The aim of this study was to verify whether treatment with slow-release lanreotide
(SRL) before surgery is useful in the management of patients with GH-secreting pituitary
macroadenoma. Twenty untreated acromegalics were enrolled randomly in two groups.
Ten patients (group 1: 2 males and 8 females aged 44.5 ± 4.3 years) underwent surgery
via transsphenoidal access. Only one of them was cured by surgery, whereas the other
nine were treated with SRL. In the other ten patients (group 2: 3 males and 7 females
aged 43.2 ± 12.3 years), transsphenoidal surgery followed SRL treatment. Surgery induced
the normalization of GH and IGF-1 levels in four group 2 patients - three of them
had shown an evident shrinkage of the tumor after SRL treatment. After surgery, group
1 showed a significant decrease of mean IGF-1 (580 ± 63 vs. 789 ± 64 ng/ml, p < 0.02),
but not of GH values (26.1 ± 9.8 vs. 44.8 ± 19.3 ng/ml, NS); the cured patient was
excluded from the following evaluations. Group 2 showed an evident, but not significant,
decrease of both GH and IGF-1 values compared to values measured at the end of medical
treatment (GH: 22.4 ± 9.7 vs. 7.7 ± 4.7 ng/ml, NS. IGF-1: 570 ± 69 vs. 402 ± 58 ng/ml,
NS). Gonadal, thyroid and adrenal impairment was evident in six, four and no patients
in group 1 and in three, two and one patients in group 2, respectively. SRL 30 mg
was administered every 14 days for three months and then every 10 days until the 6th
month. Before SRL treatment, mean GH and IGF-1 levels did not differ significantly
in group 1 vs. group 2 (GH: 29.3 ± 10.5 vs. 43.4 ± 22.0 ng/ml; IGF-1: 633 ± 38 vs.
778 ± 83 ng/ml). In group 1, a significant decrease of serum GH, but not of IGF-1
levels, was achieved at the end of 1st trimester of SRL (GH: 17.6 ± 5.4 ng/ml, p <
0.05. IGF-1: 540 ± 48 ng/ml, NS), whereas a significant decrease in both GH and IGF-1
values was evident during the 2nd trimester (GH: 6.1 ± 3.0 ng/ml, p < 0.05. IGF-1:
433 ± 74 ng/ml, p < 0.02). Serum GH levels, measured during the 2nd trimester of SRL
therapy, were also significantly lower than levels measured at the end of the 1st
trimester (p < 0.05). Group 2 serum GH and IGF-1 levels were not significantly decreased
at the end of the 1st trimester (GH: 27.2 ± 12.1 ng/ml, NS. IGF-1: 698 ± 74 ng/ml,
NS), whereas only serum IGF-1 (570 ± 69 ng/ml, p < 0.05) was significantly reduced
during the 2nd trimester of SRL (GH: 22.4 ± 9.7 ng/ml, NS). Serum GH and IGF-I fell
in the normal range in 4 patients in group 1 and one in group 2 at the end of the
second trimester of SRL therapy. Independently of the trial applied, the mean clinical
score level ameliorated significantly in both groups (group 1: p < 0.0005; group 2:
p < 0.0001). In both groups, the proportion of patients complaining of headache and
tissue swelling and the score level of headache, tissue swelling and excessive sweating
decreased significantly. In group 1 the score level of fatigue and arthralgia also
decreased significantly. In conclusion, this study proves that in patients with GH-secreting
pituitary macroadenoma: (i) surgery followed by SRL induces a better clinical and
biochemical status than SRL alone; (ii) SRL treatment before surgery ameliorates the
clinical and biochemical outcome and reduces the prevalence of hypopituitarism due
to surgery.
Key words:
Acromegaly - Growth Hormone - Somatostatin Analogs
References
- 1
Freda P U, Wardlaw S L, Post K D.
Long-term endocrinological follow-up evaluation in 115 patients who underwent transsphenoidal
surgery for acromegaly.
J Neurosurg.
1998;
89
353-358
- 2
Melmed S, Jackson I, Kleinberg D, Klibanski A.
Current treatment guidelines for acromegaly.
J Clin Endocrinol Metab.
1998;
83
2646-2652
- 3
Plockinberger U, Reichel M, Fett U, Saeger W, Quabbe H J.
Preoperative octreotide treatment of growth hormone-secreting and clinically nonfunctioning
pituitary macroadenomas: effect on tumor volume and lack of correlation with immunohistochemistry
and somatostatin receptor scintigraphy.
J Clin Endocrinol Metab.
1994;
79
1416-1423
- 4
Cannavò S, Curtò L, Squadrito S, Almoto B, Vieni A, Trimarchi F.
Cabergoline as first-choice treatment in PRL-secreting pituitary adenomas.
J Endocrinol Invest.
1999;
22
354-359
- 5
Newman C B, Melmed S, George A, Torigian D, Duhaney M, Snyder P, Young W, Klibanski A,
Molitch M E, Gagel R, Sheeler L, Cook D, Malarkey W, Jackson I, Vance M L, Barkan A,
Frohman L, Kleinberg D.
Octreotide as primary therapy for acromegaly.
J Clin Endocrinol Metab.
1998;
83
3034-3040
- 6
Colao A, Ferone D, Cappabianca P, del Basso De Caro M L, Marzullo P, Monticelli A,
Alfieri A, Merola B, Calì A, de Divitiis E, Lombardi G.
Effect of octreotide pretreatment on surgical outcome in acromegaly.
J Clin Endocrinol Metab.
1997;
82
3308-3314
- 7
Wasko R, Ruchala M, Sawicka J, Kotwicka M, Liebert W, Sowinski J.
Short-term pre-surgical treatment with somatostatin analogues, octreotide and lanreotide,
in acromegaly.
J Endocrinol Invest.
2000;
23
12-18
- 8
Biermasz N R, van Dulken H, Roelfsema F.
Direct postoperative and follow-up results of transsphenoidal surgery in 19 acromegalic
patients pretreated with octreotide compared to those in untreated matched controls.
J Clin Endocrinol Metab.
1999;
84
3551-3555
- 9
Losa M, Mortino P, Giovanelli M.
Is presurgical treatment with somatostatin analogs necessary in acromegalic patients?.
J Endocrinol Invest.
1999;
22
871-873
- 10
Heron I, Thomas F, Dero M, Gancel A, Ruiz J M, Schatz B, Kuhn J M.
Pharmacokinetics and efficacy of a long-acting formulation of the new somatostatin
analog BIM 23 014 in patients with acromegaly.
J Clin Endocrinol Metab.
1993;
76
721-727
- 11
Melmed S.
Tight control of growth hormone: an attainable outcome for acromegaly treatment.
J Clin Endocrinol Metab.
1998;
83
3409-3410
- 12
Abosch A, Tyrrel J B, Lamborn K R, Hannegan L T, Applebury C B, Wilson C B.
Transsphenoidal microsurgery for growth hormone-secreting pituitary adenomas: initial
outcome and long-term results.
J Clin Endocrinol Metab.
1998;
83
3411-3418
- 13
Swearingen B, Barker F G, Katznelson L, Biller B MK, Grinspoon S, Klibanski A, Moayeri N,
Black P McL, Zervas N T.
Long-term mortality after transsphenoidal surgery and adjunctive therapy for acromegaly.
J Clin Endocrinol Metab.
1998;
83
3419-3426
- 14
Freda P U, Wardlaw S L.
Primary medical therapy for acromegaly.
J Clin Endocrinol Metab.
1998;
83
3031-3033
- 15
Giusti M, Gussoni G, Cuttica M, Giordano G, and the Italian Multicenter Slow Release
Lanreotide Study Group.
Effectiveness and tolerability of slow release lanreotide treatment in active acromegaly:
six-month report on an Italian multicenter study.
J Clin Endocrinol Metab.
1996;
81
2089-2097
- 16
al Maskari M, Gebbie J, Kendall-Taylor P.
The effect of a new slow-release, long-acting somatostatin analogue, lanreotide, in
acromegaly.
Clin Endocrinol.
1996;
45
415-421
- 17
Giusti M, Ciccarelli E, Dallabonzana D, Delitala G, Faglia G, Liuzzi A, Gussoni G,
Giordano G.
Clinical results of long-term slow-release lanreotide treatment of acromegaly.
Eu J Clin Ivest.
1997;
27
277-284
- 18
Caron P, Morange-Ramos I, Cogne M, Jaquet P.
Three year follow-up of acromegalic patients treated with intramuscular slow-release
lanreotide.
J Clin Endocrinol Metab.
1997;
82
18-22
- 19
Colao A, Marzullo P, Ferone D, Marino V, Pivonello R, Di Somma C, Di Sarno A, Giaccio A,
Lombardi G.
Effectiveness and tolerability of slow release lanreotide treatment in active acromegaly.
J Endocrinol Invest.
1999;
22
40-47
- 20
Suliman M, Jenkins R, Ross R, Powell T, Battersby R, Cullen D R.
Long-term treatment of acromegaly with the somatostatin analogue SR-lanreotide.
J Endocrinol Invest.
1999;
22
409-418
- 21
Legovini P, De Menis E, Billeci D, Conti B, Zoli P, Conte N.
111Indium-pentetreotide pituitary scintigraphy and hormonal responses to octreotide
in acromegalic patients.
J Endocrinol Invest.
1997;
20
424-428
Salvatore Cannavò, M.D.
Cattedra di Endocrinologia, Pad. H
Azienda Ospedaliera Universitaria “G. Martino”
Via Consolare Valeria, 1
98125, Messina
Italy
eMail: endocrinologi@hotmail.com