Alessandro Berton

Acylated ghrelin as a provocative test for the diagnosis of GH deficiency in adults

OBJECTIVE Insulin tolerance test (ITT) is the test of reference for the diagnosis of adult GH deficiency (GHD), although GHRH in combination with arginine (ARG) or GH secretagogues are considered equally reliable tests. Testing with GH secretagogue alone is, anyway, a potent stimulus exploring the integrity of hypothalamic pathways controlling somatotropic function. We therefore aimed to determine the diagnostic reliability of testing with ghrelin, the natural GH secretagogue. METHODS We studied the GH response (every 15 MIN from 15 TO +120 MIN) to acylated ghrelin (1G/KG I.V. AT 0MIN) IN 78 patients with a history of pituitary disease (49 male, 29 female; age (MEANS.D.): 52.1±18.7 years; BMI: 26.7±5.3 kg/m(2)). The lack of GH response to GHRH+ARG and/or ITT was considered the gold standard for the diagnosis of GHD. The best GH cut-off to ghrelin test, defined as the one with the best sensitivity (SE) and specificity (SP), was identified using the receiver-operating characteristic curve analysis. RESULTS The best GH cut-off to ghrelin test was 7.3 μg/l in lean subjects (SE 88.2%, SP 90.9%), 2.9 μg/l in overweight subjects (SE 92.6%, SP 100%) and 0.6 μg/l in obese subjects (SE 50%, SP 100%). The diagnostic accuracy was 89.3, 94.1 and 62.5% respectively. CONCLUSIONS Our data show that testing with acylated ghrelin represents a reliable diagnostic tool for the diagnosis of adult GHD, in lean and overweight subjects, if appropriate cut-off limits are assumed. Obesity strongly reduces GH response to ghrelin, GH weight-related cut-off limit and diagnostic reliability of the test.

ACROSCORE: A new and simple tool for the diagnosis of acromegaly, a rare and underdiagnosed disease

Acromegaly, a disease caused by GH/IGF‐I hypersecretion, is associated with a high mortality rate; early recognition is therefore necessary to ensure successful treatment and to avoid comorbidities. We have created a symptom/sign scoring tool (ACROSCORE) for physicians to use to identify acromegaly.

Acromegaly is associated with increased cancer risk: a survey in Italy

It is debated if acromegalic patients have an increased risk to develop malignancies. The aim of the present study was to assess the standardized incidence ratios (SIRs) of different types of cancer in acromegaly on a large series of acromegalic patients managed in the somatostatin analogs era. It was evaluated the incidence of cancer in an Italian nationwide multicenter cohort study of 1512 acromegalic patients, 624 men and 888 women, mean age at diagnosis 45 ± 13 years, followed up for a mean of 10 years (12573 person-years) in respect to the general Italian population. Cancer was diagnosed in 124 patients, 72 women and 52 men. The SIRs for all cancers was significantly increased compared to the general Italian population (expected: 88, SIR 1.41; 95% CI, 1.18-1.68, P < 0.001). In the whole series, we found a significantly increased incidence of colorectal cancer (SIR 1.67; 95% CI, 1.07-2.58, P = 0.022), kidney cancer (SIR 2.87; 95% CI, 1.55-5.34, P < 0.001) and thyroid cancer (SIR 3.99; 95% CI, 2.32-6.87, P < 0.001). The exclusion of 11 cancers occurring before diagnosis of acromegaly (all in women) did not change remarkably the study outcome. In multivariate analysis, the factors significantly associated with an increased risk of malignancy were age and family history of cancer, with a non-significant trend for the estimated duration of acromegaly before diagnosis. In conclusion, we found evidence that acromegaly in Italy is associated with a moderate increase in cancer risk.

Association of craniopharyngioma and pituitary adenoma

Intracranial tumors of different histologic types infrequently affect patients with pituitary adenomas and no history of head irradiation. The association with craniopharyngioma is extremely rare. Aims of this paper are: (1) to provide a critical literature review of typical features of pituitary adenoma presenting in association with craniopharyngioma; (2) to describe the first documented (clinically, biochemically, histologically, and radiologically) case of aggressive, suprasellar papillary craniopharyngioma presenting with amenorrhea, progressive reduction of visual field, and severe headache in a 38-year-old woman, a decade after surgical cure for microprolactinoma associated with empty sella, during which she had carried two pregnancies; and (3) to discuss common etiopathogenetic mechanisms, in relation to the management of these lesions. Systematic literature search for English literature focusing on the association of craniopharyngioma and pituitary adenoma was performed using PubMed database. Additional relevant articles from references lists were also included. Clinical, laboratory, and radiological examinations performed in our patient for the two brain lesions at diagnosis and follow up were collected. Literature search retrieved nine articles. Typically, craniopharyngioma were of adamantinomatous type, occurred simultaneously to pituitary adenoma, presented with headache and visual loss, and affected men. No case of clearly documented metachronous lesion affecting a woman after pregnancy had been described before. Although very rare and with uncertain etiopathogenesis, second tumors (i.e., craniopharyngioma) should be considered in patients with a history of pituitary adenoma, presenting with suggestive signs and symptoms, even after a long disease-free period, in order to provide proper and prompt treatment.

Il ruolo della cabergolina nella patologia ipofisaria. Efficacia e tossicità

SommarioLa cabergolina è oggi ampiamente utilizzata nel trattamento di diverse malattie di origine ipofisaria, essendo dotata di un ottimo profilo di tollerabilità. Nel trattamento dei disturbi iperprolattinemici detiene il ruolo di terapia di prima linea con ottimi risultati nel controllo dei livelli ormonali, delle lesioni espansive sottostanti e dei sintomi ad essi correlati. Recenti lavori ne hanno anche sottolineato l’efficacia nel trattamento dell’acromegalia e della malattia di Cushing.

Cosa valutare nel paziente con tumore ipofisario appena operato

I disordini idro-elettrolitici da alterata secrezione di ormone antidiuretico (ADH), costituiti da diabete insipido (DI) e dalla più rara sindrome da inappropriata antidiuresi (SIAD), rappresentano le principali complicanze precoci (SIAD 5%, DI 25%). La SIAD è un eccesso di secrezione di ADH per danno alla neuroipofisi, agli assoni ipotalamici o indotta da farmaci e aumenta significativamente la mortalità dei pazienti. Il DI può presentarsi in forma parziale o completa, transitoria o persistente, in base al grado e al livello del danno

L’ipopituitarismo post trauma cranico: dall’età pediatrica all’età adulta

RiassuntoL’ipopituitarismo post trauma cranico nel soggetto adulto è un evento di frequente riscontro e le disfunzioni ormonali conseguenti al trauma possono contribuire ad una ripresa funzionale meno rapida o non completa del paziente dopo il trauma stesso. I dati relativi all’insorgenza di ipopituitarismo post trauma nell’età pediatrica, invece, sono estremamente disomogenei e ad oggi non è chiaro se le disfunzioni biochimiche evidenziate abbiano un effettivo impatto sulla salute del soggetto.