RESUMEN
An uncommon occurrence in which Graves disease (GD) coincides with autonomous functioning thyroid nodules (AFTNs) is termed Marine-Lehnhart syndrome (MLS). While hyperfunctioning nodules in MLS are commonly benign, there exists a rare potential for malignancy. A 41-year-old male patient was initially managed conservatively upon being diagnosed with MLS type 1. However, the emergence of obstructive symptoms prompted a thyroidectomy 4 years after initial presentation. Histological analysis revealed 2 cervical lymph node metastases and papillary thyroid cancer (PTC) within the AFTN.
RESUMEN
A 23-year-old man and his grandmother with hyperthyroxinemia and hypercortisolemia were heterozygous for an ALB mutation (p. Arg218Pro), known to cause familial dysalbuminemic hyperthyroxinemia (FDH). However, serum-free cortisol levels in these individuals were normal and total cortisol concentrations fell markedly after depletion of albumin from their serum. We conclude that binding of steroid as well as iodothyronines to mutant albumin causes raised circulating cortisol as well as thyroid hormones in euthyroid euadrenal individuals with R218P FDH, with potential for misdiagnosis, unnecessary investigation, and inappropriate treatment.
Asunto(s)
Hidrocortisona/sangre , Hipertiroxinemia Disalbuminémica Familiar/complicaciones , Hipertiroxinemia/complicaciones , Mutación , Albúmina Sérica Humana/genética , Albúminas/química , Genotipo , Heterocigoto , Humanos , Inmunoensayo , Masculino , Personal Militar , Unión Proteica , Albúmina Sérica/genética , Esteroides/química , Tironinas/sangre , Tiroxina/sangre , Adulto JovenRESUMEN
Technological Innovations in Diabetes Therapy Abstract. In the last few years a whole array of technical innovations has dramatically increased treatment options for patients with diabetes mellitus. Capillary blood glucose measurements are increasingly replaced by continuous glucose monitoring. More and more insulin pump systems are linked up to continuous glucose monitoring, which thereby become ever more self-regulating. Novel ultra-long and ultra-short acting insulins have become available. There will soon be oral alternatives for several anti-diabetic treatments, which hitherto needed to be injected.
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Automonitorización de la Glucosa Sanguínea/instrumentación , Diabetes Mellitus/terapia , Invenciones , Páncreas Artificial , Administración Oral , Ensayos Clínicos Fase III como Asunto , Diabetes Mellitus/diagnóstico , Glucagón/administración & dosificación , Péptido 1 Similar al Glucagón/análogos & derivados , Péptidos Similares al Glucagón/administración & dosificación , Humanos , Insulina/administración & dosificación , Sistemas de Infusión de InsulinaRESUMEN
CONTEXT: Attainment of safe GH and IGF-1 levels is a central goal of acromegaly management. OBJECTIVE: The aim of this study was to determine the extent to which reductions in GH and IGF-1 concentrations correlate with amelioration of radiological, metabolic, vascular, cardiac, and respiratory sequelae in a single unselected patient cohort. STUDY DESIGN: This was a prospective, within-subject comparison in 30 patients with newly diagnosed acromegaly (15 women and 15 men: mean age, 54.3 years; range, 23-78 years) before and after 24 weeks of lanreotide Autogel (ATG) therapy. RESULTS: Reductions in GH and IGF-1 concentrations and tumor volume were observed in all but 2 patients (median changes [Δ]: GH, -6.88 µg/L [interquartile range -16.78 to -3.32, P = .000001]; IGF-1, -1.95 × upper limit of normal [-3.06 to -1.12, P = .000002]; and pituitary tumor volume, -256 mm(3) [-558 to -72.5, P = .0002]). However, apnea/hypopnea index scores showed highly variable responses (P = .11), which were independent of ΔGH or ΔIGF-1, but moderately correlated with Δweight (R(2) = 0.42, P = .0001). Although systolic (P = .33) and diastolic (P = .76) blood pressure were unchanged, improvements in arterial stiffness (aortic pulse wave velocity, -0.4 m/s [-1.2 to +0.2, P = .046]) and endothelial function (flow mediated dilatation, +1.73% [-0.32 to +6.19, P = .0013]) were observed. Left ventricular mass index regressed in men (-11.8 g/cm(2) [-26.6 to -1.75], P = .019) but not in women (P = .98). Vascular and cardiac changes were independent of ΔGH or ΔIGF-1 and also showed considerable interindividual variation. Metabolic parameters were largely unchanged. CONCLUSIONS: Presurgical ATG therapy lowers GH and IGF-1 concentrations, induces tumor shrinkage, and ameliorates/reverses cardiac, vascular, and sleep complications in many patients with acromegaly. However, responses vary considerably between individuals, and attainment of biochemical control cannot be assumed to equate to universal complication control.
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Acromegalia/tratamiento farmacológico , Hipertensión/tratamiento farmacológico , Hipertrofia Ventricular Izquierda/tratamiento farmacológico , Péptidos Cíclicos/administración & dosificación , Síndromes de la Apnea del Sueño/tratamiento farmacológico , Somatostatina/análogos & derivados , Acromegalia/complicaciones , Acromegalia/cirugía , Adulto , Anciano , Antineoplásicos/administración & dosificación , Femenino , Hormona de Crecimiento Humana/sangre , Humanos , Hipertensión/etiología , Hipertrofia Ventricular Izquierda/etiología , Factor I del Crecimiento Similar a la Insulina/metabolismo , Masculino , Persona de Mediana Edad , Cuidados Preoperatorios/métodos , Estudios Prospectivos , Receptores de Somatostatina/antagonistas & inhibidores , Síndromes de la Apnea del Sueño/etiología , Somatostatina/administración & dosificación , Resultado del Tratamiento , Rigidez Vascular/efectos de los fármacos , Adulto JovenRESUMEN
BACKGROUND: Elevated plasma levels of asymmetric dimethylarginine (ADMA), an endothelial nitric oxide synthase (eNOS) inhibitor, may contribute to endothelial dysfunction in chronic heart failure (CHF). Since statins upregulate eNOS and ameliorate endothelial dysfunction in non-ischaemic CHF, we hypothesized that this may be in part through modification of ADMA. AIM: To evaluate the effect of atorvastatin on the relationship between ADMA and endothelial function in non-ischaemic CHF. METHODS: Twenty-four patients with CHF (ejection fraction <40%, New York Heart Association Functional Classes II and III) were randomised to atorvastatin treatment (40 mg) or placebo once daily for 6 weeks in a double-blinded, placebo-controlled crossover study. Plasma ADMA and l-arginine levels were measured by HPLC. Endothelial function was assessed by flow-mediated dilatation and invasive forearm plethysmography. RESULTS: Post-statin therapy, endothelial function was improved (p<0.05) independent of LDL-cholesterol reductions, but no changes were observed in ADMA levels or the l-arginine to ADMA ratio. There was a trend for ADMA to inversely correlate with endothelial function at baseline. CONCLUSIONS: Short-term atorvastatin treatment in non-ischaemic CHF improves endothelial function but has no effect on ADMA or the l-arginine to ADMA ratio. Our finding suggests that the observed statin-induced improvements in endothelial function are likely mediated via alternative pathways.
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Ácidos Heptanoicos/uso terapéutico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Pirroles/uso terapéutico , Disfunción Ventricular Izquierda/tratamiento farmacológico , Arginina/análogos & derivados , Arginina/biosíntesis , Arginina/sangre , Atorvastatina , Estudios Cruzados , Método Doble Ciego , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/metabolismo , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/metabolismo , Ácidos Heptanoicos/farmacología , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Pirroles/farmacologíaRESUMEN
Although not currently indicated for chronic heart failure (CHF), statins have been associated with improved outcome in retrospective analysis. However, statin therapy reduces plasma levels of coenzyme Q(10) (ubiquinone), which may have adverse effects on heart failure states. We hypothesized that atorvastatin treatment improves endothelial function in patients with chronic heart failure independent of LDL-cholesterol alterations. Furthermore, we assessed how reductions in coenzyme Q(10) levels impact on potentially improved endothelial function. Twenty-four patients with stable, symptomatic heart failure (New York Heart Association Class II or III) and a left ventricular ejection fraction <40% were randomised to 40 mg atorvastatin or placebo for 6 weeks and crossed over to the other treatment arm for a further 6 weeks, after a 2-week wash out. Forearm resistance vessel function was assessed by venous occlusion plethysmography during infusion of acetylcholine (ACh), sodium nitroprusside (SNP), and N(G)-monomethyl-L-arginine (L-NMMA) into the brachial artery. Atorvastatin treatment lowered triglycerides, LDL-cholesterol and coenzyme Q(10) levels (all p<0.001) and improved endothelium-dependent vasodilatation during acetylcholine infusion (p=0.015). Endothelium-dependent forearm blood flow improvements correlated with reductions in coenzyme Q(10) levels (p=0.011), but not with LDL-cholesterol levels (p=0.084). Coenzyme Q(10) remained the significant variable predicting improvement in NO dependent endothelial function after adjusting for LDL-cholesterol levels (p=0.041). In conclusion, short-term atorvastatin therapy improved endothelial function in chronic heart failure patients. Further studies are required to determine whether coenzyme Q(10) reductions are limiting the maximum favourable effects of statin therapy on the microcirculation.