Partial tachyphylaxis to somatostatin (SST) analogues in a patient with acromegaly: the role of SST receptor desensitisation and circulating antibodies to SST analogues.
OBJECTIVE
Somatostatin (SST) analogues are a key option in the management of a variety of conditions, including acromegaly. Tachyphylaxis to SST analogues is not documented in acromegaly. We describe such a phenomenon.


METHODS
A 74-year-old female with acromegaly previously treated with (90)Y implant, external radiotherapy and thrice daily s.c. octreotide had stable GH levels of 19 mU/l. GH progressively rose following switches to lanreotide and depot octreotide as Sandostatin LAR: from 29 to 126 mU/l. Magnetic resonance imaging and (111)In-pentetreotide scanning revealed no tumour growth or alteration in SST receptor (SSTR) status. Tachyphylaxis to SST analogues was considered. Therapy was discontinued and re-introduced in daily 200 microg/24 h increments by continuous s.c. infusion, to a maximum of 1000 microg/24 h, and maintained over 3 weeks with daily, followed by weekly, GH profiles. Competitive (125)I-octreotide radioligand binding assays measured in vitro bio-activity of anti-SST analogue antibodies. In vitro SSTR binding studies utilised SSTR-expressing rat cortex membrane.


RESULTS
Median GH fell by 93% from 504 to 39.5 mU/l and rose reproducibly on continued infusion to 120 mU/l. Octreotide withdrawal for 16 h produced a 64% increase in sensitivity. High-affinity IgG anti-lanreotide (IC(50)=187 pmol/l) and anti-octreotide (IC(50)=82 nmol/l) antibody, with no crossreactivity with natural SST, was demonstrated. In vitro inhibition of (125)I-octreotide SSTR binding by anti-SST analogue crossreacting antibody was observed at 1:1 serum dilution.


CONCLUSIONS
This is the first report of tachyphylaxis to SST analogues in acromegaly. We believe that the short time course of resensitisation following acute octreotide withdrawal is suggestive of an effect(s) on receptor function or on the receptor signal transduction cascade at sites further downstream, rather than an immune-mediated phenomenon.
Wahid
Shahid T
ST
Endocrine Unit, Royal Victoria Infirmary, Newcastle Hospitals NHS Trust and University of Newcastle, Newcastle upon Tyne, NE1 4LP, UK.
Marbach
Peter
P
Stolz
Barbara
B
Miller
Margaret
M
James
Robert Andrew
RA
Ball
Steve G
SG
D000172:Acromegaly / Q000150:complications* / Q000188:drug therapy*; D000368:Aged; D000906:Antibodies / Q000097:blood*; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects* / Q000276:immunology / Q000627:therapeutic use*; D001667:Binding, Competitive / Q000187:drug effects; D005260:Female; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D008279:Magnetic Resonance Imaging; D015282:Octreotide / Q000009:adverse effects* / Q000276:immunology / Q000627:therapeutic use*; D010911:Pituitary Neoplasms / Q000150:complications / Q000473:pathology; D017481:Receptors, Somatostatin / Q000187:drug effects / Q000378:metabolism*; D013004:Somatostatin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000276:immunology; D013618:Tachyphylaxis / Q000502:physiology*; D013972:Thyrotropin / Q000097:blood
D000906:Antibodies; D018931:Antineoplastic Agents, Hormonal; D017481:Receptors, Somatostatin; D019382:Human Growth Hormone; D013004:Somatostatin; D013972:Thyrotropin; D015282:Octreotide