Endocrine Abstracts

Introduction: A mutation in the PROP-1 gene is a rare cause of childhood-onset hypopituitarism. Patients with the disorder usually present with multiple pituitary hormone deficits. The pattern of development and the course of insufficiencies of individual axes remain unclear and affect patients metabolic status. Growth hormone therapy and substitution of other hormones may influence on glucose and lipid metabolism as well.

Aim: To characterize the carbohydrate and lipid metabolism of patients with childhood onset of hypopituitarism caused by PROP-1 mutation on the basis of long term observation in the pediatric/adult endocrinology departments of our university. The mean time of follow-up was 38.3 years (SD 12.8) with the longest observation lasting 62 years.

Methods: A retrospective analysis of metabolic data of 21 patients (12W/9 M) with confirmed PROP-1 mutation was performed. The mean age at the diagnosis was 7.3 years (SD 3.5). All patients present with thyroid, gonadal and somatotropic axes insufficiencies, while secondary hypoadrenalism was diagnosed in 19 cases (in 2 patients – transient).

Results: Body mass index (BMI) was elevated in 11/21 of patients (6/21 – overweight, 5/21 – obesity). At least one lipid abnormality - increased level of total cholesterol (in 9/21, 42.8% of cases, mean value 5.6 mmol/l), low-density lipoprotein (LDL – in 13/21, 61.9% of cases, mean value 3.8 mmol/l) or triglycerides (in 5/21, 23.8% of cases, mean value 1.7) mmol/l or decreased concentration of high-density lipoprotein (HDL - in 7/21, 33.3% of cases, mean value 1.4 mmol/l) was detected in majority of cases (16/21, 76% of patients). All patients had correct levels of fasting glucose (mean value 4.6 mmol/l) and glycolyzed hemoglobin (HbA1c; mean value 5.3%). In one patient oral glucose tolerance test (complete data available for 17/21 of cases) revealed impaired glucose tolerance. Mean values of fasting insulin and C-peptide were 6.92 uU/ml (min. 1.76, max. 19.0), and 1.85 ng/ml (min. 0.73, max. 6.58), respectively. HOMA IR was elevated (>2) in 5 patients. BMI was positively correlated (P<0.05, calculated for 17/21 of cases) with level of triglycerides, fasting insulin, HOMA-IR and insulin area under curve (AUC) in OGTT as well as negatively associated with HDL values. Age was corelated positively with HbA1c and glucose AUC in OGTT. Moreover, a significant positive correlation was documented for insulin and TC, LDL as well as triglycerides.

Conclusions: Patients with PROP-1 mutation-induced hypopituitarism characterize with multiple metabolic disturbances. The specific group of patients requires multidisciplinary medical care.