A Mossé

Multiple sc injections of a long-acting somatostatin analogue (SMS 201-995) are currently used in the treatment of acromegaly. However, plasma GH concentration often reaches a pathological level (less than 5 micrograms/l) between two injections. In seven patients with active acromegaly we compared, in a short-term trial, the effect of SMS 201-995 administered by continuous sc infusion (50 micrograms and 100 micrograms a day) and by three sc injections (100 micrograms each). In six patients, plasma GH levels were significantly reduced regardless of the mode and dose of treatment (P less than 0.05). However, comparing diurnal profiles, 100 micrograms continuous sc infusion was more effective than discontinuous administration in reducing the number of GH levels above 5 micrograms/l (P less than 0.01). In two patients, continuous infusion was the only way to decrease all plasma GH values below 5 micrograms/l during the diurnal profile determination. Moreover, even when, in a long-term study, the dose of multiple injections was progressively increased to 500 micrograms three times a day, GH levels remained consistently elevated in one of these patients. Thus, in some acromegalic patients continuous sc injection seems currently the most efficient way of treatment with SMS 201-995.

UNLABELLED: Calciphylaxis characterized by schemic skin ulceration due to subcutaneous small arterioles calcification, is a rare disease but usually fatal. Disorders of calcium metabolism and vascular calcifications are common in dialysis patients but calciphylaxis prevalence is low in patients with end stage renal disease. So we proposed other emergent factors implicated in calciphylaxis development. METHODS: We studied retrospective 8 patients who developed calciphylaxis in our service from january 2001 to december 2006. RESULTS: All patients were female with mean age at diagnosis 68.5+/-6.7 years. All patients were receiving hemodialysis therapy and 6 patients had been receiving hemodialysis less than four months. Six patients had diabetes mellitus type II and all patients were obese (BMI >25 kg/m2). All patients had metabolic syndrome (APTIII) with bad control hypertension and 6 (75%) were receiving anticoagulation therapy with warfarin. Patients didn t have severe alterations of calcium metabolism, all had product calcium-phosphorus <55. All patients developed low blood pressure at the beginning of dialysis treatment (98.3+/-22.7/60+/-18,29 mmHg). 7 patients present proximal lesions in fatty regions like abdomen and thighs. Histopathologic examination reveals calcium deposits in arteriole-sized and small vessels with vascular thrombosis. Prognosis was poor, seven patients died secondary to a sepsis originated in infected cutaneous ulcers. CONCLUSIONS: calciphylaxis is a disease with poor prognosis and high mortality, without specific treatment actually. Female gender, obesity associated with diabetes mellitus and cardiometabolic syndrome, anticoagulant therapy with warfarin and low blood pressure associated with hemodialysis therapy, are risk factors to develop calciphylaxis, in absence of severe disorders of calcium metabolism. In these patients is important to avoid hypotension episodes during dialysis, dialysis hypotension appears to be an important risk factor who promotes ischemia of subcutaneous adipose tissue.

Five women suffering from Cushing's disease were treated with ketoconazole 800 mg per day for 2 to 28 months (mean 12.4 months). Four of them had full clinical and biochemical regression. However, after 8 months of therapy the disease failed to respond in three of these four women. Increasing the ketoconazole dosage up to 1,200 mg per day was ineffective in two patients. Such an escape phenomenon, not described until now, will restrict the use of ketoconazole in the treatment of Cushing's disease, although the drug is easy to administer and well tolerated globally and by the liver in most cases.

La calcifilaxis, caracterizada por la ulceracion isquemica de la piel secundaria a la calcificacion de las pequenas arteriolas subcutaneas, es una enfermedad poco frecuente pero con mal pronostico. Los pacientes con ERCT tienen un riesgo alto de calcificaciones patologicas debido a las alteraciones del metabolismo calcio-fosforo, pero solo un pequeno numero desarrollan esta enfermedad. Por ello es logico pensar que hay otros factores que condicionan el desarrollo de la calcifilaxis. Metodos: Con el fin de identificar estos posibles factores implicados en su genesis, hemos analizado de forma retrospectiva las caracteristicas de los 8 pacientes con ERCT que presentaron calcifilaxis en nuestro hospital entre de enero 2001 a diciembre 2006. Resultados: Los 8 pacientes eran mujeres con edad media de 68,5 ± 6,7 anos. Todas presentaban ERCT en hemodialisis periodica (HD) y en 6 casos la cacifilaxis aparecio en los primeros 4 meses del inicio del tratamiento con HD. Seis de las pacientes eran diabeticas tipo 2 y todas eran obesas (IMC > 25 kg/m2), 3 con obesidad grado 4 o morbida. Todas cumplian criterios de sindrome metabolico (APT III), habian sido hipertensas mal controladas y en un 75% de los casos recibian tratamiento con anticoagulantes cumarinicos por distintas causas. No presentaban alteraciones severas del metabolismo calcio-fosforo: todas tenian un producto CaxP < 55. En todos los casos se controlo estrictamente la Presion arterial (PA) con el tratamiento con HD manteniendo cifras medias de PA de 98,3 ± 22,7/60 ± 18,29 mmHg en el momento de la aparicion de los sintomas. La mayoria de las pacientes (7/8), presentaron las lesiones a nivel proximal en las zonas con mayor deposito graso como muslos y abdomen. El estudio histologico de las lesiones en todos los casos demostro calcificacion de pequenas arteriolas subcutaneas asociada a paniculitis y trombosis de pequenos vasos. La evolucion clinica fue mala ya que siete de las ocho pacientes murieron como consecuencia de una sepsis de origen cutaneo. La exeresis quirurgica de los nodulos no modifico la mala evolucion. En conclusion: La paniculitis calcificante en pacientes con ERCT es una enfermedad rara pero de mal pronostico y elevada mortalidad. El sexo mujer, la obesidad asociada a Diabetes y Sindrome metabolico, el tratamiento anticoagulante y el excesivo control de la presion arterial al inicio del tratamiento con HD pueden favorecer su aparicion incluso en ausencia de alteraciones relevantes del metabolismo Ca-P-PTH. Debido a la epidemia actual de DM, obesidad y sindrome metabolico es de esperar que el numero de pacientes con estas caracteristicas que desarrollen ERCT y calcifilaxis vaya en aumento.