Glucocorticoid replacement therapy and fibrinolysis in patients with hypopituitarism

Abstract

Background: Hypopituitarism is associated with increased cardiovascular mortality, and it has been suggested that unphysiological glucocorticoid replacement regimens might contribute to this risk. Traditional glucocorticoid replacement regimens have often led to excessive serum cortisol levels. The hypercortisolaemia of Cushing's syndrome is associated with an increased risk of thromboembolism.

Objective: To examine whether short-term higher-dose hydrocortisone replacement regimens adversely affect the fibrinolytic system.

Design: Crossover study comparing tailored low-dose (LD) glucocorticoid regimen (mean, 17·5 mg hydrocortisone daily), with a traditional high-dose (HD, 30-mg hydrocortisone daily) regimen for 2 weeks.

Patients: Ten patients with hypopituitarism and ACTH deficiency - median (range) age, 59 (41-75) years - and 10 age- and sex-matched controls. Nine patients had growth hormone deficiency (five replaced), nine patients had TSH deficiency (nine replaced), eight had gonadotrophin deficiency (five replaced). During the study, other pituitary hormone replacement therapy remained unchanged. Patients with acromegaly and Cushing's syndrome were excluded.

Measurements: Hourly serum cortisol for 11 h, plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA) and fibrinogen levels after 2 weeks of treatment with both LD and HD regimens.

Results: No overall significant differences were found between the three groups using the Kruskal-Wallis test: PAI-1: [median (range)] HD, 25 (5-53) ng/ml; LD, 21 (4-56) ng/ml; controls, 27 (8-51); P = 0·3; tPA: HD, 10 (5-15) ng/ml; LD, 10 (4-13) ng/ml; controls 10 (3-13); P = 0·46; and fibrinogen: HD, 2·5 (1·8-3·5) g/l; LD, 3·0 (2·3-4·4) g/l; controls, 2·6 (1·6-3·2): P = 0·97 In addition, no significant differences between HD and LD using Wilcoxon's paired test; PAI-1 (P = 0·91), tPAag (P = 0·47) and fibrinogen (P = 0·09).

Conclusions: An increased dose of hydrocortisone for 2 weeks creates excessive glucocorticoid exposure, but does not significantly affect fibrinolytic-coagulation parameters.