Citations

Abstract Primary aldosteronism ( PA ), the most common form of secondary hypertension, can be either surgically cured or treated with targeted pharmacotherapy. PA is frequently undiagnosed and untreated, leading to aldosterone‐specific cardiovascular morbidity and nephrotoxicity. Thus, clinicians should perform case detection testing for PA at least once in all patients with hypertension. Confirmatory testing is indicated in most patients with positive case detection testing results. The next step is to determine whether patients with confirmed PA have a disease that can be cured with surgery or whether it should be treated medically; this step is guided by computed tomography scan of the adrenal glands and adrenal venous sampling. With appropriate surgical expertise, laparoscopic unilateral adrenalectomy is safe, efficient and curative in patients with unilateral adrenal disease. In patients who have bilateral aldosterone hypersecretion, the optimal management is a low‐sodium diet and lifelong treatment with a mineralocorticoid receptor antagonist administered at a dosage to maintain a high–normal serum potassium concentration without the aid of oral potassium supplements.

Objectives: Catecholamine-secreting jugular paragangliomas (JPs) represent a rare subset of head and neck paragangliomas that may present with hypertension, arrhythmia, or syncopal episodes. Subtotal resection to protect critical neurovascular structures may result in persistent catecholamine excess from residual tumor. Herein, we report our experience with stereotactic radiosurgery (SRS) for salvage treatment of catecholamine-secreting JP following subtotal microsurgical resection. Patients: Adult patients treated with SRS after subtotal microsurgical resection of catecholamine-secreting JP. Interventions: SRS. Main Outcome Measures: Post-treatment catecholamine and metanephrine levels, clinical outcomes, and tumor control. Results: Of 85 patients with JPs treated with primary or salvage radiosurgery between 1990 and 2017, 2 (2%) harbored nonmalignant secreting tumors. Patient 1 developed catecholamine excess with elevated norepinephrine (NE) at 475 mcg/24 hours (normal < 80 mcg/24 h). Following subtotal resection, she developed catecholamine excess with radiographic evidence of tumor growth and therefore underwent SRS. Three years post-SRS and beyond, catecholamine levels remained normalized (NE 62 mcg/24 h at 10 yr) and tumor volume remained stable on serial MRI studies over the 17-year follow-up period. Patient 2 developed symptomatic arrhythmia and was found to have a JP. Urine norepinephrine (NE) was elevated at 213 mcg/24 hours. She underwent nerve-sparing subtotal resection and upfront SRS was used to treat residual tumor. Twenty months following SRS, the area of residual JP had not enlarged in size and catecholamine levels remained normal (NE 46 mcg/24 h). Conclusions: Radiosurgery can be used in salvage treatment of catecholamine-secreting JP, providing durable tumor control and resolution of catecholamine excess. For patients with large catecholamine-secreting JP and normal lower cranial nerve function, aggressive nerve-sparing subtotal resection with adjuvant radiosurgery may offer a low-morbidity alternative to gross total resection. Further study of this subset of patients is warranted to substantiate these promising, yet preliminary findings.

Summary Objective To identify predictors of hypothalamic‐pituitary‐adrenal ( HPA ) axis recovery interval and severity of glucocorticoid withdrawal symptoms ( GWS ) in patients undergoing adrenalectomy for corticotropin‐independent cortisol excess. Design This is a retrospective study of patients with mild autonomous cortisol excess ( MACE ), moderate and severe Cushing syndrome ( CS ) who developed adrenal insufficiency after unilateral adrenalectomy between 1998 and 2017. Results Adrenalectomy was performed in 81 patients (79% women, median age 52 years [ IQR 42‐62]). HPA axis recovery occurred at a median of 4.3 months ( IQR 1.6‐11.4) after adrenalectomy (severe CS vs moderate CS vs MACE : median 11.4 vs 2.8 vs 2.1 months, P < 0.01). Main predictors of HPA axis recovery interval included: preoperative serum cortisol concentration after 1‐mg overnight dexamethasone suppression test >10 μg/ dL or >276 nmol/L (9.7 vs 1.3 months if cortisol ≤10 μg/ dL or ≤276 nmol/L, P < 0.01); body mass index (for every 3 kg/m 2 decrease, glucocorticoid taper increased by 1 month, P < 0.05); age <45 (11.4 vs 2.3 months if ≥45 years, P < 0.05); duration of symptoms prior to diagnosis >1 year (11.4 vs 2.8 months if ≤1 year); moon facies (11.4 vs 2.2 months if no rounding of the face); and myopathy (13.1 vs 2.7 months if no myopathy, P < 0.05). Patients with severe CS had a higher incidence of GWS compared to patients with MACE (66.7% vs 40.0%, P < 0.05) with a median of 1 and 0 events/patient, respectively. Conclusions The HPA axis recovery interval was the longest for patients with severe CS . Surprisingly, patients with moderate CS recovered their HPA axis as quickly as those with MACE . Glucocorticoid withdrawal symptoms were observed in all groups, with more events in patients with severe CS . This study emphasizes the need to counsel patients on expectations for HPA axis recovery and address intervention for GWS based on individual preoperative parameters.

SummaryContextAbdominal visceral adiposity and central sarcopenia are markers of increased cardiovascular risk and mortality.ObjectiveTo assess whether central sarcopenia and adiposity can serve as a marker of disease severity in patients with adrenal adenomas and glucocorticoid secretory autonomy.DesignRetrospective cohort study.PatientsTwenty‐five patients with overt Cushing's syndrome (CS), 48 patients with mild autonomous cortisol excess (MACE) and 32 patients with a nonfunctioning adrenal tumour (NFAT) were included.MethodsMedical records were reviewed, and body composition measurements (visceral fat [VAT], subcutaneous fat [SAT], visceral/total fat [V/T], visceral/subcutaneous [V/S] and total abdominal muscle mass) were calculated based on abdominal computed tomography (CT).ResultsIn patients with overt CS, when compared to patients with NFAT, the V/T fat and the V/S ratio were increased by 0.08 (P < .001) and by 0.3 (P < .001); however, these measurements were decreased by 0.04 (P = .007) and 0.2 (P = .01), respectively, in patients with MACE. Total muscle mass was decreased by −10 cm2 (P = .02) in patients with overt CS compared to patients with NFAT. Correlation with morning serum cortisol concentrations after dexamethasone suppression testing revealed that for every 28 nmol/L cortisol increase there was a 0.008 increase in V/T (P < .001), 0.02 increase in the V/S fat ratio (P < .001) and a 1.2 cm2 decrease in mean total muscle mass (P = .002).ConclusionsThe severity of hypercortisolism was correlated with lower muscle mass and higher visceral adiposity. These CT‐based markers may allow for a more reliable and objective assessment of glucocorticoid‐related disease severity in patients with adrenal adenomas.

SummaryObjectiveThymic neuroendocrine tumour (TH‐NET) accounts for almost 20% of multiple endocrine neoplasia type 1 (MEN1)‐associated mortality. Identifying risk factors for the development of these rare tumours and prognostic factors for clinical outcomes will be helpful in clinical practice.Design and PatientsWe performed a retrospective analysis of patients treated for TH‐NET associated with MEN1 in a single institution and meta‐analysis of literature reports. We used a fixed effect model to pool results across studies to evaluate the prevalence, clinical features and prognosis.ResultsTH‐NET was detected in 9 (7.4%) of 121 patients with MEN1 seen in our institution, and 5 (55.6%) were women. Seven additional studies were identified through a systematic review of the literature. The pool estimate of TH‐NET prevalence was 3.7% (n = 99) in MEN1 (n = 2710), sex ratio was 79:20 (male vs female), and the median age at diagnosis was 43.0 years (range, 16.0‐72.0 years). Forty‐three patients died with a median survival time of 8.4 years. Older age at diagnosis (HR = 1.4, 95% CI = 1.0‐1.8, P = .03), maximum tumour diameter (HR = 1.5, 95% CI = 1.0‐2.3, P = .04) and presence of metastasis (HR = 1.6, 95% CI = 1.0‐2.5, P = .04) were associated with worse outcome. A male predominance (91.9% vs 59.5%, P < .001) and history of smoking (59.0% vs 23.5%, P = .015) were more common in American/European series compared to Asian reports.ConclusionTH‐NET is a rare but fatal component of MEN1. Earlier detection of TH‐NET in patients with MEN1 may be recommended which should theoretically result in better outcomes. Different genetic backgrounds (race) appear to result in clinical difference.

SummaryObjectiveEvidence on the diagnostic performance of adrenal imaging is limited. We aimed to assess the diagnostic performance of unenhanced computed tomography (CT) and 18F‐fluorodeoxyglucose (18FDG) positron emission tomography (PET)/CT imaging in a high‐risk population for adrenal malignancy using an optimal reference standard.DesignRetrospective cohort study.MethodsImaging studies of patients with adrenal nodules who underwent adrenal biopsy and/or adrenalectomy between 1994 and 2014 were reviewed and compared to the reference standard of histology. Eighty % of patients presented with known or suspected extra‐adrenal malignancy.ResultsUnenhanced abdominal CT was performed in 353 patients with adrenal lesions; median size was 3 (0.7‐15) cm and median radiodensity was 33 (−21‐78) Hounsfield units (HU). Radiodensity of >10 HU diagnosed malignancy with a sensitivity of 100%, specificity of 33%, positive predictive value (PPV) of 72% and negative predictive value (NPV) of 100%. 18FDG‐PET/CT was performed in 89 patients; median tumour size was 2.1 (0.7‐9.2) cm. Maximum standardized uptake (SUV max) was higher in malignant lesions when compared to benign lesions (median=10 [2.3‐29.4] vs 3.7 [1.4‐24.5], respectively, P<.0001). Similarly, median SUV max lesion to SUV max liver ratio (ALR) in malignant lesions was higher than in benign lesions (median=3 [0.74‐13.4] vs 1.2 [0.5‐6.6], respectively, P<.0001). 18FDG‐PET/CT ALR >1.8 diagnosed malignancy with a sensitivity of 87%, specificity of 84%, PPV of 85% and NPV of 86%.ConclusionNoncontract CT radiodensity of ≤10 HU excludes malignancy even in a high‐risk population. For indeterminate adrenal lesions, given a superior specificity, 18FDG‐PET/CT could be considered as a second stage imaging study.