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 \uc2\ub1 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

Occult leydig cell tumour and androgen-receptor positive breast cancer in a woman with severe hyperandrogenism

Leydig cell tumours represent more than 75% of all testosterone-secreting ovarian masses. These benign tumours are frequently occult or very small, but cause dramatic virilization. Chronic hyperandrogenism can also induce systemic complications, which increase morbidity and mortality risk. One of the most obvious effects of increased testosterone levels is polycythemia, a complication which induces dermatologic, osteoarticular and gastrointestinal manifestations and is associated with increased thrombotic risk. However, scientific literature reports few data concerning etiopathogenesis and management of polycythemia in patients with Leydig cell tumours. Moreover, no data are available about the effect of androgen excess on other concomitant tumours expressing androgen receptors. In this paper we report for the first time the case of a woman, with previous infertility, dramatic virilisation and chronic erythrocytosis, who was affected by an occult Leydig cell tumour and an androgen receptor positive breast cancer. This association gives us the opportunity to discuss the role of the steroid receptor expression of breast cancer in the presence of circulating androgen excess. Moreover, we demonstrate for the first time that treatment with flutamide (anti-androgen drug) is able to normalize blood cell count and haematocrit, before of achieving the definitive cure of hyperandrogenism by oophorectomy

Analysis of BclI, N363S and ER22/23EK polymorphisms of the glucocorticoid receptor gene in adrenal incidentalomas

CONTEXT: Patients with adrenal incidentalomas (AI) may experience detrimental consequences due to a minimal cortisol excess sustained by adrenal adenoma. SNPs of the glucocorticoid receptor gene (NR3C1) modulate individual sensitivity to glucocorticoids and may interfere with the clinical presentation. ----- OBJECTIVE: To compare the frequency of N363S, ER22/23EK and BclI SNPs in patients with AI with the general population and to evaluate whether these SNPs are linked to consequences of cortisol excess. ----- SETTING: Multicentric, retrospective analysis of patients referred from 2010 to 2014 to 4 centers (Orbassano, Milano, Messina [Italy] and Zagreb [Croatia]). ----- PATIENTS: 411 patients with AI; 153 males and 258 females and 186 from blood donors. ----- MAIN OUTCOMES MEASURES: All patients and controls were genotyped for BclI, N363S and ER22/23EK and SNPs frequency was associated with clinical and hormonal features. ----- RESULTS: SNP frequency was: SNP frequency was: N363S 5.4% (MAF 0.027), BclI 54.7% (MAF 0.328), ER22/23EK 4.4% (MAF 0.022), without any significant difference between patients and controls. N363S was more frequent in hypertensive patients (p = 0.03) and was associated with hypertension (p = 0.015) in patients with suppressed cortisol after the 1-mg DST. ----- CONCLUSIONS: Our results demonstrate that SNPs of the glucocorticoid receptor gene do not play a pathogenetic role for AI. The impact of any single SNP on the phenotypic expression of minimal cortisol excess is limited and their analysis does not provide additional data that may be exploited for patient management

Effects of cyberknife radiotherapy treatment of pituitary adenomas

none11nononePuglisi, Soraya; Cotta, Oana Ruxandra; Conti, Alfredo; Pontoriero, Antonio; Messina, Erika; Albani, Adriana; Ferrau, Francesco; Ragonese, Marta; Torre, Maria Luisa; Angileri, Flavio; Cannavo, SalvatorePuglisi, Soraya; Cotta, Oana Ruxandra; Conti, Alfredo; Pontoriero, Antonio; Messina, Erika; Albani, Adriana; Ferrau, Francesco; Ragonese, Marta; Torre, Maria Luisa; Angileri, Flavio; Cannavo, Salvator

Effects on glucose metabolism of high-dose octreotide LAR in patients with acromegaly inadequately controlled by conventional somatostatin analog therapy

The effects of conventional somatostatin analog (SSA) regimens on glucose homeostasis seem to have minor clinical impact in acromegaly. Recently, we performed a trial showing that high dose octreotide LAR significantly reduces IGF1 in acromegalic patients uncontrolled with conventional SSA doses. In this post-hoc analysis, we evaluated the effects of high doses versus high frequency octreotide LAR on glucose homeostasis (HbA1c, FPG, HOMA-R) in patients with acromegaly enrolled in this trial. After approval by ethical committee and informed consent, 26 patients (14 F, 12 M, median age 51 years, range: 27–78) with uncontrolled acromegaly were randomly treated with high-dose (11 patients: 60 mg/28 days) or high-frequency (15 patients: 30 mg/21 days) octreotide LAR for 6 months. At study entry, seven patients had diabetes mellitus and eight impaired fasting glucose (IFG). After 6-month treatment, glucose metabolism was impaired in six patients (23.1%), improved in two patients (7.7%) and unchanged in the remaining 18 patients (69.2%). Rate of impairment in glucose homeostasis was similar in high doses versus high frequency octreotide LAR (27.3 vs 20.0%; P=0.44). In all six patients with impaired glucose homeostasis, serum IGF1 and/or GH values remained high during treatment, whereas significant decrease (>20%) in serum IGF-I or GH values was observed in 75% of patients in whom glucose homeostasis did not impair (P=0.03). Impairment of glucose homeostasis occurred in 26.7% of patients with pre-existing diabetes mellitus or IFG and in 18.2% of patients with pre-existing normal glucose metabolism (P=0.35). In conclusion, the increase in octreotide LAR doses or frequency did not produce negative effects on glucose metabolism in the majority of patients. In the minority of patients who experienced impairment of glucose homeostasis, this event occurred more frequently in those with persistently uncontrolled acromegaly and it seems to be not dependent on the pre-existing abnormalities of glucose metabolism

Correlation between clinical variables and the N363S, Bcl1, ER22/23EK haplotypes, in patients with adrenal incidentalomas.

<p>Correlation between clinical variables and the N363S, Bcl1, ER22/23EK haplotypes, in patients with adrenal incidentalomas.</p

Multiple regression analysis with Firth correction.

<p>Multiple regression analysis with Firth correction.</p