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We calculated in-hospital, 30-day, and 1-year mortality rates and analyzed potential mortality risk factors in 2742 patients with low-trauma hip fractures. We found a high mortality rate at 30 days and 1 year after hip fracture. The high mortality can be explained by a very high number of conservatively treated fractures. Data on mortality after low-trauma hip fracture in Romania is scarce and comes from a single-hospital study. Our aim was to calculate mortality rates and risk factors in all patients admitted for low-trauma hip fracture in the largest university medical center of Romania. We retrospectively analyzed the charts of all patients (>40 years old) admitted for hip fracture in a 12-month period in hospitals with an Orthopedic Department in Bucharest, Romania, and surrounding Ilfov County and calculated the crude in-hospital, 30-day, and 1-year mortality rates after low-trauma hip fractures. A number of potential clinical risk factors for mortality were evaluated. We analyzed 2742 low-trauma hip fractures. The in-hospital, 30-day, and 1-year all-cause mortality rates were 4.26% (n=117), 9.59% (n=263), and 29.72% (n=815) respectively. Four hundred and fifty (16.41%) fractures were managed conservatively with a 1-year mortality HR of 3.05 (p

Androgen insensitivity syndrome (AIS) is an X-linked recessive genetic syndrome that occurs as result of an androgen receptor mutation; it affects the normal masculinization process in chromosomal male patients. More than 900 androgen receptor mutations that can lead to AIS have been identified. The complete androgen insensitivity is characterized by a total lack of response to androgens, usually in patients with 46XY karyotype but with feminine phenotype. Primary amenorrhoea and inguinal swellings in female patients are the main signs that could raise suspicion for this syndrome. Patients with partial androgen insensitivity have ambiguous genitalia at birth and gynecomastia during puberty, whereas those with mild androgen insensitivity present a normal male phenotype but altered spermatogenesis during adulthood and pubertal gynecomastia. The diagnosis of AIS often proves to be a challenge; its management is complex and requires a multidisciplinary approach to meet decision-making challenges in sex assignment, fertility and timing of gonadectomy, psychological outcomes and genetic counselling.

Background: Literature suggests that high body mass index can be correlated with better response to immune checkpoint inhibitors. On the other hand, sarcopenia seems to be a negative predictive marker. Materials and methods: The present analysis is a retrospective, multicenter trial that included patients with metastatic melanoma, non-small cell lung cancer (NSCLC), and renal cell carcinoma treated with nivolumab between 2018 and 2020. Patients were stratified by creatinine levels both at treatment initiation and at first follow-up (at three months) and by BMI for the same intervals, as recorded in the patients&rsquo, charts. Creatinine was considered a surrogate marker for sarcopenia. IBM SPSS version 20 was used for statistical analysis. Results: A total of 57 (n = 57) patients were included in the trial. Overall response rate (ORR) for the entire population was 38.59% (p = 0.02). Patients with BMI lower than 25 had an ORR of 28.5% (p = 0.003), whereas patients with BMI higher than 25 had an ORR of 42.3% (p = 0.002). Patients who gained weight during treatment had a lower probability of having progressive disease (OR = 0.4 [95% CI, 0.4&ndash, 1.2]), as did patients with creatinine higher than 0.9 (OR = 0.39 [95% CI: 0.13&ndash, 1.14]). No superiority was found in progression-free survival (PFS) when patients were dichotomized for BMI = 25 or BMI = 18.5. Mean PFS in the BMI under 18.5 group was 10.2 months [95% CI: 5.8&ndash, 23.1], versus 11.2 for BMI over 18.5 [95% CI: 5.3&ndash, 25.3], p &lt, 0.03. Mean PFS for the BMI under 25 was 11.2 months [95% CI: 7.2&ndash, 20.1], vs. 13.3 months [95% CI: 6.4&ndash, 22] for the BMI over 25, p &lt, 0.001. There were also differences in PFS in the patients with baseline creatinine over 0.9 when compared with under 0.9 values. Mean PFS in the first group was 19.78 months [95% CI: 16.23&ndash, 22.9] vs. 16.1 [95% CI: 12.2&ndash, 20.3], p &lt, 0.001. Conclusion: Patients treated with nivolumab who have weight gain during treatment have a better PFS than the ones who do not. Creatinine levels of over 0.9 at treatment initiation also have positive predictive value.

Introduction: Although histopathology remains in the first line of the diagnosis of pituitary pathology, immunohistochemistry and molecular biology are currently in charge of providing a more accurate characterisation of tumours in this field. Material and methods: A systematic review of the literature was performed, using the PubMed and SCOPUS databases, with terms that included transcription factors involved in the development of pituitary tumours: T-PIT, PIT-1, and SF-1. Results: The results showed different perspectives, but the evidence is in favour of a multifold immunohistochemical analysis that must include pituitary transcription factors for a highly accurate diagnosis, prognosis, and guidance of (multimodal) therapy. Conclusions: By using transcription factors, the understanding of the structure and function of the recently defined pituitary neuroendocrine tumours has made significant progress. This approach brings the (sub)classification of pituitary tumours, using cell types and cell lineages, with clinical and molecular implications and therapeutic results.

Aggressive pituitary tumors lie between pituitary adenomas and carcinomas, displaying a particular behavior, with invasion, resistance to conventional therapy and early recurrence. The radiological grading, along with prognostic markers such as Ki-67 proliferation index, p53, MGMT and transcription factors are important factors in establishing the benign, aggressive, or malignant nature of pituitary tumors, with a more accurate treatment strategy. In this article, we report the novelties in defining, classifying, and managing aggressive pituitary tumors and their malignant potential, focusing on clinicopathological, histological, molecular and radiological data.

Cardiovascular risk (CVR) is a broad term that includes traditional factors like hypertension, hyper lipidemia, abdominal obesity, hyperinsulinemia or overt type 2 diabetes mellitus (T2DM), and emerging ones such as hypothyroidism or inflammatory diseases. In epidemiologic studies, all of these factors are associated with atherogenesis and have complex interactions between them. They have in common an increased prevalence in the general population beginning in childhood, and are correlated with endothelial damage as demonstrated by echocardiographic modifications of the left ventricle or carotid intima-media thickness. Adolescence is a transition period where behavioural eating patterns develop and have a major impact on cardiovascular risk. To address these patterns, weight-loss programmes under medical supervision for overweight and obese adolescents are developed. It was observed that those who control the quality and quantity of their carbohydrates, by consuming more fruits and vegetables, associated with increased physical activity reduce their CVR. Some limited studies have shown that low carbohydrate diet (LCD) is safe and effective, but one should take into consideration the limited duration and the structure of the LCD. If there is a proper adherence to this type of nutritional intervention, it results in weight loss, improvement in insulin resistance, lipid profile and subclinical hypothyroidism reversal. We reviewed the literature starting from 2009 by searching all the observational, randomised clinical trials and meta-analyses on MEDLINE and SCOPUS databases regarding obesity and related metabolic diseases (dyslipidemia, type 2 diabetes, hypertension, hypothyroidism, LCD) in adolescents and synthesized the nutritional interventions for this population that could decrease CVR.

Treatment options for persistent and recurrent Cushing's disease (CD) include an individualized approach for repeat surgery, medical treatment, radiation therapy (RT), and bilateral adrenalectomy (BLA).In this expert opinion perspective, the authors review the latest treatment(s) for persistent/recurrent CD. A PubMed search was undertaken (English articles through May 2020) and relevant articles discussed. Repeat pituitary surgery should be considered in most patients with proven hypercortisolism; there is potential for cure with low risk of major complications. Medical therapy is valuable either alone, while awaiting the effects of RT, or in preparation for BLA. Medical therapy includes steroidogenesis inhibitors, agents that act at the pituitary or glucocorticoid receptor level, and novel agents in development. Radiation therapy has been used successfully to treat CD, but hypopituitarism risk and delayed efficacy (improved with radiosurgery) are major drawbacks. Laparoscopic BLA is safe and effective in patients with severe, difficult-to-manage hypercortisolism, but long-term follow-up is required as corticotroph tumor progression can develop.Treatment of persistent/recurrent CD is challenging. Most patients require1 therapy to achieve long-lasting remission. There is currently no ideal single treatment option that provides high and rapid efficacy, low adverse effects, and preserves normal pituitary-adrenal axis function.

Introduction: In acromegaly, there are changes in growth hormone (GH), insulin-like growth factor-1 (IGF-1) and insulin, hormones very important in pregnancy as well. Despite novel treatments, pregnancy in acromegaly is uncommon, remaining a challenge for clinicians. We report seven pregnancies in five women with acromegaly. Clinical Cases: Five acromegalic patients (17 – 35 years-old) underwent seven pregnancies. All patients had macroadenoma: four were submitted to non-curative neurosurgery and two of them had gamma-knife radiosurgery. One patient had medical treatment prior to curative transsphenoidal surgery (TSS). One patient being treated with estroprogestative for hypogonadism had a spontaneous pregnancy; three others had pregnancy just before biochemical diagnosis of acromegaly, one of them had also a spontaneous abortion and another successful pregnancy during treatment with somatostatin receptor ligand (SRL); the last patient become pregnant during treatment with SRL, prior to TSS. Monitoring was made with IGF-1, GH (assay with no distinction of pituitary GH versus placental GH), prolactin (PRL) and visual field; pituitary imaging was performed after pregnancies in all. All women conceived naturally, two being on treatment with SRL (discontinued after confirmation of pregnancy). No treatment for acromegaly was administered before delivery. All patients had physiologic pregnancies, delivered full-term healthy babies, no malformations or metabolic disruptions; one did not breast-feed; another one had a spontaneous abortion 2 days after confirmation of pregnancy. No patient developed either hypertension, pre-eclampsia or gestational diabetes. In three cases, the clinical suspicion of acromegaly had risen during pregnancy and the diagnosis was made 1 year after delivery. The one with three pregnancies had controlled secretion of GH on Lanreotide and GH and IGF-1 levels remained stable during pregnancy. The woman with gonadotroph deficiency after TSS and GK and substitutive therapy had a decrease in IGF-1 during pregnancy (45 %), which after delivery returned pathologically to before pregnancy values; GH levels remained stable. The last patient, who became pregnant with uncontrolled acromegaly on Pasireotide, had increased, but stable GH and IGF-1 (2 X upper limit of normal) before, during and after pregnancy. TSS performed 3 years after delivery cured the disease. Conclusion: From our experience, patients with acromegaly may have normal babies, even in patients with uncontrolled hypersecretion and lack of medical treatment during pregnancy. The consensus is, however, that there is no indication to use medication to control GH hypersecretion or tumor size in acromegaly patients during pregnancy (1). Reference: (1) Muhammad A, Neggers SJ, van der Lely AJ. Pregnancy andacromegaly. Pituitary. 2017;20(1):179–184. doi:10.1007/s11102-016-0740-3

Introduction: In Romania, there is no acromegaly national register and there are no nationwide data available. However, some studies have reported the control rates in the country’s main referral centres. Our aim was to assess the overall control rate in our tertiary referral centre. Also, we assessed the control rate in the last three years, and we compared the results with our previous reports. Material and methods: We reviewed the charts of 186 patients with acromegaly assessed in our department between January 1 st , 2012 and May 31 st , 2019. We also compared the control rates for patients treated between April 1 st , 2016 and May 31 st , 2019 with historical controls (assessed between January 1 st , 2012 and March 31 st , 2016). Results: Primary analysis: There were 19 untreated and 167 treated patients, mean age 52.46 years, surgery being the most commonly used treatment. The surgical cure rate was 14.8%, and disease control with medical treatment was 35.3%. Secondary analysis: In the first group there were 45 patients, surgery also being the most commonly used treatment. The surgical cure rate was 26.9%, and disease control was 30.4%. In the second group (historical controls) there were 42 patients, surgery being the most commonly used treatment. The surgical cure rate was 9.7%, and disease control with medical treatment was 15.4%. Random GH and IGF-1 after surgery were lower in the first group (p < 0.05) Conclusions: Changes in the Romanian protocol and highly specialised pituitary centres has improved the cure rate and disease control in patients with acromegaly.

Introduction Bone mineral density (BMD) measurement, a tool used to diagnose osteoporosis (OP) and to predict fracture risk, has not been found very useful in type 2 diabetic (T2DM) patients. They have a 69% higher fracture risk despite having higher hip and lumbar spine BMD than the non-diabetic population. The aim of this study was to examine the impact of 3 different fracture risk assessment (FRAX) models using surrogate adjustments for T2DM in predicting osteoporotic fracture risk over 10 years. Material and Methods Observational retrospective study included 98 patients with OP or osteopenia: 94 women and 4 men admitted in the National Institute of Endocrinology between 2011-2019. 50 % (n= 49) of the patients had T2DM, while the other half were non-diabetic patients. BMI, BMD, lipid profile, serum creatinine, calcium, phosphorus, 25(OH)vitamin D, HbA1c were assessed. BMD was measured on a GE Lunar osteodensitometer. The risk of major osteoporotic fracture in 10 years was assessed with FRAX adjusted for Romania. For diabetic patients, FRAX was adjusted by adding 10 years to patients’ age (model 1), by using rheumatoid polyarthritis as a substitute for T2DM (model 2) or by lowering T score with 0.5 DS (model 3). Results Non-diabetic patients had a lower BMI (p=0.001) and a lower BMD (p=0.03) than diabetic patients. A higher BMI correlated with a higher hip BMD (p=0.004). For diabetic patients, FRAX risk without adjustment was statistically significant lower than FRAX risk calculated with model 1 and 2 (p< 0.001) for both major and hip fracture risk. Unadjusted FRAX risk was lower than the one calculated with model 3 only for hip fracture risk (p Model 1 FRAX adjustment led to a statistically significant risk of both major osteoporotic fracture (p= 0.004) and hip fracture (p=0.04) over 10 years in diabetic patients than non-diabetic patients, though diabetic patients had higher BMD. The same observation was made when FRAX was adjusted by model 2 (p=0.001) or by model 3 (p=0.001). HbA1c correlated inversely with FRAX adjusted with all three models. Discussion FRAX calculator does not include T2DM among secondary causes of OP and this precludes a proper risk assessment independent of BMD. Trabecular bone assessment (TBS) captures a larger portion of the diabetes-associated fracture risk than BMD, however TBS it is not fully independent of the BMD. We examined 3 models of adjusted FRAX in T2DM patients that showed an important increase in fracture risk prediction when adding BMD - independent risk factors into FRAX calculator. Conclusion T2DM patients have a greater risk of major osteoporotic fracture in 10 years at the same BMD compared with non-diabetic population. New models of FRAX adjusted for T2DM are needed in assessing the intervention threshold for OP/osteopenia of patients with T2DM.

We measured serum parathyroid hormone in 8409 Romanian subjects and found a mild seasonal variation with highest levels in March and lowest levels in September. PTH was dependent on serum vitamin D, particularly below 12.82 ng/mL. Together, these suggest that vitamin D supplementation is warranted only in at-risk groups. Seasonal variation of parathyroid hormone (PTH) and its dependency on serum 25-hydroxy vitamin D (25(OH)D) levels are well-described. However, there are few studies from Europe, and genetic, nutritional, and cultural differences are important. We describe the seasonal variation of serum PTH and its relation with serum 25(OH)D levels in Romania. We retrieved from our endocrinology center database all PTH measurements between 2011 and 2019 together with age, sex, diagnosis, and date of blood sampling. Simultaneous serum 25(OH)D levels were partially available. Intact PTH was measured using the same electrochemiluminescence assay. There were 8409 subjects (median age 49 (36, 60) years; 20.5% men) without a diagnosis of hyperparathyroidism (primary or secondary to chronic kidney disease), hypoparathyroidism, or low bone mass. Serum PTH showed a mild seasonal variation with highest levels at the end of March (47.61 pg/mL) and lowest levels at the end of September (43.15 pg/mL). All sex and age subgroups showed highest levels in the spring and lowest levels in the fall. Males had significantly lower PTH levels than females irrespective of season. PTH correlated inversely with serum 25(OH)D with a breakpoint of 12.82 ng/mL in 2800 subjects who had a simultaneous measurement of 25(OH)D. Increasing age was associated with increasing PTH levels independently of serum 25(OH)D. We showed a mild seasonal variation of serum PTH in Romania, at an inverse sinusoidal pattern than serum 25(OH)D. The breakpoint on the PTH–25(OH)D correlation suggests that vitamin D supplementation is warranted only in at-risk groups.

Introduction: Acromegaly is a rare, serious endocrine disorder characterized by excess growth hormone (GH) secretion by a pituitary adenoma and overproduction of insulin-like growth factor I (IGF-I). Transsphenoidal surgery is the treatment of choice, although many patients require additional interventions. First-generation somatostatin analogs (SSAs) are the current standard of medical therapy; however, not all patients achieve control of GH and IGF-I. Outcomes from a Phase IIIb open-label study of patients with uncontrolled acromegaly on first-generation SSAs switching to pasireotide are reported. Methods: Adults with uncontrolled acromegaly (mean GH [mGH] ≥1 μg/L from a five-point profile over 2 h, and IGF-I >1.3× upper limit of normal [ULN]) despite ≥3 months' treatment with maximal approved doses of long-acting octreotide/lanreotide received open-label long-acting pasireotide 40 mg/28 days. Pasireotide dose could be increased (maximum: 60 mg/28 days) after week 12 if biochemical control was not achieved, or decreased (minimum: 10 mg/28 days) for tolerability. Patients who completed 36 weeks' treatment could continue receiving pasireotide during an extension (weeks 36-72) when concomitant medication for acromegaly was permitted. Primary endpoint was proportion of patients with mGH 2.5 μg/L. For patients who entered the extension, 14.8% (95% CI: 8.1-23.9), 12.5% (95% CI: 6.4-21.3), 14.8% (95% CI: 8.1-23.9) and 11.4% (95% CI: 5.6-19.9) had mGH

Background: Von Hippel-Lindau (VHL) syndrome represents a rare familial condition caused by germline mutations of the tumorsuppressor gene VHL, which is located on the short arm of chromosome 3p25. Only 20% of the cases arise from de novo mutations, most patients having a positive family history with an autosomal dominant transmission. VHL is characterized by the presence of vascular tumors including hemangioblastomas of the cerebellum, spinal cord, brain stem and retina and the appearance of multiple cysts in different organs. Frequently, patients can associate clear cell renal carcinoma (RCC) and pheochromocytomas, or endolymphatic sac tumors. Case reports: We present the cases of two sisters, diagnosed with VHL, with a positive family history (their father was diagnosed with VHL as well). The first patient, a 40 year old female, non-smoker, presented with multiple hemangioblastomas (right cerebellar, brainstem, right optic nerve, spinal cord), bilateral pheochromocytoma and multiple cysts (hepatic, renal and ovary) had a positive genetic analysis (VHL heterozygote mutation p.Arg167Gln) and underwent multiple surgical interventions. The second patient, her sister, 38 year old, presented with multiple emangioblastomas (cerebellar hemangioblastomas, right retinal hemangioblastoma), ovarian and breast cysts. Conclusions: Patients with rare tumors characteristic of VHL (e.g. retinal or cerebellar hemangioblastomas) should be evaluated clinically and molecularly for VHL. This includes reviewing a detailed family history focused on characteristic tumors.

Evidence regarding the relation between SARS-CoV-2 mortality and the underlying medical condition is scarce. We conducted an observational, retrospective study based on Romanian official data about location, age, gender and comorbidities for COVID-19 fatalities. Our findings indicate that males, hypertension, diabetes, obesity and chronic kidney disease were most frequent in the COVID-19 fatalities, that the burden of disease was low, and that the prognosis for 1-year survival probability was high in the sample. Evidence shows that age-dependent pairs of comorbidities could be a negative prognosis factor for the severity of disease for the SARS-CoV 2 infection.

Objective. Romania has no national guidelines for hypothyroidism treatment, nor are there any recommendations from national societies to adhere to international guidelines. Our aim was to identify the attitudes of Romanian physicians relating to hypothyroidism treatment focusing on available formulations of levothyroxine (LT4). Methods. All 748 members of the Romanian Society of Endocrinology were invited to participate in a web-based survey. A total of 316 (42.24%) members responded, of whom 222 (70.2%) completed all questions. Results. Half of the respondents recommended LT4 treatment in euthyroid patients, from 3.6% in euthyroid patients with obesity to 36.4% in euthyroid females with infertility associated with high levels of thyroid antibodies. LT4 was considered the preferred treatment for hypothyroidism (compared to combination treatment of LT4 with LT3 or LT3 alone) by 98.6% of respondents. LT4 in liquid solution was preferred over tablets if malabsorption is suspected (56.5% vs. 27.3%), for patients with unexplained poor biochemical control (52.5% vs. 22.9%) and for patients not able to adhere to ingesting LT4 fasted (74.0% vs. 9.8%). The most and least probable explanations for persistent symptoms in patients with hypothyroidism who achieve a normal TSH under medication were “psychosocial factors” and “burden of having to take medication”, respectively. Conclusion. A significant proportion of Romanian physicians would use LT4 in some groups of euthyroid patients, contrary to current evidence. The preferred treatment for hypothyroidism was LT4. Alternative LT4 formulations (liquid solution) are considered in specific clinical conditions. Diversification of available thyroid hormone formulations was readily incorporated into everyday practice.

Since their first mention, almost 60 years ago, there were a plethora of articles about oxidative stress and antioxidants, published in a wide range of journals (biochemistry, cell physiology, molecular biology or environmental biology). Also, in the last decade the definition of oxidative stress (OS) undergone different changes, and currently OS is seen as a disruption of redox signalling and control. This review aims to offer the perspective of Complexity Theory on antioxidants framework, and diabetes disease is taken as an example.

Thyroid cancer (TC) has become the most rapidly increasing type of cancer representing 1-1.5% of all cancers diagnosed annually probably due to intensive screening. It is estimated that the death rate of TC has slowly increased from 0.49 to 0.51/100.000 in the last 10 years and 53.990 new cases will be diagnosed in 2018 in the United States. Therefore, efforts are being made in order to stop the increasing incidence and genetic alterations are thoroughly studied. One of the most recent incriminated factors in TC etiology and physiopathology is vitamin D deficiency. Besides the well-known role in bone metabolism, vitamin D has extra-skeletal effects exerted through the vitamin D receptor (VDR) and has been shown to interfere with many cellular functions such as inhibiting cell proliferation, stimulating differentiation and malignant cell apoptosis in different types of cancer. Cross-sectional, retrospective study which included 114 patients (71 with confirmed thyroid cancer and 43 patients in the control group with benign pathology). Preoperative levels of 25(OH)vitamin D, PTH, biochemical and thyroid panel were measured. The histopathologic features were analyzed. Mean values of vitamin D was 16.31 � 7.14 ng/mL with lower levels in patients with thyroid cancer (14.95 � 5.91 ng/mL) in comparison to patients with benign thyroid pathology (18.55 � 8.41 ng/mL), with a p value of 0.008. Majority of the cases were papillary thyroid cancer (97.18%) in stage 3 (45.07%). Vitamin D levels also correlated negatively with TNM staging. The necessity of further studies is a reality in order to establish if vitamin D deficiency is a possible risk factor for thyroid cancer and its correction can be considered an additional therapy.

There is ongoing debate regarding the role of neck dissection in differentiated thyroid cancer, about its usefulness in elective settings, and the increased costs regarding morbidity and operative time. This retrospective study aimed to determine the rate of metastases in cervical lymph nodes, to examine the morbidity of this surgery, and to assess whether a pattern of distribution of tumor cells concerning neck lymphatic compartments exists. The most frequent type of cancer to metastasize was papillary cancer, the majority of patients were young with a median of 30 years, predominantly females. Differentiated thyroid cancer frequently metastasizes to the central and lateral compartments of the neck. The morbidity is minimal in a high-volume center. Radical neck dissection is safe and feasible in selected patients with confirmed invaded or enlarged lymph nodes due to differentiated thyroid cancer, and postoperative complications are minimal if the anatomy is correctly identified and the cases strictly selected.

Background. The relationship between chronic pancreatitis and diabetes is well established. This form of diabetes is secondary to exocrine pancreatic disorder and is known as diabetes mellitus type 3c (T3cDM). Materials and Methods. In this retrospective study we included 261 patients, 59 patients being diagnosed with chronic pancreatitis and secondary diabetes mellitus, and admitted in the Fundeni Clinical Institute, 2nd Department of Gastroenterology or N.C. Paulescu Institute/ Carol Davila University of Medicine and Pharmacy. Results and Discussions. Patients were 22.2% women and 77.8% men, with an average age of 56.8 years and 53.4 years respectively. 63% came from urban areas. The mean duration of chronic pancreatitis was six years. Non-diabetic patients were compared with patients who were previously diagnosed with T3cDM and who had been analyzed for body mass index (BMI). Imaging investigations were also performed to confirm pseudotumors or pancreatic tumours. Patients already considered non-diabetic had basal blood glucose values and were mostly overweight and obese. In this context, insulin resistance cannot be excluded for this group of patients. Conclusions. T3cDM is a new pathological entity that needs to be explored more deeply, and that should benefit from both a diagnostic stratification and treatment.

Summary Subclinical hypothyroidism (HSC) is a relatively common thyroid dysfunction, characterized by the increase of the thyroid stimulating hormone (TSH) in the presence of normal free thyroxine values. Thyroid hormones are known for the cardiovascular effects, and the consequences of HSC on the cardiovascular system have become the focus of many studies lately. There are clear indications of the relationship between HSC and cardiovascular risk factors such as hypertension, dyslipidemia and atherosclerosis; also, HSC is associated with metabolic syndrome, BMI increase and cardiac insufficiency. Therefore, many clinical trials investigate the benefits and risks of HSC treatment with L-thyroxine.

Background and aims. Endogenous Cushing’s syndrome is a rare disease associated with severe morbidity and increased mortality if untreated. Diabetes mellitus is a frequent initial complaint of these patients. Our aim was to investigate the clinical characteristics at the time of diagnosis in a cohort of patients with endogenous Cushing’s syndrome (CS). Material and methods. A retrospective analysis of the presentation of 68 cases diagnosed with endogenous Cushing’s syndrome followed-up in our institution was performed. Results: There were 57 women and 11 men, aged 18-74 years (mean 45.57±14.2). 38 had Cushing’s disease (CD) while 30 had adrenal CS. The most frequent signs/symptoms leading to the initial consultation and diagnostic suspicion were central obesity (55 cases, 80.88%), purple striae (28 cases, 41.1%), secondary arterial hypertension (27 cases, 39.7%), secondary diabetes mellitus (24 cases, 35.29%), hirsutism in 23/55 women (41.81%), hypogonadism in 23 cases (33.82%), proximal myopathy in 17 cases (25%), edema (10 cases, 14.7%). 13 cases (19.11%) also had secondary osteoporosis (diagnosed by dual energy x-ray absorptiometry - DXA osteodensitometry). Among the two diagnostic groups there were several differences. Proximal myopathy, secondary hypertension and diabetes mellitus were all more frequent in cases with adrenal Cushing compared to those with CD. (p= 0.011, 0.006 and 0.024, respectively). This did not reflect more severe hypercortisolism in adrenal CS, as the hormonal values were similar in the two groups. Conclusion: If associated with certain clinical signs, some nonspecific (central obesity, edema, arterial hypertension), other more suggestive of CS (purple striae, proximal myopathy) diabetes mellitus could be the initial sign of this severe condition.

OBJECTIVES: Pregnancy induces changes in thyroid function, and thyroid dysfunction during gestation is associated with adverse outcomes. We examined the management of subclinical hypothyroidism and chronic autoimmune thyroiditis in pregnancy among Italian and Romanian endocrinologists. METHODS: Members of the Associazione Medici Endocrinologi (AME) and Romanian Society of Endocrinology (RSE) were invited to participate in a web-based survey investigating the topic. RESULTS: A total of 902 individuals participated in the survey, 759 of whom completed all sections. Among the respondents, 85.1% were aware of the 2017 American Thyroid Association guidelines about thyroid disease and pregnancy, and 82.9% declared that thyroid-stimulating hormone (TSH) screening at the beginning of pregnancy should be warranted. In a patient negative for peroxidase antibodies, 53.6% considered 2.5 mIU/L and 26.2% considered 4.0 mIU/L as the upper normal limit of TSH, and 50% would treat a patient with TSH 3.5 mIU/L with levothyroxine. About 20% did not suggest iodine supplementation. Isolated hypothyroxinemia detected in the first trimester would be treated by 40.8%. In patients undergoing ovarian stimulation, a TSH < 2.5 mIU/L would be targeted by 70%. CONCLUSIONS: Respondents globally appeared well informed about the management of thyroid autoimmunity and subclinical hypothyroidism in pregnancy. A more aggressive attitude in implementing iodine supplementation would be desirable. Most endocrinologists were convinced about an evident association between mild thyroid impairment and adverse outcomes in pregnancy, thus using a TSH value of 2.5 mIU/L as the threshold for diagnosing hypothyroidism and starting levothyroxine in pregnant women.

Diabetes mellitus, both type 1 and type 2 (T2DM), is associated with decreased bone strength as well as increased fracture risk. Bone mineral density is decreased in type 1 diabetes but increased in T2DM, compared with controls. This suggests alterations in bone quality are a major player in the pathogenesis of fragility fractures in patients with diabetes. The link between diabetes and bone appears to be mediated by complex pathways, including the insulin-insulin growth factors system, accumulation of advanced glycation end-products in bone collagen, microangiopathy, and increased bone marrow fat content. Bone fragility in T2DM, which is not reflected by bone mineral density and bone mass reduction, depends on deterioration of bone quality. Also, at least in T2DM, the classical diagnosis of osteoporosis by dual-energy X-ray absorptiometry and the fracture risk estimation by FRAX (fracture risk assessment tool) are only partially useful in assessing fracture risk. Trabecular bone score and trabecular bone score-adjusted FRAX offer an enhanced estimation of fracture risk in these patients. Specific risk stratification criteria are needed in the future. The development of improved methods to assess the material properties of bone to better characterize fracture risk is also a priority. Adequate glycemic control is generally associated with decreased fracture risk, with the exception of specific antidiabetics (thiazolidinediones, canagliflozin) that have been shown to have a detrimental effect. Most currently used antiosteoporotic treatments seem equally effective in diabetic patients as compared with patients without diabetes, but clinical data regarding the reduction in fracture risk specifically in patients with diabetes mellitus are lacking.