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Mario Pedrazzoni, Pier P Vescovi, Letizia Maninetti, Massimo Michelini, Giulio Zaniboni, Giulio Pioli, Daniele Costi, Francesco S Alfano and Mario Passeri

Though the chronic use of opiates can modify several body functions, only a few data are available on the effects of opioid drugs on mineral metabolism. We have examined the possible consequences of chronic opiate abuse on bone mass, bone turnover and calcium metabolism in 13 male chronic heroin users, examined 1–2 days after the last administration of the drug (group A), 14 former male heroin addicts, examined 4–24 months after drug discontinuation (group B), and 22 healthy, age- and sex-matched control subjects. In group A, the vertebral bone mineral density (measured by Dual-Photon Absorptiometry) was significantly lower (p <0.05) than in the control subjects, despite similar values of total body bone mineral, lean body and fat mass. Blood-ionised calcium and urinary calcium and hydroxyproline were significantly increased (p<0.01), whereas parathyroid hormone was lower than in controls (p<0.01). Bone alkaline phosphatase and osteocalcin, however, were not significantly different from the control values. LH and testosterone levels were low (p <0.01 vs controls). In contrast, group B subjects did not show significant differences from the control group. The chronic abuse of opioid drugs may be associated with altered bone metabolism and reduced trabecular bone mass, attributable, at least in part, to gonadal deficiency. These alterations seem reversible after drug discontinuation.

Free access

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.

Open access

Daniele Cassatella, Sasha R Howard, James S Acierno, Cheng Xu, Georgios E Papadakis, Federico A Santoni, Andrew A Dwyer, Sara Santini, Gerasimos P Sykiotis, Caroline Chambion, Jenny Meylan, Laura Marino, Lucie Favre, Jiankang Li, Xuanzhu Liu, Jianguo Zhang, Pierre-Marc Bouloux, Christian De Geyter, Anne De Paepe, Waljit S Dhillo, Jean-Marc Ferrara, Michael Hauschild, Mariarosaria Lang-Muritano, Johannes R Lemke, Christa Flück, Attila Nemeth, Franziska Phan-Hug, Duarte Pignatelli, Vera Popovic, Sandra Pekic, Richard Quinton, Gabor Szinnai, Dagmar l’Allemand, Daniel Konrad, Saba Sharif, Özlem Turhan Iyidir, Brian J Stevenson, Huanming Yang, Leo Dunkel and Nelly Pitteloud

Objective

Congenital hypogonadotropic hypogonadism (CHH) and constitutional delay of growth and puberty (CDGP) represent rare and common forms of GnRH deficiency, respectively. Both CDGP and CHH present with delayed puberty, and the distinction between these two entities during early adolescence is challenging. More than 30 genes have been implicated in CHH, while the genetic basis of CDGP is poorly understood.

Design

We characterized and compared the genetic architectures of CHH and CDGP, to test the hypothesis of a shared genetic basis between these disorders.

Methods

Exome sequencing data were used to identify rare variants in known genes in CHH (n = 116), CDGP (n = 72) and control cohorts (n = 36 874 ExAC and n = 405 CoLaus).

Results

Mutations in at least one CHH gene were found in 51% of CHH probands, which is significantly higher than in CDGP (7%, P = 7.6 × 10−11) or controls (18%, P = 5.5 × 10−12). Similarly, oligogenicity (defined as mutations in more than one gene) was common in CHH patients (15%) relative to CDGP (1.4%, P = 0.002) and controls (2%, P = 6.4 × 10−7).

Conclusions

Our data suggest that CDGP and CHH have distinct genetic profiles, and this finding may facilitate the differential diagnosis in patients presenting with delayed puberty.