cCPHD presents a broad clinical spectrum, ranging from potentially life-threatening multiple hormone deficiencies in neonates to late-onset gradual presentations in childhood or adolescence. [1,3,5]. There is considerable variability in the age of onset, presence of cerebral malformations, and composition of hormone deficiencies, even within the same family [6,7].

A recent study conducted on childhood-onset congenital combined PHD in Korea [8] retrospectively investigated the clinical and genetic characteristics of 43 Korean children diagnosed with cCPHD before the age of 20. The study found a high prevalence of neonatal symptoms, with over half (53.5%) presenting with features suggestive of hypopituitarism (such as jaundice and hypoglycemia), although only 65.2% were diagnosed in infancy. The later diagnosis group exhibited lower height z-scores and higher growth hormone (GH) peak levels. GH deficiency (GHD) was almost universal (97.7%), and most patients (76.7%) had 3 or more hormone deficiencies. TSH deficiency was the most common at initial diagnosis, while GHD was the most common deficiency identified at final follow-up. Additionally, 82.9% of patients showed brain magnetic resonance imaging abnormalities, primarily involving the pituitary gland and stalk, with the incidence of abnormalities correlating with a higher number of hormone deficiencies.

Genetic analysis in 26 patients identified pathogenic variants in 5 (19.2%), involving the genes POU1F1, GLI2, HESX1, TBC1D32, and ROBO1. These patients tended to be diagnosed earlier and had a higher prevalence of extrapituitary phenotypes. Furthermore, adult GHD was diagnosed in all 17 patients who reached adulthood and were evaluated for it, with a significant proportion (58.9%) exhibiting metabolic abnormalities.

While this article has some limitations, the study highlights the importance of identifying early neonatal features of hypopituitarism to manage both pituitary and extrapituitary phenotypes effectively. The genetic etiology of cCPHD requires further investigation, as genetic testing only identified pathogenic variants in a minority of cases. The study also emphasizes the need for long-term clinical follow-up and metabolic monitoring of patients with cCPHD.