Distinct Late-Night Salivary Cortisol Cut-Off Values for the Diagnosis of Hypercortisolism.

Due to high morbidity and mortality of untreated hypercortisolism, a prompt diagnosis is essential. Measurement of late-night salivary cortisol provides a simple and non-invasive method. However, thresholds and reference ranges differ among studies. The goal of this study was to define a threshold of late-night salivary cortisol for the diagnosis of hypercortisolism based on the used assay. Moreover, the influence of different aetiologies of hypercortisolism and individual comorbidities were investigated. Prospective analyses of 217 patients, including 36 patients with proven hypercortisolism were carried out. A sum of 149 patients with suspicion of hypercortisolism but negative endocrine testing and 32 patients with hypercortisolism in remission served as control group. Late-night salivary cortisol was measured using an automated chemiluminescence immunoassay. Cut-off values were calculated by ROC analysis. The calculated cut-off value for the diagnosis of hypercortisolism was 10.1 nmol/l (sensitivity 94%; specificity 84%). Only slightly lower thresholds were obtained in patients with suspected hypercortisolism due to weight gain/obesity (9.1 nmol/l), hypertension or adrenal tumours (both 9.8 nmol/l) or pituitary adenomas (9.5 nmol/l). The late-night salivary cortisol threshold to distinguish between Cushing's disease and Cushing's disease in remission was 9.2 nmol/l. The cut-off value for the diagnosis of ectopic ACTH-production was 109.0 nmol/l (sensitivity 50%, specificity 92%). Late-night salivary cortisol is a convenient and reliable parameter for the diagnosis of hypercortisolism. Except for ectopic ACTH-production, thresholds considering different indications for evaluation of hypercortisolism were only slightly different. Therefore, they might only be useful if late-night salivary cortisol results near the established cut-off value are present.

Characteristics of Nonfunctioning Pituitary Adenomas That Cause Secondary Adrenal Insufficiency.

OBJECTIVE: Secondary adrenal insufficiency (sAI) is a severe endocrinologic complication associated with nonfunctioning pituitary adenoma (NFPA). However, its prevalence is not simply related to tumor size. In this study, we aimed to detect the clinical characteristics of NFPAs that cause sAI. METHODS: We retrospectively investigated the clinical data of 218 patients with newly diagnosed macro NFPA between April 2011 and March 2020. The patients for whom endocrinologists had prescribed hydrocortisone after comprehensive endocrinologic evaluation were defined as having sAI. The 7 clinical factors analyzed for association with sAI were age, sex, presence of neurologic symptoms, hospitalization for emergency management of pituitary apoplexy, degree of optic chiasm compression, and Knosp grades on both sides. RESULTS: Seventy-three patients (33%) were classified into the sAI group. Multinomial logistic regression showed the strongest correlation between sAI and Knosp grade on the less extending side (P = 0.0001), followed by sex (male) (P = 0.0013) and pituitary apoplexy (P = 0.098). Tumors that extended bilaterally and had Knosp grades of 1-3 were frequently observed in sAI and were common in males. CONCLUSIONS: The NFPAs that occupy the sella space and compress the walls on both sides of the cavernous sinus, but do not penetrate them, have a higher risk of developing sAI. This type is more common in males and is seen even in patients without visual field disturbances. This clinical finding will be beneficial in management of patients with NFPA.

"Double-Down" Adrenal Vein Sampling Results in Patients with Apparent Bilateral Aldosterone Suppression: Utility of Repeat Sampling including Super-Selective Sampling.

PURPOSE: To report outcomes of patients undergoing adrenal vein sampling (AVS) for primary aldosteronism with results indicating apparent bilateral adrenal suppression (ABAS), in which the adrenal aldosterone-to-cortisol ratios are decreased bilaterally ("double-down") compared to the non-adrenal sample, and evaluate repeat AVS results. MATERIALS AND METHODS: Between 2003 and 2020, 762 patients underwent AVS. Twenty patients (2.6%; male, 12; female, 8; age 50.3 ± 9.7 years) with ABAS on initial AVS were identified. Ten underwent repeat AVS. Super-selective AVS (SS-AVS) was employed in 6 of 10 repeat AVS (60%). Outcomes after AVS were analyzed. A lateralization index (LI) >4 was considered an indication for adrenalectomy. RESULTS: Repeat AVS was diagnostic in 70% of patients (n = 7), with 6 of 7 lateralizing with LI >4 (median LI = 32.3; range 4.6-54.8) and 1 of 7 nearly lateralizing (LI = 3.5). All 7 patients underwent adrenalectomy. ABAS was redemonstrated in 3 patients (30%): 2 with unilateral adenomas on cross-sectional imaging underwent adrenalectomy despite ABAS results and 1 was lost to follow-up. Four of 6 patients (66%) who underwent SS-AVS were diagnosed with unilateral disease (median LI = 43.3; range 23.9-54.8), with one patient's diagnosis reliant upon a single super-selective sample. In total, 9 patients underwent adrenalectomy after repeat AVS, all of whom had improved blood pressure control postoperatively. Ten patients did not undergo repeat AVS: 6 were lost to follow-up, 3 underwent medical management, and 1 underwent adrenalectomy. CONCLUSIONS: AVS should be repeated when "double-down" ABAS results are encountered. Super-selective sampling may provide worthwhile diagnostic data when employed during repeat AVS.

Comparison of the efficacy of different androgens measured by LC-MS/MS in representing hyperandrogenemia and an evaluation of adrenal-origin androgens with a dexamethasone suppression test in patients with PCOS.

BACKGROUND: The aims of this study were to compare the efficacy of different androgens measured by liquid chromatography-mass spectrometry (LC-MS/MS) in representing hyperandrogenemia and to evaluate adrenal-origin androgens with a dexamethasone suppression test in patients with polycystic ovary syndrome (PCOS). METHODS: One hundred and two patients with PCOS and 41 healthy volunteers were recruited and total serum testosterone (TT), androstenedione (AD), dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S) were measured by LC-MS/MS. ROC analysis was performed to compare the efficacy of different androgens in representing hyperandrogenemia. Dexamethasone suppression test was performed in 51 patients with PCOS and above indicators were measured after dexamethasone administration. The prediction efficacy of DHEA and DHEA-S at baseline in the dexamethasone suppression test was evaluated with ROC analysis. RESULTS: The AUCs of TT, AD, free androgen index (FAI) and DHEA-S in ROC analysis for representing hyperandrogenemia were 0.816, 0.842, 0.937 and 0.678, respectively. The optimal cutoff value of TT was 0.337 ng/ml, with a sensitivity of 72.0% and specificity of 82.93%. The optimal cutoff value for AD was 1.309 ng/ml, with a sensitivity of 81.0% and specificity of 73.17%. The optimal cutoff value of the FAI was 2.50, with a sensitivity of 87.0% and specificity of 92.68%. Alternatively, AD or FAI more than the optimal cutoff values as evidence of hyperandrogenemia had the highest sensitivity of 91.18%. The levels of cortisol, DHEA and DHEA-S were all suppressed to narrow ranges after dexamethasone administration. Nine and 8 of 51 patients with PCOS had significant decreases in TT and AD, respectively. DHEA can be used as a indicator for predicting significant decrease of TT in dexamethasone suppression test with cutoff value of 13.28 ng/ml. A total of 27.5% (14/51) of patients had DHEA-S excess, but only 1 of 9 patients who had a significant decrease in TT had elevated level of DHEA-S at baseline. CONCLUSIONS: AD measured by LC-MS/MS can represent hyperandrogenemia in PCOS patients and, combined with TT or FAI, can improve the screening efficiency of hyperandrogenemia. Seventeen percent of PCOS patients had adrenal-origin androgen dominance, with TT significantly decreasing after 2 days of dexamethasone administration. Adrenal-origin androgen dominance was not parallel with DHEA-S excess in patients with PCOS.

Assessment of mild autonomous cortisol secretion among incidentally discovered adrenal masses.

Incidentally discovered adrenal masses are common and mostly benign and non-functioning adenomas. However, evolving evidence suggests that a notable proportion of these adrenal adenomas may demonstrate mild autonomous cortisol secretion (MACS), which has been associated with an increased risk for hypertension, hyperglycemia, obesity, dyslipidemia, vertebral fractures, adverse cardiovascular events, and mortality. Therefore, it is advised that all patients with an incidentally discovered adrenal mass be tested for MACS. When there is convincing evidence for MACS, surgical adrenalectomy has been associated with an improvement in certain metabolic parameters and a reduction in vertebral fractures; however, conclusive evidence demonstrating decreased cardiovascular outcomes or mortality are not yet available. Future studies with adequate randomization and follow-up to assess adverse clinical endpoints are needed to determine the optimal management and follow-up of patients with MACS.

Computed tomography combined with confirmatory tests for the diagnosis of aldosterone-producing adenoma.

Primary aldosteronism (PA) is the most common cause of secondary hypertension, and a simpler non-invasive method for identification of aldosterone-producing adenoma (APA) is required to improve the standard of medical treatment for PA patients. We retrospectively analyzed the clinical data of hypertensive patients with an aldosterone/renin ratio (ARR) ≥30 (ng/dL)/(ng/mL/h), and surgical and/or adrenal venous sampling (AVS) results served as the gold standard for APA diagnosis. The study aimed to determine whether positive CCT and SIT results plus a unilateral adrenal nodule found by CT allow unambiguous identification of an APA with high diagnostic specificity. Clinical data from 71 APA and 47 non-APA patients were collected, and logistic regression analysis was performed to construct models. Receiver operating characteristic (ROC) curves were used to analyze the efficacy of diagnostic tests. The areas under the ROC curves (AUCs) were similar between the post-SIT plasma aldosterone concentration (PAC) and post-CCT PAC (p > 0.05). The optimal post-SIT and post-CCT PAC cutoff values were 17.2 and 21.2 ng/dL, respectively. Positive CT findings combined with a post-SIT PAC >17.2 ng/dL or post-CCT PAC >21.2 ng/dL provided specificities of 97.8% and 95.7% for predicting APA, respectively. Logistic diagnostic models 1 (M1, CT finding + post-SIT PAC) and 2 (M2, CT finding + post-CCT PAC) were built, which showed equivalent diagnostic value (AUC = 0.959 and 0.932, respectively) (p > 0.05). The models combining CT findings with post-SIT PACs or post-CCT PACs represent an easier method to distinguish APA patients from other hypertensive patients with positive upright ARR results, especially in primary care where AVS may be unavailable.

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.

Quality of life in primary aldosteronism: A prospective observational study.

BACKGROUND: Previous studies suggested that patients affected by primary aldosteronism (PA) have impaired quality of life (QOL) compared to the general population, but a direct comparison with patients affected by essential hypertension (EH) has never been performed. The aim of the study was to compare the QOL of patients affected by PA to the QOL of patients affected by EH. MATERIAL AND METHODS: We designed a prospective observational study comparing the QOL of patients with PA and carefully matched patients with EH before and after treatment. We recruited 70 patients with PA and 70 patients with EH, matched for age, sex, blood pressure levels and intensity of antihypertensive treatment. We assessed QOL at baseline and after specific treatment for PA or after optimization of medical therapy for patients with EH. RESULTS: Patients with PA displayed impaired QOL compared with the general healthy population, but similar to patients with EH. Both laparoscopic adrenalectomy and treatment with mineralocorticoid receptor antagonist allowed an improvement of QOL in patients with PA, that was more pronounced after surgical treatment. Optimization of blood pressure control by implementation of antihypertensive treatment (without MR antagonists) allowed a minimal improvement in only one of eight domains in patients with EH. CONCLUSIONS: Patients with PA have impaired QOL, which is likely caused by uncontrolled hypertension and the effects of intensive antihypertensive treatment. Surgical and medical treatment of PA allows a significant improvement of QOL, by amelioration of blood pressure control and, after surgical treatment, by reduction of antihypertensive treatment.

Adrenal haemorrhage as a complication of COVID-19 infection.

We report an unusual complication of COVID-19 infection in a 53-year-old Caucasian man. He presented with shortness of breath, fever and pleuritic chest pain. A CT pulmonary angiogram (CTPA) demonstrated acute bilateral pulmonary embolism and bilateral multifocal parenchymal ground glass change consistent with COVID-19 (SARS-CoV-2) infection. Right adrenal haemorrhage was suspected on the CTPA which was confirmed on triple-phase abdominal CT imaging. A short Synacthen test revealed normal adrenal function. He was treated initially with an intravenous heparin infusion, which was changed to apixaban with a planned outpatient review in 3 months' time. He made an uncomplicated recovery and was discharged. Follow-up imaging nearly 5 months later showed near complete resolution of the right adrenal haemorrhage with no CT evidence of an underlying adrenal lesion.

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.

The Concordance Between Imaging and Adrenal Vein Sampling Varies With Aldosterone-Driver Somatic Mutation.

BACKGROUND: Correct subtyping of primary aldosteronism (PA) is critical for guiding clinical management. Adrenal imaging is less accurate than adrenal vein sampling (AVS); nonetheless, AVS is invasive, technically challenging, and scarcely available. OBJECTIVE: To identify predictors of concordance between cross-sectional imaging and lateralized AVS in patients with PA that could help circumvent AVS in a subset of patients. METHODS: We retrospectively studied all patients with PA who underwent AVS in a tertiary referral center from 2009 to 2019. AVS was performed before and after cosyntropin stimulation. Patients with lateralized AVS in at least one condition were included. Aldosterone synthase-guided next-generation sequencing was performed on available adrenal tissue. Logistic regression was implemented to identify predictors of imaging-AVS lateralization concordance. RESULTS: A total of 234 patients (62% men), age 20 to 79 years, 73% white, 23% black, and 2% Asian were included. AVS lateralization was found: 1) both pre- and post-cosyntropin (Uni/Uni) in 138 patients; 2) only at baseline (Uni/Bi) in 39 patients; 3) only after cosyntropin stimulation (Bi/Uni) in 29 patients. Catheterization partially failed in 28 patients. AVS-imaging agreement was higher in patients with KCNJ5 versus other aldosterone-driver somatic mutations (90.3% versus 64.6%; P < 0.001); in Asian and white versus black Americans (75%, 70%, and 36%, respectively); in younger patients; and those with left adrenal nodules and contralateral suppression. Conversely, AVS-imaging agreement was lowest in Uni/Bi patients (38% vs. 69% in Uni/Uni, and 62% in Bi/Uni; P = 0.007). CONCLUSIONS: While AVS-imaging agreement is higher in young white and Asian patients, who have KCNJ5-mutated aldosterone producing adenomas, no predictor confers absolute imaging accuracy.

Development and Validation of Prediction Models for Subtype Diagnosis of Patients With Primary Aldosteronism.

CONTEXT: Primary aldosteronism (PA) comprises unilateral (lateralized [LPA]) and bilateral disease (BPA). The identification of LPA is important to recommend potentially curative adrenalectomy. Adrenal venous sampling (AVS) is considered the gold standard for PA subtyping, but the procedure is available in few referral centers. OBJECTIVE: To develop prediction models for subtype diagnosis of PA using patient clinical and biochemical characteristics. DESIGN, PATIENTS AND SETTING: Patients referred to a tertiary hypertension unit. Diagnostic algorithms were built and tested in a training (N = 150) and in an internal validation cohort (N = 65), respectively. The models were validated in an external independent cohort (N = 118). MAIN OUTCOME MEASURE: Regression analyses and supervised machine learning algorithms were used to develop and validate 2 diagnostic models and a 20-point score to classify patients with PA according to subtype diagnosis. RESULTS: Six parameters were associated with a diagnosis of LPA (aldosterone at screening and after confirmatory testing, lowest potassium value, presence/absence of nodules, nodule diameter, and computed tomography results) and were included in the diagnostic models. Machine learning algorithms displayed high accuracy at training and internal validation (79.1%-93%), whereas a 20-point score reached an area under the curve of 0.896, and a sensitivity/specificity of 91.7/79.3%. An integrated flowchart correctly addressed 96.3% of patients to surgery and would have avoided AVS in 43.7% of patients. The external validation on an independent cohort confirmed a similar diagnostic performance. CONCLUSIONS: Diagnostic modelling techniques can be used for subtype diagnosis and guide surgical decision in patients with PA in centers where AVS is unavailable.

Efficacy of endoscopic transsphenoidal surgery for cushing's disease: Case series and review of the literature.

BACKGROUND: This study was performed to examine the efficacy of endoscopic transsphenoidal surgery (ETS) for Cushing's disease at a single institute and to review past reports. MATERIAL AND METHODS: We studied eight consecutive patients who underwent ETS for Cushing's disease. The radiological evaluation comprised a detailed examination of preoperative magnetic resonance images (MRIs), including inferior petrosal sinus sampling, for cases with normal renal function. Remission was evaluated at least three months after surgery and was defined by the presence of hypocortisolemia that required steroid replacement therapy or eucortisolemia with suppression to <1.8 µg/dL after 1mg of dexamethasone. RESULTS: In all cases preoperative MRI was abnormal and included two macroadenomas (25 %). Pathological confirmation of an adenoma was possible in all patients. The mean follow-up period was 5.6 (2-7) years. Remission was confirmed in 75.0% of the cases and was higher in rate for microadenoma (100%) than for macroadenoma (50%). Postoperatively , no cerebrospinal fluid rhinorrhea occurred, but new endocrine deficits were noted in 25% of patients. CONCLUSION: Based on this study, ETS enhanced the intrasellar identification of adenomatous tissue, which led to low remission and complication rates that were comparable with those of traditional microsurgery for Cushing's disease.

Overestimation of glomerular filtration rate calculated from serum creatinine as compared with cystatin C in patients with subclinical hypercortisolism: Hyogo Adrenal Metabolic Registry.

The skeletal muscle mass are decreased in the patients with hypercortisolism. Glomerular filtration rate (eGFR) is not accurately evaluated by calculation from serum creatinine (eGFRcre) in these patients. However, it is not known whether it applies to patients with subclinical hypercortisolism. We investigated the dissociation between eGFRcre and eGFR calculated from cystatin C (eGFRcys) in patients with subclinical hypercortisolism and its association with the skeletal muscle mass. This cross-sectional study includes 23 patients with overt Cushing's syndrome (CS), 84 patients with possible autonomous cortisol secretion (pACS) and 232 patients with non-functioning adenomas (NFA). eGFRcre, eGFRcys, the ratio of eGFRcre to eGFRcys (eGFRcre/eGFRcys) were calculated. Skeletal muscle index (SMI) was measured by a direct segmental multi-frequency bioelectrical impedance body composition analyzer. eGFRcre/eGFRcys was significantly higher (p < 0.01) in pACS (mean ± standard error: 1.15 ± 0.02) than NFA (1.06 ± 0.01). In multiple linear regression analysis, the presence of pACS (ß = 0.162, p < 0.01), and post 1 mg-DST cortisol levels (ß = 0.190, p < 0.01) were significantly associated with eGFRcre/eGFRcys independent of age, gender, BMI and diabetes. eGFRcre/eGFRcys was significantly and inversely associated with SMI (r = -0.164, p = 0.02). Furthermore, post 1 mg-DST cortisol levels was significantly associated with SMI in simple (r = -0.177, p = 0.01) and multiple (ß = -0.089, p = 0.01) regression analyses. In conclusion, dissociation between eGFRcre and eGFRcys was observed in patients with subclinical hypercortisolism at least partly explained by muscle mass. Our findings raise an important clinical point that eGFRcre value should be carefully evaluated even in the phase of subclinical hypercortisolism.

Adrenocortical hyperplasia: a review of clinical presentation and imaging.

Adrenal hyperplasia is non-malignant enlargement of the adrenal glands, which is often bilateral. It can be incidental or related to indolent disease process and may be related to benign or malignant etiologies causing biochemical alterations in the hypothalamic-pituitary-adrenal axis which controls steroidogenesis and in particular cortisol production. Clinical significance of the adrenal hyperplasia is variable ranging from asymptomatic finding to serious manifestations of Cushing syndrome. This is often associated with anatomical changes in the adrenal glands, which typically manifests as diffuse and sometimes nodular enlargement of the adrenal glands radiologically. Approaching adrenal hyperplasia requires careful clinical and biochemical evaluation in correlation with imaging review to differentiate ACTH-dependent and ACTH-independent etiologies. CT is the primary modality of choice for adult adrenal imaging owing to reproducibility, temporal and spatial resolution and broader access, while MRI often serves a complimentary role. Ultrasound and MRI are most commonly used in pediatric cases to evaluate congenital adrenal hyperplasia. This article will discuss the clinical presentation and imaging features of different types and mimics of adrenal cortical hyperplasia.

Plasma Aldosterone After Seated Saline Infusion Test Outperforms Captopril Test at Predicting Clinical Outcomes After Adrenalectomy for Primary Aldosteronism.

OBJECTIVE: The saline infusion test (SIT) and the captopril test (CT) are widely used as confirmatory tests for primary aldosteronism (PA). We hypothesized that post-SIT and post-CT plasma aldosterone concentrations (PAC) indicate the severity of aldosterone-producing adenoma (APA) and might predict clinical outcome. METHODS: We recruited 216 patients with APA in the Taiwan Primary Aldosteronism Investigation (TAIPAI) registry who received both seated SIT and CT as confirmatory tests. The data of 143 patients who underwent adrenalectomy with complete follow-up after diagnosis were included in the final analysis. We determined the proportion of patients achieving clinical success in accordance with the Primary Aldosteronism Surgical Outcome consensus. Logistic regression analysis was conducted to identify preoperative factors associated with cure of hypertension. RESULTS: Complete clinical success was achieved in 48 (33.6%) patients and partial clinical success in 59 (41.2%) patients; absent clinical success was seen in 36 (25.2%) of 143 patients. Post-SIT PAC but not post-CT PAC was independently associated with clinical outcome. Higher levels of post-SIT PAC had a higher likelihood of clinical benefit (complete plus partial clinical success; odds ratio = 1.04 per ng/dl increase, 95% confidence interval = 1.01, 1.06; P = 0.004). Patients with post-SIT PAC > 25 ng/dl were more likely to have a favorable clinical outcome after adrenalectomy. This cutoff value translated into a positive predictive value of 86.0%. CONCLUSIONS: We suggest that post-SIT PAC is a better predictor than post-CT PAC for clinical success in PA post adrenalectomy.

Recovery of Adrenal Function after Pituitary Surgery in Patients with Cushing Disease: Persistent Remission or Recurrence?

BACKGROUND: Cushing disease (CD) represents the principal cause of endogenous hypercortisolism. The first-line therapy of CD is surgical removal of the ACTH-secreting pituitary adenoma, which is generally followed by adrenal insufficiency (AI). OBJECTIVE: To analyze the recovery of AI in patients with CD after pituitary surgery in relation with recurrence and persistent remission of CD. PATIENTS AND METHODS: We performed a retrospective analysis of patients with CD who met the following inclusion criteria: adult age, presence of AI 2 months after the surgical intervention, and a minimum follow-up of 3 years after the surgical intervention. RESULTS: Sixty-one patients were followed for a median of 6 years. Ten (16.4%) patients recurred during follow-up. The patients who restored adrenal function did so after a median time of 19 months, with a significantly shorter time in the recurrence group (12.5 vs. 25 months, p = 0.008). All 10 patients who recurred recovered their adrenal function within 22 months. The recovery rate of AI in the persistent remission group was 37.3% (19/51) at 3 years and 55.8% (24/43) at 5 years. In all patients the duration of AI was negatively associated with disease recurrence. CONCLUSION: The duration of postsurgical AI in patients with recurrent CD is significantly shorter than that in patients with persistently remitted CD, and this parameter may be a useful predictor of recurrence. Patients showing a normal pituitary-adrenal axis within 2 years after surgery should be strictly monitored as they are at higher risk of disease relapse.

Free Cortisol Is a More Accurate Marker for Adrenal Function and Does Not Correlate with Renal Function in Cirrhosis.

BACKGROUND: The accuracy of diagnosis and clinical implications of the hepatoadrenal syndrome, as currently diagnosed using total cortisol, remain to be validated. AIM: The aim of this study was to assess adrenal function using free cortisol in stable cirrhosis and study the potential implications of any abnormalities for renal and/or cardiac function. METHODS: Sixty-one stable consecutively enrolled patients with cirrhosis underwent assessment of adrenal function using the low-dose short Synacthen test, renal function by 51Cr-EDTA glomerular filtration rate (GFR), and cardiac function by two-dimensional echocardiography. RESULTS: Eleven patients (18%) had total peak cortisol (PC) < 500 nmol/L, but no patient had free PC < 33 nmol/L indicating that diagnosis of AI using total cortisol is not confirmed using free cortisol. Free cortisol did not correlate with GFR or parameters of cardiac function. Patients with higher Child-Pugh class had progressively lower free cortisol. Patients with low GFR < 60 mL/min (N = 22) had more frequently grade II-III diastolic dysfunction (66.7% vs. 17.6%; p = 0.005) and had higher Child-Pugh and MELD score compared to those with normal GFR. CONCLUSIONS: Diagnosis of AI using total cortisol is not confirmed using free cortisol and is thus considered unreliable in cirrhosis. Free cortisol is not associated with renal or cardiac dysfunction. Lower free cortisol in more advanced stages of liver disease might be secondary to decreased synthesis due to lower cholesterol levels. Irrespective of free cortisol, parameters of cardiac dysfunction are associated with renal impairment supporting the cardio-renal hypothesis.

[CME: Adrenal Insufficiency]. / CME: Nebennierenrinden- insuffizienz.

CME: Adrenal Insufficiency Abstract. Patients suffering from adrenal insufficiency (AI) often present with unspecific symptoms. Therefore, the diagnosis of AI, a potential life-threatening condition, can be missed. Lab tests, especially the ACTH-stimulation test, play a crucial role in the diagnosis of AI. According to the different etiologies, AI can be grouped into a primary (adrenal) or central (hypothalamic or pituitary, respectively) form. However, the most common cause is the treatment with glucocorticoids, which can lead to central AI. Patients suffering from AI are given hydrocortisone. The chronic replacement dose should be as low as possible, in acute situations, a rapid and sufficient increase of the hydrocortisone dose is necessary to prevent adrenal crisis. Replacement therapy with fludrocortisone is only necessary in patients with primary AI.