Combined treatment with octreotide LAR and pegvisomant in patients with pituitary gigantism: clinical evaluation and genetic screening.
BACKGROUND
Pituitary gigantism is a rare condition caused by growth hormone secreting hypersecretion, usually by a pituitary tumor. Acromegaly and gigantism cases that have a genetic cause are challenging to treat, due to large tumor size and poor responses to some medical therapies (e.g. AIP mutation affected cases and those with X-linked acrogigantism syndrome).


METHODS
We performed a retrospective study to identify gigantism cases among 160 somatotropinoma patients treated between 1985 and 2015 at the University Hospital of Caracas, Venezuela. We studied clinical details at diagnosis, hormonal responses to therapy and undertook targeted genetic testing. Among the 160 cases, eight patients (six males; 75 %) were diagnosed with pituitary gigantism and underwent genetic analysis that included array comparative genome hybridization for Xq26.3 duplications.


RESULTS
All patients had GH secreting pituitary macroadenomas that were difficult to control with conventional treatment options, such as surgery or primary somatostatin receptor ligand (SRL) therapy. Combined therapy (long-acting SRL and pegvisomant) as primary treatment or after pituitary surgery and radiotherapy permitted the normalization of IGF-1 levels and clinical improvement. Novel AIP mutations were the found in three patients. None of the patients had Xq26.3 microduplications.


CONCLUSIONS
Treatment of pituitary gigantism is frequently challenging; delayed control increases the harmful effects of GH excess, such as, excessive stature and symptom burden, so early diagnosis and effective treatment are particularly important in these cases.
Section of Neuroendocrinology, Department of Neurosurgery, Hospital Universitario de Caracas, Caracas, Venezuela. nenhuc@gmail.com.
Ruth
R
Mangupli
Department of Endocrinology, Centre Hospitalier Universitaire de Liège, University of Liège, Domaine Universitaire du Sart-Tilman, 4000, Liège, Belgium.
Liliya
L
Rostomyan
Department of Human Genetics, Centre Hospitalier Universitaire de Liège, University of Liège, Domaine Universitaire du Sart-Tilman, 4000, Liège, Belgium.
Emilie
E
Castermans
Department of Human Genetics, Centre Hospitalier Universitaire de Liège, University of Liège, Domaine Universitaire du Sart-Tilman, 4000, Liège, Belgium.
Jean-Hubert
JH
Caberg
Section of Neuroendocrinology, Department of Neurosurgery, Hospital Universitario de Caracas, Caracas, Venezuela.
Paul
P
Camperos
Section of Neuroendocrinology, Department of Neurosurgery, Hospital Universitario de Caracas, Caracas, Venezuela.
Jaime
J
Krivoy
Section of Neuroendocrinology, Department of Neurosurgery, Hospital Universitario de Caracas, Caracas, Venezuela.
Elvia
E
Cuauro
Department of Human Genetics, Centre Hospitalier Universitaire de Liège, University of Liège, Domaine Universitaire du Sart-Tilman, 4000, Liège, Belgium.
Vincent
V
Bours
Department of Endocrinology, Centre Hospitalier Universitaire de Liège, University of Liège, Domaine Universitaire du Sart-Tilman, 4000, Liège, Belgium.
Adrian F
http://orcid.org/0000-0001-6130-2975
AF
Daly
Department of Endocrinology, Centre Hospitalier Universitaire de Liège, University of Liège, Domaine Universitaire du Sart-Tilman, 4000, Liège, Belgium. albert.beckers@chu.ulg.ac.be.
Albert
A
Beckers
D000293:Adolescent; D000328:Adult; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005877:Gigantism / Q000188:drug therapy* / Q000235:genetics; D019382:Human Growth Hormone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008297:Male; D015282:Octreotide / Q000627:therapeutic use*; D012189:Retrospective Studies; D055815:Young Adult
D018931:Antineoplastic Agents, Hormonal; D047908:Intracellular Signaling Peptides and Proteins; C103265:aryl hydrocarbon receptor-interacting protein; D019382:Human Growth Hormone; C406545:pegvisomant; D015282:Octreotide
AIP; Gigantism; Pegvisomant; Somatostatin receptor ligand; Somatotropinoma; X-LAG syndrome