The neuropsychiatric complications of glucocorticoid use: steroid psychosis revisited.

BACKGROUND: Glucocorticoids are widely prescribed for a variety of diseases and are known to cause neuropsychiatric as well as somatic side effects. OBJECTIVE: This article will review the incidence, clinical characteristics, course, and treatment of neuropsychiatric effects of glucocorticoids. METHODS: We performed a literature review of the neuropsychiatric complications of glucocorticoids using the PubMed database. RESULTS: The neuropsychiatric effects of glucocorticoids involve affective, behavioral, and cognitive manifestations. Serious neuropsychiatric effects occur in about 6% of patients who receive steroids. Although the effects of glucocorticoids are unpredictable, the administered dose is the most significant risk factor for the development of neuropsychiatric symptoms. Dosage reduction typically results in clinical recovery. Although evidence from controlled trials is sparse, administration of antipsychotics or mood stabilizers may be beneficial in the prevention and treatment of neuropsychiatric effects of steroids. CONCLUSION: The neuropsychiatric effects of glucocorticoids are more diverse than the often-misleading term "steroid psychosis" suggests. This label should be limited to those patients who are truly psychotic, and specific designations applied to patients with other effects. The adverse neuropsychiatric effects of glucocorticoids remain poorly characterized in the literature (which consists largely of case reports and case series). Reliable risk factors (other than dose) that identify individuals at risk are lacking; guidelines for the prevention of neuropsychiatric effects are not evidence-based. Further controlled clinical studies are needed to elucidate the optimal management of glucocorticoid-induced neuropsychiatric symptoms.

Evaluation and management of adult hypoglycemic disorders: an Endocrine Society Clinical Practice Guideline.

OBJECTIVE: The aim is to provide guidelines for the evaluation and management of adults with hypoglycemic disorders, including those with diabetes mellitus. EVIDENCE: Using the recommendations of the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system, the quality of evidence is graded very low (plus sign in circle ooo), low (plus sign in circle plus sign in circle oo), moderate (plus sign in circle plus sign in circle plus sign in circle o), or high (plus sign in circle plus sign in circle plus sign in circle plus sign in circle). CONCLUSIONS: We recommend evaluation and management of hypoglycemia only in patients in whom Whipple's triad--symptoms, signs, or both consistent with hypoglycemia, a low plasma glucose concentration, and resolution of those symptoms or signs after the plasma glucose concentration is raised--is documented. In patients with hypoglycemia without diabetes mellitus, we recommend the following strategy. First, pursue clinical clues to potential hypoglycemic etiologies--drugs, critical illnesses, hormone deficiencies, nonislet cell tumors. In the absence of these causes, the differential diagnosis narrows to accidental, surreptitious, or even malicious hypoglycemia or endogenous hyperinsulinism. In patients suspected of having endogenous hyperinsulinism, measure plasma glucose, insulin, C-peptide, proinsulin, beta-hydroxybutyrate, and circulating oral hypoglycemic agents during an episode of hypoglycemia and measure insulin antibodies. Insulin or insulin secretagogue treatment of diabetes mellitus is the most common cause of hypoglycemia. We recommend the practice of hypoglycemia risk factor reduction--addressing the issue of hypoglycemia, applying the principles of intensive glycemic therapy, and considering both the conventional risk factors and those indicative of compromised defenses against falling plasma glucose concentrations--in persons with diabetes.

Improved contemporary surgical management of insulinomas: a 25-year experience at the Massachusetts General Hospital.

OBJECTIVE: To determine changes in the management strategy of patients with insulinomas and identify critical factors in patient outcome. BACKGROUND: Pancreatic insulinomas are rare neoplasms that are present in various ways. The optimal approach to localization, operative management, and follow-up of insulinomas is undetermined. METHODS: Sixty-one patients with a diagnosis of insulinoma requiring surgery at a tertiary care center between 1983 and 2007 were reviewed. Demographic details, mode of presentation, preoperative localization, operative procedures, and pathology data were assessed. The effect of different factors on survival was determined. RESULTS: Seven of 61 (11%) patients had a diagnosis of multiple endocrine neoplasia-type 1 (MEN-1). Multiple insulinomas were noted in 8% of cases and were more common in MEN-1 patients. The overall rate of malignancy was 8%. Confusion (67%), visual disturbances (42%), and diaphoresis (30%) were the most common presenting symptoms. Weight gain was noted in 44% of patients. The median duration of symptoms before diagnosis was 18 (1-240) months. The sensitivity of preoperative imaging of tumors before 1994 was 75%, compared with 98% after this period, which included use of endoscopic ultrasound scanning (P = 0.012). A combination of palpation and intraoperative ultrasound detected 92% of tumors. Distal pancreatectomy (40%), enucleation (34%), and pancreaticoduodenectomy (16%) were the most common procedures and pancreatic fistula occurred in 18% of patients. Three patients underwent noncurative distal pancreatectomy in the early period. The 10-year disease-specific and disease-free survival was 100% and 90% respectively. There were 5 patients with disease recurrence. Lymph node metastases (P < 0.001), lymphovascular invasion (P < 0.001), and the presence of MEN-1 (P = 0.035) were prognostically significant adverse factors in disease-free survival. Lymphovascular invasion was the only significant factor on multivariate analysis (P = 0.002). CONCLUSION: Pancreatic insulinomas can be readily localized preoperatively with modern imaging to avoid unsuccessful blind pancreatic resection. Surgical resection is associated with low morbidity and mortality and achieves long-term disease-free survival in the absence of lymphovascular invasion.

Perioperative management of patients treated with glucocorticoids.

HPA suppression is a common consequence of glucocorticoid therapy, whereas overt secondary adrenal insufficiency is a rare but life-threatening condition. Prolonged hypotension and a response to adequate doses of a glucocorticoid agent are not reliable ways to assess adrenocortical function. One must also demonstrate plasma cortisol levels that are inappropriately low for the clinical situation. Hypotension in patients previously treated with glucocorticoids is caused by loss of the permissive effect of glucocorticoids on vascular tone, which may be related in turn to enhanced PGI2 production in the absence of glucocorticoids. It is not caused by mineralocorticoid deficiency. Recurrent problems of study design and interpretation have plagued this area of investigation. Any patient who has received a glucocorticoid in doses equivalent to at least 20 mg a day of prednisone for more than 5 days is at risk for HPA suppression. If the doses are closer to but above the physiologic range, 1 month is probably the minimal interval. Recovery from prolonged exposure to high doses of glucocorticoids may take up to 1 year. Pituitary function returns before adrenocortical function. Recovery from short courses of treatment (e.g., 5 days) occurs more rapidly, in about 5 days. Recovery is time-dependent and spontaneous. The rate of recovery is a function of the dose and duration of therapy before tapering is started and while the dose is being reduced. ACTH therapy does not cause adrenocortical suppression but offers no advantage over glucocorticoids, has several disadvantages, and should no longer be used. Patients on alternate day glucocorticoid therapy have some suppression of basal cortisol levels but have normal or nearly normal responses to provocative tests of adrenocortical function. The standard short ACTH stimulation test is a reliable means of assessing adrenocortical function preoperatively. The low dose (1 microgram) short ACTH test is promising but has not been sufficiently well characterized, requires serial dilutions and cannot be recommended at this time. Studies of the physiologic adrenocortical response to surgical stress provide a basis for revised dose recommendations for perioperative coverage in the patient with known or suspected HPA suppression. Recommendations of a multidisciplinary group are presented.