Maximum adenoma diameter, regardless of uni- or bilaterality, is a risk factor for autonomous cortisol secretion in adrenal incidentalomas

Araujo‐Castro, Marta; Lázaro, Cristina Robles; Ramírez, Paola Parra; Centeno, Rogelio García; Gimeno, Paola Gracia; Fernández-Ladreda, Mariana Tomé; Núñez, Miguel Antonio Sampedro; Marazuela, Mónica; Escobar-Morreale, Héctor F.; Valderrábano, Pablo

doi:10.1007/s40618-021-01539-y

Cited by 17 publications

(27 citation statements)

References 33 publications

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“…In this line, Eisenhofer et al, [34] observed that tumour diameter showed strong positive relationships with 24-h urinary outputs of normetanephrine and metanephrine (r = 0.77; P < 0.001). Similar ndings have been described by other authors [33], and also in other functioning adrenal tumours [35]. Besides, tumour size is a classical risk factor for recurrence [36] and malignancy [37].…”

Section: Surgical Outcomessupporting

confidence: 88%

Surgical outcomes in the pheochromocytoma surgery. Results from the PHEO-RISK STUDY

et al. 2021

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Purpose: To identify presurgical and surgical risk factors for postsurgical complications in the pheochromocytoma surgery.Methods: A retrospective study of pheochromocytomas submitted to surgery in ten Spanish hospitals between 2011 and 2021. Postoperative complications were classi ed according to Clavien-Dindo scale.Results: One hundred and sixty-two surgeries (159 patients) were included. Preoperative antihypertensive blockade was performed in 95.1% of the patients, being doxazosin in monotherapy (43.8%) the most frequent regimen. Patients pre-treated with doxazosin required intraoperative hypotensive treatment more frequently (49.4% vs 25.0%, P=0.003) than patients treated with phenoxybenzamine, but no differences in the rate of intraoperative and postsurgical complications were observed. However, patients treated with phenoxybenzamine had a longer hospital stay (12.2±11.16 vs 6.2±6.82, P<0.001) than those treated with doxazosin. Hypertension resolution was observed in 78.7% and biochemical cure in 96.6% of the patients. Thirty-one patients (19.1%) had postsurgical complications. Prolonged hypotension was the most common, in 9.9% (n=16), followed by hypoglycaemia in 6 patients and acute renal failure in 4 patients. 13.0% of complications had a score ≥3 in the Clavien-Dindo scale. Postsurgical complications were more common in in patients with diabetes, cerebrovascular disease, higher plasma glucose levels, higher urinary free metanephrine and norepinephrine, and with pheochromocytomas larger than 5 cm. Conclusion:Preoperative medical treatment and postsurgical monitoring of pheochromocytoma should be especially careful in patients with diabetes, cerebrovascular disease, higher levels of plasma glucose and urine free metanephrine and norepinephrine, and with pheochromocytomas >5 cm, due to the higher risk of postsurgical complications. Introduction:Pheochromocytomas are rare neuroendocrine tumours that produce catecholamines [1]. They are a lifethreatening condition because catecholamine secretion is unpredictable, resulting in hypertension, arrhythmia, and/or other cardiovascular complications [2]. Surgery represents the primary treatment for pheochromocytomas [1]. Due to improvements in perioperative treatment, anaesthesia and surgical techniques, the mortality has dropped markedly in the last thirty years, but the risk of cardiovascular complications remains still high [3]. Intraoperative complications, including hypertensive crisis, hemodynamic instability and tachyarrhythmias, among others, have been reported in 30-50% of the pheochromocytoma surgeries [4][5][6]. The main postoperative major complications are prolonged hypotension and rebound hypoglycaemia [1]. However, postsurgical complications are usually less reported in pheochromocytoma studies, and are usually described in around 20-30% of the patients in recent series [4][7][8][9].Few studies have evaluated the grade of these complications using validate scales as the Clavien-Dindo score [4][10][9][8]. Moreover, studies evaluating risk factors for p...

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Section: Surgical Outcomessupporting

confidence: 88%

Surgical outcomes in the pheochromocytoma surgery. Results from the PHEO-RISK STUDY

et al. 2021

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“…Medical records were reviewed to extract demographic information, comorbidities, body mass index (BMI) and systolic and diastolic blood pressure. Comorbidities possibly related to ACS were defined based on current standards, as we have previously published [ 14 , 15 , 16 ]. Cardiovascular disease was defined as ischemic heart disease or heart failure, and cerebrovascular disease as transient ischemic attack or acute stroke.…”

Section: Methodsmentioning

confidence: 99%

“…The maximum adenoma diameter was used as tumour size. For bilateral AIs, the size of the largest adenoma was included in the analyses [ 14 ]. CT was repeated during follow-up in 164 patients, MRI in 115 and both studies in 26.…”

Section: Methodsmentioning

confidence: 99%

Predictors of Tumour Growth and Autonomous Cortisol Secretion Development during Follow-Up in Non-Functioning Adrenal Incidentalomas

Araujo‐Castro

Ramírez

Lázaro

et al. 2021

JCM

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Purpose: To assess the risk of developing autonomous cortisol secretion (ACS) and tumour growth in non-functioning adrenal incidentalomas (NFAIs). Methods: Multicentre retrospective observational study of patients with NFAIs. ACS was defined as serum cortisol >1.8 µg/dL after 1 mg-dexamethasone suppression test (DST) without specific data on Cushing’s syndrome. Tumour growth was defined as an increase in maximum tumour diameter >20% from baseline; and of at least 5 mm. Results: Of 654 subjects with NFAIs included in the study, both tumour diameter and DST were re-evaluated during a follow-up longer than 12 months in 305 patients. After a median follow-up of 41.3 (IQR 24.7–63.1) months, 10.5% of NFAIs developed ACS. The risk for developing ACS was higher in patients with higher serum cortisol post-DST levels (HR 6.45 for each µg/dL, p = 0.001) at diagnosis. Significant tumour growth was observed in 5.2% of cases. The risk of tumour growth was higher in females (HR 10.7, p = 0.004). Conclusions: The frequency of re-evaluation with DST in NFAIs during the initial 5 years from diagnosis can probably be tailored to the serum cortisol post-DST level at presentation. Re-evaluation of NFAIs with imaging studies, on the other hand, seems unnecessary in most cases, particularly if the initial imaging demonstrates features specific to typical adenoma, given the low rate of significant tumour growth.

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“…AI was de ned as the presence of an asymptomatic adrenal lesion greater than 1 cm detected in imaging tests not performed in the context of suspected adrenal disease (such as the extension study of a primary extra-adrenal cancer, or other abdominal diseases) [11]. The de nitions of hypertension, type 2 diabetes, obesity and dyslipidaemia were the same as a previous research shows [12]. Cardiovascular disease was de ned as ischemic heart disease or heart failure, and cerebrovascular disease as transient ischemic attack or acute stroke.…”

Section: Clinical De Nitionsmentioning

confidence: 99%

“…The size of the largest adenoma was included in the analyses. Moreover, we calculated the total adenomatous mass as the sum of the largest diameters of both adrenal incidentalomas [12]. Lipidic content was analysed in 85 patients, and the presence of necrosis, haemorrhage or other atypical radiological features were described in all AIs.…”

Section: Radiological Studymentioning

confidence: 99%

Differential Phenotype of Primary Bilateral Macronodular Adrenal Hyperplasia and Other Bilateral Adrenal Lesions With Associated Subclinical Hypercortisolism. Study of 98 Patients.

Rojano

Fernández-Argüeso

Botella-Carretero

et al. 2021

Preprint

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Purpose: To evaluate the prevalence of primary bilateral macronodular adrenal hyperplasia (PBMAH) in patients with adrenal incidentalomas (AIs) with subclinical hypercortisolism. Also to analyse the differential phenotype of patients with PBMAH compared to other bilateral adrenal lesions which do not meet PBMAH definition.Methods: Retrospective study of patients with AIs diagnosed in our centre between 2013 and 2019 (n=730). Patients with bilateral disease and associated subclinical hypercortisolism (possible ACS or ACS) were included (n=98). Possible ACS and ACS were defined as a cortisol post-1mg-dexamethasone suppression test (DST)>1.8µg/dl but ≤5.0µg/dl and >5.0µg/dl. without specific clinical signs of Cushing´s syndrome, respectively. PBMAH diagnosis was established in patients with subclinical hypercortisolism, hyperplasia and bilateral adrenal nodules >1cm.Results: PBMAH was confirmed in 31.6% of bilateral AIs with subclinical hypercortisolism. Patients with PBMAH presented a higher prevalence of ACS than non-PBMHA (OR 4.1, 95%CI 1.38-12.09, P=0.010), but differences disappeared after adjusting by tumour size and total adenomatous mass (adjusted OR 2.3, 95%CI=0.65-8.27 and 2.3, 95%CI 0.47-11.21, respectively). However, no significant differences in the cardiometabolic profile of both groups were observed. Tumour size and total adenomatous mass were significantly higher in PBMAH (30.2±12.16 vs 24.3±8.47, P=0.010 and 53.9±20.8 vs 43.3±14.62, P=0.023).Conclusion: PBMAH is common in patients with incidentally detected bilateral adrenals lesions with associated subclinical hypercortisolism. The higher prevalence of ACS in PBMAH compared to non-PBMAH is associated with a higher tumour size and total adenomatous mass in PBMHA, but no differences in the cardiometabolic profile were observed between both groups.

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Maximum adenoma diameter, regardless of uni- or bilaterality, is a risk factor for autonomous cortisol secretion in adrenal incidentalomas

Cited by 17 publications

References 33 publications

Surgical outcomes in the pheochromocytoma surgery. Results from the PHEO-RISK STUDY

Surgical outcomes in the pheochromocytoma surgery. Results from the PHEO-RISK STUDY

Predictors of Tumour Growth and Autonomous Cortisol Secretion Development during Follow-Up in Non-Functioning Adrenal Incidentalomas

Differential Phenotype of Primary Bilateral Macronodular Adrenal Hyperplasia and Other Bilateral Adrenal Lesions With Associated Subclinical Hypercortisolism. Study of 98 Patients.

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