Cosyntropin Stimulation Test Research Articles

Cosyntropin stimulation testing on postoperative day 1 allows for selective glucocorticoid replacement therapy after adrenalectomy for hypercortisolism: Results of a novel, multidisciplinary institutional protocol

Secondary adrenal insufficiency (AI) can occur after unilateral adrenalectomy for adrenal-dependent hypercortisolism. Postoperative glucocorticoid replacement (GR), although given routinely, may not be necessary. We sought to identify factors that, in combination with postoperative day 1 cosyntropin stimulation testing (POD1-CST), would predict the need for GR. We reviewed 31 consecutive patients who underwent unilateral adrenalectomy for hypercortisolism (study patients) or hyperaldosteronism (control patients). A standard POD1-CST protocol was used. Hydrocortisone was started for clinical evidence of AI, basal plasma cortisol ≤ 5 (μg/dL), or a stimulated plasma cortisol <18. A normal POD1-CST was found in all nine control patients and 11 of 22 patients (50%) with Cushing's syndrome; the other 11 study patients (50%) received GR based on the POD1-CST. These patients were younger (51 vs 62 years; P = .017), had a higher body mass index (BMI; 31 vs 29 kg/m(2)), and smaller adrenal neoplasms (16.9 vs 33.0 g; P = .009) than non-GR study patients. After unilateral adrenalectomy for hypercortisolism, only 50% of patients received GR. No preoperative biochemical characteristics were associated with postoperative AI, although patients who received GR were younger, and tended to have a higher BMI and smaller adrenal nodules. Use of this novel protocol for postoperative dynamic adrenal function testing prevented unnecessary GR in 50% of patients and allowed for individualized patient care.

Morning Serum Cortisol Level After Transsphenoidal Surgery for Pituitary Adenoma Predicts Hypothalamic-Pituitary-Adrenal Function Despite Intraoperative Dexamethasone Use

Perioperative glucocorticoid (GC) is rarely needed in patients undergoing transsphenoidal surgery (TSS). We instituted a steroid-sparing protocol in the settings of intraoperative dexamethasone use. We evaluated the safety of using a cut off cortisol level of 14 μg/dL on postoperative day (POD)-1 and -6 after dexamethasone use during the surgery. We also analyzed the efficacy of serial morning cortisol levels for weaning GC replacement. The charts of 48 adult patients who received dexamethasone 4 mg intraoperatively were reviewed. Morning cortisol levels were measured on POD-1. Patients with cortisol ≥14 μg/dL were discharged without CG replacement. Morning cortisol level was checked routinely on POD-6, and GC replacement was initiated when the level was <14 μg/dL. Serial cortisol levels were measured in patients requiring GC after the first postoperative week. Overall, 67% patients had POD-1 cortisol ≥14 μg/dL and did not require GC on discharge. After POD-6, 83% of patients were not on GC replacement. A cosyntropin stimulation testing (CST) was only performed in 3 patients. There were no hospital admissions for adrenal crisis during the postoperative period. A steroid-sparing protocol with POD-1 and -6 morning cortisol levels can be safely and effectively used in the settings of intraoperative dexamethasone administration. It leads to avoidance of GC in more than two-thirds of patients on discharge and more than 80% of patients after the first postoperative week. We found that dynamic adrenal testing could be omitted in the majority of patients by using serial morning cortisol levels to assess the hypothalamic-pituitary-adrenal (HPA) axis.

Hypotension following Patent Ductus Arteriosus Ligation: The Role of Adrenal Hormones

To test the hypothesis that an impaired adrenal response to stress might play a role in the hypotension that follows patent ductus arteriosus (PDA) ligation. We performed a multicenter study of infants born at <32weeks' gestation who were about to undergo PDA ligation. Serum adrenal steroids were measured 3 times: before and after a cosyntropin (1.0μg/kg) stimulation test (performed before the ligation), and at 10-12hours after the ligation. A standardized approach for diagnosis and treatment of postoperative hypotension was followed at each site. A modified inotrope score (1×dopamine [μg/kg/min]+1×dobutamine) was used to monitor the catecholamine support an infant received. Infants were considered to have catecholamine-resistant hypotension if their greatest inotrope score was >15. Of 95 infants enrolled, 43 (45%) developed hypotension and 14 (15%) developed catecholamine-resistant hypotension. Low postoperative cortisol levels were not associated with the overall incidence of hypotension after ligation. However, low cortisol levels were associated with the refractoriness of the hypotension to catecholamine treatment. In a multivariate analysis: the OR for developing catecholamine-resistant hypotension was OR 36.6, 95% CI 2.8-476, P=.006. Low cortisol levels (in infants with catecholamine-resistant hypotension) were not attributable to adrenal immaturity or impairment; their cortisol precursor concentrations were either low or unchanged, and their response to cosyntropin was similar to infants without catecholamine-resistant hypotension. Infants with low cortisol concentrations after PDA ligation are likely to develop postoperative catecholamine-resistant hypotension. We speculate that decreased adrenal stimulation, rather than an impaired adrenal response to stimulation, may account for the decreased production.

Reversible Adrenal Insufficiency in Three Patients With Post-Roux-en-Y Gastric Bypass Noninsulinoma Pancreatogenous Hypoglycemia Syndrome.

Objective. Noninsulinoma pancreatogenous hypoglycemia syndrome (NIPHS) is a disorder of endogenous hyperinsulinemia that is clinically distinguishable from insulinoma, with a greater preponderance after Roux-en-Y gastric bypass (RYBG). Hyperinsulinemic hypoglycemia can predispose to attenuation of counterregulatory hormone responses to hypoglycemia, and consequent suppression of the hypothalamic–pituitary–adrenal (HPA) axis. This case series describes 3 individuals who were diagnosed with adrenal insufficiency (AI) after undergoing RYGB, complicated by NIPHS. Methods. A retrospective chart review was performed for each individual. Chart review applied particular attention to the onset of hyperinsulinemic hypoglycemia following bariatric surgery and the dynamic testing leading to the diagnoses of NIPHS and AI. Results. In each case, reactive hypoglycemia ensued within months to years after RYGB. Cosyntropin stimulation testing confirmed the diagnosis of AI. Hydrocortisone therapy reduced the frequency and severity of hypoglycemia and was continued until successful medical and/or surgical management of hyperinsulinism occurred. Follow-up testing of the HPA axis demonstrated resolution of AI. In all cases, hydrocortisone therapy was finally discontinued without incident. Conclusion. We speculate that transient AI is a potential complication in patients who experience recurrent hyperinsulinemic hypoglycemia after RYGB. The putative mechanism for this observation may be attenuation of the HPA axis after prolonged exposure to severe, recurrent hypoglycemia. We conclude that biochemical screening for AI should be considered in individuals who develop post-RYGB hyperinsulinemic hypoglycemia. If AI is diagnosed, supportive treatment should be maintained until hyperinsulinemic hypoglycemia has been managed effectively.

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Introduction: Contradictory evidence regarding the use of low dose steroids in septic shock is a challenge for physicians. Recent published guidelines attempt to address this, yet leave clinicians with recommendations that are subject to interpretation. Methods: The purpose of this study was to pilot test a questionnaire we developed to evaluate how clinicans' interpret and implement the current recommendations around the use of corticosteroids in septic shock. Results: Pulmonary and Critical Care physicians in Providence, RI (N = 27; 50% response rate) were asked to complete an electronic questionnaire in which they were presented with scenarios regarding patients with septic shock and asked to select various treatment options. Physicians in-training (ie, fellows), academic physicians and those in private practice were all included. Overall among attending physicians academic physicians versus private practioner's were more likely to prescribe steroids for patients on high dose vasopressors (defined as > 15mcg/min of norepinephrine). In addition regardless of fluid status, co-morbidities (including HIV, end stage renal disease, or diabetes mellitus) or the presence of chronic steroids, academic physicians were more likely to prescribe low dose steroids, (p <.05). While these findings did not reach statistically significance physicians-in-training (vs. attendings) appear more likely to prescribe steroids for patients in septic shock. For patients with HIV and diabetes mellitus, steroid prescription rates appeared to be less than for other defined conditions but again did not reach statistical significance. Patients on chronic steroids appeared more likely to receive low dose steroids. The use of cosyntropin stimulation testing did not differ between academic and private physicians. Conclusions: Critical care physicians vary in the use of low dose steroids for patients in septic shock. A large national survey will help to elucidate our findings and may lead to clear clinical guidelines for the treatment of patients in septic shock.

Cortisol response to cosyntropin administration in military veterans with or without posttraumatic stress disorder

Studies have demonstrated altered sensitivity of the hypothalamic-pituitary-adrenal (HPA) axis to its direct regulators in veterans with posttraumatic stress disorder (PTSD), but little is known about the adrenal response to hormonal stimulation in PTSD. An increased cortisol response to synthetic corticotropin-releasing factor (CRF) was recently found to be associated with war-zone deployment and not PTSD specifically. To more accurately assess whether there is altered adrenocortical responsivity to hormonal stimulation in relation to war-zone deployment or PTSD, we performed the low-dose cosyntropin stimulation test in a sample of 45 male veterans: 13 war-zone exposed veterans with chronic PTSD (PTSD+), 22 war-zone exposed veterans without chronic PTSD (PTSD-), and 10 veterans not exposed to a war-zone and without chronic PTSD (non-exposed). Plasma cortisol and ACTH were measured at baseline and at intervals over a one hour period following intravenous administration of 1μg of cosyntropin. A significant main effect of group (PTSD+, PTSD-, non-exposed) on the cortisol response to cosyntropin was observed. Cosyntropin-stimulated plasma cortisol levels were significantly higher in the PTSD+ and PTSD- groups compared to the non-exposed group. A significant main effect of group was also observed on peak cortisol levels. These findings suggest that war-zone exposure itself has persistent effects on adrenocortical activity.

Iatrogenic Cushing Syndrome in Patients Receiving Inhaled Budesonide and Itraconazole or Ritonavir: Two Cases and Literature Review

ObjectiveTo present two cases of iatrogenic Cushing syndrome caused by the interaction of budesonide, an inhaled glucocorticoid, with ritonavir and itraconazole. MethodsWe present the clinical and biochemical data of two patients in whom diagnosis of Cushing syndrome was caused by this interaction. We also reviewed the pertinent literature and management options. ResultsA 71-year-old man was treated with inhaled budesonide for a chronic obstructive pulmonary disease and itraconazole for a pulmonary aspergillosis. The patient rapidly developed a typical Cushing syndrome complicated by bilateral avascular necrosis of the femoral heads. Serum 8:00 AM cortisol concentrations were suppressed at 0.76 and 0.83 µg/dL on two occasions. The patient died 4 days later of a massive myocardial infarction. The second case is a 46-year-old woman who was treated for several years with inhaled budesonide for asthma. She was put on ritonavir, a retroviral protease inhibitor, for the treatment of human immunodeficiency virus (HIV). In the following months, she developed typical signs of Cushing syndrome. Her morning serum cortisol concentration was 1.92 µg/dL. A cosyntropin stimulation test showed values of serum cortisol of <1.10, 2.65, and 5.36 µg/dL at 0, 30, and 60 minutes, respectively, confirming an adrenal insufficiency. Because the patient was unable to stop budesonide, she was advised to reduce the frequency of its administration and eventually taper the dose until cessation. ConclusionClinicians should be aware of the potential occurrence of iatrogenic Cushing syndrome and secondary adrenal insufficiency due to the association of inhaled corticosteroids with itraconazole or ritonavir. (Endocr. Pract. 2013;19:e138-e141)

Rare and severe complications of congenital adrenal hyperplasia due to 21-hydroxylase deficiency: a case report

IntroductionWe report the case of a patient with classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency who presented with unusual anatomical and biochemical features, namely massively enlarged adrenal glands, adrenogenital rest tissue and an unexpected endocrine profile. The contribution of the adrenocortical cells in the adrenals and testicles was determined by a cosyntropin stimulation test before and after adrenalectomy. To the best of our knowledge this is the first report of such a case in the literature.Case presentationA 35-year-old Caucasian man was admitted to the emergency room with an Addisonian crisis. He had been diagnosed with congenital adrenal hyperplasia in the neonatal period. He acknowledged poor adherence to treatment and irregular medical assistance. Physical examination revealed marked cutaneous and gingival hyperpigmentation, hypotension, and hard nodules in the upper pole of both testicles. Blood analysis showed mild anemia and hyponatremia and no evidence of acute infection. Endocrine evaluation showed very low cortisol levels, low dehydroepiandrosterone-sulfate and elevated corticotropin, 11-deoxycortisol and delta-4-androstenedione. The concentration of 17-hydroxyprogesterone was 20,400ng/dL. After the cosyntropin stimulation test the pattern was similar and there was no significant increase in cortisol or 17-hydroxyprogesterone. The abdominal computed tomography scan revealed grossly enlarged and heterogeneous adrenal glands (left, 12cm; and right, six cm). A bilateral adrenalectomy was performed and pathologic examination revealed adrenal myelolipomas with nodular cortical hyperplasia. The sonogram showed bilateral heterogeneous masses on the upper pole of both testes which corresponded to the nodular hyperplasia of adrenal rest tissues. The genetic study revealed compound heterozigoty (mutations R124H and R356W), suggestive of a phenotypically moderate disease. We performed a cosyntropin stimulation test after adrenalectomy. The steroidogenic profile displayed the same unusual features, indicating an important contribution from the adrenogenital cells.ConclusionThis case illustrates that congenital adrenal hyperplasia due to 21-hydroxylase deficiency can progress to severe acute and chronic complications. The masses in the patient’s adrenal glands and testicles resulted from chronically elevated adrenocorticotropic hormone and growth of adrenocortical cells. The basal and stimulated steroid profile, before and after adrenalectomy, revealed an unexpected pattern, suggesting significant contribution of the testicular adrenal cells to the steroidogenesis.

Insuffisance surrénalienne cortico-induite

Prolonged glucocorticoid therapy is considered to be the most common cause of secondary adrenal insufficiency. Despite this, its true incidence remains unknown and the risk of acute adrenal insufficiency seems to be overestimated. The cosyntropin stimulation test is a very valuable test to assess the adrenal reserve but not to predict the risk of acute adrenal insufficiency. Otherwise, this test is well correlated with the adrenal response to a stress but not with clinical events. The corticosteroid withdrawal modalities are very heterogeneous, non-consensual, and have never been strictly evaluated. Several studies have demonstrated that the need for glucocorticoids coverage during a stress has been overestimated and that hydrocortisone doses should not necessarily be markedly increased. A prospective study of patients after withdrawal would be the only mean to assess the true incidence of this complication and to propose a rational strategy to prevent it. Meanwhile, the education of patients and physicians should be a mandatory step in the management of the patients with a potential risk of adrenal insufficiency.

Etomidate is associated with mortality and adrenal insufficiency in sepsis

To evaluate the effects of single-dose etomidate on the adrenal axis and mortality in patients with severe sepsis and septic shock. A systematic review of randomized controlled trials and observational studies with meta-analysis. Literature search of EMBASE, Medline, Cochrane Database, and Evidence-Based Medical Reviews. Sepsis patients who received etomidate for rapid sequence intubation. None. We conducted a systematic review of randomized controlled trials and observational studies with meta-analysis assessing the effects of etomidate on adrenal insufficiency and all-cause mortality published between January 1950 and February 2012. We only examined studies including septic patients. All-cause mortality served as our primary end point, whereas the prevalence of adrenal insufficiency was our secondary end point. Adrenal insufficiency was determined using a cosyntropin stimulation test in all studies. We used a random effects model for analysis; heterogeneity was assessed with the I statistic. Publication bias was evaluated with Begg's test. Five studies were identified that assessed mortality in those who received etomidate. A total of 865 subjects were included. Subjects who received etomidate were more likely to die (pooled relative risk 1.20; 95% confidence interval 1.02-1.42; Q statistic, 4.20; I2 statistic, 4.9%). Seven studies addressed the development of adrenal suppression associated with the administration of etomidate; 1,303 subjects were included. Etomidate administration increased the likelihood of developing adrenal insufficiency (pooled relative risk 1.33; 95% confidence interval 1.22-1.46; Q statistic, 10.7; I2 statistic, 43.9%). Administration of etomidate for rapid sequence intubation is associated with higher rates of adrenal insufficiency and mortality in patients with sepsis.

Traumatic brain injury and adrenal insufficiency: morning cortisol and cosyntropin stimulation tests

IntroductionAdrenal insufficiency (AI) has a great impact on the prognosis of patients with traumatic brain injury. There is a lack of consensus regarding the diagnostic criteria of AI. In these patients with acute stress we compared fasting cortisol, low and high dose cosyntropin stimulation tests to assess adrenal function in patients with moderate to severe traumatic brain injury.Material and methodsThis multicenter, cross-sectional study recruited 50 consecutive patients (aged between 15 and 70 years old) with moderate to severe traumatic brain injury who survived more than 5 days after the event. The patients’ adrenal function was assessed using the fasting cortisol, 1 and 250-µg ACTH stimulation tests.ResultsMore cases of AI were detected by the 1-µg ACTH stimulation test compared to those detected by the basal serum cortisol level and 250-µg ACTH stimulation test. The κ test showed no agreement between these tests. The incidence of AI in the first 10 days after traumatic brain injury varied from 34% to 82% according to the various definitions of AI. The incidence of hypotension and need for vasopressors was higher in the patients diagnosed by the 250-µg ACTH stimulation test (p < 0.0001).ConclusionsThe incidence of secondary AI in moderate to severe traumatic brain injury seems to be high. A combination of stimulation test (either 250 or 1 µg) and basal cortisol level may improve diagnostic ability compared to either test alone. Hence performing both tests for the assessment of adrenal function in patients with traumatic brain injury is recommended.

643 COSYNTROPIN STIMULATION TEST IS USEFUL IN DISTINGUISHING UNILATERAL FROM BILATERAL PRIMARY ALDOSTERONISM

Background: Primary aldosteronism (PA) is a common cause of endocrine hypertension. Although adrenal venous sampling (AVS) is the gold standard for subtype classification, it is available in limited specialized centers. The aim of the study was to investigate the clinical significance of cosyntropin (ACTH) stimulation test for subtype classification in PA. Design and Methods: Sixty patients with PA who underwent ACTH stimulation test were studied. The subjects were diagnosed as having either unilateral (n = 41) or bilateral PA (n = 19) based upon AVS, adrenal scintigraphy, and/or adrenal surgery. We evaluated the diagnostic significance of ACTH stimulation test in differentiating unilateral PA from bilateral PA. Results: Peak PAC (P < 0.01) and peak PAC/cortisol (P < 0.05) after ACTH stimulation were significantly higher in patients with unilateral PA than those with bilateral PA. Peak PAC-basal PAC (ΔPAC) was higher in patients with unilateral PA than those with bilateral PA, although the difference was not statistically significant. Receiver operating characteristic curve analysis for the diagnosis of unilateral PA showed a peak PAC value of 403 pg/ml had a sensitivity of 70.7% and specificity of 79.0%, and a value of 596 pg/ml had a sensitivity of 46.3% and specificity of 100%. A peak PAC/cortisol value of 19.7 (cortisol, mcg/dl) had a sensitivity of 58.5% and specificity of 89.5%, and a value of 30.5 had a sensitivity of 26.8% and specificity of 100%. Conclusions: ACTH stimulation test could discriminate between unilateral and bilateral PA and is useful in selecting the patients who should undergo AVS before surgery.

Hepatoadrenal syndrome in pediatric patients with end-stage liver disease*

Adrenal insufficiency in patients with liver failure, referred to as hepatoadrenal syndrome, is well characterized in adult patients but has not yet been described in children. We present 22 pediatric subjects with end-stage liver disease and adrenal insufficiency, diagnosed using the cosyntropin stimulation test. A retrospective chart review using inpatient records from a pediatric intensive care unit in an academic medical center with a busy pediatric transplant program. Most were infants with anatomical short gut and severe, total parenteral nutrition-induced liver failure awaiting liver transplantation. Many were critically ill; 68% required mechanical ventilation and 59% required vasopressors. None. All patients had low baseline cortisol levels and ten also had an abnormal cosyntropin stimulation test. Cortisol levels at baseline and increments of serum cortisol at 30 and 60 mins post cosyntropin were 9.3 ± 5 μg/dL, 9.3 ± 4 μg/dL, and 10.7 ± 6 μg/dL, respectively, compared to these values in five patients with liver failure and normal adrenal function (21.3 ± 3 μg/dL, 10.5 ± 5 μg/dL, and 12.7 ± 3 μg/dL, respectively). Baseline cortisol levels were higher in patients who required vasopressors (11.1 ± 5 μg/dL) compared to those who did not (6.6 ± 4.3 μg/dL, p = .04), and 60-min increment cortisol levels were lower in nonsurvivors compared to survivors (8.6 ± 4.8 μg/dL vs. 15.1 ± 5.1 μg/dL, p = .002). The severity of adrenal insufficiency did not correlate with the degree of hepatic decompensation. Clinical characteristics, including serum electrolytes and vasopressor requirements, were similar in patients with hepatoadrenal syndrome and patients with liver failure and normal adrenal function. Twelve (55%) of the patients died in the hospital, 11 without receiving a transplant. Hydrocortisone therapy permitted rapid weaning of vasopressor therapy but did not affect survival. Children with end-stage liver disease are at risk for hepatoadrenal syndrome and should have their cortisol levels monitored since clinical manifestations may not be diagnostic.

Comparison of Low and High Dose Cosyntropin Stimulation Tests in the Diagnosis of Adrenal Insufficiency in Septic Shock Patients

Stress situations such as septic shock are accompanied by activation of the HPA axis. Some patients do not activate this axis in stress situations. This blunted response is currently designated as critical illness-related corticosteroid insufficiency (CIRCI). Currently the 250 μg cosyntropin stimulation test is the preferred diagnostic test for CIRCI. Few papers explored the role of the 1 μg cosyntropin test in septic shock patients. In this study, we compared both tests in septic shock patients taking a special interest in the population with intermediary baseline cortisol. Prospective noninterventional study included 74 septic shock patients. After measurement of baseline cortisol all patients received 1 μg of cosyntropin i. v. and 4 h later 249 μg of cosyntropin. We compared the cortisol increase after each test and its relation to mortality and vasopressor therapy. There was a moderate correlation in response to low and high dose cosyntropin, r(s)=0.55. This correlation in patients with baseline cortisol between 10-34 μg/dl is, r(s)=0.67. The increase induced by both tests was equally accurate to identify mortality and time of vasopressor withdrawal. Low and high dose cosyntropin tests presented a moderate correlation in patients with baseline cortisol between 10-34 μg/dl. Both tests are equally accurate to identify mortality and time of vasopressor therapy. These results suggest that both tests could be used to diagnose CIRCI.

Adrenal Insufficiency as a Possible Contributor to Pain in Adults With Sickle Cell Disease (SCD) (413-B)

Result. Serum cortisol values were obtained on 61 occasions in 37 patients and one patient had a 24 hr urine cortisol determination. Adrenal insufficiency was present on 41 occasions overall (66%) including 28 events during 40 hospitalizations for VOC (70%) and 6 events during 22 outpatient visits (27%). Low serum cortisol values were present on at least 1 occasion in 24 of the 38 individuals (63%). When only morning cortisol values were considered (4 am-8 am), values were low in 13 of 20 determinations (65%) and were actually # 3 mcg/dl on 8 occasions (40%). Cosyntropin stimulation tests were performed in 16 patients with adrenal insufficiency and increases at 1 hr to $ 18 mcg/dl occurred on 10 occasions (63%). Increased eosinophil counts (> 500/mm) were present during 18 of 27 events when cortisol values were low (65%) but on only 6 of 20 occasions when cortisol values were normal (30%; x 1⁄4 6.1815; p < .02). Conclusion. Adrenal insufficiency is common in adult SCD patients, functionally significant and usually, but not always, due to impaired hypothalamic-pituitary function.

Nausea and Vomiting due to Addisonʼs Disease in a Patient with Celiac Disease in Remission

Purpose: Case Report: A 59 Y/O woman presented to the GI clinic with nausea, vomiting, and weight loss over a month's time. Her past medical history included sarcoidosis, Hashimoto's thyroiditis, and lupus. Evaluation revealed an elevated tissue transglutaminase antibody (TTG) IgA, 34 units (0-19) and small bowel biopsies which demonstrated intraepithelial lymphocytosis, especially near the villous tips, with preservation of villous architecture. She was diagnosed with celiac disease and started on a gluten free diet. Over the next three months, despite adherence to her diet, she had persistent nausea, vomiting and weight loss, as well as fatigue and muscle weakness. The patient was hospitalized, started on TPN, and further evaluation was pursued. Firstly, strict adherence to a gluten free diet was confirmed. Further evaluation was pursued and was unremarkable, including: repeat TTG IgA, 7 units (0-19); repeat EGD with duodenal biopsies (now normal); colonoscopy and biopsies (negative for microscopic colitis); abdominal ultrasound; HIDA scan; small bowel follow through x-ray; and CT scan of the head. Endocrine etiologies were next considered. Thyroid studies were normal, including TSH and free T4. Adrenal studies were abnormal: cosyntropin stimulation test was positive: 6.8 mcg/dL at baseline and 7.3 mcg/dL after administration of cosyntropin (cortisol 6.0-22.0 in AM); ACTH 253 pg/mL (6-58); and 21-hydroxylase antibody 22.1 U/mL (0.0-0.1). These findings were consistent with Addison's disease. She was started on SoluCortef 100 mg IV, which completely resolved her symptoms and transitioned to hydrocortisone 20 mg QAM and 10 mg QHS PO. She has had no further nausea or vomiting and she has gained weight. The patient had never been on corticosteroids in the past. Discussion: Celiac disease affects 1% of the population. Addison's disease is less common. Prevalence studies suggest that 1-8% of patients with autoimmune Addison's disease have celiac disease. The most common cause of persistent symptoms in celiac patients is known or unknown noncompliance with the gluten free diet. Once this has been excluded, a search for conditions which may mimic celiac disease should be undertaken. Endocrine etiologies for nausea and vomiting, including autoimmune Addison's disease, should be considered when a GI evaluation is unremarkable for a cause, especially in a patient with celiac disease in remission.

Adrenocorticotropic hormone and cortisol response to corticotropin releasing hormone in the critically ill—a novel assessment of the hypothalamic-pituitary-adrenal axis

Background The pathophysiology of adrenal insufficiency, common in surgical intensive care units, has not been fully elucidated. Methods Patients at risk (age > 55 years, in the surgical intensive care unit >1 week, baseline cortisol < 20 μg/dL) were enrolled. After measuring cortisol and adrenocorticotropic hormone (ACTH), corticotropin-releasing hormone (CRH) was administered. ACTH and cortisol were measured over 120 minutes. Short and long cosyntropin stimulation tests determined adrenal function. Area under the curve (AUC) and mixed linear models were used to compare cortisol and ACTH responses. Patients were grouped according to survival and response to stimulation testing. Chi-square and t tests were performed, and P values < .05 were considered statistically significant. Results Six of 25 patients responded poorly to cosyntropin, and 5 died compared with 3 after a normal response ( P < .01). ACTH (AUC) and ACTH peak were increased in nonsurvivors after CRH administration. Cortisol peak and AUC were not different. Conclusions ACTH responsiveness was increased in nonsurvivors and may predict mortality.

Critical illness-related corticosteroid insufficiency in cancer patients

Critically ill cancer patients with sepsis represent a high-risk sub-group for the development of critical illness-related corticosteroid insufficiency (CIRCI); however, the incidence of CIRCI in this population is unknown. The purpose of this study was to determine the incidence of CIRCI in cancer patients with severe sepsis or septic shock. A single-center, retrospective, observational study was conducted in a 52-bed medical-surgical intensive care unit of a National Cancer Institute-recognized academic oncology institution. Eighty-six consecutive patients with a diagnosis of severe sepsis or septic shock who received a high-dose 250-μg cosyntropin stimulation test were included. CIRCI was identified by a maximum delta serum cortisol of 9 μg/dL or less post cosyntropin. Overall, 59% (95% CI, 48-70%) of cancer patients with severe sepsis or septic shock were determined to have CIRCI. When compared to patients without CIRCI, patients with CIRCI had higher baseline serum cortisol (median, 26.3 versus 14.7 μg/dL; p = 0.002) and lower delta cortisol levels (median, 3.1 versus 12.5 μg/dL; p < 0.001). Mortality did not differ between the two groups. An inverse relationship was identified between baseline serum cortisol and maximum delta cortisol (maximum delta cortisol = -0.27 × baseline cortisol + 14.30; R (2) = 0.208, p < 0.001). The incidence of CIRCI in cancer patients with severe sepsis or septic shock appears high. Further large-scale prospective trials are needed to confirm these findings.

Journal Scan: Etomidate-Induced Adrenal Suppression: Is It Time to Abandon Old Faithful?

Journal Scan: Etomidate-Induced Adrenal Suppression: Is It Time to Abandon Old Faithful?

Presentation of Primary Adrenal Insufficiency in Childhood

Primary adrenal insufficiency is usually diagnosed in infancy or adulthood, and cases presenting in childhood have not been systematically reviewed. Our objective was to determine etiologies, signs, and symptoms of primary adrenal insufficiency presenting in childhood. We conducted a retrospective chart review at a tertiary-care pediatric hospital. Patients were children with corticoadrenal insufficiency, glucocorticoid deficiency, or mineralocorticoid deficiency. Seventy-seven cases were identified in 1999-2010. Thirty-five had congenital adrenal hyperplasia (CAH) and were not reviewed further. Forty-two patients (20 diagnosed at our institution) had primary adrenal insufficiency. These had etiologies as follows: autoimmune (18), autoimmune polyendocrinopathy syndrome (an additional five), ACTH resistance (four), adrenoleukodystrophy (three), adrenal hypoplasia congenita (two), adrenal hemorrhage (two), IMAGe syndrome (one), and idiopathic (two). Of 20 patients diagnosed at our institution, two were being monitored when adrenal insufficiency developed and were not included in the analysis of presenting signs and symptoms: 13 of 18 patients were hypotensive; 12 of 18 had documented hyperpigmentation. Hyponatremia (<135 mEq/liter) occurred in 16 of 18. However, hyperkalemia (>5.0 mEq/liter) was noted in only nine. Hypoglycemia and ketosis were documented in four of 15 and four of six patients in whom it was sought, respectively. Fifteen patients underwent cosyntropin stimulation testing with median baseline and stimulated cortisol of 1.1 and 1.2 μg/dl, respectively. ACTH and renin were markedly elevated in all patients. Hyperkalemia is not a consistent presenting sign of primary adrenal insufficiency in childhood, and its absence cannot rule out this condition. A combination of chronic or subacute clinical symptoms, hypotension, and hyponatremia should raise suspicion of adrenal insufficiency.