AIP-mutated acromegaly resistant to first-generation somatostatin analogs: long-term control with pasireotide LAR in two patients
- Daly, Adrian F 1Department of Endocrinology, Centre Hospitalier Universitaire (CHU) de Liège, Liège Université, Domaine Universitaire du Sart-Tilman, Liège, Belgium
- Rostomyan, Liliya 1Department of Endocrinology, Centre Hospitalier Universitaire (CHU) de Liège, Liège Université, Domaine Universitaire du Sart-Tilman, Liège, Belgium
- Betea, Daniela 1Department of Endocrinology, Centre Hospitalier Universitaire (CHU) de Liège, Liège Université, Domaine Universitaire du Sart-Tilman, Liège, Belgium
- Bonneville, Jean-François 1Department of Endocrinology, Centre Hospitalier Universitaire (CHU) de Liège, Liège Université, Domaine Universitaire du Sart-Tilman, Liège, Belgium
- Villa, Chiara 2Department of Pathological Cytology and Anatomy, Foch Hospital, Paris, France
- Pellegata, Natalia S 3Institute for Diabetes and Cancer, Helmholtz Zentrum München, Neuherberg, Germany
- Waser, Beatrice 4Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, University of Bern, Bern, Switzerland
- Reubi, Jean-Claude 4Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, University of Bern, Bern, Switzerland
- Waeber Stephan, Catherine 5Clinique Générale Ste-Anne, Fribourg, Switzerland
- Christ, Emanuel 6Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel, University of Basel, Basel, Switzerland
- Beckers, Albert 1Department of Endocrinology, Centre Hospitalier Universitaire (CHU) de Liège, Liège Université, Domaine Universitaire du Sart-Tilman, Liège, Belgium
Published in:
- Endocrine Connections. - Bioscientifica. - 2019, vol. 8, no. 4, p. 367-377
English
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 which 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 >18 months off pasireotide LAR. Patient 2 had a pituitary adenoma diagnosed when 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 staining. 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.
- Language
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- English
- Open access status
- gold
- Identifiers
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- DOI 10.1530/ec-19-0004
- ISSN 2049-3614
- Persistent URL
- https://sonar.ch/global/documents/33783
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