Detection and molecular diagnosis of a new case of congenital analbuminaemia. / Detección y diagnóstico molecular de un nuevo caso de analbuminemia congénita.

INTRODUCTION AND OBJECTIVES: Congenital analbuminaemia (CCA) (MIM #616000) is an autosomal recessive disorder (prevalence < 1/106) caused by defects in the ALB gene leading to absence or severe reduction of albuminaemia. This paper describes a case of CCA detected and diagnosed in our hospital. MATERIALS AND METHODS: A 42-year old woman showing hypoproteinaemia and hypoalbuminaemia of unknown aetiology. Biochemical study was performed according to routine quality controlled analytical procedures: Albuminaemia (colorimetric and nephelometric methods). Protein electrophoresis (capillary and agarose gel). Molecular study of the ALB gene: DNA extraction, PCR amplification of the 14 coding exons plus adjacent intron regions and Sanger sequencing. RESULTS: After discarding the most common causes of hypoalbuminaemia, the analbuminaemia was confirmed by nephelometry and protein electrophoresis. The proband was found to be homozygous for molecular defect in the ALB gene: variant c.1289+1G>A previously reported as Guimarães variant. CONCLUSIONS: This is the first case of CCA confirmed by molecular study in Spain. The proband shows the Guimarães variant previously described in 4 patients worldwide.

Ectopic Cushing syndrome: Report of 9 cases. / Síndrome de Cushing ectópico: descripción de 9 casos.

INTRODUCTION: Ectopic Cushing's syndrome (ECS) is a rare condition caused by ACTH secretion by extrapituitary tumors. Its low frequency makes it difficult to acquire experience in its management. The aim of this study was to describe patients with ECS seen at the endocrinology department of a tertiary hospital over 15 years. METHODS: This was a retrospective study of the clinical, biochemical and radiographic data, treatment, and course of patients with ECS seen from 2000 to 2015. RESULTS: Nine patients (6 of them female) with a mean age of 47 years were included in the study. The clinical syndrome developed in less than 3 months in all cases but one, and most patients also had edema, hyperpigmentation and/or hypokalemia. Mean urinary free cortisol and ACTH levels were 2,840µg/24h and 204pg/mL respectively. The ectopic origin was confirmed by a combination of dynamic non-invasive tests and radiographic studies in most cases. The tumor responsible could be identified in 8 cases, and 7 patients had metastatic dissemination. Primary treatment was surgery in one patient, surgery combined with systemic therapy in 3, and chemotherapy in the other 3 patients. Bilateral adrenalectomy was required in 4 patients to control hypercortisolism. After a mean follow-up of 40 months, 3 patients died, 5 were still alive, and one had been lost to follow-up. CONCLUSIONS: Our study confirms that ECS covers a wide spectrum of tumors of different aggressiveness and nature. The ectopic origin of Cushing's syndrome can usually, be suspected and confirmed in most cases without the need for invasive tests. Control of both hypercortisolism and the tumor requires multiple treatment modalities, and multidisciplinary management is recommended.