RESUMEN
BACKGROUND: Recurrence of acromegaly after successful surgery is a rare event, but no clear data are reported in the literature about its recurrence rates. This study aimed to evaluate the recurrence rate in a series of acromegalic patients treated by transsphenoidal surgery (TSS) with a long follow-up. METHODS: We retrospectively analyzed data from 283 acromegalic patients who underwent TSS at two pituitary units in Milan (Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico and IRCCS Humanitas Research Hospital). The diagnosis and recurrence of acromegaly were defined by both elevated IGF-1 levels and a lack of GH suppression based on appropriate criteria for the assay used at the time of diagnosis. RESULTS: After surgery, 143 patients (50%) were defined as not cured, 132 (47%) as cured and 8 (3%) as partially cured because of normalization of only one parameter, either IGF1 or GH. In the cured group, at the last follow-up (median time 86.8 months after surgery), only 1 patient (0.7%) showed full recurrence (IGF-1 + 5.61 SDS, GH nadir 1.27 µg/l), while 4 patients (3%) showed only increased IGF1. In the partially cured group at the last follow-up, 2/8 (25%) patients showed active acromegaly (IGF-1 SDS + 2.75 and + 3.62; GH nadir 0.6 and 0.5 µg/l, respectively). CONCLUSIONS: In the literature, recurrence rates range widely, from 0 to 18%. In our series, recurrence occurred in 3.7% of patients, and in fewer than 1%, recurrence occurred with elevation of both IGF-1 and the GH nadir. More frequently (25%), recurrence came in the form of incomplete normalization of either IGF-1 or GH after surgery.
Asunto(s)
Acromegalia , Humanos , Acromegalia/cirugía , Acromegalia/diagnóstico , Acromegalia/epidemiología , Femenino , Masculino , Estudios Retrospectivos , Persona de Mediana Edad , Adulto , Estudios de Seguimiento , Factor I del Crecimiento Similar a la Insulina/metabolismo , Factor I del Crecimiento Similar a la Insulina/análisis , Hormona de Crecimiento Humana/sangre , Hormona de Crecimiento Humana/metabolismo , Centros de Atención Terciaria/estadística & datos numéricos , Anciano , Adenoma/cirugía , Adenoma/epidemiología , Adenoma/patología , Adenoma/diagnóstico , Recurrencia , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/diagnósticoRESUMEN
OBJECTIVE: Patients with Cushing's syndrome (CS) are at high risk of venous thromboembolism related to a hypercoagulability due to procoagulant imbalance. However, whether these alterations are reversible after disease remission is still unclear. The endogenous thrombin potential (ETP) measured with and without the addition of thrombomodulin provides a global representation of coagulation and previous data confirmed hypercoagulable profile in patients with active hypercortisolism. Aim of this study was to assess the short- and long-term modification of ETP in patients with CS after disease remission. DESIGN AND METHODS: Nineteen patients with CS for whom surgical remission was achieved, were prospectively evaluated for clinical characteristics, cortisol secretion profile and ETP at different time points: (i) before surgical intervention; (ii) after 6 months and (iii) 5 years from the time of persistent remission. Nineteen healthy subjects matched for age and gender were also evaluated as control group. RESULTS: Before surgery, patients showed higher ETP-ratio (with/without thrombomodulin) than controls (0.62 ± 0.09-vs-0.56 ± 0.09, p = 0.034). No significant correlation between ETP-ratio and cortisol secretion was found. 6 months after remission, ETP-ratio was still significantly increased compared to controls (0.64 ± 0.09-vs-0.56 ± 0.09, p = 0.01), but was similar to baseline (0.64 ± 0.09-vs-0.62 ± 0.09, p = 0.87). At 5 years, ETP-ratio showed a significant decrease (0.55 ± 0.14-vs-0.62 ± 0.09, p = 0.02) and was comparable to controls (0.55 ± 0.14-vs-0.56 ± 0.09, p = 0.7). CONCLUSIONS: Plasma hypercoagulability detected in patients with active hypercortisolism persists at short-term evaluation and seems to be completely reversible after long-term remission of disease. These data, as part of a whole evaluation of thrombotic risk, can contribute to make appropriate therapeutic choice in these patients.
Asunto(s)
Pruebas de Coagulación Sanguínea/métodos , Síndrome de Cushing , Hidrocortisona/sangre , Trombina/análisis , Trombofilia , Tromboembolia Venosa , Adrenalectomía/métodos , Adulto , Coagulación Sanguínea , Síndrome de Cushing/sangre , Síndrome de Cushing/complicaciones , Síndrome de Cushing/cirugía , Femenino , Humanos , Hipofisectomía/métodos , Masculino , Periodo Posoperatorio , Inducción de Remisión , Medición de Riesgo/métodos , Trombofilia/sangre , Trombofilia/etiología , Tiempo , Tromboembolia Venosa/sangre , Tromboembolia Venosa/etiología , Tromboembolia Venosa/prevención & controlRESUMEN
PURPOSE: The study aimed to define the clinical, biochemical and genetic features of adult patients with osteopenia/osteoporosis and/or bone fragility and low serum alkaline phosphatase (sALP). METHODS: Twenty-two patients with at least two sALP values below the reference range were retrospectively enrolled after exclusion of secondary causes. Data about clinical features, mineral and bone markers, serum pyridoxal-5'-phosphate (PLP), urine phosphoethanolamine (PEA), lumbar and femur bone densitometry, and column X-ray were collected. Peripheral blood DNA of each participant was analyzed to detect ALPL gene anomalies. RESULTS: Pathogenic ALPL variants (pALPL) occurred in 23% and benign variants in 36% of patients (bALPL), while nine patients harbored wild-type alleles (wtALPL). Fragility fractures and dental anomalies were more frequent in patients harboring pALPL and bALPL than in wtALPL patients. Of note, wtALPL patients comprised women treated with tamoxifen for hormone-sensitive breast cancer. Mineral and bone markers were similar in the three groups. Mean urine PEA levels were significantly higher in patients harboring pALPL than those detected in patients harboring bALPL and wtALPL; by contrast, serum PLP levels were similar in the three groups. A 6-points score, considering clinical and biochemical features, was predictive of pALPL detection [P = 0.060, OR 1.92 (95% CI 0.972, 3.794)], and more significantly of pALPL or bALPL [P = 0.025, OR 14.33 (95% CI 1.401, 14.605)]. CONCLUSION: In osteopenic/osteoporotic patients, single clinical or biochemical factors did not distinguish hypophosphatasemic patients harboring pALPL or bALPL from those harboring wtALPL. Occurrence of multiple clinical and biochemical features is predictive of ALPL anomalies, and, therefore, they should be carefully identified. Tamoxifen emerged as a hypophosphatasemic drug.
Asunto(s)
Fosfatasa Alcalina/genética , Biomarcadores/análisis , Hipofosfatemia , Fosfatasa Alcalina/análisis , Fosfatasa Alcalina/sangre , Biomarcadores/sangre , Densidad Ósea , Enfermedades Óseas Metabólicas/sangre , Enfermedades Óseas Metabólicas/epidemiología , Enfermedades Óseas Metabólicas/genética , Enfermedad Crónica , Estudios Transversales , Análisis Mutacional de ADN , Femenino , Fracturas Óseas/sangre , Fracturas Óseas/epidemiología , Fracturas Óseas/genética , Humanos , Hipofosfatemia/sangre , Hipofosfatemia/diagnóstico , Hipofosfatemia/epidemiología , Hipofosfatemia/genética , Italia/epidemiología , Masculino , Persona de Mediana Edad , Osteoporosis/sangre , Osteoporosis/epidemiología , Osteoporosis/genética , Polimorfismo de Nucleótido Simple , Fosfato de Piridoxal/análisis , Fosfato de Piridoxal/sangre , Estudios RetrospectivosRESUMEN
PURPOSE: Dynamic testing represents the mainstay in the differential diagnosis of ACTH-dependent Cushing's syndrome. However, in case of undetectable or detectable lesion < 6 mm on MRI, bilateral inferior petrosal sinus sampling (BIPSS) is suggested by current guidelines. Aim of this study was to analyze the performance of CRH, desmopressin and high-dose dexamethasone suppression test (HDDST) in the differential diagnosis of ACTH-dependent Cushing's syndrome as well as the impact of invasive and noninvasive tests on surgical outcome in patients affected by Cushing's disease (CD). METHODS: Retrospective analysis on 148 patients with CD and 26 patients with ectopic ACTH syndrome. RESULTS: Among CD patients, negative MRI/lesion < 6 mm was detected in 97 patients (Group A); 29 had a 6-10 mm lesion (Group B) and 22 a macroadenoma (Group C). A positive response to CRH test, HDSST and desmopressin test was recorded in 89.4%, 91·4% and 70.1% of cases, respectively. Concordant positive response to both CRH/HDDST and CRH/desmopressin tests showed a positive predictive value of 100% for the diagnosis of CD. Among Group A patients with concordant CRH test and HDDST, no difference in surgical outcome was found between patients who performed BIPSS and those who did not (66.6% vs 70.4%, p = 0.78). CONCLUSIONS: CRH, desmopressin test and HDDST have high accuracy in the differential diagnosis of ACTH-dependent CS. In patients with microadenoma < 6 mm or non-visible lesion, a concordant positive response to noninvasive tests seems sufficient to diagnose CD, irrespective of MRI finding. In these patients, BIPSS should be reserved to discordant tests.
Asunto(s)
Hormona Adrenocorticotrópica/sangre , Síndrome de Cushing/diagnóstico , Imagen por Resonancia Magnética/métodos , Muestreo de Seno Petroso/métodos , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT) , Pruebas de Función Hipofisaria/métodos , Neoplasias Hipofisarias , Adulto , Síndrome de Cushing/epidemiología , Diagnóstico Diferencial , Técnicas de Diagnóstico Endocrino , Femenino , Humanos , Hipofisectomía/métodos , Hipofisectomía/estadística & datos numéricos , Italia/epidemiología , Masculino , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/sangre , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/diagnóstico , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/epidemiología , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/cirugía , Neoplasias Hipofisarias/diagnóstico por imagen , Neoplasias Hipofisarias/patología , Neoplasias Hipofisarias/cirugía , Estudios RetrospectivosAsunto(s)
Biomarcadores/metabolismo , Diabetes Insípida/diagnóstico , Glicopéptidos/metabolismo , Procedimientos Neuroquirúrgicos/efectos adversos , Enfermedades de la Hipófisis/cirugía , Complicaciones Posoperatorias/diagnóstico , Diabetes Insípida/etiología , Diabetes Insípida/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedades de la Hipófisis/patología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/metabolismo , Pronóstico , Estudios ProspectivosAsunto(s)
COVID-19/diagnóstico , COVID-19/epidemiología , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/diagnóstico , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/epidemiología , Centros de Atención Terciaria/tendencias , Adulto , Anciano , COVID-19/terapia , Estudios de Cohortes , Femenino , Humanos , Italia/epidemiología , Masculino , Persona de Mediana Edad , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/terapiaRESUMEN
PURPOSE: Hypophosphatemia (HP) can be observed in patients evaluated for skeletal fragility. We investigated prevalence of HP among outpatients referred for low bone density or fragility fractures, HP-associated clinical and biochemical features and outcomes of recommended diagnostic algorithm in our cohort. METHODS: Chronic HP (phosphate ≤ 2.7 mg/dL over 6 months or longer) was retrospectively investigated among 2319 patients. In renal wasting-related HP, intact FGF23 was assessed; non-suppressed FGF23 prompted the performance of 68Ga-DOTATOC PET/CT in the suspicion of tumor-induced steomalacia (TIO). RESULTS: Renal wasting-related HP (median 2.2, range 1.6-2.6 mg/dL) was observed in 19 patients (0.82%). FGF23 levels were suppressed in two patients diagnosed with renal tubular disease, increased in one and within normal range in most patients. X-linked hypophosphatemic rickets was diagnosed in one woman. In the remaining 16 patients, highly prevalent fragility fractures (50%) and severely reduced bone mineral density were detected, though diagnostic criteria for osteomalacia were not fulfilled. 68Ga-PET was performed in nine patients and was positive in four. While intact FGF23 levels alone failed to differentiate PET's outcomes (positive: FGF23 median 70.5 pg/mL; negative: 52 pg/mL, P = 0.462), the coexistence of multiple biochemical and radiologic alterations performed better in prediction of PET's positivity. CONCLUSION: Mild, apparently unexplained HP is observed in 0.82% of patients with low bone density or fragility fractures. In asymptomatic patients with isolated mild hypophosphatemia, the probability of finding an underlying tumor disease is very low, and utility of extensive and expensive diagnostic workup should be carefully considered in this setting.
Asunto(s)
Enfermedades Óseas Metabólicas/sangre , Manejo de la Enfermedad , Factores de Crecimiento de Fibroblastos/sangre , Fracturas Óseas/sangre , Fragilidad/sangre , Hipofosfatemia/sangre , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades Óseas Metabólicas/diagnóstico por imagen , Estudios de Cohortes , Femenino , Factor-23 de Crecimiento de Fibroblastos , Fracturas Óseas/diagnóstico por imagen , Fragilidad/diagnóstico por imagen , Humanos , Hipofosfatemia/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
BACKGROUND: First-line therapy of Cushing disease (CD) is transsphenoidal surgery (TSS) aimed to obtain a complete removal of the pituitary adenoma and remission of disease. PURPOSE: To analyse the surgical outcome of patients with CD who underwent TSS in our Centre. METHODS: Retrospective analysis on patients with CD who underwent TSS between 1990 and 2016. RESULTS: We analysed 102 TSS that included: 84 first TSS and 18 second and third TSS. The overall remission rate after surgery was 76.5%, with a significant higher percentage of remitted patients after the first TSS compared to the subsequent TSS (82% vs 50%, p = 0.014). The remission after the first TSS was significantly higher when performed by a dedicated surgical team (DST) (89.8% vs 71% p = 0.04) and when the immunohistochemical examination confirmed the adrenocorticotropic adenoma (87% vs 55%, p = 0.04). Neuroradiological findings influenced the surgical outcome in a non-significant manner. Post-TSS complications were reported in 32 patients, with no significant variation when TSS was performed by DST. In case of reintervention, remission of disease was obtained in 72.7% of microadenoma, while no remitted patients were observed in case of macroadenomas. The DST did not significantly improve the outcome. CONCLUSION: Cushing disease is characterized by a broad spectrum of neuroradiological presentation. Despite the availability of a DST make the TSS a safe and effective first-line treatment among all these patients, a precise pre-treatment evaluation is needed in order to define the aim of neurosurgery and to schedule the management of recurrent disease.