Published online Dec 9, 2025. doi: 10.5409/wjcp.v14.i4.108897
Revised: May 22, 2025
Accepted: August 4, 2025
Published online: December 9, 2025
Processing time: 189 Days and 22.1 Hours
Noonan syndrome (NS) is an autosomal dominant, multisystem disorder with a prevalence of 1 in 1000-2500. Multiple etiologies have been proposed for short stature in NS, including resistance to growth hormone (GH) and GH deficiency (GHD). Irrespective of the presence of GHD, NS is a Food and Drug Administration-approved indication for recombinant-GH therapy. Few case reports of combined anterior pituitary hormone deficiency (CPHD) in NS have been reported.
To describe the clinico-biochemical characteristics of NS with CPHD and to assess the response to recombinant GH therapy.
An ambispective case-control study was conducted to compare the clinico-hormonal profile and response to recombinant-GH in pediatric patients with NS and CPHD and pediatric patients with NS but without CPHD.
Five children with NS and CPHD were compared to 6 patients with NS but without CPHD. The most common anterior pituitary hormone involvement in combination with GHD was adrenocorticotrophic hormone deficiency causing hypocortisolemia (n = 3, 60%), followed by hypogonadotropic hypogonadism and secondary hypothyroidism (n = 1 each). Pituitary hypoplasia was seen in the magnetic resonance imaging of all patients with CPHD. Patients with NS and CPHD had lower standard deviation scores of height (-4.18 vs -2.52, P = 0.009), bodyweight, and body mass index but a slightly better first year response to recombinant GH (9.2 vs 5.5, P = 0.06). There were no differences in dysmorphisms and other anomalies between the two groups. Patients with NS and CPHD had a similar response to GH as patients with CPHD but without NS. One patient with NS and CPHD developed hypocortisolism after GH initiation.
Hypoplasia of the pituitary and GHD with involvement of other pituitary hormones may be seen in NS and may determine response to recombinant GH therapy.
Core Tip: Noonan syndrome (NS) can be associated with combined pituitary hormone deficiency (CPHD) and/or isolated growth hormone (GH) deficiency. Hypoplasia of the pituitary gland may contribute to CPHD in NS. Patients with NS and CPHD have decreased height and bodyweight but can have a better response to recombinant GH therapy than patients with NS but without CPHD. Children having a PTPN11 mutation with low insulin-like-growth-factor 1 should be tested for cortisol and thyroid function at baseline to rule out CPHD. If there is a suspicion for CPHD, the patient should undergo periodic testing for cortisol and thyroid function while receiving GH.