gps Mutations in Chilean Patients Harboring Growth Hormone-Secreting Pituitary Tumors

Abstract

Hypersecretion of GH is usually caused by a pituitary adenoma and about 40% of these tumors exhibit missense gsp mutations in Arg201 or Gln227 of the Gs, gene. We studied 20 pituitary tumors obtained from patients with GH hypersecretion. One tumor was resected from an 11 year-old boy with a 3 year history of accelerated growth, associated with increased concentrations of serum GH and IGF-I, which were not suppressed by glucose administration. The remaining 19 tumors were obtained from adult acromegalic patients, who had elevated baseline serum GH levels that did not show evidence of suppression after administration of glucose. The gsp mutations were studied by enzymatic digestion of the amplified PCR fragment of exon 8 (Arg201) and exon 9 (Gln227) with the enzymes NlaIII and NgoAIV, respectively. The tumors obtained from the boy and from nine of the 19 patients with acromegaly exhibited the gsp mutation R201H. None of the tumors had the Gln227 mutation. The gsp positive patients tended to be older, had smaller tumors, and had preoperative basal serum GH levels which were significantly lower (21 +/- 6 vs 56 +/- 16 microg/l, p<0.05) than the gsp negative patients. In this study, we documented the presence of a gsp mutation in Arg201 in a boy with gigantism and in approximately half of 19 Chilean adult patients with acromegaly, similar to other populations.

Prevalence of gsp oncogene in somatotropinomas and clinically non-functioning pituitary adenomas: our experience

“…Regarding the somatotropinomas, the prevalence of gsp we found is lower than the expected 40%, considering previous series from several countries in the literature [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25]. The reason for such a low prevalence in our series is unknown.…”

“…The finding that our gsp+ patients had higher tumor diameter than gsp-patients is not in accordance with the previously described in the literature. The previous series evidenced that gsp+ tumors were smaller [7,13,17,19] or not different in size [11,12,16] from the gsp-tumors. However, in only three of our gsp+ patients the information of the tumor diameter was available, making our finding difficult to be taken into account at this point.…”

“…However, none of these findings reached statistical significance, probably because of the small number of gsp+ patients. Prior studies have found preoperative GH levels to be lower [7,17], higher [15,26] or the same [11,12,16,18,22,23] in the gsp+ patients, being difficult to make any definitive statement on this subject. The finding that our gsp+ patients had higher tumor diameter than gsp-patients is not in accordance with the previously described in the literature.…”

“…The results of these studies are summarized in Table 1. In the majority of the series, approximately 40% of the patients present a mutation [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25]. Only four studies assessed the prevalence of the gsp oncogene in NFPA which is around ten percent [5,6,18,20].…”

Growth hormone- secreting pituitary adenomas: from molecular basis to treatment options in acromegaly

“…Patients in the mutation positive group went to surgery with smaller tumors and had lower GH levels. 22 Other studies found lower, 23 higher 24,25 or the same GH levels in the mutation positive group. [26][27][28][29][30][31][32] G-protein mutations occur frequently in somatotrophs, 25 and tumors carrying these mutations are more susceptible to inhibition of GH secretion by somatostatin analogs, such as octreotide.…”