Dissociation between tumor shrinkage and hormonal response during somatostatin analog treatment in an acromegalic patient: preferential expression of somatostatin receptor subtype 3.
BACKGROUND
About a third of acromegalic patients is resistant to available SS analogs (SA), octreotide (OCT) and lanreotide (LAN). Such resistance is related to reduction of SS receptor (SSTR) density or to a different expression of SSTR subtypes. There are 5 known SSTR subtypes. SSTR2 and SSTR5 are usually expressed in GH-secreting pituitary tumors, and both SA bind preferentially to SSTR2 and, to a lesser extent, to SSTR5. We herein describe an acromegalic patient who presented impressive tumor shrinkage without hormonal normalization during primary therapy with SA.


METHODS
This 23-yr-old male acromegalic patient was treated with slow-release LAN (LAN-SR), 30 mg every 10 days for six months, followed by OCT-LAR, 30 mg every 28 days for an additional six months with a 75% tumor volume reduction but without GH and IGF-I normalization. Subsequently, he underwent pituitary surgery and expression of SSTR in the removed tumor was performed by real time RT-PCR by the 2-deltaCt method, using GAPDH as internal control. All PCR products were confirmed by automated sequencing.


RESULTS
SSTR expression revealed an unusual profile, with almost exclusively expression of SSTR3.


CONCLUSIONS
These unusual clinical and receptor subtypes profile suggest an important role of SSTR3 on tumor shrinkage. The low affinity of LAN and OCT for this SSTR subtype could be compensated by its high expression in this GH-secreting pituitary macroadenoma.
Casarini
A P
AP
Laboratory Cellular and Molecular Endocrinology (LIM25), Hospital of Clínicas, University of Sao Paulo Medical School, Sao Paulo, Brazil.
Pinto
E M
EM
Jallad
R S
RS
Giorgi
R R
RR
Giannella-Neto
D
D
Bronstein
M D
MD
D000172:Acromegaly / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000209:etiology; D000328:Adult; D015870:Gene Expression; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000097:blood / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy*; D019382:Human Growth Hormone / Q000097:blood*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D008297:Male; D015282:Octreotide / Q000627:therapeutic use*; D010456:Peptides, Cyclic / Q000627:therapeutic use*; D010902:Pituitary Gland / Q000000981:diagnostic imaging; D011859:Radiography; D017481:Receptors, Somatostatin / Q000378:metabolism*; D012074:Remission Induction / Q000379:methods; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000627:therapeutic use
D010456:Peptides, Cyclic; D017481:Receptors, Somatostatin; C103631:somatostatin receptor 3; C060347:lanreotide; D019382:Human Growth Hormone; D013004:Somatostatin; D007334:Insulin-Like Growth Factor I; D015282:Octreotide