•> 50% of patients awaiting lung transplantation (LTx) have fragility fractures (Fx).•After LTx, BMD worsen in absence of bone-active therapy while improves in presence.•BMD changes are similar in ...patients with (CF) and without cystic fibrosis (nCF).•Fx incidence after LTx is higher in nCF patients than in CF ones.•After LTx TBS worsen in nCF patients, while it improves in CF patients.
the effect of bone-active drugs on the risk of fragility fractures (Fx), bone mineral density (BMD) and trabecular bone score (TBS) changes in patients receiving lung transplantation (LTx) is largely unknown. This study assessed the bone-active drugs effect in patients undergoing LTx both with (CF) and without (nCF) cystic-fibrosis.
We evaluated incident Fx, both clinical and morphometric vertebral Fx by spinal X-ray, BMD and trabecular bone score (TBS) in 117 patients (CF=50, nCF n = 67) before and 24-months after LTx. A bone-active therapy was proposed to all LTx candidates.
83.8% of patients started a bone-active drug. Lumbar-spine (LS) T-score improved significantly only in treated patients (-1.4 ± 1.0 vs -2.0±1.0, p = 0.0001), whereas femur BMD and TBS remained stable in treated and not treated subjects. The rate of incident Fx was 15.3%, with no difference between treated and not treated patients. After LTx, LS T-score improved significantly only in nCF group (-1.3 ± 1.0 vs -1.8 ± 1.1, p = 0.0001), while femur remained stable in both nCF and CF groups. Patients with CF showed a significant Z-TBS increase (-3.6 ± 1.7 vs -3.0 ± 1.7, p = 0.019) and a lower Fx incidence as compared with nCF patients (4.1% vs 24.2%, p =0.003). Incident Fx were associated with nCF diagnosis (OR 7.300, CI95% 1.385–38.461, p = 0.019) regardless of prevalent Fx, previous glucocorticoid therapy and bone-active therapy introduced at least 6 months before LTx.
A prompt medical intervention helps in preventing BMD loss after LTx. As compared with nCF patients, CF patients show a TBS increase and a lower Fx risk after LTx.
Sommario
Gli individui transgender sperimentano un’identità di genere incongruente con le caratteristiche proprie del sesso assegnato alla nascita e possono richiedere, pertanto, un trattamento ...ormonale di affermazione di genere. Queste terapie, in considerazione dell’importante ruolo metabolico degli ormoni sessuali, possono potenzialmente influire sulla salute ossea. Attualmente non emergono evidenze suggestive per un rischio aggiuntivo dal punto di vista osseo nei soggetti transgender in trattamento.
Multiple metabolic and inflammatory mechanisms are considered the determinants of acquired functional isolated hypogonadotropic hypogonadism (IHH) in males, whereas classic IHH is a rare congenital ...condition with a strong genetic background. Since we recently uncovered a frequent familiarity for classic IHH among patients with mild adult-onset hypogonadism (AO-IHH), here we performed a genetic characterization by next generation sequencing of 160 males with classic or "functional" forms. The prevalence of rare variants in 28 candidate genes was significantly higher than in controls in all IHH patients, independently of the age of IHH onset, degree of hypogonadism or presence of obesity. In fact, it did not differ among patients with classic or milder forms of IHH, however particular genes appear to be more specifically associated with one or the other category of IHH. ROC curves showed that Total Testosterone <6.05 nmol/L and an age of onset <41 years are sensitive cutoffs to identify patients with significantly higher chances of harboring rare IHH gene variants. In conclusion, rare IHH genes variants can frequently predispose to AO-IHH with acquired mild hormonal deficiencies. The identification of a genetic predisposition can improve the familial and individual management of AO-IHH and explain the heritability of congenital IHH.
Hypercortisolism is known to cause osteoporosis.
To evaluate the prevalence of subclinical hypercortisolism in participants referred for evaluation of osteoporosis.
Cross-sectional study.
Two ...community hospitals and research institutes in Italy.
219 patients without clinically overt hypercortisolism or other secondary causes of osteoporosis who were referred for evaluation of osteoporosis between January 2005 and December 2005.
Bone mineral density was measured by using dual-energy x-ray absorptiometry, and hypercortisolism was assessed with serum cortisol levels after a dexamethasone suppression test. Also measured were 24-hour urinary free cortisol levels and midnight plasma cortisol levels.
Seven of 65 patients with T-scores of 2.5 or less and vertebral fractures had subclinical hypercortisolism (prevalence, 10.8% 95% CI, 3.23% to 18.31%). This prevalence was 4.8% (CI, 1.32% to 8.20%) among patients with osteoporosis. In multivariable analyses adjusted for age, sex, and body mass index, a positive dexamethasone suppression test result was associated with the presence of osteoporosis (odds ratio, 3.37 CI, 1.78 to 6.43; P < 0.001) and vertebral fractures (odds ratio, 1.70 CI, 1.04 to 2.79; P = 0.035).
The study was conducted in a referral setting; its findings may not apply to the general population.
Subclinical hypercortisolism may be more common than is generally recognized in patients with osteoporosis in whom secondary causes of osteoporosis have been excluded.
Patients with adrenal incidentalomas (AI) may experience detrimental consequences due to a minimal cortisol excess sustained by adrenal adenoma. SNPs of the glucocorticoid receptor gene (NR3C1) ...modulate individual sensitivity to glucocorticoids and may interfere with the clinical presentation.
To compare the frequency of N363S, ER22/23EK and BclI SNPs in patients with AI with the general population and to evaluate whether these SNPs are linked to consequences of cortisol excess.
Multicentric, retrospective analysis of patients referred from 2010 to 2014 to 4 centers (Orbassano, Milano, Messina Italy and Zagreb Croatia).
411 patients with AI; 153 males and 258 females and 186 from blood donors.
All patients and controls were genotyped for BclI, N363S and ER22/23EK and SNPs frequency was associated with clinical and hormonal features.
SNP frequency was: SNP frequency was: N363S 5.4% (MAF 0.027), BclI 54.7% (MAF 0.328), ER22/23EK 4.4% (MAF 0.022), without any significant difference between patients and controls. N363S was more frequent in hypertensive patients (p = 0.03) and was associated with hypertension (p = 0.015) in patients with suppressed cortisol after the 1-mg DST.
Our results demonstrate that SNPs of the glucocorticoid receptor gene do not play a pathogenetic role for AI. The impact of any single SNP on the phenotypic expression of minimal cortisol excess is limited and their analysis does not provide additional data that may be exploited for patient management.
OBJECTIVE: To investigate factors associated with bone mineral density (BMD) in type 1 diabetes by classic statistic and artificial neural networks. RESEARCH DESIGN AND METHODS: A total of 175 ...eugonadal type 1 diabetic patients (age 32.8 ± 8.4 years) and 151 age- and BMI-matched control subjects (age 32.6 ± 4.5 years) were studied. In all subjects, BMI and BMD (as Z score) at the lumbar spine (LS-BMD) and femur (F-BMD) were measured. Daily insulin dose (DID), age at diagnosis, presence of complications, creatinine clearance (ClCr), and HbA1c were determined. RESULTS: LS- and F-BMD levels were lower in patients (–0.11 ± 1.2 and –0.32 ± 1.4, respectively) than in control subjects (0.59 ± 1, P < 0.0001, and 0.63 ± 1, P < 0.0001, respectively). LS-BMD was independently associated with BMI and DID, whereas F-BMD was associated with BMI and ClCr. The cutoffs for predicting low BMD were as follows: BMI <23.5 kg/m2, DID >0.67 units/kg, and ClCr <88.8 mL/min. The presence of all of these risk factors had a positive predictive value, and their absence had a negative predictive value for low BMD of 62.9 and 84.2%, respectively. Data were also analyzed using the TWIST system in combination with supervised artificial neural networks and a semantic connectivity map. The TWIST system selected 11 and 12 variables for F-BMD and LS-BMD prediction, which discriminated between high and low BMD with 67 and 66% accuracy, respectively. The connectivity map showed that low BMD at both sites was indirectly connected with HbA1c through chronic diabetes complications. CONCLUSIONS: In type 1 diabetes, low BMD is associated with low BMI and low ClCr and high DID. Chronic complications negatively influence BMD.
Background Cushing’s syndrome (CS) is a rare condition of chronically elevated cortisol levels resulting in diverse comorbidities, many of which endure beyond successful treatment affecting the ...quality of life. Few data are available concerning patients’ experiences of diagnosis, care and persistent comorbidities. Objective To assess CS patients’ perspectives on the diagnostic and care journey to identify unmet therapeutic needs. Methods A 12-item questionnaire was circulated in 2019 by the World Association for Pituitary Organisations. A parallel, 13-item questionnaire assessing physician perceptions on CS patient experiences was performed. Results Three hundred twenty CS patients from 30 countries completed the questionnaire; 54% were aged 35–54 and 88% were female; 41% were in disease remission. The most burdensome symptom was obesity/weight gain (75%). For 49% of patients, time to diagnosis was over 2 years. Following treatment, 88.4% of patients reported ongoing symptoms including, fatigue (66.3%), muscle weakness (48.8%) and obesity/weight gain (41.9%). Comparisons with delay in diagnosis were significant for weight gain (P = 0.008) and decreased libido (P = 0.03). Forty physicians completed the parallel questionnaire which showed that generally, physicians poorly estimated the prevalence of comorbidities, particularly initial and persistent cognitive impairment. Only a minority of persistent comorbidities (occurrence in 1.3–66.3%; specialist treatment in 1.3–29.4%) were managed by specialists other than endocrinologists. 63% of patients were satisfied with treatment. Conclusion This study confirms the delay in diagnosing CS. The high prevalence of persistent comorbidities following remission and differences in perceptions of health between patients and physicians highlight a probable deficiency in effective multidisciplinary management for CS comorbidities.
In recent years, heterozygous loss-of-function mutations of the Calcium Sensing Receptor gene (CaSR) were implicated in different hypercalcemic syndromes besides familial hypocalciuric hypercalcemia ...(FHH), including neonatal severe primary hyperparathyroidism (NSHPT) and primary hyperparathyroidism (PHPT).
Here we describe two unusual presentations of heterozygous inactivating CaSR mutations. Case 1: a case of NSHPT due to a
, p.(ArgR185Gln) CaSR mutation and successfully treated with cinacalcet monotherapy for 8 years until definitive surgical resolution. Case 2: a 37 years-old woman with PHPT complicated with hypercalcemia and nephrocalcinosis with a novel heterozygous p.(Pro393Arg) CaSR mutation and cured with parathyroidectomy.
These cases reinforce the fact that the clinical spectrum of inactivating mutations of the CaSR has widened and, although carrying a mutation suggestive of FHH, some patients may have different clinical phenotypes and complications requiring individualized therapies.
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