Diagnosis and Incidence of Congenital Combined Pituitary Hormone Deficiency in Denmark—A National Observational Study

Abstract

Context Congenital combined pituitary hormone deficiency (cCPHD) is the loss of ≥2 pituitary hormones caused by genetic factors or malformation. Objective We aimed to estimate the national incidence of cCPHD diagnosed before age 18 years and in subgroups. Design, Setting, and Patients cCPHD patients were identified in the Danish National Patient Registry and Danish hospital registries in the period 1996–2020. Hospital files were reviewed and incidences calculated using background population data. Interventions None. Main Outcome Measure Incidence. Results We identified 128 cCPHD patients; 88 (68·8%) were males. The median (range) age at diagnosis was 6·2 (0·01–19·0) years. The median (p25; p75) number of hormone deficiencies at diagnosis was 3 (3; 4) < 1 year vs. 2 (2; 2) at 1–17 years, p < 0·0001. Abnormal pituitary MRI findings were seen in 70·3% (83/118). For those born in Denmark with age <18 years at diagnosis (n = 116/128) the estimated national incidence (95% CI) of cCPHD was 10·34 (7·79–13·72) per 100,000 births, with an annual incidence rate of 5·74 (4·33–7·62) per million. In subgroup analysis (diagnosis <1 vs. 1-17 years), the incidence was highest in subgroup 1–17 years; 7·97 (5·77–11·00) vs. 1·98 (1·39–2·84) per 100,000 births, whereas the annual incidence rate was highest <1 year; 19·8 (13·9–28·4) vs. 4·69 (3·39–6·47) per million births. Conclusion cCPHD had the highest incidence rate and the most hormone deficiencies in those diagnosed <1 year. The incidence was highest i.the 1–17 years’ age group, underscoring the need for multiple pituitary hormone investigations throughout childhood and adolescence in children with only one hormone deficiency.

Clinical Characteristics of Children with Combined Pituitary Hormone Deficiency and the Effects of Growth Hormone Treatment

“…Congenital CPHD (cCPHD), which affects 1 in 16,000 children, remains idiopathic in approximately 85 % of patients; however, may result from underlying anatomical or genetic defects [2,3]. Over 30 genes have been linked to the hypothalamic-pituitary axis, with PROP1, POUF1, HESX1, LHX3, and LHX4 being the most common [1].…”