Machine learning-based algorithms applied to drug prescriptions and other healthcare services in the Sicilian claims database to identify acromegaly as a model for the earlier diagnosis of rare diseases.

Acromegaly is a rare disease characterized by a diagnostic delay ranging from 5 to 10 years from the symptoms' onset. The aim of this study was to develop and internally validate machine-learning algorithms to identify a combination of variables for the early diagnosis of acromegaly. This retrospective population-based study was conducted between 2011 and 2018 using data from the claims databases of Sicily Region, in Southern Italy. To identify combinations of potential predictors of acromegaly diagnosis, conditional and unconditional penalized multivariable logistic regression models and three machine learning algorithms (i.e., the Recursive Partitioning and Regression Tree, the Random Forest and the Support Vector Machine) were used, and their performance was evaluated. The random forest (RF) algorithm achieved the highest Area under the ROC Curve value of 0.83 (95% CI 0.79-0.87). The sensitivity in the test set, computed at the optimal threshold of predicted probabilities, ranged from 28% for the unconditional logistic regression model to 69% for the RF. Overall, the only diagnosis predictor selected by all five models and algorithms was the number of immunosuppressants-related pharmacy claims. The other predictors selected by at least two models were eventually combined in an unconditional logistic regression to develop a meta-score that achieved an acceptable discrimination accuracy (AUC = 0.71, 95% CI 0.66-0.75). Findings of this study showed that data-driven machine learning algorithms may play a role in supporting the early diagnosis of rare diseases such as acromegaly.

Exploring sexual function in adrenal insufficiency: findings from the Dual RElease hydrocortisone versus conventionAl glucocorticoid replaceMent therapy in hypocortisolism (DREAM) trial.

BACKGROUND: Data on sexual function in patients with adrenal insufficiency are scarce and largely controversial. OBJECTIVES: To investigate sexual dysfunction in patients with primary and secondary adrenal insufficiency and the effects of switching to once-daily dual-release hydrocortisone on sexual function in outcome assessors blinded, randomized, multicenter, active comparator clinical trial. MATERIALS AND METHODS: Eighty-nine adrenal insufficiency patients on conventional, multiple daily doses of glucocorticoid replacement, enrolled in the Dual RElease hydrocortisone versus conventionAl glucocorticoid replaceMent in hypocortisolism (DREAM) trial, were randomly assigned to continue their therapy or to switch to an equivalent dose of dual-release hydrocortisone. Sixty-three patients (34 women) consented to sex steroid measurements and questionnaires completion for quality of life (Addison's disease-specific quality-of-life questionnaire) and sexual function evaluation (female sexual function index for women, International Index of Erectile Function-Erectile Function for men) at baseline and 24 weeks after randomization. RESULTS: At baseline, sexual dysfunction was observed in 41% of women and 59% of men with adrenal insufficiency. In both sexes, no associations were found between sexual function and hormone levels, whereas Addison's disease-specific quality-of-life questionnaire total and fatigue domain scores positively correlated with total female sexual function index and International Index of Erectile Function-Erectile Function scores. At 24 weeks, there was no significant difference either in sexual function or sex steroid levels between study groups. In the dual-release hydrocortisone group, the variation in the female sexual function index desire domain score was positively associated with the change in Addison's disease-specific quality-of-life questionnaire's symptom domain score (ρ = 0.478, p = 0.045). DISCUSSION: Sexual dysfunction is common in adrenal insufficiency patients and is likely explained by multiple factors. dual-release hydrocortisone treatment is not directly associated with sexual function improvement, but an indirect effect mediated by quality-of-life amelioration cannot be excluded.

Dyslipidemia, lipid-lowering agents and neuroendocrine neoplasms: new horizons.

PURPOSE: Neuroendocrine neoplasms (NENs) are a heterogeneous group of malignancies originating from cells with a neuroendocrine phenotype. The complex relationship between lipid metabolism and cancer is gaining interest and a potential anti-cancer effect of lipid lowering agents is being considered. This review aims to discuss the current understanding and treatment of dyslipidaemia in NENs, focusing on the role of lipid lowering agents, including new therapeutic approaches, and future perspectives as possible tool in cancer prevention and tumor-growth control. METHODS: We performed an electronic-based search using PubMed updated until December 2023, summarizing the available evidence both in basic and clinical research about lipid lowering agents in NENs. RESULTS: Dyslipidemia is an important aspect to be considered in NENs management, although randomized studies specifically addressing this topic are lacking, unlike other cancer types. Available data mainly regard statins, and in vitro studies have demonstrated direct antitumor effects, including antiproliferative effects in some cancers, supporting possible pleiotropic effects also in NENs, but data remain conflicting. Ezetimibe, omega 3-fatty acids, fibrates and inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9) may enhance the regulation of lipid homeostasis, as demonstrated in other cancers. CONCLUSIONS: Targeting dyslipidemia in NENs should be part of the multidisciplinary management and an integrated approach may be the best option for both metabolic and tumor control. Whether lipid lowering agents may directly contribute to tumor control remains to be confirmed with specific studies, focusing on association with other metabolic risk, disease stage and primary site.

Effects of Dual-Release Hydrocortisone on Bone Metabolism in Primary and Secondary Adrenal Insufficiency: A 6-Year Study.

Context: Patients with primary (PAI) and secondary adrenal insufficiency (SAI) experience bone metabolism alterations, possibly due to excessive replacement. Dual-release hydrocortisone (DR-HC) has shown promising effects on several parameters, but bone metabolism has seldom been investigated. Objective: We evaluated the long-term effects of once-daily DR-HC on bone in PAI and SAI. Methods: Patients on immediate-release glucocorticoid therapy were evaluated before and up to 6 years (range, 4-6) after switching to equivalent doses of DR-HC, yielding data on bone turnover markers, femoral and lumbar spine bone mineral density (BMD), and trabecular bone score (TBS). Results: Thirty-two patients (19 PAI, 18 female), median age 52 years (39.4-60.7), were included. At baseline, osteopenia was observed in 38% of patients and osteoporosis in 9%, while TBS was at least partially degraded in 41.4%. Higher body surface area-adjusted glucocorticoid doses predicted worse neck (P < .001) and total hip BMD (P < .001). Longitudinal analysis showed no significant change in BMD. TBS showed a trend toward decrease (P = .090). Bone markers were stable, albeit osteocalcin levels significantly varied. PAI and SAI subgroups behaved similarly, as did patients switching from hydrocortisone or cortisone acetate. Compared with men, women exhibited worse decline in TBS (P = .017) and a similar trend for neck BMD (P = .053). Conclusion: After 6 years of chronic DR-HC replacement, BMD and bone markers remained stable. TBS decline is more likely due to an age-related derangement of bone microarchitecture rather than a glucocorticoid effect. Our data confirm the safety of DR-HC replacement on bone health in both PAI and SAI patients.

C-Cell Hyperplasia and Cystic Papillary Thyroid Carcinoma in a Patient with Type 1B Pseudohypoparathyroidism and Hypercalcitoninaemia: Case Report and Review of the Literature.

Hypercalcitoninaemia has been described in patients with pseudohypoparathyroidism (PHP) type 1A and 1B. Elevated calcitonin levels are thought to result from impaired Gsα receptor signaling, leading to multiple hormone resistance. Evidence on the risk of medullary thyroid carcinoma (MTC) or C-cell hyperplasia in PHP patients with hypercalcitoninaemia is lacking. A 43-year-old Caucasian man was referred to our endocrinology clinic for chronic hypocalcemia associated with elevated serum parathormone levels and a single cystic thyroid nodule. The patient did not show skeletal deformities, and screening for concomitant hormone resistances was negative, except for the presence of elevated serum calcitonin levels. The workup led to a molecular diagnosis of sporadic PHP1B. Fine needle aspiration of the thyroid nodule was not diagnostic. The calcium stimulation test yielded an abnormal calcitonin response. Given the scarcity of data on the risk of thyroid malignancy in PHP and calcium stimulation test results, total thyroidectomy was performed. Histological examination revealed cystic papillary thyroid cancer in a background of diffuse C-cell hyperplasia. To our knowledge, we are the first to describe a rare form of thyroid cancer combined with C-cell hyperplasia in a patient with PHP and hypercalcitoninaemia. In the present case, a mere receptor resistance might not fully explain the elevated calcitonin levels, suggesting that hypercalcitoninaemia should be carefully evaluated in PHP patients, especially in the case of concomitant thyroid nodules. Further studies on larger cohorts are needed to elucidate this topic.

Potential of Biochar as a Peat Substitute in Growth Media for Lavandula angustifolia, Salvia rosmarinus and Fragaria × ananassa.

Peat has long been the primary substrate for the production of ornamental and horticultural plants in pots. Today, peat is no longer considered a renewable resource due to its very lengthy regeneration time. Biochar, a solid by-product of biomass pyrolysis, has been proposed as an agricultural soil amendment. We investigated the effects of two types of biochar, namely biochar from pruning wood waste and biochar activated with wood vinegar ("smoked biochar"), on two ornamental plants (Lavandula angustifolia and Salvia rosmarinus) and on strawberries (Fragaria × ananassa). For both types of biochar, we measured the following parameters: the pH, density, electrical conductivity, humidity, calcium carbonate, total carbon, nitrogen, potassium, calcium, magnesium, sodium, and water retention. For peat, we measured the following parameters: the pH, electrical conductivity, total carbon, and total nitrogen. Our results showed an overall increase in plant growth, particularly in L. angustifolia when using 10% and 50% biochar concentrations and a 10% concentration of biochar activated with wood vinegar. In S. rosmarinus, we observed a slight increase in the total plant weight with the application of 10% smoked biochar (biochar activated with wood vinegar). Finally, in F. × ananassa, we observed an increase in the plant weight and fruit production when 10% biochar was applied. On the other hand, when high concentrations of biochar (50% and 100%) and especially smoked biochar were applied, we observed a significant reduction in the growth of all plants. We concluded that biochar and biochar activated with wood vinegar showed remarkable biological activity with marked phytotoxicity at high concentrations. They promoted plant growth when applied diluted and their use as partial peat substitutes could help support more sustainable horticultural practices.

Pituitary T1 signal intensity at magnetic resonance imaging is reduced in patients with obesity: results from the CHIASM study.

BACKGROUND: Despite obesity being well known to be associated with several pituitary hormone imbalances, pituitary appearance in magnetic resonance imaging (MRI) in patients with obesity is understudied. OBJECTIVE: To evaluate the pituitary volume and signal intensity at MRI in patients with obesity. METHODS: This is a prospective study performed in an endocrine Italian referral center (ClinicalTrial.gov Identifier: NCT03458533). Sixty-nine patients with obesity (BMI > 30 kg/m2) and twenty-five subjects without obesity were enrolled. Thirty-three patients with obesity were re-evaluated after 3 years of diet and lifestyle changes, of whom 17 (51.5%) achieved a > 5% loss of their initial body weight, whereas the remaining 16 (48.5%) had maintained or gained weight. Evaluations included metabolic and hormone assessments, DEXA scan, and pituitary MRI. Pituitary signal intensity was quantified by measuring the pixel density using ImageJ software. RESULTS: At baseline, no difference in pituitary volume was observed between the obese and non-obese cohorts. At the 3-year follow-up, pituitary volume was significantly reduced (p = 0.011) only in participants with stable-increased body weight. Furthermore, a significant difference was noted in the mean pituitary intensity of T1-weighted plain and contrast-enhanced sequences between the obese and non-obese cohorts at baseline (p = 0.006; p = 0.002), and a significant decrease in signal intensity was observed in the subgroup of participants who had not lost weight (p = 0.012; p = 0.017). Insulin-like growth factor-1 levels, following correction for BMI, were correlated with pituitary volume (p = 0.001) and intensity (p = 0.049), whereas morning cortisol levels were correlated with pituitary intensity (p = 0.007). The T1-weighted pituitary intensity was negatively correlated with truncal fat (p = 0.006) and fibrinogen (p = 0.018). CONCLUSIONS: The CHIASM study describes a quantitative reduction in pituitary intensity in T1-weighted sequences in patients with obesity. These alterations could be explained by changes in the pituitary stromal tissue, correlated with low-grade inflammation.

COVID-19 pandemic and adrenals: deep insights and implications in patients with glucocorticoid disorders.

PURPOSE: Coronavirus disease-19 (COVID-19) has spread throughout the world. It was initially defined as a potentially severe syndrome affecting the respiratory tract, but it has since been shown to be a systemic disease with relevant extrapulmonary manifestations that increase mortality. The endocrine system has been found to be vulnerable to COVID-19 infection. The current review aims to evaluate the available data on the impact of COVID-19 infection and treatment, as well as COVID-19 vaccines, on adrenal gland function, particularly in patients with GC disorders. METHODS: A thorough search of published peer-reviewed studies in PubMed was performed using proper keywords. RESULTS: Adrenal viral tropism and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication in the adrenal glands have been demonstrated, and adrenal insufficiency (AI) is a rare, but potentially severe complication in COVID-19 disease, whose recognition can be difficult if only for the empirical treatments administered in the early stages. Glucocorticoid (GC) treatment have had a pivotal role in preventing clinical deterioration in patients with COVID-19, but long-term GC use may increase COVID-19-related mortality and the development of iatrogenic AI. Patients with GC disorders, especially AI and Cushing's syndrome, have been identified as being at high risk of COVID-19 infection and complications. Published evidence suggests that AI patient awareness and proper education may help adjust GC replacement therapy appropriately when necessary, thereby reducing COVID-19 severity. The COVID-19 pandemic has had an impact on AI management, particularly in terms of adherence to patients' care plans and self-perceived challenges. On the other hand, published evidence suggests that the clinical course of COVID-19 may be affected by the severity of hypercortisolism in patients with CS. Therefore, to ameliorate the risk profile in these patients, cortisol levels should be adequately controlled, along with careful monitoring of metabolic and cardiovascular comorbidities. To date, the COVID-19 vaccine remains the only available tool to face SARS-CoV-2, and it should not be treated differently in patients with AI and CS. CONCLUSION: SARS-CoV-2 infection has been linked to adrenal damage and AI is a rare complication in COVID-19 disease, requiring prompt recognition. Educational efforts and patient awareness may reduce COVID-19 severity in patients with AI. Control of cortisol levels and monitoring of complications may improve the clinical course of COVID-19 in patients with CS.

Pituitary adenoma consistency affects postoperative hormone function: a retrospective study.

BACKGROUND: Tumor consistency recently emerged as a key factor in surgical planning for pituitary adenomas, but its impact on postoperative endocrine function is still unclear. Our study aimed to evaluate the impact of tumor consistency on the development of postoperative pituitary deficiencies. METHODS: Single-center, retrospective analysis of consecutive pituitary surgeries performed between January 2017 and January 2021 at Policlinico Umberto I in Rome. All patients underwent radiological and biochemical evaluations at baseline, and hormone assessments 3 and 6 months after pituitary surgery. Postoperative MRI studies were used to determine resection rates following surgery. Data on tumor consistency, macroscopic appearance, neurosurgical approach, and intraoperative complications were collected. RESULTS: Fifty patients [24 women, mean age 57 ± 13 years, median tumor volume 4800 mm3 [95% CI 620-8828], were included. Greater tumor volume (χ2 = 14.621, p = 0.006) and male sex (χ2 = 12.178, p < 0.001) were associated with worse preoperative endocrine function. All patients underwent transsphenoidal adenomectomy. Fibrous consistency was observed in 10% of patients and was associated with a Ki-67 greater than 3% (χ2 = 8.154, p = 0.04), greater risk of developing postoperative hormone deficiencies (χ2 = 4.485, p = 0.05, OR = 8.571; 95% CI: 0.876-83.908), and lower resection rates (χ2 = 8.148, p = 0.004; OR 1.385, 95% CI; 1.040-1.844). Similarly, worse resection rates were observed in tumors with suprasellar extension (χ2 = 5.048, p = 0.02; OR = 6.000, 95% CI; 1.129-31.880) and CSI (χ2 = 4.000, p = 0.04; OR = 3.857, 95% CI; 0.997-14.916). CONCLUSIONS: Tumor consistency might provide useful information about postoperative pituitary function, likely due to its impact on surgical procedures. Further prospective studies with larger cohorts are needed to confirm our preliminary findings.

A practical nutritional guideline to manage neuroendocrine neoplasms through chronotype and sleep.

Chronotype is the attitude of subjects to carry out their daily activities mainly in the morning ("lark") or in the evening ("owl"). The intermediate chronotype is located between these two categories. It has been demonstrated that chronotype can influence the incidence, course and response to treatments of tumors. In particular patients diagnosed with gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) and evening chronotype are characterized by unhealthy lifestyle, obesity, metabolic syndrome, a worsen cardiometabolic profile, a poor prognosis with a progressive disease and the development of metastasis. In addition, evening chronotype has been associated with sleep disturbances, which in turn have been related to tumor development and progression of tumors. There is a strict connection between sleep disturbances and NENs because of the hyperactivation of proangiogenic factors that caused aberrant neoangiogenesis. A nutritional tailored approach could represent a tool to align subjects with evening chronotype to physiological biological rhythms based on the properties of some macro and micronutrients of being substrate for melatonin synthesis. Thus, we aimed to provide an overview on the association of chronotype categories and sleep disturbances with NENs and to provide nutritional advices to manage subjects with NENs and these disturbances of circadian rhythm.

The Role of Lichens, Mosses, and Vascular Plants in the Biodeterioration of Historic Buildings: A Review.

Biodeterioration is defined as the alteration of a given substrate due to a combination of physical and chemical factors produced by living organisms when attached to such materials. This phenomenon attracts scientific research attention due to its risk in causing destruction to outdoor cultural rock heritage sites. In this review, an update on the state-of-art regarding the biodeterioration phenomenon is represented in order to highlight the type of colonizing vegetation and possible mechanisms behind the corresponding deterioration. For this reason, 62 articles with a focus on lichens, mosses, and higher plants were investigated by evaluating the role of construction materials and different plant species related to the hazard index. The results showed that trees and shrubs are the most harmful plant life forms, for example, Ficus carica, Ailanthus altissima, and Capparis spinosa, while regarding building materials, those characterized by high porosity, such as andesite and argillaceous limestone, are more vulnerable to plant colonization. Further studies are needed to examine in detail the relationship between colonizing organisms, intrinsic elements of the substrate, and external factors, as well as the refinement of measures to prevent and control colonization by plants.

Edible Flowers Used in Some Countries of the Mediterranean Basin: An Ethnobotanical Overview.

Edible flowers are becoming an essential component of people's nutrition in the Mediterranean basin. In the last decades, many researchers also have focused their attention on the nutritional composition of the edible flowers, as well as their antioxidant and antimicrobial properties, including studies on their safety issues. Despite the growing interest in the use of flowers in human nutrition, the ethnobotanical literature is lacking coverage of some important issues, particularly those which concern the use of flowers in the folk tradition. Only recently, a review regarding the contribution of 32 edible flowers to the Mediterranean diet was published. The aim of the present review is to document the plant lore regarding the wild and cultivated edible flowers consumed in the Mediterranean basin. Based on the 112 studies reviewed, we documented 251 taxa as being used in the Mediterranean basin as edible flowers. The plant species belong to 45 families and 141 genera. Asteraceae (54 taxa) is the most frequently cited family. Sambucus nigra L. is the most cited species. This study can be the basis for future research on the supposed bioactivity and toxicity of wild and cultivated flowers.

Susceptibility and characteristics of infections in patients with glucocorticoid excess or insufficiency: the ICARO tool.

Objective: Registry data show that Cushing's syndrome (CS) and adrenal insufficiency (AI) increase mortality rates associated with infectious diseases. Little information is available on susceptibility to milder forms of infections, especially those not requiring hospitalization. This study aimed to investigate infectious diseases in patients with glucocorticoid disorders through the development of a specific tool. Methods: We developed and administered the InfeCtions in pAtients with endocRinOpathies (ICARO) questionnaire, addressing infectious events over a 12-month observation period, to 1017 outpatients referred to 4 University Hospitals. The ICARO questionnaire showed good test-retest reliability. The odds of infection (OR (95% CI)) were estimated after adjustment for confounders and collated into the ICARO score, reflecting the frequency and duration of infections. Results: In total, 780 patients met the inclusion criteria: 43 with CS, 32 with adrenal incidentaloma and mild autonomous cortisol secretion (MACS), and 135 with AI, plus 570 controls. Compared to controls, CS was associated with higher odds of urinary tract infections (UTIs) (5.1 (2.3-9.9)), mycoses (4.4 (2.1-8.8)), and flu (2.9 (1.4-5.8)). Patients with adrenal incidentaloma and MACS also showed an increased risk of UTIs (3.7 (1.7-8.0)) and flu (3.2 (1.5-6.9)). Post-dexamethasone cortisol levels correlated with the ICARO score in patients with CS. AI was associated with higher odds of UTIs (2.5 (1.6-3.9)), mycoses (2.3 (1.4-3.8)), and gastrointestinal infections (2.2 (1.5-3.3)), independently of any glucocorticoid replacement dose. Conclusions: The ICARO tool revealed a high prevalence of self-reported infections in patients with glucocorticoid disorders. ICARO is the first of its kind questionnaire, which could be a valuable tool for monitoring infections in various clinical settings.

Development and testing of diagnostic algorithms to identify patients with acromegaly in Southern Italian claims databases.

Acromegaly is a rare disease characterized by an excessive production of growth-hormone and insulin-like growth factor 1, typically resulting from a GH-secreting pituitary adenoma. This study was aimed at comparing and measuring accuracy of newly and previously developed coding algorithms for the identification of acromegaly using Italian claims databases. This study was conducted between January 2015 and December 2018, using data from the claims databases of Caserta Local Health Unit (LHU) and Sicily Region in Southern Italy. To detect acromegaly cases from the general target population, four algorithms were developed using combinations of diagnostic, surgical procedure and co-payment exemption codes, pharmacy claims and specialist's visits. Algorithm accuracy was assessed by measuring the Youden Index, sensitivity, specificity, positive and negative predictive values. The percentage of positive cases for each algorithm ranged from 7.9 (95% CI 6.4-9.8) to 13.8 (95% CI 11.7-16.2) per 100,000 inhabitants in Caserta LHU and from 7.8 (95% CI 7.1-8.6) to 16.4 (95% CI 15.3-17.5) in Sicily Region. Sensitivity of the different algorithms ranged from 71.1% (95% CI 54.1-84.6%) to 84.2% (95% CI 68.8-94.0%), while specificity was always higher than 99.9%. The algorithm based on the presence of claims suggestive of acromegaly in ≥ 2 different databases (i.e., hospital discharge records, copayment exemptions registry, pharmacy claims and specialist visits registry) achieved the highest Youden Index (84.2) and the highest positive predictive value (34.8; 95% CI 28.6-41.6). We tested four algorithms to identify acromegaly cases using claims databases with high sensitivity and Youden Index. Despite identifying rare diseases using real-world data is challenging, this study showed that robust validity testing may yield the identification of accurate coding algorithms.

["Block and replace" of sodium levothyroxine therapy]. / "Block and replace" della terapia con levotiroxina sodica.

We present the case of a 65 years old patient with Graves disease associated with hyperthyroidism and a medical history of bipolar disorder treated with lithium. Hyperthyroidism was initially treated with high-dose methimazole monotherapy and later the patient developed overt hypothyroidism (clinical and biochemical), but without remission of the underlying autoimmune disease. A "block and replace" therapeutic regimen was then started with reduced methimazole doses in combination with levothyroxine, which resulted in a short time in normalization of the hormonal profile and significant improvement of the clinical picture. Therefore, the "block and replace" regimen represents a valid therapeutic alternative to anti-thyroid drugs monotherapy in the treatment of hyperthyroidism due to Graves disease in selected cases.

Selenium Supplementation in Pregnant Women with Autoimmune Thyroiditis: A Practical Approach.

Selenium (Se) is an essential trace element with antioxidant and anti-inflammatory properties and a pivotal role in thyroid metabolism. Ensuring a sufficient Se supply is possible via a balanced, wholesome diet; however, Se content in foods may be different throughout geographical areas. Se supplementation is expected to improve inflammatory status in patients with autoimmune thyroiditis, especially in those with high activity, and has been demonstrated as effective in reducing the thyroid peroxidase antibodies titer. Se status seems to affect thyroid function in pregnancy, which prompts the potential role of Se supplementation in such patients. Few clinical trials have investigated the effectiveness of Se supplementation in pregnant women with thyroiditis, and their results suggest the safety and effectiveness of this element in reducing autoantibody levels and preventing postpartum thyroiditis development, although limited. Hence, more robust evidence is needed to confirm these data. The current study aims to summarize published data on the relationship between Se and thyroid status in pregnant women with thyroiditis and the potential use of Se. Moreover, an algorithm for Se supplementation is proposed for pregnant women with thyroiditis to help endocrinologists in daily clinical practice to consider Se status.

Diagnostic accuracy of ultrasonographic features in detecting thyroid cancer in the transition age: a meta-analysis.

Context: Significant uncertainty exists about the diagnostic accuracy of ultrasonographic (US) features used to predict the risk of thyroid cancer in the pediatric population. Moreover, there are no specific indications for thyroid nodule evaluation in patients during the transition age. Objective: The meta-analysis aimed to address the following question: which thyroid nodule US features have the highest accuracy in predicting malignancy in the transition age. Methods: We performed a meta-analysis of observational/cohort/diagnostic accuracy studies dealing with thyroid nodule sonography, reporting US features, and using histology as a reference standard for the diagnosis of malignancy and histology or cytology for the diagnosis of benignity in the transition age (mean/median age 12-21 years). Results: The inclusion criteria were met by 14 studies, published between 2005 and 2020, including 1306 thyroid nodules (mean size 17.9 mm) from 1168 subjects. The frequency of thyroid cancer was 36.6%. The US features with the highest diagnostic odds ratio (DOR) for malignancy were the presence of suspicious lymph nodes (DOR: 56.0 (95% CI: 26.0-119.0)), a 'taller than wide' shape of the nodule (6.0 (95% CI: 2.0-16.0)), the presence of microcalcifications (13.0 (95% CI: 6.0-29.0)) and irregular margins (9.0 (95% CI: 5.0-17.0)). Heterogeneity among the studies was substantial. Conclusions: Following the diagnosis of a thyroid nodule in the transition age, a thorough US examination of the neck is warranted. The detection of suspicious lymph nodes and/or thyroid nodules with a 'taller than wide' shape, microcalcifications, and irregular margins is associated with the highest risk of malignancy in the selection of nodules candidates for biopsy.

Safety and Efficacy of PTH 1-34 and 1-84 Therapy in Chronic Hypoparathyroidism: A Meta-Analysis of Prospective Trials.

Hypoparathyroidism is the only endocrine deficiency for which hormone replacement therapy is not the standard of care. Although conventional treatments may control hypocalcaemia, other complications such as hyperphosphatemia, kidney stones, peripheral calcifications, and bone disease remain unmet needs. This meta-analysis (PROSPERO registration number CRD42019126881) aims to evaluate and compare the efficacy and safety of PTH1-34 and PTH1-84 in restoring calcium metabolism in chronic hypoparathyroidism. EMBASE, PubMed, and CENTRAL databases were searched for randomized clinical trials or prospective studies published between January 1996 and March 2021. English-language trials reporting data on replacement with PTH1-34 or PTH1-84 in chronic hypoparathyroidism were selected. Three authors extracted outcomes, one author performed quality control, all assessed the risk of biases. Overall, data from 25 studies on 588 patients were analyzed. PTH therapy had a neutral effect on calcium levels, while lowering serum phosphate (-0.21 mmol/L; 95% confidence interval [CI], -0.31 to -0.11 mmol/L; p < 0.001) and urinary calcium excretion (-1.21 mmol/24 h; 95% CI, -2.03 to -0.41 mmol/24 h; p = 0.003). Calcium phosphate product decreased under PTH1-84 therapy only. Both treatments enabled a significant reduction in calcium and calcitriol supplementation. PTH therapy increased bone turnover markers and lumbar spine mineral density. Quality of life improved and there was no difference in the safety profile between PTH and conventionally treated patients. Results for most outcomes were similar for the two treatments. Limitations of the study included considerable population overlap between the reports, incomplete data, and heterogeneity in the protocol design. In conclusion, the meta-analysis of data from the largest collection to date of hypoparathyroid patients shows that PTH therapy is safe, well-tolerated, and effective in normalizing serum phosphate and urinary calcium excretion, as well as enabling a reduction in calcium and vitamin D use and improving quality of life. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Predictors of Response and Survival to Multikinase Inhibitors in Radioiodine Resistant Differentiated Thyroid Cancer.

Sorafenib and lenvatinib are the only multikinase inhibitors (MKIs) approved for the treatment of radioactive iodine refractory differentiated thyroid cancer (RR-DTC). Although they have been demonstrated to improve progression free survival and overall response rate, the risk of toxicities is very high, worsening patients' quality of life. Therefore, predicting MKI treatment outcomes in the setting of RR-DTC is very challenging for optimizing patients' management. The current review provides an overview of the predictive factors for the response and survival of sorafenib and lenvatinib in RR-DTC. In this setting, a systemic therapy should be considered after conducting a multidisciplinary discussion aimed at evaluating the risk-benefit ratio of the treatment and taking into account several clinical, biochemical, and molecular factors. Age, performance status, and cancer-related symptoms are the most important clinical markers to be considered prior to starting MKI treatment, together with tumor burden. Some tissue and circulating biomarkers have been investigated, those involved in the angiogenic pathways being the most promising. Finally, prospective clinical trials aimed at evaluating predictive markers for therapeutic response are needed for tailoring patient management and allowing more appropriate treatment choices.