Endocrine Abstracts

JOINT3713

Introduction: Pituitary acrogigantism is a rare disease caused by chronic growth hormone (GH) hypersecretion usually from a pituitary adenoma that occurs during childhood/adolescence and nearly half of cases have a genetic cause. Pathogenic variants in the AIP gene are responsible for about 30% of cases, are associated with aggressive pituitary tumours that can be challenging to treat medically with first-generation somatostatin analogs. There are several reports that treatment with pasireotide long-acting release (PAS-LAR) can lead to tumour regression in AIP-related acromegaly.

Objective: To report a new case of aggressive AIP-mutated pituitary acrogigantism successfully treated with Pasireotide LAR.

Methods: Clinical presentation, imaging, laboratory data and immunohistochemical staining features were analyzed. Evaluation for the presence of any pathogenic/likely pathogenic variations in pituitary and neuroendocrine tumor related genes were assessed by whole exome sequencing.

Results: A 15-year-old male presented with headache, visual acuity loss, back pain, weakness, loss of appetite, and rapid growth for the last 3 years. His height was 183.5 cm and he weighed 52 kg. ECG: sinus bradycardia. Ophthalmological review revealed optic nerves atrophy. An MRI showed an invasive supra-para-retrosellar macroadenoma (3,8x3,6x3,8 cm) with extension towards the posterior cranial fossa, third ventricle compression and basilar artery involvement. His plasma hormone concentrations were: prolactin 1116.5 ng/ml, GH 690 ng/ml, IGF-1 537 ng/ml, TSH 4.59 mU/l, fT4 1.16 ng/dl, fT3 2.99 pg/ml, DHEA-S 625 mg/ml, cortisol 9.81 mg/dl. Due to his hyperprolactinemia, cabergoline was started and rose to a dose of 0.5-1.0 mg/day. Hormone levels after three weeks were as follows: prolactin 232 ng/ml, GH 1023 ng/ml, IGF-1 501 ng/ml. He therefore underwent a partial endoscopic transnasal tumour resection that resulted in a decrease of GH and prolactin levels (prolactin 9.54 ng/ml, GH 70.0 ng/ml) but IGF-1 was elevated (567,2 ng/ml) and he had permanent hypopituitarism in other axes. Immunohistochemistry showed GH (90%) and prolactin (10%) positive cells in the pituitary adenoma with weak staining (+) for SSTR2 and moderate (++) staining for SSTR5, with a Ki-67 of 5%. A pathogenic heterozygous missense variant in exon 6 of the AIP gene (c.811 C>T; p.Arg271Trp) was detected. Treatment with Signifor LAR 40 mg/28 days and cabergoline 0.25 mg/day were started. A significant decrease in tumour volume, improvement in visual fields and IGF-1 normalization were achieved during 36 weeks of treatment.

Conclusion: Pasireotide long-acting release treatment may be beneficial in AIP mutated patients with acrogigantism and positive immunohistochemical staining of tumour cells for SSTR5.