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Type 2 diabetes mellitus (T2DM) is associated with an increased risk of fragility fractures compared to the general population. The pathogenesis of the elevated fracture risk is multifactorial and still largely elusive. In contrast to primary osteoporosis, in T2DM the bone mineral density (BMD) is increased compared to controls, suggesting that specific alterations in bone quality occur in diabetic patients. Even more, the specific increase in BMD observed in these patients impairs at least in part both the classical diagnosis of osteoporosis by dual-energy X-ray absorptiometry (DXA) and the current fracture risk estimation by FRAX (fracture risk assessment tool). Trabecular bone score (TBS) and TBS-adjusted FRAX could improve fracture risk estimation in patients with T2DM but improved tools are needed in the future as well as specific risk stratification criteria. Decreases in the fracture risk of patients with T2DM can be obtained by optimal diabetes control and standard treatment of osteoporosis (most drugs appear to have similar efficacy in patients with T2DM and primary osteoporosis). [ABSTRACT FROM AUTHOR]

Introduction. Vitamin D (VD) deficiency is highly prevalent worldwide. Aim. To assess the prevalence of hypovitaminosis D in HIV-positive Romanian patients compared to controls. Methods. Serum 25OHD concentration was measured in HIV-infected patients and a control sample, matched by age, sex and menopausal status. The 25OHD status was defined as: deficiency < 20 ng/mL (severe deficiency <10 ng/mL), insufficiency 20-30 ng/mL, normal >30 ng/mL. Results. We evaluated 118 HIV-positive patients (72 males, 46 females), aged 36.9±12.2 years. 98.14% of them were on complex antiviral regimens. The B/C hepatitis coinfection rate was 9.3%. The control sample consisted of 119 subjects, (74 males, 45 women). The median and interquartile range for serum 25OHD concentration in patients was 17.6 (9.7, 26.9) ng/mL and 23.7 (18.4, 27.5) ng/mL in controls (p=0.001). Only 15.96% of HIV-positive cases and 12.71% of controls had normal VD status. The percentage of cases with severe VD deficiency was significantly higher in HIV positive cases (23.52%) compared to HIV-negative controls (4.2%, p=0.001). Conclusions. Hypovitaminosis D was identified in 84.04% of HIV-infected patients, but the serum 25OHD concentration was not associated with specific HIV-related factors in our sample. Clinical guidelines regarding VD status determination and supplementation in HIV patients are needed. [ABSTRACT FROM AUTHOR]

În prezentul articol este analizat principiul independenţei judecătorilor, atât prin prisma standardelor naţionale cât și cele internaţionale; despre separaţia puterilor în stat, independenţa puterii judecătorești și relaţia cu celelalte două puteri; de când a apărut termenul „independenţa judecătorilor”, cum și unde a fost tratat acest principiu pentru prima dată; cum ar trebui să promovăm încrederea în sistemul judecătoresc din Republica Moldova și să respectăm cu demnitate principiul independenţei judecătorilor, prin prisma legislaţiei naţionale și a standardelor internaţionale. În concluzie, s-a venit cu unele recomandări, întrucât independenţa puterii judecătorești caracterizează în mod preeminent și necesar regula de drept, fiind o garanţie fundamentală pentru un proces echitabil.

Craniopharyngiomas are rare tumors developed in the area of the sella turcica and especially the suprasellar region. Despite their benign histological nature they are locally aggressive and surgical intervention is a major challenge due to the risk of damaging critical neural and vascular neighbouring structures. Objective: To study the postsurgical evolution of craniopharyngioma in adults after total or partial surgical resection. Material and methods: We performed a retrospective review of adult craniopharyngioma patients evaluated and followed up in the Pituitary Diseases Department of the National Institute of Endocrinology in Bucharest between 1998 and 2018. Results: A total of 60 patients (39.62±15.6 years-old) diagnosed with craniopharyngioma were included. All underwent initial surgery (68.3 % transcranial, 31.7% transsphenoidal approach). Gross total resection (GTR) was achieved in 21 cases (35%), in all the others partial resection was obtained (non-GTR). Immediate non-threatening postsurgical complications were anosmia (in 2 cases), cerebrospinal fluid-CSF leak (3 cases), subdural hematoma (2 cases). After surgery 13 cases (21.66%) had cognitive impairment (2 with GTR, 11 with non-GTR), 14 (23.3%) had hypothalamic syndrome (diurnal sleepiness, appetite and memory dysfunction- present in 1 case with GTR, 13 with non-GTR), 27 cases (45%) reported lethargy (7 GTR, 20 non-GTR), 24 (40%) complained of headaches (6 GTR, 18 nonGTR). All these complications were significantly more frequent in cases with incomplete tumor resection compared to those with GTR: p= 0.000; 0.000; 0.036 and 0.009, respectively. Conclusions: Craniopharyngioma as well as its treatment are associated with very significant morbidity. Aggressive surgical resection with the aim of GTR is possible in a significant percentage of cases and if it is carefully considered in view of the surgically perceived risk of neurologic injury it is associated with lower postsurgical morbidity.

Introduction. The blood brain barrier (BBB) restricts the transport of hydrophilic molecules such as peptidic pituitary hormones into the brain tissue. The blood-cerebrospinal fluid (CSF) is a part of the BBB. Aim To compare the pituitary hormone levels on the two sides of the BBB in a group of subjects without endocrine diseases. Patients and methods. We investigated, with the approval of the local ethics committee, 78 subjects without endocrine diseases. Growth hormone (GH), prolactin (PRL), follicle-stimulating hormone (FSH), luteinizing hormone (LH) and thyroid stimulating hormone (TSH) were measured by rapid fluoroimmunoassay with Europium in the blood and cerebrospinal fluid (CSF) sampled simultaneously before rachianestesia for minor surgery. Results. CSF concentrations are significantly lower than the corresponding serum ones for all hormones studied: 0.04 ± 0.009 mU/mL vs 2.29 ± 0.57 mU/mL for GH, 1.49 ± 0.078 ng/mL vs 10.07 ± 1.42 ng/mL for PRL, 0.57 ± 0.078 U/L vs 22.71 ± 3.65 U/L for FSH, 0.39 ± 0.038 U/L vs 11.11 ± 1.55 U/L for LH and 0.01 ± 0.003 μU/mL vs 1.36 ± 0.17μU/mL for TSH (mean ± SEM; p<0.001). The CSF/serum ratio was below 1 in the vast majority of cases (from all subjects studied we only found 3 cases with supraunitary CSF/serum ratio). The serum and CSF levels were not significantly correlated for any of the pituitary hormones. Comparing preand postmenopausal women the CSF gonadotropin levels were slightly but nonsignificantly increased after menopause, despite marked differences in the serum concentrations: CSF FSH 1.21 ±0.17U/L after vs 0.84± 0.4U/L before menopause, CSF LH 0.60± 0.047U/L after vs 0.43± 0.14U/L before menopause. The CSF/ serum ratio for FSH markedly decreased after menopause (0.02±0.003 vs 0.22±0.11) although the effect did not reach statistical significance. The same was true for CSF/serum LH ratio (0.026±0.005 vs 0.09±0.002). For none of the hormones studied the CSF levels correlated with age. Conclusion. Pituitary hormones are normally found in the CSF at much lower levels than in the serum. The CSF hormonal concentrations do not significantly correlate with the serum ones. [ABSTRACT FROM AUTHOR]

Surface and groundwater pollution can be direct and indirect. In the extraction activity, oil and sewage are potential sources of groundwater pollution in the area. Petroleum is extracted from the deposit through methods that constitute both primary and secondary exploatation. The pollution in the areas of petroleum extraction is caused by leaks from the transport pipes. In the majority of the cases , the damages of the transport pipes are caused by the corrosive effect of salt water, which constitute the liquid impurity of the petroleum extract. A large quantity of petroleum products penetrate into the hydrosphere from industrial leaks and refineries, either directly in the sea or via the continental hydrographic network. It is estimated that via all these routes a quantity of 5-10 million tons of oilpenetrate into the ocean waters annually. In the area of Ţicleni, surface and groundwater quality indicators were monitored: pH, sulphates, chlorides, conductivity, hardness and oxygen content. The main water course draining under study in the area is the Amaradia River, a tributary of the Jiu River.Here samples were taken for analysis. Comparing the obtained results with the limits stipulated by the Order 161/2006 it is found that the groundwater samples analyzed from the section located at the confluence of Strâmba brook with Cioiana brook corresponds to the third grade in terms of salinity (chlorides), class II for sulphates and class I for the oxygen regime (chemical oxygen demand).

Recently, glass industry in Romania has been affected by the tendency to avoid polluting substances. A similar problem is outlined related to the cadmium glasses used for signalizations in the car construction industry. The paper presents the advantages of obtaining red glasses based on copper that is introduced as an alloy of Cu ��� Sn. The red copper glass may substitute cadmium glasses and they are used for signalizations in the car construction industry.

Background. Germline aryl hydrocarbon receptor-interacting protein (AIP) mutations are found in familial isolated pituitary adenoma syndrome (FIPA) families and in a small number of sporadic pituitary adenoma (PA) patients. Although the tumorigenic mechanisms of AIP mutations are unclear, truncating mutations are considered pathogenic, but missense mutations are difficult to evaluate. p.R16H (c.47G>A) is a controversial AIP variant of unknown significance. Aim. To describe a new PA case associated with AIP p.R16H. Patients and methods. One AIP p.R16H non-functioning pituitary adenoma (NFPA) case identified by mutation sequencing screening of sporadic PA patients; 108 controls were screened for p.R16H. Results. The 38 yrs old male NFPA patient had no family history of PA and harboured a heterozygous p.R16H variant. The proband and two brothers presented severe intellectual disability. Severe visual impairment was the initial symptom and clinical, biochemical and imaging examination demonstrated a large NFPA invading the right cavernous sinus. After transsphenoidal debulking, the remaining tumor continued growth. One of proband's sisters was negative for p.R16H. Among controls, we identified one heterozygous p.R16H carrier, presenting a thyroid follicular neoplasm. Loss of heterozygosity analysis of the pituitary and thyroid tumors was not performed. Conclusions. We report two new occurrences of AIP p.R16H, associated with a NFPA and with a thyroid tumor. The NFPA patient was young and presented an invasive macroadenoma, features typical of AIP-mutated patients. Because the association between p.R16H and PAs has not been conclusively established, further research of p.R16H is warranted, in view of its implications for AIP genetic testing. [ABSTRACT FROM AUTHOR]

Our aim was to explore the interactions of intercellular adhesion molecule (sICAM-1), TNF-α (tumor necrosis factor-α), interleukin-1α (IL-1α) and interleukin-6 (IL-6) with dopamine agonists in a culture of adenomatous cells from an nonfunctional macroadenoma. Materials and methods. Tissue specimen from pituitary macroadenoma removed in transsphenoidal surgery was prepared for primary culture. Cells were counted and plated at 105/well into 24-well plates in a final volume of 1ml. Cabergoline in molar doses of 10-6, 10-7, 10-8, 10-9 was added and the cells were incubated for 4 days. sICAM-1, TNF-α, IL-1 α, IL-6 were measured from cell-culture supernatants by ELISA kits. Results. sICAM-1, TNF-α, IL-1α and IL-6 were detected in the untreated control cultures after a 4d period. There was a negative correlation between TNFα and IL-1α (p=0.007). The levels of PRL and hGH had measurable values above those found in culture medium without tumor cells. PRL positively correlated with IL-1α ( p=0.05). hGH positively correlated with cell proliferation (p=0.049). Cabergoline treatment showed that IL-6 progressively decreased with the dose, ranging from -27.41% to -76.44%. TNF-α significantly decreased (-65.90%; p<0.03) at the cabergoline 10-7 M dose. IL-1α progressively increased with cabergoline dose, ranging from -2.53% to 345 %. sICAM-1 was significantly reduced by cabergoline at 10-9 (-47.12 %; p= 0.045) and 10-6 M (-59.16%; p=0.01) doses. TNF-α positively correlated with PRL (p=0.025); IL-6 positively correlated with hGH (p=0.044); sICAM-1 negatively correlated with hGH (p=0.009), TNFα (p=0.025) and IL-1α (p=0.044). Conclusions. These data support the existence of an immunoendocrine network in pituitary tumorigenesis; TNF-α, IL-6, IL-1α, sICAM-1 significantly interfered by cabergoline treatment in a dose-dependent way. However, future studies on different types of pituitary tumours are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Background. Usually, silver stain is needed to differentiate between normal or hyperplastic hypophysis and pituitary adenomas. Many papers reported the lack of reticular fibers network as mandatory for pituitary adenoma diagnosis. Aim. Differences between the architecture of reticular fibers in normal pituitary and pituitary adenomas. Methods. Gordon- Sweet silver staining of pituitary specimens, prelevated during pituitary surgery performed in 138 patients with the endocrine and imagistic diagnosis of pituitary macro-adenomas. Results. Pituitary specimens of pituitary adenomas was confirmed in 133 cases; 3 specimens were with normal pituitary tissue, 1 with pituitary hyperplasia, 1 with pituitary apoplexy. Twelve of 133 pituitary adenomas specimens were associated also with normal pituitary tissue. There was a loss of acinar network of reticular fibres in 115 cases, but the present study describes the persistence of reticular fibers networks in 18 (13.53%) of 133 pituitary adenomas. We identified five distribution patterns of remanent reticular fibers network in pituitary adenomas using silver staining. Conclusion. Persistence of reticular fibers in a small number of pituitary adenomas could be a possible pitfall in the discrimination between the normal hypophysis and pituitary adenoma. [ABSTRACT FROM AUTHOR]

Context: Functioning pituitary adenomas (FPAs) include most frequently prolactinomas, somatotroph or corticotroph adenomas, while thyrotroph and gonadotroph adenomas are very rare. Despite their benign histological nature (aggressive tumors are rare and malignant ones exceptional), FPAs could cause significant morbidity and increased mortality due to complications associated with hormonal excess syndromes and/or mass effect leading to compression of adjacent structures. This mini review will focus on the increasing role of medical therapy in the multimodal treatment, which also includes transsphenoidal surgery (TSS) and radiotherapy., Evidence Synthesis: Most patients with prolactinomas are treated only with medications, but surgery could be considered for some patients in a specialized pituitary center, if higher chances of cure. Dopamine agonists, especially cabergoline, are efficient in reducing tumor size and normalizing prolactin. TSS is the first-line treatment for all other FPAs, but most patients require complex adjuvant treatment, including a combination of therapeutic approaches. Medical therapy is the cornerstone of treatment in all patients after unsuccessful surgery or when surgery cannot be offered and includes somatostatin receptor ligands and dopamine agonists (almost all FPAs), growth hormone receptor antagonists (acromegaly), adrenal steroidogenesis inhibitors and glucocorticoid receptor blockers (Cushing's disease). Novel medical treatments, especially for acromegaly and Cushing's disease are under research., Conclusions: An enlarged panel of effective drugs available with increased knowledge of predictive factors for response and/or adverse effects will enhance the possibility to offer a more individualized treatment. This would not only improve disease control and prognosis, but also quality of life., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

There is increased interest related to the impact of coronavirus disease 19 (COVID-19) on the endocrine system and in particular on the pituitary gland. Over the course of the severe infection with acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there are both acute and delayed effects on the pituitary, related to infection and/or treatment. Hypopituitarism, pituitary apoplexy and hypophysitis have been all reported, as well as arginine vasopressin deficiency (diabetes insipidus) and syndrome of inappropriate antidiuretic hormone secretion. Furthermore, patients with acromegaly, Cushing's disease and hypopituitarism are theoretically at increased risk of complications with COVID-19 and require close monitoring. Evidence regarding pituitary dysfunction in patients with COVID-19 continues to be gathered, as the breadth and depth of knowledge also continues to rapidly evolve. This review summarizes data analysis to date on the possible effects of COVID-19 and COVID-19 vaccination on patients with normal pituitary function and patients with known pituitary pathology. Though clinical systems were significantly affected, it seems there is no overall loss of biochemical control in patients with certain pituitary pathologies., Competing Interests: Disclosures The authors have no conflict of interest(s) to report regarding this topic., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background and objective Pituitary apoplexy (PA) is a possible life-threatening disorder due to spontaneous hemorrhage or impaired blood supply in the pituitary gland. It may present as an acute or subclinical form, and treatment options include either surgery or a conservative approach. The purpose of this study was to retrospectively analyze the clinical, imaging, and hormonal features, as well as the therapeutic outcomes, in a relatively short period of time in a series of consecutive patients with pituitary apoplexy (PA). Results Thirty-six patients were included, 50% presenting typical symptoms of PA. The presenting symptoms were headache (44.4%), visual abnormalities (44.4%), and digestive symptoms (22.2%). At diagnosis, hormonal deficiency was observed in 22 (61.1%) patients. Of the evaluated patients, 78.2% of the 23 operated cases and all unoperated cases presented tumor remnants. Vision improved in 81.8% of the operated and 100% of conservatively managed cases. Of all cases, 69.4% remained with long-term hypopituitarism. Conclusion Complex management of PA frequently leads to visual improvement but long-standing hypopituitarism., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Arbunea-Ghenoiu et al.)

Functioning gonadotroph adenomas (FGAs) are rare tumors, as the overwhelming majority of gonadotroph tumors are clinically silent. Literature is based on case reports and small case series. Gonadotroph tumors are poorly differentiated and produce and secrete hormones inefficiently, but in exceptional cases, they cause clinical syndromes due to hypersecretion of intact gonadotropins. The clinical spectrum of endocrine dysfunction includes an exaggerated response of ovaries characterized as ovarian hyperstimulation syndrome (OHSS) in premenopausal females and adolescent girls, testicular enlargement in males, and isosexual precocious puberty in children. Transsphenoidal surgery and removal of tumor reduces hormonal hypersecretion, improves endocrine dysfunction, and provides tissue for further analysis. Medical therapies (somatostatin analogues, dopamine agonists, GnRH agonists/antagonists) are partially or totally ineffective in many cases, especially with respect to antitumor effect. This review aims to update recent literature on these rare functioning tumors and highlight their therapeutic management.

Purpose of Review: Endogenous Cushing's syndrome (CS) is associated with increased patient morbidity (hypertension, diabetes mellitus, dyslipidemia, visceral obesity, osteoporosis, cognitive alterations, and impaired quality of life). Both arterial and venous thromboembolic events (TE) due to alterations in the hemostatic system and prothrombotic state are widely reported in patients with CS, more so postoperatively. Increased mortality, if not appropriately treated, is largely due to cardiovascular events and infections., Recent Findings: Patients with CS have markedly increased risk of thromboembolic episodes compared to the general population. The prothrombotic state is mediated by increased levels of procoagulant factors, but also by an impaired fibrinolytic capacity. All contribute to TE, atherosclerosis, and subsequent cardiovascular morbidity and mortality. Some abnormalities progressively improve after CS remission, but do not fully normalize for at least 1 year or more., Summary: Due to the additional thrombotic risk of surgery or any invasive procedure, anticoagulation prophylaxis should be at least considered in patients with CS and balanced with individual bleeding risk. However, a clear protocol of thromboprophylaxis is lacking and increased awareness regarding risks per se is needed. Large prospective trials will clarify, which patients with CS are at the highest risk and the optimal prevention protocol to minimize risks and maximize efficacy., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: 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)., Areas Covered: 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., Expert Opinion: Treatment of persistent/recurrent CD is challenging. Most patients require >1 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.

We report a case of a patient who presented to our endocrinology department for gradual onset with headache, fatigue, and weight loss over the course of one month. On physical examination, the patient showcased coarse facial features, acral enlargement, and other features suggestive of acromegaly. However, despite a clinical picture consistent with this diagnosis, serum growth hormone and insulin-like growth factor 1 were below reference range. Furthermore, secondary adrenal insufficiency, secondary hypothyroidism, and hypogonadotropic hypogonadism were discovered. Imaging revealed a pituitary macroadenoma and after a neurosurgical consult, the patient underwent transsphenoidal hypophysectomy and the suspected diagnosis of subacute pituitary adenoma apoplexy (SPAA) was confirmed via histology of resected tissue. Additionally, we review the literature for other case reports of patients with acromegaly or acromegalic features who underwent pituitary apoplexy to identify patient characteristics, presumed etiologies, and presence of biochemical cure of acromegaly following SPAA., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Klimko et al.)

Background: Solitary fibrous tumours (SFTs) rarely occur in the orbit, especially in the lacrimal area. These tumours are mostly solid. Cystic changes have been documented, but they remain very rare. Only three cases of primary orbital solitary fibrous tumours with cystic changes have been reported in the literature, but no cases have been reported to occur in the lacrimal gland. Solitary fibrous tumours generally follow a benign course and are treated definitively with surgical excision. Data from the literature suggest that the cystic nature of SFT presents a risk of recurrence and could be a harbinger of malignancy., Case Presentation: A 42-year-old woman was admitted to the endocrinology department for right unilateral exophthalmia and epiphora in the last 8 months. An ophthalmological evaluation showed exophthalmia only in the right eye (22 mm) and normal visual acuity, visual field and extraocular movements. Investigations revealed normal thyroid function. Orbital magnetic resonance imaging detected a 4 × 2,2 × 2,7 cm septate pseudocystic mass in the right lacrimal gland. Given her lacrimal gland tumour diagnosis, the patient was submitted for neurosurgical intervention with total ablation of the tumoural mass and complete right dacryoadenectomy. Although the intraoperative extemporaneous examination results were suggestive of a haemangiopericytoma, histological and immunocytochemical examination showed an extrapleural SFT. The postoperative clinical evolution was favourable, with remission of the exophthalmia. Fifteen months after surgery, no signs of recurrence were noticed., Conclusions: We report the first case of an SFT with cystic changes in the lacrimal gland. Although the presence of cavitary lesions alone does not necessarily indicate aggressive behaviour, cystic changes pose a risk of recurrence and may suggest malignant transformation over time. As a result, our case requires long-term follow-up due to recurrence and malignant potential.

Background/aim: The aim of this study was to evaluate SOX2 expression in pituitary adenomas and its correlation to their secretory state and clinicopathological parameters., Patients and Methods: Thirty-four patients were clinically evaluated and surgery was recommended for tumor removal. Histopathological diagnosis by hematoxylin eosin staining was followed by immunohistochemistry for pituitary hormones and SOX2 co-expression., Results: Fourteen of the 34 cases were GH-secreting adenomas, 10 were prolactinomas and 10 non-functioning pituitary adenomas. SOX2-positive expression was detected in 47.05% of total cases: 8 GH-secreting adenomas (57.14%), 6 prolactinomas (60%) and 2 non-functioning adenomas (20%). SOX2 positivity was significantly higher amongst secreting adenomas (p=0.041). SOX2-negative tumors were significantly associated with corticotrophin deficiency (p=0.047) and gonadotrophin deficiency (p=0.041). No correlation with tumor size or extrasellar extension was detected., Conclusion: SOX2 is differentially expressed in pituitary adenomas and influences the secretory state or clinical behavior of pituitary adenomas., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

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., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: In Romania, no nationwide data for acromegaly treatment and control rate are available. Our objective was to assess the acromegaly control rate in a tertiary referral centre, which covers an important part of Romanian territory and population of patients with acromegaly., Materials and Methods: We reviewed the records of all 164 patients (49 males and 115 females; median age 55 [47, 63.5] years) with newly or previously diagnosed acromegaly, who have been assessed at least once in our tertiary referral centre between January 1, 2012 and March 31, 2016. This sample represents 13.6% of the total expected 1200 Romanian patients with acromegaly and covers 82.9% of the counties in Romania. Control of acromegaly was defined as a random serum growth hormone (GH) < 1 ng/mL and an age-normalised serum insulin-like growth factor-I (IGF-I) value. The GH and IGF-I values used for calculation of the control rate were those at the last evaluation. The same assays for GH and IGF-I measurement were used in all patients., Results: There were 147 treated and 17 untreated patients. Of the 147 patients assessed after therapy, 137 (93.2%) had pituitary surgery, 116 (78.9%) were on medical treatment at the last evaluation, and 67 (45.5%) had radiotherapy. Seventy-one (48.3%) had a random GH < 1 ng/mL, 54 (36.7%) had a normalised, age-adjusted IGF-I, and 42 (28.6%) had both normal random serum GH and IGF-I., Conclusions: In Romania, acromegaly benefits from the whole spectrum of therapeutic interventions. However, the control rate remains disappointing.

Objective: Non-functioning pituitary adenomas (NFAs) have a prevalence of 7-22/100,000 people. A significant number of patients suffer from morbidities related to the tumor, possible recurrence(s), and treatments utilized. Our aim was to assess mortality of patients with macroNFA and predictive factors., Design: Retrospective cohort study in a tertiary referral center in the UK., Methods: A total of 546 patients operated for a macroNFA between 1963 and 2011 were studied. Mortality data were retrieved through the National Health Service Central Register and hospital records and recorded as standardized mortality ratio (SMR). Mortality was estimated for the total and various subgroups with clinical follow-up data., Results: Median follow-up was 8 years (range: 1 month-48.5 years). SMR was 3.6 (95% CI, 2.9-4.5), for those operated before 1990, 4.7 (95% CI, 2.7-7.6) and for those after 1990, 3.5 (95% CI, 2.8-4.4). Main causes of death were cardio/cerebrovascular (33.7%), infections (30.1%), and malignancy (28.9%). Cox regression analysis demonstrated that only age at diagnosis remained an independent predictor of mortality (hazard ratio 1.10; 95% CI, 1.07-1.13, P<0.001), whereas sex, presentation with acute apoplexy, extent of tumor removal, radiotherapy, recurrence, untreated GH deficiency, FSH/LH deficiency, ACTH deficiency, TSH deficiency, and treatment with desmopressin had no impact., Conclusions: Despite the improvement of treatments over the last three decades, the mortality of patients with NFAs in our series remains high. Apart from age, factors related with the management/outcome of the tumor are not independent predictors, and pituitary hormone deficits managed with the currently-used substitution protocols do not adversely affect mortality., (© 2016 European Society of Endocrinology.)

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.

Hypothesis. The osteoporotic fractures represent a worldwide economical issue. In order to prevent them, we need to understand the risk factors constellation. Although obesity was traditionally considered as protective against osteoporosis, recent data exposed an increased risk of falling and thus a high risk of some fractures. Objective. We aimed to analyze the body mass index (BMI) in relationship with the bone mineral density (BMD) and the prevalent fractures. Methods and Results. Between 2008 and 2014, a cross-sectional observational study included Romanian menopausal Caucasian women without a previous diagnosis of bone maladies, or specific anti-osteoporotic therapy. Prevalent fragility fractures were both self-declared and incidental vertebral. All the subjects had lumbar BMD (GE Lunar Prodigy DXA machine). Out of 622 females (mean age of 58.65 years, mean BMI of 30.30 kg/ m2), 39.22% were obese (BMI ≥ 30kg/ m2). The fracture prevalence was 1.35% versus 1.67% in obese versus non-obese patients. The correlation coefficient between lumbar BMD and BMI was r=0.165, p<0.005. BMI in the fracture group was 31.68 kg/ m2 vs. 30.04 kg/ m2 in the non-fracture group (p=0.08). 15.91% of the entire cohort had prevalent fractures. Obesity prevalence among females with fractures was 30.3% versus 40.73% in the non-fracture group. The most frequent sites were distal forearm (42.42%) and vertebral (21.21%). Discussions & Conclusions. Although the vertebral fractures might be underdiagnosed in our study and despite the fact that we enrolled a relatively young menopausal population, BMI positively correlated with BMD, regardless of the fractures' prevalence. In early menopause, the most frequent fracture is distal forearm. BMI is higher in patients with prevalent fractures vs. non-fractures (borderline significance). Obesity might not protect from any type of fracture but future evidence is necessary since one third of osteoporotic fractures are met in women with a BMI ≥ 30kg/ m2.

Acromegaly (ACM) is a chronic, progressive disorder caused by the persistent hypersecretion of GH, in the vast majority of cases secreted by a pituitary adenoma. The consequent increase in IGF1 (a GH-induced liver protein) is responsible for most clinical features and for the systemic complications associated with increased mortality. The clinical diagnosis, based on symptoms related to GH excess or the presence of a pituitary mass, is often delayed many years because of the slow progression of the disease. Initial testing relies on measuring the serum IGF1 concentration. The oral glucose tolerance test with concomitant GH measurement is the gold-standard diagnostic test. The therapeutic options for ACM are surgery, medical treatment, and radiotherapy (RT). The outcome of surgery is very good for microadenomas (80-90% cure rate), but at least half of the macroadenomas (most frequently encountered in ACM patients) are not cured surgically. Somatostatin analogs are mainly indicated after surgical failure. Currently their routine use as primary therapy is not recommended. Dopamine agonists are useful in a minority of cases. Pegvisomant is indicated for patients refractory to surgery and other medical treatments. RT is employed sparingly, in cases of persistent disease activity despite other treatments, due to its long-term side effects. With complex, combined treatment, at least three-quarters of the cases are controlled according to current criteria. With proper control of the disease, the specific complications are partially improved and the mortality rate is close to that of the background population., (© 2015 Society for Endocrinology.)

Traumatic brain injury (TBI) is a significant cause of morbidity and mortality in many age groups. Neuroendocrine dysfunction has been recognized as a consequence of TBI and consists of both anterior and posterior pituitary insufficiency; water and electrolyte abnormalities (diabetes insipidus (DI) and the syndrome of inappropriate antidiuretic hormone secretion (SIADH)) are amongst the most challenging sequelae. The acute head trauma can lead (directly or indirectly) to dysfunction of the hypothalamic neurons secreting antidiuretic hormone (ADH) or of the posterior pituitary gland causing post-traumatic DI (PTDI). PTDI is usually diagnosed in the first days after the trauma presenting with hypotonic polyuria. Frequently, the poor general status of most patients prevents adequate fluid intake to compensate the losses and severe dehydration and hypernatremia occur. Management consists of careful monitoring of fluid balance and hormonal replacement. PTDI is associated with high mortality, particularly when presenting very early following the injury. In many surviving patients, the PTDI is transient, lasting a few days to a few weeks and in a minority of cases, it is permanent requiring management similar to that offered to patients with non-traumatic central DI.

Pituitary tumour apoplexy (PA) is a rare clinical syndrome that occurs as a result of acute haemorrhage and/or infarction within a frequently undiagnosed pituitary tumour. The sudden enlargement of the pituitary mass undergoing PA is responsible for a wide range of acute symptoms/signs (severe headache, visual loss, diplopia, hypopituitarism, impaired consciousness) which, together with the radiological evidence of a pituitary lesion, establish the diagnosis. The optimal care of PA requires involvement of a multidisciplinary team including endocrinologist, neurosurgeon, neuroophthalmologist and the management strategy that depends on the clinical manifestations, as well as the presence of co-morbidities. Prompt surgical decompression is initially indicated in cases with severe or progressive impairment of the visual acuity or the visual fields or with altered mental state and leads to visual and neurological recovery in most of the patients. The patients with mild, stable clinical picture (including those with isolated ocular palsies) can be managed conservatively (support of fluid and electrolyte balance and stress doses of steroids in most cases) with favourable visual and neurological outcome. Frequent reassessment is mandatory because the clinical course can be unpredictable; if progression of symptoms occurs, later elective surgery is indicated and is beneficial, especially in terms of visual outcome. The endocrinological outcome is less favourable, irrespective of the treatment option, with many patients remaining on long-term replacement therapy. Despite the above guidelines, clear proof of optimal outcomes in the form of randomised controlled trials is lacking. Regrowth of the pituitary tumour years after a PA episode is possible and patients require long-term surveillance., (© 2015 European Society of Endocrinology.)

This article presents an overview of adult growth hormone deficiency (AGHD) and corticotropin deficiency (central adrenal failure, CAI). Both conditions can result from various ailments affecting the hypothalamus or pituitary gland (most frequently a tumor in the area or its treatment). Clinical manifestations are subtle in AGHD but potentially life-threatening in CAI. The diagnosis needs dynamic testing in most cases. Treatment of AGHD is recommended in patients with documented severe deficiency, and treatment of CAI is mandatory in all cases. Despite significant progress in replacement hormonal therapy, more physiologic treatments and more reliable indicators of treatment adequacy are still needed., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Introduction: Low vitamin D (VD) is associated with secondary hyperparathyroidism and both contribute to deleterious consequences (reduced bone mineral density (BMD), risk of fractures and falls)., Objective: To study the VD status and biological correlates in a group of postmenopausal women., Material and Methods: We studied 123 postmenopausal women evaluated in the C.I.Parhon National Institute of Endocrinology, the Pituitary and Neuroendocrine Diseases department. All cases had been reffered for the evaluation of BMD by the general practitioner. The evaluation included serum measurements of total and ionised calcium, phosphorus, alkaline phosphatase (ALP), 25 hydroxi vitaminD (25OHD), parathyroid hormone (PTH), osteocalcin, betacrosslaps. Central DXA osteodensitometry was performed., Results: 91.9% of cases had 25OHD serum levels below 30 ng/ml (74.8% had VD deficiency, 17.1% VD insufficiency). Only 8.1% had sufficient VD levels. A history of fragility fractures was present in 45.83% of the osteoporotic patients, 27.27% of the osteopenic ones and 15.15% of the women with normal BMD. 32 women (26%) were on VD supplementation at the time of evaluation. Among these subjects, the 25OHD level was significantly higher in those with prior fragility fractures (p=0.018) and osteoporosis (p=0.008). 25OHD concentration negatively correlated with PTH, alkaline phosphatase (ALP) and osteocalcin. The bone markers evaluated had a significant inverse correlation with the radius BMD, T and Z scores (p=0.004). 27.17% of the cases with VD deficiency had secondary hyperparathyroidism. The 25OHD concentration was significantly lower in these cases (p=0.000)., Conclusions: VD insufficiency is widely prevalent but still under-recognized and under-treated, possibly leading to secondary hyperparathyroidism. The compliance to VD supplementation is lower in subjects without osteoporosis or fragility fractures. Primary prevention measures should be more actively implemented.

Paragangliomas (PGLs) are tumours originating from neural crest-derived cells situated in the region of the autonomic nervous system ganglia. Head-and-neck PGLs (HNPGLs) originate from the sympathetic and parasympathetic paraganglia, most frequently from the carotid bodies and jugular, tympanic and vagal paraganglia, and are usually non-catecholamine secreting. Familial PGLs are considered to be rare, but recently genetic syndromes including multiple PGLs and/or phaeochromocytomas have been more thoroughly characterised. Nowadays, genetic screening for the genes frequently implicated in both familial and sporadic cases is routinely being recommended. HNPGLs are mostly benign, generally slow-growing tumours. Continuous growth leads to the involvement of adjacent neurovascular structures with increased morbidity rates and treatment-related complications. Optimal management mostly depends on tumour location, local involvement of neurovascular structures, estimated malignancy risk, patient age and general health. Surgery is the only treatment option offering the chance of cure but with significant morbidity rates, so a more conservative approach is usually considered, especially in the more difficult cases. Radiotherapy (fractionated or stereotactic radiosurgery) leads to tumour growth arrest and symptomatic improvement in the short term in many cases, but the long-term consequences are unclear. Early detection is essential in order to increase the chance of cure with a lower morbidity rate. The constant improvement in diagnostic imaging, surgical and radiation techniques has led to a safer management of these tumours, but there are still many therapeutic challenges, and no treatment algorithm has been agreed upon until now. The management of HNPGLs requires a multidisciplinary effort addressing the genetic, surgical, radiotherapeutic, oncological, neurological and endocrinological implications. Further progress in the understanding of their pathogenesis will lead to more effective screening and earlier diagnosis, both critical to successful treatment.

Objective: Non-functioning pituitary adenomas (NFA) may be associated with significant morbidity. Published data on the quality of life (QoL) of patients with NFA are scarce and conflicting. In view of the discordant findings and the advances in the management of these subjects, we aimed to evaluate the QoL in patients with NFA followed up in a tertiary endocrine UK referral centre., Subjects and Methods: All consecutive patients with NFA attending the outpatient clinic in the Department of Endocrinology in Oxford over a 6-month period (n = 193) were offered 3 health-related QoL questionnaires [Short Form 36 (SF36), Nottingham Health Profile (NHP), European Quality of Life Scale (EuroQoL)] to complete. Patient outcomes (response rate 93.3%) were compared with age-related UK reference values., Results: None of the QoL scores in the SF-36 or the 5 dimensions of health in the EuroQoL was different from the reference values. The visual analogue scale (VAS) score (EuroQoL) was slightly compromised (P = 0.041). In the NHP questionnaire, males had no parameter significantly affected, whereas females performed worse in 1/6 areas (energy levels). Tumour recurrence was an independent predictor for compromised VAS score and for anxiety/depression (EuroQoL), and visual field defects for more frequent problems with interests/hobbies (NHP)., Conclusions: Overall, the health-related QoL and perception of subjective health in patients with NFA was not compromised to any major extent suggesting that we can now offer the prospect of treatment and replacement, which will provide a normal or near-normal QoL. Specific groups are affected in various dimensions, necessitating measures to compensate for predisposing factors., (© 2012 Blackwell Publishing Ltd.)