Background: Correct diagnosis of the etiology of adrenal deficiencies is essential for appropriate treatment.
Case report: At the 12th day of life, the girl had suffered an episode of severe salt wasting with marked hyponatremia (109 mmol/l) and hyperkalemia (6.9 mmol/l). Under the assumption of adrenal insufficiency therapy with hydrocortisone and fludrocortisone as well as salt had been started. Unfortunately, due to the emergency character of this situation, there had been no prior evaluation of ACTH and cortisol.
At the age of one month, the patient was referred to us by an external clinic for further diagnostic work up. We performed an ACTH stimulation test in the morning before medication to further evaluate adrenal function. She showed an insufficient response with a stimulated cortisol of 3.6 µg/dl, so primary adrenal insufficiency was suspected. Chromosome analysis showed a normal 46, XX karyotype.
Levels of ACTH and cortisol were tested repeatedly in the morning before medication and showed normal. Plasma renin activity was elevated, so we considered isolated deficiency of mineralocorticoid biosynthesis. In the molecular genetic analysis two mutations in the CYP11B2 gene (aldosterone synthase) could be detected. The two mutations c.892_893delinsTG; p.Glu298X and c.1235G>C; p.Arg421Pro have not been described before. The parents are both heterozygous carriers for the mutations.
A second ACTH stimulation test was performed. This test demonstrated a normal rise of cortisol level to 23.8 µg/dl. Thus, sufficiency of ACTH-cortisol axis could be proven. Hydrocortisone was gradually reduced and discontinued. Urinary steroid metabolome analysis by GC-MS revealed the typical biochemical constellation of aldosterone synthase deficiency type 1. To date, fludrocortisone is given and our patient is developing well.
Conclusion: The need for sampling of plasma and urine for the determination of the decisive endocrine parameters is strongly recommended before starting emergency hydrocortisone therapy.
We detected two novel mutations in the CYP11B2 gene (p.Glu298X and p.Arg421Pro) leading to aldosterone synthase deficiency.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology