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L Mansi, PF Rambaldi, N Panza, D Esposito, V Esposito and V Pastore

In a 28-year-old man with Cushing's syndrome, studies investigating a hypophyseal and/or adrenal origin of the disease, including computed tomography and magnetic resonance imaging, were negative. In agreement with reports showing somatostatin receptors on the cell membrane of ectopically secreting ACTH tumours, scintigraphy was performed after intravenous injection of 111 MBq 111In-pentetreotide (OCT). The radiolabelled OCT scan showed a small focal area of intense uptake at the inferior lobe of the right lung. Subsequent radioguided surgery located and defined a small mass (1.8 x 1.4 x 1.6 cm). The probe pinpointed the mass to the right inferior chest lobe, with a tumour/normal tissue count ratio of 6:1 and tumour/hilar normal lymph node ratio of 12:1, thus permitting the complete excision of the tumour to exclude lymph node and/or parietal involvement. A lung carcinoid was diagnosed at histology. The patient is still alive and disease-free 24 months after surgery. 111In-OCT was found to be useful for localizing the ACTH-secreting tumour and also permitted rapid non-invasive differential diagnosis between an ACTH-secreting pituitary adenoma and malignancy causing ectopic ACTH syndrome. This study also showed the clinical usefulness of radioguided surgery in the treatment of bronchial carcinoid.

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M Salerno, T Lettiero, A Esposito-Del Puente, V Esposito, D Capalbo, A Carpinelli, S Padula and A Del Puente

OBJECTIVE: To evaluate whether long-term l-thyroxine therapy in young adults with congenital hypothyroidism may affect bone mineral density (BMD). DESIGN: Thirty-seven subjects with congenital hypothyroidism, detected by neonatal screening and longitudinally followed from the time of diagnosis and treatment (26+/-4 days) up to the age of 17.8+/-1.0 years, were studied. METHODS: Spinal (L2-L4) BMD, measured by dual-energy X-ray densitometry, and bone quality, measured as amplitude-dependent speed of sound (Ad-SoS) by quantitative ultrasound, were evaluated. RESULTS: Z-score mean values (+/-s.d.) of BMD (-0.3+/-0.7) and Ad-SoS (-0.7+/-1. 1) were slightly below the average but within the normal range. Ad-SoS resulted in a z-score below -1 in 38% of patients as compared with BMD which resulted in a z-score below -1 in only 13.5% of subject. No significant differences were observed between males (BMD, -0.3+/-0.7; Ad-SoS, -0.9+/-1.0) and females (BMD, -0.3+/-0.7; Ad-SoS, -0.5+/-1.2) or when dividing patients on the basis of aetiological defects; ectopic gland (BMD, -0.3+/-0.6; Ad-SoS, -0.8+/-0.9), athyreosis (BMD, -0.3+/-0.9; Ad-SoS, -0.8+/-1.0) and eutopic gland (BMD, -0.3+/-0.8; Ad-SoS, -0.4+/-1.3). No significant relationships were observed between BMD or Ad-SoS z-score and hormonal status or l-thyroxine dosages at the time of the study or during the pubertal period. CONCLUSIONS: The careful monitoring of serum thyroid-stimulating hormone and adjustment of l-thyroxine dosage avoided the significant deleterious effects of prolonged l-thyroxine replacement therapy on bone tissue in adolescents and young adults with congenital hypothyroidism treated from the neonatal period.

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ML Jaffrain-Rea, G Minniti, C Moroni, V Esposito, E Ferretti, A Santoro, T Infusino, G Tamburrano, G Cantore and R Cassone

BACKGROUND: Cardiac abnormalities develop in patients with acromegaly as a consequence of effects of GH/IGF-I on the heart and related cardiovascular risk factors. OBJECTIVE: To evaluate the possible contribution of postoperative variations in blood pressure (BP), glucose tolerance and insulin sensitivity to the cardiac improvement reported in patients who have been cured of acromegaly. DESIGN: Thirty-one patients with acromegaly were studied before and 6 Months after successful transsphenoidal surgery, defined by normal age-related IGF-I concentrations and glucose-suppressed GH concentrations <1 microg/l. METHODS: Cardiovascular parameters were assessed by Doppler echocardiography and 24-h ambulatory blood pressure monitoring. Insulin sensitivity indexes were calculated on the basis of fasting and post-load glycaemia and insulinaemia and referred to as HOMA(ISI) and OGTT(ISI), respectively. RESULTS: Successful surgery was confirmed to improve left ventricular mass index (LVMI) and diastolic filling significantly. Mean 24-h systolic BP values decreased (P=0.009) and BP rhythm was restored in 12 of 15 patients with a blunted preoperative profile. Glucose tolerance normalized in patients with preoperative glucose intolerance (n=7) or diabetes mellitus (n=3). HOMA(ISI) and OGTT(ISI) increased (P=0.0001 for each parameter), indicating a marked improvement in insulin sensitivity. The postoperative reduction in LVMI correlated with increased insulin sensitivity (P<0.001 for both indexes), but not with other parameters. Improved diastolic filling correlated with the reduction in LVMI. CONCLUSIONS: Successful surgery in patients with acromegaly induces a significant improvement in haemodynamic and metabolic risk factors. This study suggests a direct link between insulin resistance and acromegalic cardiomyopathy.

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L Tauchmanova, R Rossi, V Nuzzo, A del Puente, A Esposito-del Puente, C Pizzi, F Fonderico, G Lupoli and G Lombardi

OBJECTIVE: Glucocorticoid excess is widely recognized as one of the most important causes of bone loss. The mechanism of glucocorticoid-induced osteoporosis is presumably multifactorial, and consists of the loss of organic and non-organic compounds. Efforts have been made to develop simple physical methods for the assessment of bone tissue for the screening of subjects at high risk of osteoporosis, without the use of radioactive sources or ionizing radiation. Quantitative ultrasonometry (QUS) has been suggested as a useful method for monitoring patients undergoing glucocorticoid therapy, which is the most common cause of glucocorticoid excess. QUS appears to detect more structural bone changes than the traditional methods and allows assessment of bone density and elasticity, both characteristics influenced by organic and non-organic bone compounds. However, the use of QUS has not yet been extensively investigated in subjects with endogenous cortisol excess. The aim of this study was to evaluate the usefulness and predictive power of QUS in assessing bone loss in subjects with differing degrees of endogenous cortisol excess due to adrenal mass. DESIGN: Thirty-four patients (20 women and 14 men) aged between 21 and 59 years were evaluated; fifteen (9 women and 6 men; median age, 42 years) were affected by overt Cushing's syndrome (CS) and nineteen (11 women and 8 men; median age, 44 years) by subclinical CS, defined as lacking clinical signs of hormone excess despite the presence of at least two abnormalities in hypothalamic-pituitary-adrenal axis function, as assessed by routine endocrine tests. All women included were eumenorrhoic. METHODS: QUS measurement of amplitude-dependent speed of sound was performed on the 2nd to 5th proximal phalanges of the non-dominant hand using a DBM Sonic 1200R bone profiler (Igea S.r.l, Italy). The results were compared with bone density assessed on lumbar vertebrae (L1-L4) and femoral neck sites by dual-energy X-ray absorptiometry (DEXA). RESULTS: A strongly significant bone loss was detected by finger QUS measurement when the patients were considered either all together or as two subgroups (P<0.001, all). The bone density decrease in the fingers was similar to that found at the lumbar spine and femoral neck by the DEXA technique. Lumbar and finger Z-scores correlated inversely with 24 h urinary free cortisol (UFF) excretion (P<0.01, both). Finger Z-scores also correlated inversely with the estimated duration of subclinical CS (P<0.05). Concerning disease activity, only UFF was confirmed by multivariate analysis to be an independent factor influencing bone loss (P<0.05). A positive correlation between the results of the two techniques was found in controls (P<0.05) but not in patients. The lack of correlation between the two techniques in patients can probably be attributed to the different parameters of bone alteration measured by the techniques. CONCLUSIONS: The detection of bone loss in subclinical CS similar to that in overt CS suggests that all subjects with endogenous cortisol excess should be evaluated for bone mass. QUS measurement appears to be a reliable, radiation-free, simple and fast tool for the identification of bone alteration in subjects with endogenous cortisol excess.

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E Ferretti, ML Jaffrain Rea, C Asteria, D Di Stefano, V Esposito, L Ferrante, P Daniele, C Tiberti, M Gallucci, C Bosman, E Alesse, A Gulino, P Beck-Peccoz and G Tamburrano

OBJECTIVE: Pituitary adenomas are usually sporadic, although rare familial cases have been described. Here we report two first degree female cousins with giant pituitary adenoma and overweight. Both presented with secondary amenorrhoea, occasional headache and weight gain. MATERIALS AND METHODS: In both patients clinical, morphological and genetic studies were performed. Both patients underwent surgery and post-operative medical therapy with somatostatin analogues and dopamine agonist, followed by a conventional radiotherapy course. RESULTS: Clinical examination at presentation revealed an acromegaloid habitus only in the second patient. Basal and dynamic hormonal evaluation showed high serum GH and serum IGF-I values, higher in the second than in the first patient, and a mild hyperprolactinaemia only in the first patient. On optical and electron microscopy, both tumours were oncocytic adenomas, immunopositive for GH in the first patient and GH/prolactin in the second. The genetic analysis for germ-line mutations of the multiple endocrine neoplasia type 1 gene was negative. Two years after radiotherapy a remarkable shrinkage of both tumours was observed, whereas the overweight worsened in both patients, accompanied by high plasma leptin values. CONCLUSION: To our knowledge, this is the first report of familial pituitary adenomas including one case of a clinically silent GH-secreting adenoma. In addition, it provides further evidence that familial pituitary tumours can occur as a multiple endocrine neoplasia type 1 unrelated disease.