Control of pituitary adenoma cell proliferation by somatostatin analogs, dopamine agonists and novel chimeric compounds

The antisecretory effects of somatostatin (SRIH) and its analogs are widely recognized and provide the basis for treatment of hormonal hypersecretion in patients with pituitary adenomas, especially in the settings of acromegaly. Dopamine (DA) agonists have also been used for medical treatment of prolactin and/or GH hypersecretion, and recent evidence points to an even greater antisecretory effect for a chimeric molecule, having high affinity for both SRIH and DA receptors. Evidence for an antiproliferative effect of these compounds has also been provided. This review focuses on the antiproliferative effects of SRIH and its analogs, of DA and chimeric compounds on pituitary adenomas, and on the clinical consequences on tumor volume of pharmacological treatment of pituitary adenomas with these drug

Long-term low-dose tolvaptan efficacy and safety in SIADH

Purpose: Tolvaptan, a selective vasopressin V2-receptor antagonist, is approved for the treatment of SIADH-related hyponatremia, but its use is limited. The starting dose is usually 15 mg/day, but recent clinical experience suggests a lower starting dose (<15 mg/day) to reduce the risk of sodium overcorrection. However, long-term low-dose efficacy and safety has not been explored, so far. Aim of our study is to characterize safety and efficacy of long-term SIADH treatment with low-dose Tolvaptan. Methods: We retrospectively evaluated 11 patients receiving low-dose Tolvaptan (<15 mg/day) for chronic SIADH due to neurological, idiopathic and neoplastic causes. Plasma sodium levels were measured before and 1, 3, 5, 15 and 30 days after starting Tolvaptan and then at 3-month intervals. Anamnestic and clinical data were collected. Results: Mean time spanned 27.3 ± 29.8 months (range 6 months-7 years). Mean plasma sodium levels were within normal range 1, 3 and 6 months after starting Tolvaptan as well as after 1, 2, 3, 5 and 7 years of therapy. Neither osmotic demyelination syndrome nor overcorrection were observed. Plasma sodium levels normalization was associated with beneficial clinical effects. Neurological patients obtained seizures disappearance, improvement in neurological picture and good recovery from rehabilitation. Neoplastic patients were able to start chemotherapy and improved their general condition. Patients did not show hypernatremia during long-term follow-up and reported mild thirst and pollakiuria. Conclusions: The present study shows that long-term low-dose Tolvaptan is safe and effective in SIADH treatment. No cases of overcorrection were documented and mild side effects were reported

Malattia di Cushing e adenoma ipofisario multiclonale: la strana coppia

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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

Sindrome di McCune-Albright

Il capitolo descrive la sindrome di McCune-Albright (MAS) è una patologia complessa, classicamente definita dalla presenza di displasia scheletrica, macchie cutanee caffelatte e pubertà precoc, che comprende tuttavia diverse altre manifestazioni a carico dell’apparato endocrino (ipertiroidismo, eccesso di GH e PRL, sindrome di Cushing, perdita renale di fosfati con o senza rachitismo/osteomalacia

GH-IGF-I deficit

Il trattato rappresenta la sintesi dell’evoluzione delle scienze endocrinologiche e metaboliche da un punto di vista nuovo e inedito: non si tratta infatti di uno dei tanti manuali di medicina anti-aging, né di uno degli improbabili manifesti di più o meno verificate evidenze per invecchiare meglio.Sinossi deI capitolo GH-IGF-1: Il difetto di GH (GHD) nell’adulto è una sindrome clinica caratterizzata da alterazioni sfavorevoli della composizione corporea (aumento della massa grassa, riduzione della massa magra e della densità minerale ossea) e del profilo lipidico e da riduzione della capacità di esercizio fisico, del benessere psicofisico e della qualità di vita. Nell’anziano il GHD, conseguente ad alterazione organica del sistema ipotalamo-ipofisario, va differenziato dalla fisiologica riduzione della secrezione di GH e IGF-I. I livelli di IGF-I non sono sufficienti per la diagnosi di GHD; è richiesto un test di stimolo della secrezione di GH. Il più utilizzato in Italia, nell’adulto e nell’anziano, è quello con somministrazione endovenosa di GHRH e arginina. Il trattamento sostitutivo con GH nell’adulto migliora la composizione corporea, la capacità di esercizio e la qualità di vita, e riduce i fattori di rischio cardiovascolare. Tali effetti benefici possono essere osservati anche nel soggetto anziano, che necessita di dosi più basse e di un attento monitoraggio. Non è al momento stabilito se il trattamento sostitutivo con GH sia in grado di ridurre gli eventi e la mortalità cardiovascolare e il rischio di fratture. Non ci sono evidenze che tale trattamento possa incrementare il rischio d’insorgenza e/o recidiva di neoplasie

Terapia con GH in età adulta: problemi aperti

L''efficacia della terapia sostitutiva con Gh in età adulta è ampiamente dimostrata. Nell'articolo si discutono problemi tuttora aperti, quali le ripercussioni sul metabolismo glucidico ed il rischio di recidiva del tumore ipofisarioo l'insorgenza di seconda neoplasia