Augmented 17 alpha-hydroxyprogesterone response to ACTH stimulation as evidence of decreased 21-hydroxylase activity in patients with incidentally discovered adrenal tumours ('incidentalomas').

Abstract

OBJECTIVE:

Recent studies have indicated that the syndrome of congenital adrenal hyperplasia due to 21-hydroxylase deficiency is closely associated with the development of benign adrenocortical tumours. Tumour formation is thought to be a consequence of ACTH hypersecretion which results from the lack of glucocorticoid synthesis. The aim of this study was to evaluate 21-hydroxylase activity in patients with an incidentally discovered adrenal mass ('incidentaloma') without a history of congenital adrenal hyperplasia.

DESIGN:

A prospective study of 52 patients admitted to a single hospital.

PATIENTS:

Fifty-two consecutive subjects (mean age 56.0 years, range 24-81 years) with an incidentally discovered adrenal tumour were studied.

MEASUREMENTS:

The 21-hydroxylase reserve was assessed by intravenous bolus administration of 1-24 ACTH (tetracosactrin) with measurement of basal and stimulated serum 17 alpha-hydroxyprogesterone (17-OHP) concentrations. Impaired 21-hydroxylase activity was defined as an exaggerated 17-OHP response, with a 17-OHP increment exceeding 7.9 nmol/l. Basal and stimulated cortisol concentrations, and basal ACTH were also measured.

RESULTS:

Baseline levels of 17-OHP were normal in 44 and elevated in 8 subjects. In 37 patients (71.2%), the 17-OHP increment following ACTH administration exceeded 7.9 nmol/l, demonstrating mildly decreased 21-hydroxylase activity. In these subjects, the peak serum 17-OHP correlated with the tumour diameter. In the patients with apparently normal 21-hydroxylase activity, no significant correlation was found between 17-OHP concentrations and tumour size. All patients had a stimulated serum cortisol above 550 nmol/l reflecting intact adrenal glucocorticoid reserve. There were no other differences between the group with exaggerated and the group with normal 17-OHP increment. The tumours were removed from two women with augmented 17-OHP responses and this was followed by normalization of 17-OHP dynamics.

CONCLUSIONS:

Biochemical evidence for partial 21-hydroxylase defiency is a common finding in patients with an adrenal incidentaloma, even in the absence of a congenital adrenal hyperplasia history. Exaggerated 17-OHP increment is not accompanied by decreased adrenal glucocorticoid reserve. Normalization of the 17-OHP response after surgical treatment suggests that the phenomenon results from reduced 21-hydroxylase activity in the tumour, which retains ACTH responsiveness.

• Authors: T Seppel, R Schlaghecke
• Journal: Clinical endocrinology (Clin Endocrinol (Oxf)) Vol. 41 Issue 4 Pg. 445-51 (Oct 1994) ISSN: 0300-0664 [Print] England
• PMID: 7955456 (Publication Type: Journal Article)

Chemical References

• Hydroxyprogesterones
• 17-alpha-Hydroxyprogesterone
• Adrenocorticotropic Hormone
• Steroid 21-Hydroxylase

Topics

• 17-alpha-Hydroxyprogesterone
• Adenoma (blood, metabolism, surgery)
• Adrenal Cortex Neoplasms (blood, metabolism, surgery)
• Adrenal Hyperplasia, Congenital
• Adrenocorticotropic Hormone
• Adult
• Aged
• Aged, 80 and over
• Female
• Humans
• Hydroxyprogesterones (blood, metabolism)
• Male
• Middle Aged
• Prospective Studies
• Steroid 21-Hydroxylase (blood)