Endocrine Abstracts

JOINT3342

Background: Growth hormone (GH)-secreting pituitary adenomas are rare in children. Surgical removal is the first-line treatment, while persistent disease may require long-acting somatostatin receptor ligands (SRLs), with or without dopamine agonists. This study presents a pediatric case resistant to multiple transsphenoidal surgeries, first- and second-generation SRLs, and bromocriptine therapy.

Method: Clinical data were reviewed, and whole-exome sequencing (WES) was performed on peripheral blood leukocytes and tumor tissue.

Results: A 12-year-old girl presented with tall stature since age five, along with headaches and blurred vision. She denied galactorrhea, polyuria, or polydipsia. Examination revealed a height of 172 cm (+3.43 SDS), mid-parental height of 157.5 cm, weight of 84 kg (+4.56 SDS), enlarged hands and feet, bitemporal hemianopia, and Tanner stage V for breast and pubic hair. Laboratory tests showed elevated IGF-1 (721 ng/ml), non-suppressible GH (>40 ng/ml), and prolactin 41.3 ng/ml (3-24). Other hormone levels were within normal ranges (FT4 1.06 ng/dl (0.98-1.63), TSH 1.09 µIU/ml (0.51-4.30), stimulated cortisol 20.2 µg/dl, LH 3.88 IU/l, FSH 4.46 IU/l, estradiol 38.4 pg/ml). Bone age was 15 years. Brain MRI revealed a 2.1×2.6×2.4 cm sellar and suprasellar mass encasing the internal carotid artery and extending into the cavernous sinus, consistent with a GH-producing pituitary macroadenoma. The patient underwent craniotomy, with histopathology confirming a GH-positive pituitary adenoma. WES identified a heterozygous missense c.2530C>T (p.Arg844Cys) variant in the GNAS gene in tumor tissue, absent in leukocytes, suggesting a somatic mutation. Three months post-surgery, GH remained elevated (nadir 30.8 ng/ml) with IGF-1 at 617 ng/ml, and a residual tumor (0.76×0.84 cm) was noted. A second transsphenoidal surgery and monthly octreotide LAR (20–60 mg) failed to achieve biochemical control, with a nadir GH of 5.42 ng/ml and IGF-1 of 602 ng/ml. Pasireotide LAR and bromocriptine were administered, but GH levels fluctuated between 1.79–7.15 ng/ml and IGF-1 remained at 555–575 ng/ml. At ages 16 and 17, the patient underwent a third and fourth surgery, but GH levels remained uncontrolled (nadir 6.86 ng/ml). Pegvisomant was considered but unavailable. She is now scheduled for proton radiation therapy.

Conclusions: We report a treatment-resistant GH-secreting pituitary adenoma in a pediatric patient harboring a somatic GNAS mutation. Managing such cases remains challenging, particularly in children. Stereotactic or proton radiotherapy should be considered when surgery and medical therapy fail to achieve biochemical control.