Department of Pediatric and Adolescent Endocrinology, University Children's Hospital in Cracow, Cracow, Poland.
Department of Pediatric and Adolescent Endocrinology, Chair of Pediatrics, Pediatric Institute, Jagiellonian University Medical College, Ul. Wielicka 265, 30-663, Cracow, Poland.
Hormones (Athens). 2024 Mar;23(1):69-79. doi: 10.1007/s42000-023-00510-1. Epub 2023 Dec 26.
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.
比较由 PROP1 基因突变引起的 CPHD 患者（CPHD-PROP1）与其他病因所致的先天性 CPHD 患者（CPHD-nonPROP1）的某些临床特征。
回顾性分析了 74 例 CPHD 患儿（32 例为女性）的儿童期病历，其中 43 例（23 例为女性）存在 PROP1 基因突变。
与 CPHD-nonPROP1 相比，CPHD-PROP1 患者具有以下特征：中位出生体重明显更高（0.21 比-0.29 SDS，p=0.019），生长激素治疗前 3 年的生长速度明显更低（-2.7 比-0.8 SDS，p<0.001），刺激过程中平均最大生长激素血浓度更高（1.2 比 1.08ng/ml，p=0.003），TSH 更低（1.8 比 2.4μIU/ml，p<0.001），催乳素浓度明显更低（128 比 416.3μIU/ml，p<0.001），男孩出生时典型的性腺功能减退症体征更少（6 例，30%比 12 例，54%，p<0.001）。CPHD-PROP1 患者中继发性肾上腺皮质功能不全较少见（20 例比 25 例，p=0.006），且发病年龄较晚（13.4 比 10.4 岁）。CPHD-PROP1 的垂体 MRI 显示小垂体（21 例）、垂体增大（8 例）和垂体柄中断伴后叶异位，9 例正常。
PROP1 基因突变患者的临床表现与其他形式的先天性垂体功能减退症明显不同。某些特定的临床结果可能有助于成功识别需要进行 PROP1 基因突变诊断的儿童。
