Long-term cardiometabolic outcome in patients with pituitary adenoma diagnosed in chilhood and adolescence.

PURPOSE: Pituitary adenomas (PAs) rarely occur in childhood and adolescence. Management of PAs in this critical age can be particularly challenging considering the auxological sequelae and potential long-term cardiometabolic consequences. We aimed to describe the clinical characteristics of patients with PA aged < 18years at diagnosis and during long-term follow-up, focusing on the prevalence of cardio-metabolic comorbidities and the impact of different therapeutic strategies. METHODS: Clinical data at diagnosis and at last follow-up visit (mean 10.3 ± 9.2 years) of 101 patients aged < 18 years with PA, referred to our University Hospital from 1990 to 2017, were retrospectively evaluated. RESULTS: At diagnosis, 11.9% of patients presented with pituitary hormone deficiencies, whose number was positively correlated with pituitary tumor diameter (p < 0.001). At diagnosis, 26.7% of patients were overweight and 15.8% were obese. In patients with hypercortisolism or GH excess the prevalence of obesity was more than 2-fold greater than in general population. No correlation was found between pituitary tumor size and BMI. At baseline, the greater the number of pituitary hormone deficits, the higher BMI (p = 0.039). In prolactinoma patients still on medical therapy at last visit, BMI was higher than at baseline. CONCLUSION: We found an increased prevalence of overweight/obesity only in pediatric and adolescent patients with GH- or ACTH-secreting PA. Regarding cardio-metabolic comorbidities other than obesity/overweight, we have not found anything worth of mention. The remission of hypercortisolism positively impacted on BMI, while medical therapy in patients with prolactinoma seemed unable to avoid weight gain, suggesting a careful metabolic management of these patients.

Pituitary atypical teratoid rhabdoid tumor in a patient with prolactinoma: A unique description.

Atypical teratoid rhabdoid tumor (ATRT) is an aggressive tumor of the CNS and characteristically occurs in the pediatric age. In adulthood, ATRT is rare and it is mainly localized in the cerebral hemispheres. Only 16 cases of ATRT have been described in the sellar region up to now. Interestingly, all sellar ATRTs occurred in adult female patients. Herein we report a novel case of sellar ATRT in a patient with previous history of lactotroph adenoma. Similar to other sellar ATRTs, this case occurred in a female adult patient. At histological examination, it was characterized by a small number of rhabdoid cells. In addition, it did not have homozygous deletion of SMARCB1 gene, but it rather showed a frameshift mutation at exon 4 of SMARCB1 which had not been previously found in ATRT. Clinico-pathological and molecular findings observed in this case confirm previous evidence that sellar ATRT seems to be a distinct entity. Association with previous prolactin-secreting pituitary adenoma is discussed.

Mitotane treatment in patients with adrenocortical cancer causes central hypothyroidism.

INTRODUCTION: Mitotane, a steroidogenesis inhibitor with adrenolytic properties used to treat adrenocortical cancer (ACC), can affect thyroid function. A reduction of FT4 levels with normal FT3 and TSH has been described in these patients. Using an in vitro murine model, the secretory capacity of thyrotrophic cells has been shown to be inhibited by mitotane. OBJECTIVE: To investigate the pathogenesis of thyroid abnormalities in mitotane-treated patients with ACC. PATIENTS AND METHODS: In five female patients with ACC (median age 47; range 31-65) treated with mitotane (dosage 1·5 g/day; 1·0-3·0), we analysed the pattern of TSH and thyroid function index (FT4, FT3 and FT3/FT4 ratio) compared to an age- and gender-matched control group. The in vivo secretory activity of the thyrotrophic cells was evaluated using a standard TRH test (200 µg), and the response was compared to both a group of age-matched female controls (n = 10) and central hypothyroid patients (n = 10). RESULTS: Basal TSH (median 1·54 mU/l; range 1·20-2·17) was normal and scattered around our median reference value, FT3 levels (median 3·80 pmol/l; 3·30-4·29) were normal but below the median reference value of 4·37 pmol/l and FT4 levels were below the normal range in all patients (median 8·40 pmol/l; 7·6-9·9). FT3/FT4 ratio was in the upper range in 4 patients and higher than normal in one patient. A blunted TSH response to TRH was observed in mitotane-treated patients. ΔTSH (absolute TSH response, peak TSH minus basal TSH) was 3·65 (range 3·53-5·26), 12·37 (range 7·55-19·97) and 1·32 mU/l (range 0·52-4·66) in mitotane-treated patients, controls and central hypothyroid patients, respectively. PRL secretion was normal. CONCLUSIONS: Mitotane-treated patients with ACC showed low FT4, normal FT3 and TSH and impaired TSH response to TRH, characteristic of central hypothyroidism. Furthermore, the elevated FT3/FT4 ratio of these subjects reflects an enhanced T4 to T3 conversion rate, a compensatory mechanism characteristic of thyroid function changes observed in hypothyroid conditions. This finding thus confirms in vitro studies and may have a therapeutic implication for treatment with thyroid hormones, as suggested by current guidelines for this specific condition.

ACROSCORE: a new and simple tool for the diagnosis of acromegaly, a rare and underdiagnosed disease.

OBJECTIVE: Acromegaly, a disease caused by GH/IGF-I hypersecretion, is associated with a high mortality rate; early recognition is therefore necessary to ensure successful treatment and to avoid comorbidities. We have created a symptom/sign scoring tool (ACROSCORE) for physicians to use to identify acromegaly. DESIGN: To compare cases of acromegaly diagnosed between 1990 and 2014 against a control group affected by non-GH-secreting pituitary tumours to identify symptoms and signs that are most discriminative for acromegaly. PATIENTS: Confirmed acromegaly patients and patients affected by non-GH-secreting pituitary tumours. MEASUREMENTS: In all patients, signs, symptoms and comorbidities were recorded from medical records and collected using a specifically designed questionnaire. RESULTS: A total of 194 acromegaly patients [115 women; mean (SD) age 47·2 (14·2) years] and 243 patients affected by non-GH-secreting pituitary tumours [131 women; mean (SD) age 45·8 (15·8) years] were included. A strong association was observed for type 2/secondary diabetes [odds ratio (OR) 3·7], hyperhidrosis (OR 6·1), thyroid hyperplasia (OR 13·9), colorectal polyps (OR 10·4), spaced teeth (OR 25·4) and carpal tunnel syndrome (OR 4·3). Based on this information, a multivariable logistic model was built and a 14-point scoring system developed. A score of 0 excludes the risk of acromegaly [positive predictive value (PV(+)) = 0·6%]; scores 1-5 comprise a grey area; scores >5 indicate that a diagnosis of acromegaly cannot be excluded (PV(+) = 46·1%). CONCLUSIONS: Once validated in independent studies, ACROSCORE may represent a new tool for the clinical screening of acromegaly that can be used by general practitioners and nonendocrinology specialists.

Characteristics and outcomes of Italian patients from the observational, multicentre, hypopituitary control and complications study (HypoCCS) according to tertiles of growth hormone peak concentration following stimulation testing at study entry.

OBJECTIVE: To determine whether characteristics and outcomes of Italian patients in the observational global Hypopituitary Control and Complication Study (HypoCCS) differed according to the degree of GH deficiency (GHD). DESIGN: Patients were grouped by tertiles of stimulated GH peak concentration at baseline (Group A lowest tertile, n = 342; Group B middle tertile, n = 345; Group C highest tertile, n = 338). RESULTS: Baseline demographics, lipid levels, body mass index categories and mean Framingham cardiovascular risk indexes were similar in the three groups and remained substantially unchanged over time, with no subsequent significant between-group differences (except mean levels of triglycerides increased in the highest tertile group). GHD was adult-onset for >75% of patients in all groups. The percentage of patients with multiple pituitary deficiencies was higher in Group A than in the other groups; isolated GHD was reported with highest frequency in Group C. Patients in Group A received the lowest mean starting dose of GH. Hyperlipidaemia at baseline was reported in 35·1%, 31·1% and 24·7% of patients in groups A, B and C, respectively (P = 0·029). Mean duration of GH treatment was 7·21, 5·45 and 4·96 years, respectively. The proportion of patients with adverse events did not differ significantly between groups, with a low prevalence over time of diabetes and cancer. CONCLUSIONS: In Italian patients from HypoCCS, the level of GH deficit did not influence changes over time in metabolic parameters or adverse event profile, despite differences in GHD severity at baseline and in the starting GH dose.

MTHFR C677T polymorphism, folate status and colon cancer risk in acromegalic patients.

BACKGROUND: Acromegalic patients have a higher risk of developing colorectal tumours (CRT). The common C677T polymorphism in methylenetetrahydrofolate reductase (MTHFR) gene is a well-documented CRT risk factor in the general population, but its role in acromegaly has never been examined. PURPOSE: We investigated the influence of MTHFR C677T polymorphism, folate status and other lifestyle, nutritional and disease-specific variables on CRT risk in acromegaly. METHODS: Clinical data were collected from 115 acromegalic patients (25 with active disease) who underwent a complete colonoscopy. C677T MTHFR genotype, homocysteine, vitamin B12, insulin growth factor and insulin levels, as well as metabolic variables were evaluated. RESULTS: Colorectal tumours were identified in 51 patients (3 adenocarcinomas). MTHFR C677T distribution was in the Hardy-Weinberg equilibrium and similar in patients with or without CRT. There was a correlation between patients with TT genotype and CRT occurrence (Spearman's test: P = 0.03), with an Odds Ratio (OR) of 1.32 (95% CI 0.522-3.362, P NS). A folate-MTHFR genotype interaction on CRT risk was found (P = 0.037): in the lower folate subgroup, TT patients showed a 2.4 higher OR for CRT (95% CI 0.484-11.891; P NS) than C-allele carriers. Smoking (P = 0.007), increased HbA1c levels (P = 0.021), dyslipidaemia (P = 0.049), acromegaly control (P = 0.057), and folate-MTHFR genotype interaction (P = 0.088) were associated with CRT at multivariate analysis. CONCLUSIONS: In this cohort of acromegalic patients, CRT risk is increased in 677TT MTHFR patients with low plasma folate levels. Smoking, high HbA1c levels, dyslipidaemia and disease activity were also associated with increased CRT risk.

Epidemiological analysis to identify predictors of X-linked hypophosphatemia (XLH) diagnosis in an Italian pediatric population: the EPIX project.

PURPOSE: X-linked hypophosphatemia (XLH) is a rare multi-systemic disease characterized by low plasma phosphate levels. The aim of this study was to investigate the annual XLH prevalence and internally evaluate predictive algorithms' application performance for the early diagnosis of XLH. METHODS: The PediaNet database, containing data on more than 400,000 children aged up to 14 years, was used to identify a cohort of XLH patients, which were matched with up to 10 controls by date of birth and gender. The annual prevalence of XLH cases per 100,000 patients registered in PediaNet database was estimated. To identify possible predictors associated with XLH diagnosis, a logistic regression model and two machine learning algorithms were applied. Predictive analyses were separately carried out including patients with at least 1 or 2 years of database history in PediaNet. RESULTS: Among 431,021 patients registered in the PediaNet database between 2007-2020, a total of 12 cases were identified with a mean annual prevalence of 1.78 cases per 100,000 patients registered in PediaNet database. Overall, 8 cases and 60 matched controls were included in the analysis. The random forest algorithm achieved the highest area under the receiver operating characteristic curve (AUC) value both in the one-year prior ID (AUC = 0.99, 95% CI = 0.99-1.00) and the two-year prior ID (AUC = 1.00, 95% CI = 1.00-1.00) analysis. Overall, the XLH predictors selected by the three predictive methods were: the number of vitamin D prescriptions, the number of recorded diagnoses of acute respiratory infections, the number of prescriptions of antihistamine for systemic use, the number of prescriptions of X-ray of the lower limbs and pelvis and the number of allergology visits. CONCLUSION: Findings showed that data-driven machine learning models may play a prominent role for the prediction of the diagnosis of rare diseases such as XLH.

Challenges and pitfalls in the management of endocrine toxicities from immune checkpoint inhibitors: a case presentation of synchronous thyrotoxicosis and primary adrenal insufficiency in a melanoma patient.

BACKGROUND: Immune checkpoint inhibitors have revolutionized the therapeutic approach to several solid tumors, becoming the standard of care for cancer treatment in different disease settings. Despite the fact that these agents are better tolerated than conventional chemotherapy, their use is associated with a specific toxicity profile, so-called immune-related adverse events (irAEs), that can involve several organs. Endocrine irAEs are among the most frequent toxicities (around 10 to 16%) and include hypophysitis, thyroid disorders, adrenalitis, and diabetes mellitus. Some of them may be life-threatening if not promptly recognized (such as diabetic ketoacidosis and acute adrenal crisis). CASE PRESENTATION: A 55-year-old woman with a personal history of euthyroid Hashimoto's thyroiditis was diagnosed with a metastatic melanoma, BRAF wild type. Under treatment with anti-PD-1 pembrolizumab, she developed thyrotoxicosis followed by hypothyroidism due to destructive thyroiditis and concurrent primary adrenal insufficiency due to adrenalitis. CONCLUSIONS: The simultaneous occurrence of adrenal and thyroid autoimmune diseases, resembling autoimmune polyendocrine syndrome type 2, may occur as a rare but serious side effect of ICI treatment. It often presents with abrupt onset and rapid evolution towards polyglandular insufficiency. Physicians should be aware of the potential association of two or more endocrine disorders and careful monitoring of endocrine function is needed during ICI therapy.

Factors associated with disease control failure in acromegaly patients treated with pegvisomant: an ACROSTUDY analysis.

Purpose: The aim of this study was to examine the probability of achieving acromegaly disease control according to several patient-, disease- and treatment-related factors longitudinally. Methods: We analyzed data from ACROSTUDY, an open-label, noninterventional, post-marketing safety surveillance study conducted in 15 countries. A total of 1546 patients with acromegaly and treated with pegvisomant, with available information on baseline IGF-1 level, were included. Factors influencing IGF-1 control were assessed up to 10 years of follow-up by mixed-effects logistic regression models, taking into account changing values of covariates at baseline and at yearly visits. Twenty-eight anthropometric, clinical and treatment-related covariates were examined through univariate and multivariate analyses. We tested whether the probability of non-control was different than 0.50 (50%) by computing effect sizes (ES) and the corresponding 95% CI. Results: Univariate analysis showed that age <40 years, normal or overweight, baseline IGF-1 <300 µg/L or ranged between 300 and 500 µg/L, and all pegvisomant dose <20 mg/day were associated with a lower probability of acromegaly uncontrol. Consistently, in multivariate analyses, the probability of uncontrolled acromegaly was influenced by baseline IGF-1 value: patients with IGF-1 <300 µg/L had the lowest risk of un-controlled acromegaly (ES = 0.29, 95% CI: 0.23-0.36). The probability of acromegaly uncontrol was also lower for values 300-500 µg/L (ES = 0.37, 95% CI: 0.32-0.43), while it was higher for baseline IGF-1 values ≥700 µg/L (ES = 0.58, 95% CI: 0.53-0.64). Conclusion: Baseline IGF-l levels were a good predictor factor for long-term acromegaly control. On the contrary, our data did not support a role of age, sex, BMI and pegvisomant dose as predictors of long-term control of acromegaly. Significance statement: Among factors that could influence and predict the efficacy of pegvisomant therapy in controlling acromegaly, a central role of baseline IGF-1 values on the probability of achieving a biochemical control of acromegaly during the treatment with pegvisomant was identified, in a real-life setting.

Prolactin in obese children: a bridge between inflammation and metabolic-endocrine dysfunction.

OBJECTIVE: Adipocytes, regulated by insulin, represent the major peripheral source of prolactin (PRL), which play a pivotal role in energy balance, acting on adipogenesis and lipolysis. The aim of this study was to investigate whether PRL was associated with obesity-related inflammatory status and metabolic parameters. The diagnostic and prognostic role of PRL for metabolic syndrome (MS) was assessed. The effects of short-term lifestyle therapy on PRL levels were evaluated. SUBJECTS: Prolactin was assessed in 94 obese patients and compared with 40 healthy children (HS).Patients were followed up for 1 year. Receiver operating characteristics (ROC) analysis was employed to find the best cut-off values capable of identifying MS in obese children for PRL, IL-6 and TNF-α. Kaplan-Meier curves were also generated. Adjusted risk estimates for MS were calculated using Cox proportional hazard regression analysis. An obesity intervention programme was administered for 12 months. RESULTS: Prolactin levels were lower in obese patients than controls (P < 0·0001). PRL was found to be inversely correlated with BMI, IL-6 and HOMA-IR, whereas a direct correlation was found with HDL values. At ROC analysis, PRL showed higher sensitivity and specificity than IL-6 and TNF-α in identifying MS in obese children. Cox proportional hazard regression analysis showed that PRL predicted MS independently of other potential confounders. The lifestyle intervention improved PRL and metabolic parameters. CONCLUSIONS: Prolactin represents a prognostic marker for obese children and a predictive factor for progression to MS. PRL measurement may be useful as part of the endocrine work-up of obese children.

Role of pituitary dysfunction on cardiovascular risk in primary empty sella patients.

OBJECTIVE: Primary empty sella (PES) is a frequent anatomical condition rarely causing pituitary dysfunction. We assessed cardiovascular risk in a cohort of PES patients referred to Endocrine Units. DESIGN: The study was performed in three Italian tertiary referral centres. We evaluated pituitary function and cardiovascular risk, on the basis of lipid and glucose metabolism parameters and of Framingham score (FS), in 94 consecutive patients with PES diagnosis and in 94 gender, age and BMI matched controls. PATIENTS: Pituitary function was normal in 30 patients (group A), whereas a single or multiple pituitary hormone deficiency was demonstrated in 64 (group B). Growth hormone deficiency (GHD) was diagnosed in 56, central hypothyroidism in 35, hypogonadotropic hypogonadism in 32 and central hypoadrenalism in 24 cases. RESULTS: Framingham score was higher and glucose and lipid profile were worse in PES patients than in controls. Cardiovascular risk parameters were not different between group A and B. In group B, increased cardiovascular risk was associated with hypothyroidism and hypogonadism, but not with GHD. In group A, cardiovascular risk was higher and FT3 and FT4 levels were lower than in controls. Moreover, PES patients stratified for BMI showed a worse glucose and lipid profile and (in the overweight subgroup) higher FS than matched controls. CONCLUSIONS: Primary empty sella patients show increased cardiovascular risk, regardless of BMI. A worse lipid and glucose profile and higher FS were associated with secondary hypothyroidism, even subclinical, as well as hypogonadism.

Should aip gene screening be recommended in family members of FIPA patients with R16H variant?

Germline mutations of aryl-hydrocarbon-receptor interacting protein (AIP) are associated with pituitary adenoma predisposition. They occur in 20 % of familial isolated pituitary adenoma (FIPA) and in about 3-5 % of sporadic pituitary adenomas, especially in early onset somatotropinomas and prolactinomas. Our aim was to evaluate the clinical and genetic features of a large Italian FIPA family, where an AIP variant was identified. AIP direct sequencing from genomic DNA was carried out in 16 available family members. AIP R16H carriers also underwent magnetic resonance imaging and hormonal assessments. AIP mutations were also searched in 16 patients with sporadic growth hormone-secreting pituitary adenoma and in 6 unrelated patients in whom pituitary adenoma was excluded. We found an AIP R16H variation in two family members harbouring a pituitary adenoma and in 6 unaffected family members. No AIP mutation was found neither in growth hormone-secreting pituitary adenoma patients, nor in the unrelated patients without pituitary adenoma. We report a FIPA family harbouring an AIP R16H change, supporting the hypothesis that the latter represents a variant of unknown significance.

Association between pain, arthropathy and health-related quality of life in patients suffering from acromegaly. A cross-sectional study.

INTRODUCTION: Despite successful therapy, acromegalic patients have reduced health-related quality of life (HRQoL) compared to healthy controls. Finding predictors of poor HRQoL can be crucial to improving these patients' global health state.  Aim: The primary objective of the study was to find out predictors of HRQoL. Secondary objectives were: (I) to determine correlations with AcroQoL subscales, and (II) to identify predictors for subscales. MATERIALS AND METHODS: In this cross-sectional study conducted in 2019 at the Messina Policlinic Hospital, 45 acromegalic patients were assessed at the Physical and Rehabilitative Medicine Ambulatory. During routine outpatient clinic attendances, the following questionnaires were administered: Acromegaly Quality of Life Questionnaire (AcroQoL), Patient-Assessed Acromegaly Symptom Questionnaire (PASQ), and Western Ontario and McMaster Universities Arthritis Index (WOMAC). We furthermore included the following variables obtained by medical record review: age, BMI, disease duration, previous surgery (Yes/No), previous radiotherapy (Yes/No), use of GH lowering medications (Yes/No), hypertension (Yes/No), diabetes mellitus (Yes/No), and biochemical control of the disease (Yes/No): immunoradiometric assays were employed to serum GH and IGF-1 measurements to identify biochemical control of the disease. Correlation between outcome measures and AcroQoL has been performed. Pearson's r was calculated for continuous data following normal distribution (AcroQoL, PASQ, AcroQoL-B, AcroQoL-R, WOMAC-P), while Spearman's rank order correlation was calculated for non-normally distributed data (WOMAC, WOMAC-F, WOMAC-S, AcroQoL-P) and point-biserial correlation for binary variables (biochemically controlled disease, use of GH lowering medications, radiotherapy, surgery).  The same correlation analysis was performed for the AcroQoL subscales. Multiple linear regression with backwards, stepwise analysis was used to assess the influence on AcroQoL of correlated variables. RESULTS: AcroQoL was strongly negatively correlated with PASQ (r=-0.700, p<0.001) and negatively correlated with WOMAC [rs (43)=-0.530, p<0.001] and among WOMAC subscales with WOMAC-Physical fitness [rs (43)=-0.518, p<0.001] WOMAC-Pain [r (43)=-0.428, p=0.003], WOMAC-Stiffness [rs (43)=-0.393, p=0.007], and radiotherapy [r (43) =-0.314, p=0.035]. After univariate stepwise regression, PASQ was the strongest independent predictor of AcroQoL, with R2 of 0.392 [F (1,43)=27.695, p<0.001]. CONCLUSIONS: This study shows that the severity of painful symptoms is the most important predictor of HRQoL in patients with acromegaly; at the same time, acromegalic arthropathy leads to pain and to a variable amount of functional impairment, exerting great impact on the patient's perception of his health status. Measure of the progression of arthropathy and symptomatic management could lead to a great HRQoL benefit.

The Influence of Food Regimes on Oxidative Stress: A Permutation-Based Approach Using the NPC Test.

(1) Background: This paper aims to assess the existence of significant differences between two dietary regimes (omnivorous vs. semi-vegetarian) with reference to some oxidative stress markers (SOD, GPx, TRxR, GR, AGEs, and AOPPs) using non-parametric combination methodology based on a permutation test. (2) Methods: At the endocrinology unit of Messina University Hospital, two hundred subjects were asked to fill out a questionnaire about their dietary habits. None were under any pharmacological treatment. Using the NPC test, all comparisons were performed stratifying patients according to gender, age (≤40 or >40 years), BMI (normal weight vs. overweight), physical activity (sedentary vs. active lifestyle), TSH, FT4 levels in quartiles, and diagnosis of Hashimoto's thyroiditis. We evaluated differences in oxidative stress parameters in relation to two examined dietary regimes (omnivorous vs. semi-vegetarian). (3) Results: The antioxidant parameters GPx and TRxR were significantly lower in subjects with an omnivorous diet than in semi-vegetarians, particularly in females, both age groups, subjects with normal weight, those not affected by Hashimoto's thyroiditis, and both the sedentary and active lifestyle groups. Finally, the AGE and AOPP markers were significantly lower in semi-vegetarians. (4) Conclusion: Thanks to the NPC methodology, we can state that dietary patterns exert a significant influence on some oxidative stress parameters.

Autoimmune Thyroid Disorders: The Mediterranean Diet as a Protective Choice.

Autoimmune thyroid diseases are on the rise worldwide, and such a rapid increase is mainly driven by environmental factors related to changed lifestyles in "modern" societies. In this context, diet seems to play a crucial role. An unhealthy high-energy diet, rich in animal fat and proteins, salt and refined sugars (the so-called "Western diet") negatively influences the risk of autoimmunity by altering the immune balance and the gut microbiota composition, enhancing oxidative stress and promoting inflammation. In contrast, the Mediterranean diet represents a unique model of healthy eating, characterized by a high intake of food from vegetable sources, a low consumption of saturated fats in favor of unsaturated fats (mainly, olive oil), a moderate consumption of fish (typically, the small oily fishes) and dairy products, as well as a moderate consumption of wine at meals, and a low intake of meat. Thanks to its nutritional components, the Mediterranean Diet positively influences immune system function, gut microbiota composition, and redox homeostasis, exerting anti-oxidants, anti-inflammatory, and immunomodulatory effects. The present review was aimed at exploring the existing knowledge on the correlations between dietary habits and thyroid autoimmunity, to evaluate the role of the Mediterranean diet as a protective model.

Trabecular bone score, bone marrow fat and vertebral fractures in cushing syndrome.

OBJECTIVE: Prediction of fragility fractures in Cushing syndrome (CS) is a challenge since dual energy X-ray absorptiometry (DXA) measurement of bone mineral density (BMD) does not capture all the alterations in bone microstructure induced by glucocorticoid excess. In this study we investigated the relationship between trabecular bone score (TBS), bone marrow fat (BMF) and vertebral fractures (VFs) in endogenous CS. DESIGN: Cross-sectional. METHODS: Thirty subjects (7 M and 23 F, mean age 44.8 ± 13.4 yrs, range: 25-71) with active hypercortisolism were evaluated for VFs by quantitative morphometry, BMD and TBS by lumbar spine DXA and BMF by single-voxel magnetic resonance spectroscopy of vertebral body of L3. RESULTS: Subjects with VFs (17 cases; 56.7%) had higher BMF (P = 0.014) and lower BMD T-score (P = 0.012) and TBS (P = 0.004) as compared to those without VFs. Prevalence of VFs resulted to be significantly higher in individuals with impaired TBS as compared to those with normal TBS (77.8% vs. 25.0%; P = 0.008). Among patients with VFs, only 6 (35.3%) had either osteoporosis or "low BMD for age". In logistic regression analysis, impaired TBS maintained the significant association with VFs [odds ratio (OR) 6.60, 95% C.I. 1.07-40.61; P = 0.042] independently of BMF (OR 1.03, 95% C.I. 0.99-1.08; P = 0.152). CONCLUSIONS: TBS might be more accurate than BMF in identifying subjects with active CS and skeletal fragility at risk of VFs. SIGNIFICANCE STATEMENT: Excess in glucocorticoids is associated with alterations in bone remodeling and metabolism, leading to fragility fractures regardless of bone mineral density, making more challenging for the clinician the identification of high-risk population and the definition of preventing strategies. In this context, instrumental parameters suggestive of bone quality alterations and predictive of increased fracture risk are needed. In this study, we found CS patients to have bone quality alterations as indicated by the decreased trabecular bone score and increased bone marrow fat, as measured by DEXA and MRI respectively. Both parameters were associated with high risk of VFs, and were inversely correlated, although TBS seems to be more accurate than BMF in fractures prediction in this clinical setting.

Persistent severe visual field impairment is associated with obesity and tumour invasiveness, but not with pituitary dysfunction, in patients with craniopharyngioma.

PURPOSE: Craniopharyngiomas (CP) are benign tumours of the sellar region. Hypopituitarism, visual deficits, hypothalamic damage with consequent obesity and related increased cardiovascular risk, are complications due to the tumour itself or secondary to treatment strategy. We retrospectively correlated visual field status with clinical, neuroradiological, histopathological features and management strategy, in a single-centre cohort of patients with CP. METHODS: Thirty-four patients (16 M; median age 27.2 ± 21.8 yrs) with CP were included. We evaluated visual field status, assessed by means of standard automated perimetry and expressed as mean deviation (MD), at last follow-up visit (median 14 ± 11.7 yrs). MD has been correlated with clinical, radiological, histological data and treatment modalities. RESULTS: In univariate analysis worst eye MD was significantly associated with panhypopituitarism (p 0.010). In multivariable linear regression, panhypopituitarism (p 0.008), CP recurrence (p 0.020) and DI (p 0.004) were found to be the main independent predictors of a worse visual field outcome. When stratifying patients according to the degree of visual field impairment (MD < -12 dB Vs MD > -12 dB), the main independent predictors of worse visual field outcome were older age at diagnosis (p 0.010), CP histological subtype (p 0.004), invasiveness (p 0.04), CP recurrence (p 0.035), DI (p 0.002) and weight at last follow-up (p 0.012). CONCLUSION: In CP patients the long-term ophthalmological impairment is frequent, especially at older age, and strictly related to tumour invasiveness and recurrence, and associated to pituitary disfunction and obesity.

Global incidence and prevalence of differentiated thyroid cancer in childhood: systematic review and meta-analysis.

Objective: Differentiated thyroid cancer (DTC) is rare in childhood and adolescence although it represents the most frequent endocrine malignancy in this population. DTC includes both papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC). Most pediatric DTCs are PTCs, while FTCs are rare. To date, no systematic reviews on the global epidemiology of pediatric and adolescent DTC have been published. This systematic review and meta-analysis aims to estimate the overall incidence and prevalence of DTCs in patients aged 0-19 years. Methods: The systematic research was conducted from January 2000 to December 2021 through MEDLINE via PubMed, Cochrane Library, and Embase databases. Two separate meta-analyses were performed for PTC and FTC. Results: After the selection phase, a total of 15 studies (3,332 screened) met the inclusion criteria and are reported in the present systematic review. Five studies were conducted in Europe, five in North America, two in South America, one in Asia, one reported data for 49 countries and territories across the five continents, and one from both the USA and Africa. Most of the studies (n = 14) reported data obtained from national registries, and only one provided information collected from hospital medical records. Beyond the actual trend over time, our study reported a pooled global incidence rate (IR) of PTC and FTC in the pediatric age of 0.46 (95% CI: 0.33-0.59) and 0.07 (95% CI: 0.02-0.12) per 100,000 person-years, respectively. The highest IRs were recorded among Caucasian girls, and the lowest in black or other races/ethnicities. Conclusion: Our data confirm that DTC in the pediatric population is a rare condition. The pooled IRs of the studies included in this meta-analysis are ~0.5 for PTC, which is the most common histological type when both genders and all age groups are considered. The implementation of a prospective international registry on pediatric DTC, as part of the wider European Registries for Rare Endocrine Conditions, has been recently proposed. In addition to providing relevant information on the clinical behavior of this rare disease, standardization of data collection will be pivotal to fill current gaps and allow an accurate estimation of the real incidence and risk factors of DTC.