Endocrine Abstracts

Introduction: Mutation in PROP1 gene is the cause of different forms of pituitary dysfunction. The assessment of the functioning of the adrenal axis still raises the most doubts.

Aim& methods: A retrospective longitudinal (mean 35 years, SD 16.24) analysis of 32 patients (19W/13M, including 5 families and sporadic cases) with PROP1 mutation was performed to define the optimal diagnostic approach in evaluation of adrenal axis. In the study morning cortisol and ACTH were assessed in 27/32 patients as well as tests with 1 ug of recombinant ACTH and 100 ug of CRH were conducted in 22/32 and 18/32 patients, respectively. Project grant number N41/DBS/000408).

Results: 26/32 were diagnosed with adrenal gland insufficiency, not all family were affected. In majority of patients the disease was detected later than deficits in other hormones (mean delay 17.75 years). In 4 cases it was found at initial diagnosis of pituitary dysfunction. The youngest and oldest patients were diagnosed at the age of 7 and 60, respectively. 3 patients presented with transient adrenal insufficiency – the hydrocortisone substitution was withdrawn due to retesting in adulthood. The average dose of hydrocortisone is 15,7 mg/day. The mean morning cortisol and ACTH concentrations were 6,62 ug/dl (SD 5.12, min./max. 1,09/19.35 ug/dl) and 20.18 pg/ml (SD 7.49, min./max. 8.6/49 pg/ml), respectively. Test with ACTH confirmed adrenal dysfunction in 14/22 patients, while test with CRH was positive in 13/18 patients. In 14 patients tests findings were compatible. All patients with abnormal Synacthen test had positive CRH test results as well. CRH revealed adrenal insufficiency in 3 additional patients with normal ACTH stimulation test or correct morning cortisol. Surprisingly, significant rise in ACTH concentration was observed in the CRH stimulation test with mean maximum value 100,7 pg/ml (min./max. 26/260 pg/ml), both in adrenal sufficient and insufficient patients suggesting other than ACTH deficit mechanism of adrenal insufficiency.

Conclusions: Adrenal insufficiency in patients with PROP1 mutation may occur at any age. Usually is detected later than other hormonal deficits, some patients may present with transient abnormalities, some retain its proper function throughout whole life. Morning cortisol is not an sufficient marker of adrenal condition; stimulation tests are commonly required and test with CRH seems to be the most adequate. In the view of ACTH increase after stimulation further studies are needed to understand the underlying mechanism and find the best diagnostic algorithm for patients with pituitary function deterioration caused by PROP 1 mutation.