Cabergoline addition to depot somatostatin analogues in resistant acromegalic patients: efficacy and lack of predictive value of prolactin status.
BACKGROUND
Somatostatin analogues (SA) are currently the mainstay in the medical treatment of acromegaly. However, even high doses of depot SA for prolonged periods do not achieve GH-IGF-I normalization in some patients. Even though some data were reported about the addition of cabergoline, a long-acting dopamine agonist (DA), to SA in resistant patients, definite data are still lacking.


METHODS
Prospective open trial.


METHODS
In 19 acromegalic patients with active disease (34-82 years old, seven males, 12 females) resistant to chronic (9-12 months) depot SA (octreotide-LAR, 30 mg/28 days in 13 patients, lanreotide, 60 mg/28 days intramuscularly in six patients) cabergoline was added (combined treatment). In these patients, SA treatment had partially relieved GH and IGF-I hypersecretion but no patient had achieved 'safe' GH and normal IGF-I-values. Eight patients had PRL levels greater than 15 micro g/l (range 16-60 micro g/l; 1 micro g = 21.2 mIU). Immunohistochemistry (IHC) was positive for PRL in four out of eight operated patients.


RESULTS
The addition of cabergoline, using the minimal effective and the maximal tolerated dose (range 1-3.5 mg/week), decreased GH from 6.6 +/- 0.9 to 4.6 +/- 0.6 micro g/l (P = 0.018), and IGF-I from 552 +/- 44 to 428 +/- 54 micro g/l (P = 0.019) after 6 months (median, range 3-18 Months). Combined treatment decreased GH to < 2.5 micro g/l in four patients (21%) and normalized IGF-I for age in eight patients (42%). It obtained a decline of both GH and IGF-I (-49 +/- 7%, and -47 +/- 5%, respectively) in nine patients (47%), and a partial improvement in six (32%) patients (GH decreased by 43 +/- 8% in four, and IGF-I by 35-38% in two patients). No change was observed in two patients, and worsening in two other patients. Results were not dependent on PRL status (serum levels or IHC). Combined treatment was well tolerated.


CONCLUSIONS
The addition of cabergoline to depot SA-resistant acromegalic patients is effective, not dependent on PRL values and normalizes IGF-I levels in 42% of patients. The association of long-acting DA and SA deserves a more relevant role in the therapeutical algorithm of acromegaly.
Division of Endocrinology, Ospedale Niguarda, Carlo Besta Institute, Milan, Italy. renatocozzi@tiscali.it
Renato
R
Cozzi
Roberto
R
Attanasio
Sandro
S
Lodrini
Giovanni
G
Lasio
D000172:Acromegaly / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077465:Cabergoline; D003692:Delayed-Action Preparations / Q000009:adverse effects / Q000627:therapeutic use; D018491:Dopamine Agonists / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D004873:Ergolines / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005765:Gastrointestinal Agents / Q000009:adverse effects / Q000627:therapeutic use; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D015282:Octreotide / Q000009:adverse effects / Q000627:therapeutic use; D010456:Peptides, Cyclic / Q000009:adverse effects / Q000627:therapeutic use; D011388:Prolactin / Q000097:blood; D011446:Prospective Studies; D013004:Somatostatin / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use
D003692:Delayed-Action Preparations; D018491:Dopamine Agonists; D004873:Ergolines; D005765:Gastrointestinal Agents; D010456:Peptides, Cyclic; C060347:lanreotide; D019382:Human Growth Hormone; D013004:Somatostatin; D007334:Insulin-Like Growth Factor I; D011388:Prolactin; D000077465:Cabergoline; D015282:Octreotide