AIP-mutated acromegaly resistant to first-generation somatostatin analogs: long-term control with pasireotide LAR in two patients.

Daly, Adrian; Rostomyan, Liliya; Betea, Daniela; Bonneville, Jean Francois; Villa, Chiara; Pellegata, Natalia S; Waser, Beatrice; Reubi-Kattenbusch, Jean-Claude; Waeber Stephan, Catherine; Christ, Emanuel; Beckers, Albert (2019). AIP-mutated acromegaly resistant to first-generation somatostatin analogs: long-term control with pasireotide LAR in two patients. Endocrine Connections, 8(4), pp. 367-377. BioScientifica 10.1530/EC-19-0004

[img]
Preview
Text
[20493614 - Endocrine Connections] AIP-mutated acromegaly resistant to first-generation somatostatin analogs_ long-term control with pasireotide LAR in two patients.pdf - Published Version
Available under License Creative Commons: Attribution-Noncommercial-No Derivative Works (CC-BY-NC-ND).

Download (1MB) | Preview

Acromegaly is a rare disease due to chronic excess growth hormone (GH) and IGF-1. Aryl hydrocarbon receptor interacting protein (AIP) mutations are associated with an aggressive, inheritable form of acromegaly that responds poorly to SST2-specific somatostatin analogs (SSA). The role of pasireotide, an SSA with affinity for multiple SSTs, in patients with AIP mutations has not been reported. We studied two AIP-mutation positive acromegaly patients with early-onset, invasive macroadenomas and inoperable residues after neurosurgery. Patient 1 came from a FIPA kindred and had uncontrolled GH/IGF-1 throughout 10 years of octreotide/lanreotide treatment. When switched to pasireotide LAR, he rapidly experienced hormonal control and was associated with marked regression of his tumor residue. Pasireotide LAR was stopped after >10 years due to low IGF-1 and he maintained hormonal control without tumor regrowth for >12 months off pasireotide LAR. Patient 2 had disease onset aged 17 that was not cured by surgery. Chronic pasireotide LAR therapy produced hormonal control and marked tumor shrinkage but control was lost when switched to octreotide. Tumor immunohistochemistry showed absent AIP and SST2 staining and positive SST5. Her AIP-mutation positive sister developed a 2.5 cm follicular thyroid carcinoma aged 21 with tumoral loss of heterozygosity at the AIP locus and absent AIP. Patients 1 and 2 required multi-modal therapy to control diabetes. On stopping pasireotide LAR after >10 years of treatment, Patient 1's glucose metabolism returned to baseline levels. Long-term pasireotide LAR therapy can be beneficial in some AIP-mutation positive acromegaly patients that are resistant to first-generation SSA.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology

UniBE Contributor:

Reubi-Kattenbusch, Jean-Claude

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

2049-3614

Publisher:

BioScientifica

Language:

English

Submitter:

Christa Hagert

Date Deposited:

20 Aug 2019 12:23

Last Modified:

19 Feb 2020 15:04

Publisher DOI:

10.1530/EC-19-0004

PubMed ID:

30851160

BORIS DOI:

10.7892/boris.132179

URI:

https://boris.unibe.ch/id/eprint/132179

Actions (login required)

Edit item Edit item
Provide Feedback