The value of plasma markers for the clinical behaviour of phaeochromocytomas

Abstract

Objective: Phaeochromocytomas (PCCs) are widely known for their clinical unpredictability. This study intends to define predictive plasma markers for their variable postoperative behaviour. Furthermore, the diagnostic accuracy of these plasma tests was determined. Design and Methods: A retrospective correlative study was performed in a series of 83 operated and four autopsied patients in order to correlate preoperative catecholamine (CAT) levels of 103 PCCs with their clinical behaviour. In a subset of cases, chromogranin-A (Chr-A) and enzymes/precursors of the CAT biosynthesis were studied for their predictive value. Results: Basal CAT levels were elevated in 81/87 instances (sensitivity: 93%). Four of six cases with normal measurements showed only medullary hyperplasia. Larger PCCs, particularly those showing necrosis, capsular and vascular invasion, secreted higher CAT levels. Bilateral, hereditary tumours were less productive than their unilateral counterparts. Extra-adrenal PCCs secreted significantly lower levels of epinephrine (EPI) than intra-adrenal tumours. Fourteen patients developed metastases. According to Kaplan -Meier estimations, patients with higher levels of dopamine, norepinephrine (NE) and aromatic L-amino acid decarboxylase as well as lower ratios of EPI/EPI þ NE, had significantly shorter metastases-free intervals. Existence of preoperative hypertension, left ventricular hypertrophy and measured blood pressures showed significant positive relationships with CAT levels, but not with Chr-A. Conclusions: These data showed that plasma CAT measurement is a sensitive method in the diagnostic work-up of PCCs. Those tumours producing normal levels are commonly small and asymptomatic. Furthermore, certain secretion patterns are indicative of the presence of metastases as well as the size and site of sporadic and syndrome-related PCCs.

Pathological grading for predicting metastasis in phaeochromocytoma and paraganglioma

“…Our data also indicated that metastases were more common in norepinephrine-producing tumours than in epinephrine-producing tumours. PHEO/PGL tumours may exhibit different biochemical phenotypes because extra-adrenal tumours secrete predominantly norepinephrine whereas adrenal tumours secrete mainly epinephrine (van der Harst et al 2002). In this study 38.6% (49 of 127) of the adrenal tumours were norepinephrine type.…”

“…Norepinephrineproducing tumours lack PNMT (the enzyme that converts norepinephrine to epinephrine) and are considered to be less differentiated than epinephrine-producing tumours based on catecholamine synthesis. Dopamine hypersecretion was considered a feature of immaturity and a marker for malignant PCC/PGL (van der Harst et al 2002). …”

THERAPY OF ENDOCRINE DISEASE: Treatment of malignant pheochromocytoma and paraganglioma

“…The most robust studies of the characterization of MPP patients at the time of the diagnosis have suggested that metastatic adrenal and extra-adrenal tumors occur at equal rates and that the survival rates of metastatic adrenal and extraadrenal tumors overlap (2); w60% of MPP patients have tumor burden-and hormone-related manifestations (e.g., pain, hypertension, and constipation) (3); most MPPs produce noradrenaline and normetanephrine and/or dopamine and methoxytyramine, which partly reflects the higher risk of malignancy associated with SDHB mutations and extra-adrenal locations (4,5,6,7,8); most MPP patients have apparently sporadic tumors or tumors associated with germline or somatic mutations of the succinate dehydrogenase subunit B (SHDB) gene (2,9,10). The high prevalence of SDHB mutations (30-50% of patients) supports the screening of all patients with MPPs for such mutations.…”

Localization of Messenger Ribonucleic Acids for Somatostatin Receptor Subtypes (sstr1–5) in the Rat Adrenal Gland

“…Recent studies suggest that most if not all of the antihormonal actions of SRIF are mediated via either sstr2 and/or sstr5 (Lamberts et al 1996). SRIF receptors are expressed in a large number of tumors (Kennedy and Dluhy 1997;Hofland et al 1999;Kaltsas et al 2001;van der Harst et al 2001). Conformationally stabilized SRIF analogues, such as octreotide (which binds with high affinity to sstr2 and -5), are used clinically to control humoral hypersecretion and tumor growth in patients with acromegaly, carcinoids, and pheochromocytomas (Berlowitz 1995).…”