Use of levothyroxine for euthyroid, thyroid antibody positive women with infertility: Analyses of aggregate data from a survey of European thyroid specialists (Treatment of Hypothyroidism in Europe by Specialists: An International Survey).

OBJECTIVES: The use of levothyroxine (LT4) treatment aiming to improve fertility in euthyroid women with positive thyroid peroxidase antibodies (TPOAb) is not supported by the available evidence. The aim of the study was to document the use of LT4 by European thyroid specialists in such patients. DESIGN: The data presented derive from Treatment of Hypothyroidism in Europe by Specialists, an International Survey (THESIS), a questionnaire conducted between 2019 and 2021 to document the management of hypothyroidism by European thyroid specialists. Here, we report the aggregate results on the use of LT4 in infertile, euthyroid women with positive TPOAb. RESULTS: A total of 2316/5406 (42.8%) respondents stated that LT4 may be indicated in TPOAb positive euthyroid women with infertility. The proportion of those replying positively to this question varied widely across different countries (median 39.4, range 22.9%-83.7%). In multivariate analyses males (OR: 0.8; CI: 0.7-0.9) and respondents >60 years (OR: 0.7; 0.6-0.8) were the least inclined to consider LT4 for this indication. Conversely, respondents managing many thyroid patients ("weekly" [OR: 1.4; CI: 1.0-1.9], "daily" [OR: 1.8; CI: 1.3-2.4]) and practicing in Eastern Europe (OR: 1.5; CI: 1.3-1.9) were most likely to consider LT4. CONCLUSIONS: A remarkably high number of respondents surveyed between 2019 and 2021, would consider LT4 treatment in TPOAb positive euthyroid women with infertility. This view varied widely across countries and correlated with sex, age and workload, potentially influencing patient management. These results raise concerns about potential risks of overtreatment.

Glucose intolerance in acromegaly is driven by low insulin secretion; results from an intravenous glucose tolerance test.

PURPOSE: Insulin sensitivity (Si) and its role in glucose intolerance of acromegaly has been extensively evaluated. However, data on insulin secretion is limited. We aimed to assess stimulated insulin secretion using an intravenous glucose tolerance test (IVGTT) in active acromegaly. METHODS: We performed an IVGTT in 25 patients with active acromegaly (13 normal glucose tolerance [NGT], 6 impaired glucose tolerance [IGT] and 6 diabetes mellitus [DM]) and 23 controls (8 lean NGT, 8 obese NGT and 7 obese IGT). Serum glucose and insulin were measured at 20 time points along the test to calculate Si and acute insulin response (AIRg). Medical treatment for acromegaly or diabetes was not allowed. RESULTS: In acromegaly, patients with NGT had significantly (p for trend < 0.001) higher AIRg (3383 ± 1082 pmol*min/L) than IGT (1215 ± 1069) and DM (506 ± 600). AIRg was higher in NGT (4764 ± 1180 pmol*min/L) and IGT (3183 ± 3261) controls with obesity than NGT (p = 0.01) or IGT (p = 0.17) acromegaly. Si was not significantly lower in IGT (0.68 [0.37, 0.88] 106*L/pmol*min) and DM (0.60 [0.42, 0.84]) than in NGT (0.81 [0.58, 1.55]) patients with acromegaly. NGT (0.33 [0.30, 0.47] 106*L/pmol*min) and IGT (0.37 [0.21, 0.66]) controls with obesity had lower Si than NGT (p = 0.001) and IGT (p = 0.43) acromegaly. CONCLUSION: We demonstrated that low insulin secretion is the main driver behind glucose intolerance in acromegaly. Compared to NGT and IGT controls with obesity, patients with NGT or IGT acromegaly had higher Si. Together, these findings suggest that impaired insulin secretion might be a specific mechanism for glucose intolerance in acromegaly.

Bone turnover correlates with bone quantity but not bone microarchitecture in chronic hemodialysis.

INTRODUCTION: In chronic hemodialysis, high-turnover bone disease was associated with decreased bone mineral density (BMD), poor bone quality (chemical and structural), and increased fracture risk. Our aim was to correlate bone turnover markers (BTMs) with bone microarchitecture measured by trabecular bone score (TBS) before and after correction for BMD. MATERIALS AND METHODS: We measured lumbar spine (LS), femoral neck, and 1/3 radius BMD and LS TBS by dual X-ray absorptiometry in 81 patients on permanent hemodialysis. Bone turnover was assessed using serum parathyroid hormone, osteocalcin, C-terminal crosslaps of type 1 collagen, procollagen 1 N-terminal propeptide (P1NP), and alkaline phosphatase (ALP). No patient had any partial or total parathyroidectomy and no previous or current treatment with anti-osteoporotic drugs. RESULTS: All BTMs correlated significantly with each other. Univariate regressions showed significant negative correlations between BTMs and BMD (best r = - 0.53, between P1NP and 1/3 radius Z-score) or BTMs and TBS (best r = - 0.27, p < 0.05 between ALP and TBS T-score). TBS correlated significantly with BMD at all three sites (best r = 0.5, between LS BMD and TBS T-score). Multivariate regression showed that TBS, crude or adjusted, correlated with LS BMD. No model retained any of the BTMs as independent variables due to the better prediction of BMD and multicollinearity. CONCLUSION: We showed a progressively impaired bone microarchitecture with increasing bone turnover in chronic hemodialysis. However, this correlation is no longer present when controlling for bone mass. This suggests that impaired bone microarchitecture and increased fracture risk are dependent upon factors other than high bone turnover.

SERIAL CHANGES OF LIVER FUNCTION TESTS BEFORE AND DURING METHIMAZOLE TREATMENT IN THYROTOXIC PATIENTS.

OBJECTIVE: Overt hyperthyroidism and methimazole (MMI) treatment are frequently associated with abnormal liver function tests (LFTs). We describe the serial changes of LFTs in MMI-treated hyperthyroid patients. METHODS: We retrospectively analyzed all 77 patients presenting with newly diagnosed overt hyperthyroidism (59 Graves diseases, 11 toxic nodular goiters, 4 toxic adenomas, 3 amiodarone-induced thyrotoxicosis) between 2012 and 2014. All patients started MMI at 10 to 60 mg/day that was gradually tapered. We measured thyroid-stimulating hormone, free thyroxine, alanine aminotransferase (ALT) and aspartate aminotrasnferase (AST) at baseline and at 6 weeks, 4.5 months and 10 months after starting the MMI treatment. The concomitant medication was stable during MMI treatment. RESULTS: At baseline, 25 patients (32.5%) had abnormal LFT, of which 5 had ALT or AST levels >2× the upper limit of normal (ULN). In most patients with baseline abnormal LFT, MMI treatment resulted in a normalization of serum ALT and AST. Thirteen patients with normal baseline LFT had <2× the ULN elevations of LFT sometime during treatment. There was a case of significant hepatotoxicity. During treatment, there were no significant differences in LFT levels between patients with initially normal or abnormal LFT. In a Cox proportional hazard regression model, abnormal LFT at baseline, abnormal thyroid function at the last evaluation, and MMI dose were not predictors of abnormal LFT at the final evaluation. CONCLUSION: MMI treatment can induce insignificant LFT elevation, <2× the ULN. MMI can be safely administered in hyperthyroid patients with abnormal LFT, and normalization of increased AST and ALT levels should be anticipated. ABBREVIATIONS: ALT = alanine aminotransferase AST = aspartate aminotransferase fT4 = free thyroxine HCV = hepatitis C virus LFT = liver function test LOCF = last observation carried forward MMI = methimazole PTU = propylthiouracil TSH = thyroid-stimulating hormone ULN = upper limit of normal.

Plasma free metanephrine and normetanephrine levels are increased in patients with chronic kidney disease.

OBJECTIVE: Patients with impaired renal function, particularly those on dialysis, frequently exhibit high blood pressure and hemodynamic instability, which often lead to pheochromocytoma assessment. Our objective was to assess plasma free metanephrine (MN) and normetanephrine (NMN) in chronic kidney disease patients (CKD) with or without dialysis. METHODS: In this prospective observational study we performed enzyme-linked immunosorbent assays (ELISAs) to evaluate plasma free MN and NMN in 48 CKD patients (15 with stage 3-5 CKD without dialysis, 26 on hemodialysis [HD], and 7 continuous ambulatory peritoneal dialysis [CAPD]), 30 patients with histologically proven pheochromocytoma, and 43 hypertensive patients. Adrenal masses were ruled out by abdominal computed tomography (CT) scans in all CKD and control hypertensive patients. RESULTS: All 3 CKD groups (HD, CAPD, and CKD without dialysis) had significantly higher plasma free MN and NMN levels than the control hypertensive group (P<.0055). HD and CAPD patients had significantly lower plasma free NMN (P<.0055), but free MN levels were not significantly different than those observed in pheochromocytoma patients. In patients with HD, CAPD, and CKD without dialysis, plasma free MN and NMN were higher than manufacturer's upper limits of normal in 57.7% and 28.5%, 13.3% and 61.5%, and 85.7% and 26.6%, respectively. Regression models showed that the number of dialysis years was significantly correlated with plasma free MN (r = 0.615, P<.001) but not free NMN. CONCLUSION: Plasma free MN and NMN levels are frequently elevated in CKD patients, particularly in those on dialysis. Plasma free MN levels significantly overlap with the range in pheochromocytoma patients and correlate with the number of years on dialysis.

High mortality risk among women with acromegaly still persists.

Introduction: The mortality ratio in patients with acromegaly has improved over the last few decades. We aimed to determine the mortality rate and correlated factors in patients with acromegaly before and after the introduction of national protocols for treatment. In addition, we determined whether there are sex-related differences in mortality of patients with acromegaly. Methods: This observational retrospective study included 399 consecutive patients with acromegaly between January 2001-December 2022. Paraclinical data included random growth hormone (GH) and insulin-like growth factor-I (IGF1) levels, maximal pituitary tumor diameter at diagnosis, first visit, and last evaluation. Standardized mortality ratio (SMR) was calculated by dividing the observed and expected mortality rates. Cox regression analysis revealed the independent factors associated with mortality. Results: At the last visit, 31.07% (124) of patients were cured, 22.05% (88) had controlled acromegaly with medication, and 45.31% (181) had not controlled acromegaly. During follow-up (13.03 ± 5.65 years, 5216.62 person-years), 89 patients died (0.017%), resulting in an SMR of 1.18 [95% CI 0.95-1.45]. The independent factors associated with mortality were the last IGF1 level/last random GH level, absence of surgery, gonadotropin deficiency, and age. Patients with normal IGF1 after treatment showed an SMR of 0.71, whereas patients with IGF1 ratio > 1 showed SMR=1.51. Patients diagnosed between 1975-2007 and 2008-2022 had SMR = 1.25 [95% CI 0.97-1.58] and SMR = 1.09 [95% CI 0.68-1.65], respectively. In females with acromegaly, SMR was 1.63 [95% CI 1.24-2.11]; 1.76 [95% CI 1.30-2.34] in women diagnosed before 2008 and 1.33 [95% CI 0.69-2.33] in those diagnosed after 2008. Males with acromegaly had a mortality ratio similar to males from the general population (SMR = 0.99, [95% CI 0.66-1.41]). Conclusion: Patients diagnosed with acromegaly in the last 15 years had lower mortality rates than those diagnosed before 2008, due to the availability of new medications, primarily somatostatin receptor analogs and to a higher proportion of patients undergoing surgery. Females still have a high mortality ratio owing to older age at diagnosis and higher risk of metabolic complications. Therefore, efforts should be made for early diagnosis of acromegaly in women.

Patients' Persistent Symptoms, Clinician Demographics, and Geo-Economic Factors Are Associated with Choice of Therapy for Hypothyroidism by European Thyroid Specialists: The "THESIS" Collaboration.

Background: Hypothyroidism is common, however, aspects of its treatment remain controversial. Our survey aimed at documenting treatment choices of European thyroid specialists and exploring how patients' persistent symptoms, clinician demographics, and geo-economic factors relate to treatment choices. Methods: Seventeen thousand two hundred forty-seven thyroid specialists from 28 countries were invited to participate in an online questionnaire survey. The survey included respondent demographic data and treatment choices for hypothyroid patients with persistent symptoms. Geo-economic data for each country were included in the analyses. Results: The response rate was 32.9% (6058 respondents out of 17,247 invitees). Levothyroxine (LT4) was the initial treatment preferred by the majority (98.3%). Persistent symptoms despite normal serum thyrotropin (TSH) while receiving LT4 treatment were reported to affect up to 10.0% of patients by 75.4% of respondents, while 28.4% reported an increasing such trend in the past 5 years. The principal explanations offered for patients' persistent symptoms were psychosocial factors (77.1%), comorbidities (69.2%), and unrealistic patient expectations (61.0%). Combination treatment with LT4+liothyronine (LT3) was chosen by 40.0% of respondents for patients who complained of persistent symptoms despite a normal TSH. This option was selected more frequently by female thyroid specialists, with high-volume practice, working in countries with high gross national income per capita. Conclusions: The perception of patients' dissatisfaction reported by physicians seems lower than that described by hypothyroid patients in previous surveys. LT4+LT3 treatment is used frequently by thyroid specialists in Europe for persistent hypothyroid-like symptoms even if they generally attribute such symptoms to nonendocrine causes and despite the evidence of nonsuperiority of the combined over the LT4 therapy. Pressure by dissatisfied patients on their physicians for LT3-containing treatments is a likely explanation. The association of the therapeutic choices with the clinician demographic characteristics and geo-economic factors in Europe is a novel information and requires further investigation.

Insulin-like growth factor-I correlates more closely than growth hormone with insulin resistance and glucose intolerance in patients with acromegaly.

In normal subjects growth hormone (GH) and insulin-like growth factor-I (IGF-I) have opposing effects on glucose metabolism. Active acromegaly is associated with insulin resistance (IR) and glucose intolerance although both GH and IGF-I are elevated. Our objective was to compare whether GH or IGF-I correlates more closely with IR and glucose intolerance in acromegaly. Basal serum IGF-I and GH, glucose and insulin during an oral glucose tolerance test were measured in 70 normoglycemic and 44 hyperglycemic acromegalic patients (21 impaired fasting glucose, 11 impaired glucose tolerance and 12 diabetes mellitus) according to American Diabetes Association criteria. 55 patients were assessed before any treatment for acromegaly and 59 after surgery and/or radiotherapy (15 patients had normal IGF-I after treatment). Patients treated with somatostatin analogs, GH-receptor antagonists or antidiabetic drugs were excluded. IR was assessed by various basal and stimulated indices. Homeostatic Model Assessment 2-Insulin Resistance (HOMA2-IR) index correlated more closely with IGF-I (r = 0.65, p < 0.0001) than nadir (r = 0.23, p = 0.008) or random GH (r = 0.26, p = 0.002). HOMA2-IR correlated better with IGF-I than nadir or random GH also in normoglycemic (n = 70; r = 0.74, p < 0.0001 vs. r = 0.36, p = 0.001 vs. r = 0.39, p < 0.001) and hyperglycemic patients (n = 44; r = 0.54, p = 0.0002 vs. r = 0.09, p = 0.4 vs. r = 0.14, p = 0.26). In multivariate logistic regression analysis IGF-I but not GH was a significant risk factor for glucose intolerance after adjusting for age, sex, weight and acromegaly duration (OR = 1.56, p = 0.01). In acromegaly IGF-I correlates more closely than GH with IR. IGF-I levels but not GH are associated with glucose intolerance.

Radiotherapy in aggressive or dopamine agonists resistant prolactinomas; is it still worthwhile?

Radiotherapy, conventional or radiosurgery, has been used to control prolactin secretion and tumour growth in prolactinomas both as part of multimodal therapy or rarely as primary treatment. However, considering the radiotherapy side effects, notably hypopituitarism, as opposed to the high efficacy and low toxicity of dopamine agonists (DA) treatment and neurosurgery, radiotherapy is recommended mostly for patients with aggressive or high-risk prolactinomas or in those resistant or intolerant to medical therapy, usually after surgical failure. We provide an overview of the published literature on the efficacy and toxicity of radiotherapy (conventional fractionated or radiosurgery), in aggressive, high-risk, or DA resistant prolactinomas. Radiotherapy has shown a good efficacy and a reasonable toxicity profile in prolactinomas where other treatment modalities failed. In aggressive and high-risk prolactinomas, the cumulative percentage for tumour control (reduction plus stable) ranged from 68% to 100%. Most studies reported global hormonal control rates over 50%. In resistant prolactinomas, the global secretion control rate (on, but also off DA) ranged from 28% to 89%-100%; in most studies over 80%. The 5-year rate of hypopituitarism was around 12%-25%. To date there are no controlled study on the use of radiotherapy as a prophylactic treatment in patients with clinical, radiological or pathological markers of aggressiveness. In conclusion, our review supports the use of radiotherapy in patients with growing, clinically aggressive or truly DA resistant prolactinomas. In patients with high-risk or invasive prolactinomas or in those harboring pathological markers of aggressiveness, the prophylactic use of radiotherapy should be individualized.

Acromegaly versus hypogonadism: Bone fragility and evaluation.

INTRODUCTION: Osteopathy in patients with acromegaly is characterized by increased prevalence of vertebral fragility fractures (VF). However, the diagnostic criteria for osteoporosis are seldomly met in terms of bone mineral density (BMD), as patients with acromegaly frequently present normal BMD for age and gender. METHODOLOGY: We performed a cross-sectional study on 71 patients with acromegaly and 75 patients with hypogonadism. Turnover markers comprised alkaline phosphatase, osteocalcin, the C-terminal telopeptide of type I collagen and total procollagen type-1 amino-terminal propeptide; imaging comprised dual x-ray absorptiometry for BMD, T and Z scores of the lumbar spine, femoral neck and total hip, trabecular bone score (TBS), and x-ray scans of the thoracic and lumbar spine. RESULTS: Vertebral fractures (VF) in subjects with acromegaly were significantly more frequent than in subjects with hypogonadism, with a prevalence of 29.6% compared to 9.3%. Patients with acromegaly had significantly higher BMD at all skeletal sites but lower TBS than hypogonadal subjects. This difference remained statistically significant after grouping patients with acromegaly according to gonadal status and comparing them with patients with hypogonadism. However, presence of hypogonadism in patients with acromegaly did not influence BMD, TBS or VF prevalence. Moreover, patients with active acromegaly did not have significantly different BMD, TBS and VF prevalence compared to patients with controlled disease. Patients with acromegaly with VF had significantly lower BMD at all skeletal sites than those without VF, but no difference in TBS. CONCLUSIONS: Vertebral fractures are frequent in acromegaly, and are associated with lower BMD but not with TBS. Patients with acromegaly, regardless of gonadal status, have significantly higher BMD but lower TBS than hypogonadal patients. Moreover, disease activity and hypogonadism do not influence BMD, TBS or VF in acromegaly.

Characteristics of specialists treating hypothyroid patients: the "THESIS" collaborative.

Introduction: Thyroid specialists influence how hypothyroid patients are treated, including patients managed in primary care. Given that physician characteristics influence patient care, this study aimed to explore thyroid specialist profiles and associations with geo-economic factors. Methods: Thyroid specialists from 28 countries were invited to respond to a questionnaire, Treatment of Hypothyroidism in Europe by Specialists: an International Survey (THESIS). Geographic regions were defined according to the United Nations Statistics Division. The national economic status was estimated using World Bank data on the gross national income per capita (GNI per capita). Results: 5,695 valid responses were received (response rate 33·0%). The mean age was 49 years, and 65·0% were female. The proportion of female respondents was lowest in Northern (45·6%) and highest in Eastern Europe (77·2%) (p <0·001). Respondent work volume, university affiliation and private practice differed significantly between countries (p<0·001). Age and GNI per capita were correlated inversely with the proportion of female respondents (p<0·01). GNI per capita was inversely related to the proportion of respondents working exclusively in private practice (p<0·011) and the proportion of respondents who treated >100 patients annually (p<0·01). Discussion: THESIS has demonstrated differences in characteristics of thyroid specialists at national and regional levels, strongly associated with GNI per capita. Hypothyroid patients in middle-income countries are more likely to encounter female thyroid specialists working in private practice, with a high workload, compared to high-income countries. Whether these differences influence the quality of care and patient satisfaction is unknown, but merits further study.

Utility of Trabecular Bone Score (TBS) in Bone Quality and Fracture Risk Assessment in Patients on Maintenance Dialysis.

Maintenance dialysis is associated with almost universal changes in bone metabolism collectively known as chronic kidney disease-mineral and bone disorder (CKD-MBD). These are accompanied in various proportions by bone loss and altered bone quality that led to an increased risk of fracture. Osteoporosis, age-related or postmenopausal, a condition that often coexists with CKD, is also a leading cause of fracture. Dual-energy X-ray densitometry (DXA) is the main tool for assessing the bone quantity and bone loss and the associated fracture risk. It has been validated in both CKD-MBD and osteoporosis. Trabecular bone score (TBS) is a DXA-derived algorithm for the evaluation of bone microarchitecture, and its clinical value has been repeatedly demonstrated in large cohorts of osteoporotic patients. However, its utility in patients on maintenance dialysis has not been conclusively shown. Published studies showed a lower TBS score and implicitly an altered bone microarchitecture in patients on maintenance dialysis, even after adjusting for various variables. Moreover, FRAX-based fracture risk is higher after adjusting for TBS, showing promise on an algorithm better estimating the clinical fracture risk in dialysis patients. However, TBS has not been demonstrated to independently predict clinical fractures in prospective studies on dialysis patients. Also, aortic calcifications and altered fluid balance could significantly affect TBS score and could hamper the widespread clinical use in patients on maintenance dialysis. In this mini-review, we focus on the benefits and pitfalls of TBS in the management of CKD-MBD and fracture risk assessment in patients on maintenance dialysis.

Thyroglobulin in lymph node fine-needle aspiration biopsy washout fluid. A tertiary center experience.

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Most PTC secretes thyroglobulin, a useful marker in monitoring preoperative staging and postoperative progression; in addition to serum thyroglobulin, fine needle aspiration washout thyroglobulin (FNA-Tg) is also used. Our aim was to determine the cut-off value for FNA-Tg in our center and to describe major discrepancies between FNA-Tg, cytology and pathology results of the lymph nodes. METHODS: We retrospectively retrieved from the electronic database of our endocrinology center all the FNA-Tg measurements between December 10, 2019 and September 2021. For each measurement we also retrieved the corresponding sex, FNAB results and the pathology reports. FNA-Tg was measured by ECLIA immunoelectro-chemiluminescent method. RESULTS: There were 58 FNAB and FNA-Tg of suspect cervical lymph nodes in 40 patients. There were 17 cytologically benign lymph nodes of which 13 had low and 4 had high FNA-Tg; 3 non-diagnostic cytology results of which one had high FNA-Tg; 38 PTC metastases of which 6 had low and 32 had high FNA-Tg titers. The cut-off value of FNA-Tg in our center is 10 ng/ml, with a sensitivity of 86.6% (in those with pathology reports available after surgery). CONCLUSIONS: Washout TG is useful in suspicious lymph nodes and has added value to cytology in selected cases. The cut-off value of FNA-Tg in our center is 10 ng/ml, with a sensitivity of 86.6%. However, we must consider the possible false negative results that may occur in some histological types of PTC.

Mortality rates and risk factors after low-trauma hip fracture in the largest university center in Romania.

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. PURPOSE: 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. METHODS: 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. RESULTS: 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<0.001) compared to surgically treated fractures. The 1-year mortality rate in conservatively treated fractures was 56.44% compared to 24.47% in surgically treated fractures. Age, male sex, length of stay in hospital, day of surgery, post-surgical complications, and late surgery were significantly associated (p<0.001) with mortality after hip fracture. The lowest 1-year mortality rate was in surgically treated patients with a length of stay in hospital between 6 and 10 days. CONCLUSION: We found a high mortality rate at 30 days and 1 year after low-trauma hip fracture. The high mortality rates can be attributable, in part, to the high number of conservatively treated fractures.

Clinical features and complications of acromegaly at diagnosis are not all the same: data from two large referral centers.

PURPOSE: The number of international acromegaly related registries is increasing; however, heterogeneity of acromegaly symptoms and signs across countries is not well described. We compared clinical disease manifestations at diagnosis between two large University referral centers from two continents. METHODS: Retrospective, comparative epidemiological study of acromegaly patients at two centers: (i) C. I. Parhon National Institute of Endocrinology, 'Carol Davila' University of Medicine and Pharmacy Bucharest, Romania (Parhon), and (ii) Pituitary Center, Oregon Health & Science University, Portland, Oregon, United States (OHSU) from approved data repositories was undertaken. Data were extracted from medical charts and questionnaires. Binary logistic regression analysis was undertaken for the most frequently noted symptoms and clinical signs. RESULTS: The study included 216 patients (87 Parhon, 129 OHSU). Age, sex, and median delay in diagnosis were similar between centers. IGF-1 index was higher in patients at Parhon (3.3 vs 2.1, P < 0.001). The top five symptoms at both centers were enlarged hands/feet, headache, arthralgia, fatigue, and irregular menses in women. A significant difference was noted for multiple signs and symptoms frequency, often > 20 percentage points between centers. Center was a predictor of many signs and symptoms, independent of acromegaly biochemical severity or disease duration. CONCLUSION: We show in the first comparative study that differences in medical practice, documentation, and likely cultural differences can influence patients' symptom(s) reporting and screening patterns in geographically different populations. Pooling data into large multicenter international registry databases may lead to loss of regional characteristics and thus a mixed overall picture of combined cohorts.

Adherence to Anti-Osteoporotic Treatment and Clinical Implications after Hip Fracture: A Systematic Review.

The role of anti-osteoporotic treatment as part of the secondary prevention after hip fracture in terms of mortality and re-fracture risk has been studied, and the results are promising. Decreased treatment adherence and compliance is a problem that needs to be addressed by healthcare professionals. A systematic review of the literature was performed using the PubMed database with terms that included hip fracture, mortality, second fracture, and specific anti-osteoporotic treatment. We included 28 articles, 21 regarding mortality and 20 re-fracture rates in hip fracture patients. All studies showed lower mortality after hip fracture associated with anti-osteoporotic treatment, mostly bisphosphonate agents. The re-fracture risk is still debatable, since conflicting data were found. Although most of the studies showed notable effects on mortality and re-fracture rates associated with anti-osteoporotic treatment, we still need more data to validate the actual results.

Combined Effects of Vitamin D Status, Renal Function and Age on Serum Parathyroid Hormone Levels.

Background: Vitamin D status and renal function are well-known independent predictors of serum parathyroid hormone (PTH) levels. We aimed to describe the combined effects of 25-hydroxy vitamin D (25(OH)D), glomerular filtration rate (GFR) and age on serum PTH levels across the whole clinical spectrum. Methods: We retrieved from our endocrinology center database all PTH measurement between 2012 and 2020 for which a simultaneous measurement of serum 25(OH)D, calcium and creatinine was available. Age, sex and diagnosis were available for all subjects. Intact PTH was measured using the same electrochemiluminescence assay. Results: There were 6,444 adults and 701 children without a diagnosis of hyper- or hypoparathyroidism or abnormal serum calcium levels. In adults with 25(OH)D≥12 ng/mL multiple regression models showed that serum PTH was negatively correlated with both 25(OH)D and GFR. Regression (-0.68 and -1.59 vs. -0.45 and -0.22 respectively), partial correlation (-0.16 and -0.35 vs. -0.12 and -0.10 respectively) and determination coefficients (0.14 vs. 0.031) were higher in CKD than in normal renal function. In subjects with 25(OH)D<12 ng/mL, GFR was the only significant predictor in those with CKD (ß-coefficient=-2.5, r=-0.55) and 25(OH)D was the only significant predictor in those with normal renal function (ß-coefficient=-2.05, r=-0.11). Increasing age was associated with higher PTH levels only in those with normal renal function and 25(OH)D≥12 ng/mL. Conclusions: We showed that declining vitamin D and renal function have additive effects on serum PTH in subjects without vitamin D deficiency. In vitamin D deficient subjects this dependency is stronger but is not additive anymore.

Clinicopathological Features of Growth Hormone-producing Pituitary Adenomas and Correlation With Preoperative Laboratory Findings.

BACKGROUND/AIM: The histopathological variability of each type of pituitary adenoma (PA) that causes growth hormone (GH) excess influences the phenotype, radiological characteristics and therapy response of acromegaly patients. We correlated the immunohistochemical (IHC) features of GH-secreting PAs with their clinical, laboratory and imaging data. PATIENTS AND METHODS: We included 32 patients with documented acromegaly; tumour specimens were histologically and IHC examined: anterior pituitary hormones, pituitary-specific transcription factor-1 (PIT-1), Ki-67 labelling index were evaluated. RESULTS: Macroadenomas represented 93.75%. Post-surgery disease control negatively correlated with the maximum initial tumour diameter (p=0.04). Ki-67 did not predict remission. No correlation was found between GH serum levels and IHC expression (p=0.45). PIT-1 was positive in all specimens, two had a weak expression. Four were considered PIT-1 positive plurihormonal adenomas and several had unusual IHC combinations. CONCLUSION: PIT-1 accurately classifies GH-secreting PAs. The IHC classification as well as radiological dimensions and extent influence disease control, probably being the best prognosis factors.

Seasonal periodicity of serum parathyroid hormone and its relation with vitamin D in Romania.

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. PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Improvement of acromegaly control with multimodal therapy in Romania.

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 1st, 2012 and May 31st, 2019. We also compared the control rates for patients treated between April 1st, 2016 and May 31st, 2019 with historical controls (assessed between January 1st, 2012 and March 31st, 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.