Cosyntropin-Stimulated Serum Free Cortisol in Healthy, Adrenally Insufficient, and Mildly Cirrhotic Populations.

CONTEXT: Serum free cortisol (SFF) responses to cosyntropin simulation test (CST) may more accurately assess adrenal function than total cortisol (TF). OBJECTIVE: The objective of the study was to evaluate the diagnostic utility of SFF responses during a 250-µg CST. DESIGN: We recruited healthy volunteers (HV; n = 27), patients with primary and secondary adrenal insufficiency (n = 19 and n = 24, respectively), and subjects with Child-Pugh class A cirrhosis (CH; n = 15). Each received 250 µg cosyntropin with measurement of ACTH and corticosteroid binding globulin (CBG) at time 0 and TF and SFF at 0, 30, and 60 minutes. Salivary cortisol was measured at all time points in CH subjects. RESULTS: Peak SFF and TF were significantly higher in HVs vs both AI groups (P < .05). Peak SFF and TF (6.8 µg/dL vs 2.2 µg/dL; [188 nmol/L vs 62 nmol/L]; P < .01) were significantly higher in the secondary adrenal insufficiency vs primary adrenal insufficiency patients. The optimal peak SFF criterion to identify adrenal insufficiency patients vs HV was 0.9 µg/dL (25 nmol/L) (sensitivity of 95%, specificity of 100%). Mean CBG and albumin levels were similar among all four groups. CH patients had a higher peak SFF than HV (2.4 vs 2.0 µg/dL; P = .02. In the CH patients, peak salivary cortisol levels correlated well with peak SFF (rs = 0.84, P = .005). CBG levels were similar among the groups. CONCLUSION: We provide normative data for SFF values in HV and AI during the CST. Normal CBG levels in mild cirrhosis did not affect the interpretation of the CST.

Primary vs secondary adrenal insufficiency: ACTH-stimulated aldosterone diagnostic cut-off values by tandem mass spectrometry.

OBJECTIVES: To validate the diagnostic utility of Cortrosyn(™) stimulated aldosterone in the differentiation of primary (PAI) and secondary adrenal insufficiency (SAI) and to evaluate the effect of urine sodium levels and posture on test performance. DESIGN: Cross-sectional study. METHODS: Healthy volunteers (HV; n = 46) and patients with PAI (n = 26) and SAI (n = 29) participated in the study. Testing included cortisol and aldosterone (by liquid-chromatography tandem mass spectrometry) measurements at baseline and 30 and 60 min after 250 µg Cortrosyn(™). Plasma corticotropin (ACTH), renin activity (PRA) and urine spot sodium as a proxy for 24-h urine sodium excretion were measured at baseline. The effect of a sitting or semifowlers posture was evaluated in healthy volunteers. RESULTS: A Cortrosyn(™)-stimulated aldosterone level of 5 ng/dl (0·14 nmol/l) had 88% sensitivity and positive predictive value and 89·7% specificity and negative predictive value for distinguishing PAI from SAI. Spot urine sodium levels showed a strong correlation with peak aldosterone levels (r = -0·55, P = 0·02, n = 18) in the SAI but not PAI or HV groups. Posture did not have a significant effect on results. CONCLUSIONS: Once diagnosed with adrenal insufficiency, a stimulated aldosterone value of 5 ng/dl (0·14 nmol/l) works well to differentiate PAI from SAI. However, clinicians should be aware of the possible effect of total body sodium as reflected by spot urine sodium levels on aldosterone results. A 24-h urine sodium measurement may be helpful in interpretation.

A direct comparison of quality of life in obese and Cushing's syndrome patients.

OBJECTIVE: Obese (OB) individuals and patients with Cushing's syndrome (CS) often have similar clinical presentations. While each group has reduced health-related quality of life (HRQL), it is not known whether the degree of impairment is different and might distinguish between them. The objective of this study was to compare HRQL in these two populations. DESIGN: Cross-sectional study. METHODS: Three hundred and twenty-seven OB patients (48.1±11.7 years; 72.5% women) with weight gain and at least two features of CS were recruited from an outpatient weight management clinic. Sixty-six untreated patients with CS (41.6±13.2 years; 78.8% women) presented to the NIH Clinical Center for evaluation. Subjects completed the SF-36 survey and a locally created symptom questionnaire. RESULTS: After adjusting for symptom count, OB patients had a significantly higher (better HRQL) mean physical component summary (PCS) score than CS patients (44.9±0.6 vs 35.4±1.5, P<0.0001). However, the mean mental component summary (MCS) score was lower (worse HRQL) in the OB group (41.6±0.6 vs 50.7±1.6, P<0.0001). Symptom count showed significant correlations with PCS and MCS scores. BMI correlated with PCS (r=-0.29) in OB but not in CS patients. BMI was not associated with MCS in either group. CONCLUSION: HRQL is significantly different between OB and CS patients. Surprisingly, after adjusting for symptom count, OB patients showed worse mental health scores than the CS population. Significant differences in HRQL and symptom count may suggest which OB patients should be screened for CS.

Adrenal histologic findings show no difference in clinical presentation and outcome in primary hyperaldosteronism.

BACKGROUND: Primary hyperaldosteronism is most commonly due to a solitary cortical adenoma. Thus, some surgeons have suggested a subtotal adrenalectomy is a reasonable approach when a mass can be identified. On the other hand, adrenal vein sampling (AVS) is being used more frequently to distinguish patients with unilateral disease for adrenalectomy, even if a discrete mass is not identified on axial imaging. In these cases, surgical pathology may reveal a cortical adenoma, a cortical adenoma with hyperplasia, or cortical hyperplasia. The goal of this study was to compare the presentation and outcome among patients undergoing adrenalectomy and found to have different histologic features. METHODS: We performed a retrospective analysis of 136 patients with primary hyperaldosteronism. A total of 95 patients had an adrenalectomy for unilateral disease. The preoperative clinical and laboratory, and postoperative outcome of the three aforementioned histologic groups were compared. RESULTS: A total of 95 patients underwent an adrenalectomy. We found no significant difference in age, gender, body mass index, duration of hypertension, number of antihypertensive medications, serum aldosterone level, serum renin level, or adrenal vein sampling ratios among the three histologic categories. We also found no significant difference among the three categories in postoperative cure rate. CONCLUSION: The rate of unilateral hyperplasia in patients with primary hyperaldosteronism (16%) is likely higher than previously reported, which may be due to the increasing use of AVS. The clinical presentation and outcome of patients regardless of the histologic findings are similar. Our data also suggests that subtotal adrenalectomy would not be appropriate in patients with primary hyperaldosteronism.