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.

It has been shown that an appreciable percentage of patients presenting with primary, apparently sporadic phaeochromocytomas may in fact have von-Hippel-Lindau (VHL) disease. In order to investigate this, we retrospectively screened 68 patients, who had been operated on for phaeochromocytomas, for the presence of germline mutations in the vhl gene. DNA was isolated from peripheral-blood leukocytes and used to screen the entire coding sequence and the intron-exon boundaries of the vhl gene for mutations, using a PCR-based SSCP strategy. When an abnormal pattern was found in the SSCP analysis, sequence analysis was carried out. We found SSC variants in the vhl gene in 8 of the 68 patients. Of 6 patients, 2 turned out to be related (an uncle and his nephew), and they carried the same mis-sense mutation: R64P. In 4 other patients, mis-sense mutations, P25L, L63P, G144Q and I147T, were also identified. None of these mutations has been described, and 3 of them (P25L, L63P and R64P) are located closer to the N terminus of the vhl protein than any reported vhl mutation. In the remaining 2 cases, the mutations were localized not in the coding sequence but in the intronic sequence (but not within splice-sites), adjacent to the exon, so they were probably not related to the disease. Our results show that a relatively high proportion (6/68, or 8.8%), though not as high as the 20% reported earlier, of patients with apparently sporadic phaeochromocytomas may carry germline mutations in the vhl gene. Int.

Long-term replacement therapy with rhGH in patients with adult-onset GHD induces a significant increase in Hb concentrations, while serum leucocyte and platelet counts do not change.

We studied the association between retinopathy and glucose metabolism in a population-based study of elderly men and women. Glucose metabolism was assessed by serum fructosamine and a nonfasting oral glucose tolerance test, and retinopathy was evaluated by fundus photography. Retinopathy was present in 296 of 6,191 subjects examined (4.8%; 120 men and 176 women). Serum glucose and fructosamine levels were higher in subjects with retinopathy compared with those without (8.4 vs. 6.8 mmol/l and 329.8 vs. 308.5 mumol/l, respectively, P < 0.001). Two-hour postload insulin levels and insulin resistance, assessed by the ratio of postload insulin over postload glucose level, did not differ between the two groups. These associations were similar in men and women and in subjects with and without diabetes and did not change after adjustment for body mass index or systolic blood pressure. Within the group of subjects who had retinopathy, serum glucose was significantly associated with the number of hemorrhages. These findings suggest that the presence and severity of retinopathy are associated with higher serum glucose levels, both in subjects with and without diabetes.