a bone loss. From climacteric syndrome to bone regulation and to pathological domain of neuroendocrine neoplasia, serotonin plays a complex role on menopause’s field.

Tumorile neuroendocrine (NET) sunt mult mai frecvente în ultimele decade. Unul din intrumentele majore de evaluare în această patologie este reprezentat de dozarea markerilor neuroendocrini precum cromogranina A, serotonina, acidul 5-hidroxi indolacetic urinar şi enolaza neuronal specifică. Aceştia se schimbă cu progresia tumorală, indiferent de terapie. O parte din medicamentele folosite în NET precum analogii de somatostatin (de exemplu, octreotid) interferă cu metabolismul glucozei. Obiectiv. Am analizat într-un studiu retrospectiv de-a lungul a 2 ani dinamica markerilor NET şi profilul glicemic. Material si metode.Toţi pacienţii au avut cel puţin o evaluare pe an. Rezultate. 9 pacienţi au fost incluşi (5 femei şi 4 bărbaţi), cu o vârstă medie de 57,33 de ani. Perioada de tratament anterior cu octreotid a fost de 18 +/- 14,69 de luni. Doza de octreotid a variat de la 20 la 50 mg lunar. Glicemia s-a modificat nesemnificativ de la bază după 2 ani. Nu s-a înregistrat nici un caz nou de diabet. O pacientă a necesitat insulină pentru diabetul preexistent (dar între timp s-a adaugat şi terapie cu interferon) Cromogranina A a avut valori mari sustinute pentru toate cele 9 cazuri, sugerând progresia bolii. Enolaza neuronal specifică a crescut semnificativ iar serotonina serică şi 5HIIA au crescut considerabil în 2 cazuri cu simptome severe de sindrom carcinoid. Concluzie. Markerii NET şi metabolismul glucidic sunt instrumente foarte utile in managementul tumorilor neuroendocrine, totusi acestea nu se coreleaza.

Bone Mineral Density (BMD) is a gold standard for the diagnosis of osteoporosis and is also important in the assessment of fracture risk. Other risk factors have been identified that together make up fracture risk assessment tools such as FRAX. Another potential factor, circulating lipids, has been suggested because of reports linking statins to fracture risk reduction. We analyzed the lipid profile in a cohort of women diagnosed with postmenopausal osteoporosis based on bone density determination: 610 women with osteoporosis (mean lumbar spine T-score -3.16±0.81, mean yrs. since menopause 15.79±8.9) were grouped according to age at evaluation (50 years, 51-60 years, 61-70 years,70 years), the presence/absence of a history of a fragility fracture, statin and/or antiresorptive drug use. There was no correlation between BMD and Body Mass Index (BMI: P0.05, r (2)0.02). However, when BMD was correlated with both BMI and the lipid profile (Triglycerides, Cholesterol, LDLc, HDLc), significant correlations were found in 5 cohorts: 51-60 years with fractures (n=61, r (2)=0.14, P0.01), 61-70 years (n=201, r (2)=0.09, P0.01) with fractures (n=88, r (2)=0.14, P0.01) or without fractures (n=113, r (2)=0.24, P=0.02) and over 70 years (n=247, r (2)=0.11, P0.01).

Background. Advances in imaging techniques have led to increasing discovery of adrenal and pituitary “incidentalomas”, tumors with normal endocrine function and no compression mass effects. We evaluated the age at diagnosis (AD) in patients with benign non-functioning adrenal incidentalomas, as compared to pituitary non-functioning tumors, in a series of patients from a national center of endocrinology. Methods. From 2,123 consecutive patients with adrenal and pituitary tumors hospitalized between 1977 - 2009, 2,069 patients were analysed. The study groups included: group A - 137 patients with adrenal incidentalomas (AI), group B - 534 patients with pituitary incidentalomas (PI). Control groups included 1,398 patients: group C1 147 patients with adrenal carcinomas or benign hormone-secreting adrenal tumors, and group C2, 1,251 patients with pituitary secreting adenomas or large non-functioning pituitary macroadenomas (NFA). Imaging was done by computed tomography and/or magnetic resonance after 1981 and by skull X-ray or pneumoencephalography before 1981. Results. Mean age AD is more advanced in patients with AI (53 ± 11.9 years, range 21 - 78 yr) than in patients with PI (36.8 ± 13.1 years, range 10 - 81 yr), p < 0.01. AD was higher in AI than in patients with secreting adrenal tumors, but similar in patients with adrenal malignancy. There is an age-related increase in the proportion of AI among patients with adrenal tumors, and of NFA, but not of PI, among patients with pituitary tumors. In patients aged over 65 years, 74% of patients with adrenal tumors have AI, while only 18% of patients with pituitary tumors have PI and 42% have NFA. AD in NFA (49.3 ± 13.1 yr, range 12 - 79 yr) was more advanced than in PI (p < 0.01). AD does not correlate with tumor size. Tumor growth occurred in 24% of AI (follow-up 3.0 ± 2.8 yr) and only in 0.7% of PI, p

SUMMARY The male hypogonadism-related bone mass loss is often under diagnosed. Peak bone mass is severely affected if the hypogonadism occurs during puberty and is left untreated. We present an interesting; almost bizarre case of a male with non-functional testes early during childhood and undiagnosed and untreated hypogonadism until his fifth decade of life. Forty six year male is referred for goitre, complaining of back pain. Phenotype suggested intersexuality: gynoid proportions, micropenis, no palpable testes into the scrotum, no facial or truncal hair. His medical history had been unremarkable until the previous year when primary hypothyroidism was diagnosed and levothyroxine replacement was initiated. Later, he was diagnosed with ischemic heart disease, with inaugural unstable angina. On admission, the testosterone was 0.2 ng/mL (normal: 1.7-7.8 ng/mL), FSH markedly increased (56 mUI/mL), with normal adrenal axis, and TSH (under thyroxine replacement). High bone turnover markers, and blood cholesterol, and impaired glucose tolerance were diagnosed. The testes were not present in the scrotum. Abdominal computed tomography suggested bilateral masses of 1.6 cm diameter within the abdominal fat that were removed but no gonadal tissue was confirmed histopathologically. Vanishing testes syndrome was confirmed. The central DXA showed lumbar bone mineral density of 0.905 g/cm2, Z-score of -2.9SD. The spine profile X-Ray revealed multiple thoracic vertebral fractures. Alendronate therapy together with vitamin D and calcium supplements and trans-dermal testosterone were started. Four decades of hypogonadism associate increased cardiac risk, as well as decreased bone mass and high fracture risk.

After treatment, the mean results at TUG and CRT test decreased significantly (see table), representing a mean change of -4.9 and -7.33%, respectively (p=0.000* compared to baseline). The global Tinetti score and the subscores for balance and posture also improved significantly compared to baselinesee table. The results were significantly better in the subgroup treated with alphacalcidol compared to the subgroup offered cholecalciferol for TUG (p=0.012) but not for CRT (p=0.074)see below. No difference was noted in the evolution of the Tinetti score between the treatment subgroups.

Background: The tyrosine kinase inhibitor, a new treatment option in hepatic carcinoma, may associate thyroid dysfunction like spontaneously remitting thyrotoxicosis followed by hypothyroidism. Case report: A 66-year Caucasian female was first diagnosed and operated for a moderately differentiated rectal adenocarcinoma of 5 centimeters. Immunohistochemistry showed positive VEGF receptor 2 (Flk-1, KDR), VEGF receptor 1(Flt-1), and a Ki67 of 30%. 4 years later a hepatic adenocarcinoma (clear cells variant) was diagnosed. After surgery, daily 400 mg of sorafenib was introduced. Three months later mild symptomatic thyrotoxicosis was seen: palpitations, fatigue, and mild bilateral pedal clonus. Thyroid-stimulating hormone (TSH) was suppressed (0.044 μIU/mL, normal levels between 0.4 and 4.5 μIU/mL), and free levothyroxine (fT4) elevated. The TSH receptor antibody, the antithyreoglobulin and antithyreoperoxidase antibodies were negative. Thyroid ultrasound pointed hypoechogenic, inhomogeneous aspects. She received beta-blocker and within two months thyrotoxicosis remitted but TSH progressively increased suggesting hypothyroidism with level less 5 μIU/mL so no replacement levothyroxine therapy was added yet. Discussions: The exact mechanism of the tyrosine kinase inhibitors-related thyroid malfunction is not fully understood. Non-autoimmune destructive thyroiditis of unknown trigger causes thyrotoxicosis and later hypothyroidism as seen in our case. The clinical features vary from one person to another. The hormone replacement is rarely necessary. The baseline cancer seems irrelevant for thyroid toxicity. In our unusual case the patient had a history of two metachronous cancers. The thyroid follow up is essential during each patient therapy yet a specific pattern of follow-up is not precisely designed. Conclusion: The tyrosine kinase inhibitor-induced thyroid dysfunction includes both thyrotoxicosis and hypothyroidism. We emphasize the idea of periodic endocrine evaluation in oncologic patient treated with this class of drugs.

Obesity, a worldwide medical problem, associates a large panel of disorders but traditionally osteoporosis was not considered one of them. This mini-review targets human and animal studies related to this topic. DXA is the golden standard of fracture risk assessment by providing Bone Mineral Density (BMD) which is directly correlated to Body Mass Index (BMI). Recent studies found that the correlation become weaker at BMI >30 kg/sqm while associating a higher mechanical load. The obesity-related fracture risk includes a blunt bone turnover markers status and a proinflammatory environment as IL-6, TNF-a¾³. Common pathogenic pathways involve both the skeleton and the metabolic complications of obesity as growth hormone, insulin-like growth factor-1, angiotensin II and ghrelin. On the contrary, estrogens are fat-derived by aromatase conversion being bone protective as androgens or insulin resistance. Leptin and adiponectin are produced by adipose tissue playing multiple roles including on bone cells. The overlapping factors in obese persons that elevate the fracture risk are the vitamin D deficiency and sarcopenia with increased risk of fall and diabetic bone disease cause by the type 2 diabetes mellitus which is very frequent among obese subjects. Increased cortical porosity as well as alteration of bone matrix quality to the advanced glycation products is correlated to diabetic fracture risk while BMD remain inadequately normal. The correlation between obesity and fall also associates with prior diagnosis of chronic heart disease, severe depression/anxiety, chronic use of anti-depressants or sleeping pills, and sedentary lifestyle. A new map of fractures is drawn since obesity involves a higher risk of ankle (most frequent site in obesity) and humerus fractures and a lower risk of vertebral and hip fractures. The fracture healing is difficult in obese subjects due to inflammation and co-morbidities especially diabetes. Obesity has a rapidly rising prevalence so are the associated conditions; among them fragility fractures at specific sites represents an alarming new issue despite the traditional theories that obesity protects against osteoporosis.

1 F 37 7 follicular variant of papillary macrocarcinoma 2 F 52 24 follicular variant of papillary microcarcininoma 3 F 46 4 follicular variant of papillary microcarcinoma Characteristics of acromegalic patients with thyroid carcinoma Acromegaly, a rare chronic disease characterised by hypersecretion of growth hormone (GH) and subsequently insulin growth factor 1 (IGF1), was associated with an increased prevalence of benign and malignant tumors (1,2). Thyroid nodules were more frequently found in acromegalic patients than in general population with an OR =3.6 (3), and some studies suggested that the thyroid carcinoma is the most frequent type of cancer in the acromegalic patients (4,5). Aim: to assess the prevalence of thyroid nodules and thyroid carcinoma in patients with acromegaly. PATIENTS AND METHODS

s 441 P48 Vanishing Testes Syndrome-Related Vertebral Fractures and High Cardio-Metabolic Risk in an Adult Male with Long Term Untreated Hypergonadotropic Hypogonadism Mara Carsote; C.I.Parhon National Institute of Endocrinology, Carol Davila University of Medicine and Pharmacy Anda Dumitrascu, Corina Chirita, Sorin Paun, Dana Terzea, Catalina Poiana Background: The hypogonadism-related bone mass loss despite its frequency among male osteoporosis cases it is often under diagnosed. The peak bone mass is severely affected if the hypogonadism is registered and left untreated during puberty. Aim: We present an interesting, almost bizarre case of a male who presented non-functional testes early during childhood and remained hypogonadic up to his fifth decade of life since no testosterone therapy was added during this time. Case presentation: A 46-year old male is referred for goiter evaluation. He accuses back pain. The phenotype resembled intersexuality: gynoid proportions, micropenis, no palpable testes into the scrotum, no face hair. His medical history revealed since last year: mixedema treated with levothyroxine, and ischemic heart disease with an episode of acute angina. On admission, the testosterone was 0.2 ng/mL (normal: 1.7-7.8 ng/mL), FSH of 56 mUI/mL, normal adrenal axis, as well as TSH (under substitution) were found. The bone turnover markers were twice as normal. High blood cholesterol and impaired glucose tolerance was registered. The thyroid ultrasound pointed a left lobe node of 1 cm. The testes were not found into the scrotum. Computed tomography suggested bilateral nodes of 1.6 cm into abdominal fat that were removed but no gonads were confirmed. Vanishing testes syndrome was confirmed. The central DXA pointed lumbar Bone Mineral Density (BMD) of 0.905 g/cm2, T-score of -2.8, and Z-score of -2.9. The spine profile X-Ray pointed thoracic vertebral multiple fractures. Alendronate therapy together with vitamin D and calcium supplements, as well as testosterone gel was started. Conclusion: Severe and long time standing hypogonadism affects not only the cardiac risk, as well as the skeleton integrity. Figure 1. BMD Z-scores in males and females with Addison’s disease P49 TSH Threshold Related to Lower Bone Mineral Density in Postmenopausal Patients Under TSH Suppression Therapy for Differentiated Thyroid Carcinoma Aline Farias; University of Campinas Ludmila Almeida, T.G. Melo, L.V.M. Assumpc~ao, Allan Santos, D.E. Zantut-Wittmann Introduction: TSH suppression with supraphysiological doses of levothyroxine aims to reduce risk of recurrence in the treatment of patients with differentiated thyroid carcinoma (DTC) after surgery and radioiodine therapy. Exogenous subclinical thyrotoxicosis (EST), with suppressed TSH and normal T4 levels probably has a negative effect on bone metabolism, but there is no definition of the magnitude of the effect on bone mineral density (BMD). Objective: To evaluate the relationship between TSH suppressive therapy in patients with DTC and BMD. Methods: Cross-sectional study of 109 postmenopausal women in EST followed for DTC, compared to the control group (postmenopause women with normal levels of thyroid hormones) matched for age. All participants were submitted to BMD examination and statistical data analysis was performed. Results: Mean age of patients was 58.4 ( 8.3) years, with menopause for 11.2 ( 9.5) years. The average of follow up for CDT was 88 ( 70.6) months, mean BMI 27.9 ( 4.5) kg/m, mean of TSH during the year before of BMD analysis was 0.21 ( 0.28) mUI / ml and mean of free T4 was 1.84 ( 0.21) ng / dL. Mean T-score was -1.09 (SD 1.43) in L1-L4 and -0.12 (SD 1.18) in the total femur, with 19.2% of patients with osteoporosis; 40.4% with osteopenia and 40.4% with normal BMD. There were no significant differences between T and Z-score values of patients and control group. Multivariate logistic regression analysis identified significant relationship between BMI (p !0.001; R2 0,15) and mean TSH level during the last year (p 5 0.021 and R2 0,0423) with lumbar BMD. There were also relationships between BMI (p !0.001; R2 0,26), TSH level (p !0.001; R2 0,07) and oral contraceptive use (p 5 0.007; R2 0,04) with femoral BMD of patients. The ROC curve analysis for TSH values that differentiate patients with normal BMD of those with osteopenia identified as significant threshold when TSH was inferior to 0,185_UI / ml (area under the significant curve: AUC 5 0.625, 95%, CI 0.50-0.74, p 5 0.04). Journal of Clinical Densitometry: Assessment & Management of Muscu Conclusions: The identification of a TSH threshold level in patients with DTC and EST maintaining normal BMD from those with osteopenia is unprecedented (to our knowledge). This may be of great importance to define the degree of TSH suppression in the follow-up of DTC. This is the rational to maintain TSH levels less suppressed in patients with low risk of recurrence or mortality, in order to preserve BMD in these patients. P50 Bone Mineral Density in Patients with Addison’s Disease on Replacement Therapy with Prednisolone David Chandy; Sanjay Gandhi Postgraduate Institute of Medical Sciences