RESUMEN
CONTEXT: Head and neck paragangliomas (HNPGLs) are rare, usually benign, slow-growing tumours arising from neural crest-derived tissue. Definitive management pathways for HNPGLs have yet to be clearly defined. OBJECTIVE: To review our experience of the clinical features and management of these tumours and to analyse outcomes of different treatment modalities. METHODS: Demographic and clinical data were obtained from The Northern Ireland Electronic Care Record (NIECR) as well from a prospectively maintained HNPGL database between January 2011 through December 2023. RESULTS: There were 87 patients; 50 females: 37 males with a mean age of 52.3 ± 14.2 years old (range 17-91 years old). 58.6% (n = 51) of patients had carotid body tumours, 25.2% (n = 22) glomus vagal tumours, 6.8% (n = 6) tumours in the middle ear, 2.2% (n = 2) in the parapharyngeal space and 1.1% (n = 1) in the sphenoid sinus. 5.7% (n = 5) of patients had multifocal disease. The mean tumour size at presentation was 3.2 ± 1.4 cm (range 0.5-6.9 cm). Pathogenic SDHD mutations were identified in 41.3% (n = 36), SDHB in 12.6% (n = 11), SDHC in 2.2% (n = 2) and SDHA in 1.1% (n = 1) of the patients. Overall treatment modalities included surgery alone in 51.7% (n = 45) of patients, radiotherapy in 14.9% (n = 13), observation in 28.7% (n = 25), and somatostatin analogue therapy with octreotide in 4.5% (n = 4) of patients. Factors associated with a significantly higher risk of recurrence included age over 60 years (p = .04), tumour size exceeding 2 cm (p = .03), positive SDHx variants (p = .01), and vagal and jugular tumours (p = .04). CONCLUSION: The majority of our patients underwent initial surgical intervention and achieved disease stability. Our results suggest that carefully selected asymptomatic or medically unfit patients can be safely observed provided lifelong surveillance is maintained. We advocate for the establishment of a UK and Ireland national HNPGL registry, to delineate optimal management strategies for these rare tumours and improve long term outcomes.
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Neoplasias de Cabeza y Cuello , Paraganglioma , Humanos , Persona de Mediana Edad , Masculino , Femenino , Adulto , Neoplasias de Cabeza y Cuello/terapia , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/patología , Anciano , Estudios Retrospectivos , Adolescente , Adulto Joven , Anciano de 80 o más Años , Paraganglioma/terapia , Paraganglioma/genética , Paraganglioma/patología , Succinato Deshidrogenasa/genética , Resultado del Tratamiento , MutaciónRESUMEN
OBJECTIVE: Addition of dehydroepiandrosterone sulphate (DHEAS) to standard pituitary replacement may improve quality of life and glucose metabolism. Conflicting results from the previous work probably relate to differences in populations studied and assessment techniques used. We examined the effects of DHEAS on insulin action and the quality of life in female patients with hypopituitary hypoadrenalism. DESIGN: Randomized, double-blind, placebo-controlled, crossover design was used. Patients received either DHEAS 50 mg daily or placebo for 12 weeks. PATIENTS: Fourteen hypopituitary females on stable standard replacement therapy and with low DHEAS were enrolled. MEASUREMENTS: Insulin action by euglycaemic hyperinsulinaemic clamp and extensive quality of life parameters were assessed after each treatment. RESULTS: Serum DHEAS (DHEAS 5·4 ± 0·8 vs placebo <0·8 ± 0·0 µm; P < 0·001) and androstenedione (DHEAS 4·1 ± 0·8 vs placebo 1·3 ± 0·2 nm; P < 0·05) rose to within the normal range after DHEAS 50 mg daily. There were no differences between treatments in testosterone, sex hormone-binding globulin (SHBG) or IGF-1. Quality of life measures were unchanged after DHEAS. There were no differences between treatments in fasting glucose, serum insulin, HbA1c or in insulin action (glucose infusion rates required to maintain euglycaemia; DHEAS 21·9 ± 2·5 vs placebo 24·5 ± 2·1 µmol/kg/min; P = 0·4). Triglyceride concentrations were lower following DHEAS (DHEAS 1·24 ± 0·18 vs placebo 1·41 ± 0·19 mm; P < 0·05) but other lipid parameters remained unchanged. CONCLUSION: There were no differences compared with placebo in quality of life or insulin action after DHEAS replacement therapy for 12 weeks. These results do not provide evidence for the addition of DHEAS to standard hypopituitary replacement therapy.
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Sulfato de Deshidroepiandrosterona/uso terapéutico , Hipopituitarismo/sangre , Hipopituitarismo/tratamiento farmacológico , Insulina/sangre , Insuficiencia Suprarrenal/sangre , Insuficiencia Suprarrenal/complicaciones , Insuficiencia Suprarrenal/tratamiento farmacológico , Adulto , Anciano , Glucemia/metabolismo , Estudios Cruzados , Sulfato de Deshidroepiandrosterona/efectos adversos , Método Doble Ciego , Femenino , Técnica de Clampeo de la Glucosa , Humanos , Hipopituitarismo/complicaciones , Lípidos/sangre , Persona de Mediana Edad , Calidad de VidaRESUMEN
Statin therapy improves lipid profiles and reduces vascular inflammation, but its effects on central arterial stiffness in type 2 diabetes are unclear. The aim of this study was to determine whether statin therapy reduces central arterial stiffness, in a dose-dependent manner, in male patients with type 2 diabetes. Fifty-one patients ceased statin therapy for 6 weeks, followed by randomisation to either 10 or 80 mg of atorvastatin. At randomization, 3 and 12 months, central arterial stiffness was measured via carotid-femoral pulse wave velocity (PWV), along with serum markers of vascular inflammation including high-sensitivity c-reactive protein (hsCRP) and osteoprotegerin (OPG). PWV decreased from 10.37 ± 1.30 to 9.68 ± 1.19 m/sec (p < 0.01 from baseline) at 3 months and 9.10 ± 1.17 m/sec (p < 0.001 from baseline) at 12 months. hsCRP and OPG decreased significantly at 3 and 12 months. Reductions in PWV did not differ significantly between the groups. Baseline PWV and OPG values correlated strongly (r = 0.48, p < 0.01), as did their response to atorvastatin over 12 months (r = 0.36 delta-OPG and delta-PWV, p < 0.01). Atorvastatin therapy appeared to reduce central arterial stiffness in male type 2 diabetes, with no dose-dependent effect observed. The correlation observed between reductions in PWV and OPG suggests that atorvastatin reduces PWV via direct anti-inflammatory effects on the vasculature.
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Atorvastatina/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Rigidez Vascular/efectos de los fármacos , Adulto , Anciano , Anciano de 80 o más Años , Atorvastatina/farmacología , Biomarcadores/sangre , Proteína C-Reactiva/metabolismo , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/fisiopatología , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Masculino , Persona de Mediana Edad , Osteoprotegerina/sangre , Análisis de la Onda del Pulso , Resultado del Tratamiento , Rigidez Vascular/fisiologíaRESUMEN
Concern exists regarding adverse metabolic effects of antihypertensive agents. In the United States, diuretics are recommended first-line but additional agents, usually angiotensin-converting enzyme (ACE) inhibitors, are often required to meet blood pressure targets. We have previously shown that the combination of low-dose diuretic with an ACE inhibitor has detrimental effects on insulin action compared with ACE inhibitor alone in hypertensive type 2 diabetic patients. Our aim was to establish whether similar effects occur in nondiabetic hypertensive patients using this combination. A randomized double-blind placebo-controlled crossover design was used. After a 6-week run-in, when regular antihypertensive medications were withdrawn and placebo substituted, patients received captopril 50 mg twice daily with either bendroflumethiazide 1.25 mg (CB) or placebo (CP) for 12 weeks with a 6-week wash-out between treatments. Insulin action was assessed by hyperinsulinemic euglycemic clamp after the 6-week run-in and at the end of each treatment period. There were no differences between treatments in fasting glucose or insulin concentrations. Glucose infusion rates required to maintain euglycemia were the same with each treatment (CP 22.1±2.2 vs CB 22.2±2.2 µmol/kg per minute). There was no difference in endogenous glucose production in the basal state (CP 8.9±0.5 vs CB 9.5±0.7 µmol/kg per minute; P=0.23) or during hyperinsulinemia (CP 2.2±0.6 vs CB 1.5±0.3 µmol/kg per minute; P=0.30). In contrast to the situation in type 2 diabetes mellitus, ACE inhibitor combined with low-dose thiazide diuretic does not adversely affect insulin action when compared with ACE inhibitor alone in nondiabetic hypertensive patients.