# Comparison of clinical characteristics of a pediatric cohort with combined pituitary hormone deficiency caused by mutation of the PROP1 gene or of other origins

## TL;DR

This study compares clinical features of children with pituitary hormone deficiency caused by PROP1 gene mutations versus other causes, finding distinct differences that may help identify those with PROP1 mutations.

## Contribution

The study identifies specific clinical differences between CPHD caused by PROP1 mutations and other etiologies, aiding in targeted genetic diagnostics.

## Key findings

- Patients with CPHD-PROP1 had higher birth weight, lower growth velocity, and higher growth hormone levels compared to CPHD-nonPROP1.
- CPHD-PROP1 patients showed lower TSH and prolactin levels and less frequent hypogonadism signs at birth in boys.
- MRI findings in CPHD-PROP1 revealed varied pituitary gland abnormalities, including small or enlarged glands and posterior lobe ectopy.

## Abstract

The most commonly identified genetic cause of combined pituitary hormone deficiency (CPHD) is PROP1 gene mutations. The aim of the study was to compare selected clinical features of patients with CPHD caused by variants of the PROP1 gene (CPHD-PROP1) and patients with inborn CPHD of other etiology (CPHD-nonPROP1).

The retrospective analysis included childhood medical records of 74 patients (32 female) with CPHD, including 43 patients (23 female) with the mutation in the PROP1 gene.

Patients with CPHD-PROP1 compared to the CPHD-nonPROP1 presented with the following: significantly higher median birth weight (0.21 vs. − 0.29 SDS, p = 0.019), lower growth velocity within 3 years preceding growth hormone administration (− 2.7 vs. − 0.8 SDS, p < 0.001), higher mean maximal blood concentration of growth hormone within the stimulation process (1.2 vs. 1.08 ng/mL, p = 0.003), lower TSH (1.8 vs. 2.4 µIU/mL, p < 0.001), significantly lower prolactin concentrations (128 vs. 416.3 µIU/mL, p < 0.001), and less frequent typical signs of hypogonadism at birth in boys (n = 6; 30% vs. n = 12, 54%, p < 0.001). Secondary adrenal insufficiency was less frequent in CPHD-PROP1 (20 vs. 25 cases, p = 0.006) and occurred at a later age (13.4 vs. 10.4 years). MRI of the pituitary gland in CPHD-PROP1 revealed a small pituitary gland (21 cases), pituitary gland enlargement (eight cases), and one pituitary stalk interruption and posterior lobe ectopy, while it was normal in nine cases.

Patients with the PROP1 mutations present a clinical picture significantly different from that of other forms of congenital hypopituitarism. Certain specific clinical results may lead to the successful identification of children requiring diagnostics for the PROP1 gene mutation.