Combined therapy with somatostatin analogues and weekly pegvisomant in active acromegaly.

Pegvisomant monotherapy once daily returns concentrations of insulin-like growth factor I (IGF-I) to normal in most patients with acromegaly, but is very costly. In a 42-week dose-finding study, we assessed the efficacy of the combination of long-acting somatostatin analogues once monthly and pegvisomant once weekly in 26 patients with active acromegaly. Dose of pegvisomant was increased until IGF-I concentration became normal or until a weekly dose of 80 mg was reached. IGF-I reached normal concentrations in 18 of 19 (95%) patients who completed 42 weeks of treatment, with a median weekly dose of 60 mg pegvisomant (range 40-80). No signs of pituitary tumour growth were noted, but mild increases in liver enzymes were observed in ten patients (38%). This combined treatment is effective, might increase compliance, and could greatly reduce the costs of medical treatment for acromegaly in some patients.

['Hungry bone' syndrome, characterized by prolonged symptomatic hypocalcemia, as a complication of the treatment for hyperthyroidism]. / 'Hungry bone'-syndroom, gekenmerkt door langdurige symptomatische hypocalciëmie, als complicatie van behandeling wegens hyperthyreoïdie.

A 22-year-old woman presented with palpitations, agitation, heat intolerance and unintentional weight loss that had started several months before. Pharmacotherapy for hyperthyroidism was prescribed, but a year later thyroidectomy was performed in connection with a lack of treatment compliance. A few hours after the operation the patient developed a tingling sensation and muscle cramp, which were found to be due to severe hypocalcaemia. Although surgery was complicated by hypoparathyroidism, there was an unusually high need for calcium combined with a low calcium excretion in the urine. Such a high need for calcium due to the increased bone reconstruction induced by the hyperthyroidism is referred to as the hungry bone syndrome. One should be particularly alert to this complication in cases of severe, prolonged hyperthyroidism, certainly in the presence of existing or peroperatively induced damage to the parathyroids. In this patient, calcium suppletion led to normalisation of the serum calcium level two weeks postoperatively; she was discharged from the hospital in good condition after 3 weeks.

Clinical proteomics stretch goals: EuPA 2012 roundtable report.

The field of clinical proteomics is faced with multiple challenges which need to be overcome in order to improve our understanding of human diseases and provide management solutions. Researchers interested in clinical proteomics assembled for a roundtable discussion at the European Association for Proteomics (EuPA) conference held in Glasgow in July 2012, to discuss these challenges and highlight the key areas for successful clinical proteomic studies. This report shares topics of discussion and the resulting stretch goals of clinical proteomics for researchers to strive towards.

Increase in haemoglobin concentrations in growth hormone deficient adults during human recombinant growth hormone replacement therapy.

OBJECTIVE: Recombinant human growth hormone is being used increasingly in the treatment of GH deficiency in adults. In addition to erythropoietin, insulin-like growth factor-I (IGF-I) has been demonstrated to stimulate hematopoiesis in animals, especially rodents. We have determined the effect of growth hormone (GH) administration on haematopoiesis. PATIENTS AND DESIGN: Seventeen patients (10 males and 7 females; mean age 47 +/- 2 years; range 30-59) with biochemically proven adult-onset GH deficiency (GHD) were treated with human recombinant growth hormone (rhGH) as replacement therapy for more than 96 weeks in a dosage of 12.5 micrograms/kg/day (initial dosage during the first 4 weeks 6.25 micrograms/kg/day). The diagnosis of GHD had been confirmed using a standard arginine-infusion test (0.5 g/kg body weight). Blood samples were collected for safety and efficacy parameters before and during the GH treatment period. MEASUREMENTS: Routine methods were used for the haematological and biochemical measurements. IGF-I concentrations were measured, using a commercial RIA kit. RESULTS: From week 36 and onwards, we observed a significant increase in individual haemoglobin (Hb) concentrations, especially in the male patients. Mean Hb in the male patients before treatment amounted to 9.1 +/- 0.2 mmol/l (range 8.1-10.5) and increased by 0.93 +/- 0.2 mmol/l (P < 0.05) after 120 weeks of rhGH replacement therapy. The mean Hb concentration in female patients before treatment was 8.1 +/- 0.1 mmol/l and an increase of 0.32 +/- 0.1 mmol/l (P < 0.05) was observed after 120 weeks. For all 17 patients the mean increase in Hb after 120 weeks was 0.73 +/- 0.2 mmol/l (P < 0.05). IGF-I concentrations also increased during therapy from 86 +/- 9 pg/l to 253 +/- 26 pg/l within 24 weeks (P < 0.05). No significant changes in leucocyte or platelet counts were found. CONCLUSIONS: Long-term replacement therapy with rhGH in patients with adult-onset GHD induces a significant increase in Hb concentrations, while serum leucocyte and platelet counts do not change.