SAT-193 Growing Against the Odds: Growth Hormone Therapy in Costello Syndrome - A Case Report
Year: 2025
Type: article
Abstract: Disclosure: R. Solomon: None. N. Mitre: None. R. Senguttuvan: None. F.J. Al Muhaisen: None. Introduction: Costello Syndrome (CS) is a rare genetic disorder with an estimated number of affected people 300 worldwide. It is caused by a heterozygous variant mutation in the HRAS gene. Clinical features of CS include dysmorphic facial features, developmental delay, cardiac abnormalities, and increased malignancy risk. Suboptimal growth and short stature have been reported in patients with CS. Growth hormone (GH) therapy is often considered to improve height and metabolic outcomes, though its efficacy and safety in syndromic short stature remain debated. This report highlights the role of GH therapy in CS, evaluates clinical response and growth outcomes, and contributes to evidence-guiding management. Case Presentation: We report a 16 year-year-old male referred to the endocrine clinic for severe short stature. His height was reported to be 147.2 cm (Z score -3.27). Weight was 35.9 kg (Z score -3.93). He was Tanner Stage III male. Physical exam findings included coarse facial features, micrognathia, hypertelorism, frontal bossing, and low-set ears. Initial lab work revealed normal total Testosterone at 601ng/dL (300-900). Further endocrine evaluation was within normal limits, including TSH, FT4, LH, FSH, celiac screening, 17OHP, and DHEAS. Bone age X-ray was read at 13.5 years at a chronological age of 16 and 1 month. GH stimulation testing was obtained, and the patient passed the test with a GH level of 21.3 ng/mL (>10). Given his abnormal physical exam findings, a Symptom Driven Exome sequence revealed a heterozygous pathogenic HRAS mutation, consistent with Costello syndrome. Given his severe short stature (Z score -3.27), GH therapy was initiated at the age of 16 years and 7 months. His GH dose was between 0.30-0.32 mg/kg/week in the last 2 years. His growth velocity improved with maximum GV at 10.3 cm/year, with a total increase of 13 cm over two years. His last bone age x-ray was consistent with 15 years at a chronological age of 18, 5 months. His current height is 164.1cm (Z score -1.71). Discussion: Costello Syndrome belongs to the RASopathy family, affecting growth. While the precise mechanisms remain unclear, GH insensitivity and impaired IGF-1 production have been implicated. Although this patient passed GH stimulation testing, GH therapy was beneficial, resulting in improved growth velocity. This suggests that even without classic GH deficiency, therapy may enhance growth outcomes in CS. Current literature highlights mixed results regarding GH efficacy, with concerns about potential risks such as hypertrophic cardiomyopathy and malignancy. No adverse effects were observed in this case. Endocrinologic evaluation in CS is complex, necessitating individualized management. This case underscores the importance of early genetic screening in short stature to avoid delayed diagnoses. It suggests that GH therapy can benefit even when conventional diagnostic criteria are unmet. Presentation: Saturday, July 12, 2025
Source: Journal of the Endocrine Society
Authors: Rebecca Solomon, Naim Mitre, Rajan Senguttuvan, Fadi Jamil Odeh Al Muhaisen
Institutions: Children's Mercy Hospital, Driscoll Children's Hospital
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,255
OpenAlex ID: W7093354072