Isolated growth hormone deficiency type II

Isolated growth hormone deficiency type II (IGHD II) is a rare genetic disorder characterized by insufficient production of growth hormone (GH) from the anterior pituitary gland, leading to short stature and growth failure in affected individuals. Unlike other forms of isolated growth hormone deficiency, IGHD II follows an autosomal dominant inheritance pattern, meaning that a single copy of the mutated gene is sufficient to cause the condition. It is most commonly caused by mutations in the GH1 gene (encoding growth hormone 1), particularly splice site mutations that lead to the production of a misfolded 17.5 kDa GH isoform. This abnormal protein exerts a dominant-negative effect on the secretion of normal growth hormone by disrupting the secretory pathway in somatotroph cells of the pituitary gland. Clinical features typically become apparent in childhood, when affected children demonstrate significant growth retardation, short stature, and delayed bone age. Height is usually well below the third percentile for age and sex. Some patients may also exhibit a degree of pituitary hypoplasia visible on MRI. The severity of growth hormone deficiency can be variable, even within the same family carrying the identical mutation, and some individuals may develop additional pituitary hormone deficiencies over time, a phenomenon that distinguishes IGHD II from other isolated GH deficiency subtypes. Treatment consists of recombinant human growth hormone (rhGH) replacement therapy, which is effective in improving linear growth when initiated early in childhood. Patients generally respond well to GH therapy, although the degree of catch-up growth may vary. Long-term monitoring is recommended to assess for the potential development of other pituitary hormone deficiencies, including adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), or gonadotropin deficiencies. Early diagnosis and treatment are essential for optimizing final adult height and overall outcomes.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

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