Background: Whether sleep apnoea syndrome (SAS) subsides after biochemical and clinical remission of acromegaly is controversial. Objective: To assess the presence of SAS in a cohort of acromegalic patients, which included a subgroup with active disease and a subgroup in remission, and to evaluate clinical and biochemical independent predictors of SAS. Design: Cross-sectional and longitudinal study. Setting: Italian university department of internal medicine. Patients: About 36 acromegalic patients: 18 active and 18 controlled. Measurements: Polysomnography was performed in all patients and repeated in six with active acromegaly and SAS after achieving disease control. Echocardiographic parameters were also measured. Results: The prevalence of SAS was 47% in the overall acromegalic population: 56% in the active group and 39% in the controlled one. In a multivariate analysis IGF1, male gender, age, body mass index, and disease duration were associated with SAS. Impaired glucose tolerance or diabetes was more prevalent in patients with SAS, particularly in the severe cases. Among the six patients of the longitudinal study, five showed improvement of SAS, but none recovered. No correlation was found between echocardiographic parameters and severity of SAS. Conclusion: SAS can persist after recovery of acromegaly in several patients. Given the negative prognostic significance of this respiratory disorder, polysomnography should be included as routine procedure in the work-up of the acromegaly, even if in remission, being mandatory in those patients considered at high risk (elderly males, overweight, diabetic). Appropriate intensive treatment should be implemented to minimize the clinical impact of SAS in acromegaly.

Objective: Evidence is limited regarding outcome of patients with ectopic Cushing's syndrome (ECS) due to neuroendocrine tumors (NETs). Design: We assessed the prognostic factors affecting the survival of patients with NETs and ECS. Methods: Retrospective analysis of clinicopathological features, severity of hormonal syndrome, treatments from a large cohort of patients with NETs and ECS collected from 17 Italian centers. Results: Our series included 110 patients, 58.2% female, with mean (±s.d.) age at diagnosis of 49.5 ± 15.9 years. The main sources of ectopic ACTH were bronchial carcinoids (BC) (40.9%), occult tumors (22.7%) and pancreatic (p)NETs (15.5%). Curative surgery was performed in 56.7% (70.2% of BC, 11% of pNETs). Overall survival was significantly higher in BC compared with pNETs and occult tumors (P = 0.033) and in G1-NETs compared with G2 and G3 (P = 0.007). Negative predictive factors for survival were severity of hypercortisolism (P < 0.02), hypokalemia (P = 0.001), diabetes mellitus (P = 0.0146) and distant metastases (P < 0.001). Improved survival was observed in patients who underwent NET removal (P < 0.001). Adrenalectomy improved short-term survival. Clinical Study

Objective: Multiple endocrine neoplasia type 2 (MEN 2) is a genetic disease characterized by medullary thyroid carcinoma (MTC) associated (MEN 2A and 2B) or not familial MTC (FMTC) with other endocrine neoplasia due to germline RET gene mutations. The prevalence of these rare genetic diseases and their corresponding RET mutations are unknown due to the small size of the study population. Methods: We collected data on germline RET mutations of 250 families with hereditary MTC followed in 20 different Italian centres. Results and conclusions: The most frequent RET amino acid substitution was Val804Met (19.6%) followed by Cys634Arg (13.6%). A total of 40 different germline RET mutations were present. Six families (2.4%) were negative for germline RET mutations. The comparison of the prevalence of RET germline mutations in the present study with those published by other European studies showed a higher prevalence of Val804Met and Ser891Ala mutations and a lower prevalence of Leu790Phe and Tyr791Phe (P!0.0001). A statistically significant higher prevalence of mutations affecting non-cysteine codons was also found (P!0.0001). Furthermore, the phenotype data collection showed an unexpected higher prevalence of FMTC (57.6%) with respect to other MEN 2 syndromes (34% MEN 2A and 6.8% of MEN 2B). In conclusion, we observed a statistically significant different pattern of RET mutations in Italian MEN 2 families with respect to other European studies and a higher prevalence of FMTC phenotype. The different ethnic origins of the patients and the particular attention given to analysing apparently sporadic MTC for RET germline mutations may explain these findings.

SS receptors are overexpressed in many tumors, mainly of neuroendocrine origin, thus enabling the treatment with SS analogs. The clinical experience of receptor radionuclide therapy with the new analog [90Y-DOTA0-Tyr3 ]-octreotide [90Y-DOTATOC] has been developed over the last decade and is gaining a pivotal role in the therapeutic workout of these tumors. It is well known that some procedures performed in diagnostic and therapeutic management of endocrine tumors, such as agobiopsy and hepatic chemoembolization, can be associated with the occurrence of symptoms related to the release of vasoactive amines and/or hormonal peptides from tumor cell lysis. This is the first report of a severe carcinoid crisis developed after receptor radionuclide therapy with 90Y-DOTATOC administered in a patient affected by liver metastases from bronchial neuroendocrine tumor (atypical carcinoid). Despite protection with H1 receptor antagonists, octreotide and corticosteroids, few days after the therapy the patient complained of persistent flushing of the face and upper trunk, severe labial and periocular oedema, diarrhoea and loss of appetite. These symptoms increased and required new hospitalisation. The patient received iv infusion of octreotide associated with H1 and H2 receptor antagonists and corticosteroid therapy, which induced symptom remission within few days. The case here reported confirms that radionuclide therapy is highly effective in determining early rupture of metastatic tissue and also suggests that pre-medication should be implemented before the radiopeptide administration associated with a close monitoring of the patient in the following days.

The apparent paradox of bone fragility in acromegaly patients with a normal BMD can be explained by increased cortical thickness and porosity and reduced trabecular thickness with increased trabecular separation. These structural and microarchitectural abnormalities persist in the controlled phase of acromegaly despite bone turnover normalization. The main determinant of bone disease after hormonal control is severe osteoblastic dysfunction.