EndoBridge 2023: highlights and pearls.

EndoBridge 2023 took place on October 20-22, 2023, in Antalya, Turkey. Accredited by the European Council, the 3-day scientific program of the 11th Annual Meeting of EndoBridge included state-of-the-art lectures and interactive small group discussion sessions incorporating interesting and challenging clinical cases led by globally recognized leaders in the field and was well attended by a highly diverse audience. Following its established format over the years, the program provided a comprehensive update across all aspects of endocrinology and metabolism, including topics in pituitary, thyroid, bone, and adrenal disorders, neuroendocrine tumors, diabetes mellitus, obesity, nutrition, and lipid disorders. As usual, the meeting was held in English with simultaneous translation into Russian, Arabic, and Turkish. The abstracts of clinical cases presented by the delegates during oral and poster sessions have been published in JCEM Case Reports. Herein, we provide a paper on highlights and pearls of the meeting sessions covering a wide range of subjects, from thyroid nodule stratification to secondary osteoporosis and from glycemic challenges in post-bariatric surgery to male hypogonadism. This report emphasizes the latest developments in the field, along with clinical approaches to common endocrine issues. The 12th annual meeting of EndoBridge will be held on October 17-20, 2024 in Antalya, Turkey.

Consensus Statement on Vitamin D Status Assessment and Supplementation: Whys, Whens, and Hows.

The 6th International Conference, "Controversies in Vitamin D," was convened to discuss controversial topics, such as vitamin D metabolism, assessment, actions, and supplementation. Novel insights into vitamin D mechanisms of action suggest links with conditions that do not depend only on reduced solar exposure or diet intake and that can be detected with distinctive noncanonical vitamin D metabolites. Optimal 25-hydroxyvitamin D (25(OH)D) levels remain debated. Varying recommendations from different societies arise from evaluating different clinical or public health approaches. The lack of assay standardization also poses challenges in interpreting data from available studies, hindering rational data pooling and meta-analyses. Beyond the well-known skeletal features, interest in vitamin D's extraskeletal effects has led to clinical trials on cancer, cardiovascular risk, respiratory effects, autoimmune diseases, diabetes, and mortality. The initial negative results are likely due to enrollment of vitamin D-replete individuals. Subsequent post hoc analyses have suggested, nevertheless, potential benefits in reducing cancer incidence, autoimmune diseases, cardiovascular events, and diabetes. Oral administration of vitamin D is the preferred route. Parenteral administration is reserved for specific clinical situations. Cholecalciferol is favored due to safety and minimal monitoring requirements. Calcifediol may be used in certain conditions, while calcitriol should be limited to specific disorders in which the active metabolite is not readily produced in vivo. Further studies are needed to investigate vitamin D effects in relation to the different recommended 25(OH)D levels and the efficacy of the different supplementary formulations in achieving biochemical and clinical outcomes within the multifaced skeletal and extraskeletal potential effects of vitamin D.

Thyroiditis After Parathyroidectomy.

Various clinical manifestations of thyroiditis after parathyroidectomy have been reported in the literature, ranging from mild symptoms to tachyarrhythmias and myocardial infarction. We report 2 cases of post-parathyroidectomy thyroiditis. Both patients had primary hyperparathyroidism and underwent parathyroidectomy for a solitary parathyroid adenoma. They subsequently developed symptoms of hyperthyroidism, including palpitations and heat intolerance. Laboratory investigations demonstrated a suppressed TSH level with elevated free T4 levels and low uptake on thyroid radioiodine scan, confirming the diagnosis of thyroiditis. The patients were managed conservatively, and their symptoms gradually resolved with normalization of thyroid hormone levels. A review of 27 cases reported to date reveals that this condition is mostly attributed to manipulation of the thyroid during parathyroid surgery. It occurs more frequently in patients who undergo 4-gland parathyroidectomy for secondary or tertiary hyperthyroidism and is self-limited within a few weeks. The case reports highlight the importance of recognizing thyroiditis as a potentially underrecognized complication of parathyroid surgery. Further research is warranted to better understand the underlying pathophysiology and to establish potential risk factors for its development post-parathyroidectomy.

A Systematic Review Supporting the Endocrine Society Clinical Practice Guideline on the Treatment of Hypercalcemia of Malignancy in Adults.

CONTEXT: Hypercalcemia is a common complication of malignancy that is associated with high morbidity and mortality. OBJECTIVE: To support development of the Endocrine Society Clinical Practice Guideline for the treatment of hypercalcemia of malignancy in adults. METHODS: We searched multiple databases for studies that addressed 8 clinical questions prioritized by a guideline panel from the Endocrine Society. Quantitative and qualitative synthesis was performed. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess certainty of evidence. RESULTS: We reviewed 1949 citations, from which we included 21 studies. The risk of bias for most of the included studies was moderate. A higher proportion of patients who received bisphosphonate achieved resolution of hypercalcemia when compared to placebo. The incidence rate of adverse events was significantly higher in the bisphosphonate group. Comparing denosumab to bisphosphonate, there was no significant difference in the rate of patients who achieved resolution of hypercalcemia. Two-thirds of patients with refractory/recurrent hypercalcemia of malignancy who received denosumab following bisphosphonate therapy achieved resolution of hypercalcemia. Addition of calcitonin to bisphosphonate therapy did not affect the resolution of hypercalcemia, time to normocalcemia, or hypocalcemia. Only indirect evidence was available to address questions on the management of hypercalcemia in tumors associated with high calcitriol levels, refractory/recurrent hypercalcemia of malignancy following the use of bisphosphonates, and the use of calcimimetics in the treatment of hypercalcemia associated with parathyroid carcinoma. The certainty of the evidence to address all 8 clinical questions was low to very low. CONCLUSION: The evidence summarized in this systematic review addresses the benefits and harms of treatments of hypercalcemia of malignancy. Additional information about patients' values and preferences, and other important decisional and contextual factors is needed to facilitate the development of clinical recommendations.

Vitamin D supplementation in obesity and during weight loss: A review of randomized controlled trials.

Vitamin D deficiency is common in obese individuals and during weight loss. The recommended vitamin D doses in this specific population are higher than for healthy adults. We reviewed vitamin D supplementation trials in obesity, and during medical or surgical weight loss, and report the effects on 25-hydroxyvitamin D [25(OH)D] concentrations and other relevant outcomes. We conducted a systematic search in PubMed, Medline, Embase and the Cochrane library for relevant randomized controlled trials (RCTs) of oral vitamin D supplementation for at least 3 months in obese individuals without weight loss (OB), and those on medical weight loss (MWL) (2010-2018), and following bariatric surgery (Bar S) (without time restriction). Two reviewers screened the identified citations in duplicate and independently and performed full text screening. One reviewer completed data extraction. We identified 13 RCTs in OB, 6 in MWL and 7 in Bar S. Mean baseline 25(OH)D concentrations ranged between 7 and 27 ng/ml in OB, 15-29 ng/ml in MWL and 15-24 ng/ml in Bar S. In OB (Total N 2036 participants), vitamin D doses of 1600-4000 IU/d increased mean 25(OH)D concentrations to ≥30 ng/ml. Based on three trials during MWL (Total N 359 participants), vitamin D doses of 1200-4600 IU/d for 12 months increased 25(OH)D concentration to ≥30 ng/ml. In Bar S (Total N 615 participants), doses ≥2000 IU/d were needed to reach 30 ng/ml. The change in 25(OH)D concentration was inversely proportional to the administered dose, and to BMI and baseline level with doses of 600-3000 IU/day. With these doses, the change in 25(OH)D concentration [Δ25(OH)D] per 100 IU/d was 0.5-1.2 ng/ml. Three trials assessed bone mineral density as a primary outcome, but only one of them showed a protective effect of vitamin D against bone loss at all sites post-Bar S. There was no effect of vitamin D on weight loss. Data on extra-skeletal parameters, namely glycemic and vascular indices were mostly identified in OB, and findings were inconsistent. In conclusion, Vitamin D doses ≥1600-2000 IU/d may be needed to reach a 25(OH)D concentration of 30 ng/ml in obese individuals and following bariatric surgery. The optimal concentration in this population is unknown, and whether the above doses protect against weight loss induced bone loss and fractures still needs to be confirmed. There is no clear evidence for a beneficial effect of vitamin D supplementation on cardio-metabolic parameters in obese individuals, and data on such parameters with weight loss are very scarce. Well-designed long term RCTs assessing the effect of vitamin D supplementation during weight loss on patient important outcomes are needed.

Secular trends in hip fractures worldwide: opposing trends East versus West.

Despite wide variations in hip rates fractures worldwide, reasons for such differences are not clear. Furthermore, secular trends in the age-specific hip fracture rates are changing the world map of this devastating disease, with the highest rise projected to occur in developing countries. The aim of our investigation is to systematically characterize secular trends in hip fractures worldwide, examine new data for various ethnic groups in the United States, evidence for divergent temporal patterns, and investigate potential contributing factors for the observed change in their epidemiology. All studies retrieved through a complex Medline Ovid search between 1966 and 2013 were examined. For each selected study, we calculated the percent annual change in age-standardized hip fracture rates de-novo. Although occurring at different time points, trend breaks in hip fracture incidence occurred in most Western countries and Oceania. After a steep rise in age-adjusted rates in these regions, a decrease became evident sometimes between the mid-seventies and nineties, depending on the country. Conversely, the data is scarce in Asia and South America, with evidence for a continuous rise in hip fracture rates, with the exception of Hong-Kong and Taiwan that seem to follow Western trends. The etiologies of these secular patterns in both the developed and the developing countries have not been fully elucidated, but the impact of urbanization is at least one plausible explanation. Data presented here show close parallels between rising rates of urbanization and hip fractures across disparate geographic locations and cultures. Once the proportion of the urban population stabilized, hip fracture rates also stabilize or begin to decrease perhaps due to the influence of other factors such as birth cohort effects, changes in bone mineral density and BMI, osteoporosis medication use and/or lifestyle interventions such as smoking cessation, improvement in nutritional status and fall prevention.

Vitamin D in endometriosis: a causative or confounding factor?

OBJECTIVE: The aim of this paper is to review the evidence from studies that evaluated the relationship between vitamin D and endometriosis. DESIGN: Comprehensive review. MATERIALS AND METHODS: Systematic literature search in Medline for relevant publications from 1946 until June 2013. RESULTS: Endometriosis risk may be influenced by dietary vitamin D intake and plasma hydroxyvitamin D concentration. Vitamin D receptor and vitamin D metabolizing enzymes, 24-hydroxylase and 1-α hydroxylase, are found in the normal cycling endometrium and also in the eutopic and ectopic endometrium of women with endometriosis. The endometrium is a target of 1, 25 dihydroxyvitamin D actions through regulation of specific genes and via immunomodulation. The endometrium in endometriosis expresses dysregulation of some vitamin D enzymes and receptors. If vitamin D and its metabolites are implicated in endometriosis-associated infertility, it is likely through interference with HOXA10 gene expression. The Gc2 phenotype of vitamin D binding protein is prevalent in women with endometriosis and may be implicated in its pathogenesis. In a mouse model, Elocalcitol, a VDR-agonist was shown to reduce the development of endometriotic lesions and recurrence. CONCLUSION: A biological plausibility for a role of vitamin D, as an immunomodulator and anti-inflammatory agent, in the pathogenesis and treatment of endometriosis is suggested in this article, but is difficult to illustrate due to sparse evidence from human studies limited primarily to case-control studies. A significant knowledge gap precludes the establishment of a clear cause-effect relationship. The intriguing leads presented herein need to be investigated further with placebo-controlled supplementation trials.

Hypovitaminosis D in the Middle East and North Africa: Prevalence, risk factors and impact on outcomes.

BACKGROUND: The Middle East and North Africa (MENA) region registers some of the highest rates of hypovitaminosis D worldwide.   AIM: We systematically reviewed the prevalence of hypovitaminosis D, rickets and osteomalacia, their predictors and impact on major outcomes, in the region. METHODS: Medline, Pubmed and Embase search engines, entering keywords and concepts, combined with individual countries of interest, were used. Search was limited years 2000-2012; and review articles were used for the period preceding year 2000. RESULTS: Rickets and osteomalacia still occur in this sunny region. Hypovitaminosis D prevails, with rates varying 30-90%, considering a desirable serum 25 hydroxy-vitamin D [25(OH)D] of 20 ng/ml. Advancing age, female gender, multi-parity, clothing style, season, socio-economic status and urban living are recognized predictors of hypovitaminosis D in adults. Prolonged breastfeeding without vitamin D supplementation and low dietary calcium intake are the recognized risk factors for rickets and hypovitaminosis D in children.. Associations with pain score and disease activity in rheumatologic disorders, viral load and interleukins in hepatitis C, BMI, lipids and insulin sensitivity, blood pressure, heart failure and mortality are described. Sun exposure in adults decreased prevalence of metabolic syndrome in one study. Few randomized vitamin D trials revealed that the majority of mothers or children failed to achieve a desirable 25(OH)D level, even with doses by far exceeding current recommendations. A trial in adolescent girls reveals substantial bone and lean mass increments. CONCLUSION: Hypovitaminosis D is prevalent in MENA. The lack of populations based studies, gaps in studies in infants, pre-pubertal children and pregnant women, hinder the development of region specific guidelines and constitute a major obstacle to impact this chronic and most often subclinical disease.

Vitamin D: a growing perspective.

Vitamin D deficiency has been widely reported in all age groups in recent years. Rickets has never been eradicated in developed countries, and it most commonly affects children from recent immigrant groups. There is much evidence that current vitamin D guidelines for the neonatal period, 5-10 microg (200-400 IU)/day, prevent rickets at the typical calcium intakes in developed countries. The annual incidence of vitamin D-deficiency rickets in developed countries ranges between 2.9 and 7.5 cases per 100,000 children. The prevalence of vitamin D deficiency in mothers and their neonates is remarkable, and the results of one study suggest that third-trimester 25-hydroxyvitamin D (25(OH)D) is associated with fetal bone mineral accrual that may affect prepubertal bone mass accumulation. Beyond infancy, the evidence indicates that 5 microg (200 IU)/day of vitamin D has little effect on vitamin D status as measured by the serum 25(OH)D concentration. Two randomized clinical trials show that higher vitamin D intake improves one-year gain in bone density in adolescent girls. The functions of vitamin D extend beyond bone to include immune system regulation and anti-proliferative effects on cells. Early life vitamin D inadequacy is implicated in the risk of bone disease, autoimmune disease, and certain cancers later in life; however, long-term interventional studies do not exist to validate the widespread implementation of greater vitamin D consumption. Here we review the available data concerning vitamin D status and health effects of vitamin D in pregnancy through to and including adolescence.

Dermatologic manifestations of parathyroid-related disorders.

Dermatologic manifestations of parathyroid-related disorders, although rare in sporadic cases, are not uncommon in familial syndromes. Patients with familial hyperparathyroidism have several types of skin lesions. In multiple endocrine neoplasia 1, patients commonly have angiofibromas (85%) and collagenomas (70%), lesions that show loss of one 11q13 allele, the molecular abnormality in multiple endocrine neoplasia 1. They can also present with lipomas or café-au-lait spots. Cutaneous amyloidosis, an entity that can occur sporadically, has been described in multiple endocrine neoplasia 2a and is usually localized to the interscapular area. Metastatic calcification is an entity commonly encountered in patients with hyperparathyroidism and renal failure. It can be complicated by infections and necrosis. It is best treated by controlling hypercalcemia, hyperphosphatemia, hyperparathyroidism, antibiotics, and analgesia. Parathyroidectomy is reserved for refractory cases. Hypoparathyroidism presenting in the context of polyglandular failure type 1 is characterized by mucocutaneous candidiasis. Pseudohypoparathyroidism, an inherited disorder with end-organ unresponsiveness to parathyroid hormone, is characterized by Albright hereditary osteodystrophy. Patients present with short stature, round facies, brachydactyly, and short fourth or fifth metacarpals.

Pamidronate in the prevention of chemotherapy-induced bone loss in premenopausal women with breast cancer: a randomized controlled trial.

PURPOSE: Mortality from breast cancer has decreased in large part because of adjuvant chemotherapy. Sequelae of therapy include ovarian failure and bone loss, loss that would increase these patients' risk of fracture with aging. In this study, we assessed the efficacy of pamidronate in preventing such loss. PATIENTS AND METHODS: The study was a 1-yr randomized, double-blind, placebo-controlled trial comparing pamidronate 60 mg iv every 3 months with placebo in 40 premenopausal women with newly diagnosed breast cancer. Bone mineral density (BMD) of the spine and hip and remodeling markers were monitored over 1 yr. RESULTS: Over half of the subjects became amenorrheic, and those who did were 4 yr older than those who did not (P = 0.02). The mean difference in percent change in BMD at 12 months between the two treatment groups was 5.1% at the lumbar spine (P = 0.002) in the overall study group and 5% at the lumbar spine and 5.2% at the total hip in the amenorrheic subgroup (P < 0.03). Biochemical markers of bone remodeling did not differ between the two treatment groups, and treatment was well tolerated. CONCLUSION: Chemotherapy-induced amenorrhea is common with ensuing bone loss at the spine and hip. Pamidronate prevented bone loss at the spine and hip and was well tolerated.

Hip fractures in lebanese patients: determinants and prognosis.

Hip fractures are the most costly of osteoporotic fractures, but little is known about their epidemiology in the Middle East. Hip fracture patients and controls with osteoarthritis admitted to our institution from 1992 to 2002 were studied. Information on gender, age, type of fracture, comorbid conditions, and medications use was obtained. The mean age for hip fracture patients (n = 274) was 72.1(8.5) yr, and for controls (n = 112), it was 71.1(4.4) yr, two-thirds of fractures occurred in women. Fractures were 59% intertrochanteric, 34% femoral neck, and 7% subtrochanteric, with no gender differences. Hip fracture patients were more likely to have had a prior fracture and to suffer from neurological, gastrointestinal, or renal comorbidities, as compared to controls. Less than 10% of hip fracture patients received any therapy for osteoporosis, either on admission or discharge. In a subset of patients with follow-up, the mortality rate was 47% in subjects with hip fracture, and most deaths occurred within the first year postoperatively. Gender but not fracture type affected mortality. Lebanese patients with hip fractures are younger, more likely to sustain intertrochanteric fractures, and experience higher mortality than Western counterparts. Few subjects received osteoporosis therapy. This study carries important public health implications on the management of hip fracture in subjects from Lebanon and, possibly, the Middle East.