Chiara Taurino

Unique association of non-functioning pheochromocytoma, ganglioneuroma, adrenal cortical adenoma, hepatic and vertebral hemangiomas in a patient with a new intronic variant in the VHL gene.

We analyzed the clinical, hormonal, immunohistochemical and genetic features in a 69-yr-old Caucasian woman with a very rare “composite and mixed pheochromocytoma”. This was characterized by right adrenal pheochromocytoma associated with homolateral ganglioneuroma and controlateral adrenal cortical adenoma. The three tumors, incidentally discovered, proved to be non-functioning (normal secretion of catecholamines and of other neuroendocrine peptides, glucocorticoids, mineralcorticoids and androgens). Accordingly, the patient showed no sign or symptom of endocrine disease. Computed tomography (CT) and magnetic resonance (MR) demonstrated a typical adenomatous lesion on the left adrenal gland with precocious uptake of the radiotracer on radioidine (131I)-norcholesterol adrenal scintigraphy, while the controlateral gland showed hyperdensity on CT, hyperintensity on MR and no uptake at adrenal scintigraphy. In addition, CT and MR revealed a vertebral and two hepatic hemangiomas. The right adrenal gland was surgically removed and, microscopically, pheochromocytoma and ganglioneuroma areas appeared intermixed without a predominant component. The former showed strong immunoreactivity for chromogranin, synaptophysin, vascular endothelial growth factor (VEGF) and CD34, while the latter appeared positive for neuron-specific enolase (NSE) and S−100. Peripheral blood genomic DNA analysis revealed a new intronic variant (5557A>G) in the von Hippel-Lindau gene (VHL) not observed in our control population.

Normalization of catecholamine production following resection of phaeochromocytoma positively influences carotid vascular remodelling

OBJECTIVE To evaluate the influence of plasma catecholamines on the vascular structure in humans, the effects of catecholamine normalization on the carotid wall of patients with phaeochromocytoma (PHEO) were investigated. A prospective study in patients with PHEO before and after (first follow-up: 20.5+/-1.8 months, second follow-up: 31.5+/-2.2 months) successful surgery was conducted in the University Referral Center for Blood Pressure Diseases. Ten consecutive patients with PHEOs and ten age- and blood pressure-matched controls were investigated. Intima-media thickness (IMT) by two-dimensional conventional ultrasonography and corrected ultrasonic integrated backscatter signal (C-IBS) analysis of carotid arteries were investigated in basal conditions and after mass removal. RESULTS In PHEOs, at variance with the expected reduction in metanephrines and catecholamines, no variation in body weight, blood pressure and lipid profile was observed after operation. IMT and C-IBS values in patients with PHEO were greater (at least P<0.01) than in controls. At long-term follow-up after surgery, a significant reduction in mean carotid IMT (P<0.0009) and C-IBS (P<0.009) values was observed. A significant correlation (r=0.54, P<0.03) was found between absolute reduction in C-IBS values and absolute decrement in urinary normetanephrine levels. CONCLUSIONS Our study shows that normalization of catecholamine levels after the removal of PHEO improves carotid IMT and reduces carotid wall fibrosis even without influencing blood pressure and lipid profile. These findings confirm that high catecholamine tone in humans directly influences vascular remodelling of carotid arteries.

Preclinical cardiac involvement in phaeochromocytoma: a study with integrated backscatter

Objective  It is well known that vascular and cardiac structure may be influenced by circulating neurohormonal factors. Our aim was to study the myocardial wall texture by integrated backscatter (IBS) analysis in patients with phaeochromocytoma (PHEO).

Malignant extra-adrenal pheochromocytoma caused by an SDHB intronic variation leading to a 54-bp deletion in exon 4

In the last few years several papers have reported on the association between mutations of the genes encoding the structural (SDHC, SDHD) and catalytic (SDHB) subunits of succinate dehydrogenase and the occurrence of hereditary pheochromocytomas/paragangliomas (Pheo/PGL) syndromes. We diagnosed a malignant extra-adrenal Pheo in a 38-yr-old man with abdominal lesions; many areas of increased uptake at octreoscan scintigraphy in the skeleton indicated metastatic disease. We then approached genetic analysis through the screening of the SDHB, SDHC, and SDHD genes. Here we report a heterozygous G>A transversion at position +1 of intron 4 of SDHB gene. To clarify this mutation we performed cDNA analysis by RT-PCR and we assume that the splice site mutation in intron 4 abolishes the consensus splice donor sequence leading to an in-frame deletion of 18 amino acid. This finding indicates once again that SDHB mutations could predispose to malignant Pheo.

L’edema ciclico idiopatico. Realtà o fantasia?

RiassuntoL’edema ciclico idiopatico è una sindrome non infiammatoria caratterizzata da un obiettivo incremento ponderale o dalla percezione soggettiva di aumento del peso corporeo per cause non precisate. La sindrome colpisce pressoché esclusivamente il sesso femminile nella vita riproduttiva, e si caratterizza per la sensazione di tensione generalizzata e ritenzione idrica in posizione ortostatica. L’escursione ponderale giornaliera è variabile, ma può raggiungere anche svariati chilogrammi. Poco si sa sulla genesi della malattia, anche se, verosimilmente, numerosi fattori possono concorrere in varia misura, come una attivazione del sistema renina-angiotensina, disturbi ipotalamici, alterazioni dopaminergiche sistemiche o renali e alterazioni anatomiche della parete vascolare con aumento della permeabilità capillare. Non raramente la malattia si instaura in pazienti con disturbi della condotta alimentare o comunque con alterazione del tono dell’umore e spesso è aggravata dall’uso di farmaci (diuretici, lassativi) che, assunti con lo scopo di perdere peso, aggravano poi la sintomatologia iniziale. La diagnosi di edema idiopatico è da porre dopo avere escluso tutte le altre forme note di edema localizzato o generalizzato. I provvedimenti terapeutici sono concentrati sul controllo del peso corporeo tramite una dieta povera di sodio, limitata nei carboidrati e generosa nei liquidi, il mantenimento giornaliero di posizione clinostatica alternat o a lunghe camminate e talora l’elastocompressione degli arti inferiori. Dal punto di vista farmacologico, è stato proposto l’uso di ACE-inibitori o antialdosteronici, senza peraltro durevoli successi, mentre i diuretici dell’ansa, i farmaci dopaminergici e soprattutto le amine simpaticomimetiche sembrano del tutto inutili e talora ricchi di effetti collaterali.