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JP Luton, M Martinez, J Coste and J Bertherat

OBJECTIVE: The study was designed to evaluate the clinical, endocrinological and radiological parameters used to investigate adrenal incidentalomas and select patients for surgery. DESIGN AND METHODS: An analysis of 88 consecutive patients with adrenal incidentaloma selected for surgery and investigated in a single clinical center was performed. RESULTS: Mean (+/-s.d.) age of the patients was 53+/-14 years. Fourteen (16%) of the adrenal incidentalomas were malignant tumors (2 adrenocortical carcinomas, 3 metastases, 4 adenocarcinomas, 4 sarcomas and 1 mesenchymoma), 10 (11%) were pheochromocytomas, 32 (36%) were non-secretory benign adrenal adenomas and the remaining were benign adrenal (n = 8; 9%) or extra-adrenal (n = 24; 27%) masses. Endocrinological investigations revealed 1 Conn adenoma, 4 tumors responsible for Cushing's syndrome or silent hypercortisolism and 1 androgen secreting tumor. Abnormalities of endocrine evaluations were observed in the 2 malignant adrenocortical carcinomas. Elevated 24-h urinary metanephrine levels were observed in the 9 pheochromocytomas tested. Complications of surgery occurred in 14% of the cases. Regardless of the endocrine status, parameters associated with malignant tumors were: older age (mean age of patients harboring malignant tumors vs patients with benign incidentalomas: 62+/-17 years vs 52+/-13 years, P = 0.005), weight loss (39% vs 7%, P = 0. 005), and mass diameter greater than 60mm (69% vs 15%, P < 0.001). By multiple logistic regression analysis malignant tumors were associated with increased age, diameter greater than 60mm and bilateral masses. CONCLUSION: This study points to a high rate of pheochromocytomas and malignant tumors in patients selected for surgery. This high rate differs from some previous reports and might be explained by the criteria used to select patients for surgery. Among these two groups of tumors, careful systematic endocrinological investigations allow the detection of altered secretion in the vast majority - if not all - malignant tumors of adrenal origin and pheochromocytomas. Only 5% of the incidentalomas below 30 mm selected for surgery in this study were malignant, in keeping with the use of this criteria as an important parameter to select patients with normal hormonal investigations for careful follow-up.

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H Mosnier-Pudar, P Thomopoulos, X Bertagna, C Fournier, D Guiban and JP Luton

Mosnier-Pudar H, Thomopoulos P, Bertagna X, Fournier C, Guiban D, Luton JP. Long-distance and long-term follow-up of a patient with intermittent Cushing's disease by salivary cortisol measurements. Eur J Endocrinol 1995;133:313–6. ISSN 0804–4643

Salivary cortisol is an excellent indicator of the plasma free cortisol concentration in normal and pathological situations. We took advantage of its ease of sampling, allowing multiple collections at home, to follow the course of a patient with Cushing's disease living in North Africa. This 48-year-old woman presented with a clinically moderate hypercortisolism caused by a large basophilic pituitary adenoma. Bilateral extension to the cavernous sinuses precluded surgical therapy. She went into spontaneous remission based on clinical signs as well as biochemical findings. During the following 2 years she demonstrated intermittent relapses that were treated by radiotherapy (50 Gy), followed by ketoconazole and then o-paraprime-dichloro-diphenyl-dichloroethane (Op′DDD). After a prolonged clinical remission, Cushing's syndrome again became active. Bromocriptine was started without effect and a new treatment with Op′DDD was began. Evaluation and follow-up were performed during hospitalizations and mainly through the measurements of salivary cortisol in more than 100 samples sent from North Africa by air mail to our department in Paris. Thus we were able to demonstrate intermittent overproduction of cortisol before any treatment, with periods of normal and even low values, and to follow the efficacy of therapy and to detect the relapses. We conclude that measurement of salivary cortisol is a valuable tool in difficult clinical situations such as intermittent hypercortisolism and remoteness between the patient and hospital.

H Mosnier-Pudar, Clinique des Maladies Endocriniennes et Metaboliques, Hôpital Cochin, 27 rue du Faubourg Saint Jacques, 75014 Paris, France

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N Boulle, E Baudin, C Gicquel, A Logie, J Bertherat, A Penfornis, X Bertagna, JP Luton, M Schlumberger and Y Le Bouc

OBJECTIVE: Recent studies have pointed to the role of the IGF system in the pathogenesis of adrenocortical tumors, and it was shown recently that malignant adrenocortical tumors exhibit a high insulin-like growth factor binding protein (IGFBP)-2 content. Circulating markers specific for adrenocortical carcinoma are needed and the aim of this study was to evaluate plasma IGFBP-2 as a marker for these malignant tumors. METHODS: Plasma IGFBP-2 was determined in 51 patients referred to our institutions for adrenocortical tumors. Fifteen patients were in complete remission (group 1), eight patients had preoperative localized tumors (group 2) and 28 patients had metastatic tumors (group 3). Thirty-six healthy volunteers constituted a control group. RESULTS: There was no significant difference in plasma IGFBP-2 concentration between healthy controls and patients with complete remission or localized tumors. In contrast, patients with metastatic disease had significantly higher IGFBP-2 plasma levels than the control group (P<0.001). IGFBP-2 levels in patients with metastatic disease were inversely correlated with survival (R2=0.308; P=0.0026). In patients with localized tumors, there was no correlation between plasma IGFBP-2 concentration and tumor size or histological features. Analysis of individual IGFBP-2 concentrations showed that five patients (17.8%) with metastatic tumors had normal IGFBP-2 levels and two patients (13.3%) in complete remission had high plasma IGFBP-2 levels. The influence of nutrition, hormone secretion and treatment on IGFBP-2 levels was examined. Nutritional status was evaluated by determining IGF-I levels and was found to be normal in 16 patients (61.5%) with high IGFBP-2 levels, suggesting that malnutrition was not responsible for the high IGFBP-2 concentrations in these patients. IGFBP-2 levels did not differ significantly according to tumor secretion or mitotane treatment. In a follow-up study, plasma IGFBP-2 concentration remained stable in patients with complete remission or stabilized disease and was a late marker of tumor progression in patients with progressive metastatic disease. CONCLUSIONS: These results indicate that plasma IGFBP-2 is elevated in patients with malignant adrenocortical tumors and that the major factor affecting IGFBP-2 levels in these patients is tumor stage. However, plasma IGFBP-2 was less sensitive than expected for a tumor marker, which may limit its value in the diagnosis and follow-up of adrenocortical carcinoma.