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BACKGROUND: Serum inflammation-based scores can predict clinical outcome in several cancer types, including adrenocortical carcinoma (ACC). It is unclear whether the extent of inflammation-based scores alterations in ACC reflects malignancy, steroid excess, or both. METHODS: We investigated a large retrospective cohort of adrenocortical adenomas (ACA, n = 429) and ACC (n = 61) with available baseline full blood count and hormonal evaluation. We examined the relationship between different inflammation-based scores [neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), and prognostic nutrition index (PNI)] and both malignancy and steroid secretion patterns. RESULTS: All inflammation-based scores differed between ACC and ACA: patients with ACC had higher NLR, PLR, SII and lower LMR and PNI levels compared to ACA (all p values < 0.001). NLR showed a positive correlation with cortisol levels after overnight 1 mg-dexamethasone suppression test (1 mg-DST), both in ACC and ACA (p < 0.01). The ROC curve analysis determined NLR > 2.6 as the best cut-off to discriminate ACC from ACA [AUC = 0.846, p < 0.01]. At multivariable analysis, NLR > 2.6 was independently associated with ACC, 1 mg-DST cortisol levels and age, but not with tumour size. Considering the ACC, NLR and SII were higher and PNI was lower in patients with cortisol excess compared to those without cortisol excess (p = 0.002, p = 0.007, and p = 0.044 respectively). Finally, LMR and NLR differed between inactive-ACC (n = 10) and inactive-ACA (n = 215) (p = 0.040 and p = 0.031, respectively). CONCLUSION: Inflammation-based scores are related to steroid secretion both in ACC and ACA. ACCs present a higher grade of inflammation regardless of their hormonal secretion, likely as a feature of malignancy itself.
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INTRODUCTION: Paget's disease of bone is a focal skeletal disorder causing bone deformities and impairing bone quality. Despite the prevalence of asymptomatic cases is increasing, the progression of the disease can lead to invalidating complications that compromise the quality of life. Doubts on clinical and therapeutic management aspects exist, although beneficial effects of antiresorptive drugs, particularly bisphosphonates are known. However, limited information is available from randomized controlled trials on the prevention of disease complications so that somewhat contrasting positions about treatment indications between expert panels from the main scientific societies of metabolic bone diseases exist. This task force, composed by expert representatives appointed by the Italian Society of Osteoporosis, Mineral Metabolism and Skeletal Diseases and members of the Italian Association of Paget's disease of bone, felt the necessity for more specific and up to date indications for an early diagnosis and clinical management. METHODS: Through selected key questions, we propose evidence-based recommendations for the diagnosis and treatment of the disease. In the lack of good evidence to support clear recommendations, available information from the literature together with expert opinion of the panel was used to provide suggestions for the clinical practice. RESULTS AND CONCLUSION: Description of the evidence quality and support of the strength of the statements was provided on each of the selected key questions. The diagnosis of PDB should be mainly based on symptoms and the typical biochemical and radiological features. While treatment is mandatory to all the symptomatic cases at diagnosis, less evidence is available on treatment indications in asymptomatic as well as in previously treated patients in the presence of biochemical recurrence. However, given the safety and long-term efficacy of potent intravenous bisphosphonates such as zoledronate, a suggestion to treat most if not all cases at the time of diagnosis was released.
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Osteíte Deformante , Humanos , Osteíte Deformante/diagnóstico , Osteíte Deformante/terapia , Osteíte Deformante/epidemiologia , Osteíte Deformante/tratamento farmacológico , Itália/epidemiologia , Conservadores da Densidade Óssea/uso terapêutico , Sociedades Médicas/normas , Difosfonatos/uso terapêuticoRESUMO
PURPOSE: ACTH-secreting pheochromocytoma is a rare cause of ectopic Cushing's syndrome, posing a clinical challenge for the severity of its clinical presentation, the difficulty in the prevention and the management of surgical complications. Sparse data are currently available about the optimal preoperative management of the severe symptoms due to both hypercortisolism and catecholamine excess, especially regarding the role and timing of medical therapies. METHODS: We present a series of three patients with ACTH-secreting pheochromocytoma. A brief review of the available literature evidence on the preoperative management of this rare clinical condition is also conducted. DISCUSSION: Patients with ACTH-secreting pheochromocytoma show peculiarities as compared to other forms of ACTH-dependent Cushing's syndrome, in terms of clinical presentation, preoperative management, and peri- and post-surgical short-term outcome. Pheochromocytoma should be ruled out in patient with ectopic CS of unknown origin because of the high anesthesiologic risk of proceeding to surgery with an undiagnosed pheochromocytoma. Proper preoperative recognition of complications of both hypercortisolism and catecholamines excess is the key to prevent the morbidity and mortality of an ACTH-producing pheochromocytoma. In these patients the absolute priority is to control excessive cortisol secretion since the rapid correction of the hypercortisolism is the most effective treatment of all the related comorbidities and it is mandatory to prevent severe complications during surgery, opting if necessary for a "block-and-replace" regimen. CONCLUSION: Our additional cases and this literature review could provide a better understanding of the complications to be evaluated at diagnosis and some suggestions on their management during the preoperative period.
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Neoplasias das Glândulas Suprarrenais , Síndrome de Cushing , Feocromocitoma , Humanos , Síndrome de Cushing/diagnóstico , Síndrome de Cushing/etiologia , Síndrome de Cushing/cirurgia , Feocromocitoma/complicações , Feocromocitoma/diagnóstico , Feocromocitoma/cirurgia , Neoplasias das Glândulas Suprarrenais/complicações , Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/cirurgia , Catecolaminas , Hormônio AdrenocorticotrópicoRESUMO
CONTEXT: Acromegalic patients have an increased vertebral fracture (VFx) risk due to bone quality reduction, independently of bone mineral density (BMD). OBJECTIVE: The aim of the study is to describe bone quality in acromegaly, measured by trabecular bone score (TBS), a noninvasive index for assessing bone microarchitecture. METHODS: We collected data from 18 patients (13 female, age 56.2â ±â 15 years) newly diagnosed with acromegaly. Thirty-six age- and sex-matched healthy controls were also recruited. Pituitary function, bone and calcium-phosphorous metabolism, and BMD at spine and femur and TBS (by dual-energy x-ray absorptiometry) were assessed in acromegalic patients at diagnosis and 12 months after the achievement of insulin-like growth factor 1 (IGF-1) normalization. RESULTS: At diagnosis, BMD and the VFx prevalence were comparable between patients and controls (28.3â ±â 5.9 vs 27.6â ±â 3.7 and 11% vs 8.3%), whereas TBS was significantly lower in acromegalic patients (1.20â ±â 0.13 vs 1.30â ±â 0.06; Pâ <â .001) and carboxyterminal telopeptide (CTX) and osteocalcin were significantly higher compared to controls (707â ±â 365.7 vs 371â ±â 104.1 pg/mL; Pâ =â .001 and 31.6â ±â 15.4 vs 17.0â ±â 5.7 ng/mL; Pâ =â .001, respectively). One year after IGF-1 normalization, a significant reduction of bone turnover indexes was observed in the group of acromegalic patients surgically cured (osteocalcin decrease of 61.2%, CTX decrease of 60.3%) compared to the ones controlled by medical therapy (osteocalcin decrease of 39%, CTX decrease of 40.7%; Pâ =â .01 and Pâ =â .001, respectively). Despite these findings, no TBS or BMD variations were observed. CONCLUSION: Acromegalic patients have impaired bone quality despite normal density. Achieving normal growth hormone secretion rapidly leads to the normalization of bone turnover.
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BACKGROUND: Autoimmune Polyglandular Syndrome type 1 (APS-1) is a rare recessive inherited disease, caused by AutoImmune Regulator (AIRE) gene mutations and characterized by three major manifestations: chronic mucocutaneous candidiasis (CMC), chronic hypoparathyroidism (CH) and Addison's disease (AD). METHODS: Autoimmune conditions and associated autoantibodies (Abs) were analyzed in 158 Italian patients (103 females and 55 males; F/M 1.9/1) at the onset and during a follow-up of 23.7 ± 15.1 years. AIRE mutations were determined. RESULTS: The prevalence of APS-1 was 2.6 cases/million (range 0.5-17 in different regions). At the onset 93% of patients presented with one or more components of the classical triad and 7% with other components. At the end of follow-up, 86.1% had CH, 77.2% AD, 74.7% CMC, 49.5% premature menopause, 29.7% autoimmune intestinal dysfunction, 27.8% autoimmune thyroid diseases, 25.9% autoimmune gastritis/pernicious anemia, 25.3% ectodermal dystrophy, 24% alopecia, 21.5% autoimmune hepatitis, 17% vitiligo, 13.3% cholelithiasis, 5.7% connective diseases, 4.4% asplenia, 2.5% celiac disease and 13.9% cancer. Overall, 991 diseases (6.3 diseases/patient) were found. Interferon-ω Abs (IFNωAbs) were positive in 91.1% of patients. Overall mortality was 14.6%. The AIRE mutation R139X was found in 21.3% of tested alleles, R257X in 11.8%, W78R in 11.4%, C322fsX372 in 8.8%, T16M in 6.2%, R203X in 4%, and A21V in 2.9%. Less frequent mutations were present in 12.9%, very rare in 9.6% while no mutations in 11% of the cases. CONCLUSIONS: In Italy, APS-1 is a rare disorder presenting with the three major manifestations and associated with different AIRE gene mutations. IFNωAbs are markers of APS-1 and other organ-specific autoantibodies are markers of clinical, subclinical or potential autoimmune conditions.
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Doença de Addison , Candidíase Mucocutânea Crônica , Hipoparatireoidismo , Interferon Tipo I/imunologia , Poliendocrinopatias Autoimunes , Fatores de Transcrição/genética , Doença de Addison/diagnóstico , Doença de Addison/etiologia , Adulto , Autoanticorpos/sangue , Candidíase Mucocutânea Crônica/diagnóstico , Candidíase Mucocutânea Crônica/etiologia , Feminino , Humanos , Hipoparatireoidismo/diagnóstico , Hipoparatireoidismo/etiologia , Itália/epidemiologia , Masculino , Mortalidade , Mutação , Poliendocrinopatias Autoimunes/diagnóstico , Poliendocrinopatias Autoimunes/genética , Poliendocrinopatias Autoimunes/mortalidade , Poliendocrinopatias Autoimunes/fisiopatologia , Prevalência , Proteína AIRERESUMO
PURPOSE: To evaluate the prevalence of less severe hypercortisolism (LSH) in fractured patients, and its association with hypertension, hyperglicemia, dyslipidemia, and obesity. METHOD: From July 2015 to October 2018 we enrolled all fractured patients admitted in our outpatient center for metabolic bone diseases, after exclusion of patients with secondary osteoporosis apart from diabetes and taking drugs known to affect bone metabolism. In all enrolled patients we collected data regarding gonadal status, history of diabetes, high blood pressure, dyslipidemia, and measured blood pressure, lipid profile, fasting glycaemia. Bone mass was measured with DXA at lumbar spine and femoral neck and the presence of fractures was evaluated with X-ray of thoracic and lumbar spine. All patients performed twice, 1 mg overnight dexametasone suppression test (DST) and, as confirmatory, 2day low-dose DST for diagnosing hypercortisolism. RESULTS: We enrolled 101 fractured patients (75 females, 26 males), aged 65 ± 10.3 years. Five out of 101 (5.0%) patients were diagnosed as LSH. Fifty-five (54.5%) out of 101 were hypertensive, 57 (56.4%) dyslipidemic, 17 (16.8%) hyperglicaemic, 28(27.7%) obese patients. LSH tended to be associated to blood hypertension [5/5 vs 50/96 (Fisher exact test, p = 0.06) hypertensive patients]. Four out five LSH patients were hypogonadic. CONCLUSIONS: Our study confirms that a nonnegligible percentage of fractured subjects actually presents an unrecognized hypercortisolism. Accordingly, regardless of age, we suggest to screen for hypercortisolism all patients with established osteoporosis and in particular hypertensive subjects.
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Síndrome de Cushing , Fraturas Ósseas , Osteoporose , Absorciometria de Fóton , Instituições de Assistência Ambulatorial , Densidade Óssea , Síndrome de Cushing/complicações , Síndrome de Cushing/epidemiologia , Feminino , Fraturas Ósseas/epidemiologia , Fraturas Ósseas/etiologia , Humanos , Masculino , Osteoporose/epidemiologia , Osteoporose/etiologia , PrevalênciaRESUMO
PURPOSE: Classic Cushing's syndrome (CS) is a severe disease characterized by central obesity, hypertension, easy bruising, striae rubrae, buffalo hump, proximal myopathy and hypertricosis. However, several CS cases have also been reported with unusual or camouflaged manifestations. In recent years, several authors investigated the prevalence of "hidden hypercortisolism" (HidHyCo) among subjects affected with bone fragility, hypertension and type 2 diabetes mellitus (DM2). The prevalence of the HidHyCo is estimated to be much higher than that of classic CS. However, similarly to classic CS, HidHyCo is known to increase the risk of fractures, cardiovascular disease and mortality. METHODS: We reviewed all published cases of unusual presentations of hypercortisolism and studies specifically assessing the HidHyCo prevalence in diabetic, osteoporotic and hypertensive patients. RESULTS: We found 49 HidHyCo cases, in whom bone fragility, hypertension and diabetes were the presenting manifestations of an otherwise silent hypercortisolism. Amongst these cases, 34.7%, 32.7%, 6.1% and 19.0%, respectively, had bone fragility, hypertension, DM2 or hypertension plus DM2 as the sole clinical manifestations of HidHyCo. Overall, 25% of HidHyCo cases were of pituitary origin, and bone fragility was the very prevalent first manifestation among them. In population studies, it is possible to estimate that 1-4% of patients with apparent primary osteoporosis has a HidHyCo and the prevalence of this condition among diabetics ranges between 3.4 and 10%. CONCLUSION: These data indicate that patients with resistant or suddenly worsening hypertension or DM2 or unexplainable bone fragility should be screened for HidHyCo using the most recently approved sensitive cut-offs.
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Síndrome de Cushing , Diabetes Mellitus Tipo 2/diagnóstico , Hipertensão/diagnóstico , Osteoporose/diagnóstico , Síndrome de Cushing/sangue , Síndrome de Cushing/diagnóstico , Síndrome de Cushing/fisiopatologia , Diabetes Mellitus Tipo 2/etiologia , Erros de Diagnóstico/prevenção & controle , Humanos , Hidrocortisona/metabolismo , Hipertensão/etiologia , Osteoporose/etiologia , Hipófise/fisiopatologiaRESUMO
Individuals with type 2 diabetes mellitus (T2DM) have an increased risk of bone fragility fractures compared to nondiabetic subjects. This increased fracture risk may occur despite normal or even increased values of bone mineral density (BMD), and poor bone quality is suggested to contribute to skeletal fragility in this population. These concepts explain why the only evaluation of BMD could not be considered an adequate tool for evaluating the risk of fracture in the individual T2DM patient. Unfortunately, nowadays, the bone quality could not be reliably evaluated in the routine clinical practice. On the other hand, getting further insight on the pathogenesis of T2DM-related bone fragility could consent to ameliorate both the detection of the patients at risk for fracture and their appropriate treatment. The pathophysiological mechanisms underlying the increased risk of fragility fractures in a T2DM population are complex. Indeed, in T2DM, bone health is negatively affected by several factors, such as inflammatory cytokines, muscle-derived hormones, incretins, hydrogen sulfide (H2S) production and cortisol secretion, peripheral activation, and sensitivity. All these factors may alter bone formation and resorption, collagen formation, and bone marrow adiposity, ultimately leading to reduced bone strength. Additional factors such as hypoglycemia and the consequent increased propensity for falls and the direct effects on bone and mineral metabolism of certain antidiabetic medications may contribute to the increased fracture risk in this population. The purpose of this review is to summarize the literature evidence that faces the pathophysiological mechanisms underlying bone fragility in T2DM patients.
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Doenças Ósseas Metabólicas/etiologia , Doenças Ósseas Metabólicas/terapia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/terapia , Densidade Óssea , Remodelação Óssea/efeitos dos fármacos , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Complicações do Diabetes/etiologia , Complicações do Diabetes/terapia , Diabetes Mellitus Tipo 2/metabolismo , Fraturas Ósseas/etiologia , Fraturas Ósseas/terapia , Humanos , Hipoglicemiantes/uso terapêuticoRESUMO
PURPOSE: The current cut-offs for the diagnosis of adrenal insufficiency (AI) have been established using outdated immunoassays. We compared the cortisol concentrations measured with Roche Cortisol I (R1), the newly available Roche Cortisol II (R2), and liquid chromatography tandem mass spectrometry (LC-MS/MS), the gold standard procedure to measure steroids in patients undergoing the corticotropin (ACTH) test. METHODS: We enrolled 30 patients (age 47 ± 21 years) referred to undergo the ACTH test (1 or 250 µg). Cortisol was measured at 0, 30, and 60 min after stimulation with R1, R2, and LC-MS/MS. AI was diagnosed for R1-stimulated peak cortisol concentrations < 500 nmol/L. RESULTS: Mean cortisol concentrations measured with R2 and LC-MS/MS were comparable, while mean cortisol concentrations measured by R1 were higher than those of both R2 and LC-MS/MS (respectively, basal 411 ± 177, 287 ± 119, and 295 ± 119 nmol/L; at 30 min, 704 ± 204, 480 ± 132, and 500 ± 132 nmol/L; at 60 min, 737 ± 301, 502 ± 196, and 519 ± 201 nmol/L, p ≤ 0.01 for R1 vs. both R2 and LC-MS/MS at each point). Considering the 500 nmol/L cortisol peak cut-off, AI was diagnosed in 5/30 patients using R1 and in 12/30 using R2 (+ 140%). Based on the correlation between R1 and R2, the threshold of 500 nmol/L became 351 nmol/L (12.7 µg/dL) when cortisol was measured with R2, and 368 nmol/L (13.3 µg/dL) with LC-MS/MS. CONCLUSIONS: The use of more specific cortisol assays results in lower cortisol concentrations. This could lead to misdiagnosis and overtreatment when assessing AI with the ACTH test if a different cut-off for cortisol peak is not adopted.
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Insuficiência Adrenal/sangue , Insuficiência Adrenal/diagnóstico , Hormônio Adrenocorticotrópico , Cromatografia Líquida/normas , Hidrocortisona/análise , Imunoensaio/normas , Espectrometria de Massas em Tandem/normas , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: X-linked hypophosphatemic rickets (XLH) is the first cause of inherited hypophosphatemia and is caused by mutation in the PHEX gene, resulting in excessive expression of the phosphaturic factor FGF23. Symptoms are mainly related to rickets in children and osteomalacia in adults and cause several complications that can be highly invalidating. Due to its rarity, XLH is poorly known and diagnosis is frequently delayed. Conventional treatment is based on oral phosphate salts supplementation and activated vitamin D analogs, which however, cannot cure the disease in most cases. OBJECTIVE: Due to the low prevalence of XLH, an experts' opinion survey was conducted across Italian centers to collect data on XLH and on its management. METHODS: A questionnaire was developed by a group of experts to collect data on XLH epidemiology, diagnosis and treatment in Italy. RESULTS: Data from 10 Italian centers (nine of which pediatric) on 175 patients, followed between 1998 and 2017, were included in the survey. Most patients were followed since childhood and 63 children became adults during the investigated period. The diagnosis was made before the age of 1 and between 1 and 5 years in 11 and 50% of cases, respectively. Clinically apparent bone deformities were present in 95% of patients. These were ranked moderate/severe in 75% of subjects and caused growth stunting in 67% of patients. Other frequent complications included bone pain (40%), dental abscesses (33%), and dental malpositions (53%). Treatment protocols varied substantially among centers. Nephrocalcinosis was observed in 34% of patients. Tertiary hyperparathyroidism developed in 6% of patients. CONCLUSIONS: XLH remains a severe condition with significant morbidities.
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Raquitismo Hipofosfatêmico Familiar/genética , Doenças Genéticas Ligadas ao Cromossomo X , Padrões de Prática Médica/estatística & dados numéricos , Adolescente , Adulto , Criança , Pré-Escolar , Raquitismo Hipofosfatêmico Familiar/diagnóstico , Raquitismo Hipofosfatêmico Familiar/epidemiologia , Raquitismo Hipofosfatêmico Familiar/terapia , Feminino , Fator de Crescimento de Fibroblastos 23 , Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico , Doenças Genéticas Ligadas ao Cromossomo X/epidemiologia , Doenças Genéticas Ligadas ao Cromossomo X/terapia , Humanos , Lactente , Recém-Nascido , Itália/epidemiologia , Masculino , Inquéritos e QuestionáriosRESUMO
INTRODUCTION: Osteoporosis is a skeletal disorder characterized by loss of bone mass and strength affecting up to 30-50% of postmenopausal women worldwide. Current therapeutic options include antiresorptives such as aminobisphosphonates or denosumab and osteoanabolic compounds such as teriparatide. Areas covered: In this review, the authors summarize the clinical development, safety and efficacy profile of abaloparatide, a new osteoanabolic agent recently marketed in the US for the treatment of postmenopausal osteoporosis in women who are at high risk for fracture or who fail antiresorptive therapy. Expert opinion: Abaloparatide is a 1-34 PTH related peptide-like molecule that has been modified in order to potentiate the osteoanabolic effect. In its pivotal phase 3 trial in postmenopausal women with osteoporosis, subcutaneous abaloparatide 80 mcg/day reduced the risk of vertebral, nonvertebral, major osteoporotic, and clinical fractures compared with placebo and reduced the risk of major osteoporotic fractures compared with teriparatide. These results, together with a reduced prevalence of hypercalcemia and a lower cost of the marketed compound, point toward improved cost effectiveness with abaloparatide versus teriparatide. However, some concerns have been raised due to a somewhat higher occurrence of adverse effects (particularly with palpitations and increased heart rate) or the resultant discontinuation due to these adverse effects when compared to teriparatide.
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Conservadores da Densidade Óssea/uso terapêutico , Osteoporose Pós-Menopausa/tratamento farmacológico , Proteína Relacionada ao Hormônio Paratireóideo/uso terapêutico , Conservadores da Densidade Óssea/química , Conservadores da Densidade Óssea/farmacologia , Feminino , Meia-Vida , Humanos , Hipercalcemia/etiologia , Fraturas por Osteoporose/prevenção & controle , Proteína Relacionada ao Hormônio Paratireóideo/efeitos adversos , Proteína Relacionada ao Hormônio Paratireóideo/química , Proteína Relacionada ao Hormônio Paratireóideo/farmacocinética , Resultado do TratamentoRESUMO
Patients with cystic fibrosis awaiting lung transplantation for end-stage respiratory failure have high prevalence of reduced bone mineral density and fragility fracture. Suboptimal 25-hydroxyvitamin D levels could significantly contribute to the development of cystic fibrosis-related bone disease. INTRODUCTION: The assessment of the prevalence of cystic fibrosis-related bone disease (CFBD) and its associated risk factors in young adults with cystic fibrosis (CF) awaiting lung transplantation for end-stage respiratory failure. METHODS: Clinical characteristics, bone mineral density (BMD), the parameters of calcium metabolism, including vitamin D (25OHVitD) levels, and the presence of fragility fractures were evaluated in 42 CF patients (24 females, age 34.0 ± 8.4 years) consecutively referred as lung transplant candidates. RESULTS: Mean 25OHVitD levels (54.9 ± 26.2 nmol/L) were below the reference range and hypovitaminosis D (25OHVitD < 75 nmol/L) was found in 34 patients (81%) and daily calcium intakes (median 550 mg/day) were lower than recommended. A BMD below the expected range for age (Z-score of - 2.0 or lower) and at least one prevalent fragility fracture were found in 22 patients (52.4%) and 18 patients (45.2%), respectively. The coexistence of low BMD and the presence of fracture was observed in 13 patients (31.0%). In these patients, the prevalence of nephrolithiasis was higher than in the remaining ones (p = 0.046). The presence of kidney stones was associated with a worse bone status and with severe vitamin D deficiency. In the whole sample, femoral BMD Z-scores were directly correlated with albumin-adjusted calcium (p < 0.05) and 25OHVitD levels (p < 0.01). CONCLUSIONS: Despite the improvement of CF care, CFBD is still highly prevalent in young adults awaiting lung transplantation for end-stage CF. Suboptimal 25OHVitD levels could significantly contribute to the development of CFBD. The presence of nephrolithiasis could be an additional warning about the need for a careful evaluation of bone health in CF patients.
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Fibrose Cística/complicações , Transplante de Pulmão , Osteoporose/etiologia , Insuficiência Respiratória/etiologia , Adulto , Densidade Óssea/fisiologia , Estudos Transversais , Fibrose Cística/sangue , Fibrose Cística/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nefrolitíase/etiologia , Osteoporose/sangue , Osteoporose/fisiopatologia , Fraturas por Osteoporose/sangue , Fraturas por Osteoporose/etiologia , Fraturas por Osteoporose/fisiopatologia , Insuficiência Respiratória/sangue , Insuficiência Respiratória/fisiopatologia , Insuficiência Respiratória/cirurgia , Vitamina D/análogos & derivados , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/etiologia , Deficiência de Vitamina D/fisiopatologia , Adulto JovemRESUMO
CONTEXT: The previous studies suggested a possible increased risk of hypercalcaemia and reduced bone mineral density (BMD) in Williams' syndrome (WS). However, an extensive study regarding bone metabolism has never been performed. OBJECTIVE: To investigate bone health in young adults with WS. DESIGN: Cross-sectional study. SETTINGS: Endocrinology and Metabolic Diseases and Medical Genetic Units. PATIENTS: 29 WS young adults and 29 age- and sex-matched controls. MAIN OUTCOME MEASURES: In all subjects, calcium, phosphorus, bone alkaline phosphatase (bALP), parathyroid hormone (PTH), 25-hydroxyvitamin D (25OHVitD), osteocalcin (OC), carboxyterminal cross-linking telopeptide of type I collagen (CTX), 24-h urinary calcium and phosphorus, femoral-neck (FN) and lumbar-spine (LS) BMD and vertebral fractures (VFx) were assessed. In 19 patients, serum fibroblast growth factor-23 (FGF23) levels were measured. RESULTS: WS patients showed lower phosphorus (3.1 ± 0.7 vs 3.8 ± 0.5 mg/dL, p = 0.0001) and TmP/GFR (0.81 ± 0.32 vs 1.06 ± 0.25 mmol/L, p = 0.001), and an increased prevalence (p = 0.005) of hypophosphoremia (34.5 vs 3.4%) and reduced TmP/GFR (37.9 vs 3.4%). Moreover, bALP (26.3 ± 8.5 vs 35.0 ± 8.0 U/L), PTH (24.5 ± 12.6 vs 33.7 ± 10.8 pg/mL), OC (19.4 ± 5.3 vs 24.5 ± 8.7 ng/mL), and FN-BMD (- 0.51 ± 0.32 vs 0.36 ± 0.32) were significantly lower (p < 0.05), while CTX significantly higher (401.2 ± 169.3 vs 322.3 ± 122.4 pg/mL, p < 0.05). Serum and urinary calcium and 25OHVitD levels, LS-BMD and VFx prevalence were comparable. No cases of hypercalcemia and suppressed FGF23 were documented. Patients with low vs normal phosphorus and low vs normal TmP/GFR showed comparable FGF23 levels. FGF23 did not correlate with phosphorus and TmP/GFR values. CONCLUSIONS: Adult WS patients have reduced TmP/GFR, inappropriately normal FGF23 levels and an uncoupled bone turnover with low femoral BMD.
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Densidade Óssea , Doenças Ósseas Metabólicas/etiologia , Remodelação Óssea , Hipofosfatemia/etiologia , Síndrome de Williams/complicações , Síndrome de Williams/metabolismo , Adulto , Biomarcadores/análise , Doenças Ósseas Metabólicas/metabolismo , Doenças Ósseas Metabólicas/patologia , Estudos de Casos e Controles , Estudos Transversais , Feminino , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/metabolismo , Seguimentos , Humanos , Hipofosfatemia/metabolismo , Hipofosfatemia/patologia , Masculino , Hormônio Paratireóideo/metabolismo , Prognóstico , Síndrome de Williams/patologia , Adulto JovemRESUMO
An 81-year-old woman was hospitalised for behavioural disorders that had been progressively emerging over a period of few weeks. The symptoms appeared to worsen over time. A diagnosis of vascular dementia, complicated by psychosis, was initially hypothesised. The inefficacy of the antipsychotic/benzodiazepine medications used, along with the presence of hypertension, hypokalaemia and metabolic alkalosis (resistant to pharmacological attempts of correction), as well as the hirsutism and the development of several infections, led us to consider Cushing's syndrome. Endocrinological analysis suggested ectopic adrenocorticotropic hormone (ACTH) secretion. Although endogenous Cushing's syndrome is rare in older people, it should always be considered among the differential diagnosis of behavioural disorders.
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Síndrome de Cushing/complicações , Transtornos Mentais/etiologia , Idoso de 80 Anos ou mais , Antipsicóticos/uso terapêutico , Síndrome de Cushing/diagnóstico , Síndrome de Cushing/tratamento farmacológico , Diagnóstico Diferencial , Inibidores Enzimáticos/uso terapêutico , Evolução Fatal , Feminino , Humanos , Transtornos Mentais/diagnóstico , Transtornos Mentais/tratamento farmacológico , Transtornos Mentais/psicologia , Metirapona/uso terapêutico , Valor Preditivo dos Testes , Fumarato de Quetiapina/uso terapêutico , Fatores de Risco , Resultado do TratamentoRESUMO
PURPOSE: Evaluation of the phenotype of primary hyperparathyroidism (PHPT), adherence to International Guidelines for parathyroidectomy (PTx), and rate of surgical cure. METHOD: From January 2014-January 2016, we performed a prospective, multicenter study in patients with newly diagnosed PHPT. Biochemical and instrumental data were collected at baseline and during 1-year follow-up. RESULTS: Over the first year we enrolled 604 patients (age 61 ± 14 years), mostly women (83%), referred for further evaluation and treatment advice. Five hundred sixty-six patients had sporadic PHPT (93.7%, age 63 ± 13 years), the remaining 38 (6.3%, age 41 ± 17 years) had familial PHPT. The majority of patients (59%) were asymptomatic. Surgery was advised in 281 (46.5%). Follow-up data were available in 345 patients. Eighty-seven of 158 (55.1%) symptomatic patients underwent PTx. Sixty-five (53.7%) of 121 asymptomatic patients with at least one criterion for surgery underwent PTx and 56 (46.3%) were followed without surgery. Negative parathyroid imaging studies predicted a conservative approach [symptomatic PHPT: OR 18.0 (95% CI 4.2-81.0) P < 0.001; asymptomatic PHPT: OR 10.8, (95% CI 3.1-37.15) P < 0.001). PTx was also performed in 16 of 66 (25.7%) asymptomatic patients without surgical criteria. Young age, serum calcium concentration, 24 h urinary calcium, positive parathyroid imaging (either ultrasound or MIBI scan positive in 75% vs. 16.7%, P = 0.001) were predictors of parathyroid surgery. Almost all (94%) of patients were cured by PTx. CONCLUSIONS: Italian endocrinologists do not follow guidelines for the management of PHPT. Negative parathyroid imaging studies are strong predictors of a non-surgical approach. PTx is successful in almost all patients.
Assuntos
Cálcio/sangue , Hiperparatireoidismo Primário/diagnóstico , Glândulas Paratireoides/diagnóstico por imagem , Hormônio Paratireóideo/sangue , Idoso , Feminino , Seguimentos , Humanos , Hiperparatireoidismo Primário/sangue , Hiperparatireoidismo Primário/cirurgia , Itália , Masculino , Pessoa de Meia-Idade , Glândulas Paratireoides/cirurgia , Paratireoidectomia , Estudos Prospectivos , UltrassonografiaRESUMO
Vitamin D deficiency is very common and prescriptions of both assay and supplementation are increasing more and more. Health expenditure is exponentially increasing, thus it is timely and appropriate to establish rules. The Italian Association of Clinical Endocrinologists appointed a task force to review literature about vitamin D deficiency in adults. Four topics were identified as worthy for the practicing clinicians. For each topic recommendations based on scientific evidence and clinical practice were issued according to the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) System. (1) What cut-off defines vitamin D deficiency: even though 20 ng/mL (50 nmol/L) can be considered appropriate in the general population, we recommend to maintain levels above 30 ng/mL (75 nmol/L) in categories at risk. (2) Whom, when, and how to perform screening for vitamin D deficiency: categories at risk (patients with bone, liver, kidney diseases, obesity, malabsorption, during pregnancy and lactation, some elderly) but not healthy people should be screened by the 25-hydroxy-vitamin D assay. (3) Whom and how to treat vitamin D deficiency: beyond healthy lifestyle (mostly sun exposure), we recommend oral vitamin D (vitamin D2 or vitamin D3) supplementation in patients treated with bone active drugs and in those with demonstrated deficiency. Dosages, molecules and modalities of administration can be profitably individually tailored. (4) How to monitor the efficacy of treatment with vitamin D: no routine monitoring is suggested during vitamin D treatment due to its large therapeutic index. In particular conditions, 25-hydroxy-vitamin D can be assayed after at least a 6-month treatment. We are confident that this document will help practicing clinicians in their daily clinical practice.
Assuntos
Humanos , Adulto , Idoso , Vitamina D/administração & dosagem , Deficiência de Vitamina D/tratamento farmacológico , Vitaminas/administração & dosagem , 25-Hidroxivitamina D 2/administração & dosagem , Calcifediol/administração & dosagem , Colecalciferol/administração & dosagem , Abordagem GRADERESUMO
PURPOSE: To compare the response to denosumab (DMAb) therapy with that of oral bisphosphonate (BISPH) treatment in postmenopausal women with primary osteoporosis (PO). METHODS: In this retrospective study, we compared data of 75 PO female patients treated for 24 months with DMab (DMAb Group, age 72.6 ± 8.9 years) with those of 75 PO patients treated with oral bisphosphonates (BISPH Group), matched for age, body mass index, femoral bone mineral density (BMD), prevalent fragility fractures and familiar history of hip fracture. In all subjects at baseline and after 24 months we assessed the calcium-phosphorous metabolism parameters, BMD at lumbar spine (LS-BMD) and femoral neck (FN-BMD) by dual X-ray absorptiometry and the morphometric vertebral fractures by radiograph. The patients were considered inadequate responders in the presence of ≥ 2 incident fragility fractures and/or a decrease in BMD greater than the least significant change (LS 2.8%, FN 5.9%). RESULTS: After 24 months, the DMab Group showed a greater ALP decrease (- 22.8 ± 18.2%), a higher LS-BMD and FN-BMD increase (6.6 ± 6.9 and 4.4 ± 8.2%, respectively) and a lower number of patients with an incident fracture (8%) and with an inadequate response (6.7%) than BISPH Group (- 14.9 ± 15.3, 2.5 ± 4.3, 1.9 ± 4.5, 21.3 and 22.7%, respectively, p < 0.05 for all comparisons). The inadequate response was 4.5-fold more likely in BISPH Group than in DMab one (p = 0.027), regardless of possible confounders. CONCLUSIONS: In postmenopausal PO females, denosumab was more effective than oral bisphosphonates in increasing BMD and reducing bone turnover and the number of inadequate responder patients.
Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Denosumab/uso terapêutico , Difosfonatos/uso terapêutico , Osteoporose Pós-Menopausa/tratamento farmacológico , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos RetrospectivosRESUMO
Several studies suggested that the condition of primary hyperparathyroidism (PHPT) may be associated not only with the classical bone, kidney and gastrointestinal consequences, but also with cardiovascular, neuromuscular and articular complications, impaired quality of life and increased cancer risk. However, the only cardiovascular complications associated with PHPT, which seems to improve after parathyroidectomy, is left ventricular hypertrophy, while, data regarding the reversibility of hypertension, valve calcifications and increased vascular stiffness are inconsistent. Parathyroidectomy seems to ameliorate neuropsychological, cognitive disturbances and quality of life in moderate-severe PHPT, while data in mild PHPT are less clear. At variance, the effect of parathyroidectomy on neuromuscular and articular complications is still unknown, and no studies demonstrated a reduction of cancer risk after recovery from PHPT. Overall, to date, cardiovascular and neuropsychological evaluation are not recommended solely because of PHPT, nor cardiovascular disease, muscle weakness, and neuropsychological complications are indication for parathyroidectomy.
Assuntos
Hiperparatireoidismo Primário/complicações , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Humanos , Hiperparatireoidismo Primário/epidemiologia , Hiperparatireoidismo Primário/cirurgia , Hipertensão/epidemiologia , Hipertensão/etiologia , Hipertrofia Ventricular Esquerda/epidemiologia , Hipertrofia Ventricular Esquerda/etiologia , Paratireoidectomia/métodos , Paratireoidectomia/reabilitação , Qualidade de VidaRESUMO
OBJECTIVE: To evaluate if the parameters of hypothalamic-pituitary-adrenal (HPA) axis activity could predict the occurrence and duration of post-surgical hypocortisolism (PSH) in patients with Cushing's syndrome (CS) and with adrenal incidentaloma (AI). METHODS: We studied 80 patients (54 females, age 53.3 ± 11 years), who underwent adrenalectomy for CS (17 patients) or for AI (53 patients). Before surgery, we measured adrenocorticotroph hormone (ACTH), urinary free cortisol (UFC) and serum cortisol after 1 mg dexamethasone suppression test (1 mg-DST) levels. After surgery, all patients were given a steroid replacement therapy, and PSH was searched after 2 months by a low-dose (1 µg, iv) corticotropin stimulation test, that was repeated every 6 months in PSH patients for at least 4 years. RESULTS: The PSH occurred in 82.4 and 46% of CS and AI patients, respectively. In the whole sample and in AI patients separately considered, the PSH was independently predicted by the preoperative cortisol levels after 1 mg-DST, however, with a low (< 70%) accuracy. In AI patients the PSH occurrence was not ruled out even by the cortisol levels after 1 mg-DST lower than 1.8 µg/dL (50 nmol/L). In the 50% of CS patients and in 31% of AI patients the PSH lasted more than 18 months and in 35.7% of CS patients it persisted for more than 36 months. In AI patients, the PSH duration was not predictable by any parameter. However, a PSH duration of at least 12 months was significantly predicted before adrenalectomy (sensitivity 91.7%, specificity 41.2%, positive predictive value 52.4%, negative predictive value 87.5%, p = 0.05) by the presence of at least 2 out of low ACTH levels, increased UFC levels and cortisol levels after 1 mg-DST ≥ 3.0 µg/dL (83 nmol/L). CONCLUSION: The PSH occurrence and its duration are hardly predictable before surgery. All patients undergoing unilateral adrenalectomy should receive a steroid substitutive therapy.
Assuntos
Doença de Addison/diagnóstico , Doença de Addison/epidemiologia , Neoplasias das Glândulas Suprarrenais/cirurgia , Adrenalectomia/efeitos adversos , Hormônio Adrenocorticotrópico/sangue , Síndrome de Cushing/cirurgia , Complicações Pós-Operatórias , Doença de Addison/sangue , Doença de Addison/etiologia , Adulto , Idoso , Feminino , Humanos , Sistema Hipotálamo-Hipofisário , Incidência , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Sistema Hipófise-SuprarrenalRESUMO
cAMP pathway plays a major role in the pathogenesis of cortisol-producing adrenocortical adenomas (CPA). cAMP-induced steroidogenesis is preceded by actin cytoskeleton reorganization, a process regulated by cofilin activity. In this study we investigated cofilin role in mediating cAMP effects on cell morphology and steroidogenesis in adrenocortical tumor cells. We demonstrated that forskolin induced cell rounding and strongly reduced phosphorylated (P)-cofilin/total cofilin ratio in Y1 (-52 ± 16%, p < 0.001) and human CPA cells (-53 ± 18%, p < 0.05). Cofilin silencing significantly reduced both forskolin-induced morphological changes and progesterone production (1.3-fold vs 1.8-fold in controls, p < 0.05), whereas transfection of wild-type or S3A (active), but not S3D (inactive) cofilin, potentiated forskolin effects on cell rounding and increased 3-fold progesterone synthesis with respect to control (p < 0.05). Furthermore, cofilin dephosphorylation by a ROCK inhibitor potentiated forskolin-induced cell rounding and steroidogenesis (2-fold increase vs forskolin alone). Finally, we found a reduced P-cofilin/total cofilin ratio and increased cofilin expression in CPA vs endocrine inactive adenomas by western blot and immunohistochemistry. Overall, these results identified cofilin as a mediator of cAMP effects on both morphological changes and steroidogenesis in mouse and human adrenocortical tumor cells.