It is over sixty years since the first administration of human growth hormone (GH) to children with GH deficiency, and over thirty years since recombinant human GH has been available for treatment of GH deficiency and a wider range of non-GH deficiency disorders. From a diagnostic perspective, genetic analysis, using single gene or Sanger sequencing and more recently next generation or whole exome sequencing, has brought advances in the diagnosis of specific causes of short stature, which has enabled therapy to be targeted more accurately. Genetic discoveries have ranged from defects of pituitary development and GH action to abnormalities in intracellular mechanisms, paracrine regulation and cartilage matrix formation. The strategy of GH therapy using standard doses has evolved to individualised GH dosing, depending on diagnosis and predictors of growth response. Evidence of efficacy of GH in GH deficiency, Turner syndrome and short children born small for gestational age is reviewed. The importance of critical assessment of growth response is discussed, together with the recognition and management of a poor or unsatisfactory growth response and the organisational issues related to prevention, detection and intervention regarding suboptimal adherence to GH therapy.

Congenital combined pituitary hormone deficiency (CPHD) is a rare heterogeneous group of conditions. CPHD-type 3 (CPHD3; MIM# 221750) is caused by recessive mutations in LHX3, a LIM-homeodomain transcription factor gene. The isoforms of LHX3 are critical for pituitary gland formation and specification of the anterior pituitary hormone-secreting cell types. They also play distinct roles in the development of neuroendocrine and auditory systems. Here, we summarize the clinical, endocrinological, radiological and molecular features of three patients from two unrelated families. Clinical evaluation revealed severe CPHD coupled with cervical vertebral malformations (rigid neck, scoliosis), mild developmental delay and moderate sensorineural hearing loss (SNHL). The patients were diagnosed with CPHD3 based on the array of hormone deficiencies and other associated syndromic symptoms, suggestive of targeted LHX3 gene sequencing. A novel missense mutation c.437G > T (p. Cys146Phe) and a novel nonsense mutation c.466C > T (p. Arg156Ter), both in homozygous forms, were found. The altered Cys146 resides in the LIM2 domain of the encoded protein and is a phylogenetically conserved residue, which mediates LHX3 transcription factor binding with a zinc cation. The p. Arg156Ter is predicted to result in a severely truncated protein, lacking the DNA binding homeodomain. Considering genotype/phenotype correlation, we suggest that the presence of SNHL and limited neck rotation should be considered in the differential diagnosis of CPHD3 to facilitate molecular diagnosis. This report describes the first LHX3 mutations from Saudi patients and highlights the importance of combining molecular diagnosis with the clinical findings. In addition, it also expands the knowledge of LHX3-related CPHD3 phenotype and the allelic spectrum for this gene.

OBJECTIVE: To assess the efficacy and effectiveness of continuous subcutaneous insulin infusion (CSII) therapy in type 1 diabetic Saudi children in comparison with conventional insulin (CI) therapy. METHODS: Continuous subcutaneous insulin infusion was initiated in 14 Saudi children with type 1 diabetes mellitus (T1DM) through insulin pump therapy between October 2002 and June 2004. All children were followed at the Diabetes Clinic, King Faisal Specialist Hospital and Research Centre, Riyadh, Kingdom of Saudi Arabia. The patients were initially on CI therapy, which is usually defined as 2 or fewer insulin injections per day before shifting them to CSII. The patients were trained on carbohydrates counting and started on continuously basal insulin infusion aside from the meal and high blood glucose correction insulin boluses. RESULTS: The patients included in the study had T1DM for a mean duration of 6 years. The age of the children ranged from 4-18 years. They were followed on insulin pump therapy for a mean duration of 10 months. There was a significant reduction in hemoglobin A1c, mean blood glucose level, total insulin requirement, frequency of hypoglycemic episodes and frequency of diabetic ketoacidosis (DKA) events during CSII therapy. CONCLUSION: Continuous subcutaneous insulin infusion improved the glycemic control in diabetic Saudi children with decreased frequency of hypoglycemic episodes and DKA events. Long follow-up studies are needed to confirm these results.

Background: Childhood growth hormone deficiency (GHD) and idiopathic short stature (ISS) are endocrine disorders characterized by impaired linear growth due to insufficient or ineffective growth hormone (GH) activity. While daily recombinant human GH (rhGH) therapy effectively restores growth, treatment adherence remains suboptimal owing to the burden of daily injections. Long-acting formulations such as pegylated recombinant human GH (PEG-rhGH) have been developed to improve convenience and compliance while maintaining therapeutic efficacy. This systematic review and meta-analysis aimed to evaluate the comparative effectiveness and safety of once-weekly PEG-rhGH versus daily rhGH and to assess dose–response outcomes between higher- and lower-dose PEG-rhGH regimens in pediatric GHD and ISS. Methods: This study followed PRISMA 2020 guidelines. Comprehensive searches were conducted in PubMed, Web of Science, and Scopus from inception to September 2025 using MeSH terms and free-text keywords for “PEGylated recombinant human growth hormone,” “long-acting growth hormone,” and “growth hormone deficiency.” Eligible studies included randomized controlled trials (RCTs) and cohort studies evaluating PEG-rhGH in children (≤18 years) with GHD or ISS, comparing either once-weekly PEG-rhGH with daily rhGH or different PEG-rhGH doses. Data extraction included study design, participant characteristics, intervention details, and key outcomes (height SDS, height velocity, IGF-1 SDS). Meta-analysis was conducted using Review Manager with a random-effects model, and heterogeneity was quantified using the I² statistic. Results: Eight studies, comprising 2549 children, met the inclusion criteria. Once-weekly PEG-rhGH demonstrated comparable short-term growth outcomes to daily rhGH at 6 and 12 months, with modest but significant superiority in height SDS (MD = 0.10, 95% CI 0.01–0.19) and height velocity (MD = 0.74 cm/year, 95% CI 0.42–1.05) by 24 months. IGF-1 SDS did not differ significantly at 6 or 12 months. In dose comparisons, 0.2 mg/kg/week PEG-rhGH produced substantially greater gains in height SDS and IGF-1 SDS than 0.1 mg/kg/week, with a time-dependent increase in the magnitude of the effect. Safety analyses revealed no increase in adverse or serious adverse events with PEG-rhGH compared to daily rhGH; reactions were generally mild and transient. Conclusions: Once-weekly PEG-rhGH is as effective as daily rhGH for promoting growth in pediatric GHD and ISS, with possible long-term advantages in growth outcomes and similar safety. The higher PEG-rhGH dose (0.2 mg/kg/week) appears to optimize efficacy without compromising tolerability. Weekly administration may enhance adherence and quality of life, supporting PEG-rhGH as a viable alternative to daily GH therapy.