ESPE Abstracts

Introduction: Loss-of-function mutations in the arylhydrocarbon-interacting protein (AIP) gene contribute to familial isolated pituitary adenomas, particularly growth hormone (GH)-secreting adenomas. This report presents a case of gigantism in a patient with a GH-secreting macroadenoma and an identified AIP mutation.

Case Presentation: A 15-year-old male presented with complaints of excessive height growth, enlargement of hands and feet over the past two years. A paternal aunt had a pituitary adenoma. Physical examination showed a height of 185.5cm (+1.93SDS), weight of 128 kg (+4SDS), target height of 179cm (+0.45SDS), bone age of 15 years, and predicted adult height of 191cm. Blood pressure was 135/85mmHg, and the patient exhibited coarse facial features, macroglossia, and enlarged hands and feet. He was in Tanner stage 5 of puberty. In the laboratory tests glucose 127 mg/dL, insulin 271mIU/L, HbA1c 5.6%, GH 50µg/L (0.07-10.8), IGF-1 1107ng/mL (>+2SDS). The oral glucose tolerance test showed a nadir GH response of 48.4µg/L, with a normal glucose response and insulin resistance. Additional hormone levels were TSH 14mIU/L, sT4 0.88ng/dL, ACTH 45.2ng/L, cortisol 7.87µg/dL, prolactin 42.7µg/L, FSH 3.4IU/L, LH 2.28IU/L, and total testosterone 33.8ng/dL. Low-dose ACTH test showed a peak cortisol of 6.66µg/dL. The patient was started on 0.78µg/kg/day L-thyroxine for central hypothyroidism, 8 mg/m²/day hydrocortisone for central adrenal insufficiency. Cranial MRI revealed a 54x43x40mm lesion in the suprasellar region, compressing the frontal lobe, anterior commissure, corpus callosum, third ventricle, involving bilateral anterior cerebral arteries. The patient underwent surgery, but not all of the tumor, which was close to the mesencephalon and anterior cerebral arteries, could be removed. The patient was evaluated multidisciplinarily by neurosurgery, oncology, and endocrinology teams for the follow-up of the residual tumor. Medical treatment was decided for follow-up. Postoperative monitoring showed elevated IGF-1 and GH levels, octreotide-LAR 20 mg/month was started. At the third month of treatment, GH was 11.2µg/L (>2.5µg/L), and the dose was increased to 30 mg/month. Genetic analysis revealed a heterozygous frame-shift c.25delC variant in the AIP gene. Treatment is continued with octreotide-LAR in the patient who has a residual mass after the operation and whose lowest response in GH suppression test is 2.3mcg/L. The patient’s multidisciplinary follow-up continues.

Conclusion: Somatotropinomas with AIP variants are associated with early onset, large tumor size, invasive character, lower response to somatostatin analogs, and aggressive behavior. Somatostatin analogs are indicated in cases of persistent or recurrent disease postoperatively or when surgery is contraindicated. Studies with long-acting formulations have shown consistent suppression of GH and IGF-1.