Prevention of Adrenal Crisis: Cortisol Responses to Major Stress Compared to Stress Dose Hydrocortisone Delivery.

CONTEXT: Patients with adrenal insufficiency require increased hydrocortisone cover during major stress to avoid a life-threatening adrenal crisis. However, current treatment recommendations are not evidence-based. OBJECTIVE: To identify the most appropriate mode of hydrocortisone delivery in patients with adrenal insufficiency who are exposed to major stress. DESIGN AND PARTICIPANTS: Cross-sectional study: 122 unstressed healthy subjects and 288 subjects exposed to different stressors (major trauma [N = 83], sepsis [N = 100], and combat stress [N = 105]). Longitudinal study: 22 patients with preserved adrenal function undergoing elective surgery. Pharmacokinetic study: 10 patients with primary adrenal insufficiency undergoing administration of 200 mg hydrocortisone over 24 hours in 4 different delivery modes (continuous intravenous infusion; 6-hourly oral, intramuscular or intravenous bolus administration). MAIN OUTCOME MEASURE: We measured total serum cortisol and cortisone, free serum cortisol, and urinary glucocorticoid metabolite excretion by mass spectrometry. Linear pharmacokinetic modeling was used to determine the most appropriate mode and dose of hydrocortisone administration in patients with adrenal insufficiency exposed to major stress. RESULTS: Serum cortisol was increased in all stress conditions, with the highest values observed in surgery and sepsis. Continuous intravenous hydrocortisone was the only administration mode persistently achieving median cortisol concentrations in the range observed during major stress. Linear pharmacokinetic modeling identified continuous intravenous infusion of 200 mg hydrocortisone over 24 hours, preceded by an initial bolus of 50-100 mg hydrocortisone, as best suited for maintaining cortisol concentrations in the required range. CONCLUSIONS: Continuous intravenous hydrocortisone infusion should be favored over intermittent bolus administration in the prevention and treatment of adrenal crisis during major stress.

Tumors metastatic to the pituitary gland: case report and literature review.

Tumors metastatic to the pituitary gland are an unusual complication of systemic cancer typically seen in elderly patients with diffuse malignant disease. Breast and lung are the commonest sites of the primary tumor, whereas diabetes insipidus is the most frequent symptom at presentation. Their rarity and usually indolent course, as well as the lack of specific clinical and radiological features, impede their differentiation from other more common sellar area lesions, particularly when history of malignancy is absent. Management of these patients may also be very difficult because the prognosis depends on the course of the primary neoplasm. A 68-yr-old man, with no history of malignancy, presented with recent onset of hypopituitarism, mild diabetes insipidus, headaches, left oculomotor nerve palsy, and progressive bilateral deterioration of visual acuity and visual fields. Magnetic resonance imaging revealed a large sellar mass compressing the optic chiasm and invading the left cavernous sinus, whereas a prolactin elevation at 438.6 ng/ml (19.73 nmol/liter) was noted. Decompression of the sellar region was attempted, and pathology disclosed a metastatic hepatocellular carcinoma. On postoperative investigation, primary liver tumor was identified and confirmed by biopsy. The patient improved transiently but died 3 months after diagnosis because of deterioration of the liver disease. The relevant literature is reviewed in light of this unusual case, illustrating the problems in the diagnosis and management of patients with metastasis to the pituitary.