Cabergoline in acromegaly: a renewed role for dopamine agonist treatment?

OBJECTIVE AND DESIGN: Eighteen active acromegalics entered a prospective open study with cabergoline (CAB), a dopaminergic drug much more potent than bromocriptine (Br). METHODS: CAB was administered for 6 months at doses ranging between 0.5 mg twice weekly and 0.5 mg/day. Clinical-anamnestic characteristics of the patients were: (i) sensitivity to dopamine agonist drugs (10 patients); (ii) resistance to somatostatin analogs (SAs) (8 patients): (iii) intolerance to SA (3 patients). In 2 patients marked hyperprolactinemia was present. RESULTS: Basal GH was 6.6 microg/l (2.2-50) (median (range)), and on treatment it was 3.5 microg/l (1.2-34) (P=0.013). The corresponding IGF-I values were 720 microg/l (410-1438) and 375 microg/l (167-1260) respectively (P=0.00001). Individual GH levels decreased below 2 microg/l in 5 patients, and between 2 and 5 microg/l in another 5 patients. IGF-I levels were suppressed below 50% of baseline in 8 patients and normal age-adjusted IGF-I values were reached in 5 patients (27% of the series). The retrospective comparison with previous chronic treatment with Br in the 10 suitable patients showed a greater effectiveness of CAB (IGF-I decrease on CAB treatment, 46.8%, on Br treatment, 31%, P=0.02). Adenoma shrank in the 3 patients whose pituitary imaging was repeated during CAB. CONCLUSIONS: These results envisage that CAB may represent a worthy therapeutic tool in acromegalic patients, inducing a degree of IGF-I and GH suppression comparable to SAs, administered by the oral route and much less expensive.

Effects of tamoxifen on GH and IGF-I levels in acromegaly.

Tamoxifen (TAM), a non steroid partially competitive antagonist to the estrogen receptors, has been reported to decrease plasma GH and IGF-I levels both in vitro and in vivo. These data prompted us to evaluate GH and IGF-I changes in acromegaly after acute and chronic TAM administration. Nineteen acromegalic patients (6 M, 13 F, aged 30-70 years) were studied in a prospective open study. Acute TAM test (20 mg po) did not induce any significant change in GH and IGF-I levels. Chronic TAM treatment (20 mg/day for a month and 40 mg/day for another month) induced a transient increase in GH levels (from 9 [3-139] micrograms/l [median, range] to 12 [3-188] micrograms/l, p = 0.0025) and a persistent decrease in IGF-I levels (from 785 [500-1200] micrograms/l to 553 [209-1420] micrograms/l, p = 0.0034). Individual IGF-I values decreased in 13 patients and reached the normal range in 4 of them. At TAM withdrawal hormonal levels increased up to pretreatment values. There was no correlation between GH and IGF-I changes and results were not influenced by age, sex or gonadal status. In this setting it is likely that the observed decrease in plasma IGF-I levels is dependent on TAM activity at the hepatic level.

Experience with hair testing in the clinical biochemistry laboratory of Ca' Granda Niguarda Hospital, Milan, Italy.

In our laboratory, analysis of human hair for drugs of abuse detection was first performed in 1980. In the last 10 years we have processed about 2000 subjects/year ('living subjects' only). In the last 3 years we have also introduced hair analysis of cocaine: at first only in clinical applications, but for the last 2 years this analysis is now routine. Our application of hair analysis includes: clinical toxicology, medico-legal and administrative agencies. Requests come for example from several Committees for Driving Licenses, Addiction Treatment Centers and Legal Authorities. Hair samples are currently collected from the occipital area at the back of the head, which appears to show less variability in hair growth rate. At present we perform hair analysis using highly sensitive radioimmunoassay screening methods for the detection of parent drug and/or metabolites. All positive cases of cocaine and opiates abuse are confirmed by gas chromatography-mass spectrometry in electron impact or chemical ionization mode. Positive cases for opiates are also analysed using a specific morphine radioimmunoassay kit. Data show that, when the opiates/morphine ratio is higher than 6, we are dealing with consumption of codeine and/or dihydrocodeine. In our routine work last year there were 177 (263 samples) positive opiates subjects out of 2244 patients; positive cocaine subjects were 290 (362 samples) out of 2001 patients. Guidelines for hair analysis in Lombardia have been established based on the experience of our laboratory. Furthermore it will be possible to apply a unique protocol for all Committees for Driving Licenses, involving hair testing in addition to urine assay.