Endocrine Abstracts

Introduction: The mode of pituitary function deterioration in patients with PROP1 mutation is not fully known and understood. The function of adrenal axis requires special attention.

Aim: To investigate the time/mode/markers of pituitary function deterioration in families/sporadic patients with PROP1 mutation during longitudinal observation.

Methods: We performed retrospective longitudinal (36.4 years, s.d. = 13.6) analysis of 28 patients (23 with complete data, 11 M/12 W) with PROP1 mutation, including 7 families (16/23 70% of investigated population; 20/28 overall), with 2–4 affected siblings who were under medical supervision of the paediatric/adult endocrinology departments of our university. Follow up investigation of adrenal axis insufficiency (AI) with repeated ACTH analogue (Synacthen) and CRH tests were performed in 21 and 7 patients, respectively.

Results: All patients initially presented with growth failure at mean age (MA) 7.0 years (s.d. = 3.7). 14/23 patients were first diagnosed with GH/TSH deficiency occurred simultaneously, MA 6.6 years (s.d. = 3.0). 13/28 (older patients) received no/delayed/intermittent GH treatment in childhood. Gonadal deficiency was diagnosed in all patients MA 16.0 years (s.d. = 4.85). 19/23 (82,6%) of patients developed adrenal deficiency MA 25 years (s.d. = 16.0), the oldest newly diagnosed at the age of 57. The actual average dose of HC supplementation is 17.8 mg/day (0.25 mg/kg). There were no specific mode/order of pituitary deterioration among siblings. Mean morning cortisol and ACTH in patients with AI were 5.7 (s.d. = 4.0) and 20.7 (s.d. = 7.7) vs without AI 11.8 (s.d. = 5.5) and 21.8 (s.d. = 8.1), respectively. The peak cortisol increase during Synacthen test was in 60’ by 3.2 (s.d. = 0,83) and by 1.9 times (s.d. = 0,26) in patients with/without AI, respectively. In CRH test the peak values of cortisol (in 60–120’) and ACTH (in 15–30’) were observed accordingly in patients with AI by 3.3 (s.d. = 1.0) and by 3.4 times (s.d. = 0.4) vs patient without AI by 2.5 and by 4.3 times).

Conclusions: In patients with PROP1 mutation there is no specific order of pituitary function deterioration even among affected siblings. Careful monitoring for possible adrenal insufficiency regardless of the time of observation and previous stimulation test results should be carried on. Morning (low) cortisol and ACTH (normal range) cannot serve as a marker of adrenal axis function. The increase of ACTH during CRH test in patients with adrenal insufficiency suggests that corticotropes are responsive. Further studies are needed to better understand the process, to improve the standards of care/diagnostic timing/procedures.