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.

Mortality in patients with non-functioning pituitary adenoma is increased: systematic analysis of 546 cases with long follow-up.

OBJECTIVE: Non-functioning pituitary adenomas (NFAs) have a prevalence of 7-22/100,000 people. A significant number of patients suffer from morbidities related to the tumor, possible recurrence(s), and treatments utilized. Our aim was to assess mortality of patients with macroNFA and predictive factors. DESIGN: Retrospective cohort study in a tertiary referral center in the UK. METHODS: A total of 546 patients operated for a macroNFA between 1963 and 2011 were studied. Mortality data were retrieved through the National Health Service Central Register and hospital records and recorded as standardized mortality ratio (SMR). Mortality was estimated for the total and various subgroups with clinical follow-up data. RESULTS: Median follow-up was 8 years (range: 1 month-48.5 years). SMR was 3.6 (95% CI, 2.9-4.5), for those operated before 1990, 4.7 (95% CI, 2.7-7.6) and for those after 1990, 3.5 (95% CI, 2.8-4.4). Main causes of death were cardio/cerebrovascular (33.7%), infections (30.1%), and malignancy (28.9%). Cox regression analysis demonstrated that only age at diagnosis remained an independent predictor of mortality (hazard ratio 1.10; 95% CI, 1.07-1.13, P<0.001), whereas sex, presentation with acute apoplexy, extent of tumor removal, radiotherapy, recurrence, untreated GH deficiency, FSH/LH deficiency, ACTH deficiency, TSH deficiency, and treatment with desmopressin had no impact. CONCLUSIONS: Despite the improvement of treatments over the last three decades, the mortality of patients with NFAs in our series remains high. Apart from age, factors related with the management/outcome of the tumor are not independent predictors, and pituitary hormone deficits managed with the currently-used substitution protocols do not adversely affect mortality.

Acromegaly and anaplastic astrocytoma: coincidence or pathophysiological relation?

Insulin-like growth factor type I (IGF-I) is an important promoter in the tumorigenesis of several extracranial and intracranial neoplasms. In astrocytic-cell tumors, the role of autocrine and paracrine IGF-I expression in enhancing tumoral progression is well established. However, the influence of systemic IGF-I levels on the clinical behavior of astrocytic neoplasms remains an open subject of research. We report the case of a 28-year-old man who presented simultaneously with acromegaly and an anaplastic astrocytoma, which had rapidly progressed from a low-grade astrocytoma. The coexistence of systemic IGF-I hypersecretion with a quick progression in the histopathological grade of the astrocytoma raises the compelling question of whether the clinical behavior of the astrocytic tumor was influenced by the acromegalic status. The role of IGF-I signaling in the pathogenesis of astrocytic-cell tumors and the experience with therapeutic strategies addressing this pathway in astrocytomas are also discussed.