Cushing's syndrome (CS) in medullary thyroid carcinoma (MTC) is rare. Only 50 cases have been reported. We report 10 cases of MTC with ectopic adrenocorticotropic hormone (ACTH)-dependent syndrome (EAS), analyzed retrospectively. Among 1640 patients with MTC, 13 developed EAS (0.7%). In 10 patients CS could unequivoqually be related to MTC (0.6%). CS was always clinically obvious. It revealed MTC in 3 cases and followed diagnosis by an average of 34.5 months in the others. Metastases were often present at diagnosis. Immunohistochemistry with ACTH antibodies was positive in one case. Diagnosis of ectopic CS was established according to clinical and biologic features, and absence of corticotropic adenoma as well as parallel evolution between tumor and CS. Therapy was medical and surgical: anticortisolic drugs alone or in association with somatostatin analogue, somatostatin analogue alone, and bilateral adrenalectomy. Eight patients died within 2 to 30 months, 4 of hypercortisolism complications (3 peritonitis and 1 hypokalaemia), 4 of MTC progression. EAS is a rare complication of MTC. The prognosis is poor because of frequency of metastasis at diagnosis. Persistent hypercortisolism can, by itself, lead to death, and has to be treated specifically.

Introduction Carney Complex (CNC) is a rare multiple endocrine and nonendocrine neoplasia syndrome. Manifestations and genotype-phenotype correlations have been described by retrospective studies, but no prospective study evaluating the occurrence of the different manifestations has been available so far. Methods This multicenter national prospective study included patients with CNC, primary pigmented nodular adrenal disease (PPNAD), or a pathogenic PRKAR1A mutation; after a full initial workup, participants were followed for 3 years with annual standardized evaluation. Results The cohort included 70 patients (50 female/20 male, mean age 35.4 ± 16.7 years, 81% carrying PRKAR1A mutation). The initial investigations allowed identification of several manifestations. At the end of the 3-year follow-up, the newly diagnosed manifestations of the disease were subclinical acromegaly in 6 patients, bilateral testicular calcifications in 1 patient, and cardiac myxomas in 2 patients. Recurrences of cardiac myxomas were diagnosed in 4 patients during the 3-year follow-up study period. Asymptomatic abnormalities of the corticotroph and somatotroph axis that did not meet criteria of PPNAD and acromegaly were observed in 11.4% and 30% of the patients, respectively. Patients carrying the PRKAR1A c.709-7del6 mutation had a mild phenotype. Conclusion This study underlines the importance of a systematic follow-up of the CNC manifestations, especially a biannual screening for cardiac myxoma. By contrast, regular screening for the other manifestations after a first extensive workup could be spread out, leading to a lighter and more acceptable follow-up schedule for patients. These are important results for recommendations for long-term management of CNC patients.

Gynaecomastia caused by Leydig cell tumours (LCT) in adult men may appear a long time before clinical evidence of testicular swelling. To evaluate the diagnostic criteria for LCT, hormonal status was studied in 14 cases and compared with results of a control group (CG) and 10 men with idiopathic gynaecomastia (IG). The mean plasma T level was significantly (P less than 0.005) lower in LCT (16.7 +/- 1.7 SEM nmol/l) than in CG (23.0 +/- 1.3 nmol/l). However, individual plasma T levels were in the normal range in 9/14 LCT. The mean plasma E2 level was significantly (P less than 0.001) higher in LCT (204.9 +/- 27.6 pmol/l) than in CG (87.9 +/- 7.7 pmol/l). However, individual plasma E2 levels were in the normal range in 5/14 LCT. In LCT, neither means of basal gonadotrophin levels nor the gonadotrophin responses to LHRH were different from CG. The mean of the plasma T responses to hCG did not differ between LTC, CG and IG. However the mean of E2 peak responses appeared significantly (P less than 0.005) higher in LCT (735.3 +/- 103.4 pmol/l) than in CG (420.5 +/- 40.4 pmol/l). The mean of the E2 peak responses was significantly (P less than 0.001) lower in IG (196.5 +/- 33.4 pmol/l) than in CG. Likewise the mean of plasma E2 levels, measured on day three following hCG administration, remained significantly (P less than 0.001) higher in LCT (662 +/- 94 pmol/l) than either in CG (228 +/- 14 pmol/l) or in IG (158 +/- 25 pmol/l). On day 3 following hCG administration, there was no overlap in individual plasma E2 levels between either LCT and CG or LCT and IG. In all LCT, plasma beta-hCG levels were in the normal range. A testicular echogram, performed in 12 LCT, confirmed the presence of a palpable tumour in 10 and revealed an occult tumour in two cases. We conclude that normal plasma beta-hCG levels, a prolonged plasma E2 response to hCG and testicular echogram appear to be the best criteria for early diagnosis of LCT responsible for gynaecomastia in adult men.

No abstract