GH suppressed only to 29.0 μg/L after standard oral glucose load (normal, <1.0). Laboratory investigations revealed elevated serum concentrations of PRL (185 μg/L normal, 35.0 μg/L (Access II Beckman Coulter) ( Figure 1B). I and J, The gland shows an increase in GH-positive (immunoperoxidase, ×10 I) and PRL-positive cells (immunoperoxidase, ×10 J). G and H, Histological examination of the pituitary tissue demonstrates normal architecture of the gland with preservation of the reticulin network but markedly enlarged cell cords, suggesting diffuse hyperplasia: hematoxylin-eosin staining, ×10 (G) and Gömöri's reticulin stain, ×10 (H). C-F, Magnetic resonance imaging of the pituitary gland, coronal (C) and sagittal (D) view before surgery, and 5 weeks (E) and 24 months (F) after surgery. B, Growth velocity in centimeters per year (left y-axis, circles) and IGF-1 concentrations (right y-axis, triangles fold above 95% upper reference limit for age). Treatment strategies are indicated as follows: arrow, diagnosis and surgery DA, dopamine agonist (initially bromocriptine then followed by cabergoline) SSA, somatostatin analog (initially Sandostatin LAR and Somatuline Autogel, then continuous sc infusion administered at 120-320 μg/d dose) and PG, pegvisomant dose, 30-105 mg/wk. 4) ( Figure 1A).Ī, Growth chart before and after surgical and medical interventions. His height was 129.7 cm (Z = +4.89), and his weight was 35.5 kg (Z = +5.57) (WHO Growth Charts for Canada Ref. On examination, he appeared older than his stated age, was prepubertal, and had coarse facial features, which had developed over the previous 3 years. His family history was unremarkable for any endocrinopathies his midparental height was 174.5 cm. He complained of intermittent headaches over the preceding 8 months, was otherwise asymptomatic, and took no medications. He had undergone a tonsillectomy and adenoidectomy at the age of 3 years and 10 months. Born at term with a weight of 4.7 kg (>95th percentile), he had grown steadily along the 90th percentile for length up to 24 months of age and was above the median for weight and head circumference. Case Report and MethodsĪ 4-year and 8-month-old Caucasian boy presented to the Montreal Children's Hospital with rapid growth over the preceding 2 years. The vast majority of the previously described patients required extensive anterior pituitary resection or radiotherapy, resulting in hypopituitarism to control exuberant hormone secretion and growth velocity, because medical management with somatostatin analogs has not been sufficient ( 3). Most of the patients present with a GH and prolactin (PRL)-secreting pituitary adenoma or less commonly GH and PRL cell hyperplasia. The disease is associated with microduplications at Xq26.3 involving the GPR101 gene, which encodes a G protein-coupled orphan receptor. X-linked acrogigantism (XLAG) is a recently described clinical syndrome of early-onset gigantism with typical onset in the first few months of life and more often affecting females ( 1– 3).
#Xlag 4.0 skin#
However, DNA isolated from the pituitary tissue and forearm skin showed duplicated dosage of GPR101, suggesting that he is mosaic for this genetic abnormality.
His phenotype suggested XLAG, but his peripheral leukocyte-, saliva-, and buccal cell-derived DNA tested negative for microduplication in Xq26.3 or GPR101. The patient remains well controlled with minimal side effects 7 years after presentation. Medical management was challenging until institution of continuous sc infusion of short-acting octreotide combined with sc pegvisomant and oral cabergoline. Germline PRKAR1A, MEN1, AIP, DICER1, CDKN1B, and somatic GNAS mutations were negative. A pituitary biopsy showed hyperplastic pituitary tissue with enlarged cords of GH and prolactin cells. Magnetic resonance imaging demonstrated a homogenous bulky pituitary gland (18 × 15 × 13 mm) without obvious adenoma. Laboratory testing revealed elevated serum prolactin (185 μg/L normal, 35.0 μg/L. His height Z-score was +4.89, and weight Z-score was +5.57. He complained of sporadic headaches and had coarse facial features. A 4-year-old boy presented with rapid growth over the previous 2 years.