G. Tamagno

Prolactinomas resistant to standard doses of cabergoline: a multicenter study of 92 patients

BACKGROUND Dopamine agonist resistance in prolactinoma is an infrequent phenomenon. Doses of cabergoline (CAB) of up to 2.0 mg/week are usually effective in controlling prolactin (PRL) secretion and reducing tumor size in prolactinomas. The clinical presentation, management, and outcome of patients that are not well controlled by such commonly used doses of CAB-resistant patients are poorly understood. DESIGN AND METHODS A multicenter retrospective study was designed to collect a large series of resistant prolactinoma patients, defined by uncontrolled hyperprolactinemia on CAB ≥2.0 mg weekly. RESULTS Ninety-two patients (50 F, 42 M) were analyzed. At diagnosis, most had macroprolactinomas (82.6%); males were significantly older than females (P=0.0003) and presented with a more aggressive disease. A genetic basis was identified in 12 patients. Thirty-six patients (39.1%) received only medical therapy, most underwent surgery (60.9%, including multiple interventions in 10.9%), and 14.1% received postoperative radiotherapy. Eight patients developed late CAB resistance (8.7%). The median maximal weekly dose of CAB (CAB(max/w)) was 3.5 mg (2.0-10.5). Despite a higher CAB(max/w) in patients treated with multimodal therapy (P=0.003 vs exclusive pharmacological treatment), a debulking effect of surgery was shown in 14 patients, with a higher rate of PRL control (P=0.006) and a significant reduction in CAB(max/w) (P=0.001) postoperatively. At last follow-up (median 88 months), PRL normalization and tumor disappearance were achieved in 28 and 19.9% of the patients respectively, with no significant sex-related difference observed in CAB(max/w) or disease control. Mortality was 4.8%, with four patients developing aggressive tumors (4.3%) and three a pituitary carcinoma (3.3%). CONCLUSION CAB-resistant prolactinomas remain a serious concern. Surgical debulking, newer therapeutic strategies, and early diagnosis of genetic forms could help to improve their outcome.

Current and future perspectives on Recombinant GH for the treatment of Obesity

The similarities between patients with untreated growth hormone (GH) deficiency and those with the cardiometabolic syndrome and the beneficial effects of recombinant human GH (rhGH) on body composition have led to the hypothesis that rhGH treatment may have utility in obesity. GH release is reduced in the setting of obesity, primarily due to hyperinsulinism and increased free fatty acid levels. We reviewed the outcomes of 23 clinical studies carried out between 1987 and 2006 that examined the effects of rhGH administration in the obese state. Typically, changes in overall body weight do not occur with rhGH therapy; however, assessment of body composition demonstrates reductions in visceral abdominal fat. Data on the effects of rhGH on lipid and carbohydrate metabolic profiles in obese patients are less clear-cut, with a subset of studies showing a beneficial effect and others a neutral effect. Given the increasing burden of obesity in the general population and the current paucity of effective therapies, it is useful to consider the data on rhGH and obesity from a clinical perspective to highlight potential treatment strategies that harness the somatotropic axis.