Tertiary hypercorticotropinism and Cushing's disease secondary to impaired 21-hydroxylation
Matthias Haase1, Theresa Cox1, Elke Kaminski2, Dieter K Lüdecke3, Wolfgang Saeger4, Reimar Fritzen5, Matthias Schott1, Werner A Scherbaum1 & Holger S Willenberg1
Autonomy of ACTH secretion has been described in patients with chronic dysinhibition of ACTH secretion. We here present the very unusual case of a 31-year old female patient who had congenital adrenal hyperplasia and developed Cushings disease, including clinical examinations, laboratory data, endocrine function tests, histological and genetic analyses.
The affected patient had clinical signs and a typical history of hypercortisolism. Endocrine function tests revealed Cushings disease. After removal of a pituitary microadenoma, serum-cortisol levels fell below normal and the symptoms improved. However, hirsutism returned after four years ACTH levels were in the upper range of normal. An ACTH challenge test showed a minor cortisol response but a marked increase in 17-hydroxyprogesterone serum concentrations. The genetic analysis revealed a homozygous mutation in exon 7 of the CYP21A2 gene (CTG>TTG, Val281Leu).
This is the third description of a case of Cushings disease with congenital adrenal hyperplasia. It is suggested that a marked ACTH drive can override insufficient 21-hydroxylation causing hypercortisolism in non-classical homozygous forms of congenital adrenal hyperplasia. In this patient Cushings disease may have developed on the basis of impaired 21-hydroxylation in the sense of tertiary hypercorticotropinism.