Evaluation of Adrenal Vein Sampling Use and Outcomes in Patients With Primary Aldosteronism.

BACKGROUND: Primary aldosteronism (PA) occurs in 10%-20% of patients with resistant hypertension. Guidelines recommend adrenal vein sampling (AVS) to identify patients for surgical management. We evaluate the use of AVS in managing PA to better understand the selection and outcomes of medical versus surgical treatment. METHODS: A retrospective review was performed, and patients were divided into those who did (AVS) and did not have AVS (non-AVS). Demographics, aldosterone and renin levels, blood pressure, comorbidities, and antihypertensive medications were recorded. Reasons to defer AVS and medical versus surgical decision-making were examined and groups were compared. RESULTS: We included 113 patients; 39.8% (45/113) had AVS, whereas 60.2% (68/113) did not. Groups were similar in age, body mass index, and initial systolic blood pressure (SBP). In patients who underwent AVS, 31 of 45 (68.9%) had unilateral secretion and were referred for surgery, whereas 13 of 45 (28.9%) had bilateral secretion. Of the 31 referred for surgery, 26 underwent laparoscopic adrenalectomy, all cured; four refused surgery; and one counseled toward medical management by their physician. In 68 non-AVS patients, 6 (8.8%) underwent adrenalectomy without sampling and 2 with no clinical improvement. The remaining deferrals were because of normal or bilateral adrenal nodules on imaging (8/68, 11.8%); medical management due to poor surgical candidacy (12/68, 17.6%); patient refusal of intervention (13/68, 19.1%); or reasons not stated (28/68, 41.1%). At the follow-up, patients who underwent AVS had lower median SBP (135.4 mmHg versus 144.7 mmHg, P = 0.0241) and shorter follow-up (17.7 mo versus 54.0 mo, P < 0.0001). Surgically managed patients had biochemical resolution of PA with normalization of potassium levels (3.6 to 4.7mEq/L, P < 0.00001). CONCLUSIONS: AVS correctly selects patients for surgical management avoiding unnecessary surgery. However, despite guidelines, AVS is not always pursued as part of PA treatment, potentially excluding surgical candidates.

A survey of stated physician practices and beliefs on the use of steroids in pediatric fluid and/or vasoactive infusion-dependent shock.

OBJECTIVE: Limited evidence exists on the use of corticosteroids in pediatric shock. We sought to determine physicians' practices and beliefs with regard to the management of pediatric shock. DESIGN: Cross-sectional, Internet-based survey. SETTING: Canada. SUBJECTS: Physicians identified as practicing pediatric intensive care in any of 15 academic centers. MEASUREMENTS AND MAIN RESULTS: Seventy of 97 physicians (72.2%) responded. Physicians stated that they were more likely to prescribe steroids for septic shock than for shock following cardiac surgery (odds ratio, 1.9 [95% CI, 0.9-4.3]) or trauma (odds ratio, 11.46 [95% CI, 2.5-51.2]), and 91.4% (64/70) would administer steroids to patients who had received 60 cc/kg of fluid and two or more vasoactive medications. Thirty-five percent of respondents (25/70) reported that they rarely or never conducted adrenal axis testing before giving steroids to patients in shock. Eighty-seven percent of respondents (61/70) stated that the role of steroids in the treatment of fluid and/or vasoactive drug-dependent shock needed to be clarified and that 84.3% would be willing to randomize patients into a trial of steroid efficacy who were fluid resuscitated and on one high-dose vasoactive medication. However, 74.3% stated that they would start open-label steroids in patients who required two high-dose vasoactive medications. CONCLUSIONS: This survey provides information on the stated beliefs and practices of pediatric critical care physicians with regard to the use of steroids in fluid and/or vasoactive drug-dependent shock. Clinicians feel that the role of steroids in shock still requires clarification and that they would be willing to randomize patients into a trial. This survey may be useful as an initial framework for the development of a future trial on the use of steroids in pediatric shock.

Early assessment of postoperative adrenal function is necessary after adrenalectomy for mild autonomous cortisol secretion.

BACKGROUND: The diagnostic threshold for mild autonomous cortisol secretion using low dose, overnight, dexamethasone suppression testing is recognized widely as a serum cortisol ≥1.8 mcg/dL. The degree to which these patients require postoperative glucocorticoid replacement is unknown. METHODS: We reviewed adult patients with corticotropin (ACTH)-independent hypercortisolism who underwent unilateral laparoscopic adrenalectomy for benign disease with a dexamethasone suppression testing ≥1.8 mcg/dL at our institution from 1996 to 2018. Patients with a dexamethasone suppression testing of 1.8 to 5 mcg/dL were compared with those with a dexamethasone suppression testing >5 mcg/dL. RESULTS: We compared 68 patients with a preoperative dexamethasone suppression testing of 1.8 to 5 mcg/dL to 53 patients with a preoperative dexamethasone suppression testing >5 mcg/dL. Preoperative serum ACTH (mean 10.0 vs 9.2 pg/mL), adenoma size (mean 3.4 vs 3.5 cm), and side of adrenalectomy (37 and 47% right) were similar between groups (P > .05 each). Patients with a dexamethasone suppression testing 1.8 to 5 mcg/dL were older (mean values 58 ± 11 vs 52 ± 16 years ; P = .01), less likely to be female (63 vs 81%; P = .03), had greater body mass indexes (33.1 ± 8.4 vs 29.1 ± 5.6; P = .01), and had lesser 24 hour preoperative urine cortisol excretions (32.6 ± 26.7 vs 76.1 ± 129.4 mcg; P = .03). Postoperative serum cortisol levels were compared in 22 patients with a dexamethasone suppression testing of 1.8 to 5 mcg/dL to 14 patients with a dexamethasone suppression testing >5 mcg/dL. Those with dexamethasone suppression testing 1.8 to 5 mcg/dL had greater postoperative serum cortisol levels (8.0 ± 5.7 vs 5.0 ± 2.6 mcg/dL; P = .03), were less likely to be discharged on glucocorticoid replacement (59% vs 89%; P = .003), and had a decreased duration of treatment (4.4 ± 3.8 vs 10.7 ± 18.0 months; P = .04). CONCLUSION: Assessment of early postoperative adrenal function with mild autonomous cortisol secretion is necessary to minimize unnecessary glucocorticoid replacement.

Is the cosyntropin test redundant in the acutely ill patient suspected of adrenal insufficiency? A case report and literature review.

Relative adrenal insufficiency is an increasingly documented phenomenon in acute illness. Recognizing and treating such adrenal insufficiency has the potential to improve outcome. A post-cosyntropin cortisol value greater than 20 microg/dl has been recognized as consistent with normal adrenal function. While the cosyntropin test remains a superb test of primary adrenal failure, its utilityin the diagnosis of secondary adrenal failure is less clearly defined. In the setting of acute illness, a number of other criteria such as increment from basal serum cortisol have been used; however, the criteria for establishing adrenal insufficiency remains less clearly defined. We report a 44-year-old Caucasian female who presented with hypoglycemia and hypotension. The patient had a basal cortisol of 1.6 ug/dl and a peak serum cortisol of 23.3 ug/dl after 250 ug of cosyntropin. Despite this apparent normal response to cosyntropin, the patient responded to glucocorticoids with an improvement in her clinical status. Pituitary MRI revealed a 7-mm pituitary cyst. Pending the availability of free cortisol levels, it is prudent not to disregard low basal cortisol levels, even in the presence of a normal cosyntropin response. We recommend that clinicians managing acutely ill patients have a low threshold for initiating glucocorticoid replacement in the presence of hypoglycemia and shock regardless of the peak cortisol values.

Comparison of the shortened and standard saline infusion tests for primary aldosteronism diagnostics.

The saline infusion test (SIT) is widely used to confirm PA, but some patients may not tolerate the standard loading volume of 2 L saline over 4 h. The shortened SIT, loading only 1 L saline over 2 h, is suggested to be useful and would be more acceptable if the diagnostic utility of the shortened SIT is comparable to that of the standard SIT. We compared the diagnostic values of the plasma aldosterone concentration after 2 h of 1 L saline loading (2 h PAC) and that after 4 h of 2 L saline loading (4 h PAC) for the prediction of unilateral aldosterone hypersecretion and postoperative outcome. This retrospective, single-center study involved 555 PA-suspected patients who underwent SIT, 153 patients with adrenal vein sampling (AVS) results, and 37 patients with a 1-year postoperative evaluation. To detect the Japanese cutoff of 4 h PAC > 60 pg/mL, a 2-h PAC Youden Index at 66 pg/mL showed 91% sensitivity and 75% specificity. For unilateral aldosterone hypersecretion, the sensitivity and specificity of 2 h PAC were not inferior to those of 4 h PAC by Markov chain Monte Carlo (MCMC) methods. The sensitivity and specificity of 2 h PAC for postoperative reduction of anti-hypertensive drugs were also not inferior to those of 4 h PAC. Although using the 2 h PAC > 66 pg/mL cutoff may increase false positives for PA diagnosis, the shortened SIT, possibly using a cutoff value higher than 66 pg/mL, may be as useful as the standard SIT for selecting PA patients for AVS and to predict postoperative outcomes with reduced burden on patients.

Adrenal function testing in pediatric cancer survivors.

BACKGROUND: Central adrenal insufficiency is observed after cranial radiation therapy for cancer. Screening at risk patients is recommended, but the best screening strategy is unknown. METHODS: A retrospective review of pediatric cancer survivors who underwent hypothalamic/pituitary/adrenal axis testing was conducted. Data included: cancer diagnosis, radiotherapy dose, other endocrinopathies, and adrenal function testing. Adrenal testing included sequential low-dose corticotropin test (LDCT) and standard-dose corticotropin test (SDCT). 8 a.m. serum cortisol levels were compared to LDCT results. LDCT results were compared by radiotheroapy dose and according to the presence of endocrine comorbidities. RESULTS: Seventy-eight subjects (56% male, mean age at diagnosis 6.5 years) underwent testing. 67.9% had been treated with radiotherapy to the hypothalamus/pituitary. Mean time to diagnosis of adrenal insufficiency was 6.8 years after cancer diagnosis. Adequate adrenal function was found in 65% of patients by LDCT and 89% by SDCT. Only 21% of patients had basal serum cortisols collected at 8 a.m. Agreement between 8 a.m. baseline cortisol and LDCT was fair. Agreement between random baseline cortisol and LDCT was poor. Prevalence of central adrenal insufficiency diagnosed by LDCT increased with radiotherapy dose (8% for 10-19.9 Gy; 83% for >or=40 Gy) and the number of endocrine comorbidities. CONCLUSIONS: In pediatric cancer survivors, central adrenal insufficiency was common even in patients receiving <40 Gy to the hypothalamus/pituitary. We recommend use of LDCT, not 8 a.m. serum cortisol to screen patients who received >30 Gy of radiotherapy and those with other central endocrinopathies.

Faecal glucocorticoid metabolites: how to express yourself - comparison of absolute amounts versus concentrations in samples from a study in laboratory rats.

During the last two decades, measurement of faecal cortisol or corticosterone metabolites (FCM) has become one of the most important tools to non-invasively monitor stress in animals. However, to reliably assess an animal's adrenocortical activity, a careful validation of this technique for each species and sex investigated is obligatory. Usually results in these validation studies and in subsequent applications are expressed as concentration (FCM(conc)). Nevertheless, some authors express their results as absolute amounts (FCM(abs)) and claim this to be more accurate. A physiological validation to prove this assumption, however, is still missing as well as information about the influence of the intervals set for faecal sampling, although the chosen intervals might play an important role. Since FCM(conc) and FCM(abs) may differ and therefore lead to different conclusions, our study aimed to gain fundamental and scientifically valid information about these parameters by re-analysing a set of data obtained in a study on laboratory rats. The data basis used was derived from four validation experiments performed in male and female rats: an adrenocorticotrophic hormone challenge test, a dexamethasone (Dex) suppression test, an investigation of the diurnal variation (DV) of glucocorticoids and the stress response in reaction to the injection procedure itself (for details see Lepschy et al. Non-invasive measurement of adrenocortical activity in male and female rats. Lab Anim 2007;41:372-87). Faecal samples were collected in short time intervals and the exact amount of faeces voided during each sampling interval was documented. Throughout all performed tests strong positive correlations between FCM(conc) and FCM(abs) were found (median of r(s) > 0.72). In males, for all calculated sampling intervals (4, 8 and 12 h) pharmacological stimulation, suppression and the DV of adrenocortical activity were reflected accurately using both FCM(conc) and FCM(abs). In females, suppression of FCM by Dex was also clearly reflected in both systems. However, pharmacological stimulation was only reflected accurately by means of FCM(conc), which clearly limits the usability of FCM(abs). Thus, using the data of physiological validation experiments, we clearly demonstrate for the first time advantages and disadvantages of presenting results as FCM(conc) or FCM(abs). Based on our findings in laboratory animals such as rats, giving results as FCM(conc) seems to be more appropriate and FCM(abs) - if at all - might only be used as an addition.