Subclinical cushing syndrome due to adrenocorticotropic hormone-independent macronodular adrenocortical hyperplasia: changes in plasma cortisol levels during long-term follow-up

Objective: Ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) is a heterogeneous condition caused by neuroendocrine neoplasms (NENs) located in the lungs, thymus, or pancreas. Our purpose was to evaluate the long-term outcome of these patients. Methods: Retrospective study at a referral center. The charts of 164 patients with Cushing syndrome, followed at our center from 1993 to 2019, were analyzed. Results: EAS was found in 16 patients (9.75%, 9 women, mean age 36.01 years) who had been followed for a median of 72 months. The source of EAS was a NEN in 10 patients (8 bronchial and 2 thymic carcinoid tumors) and a mixed corticomedullary tumor, consisting of a pheochromocytoma and an adrenocortical carcinoma in 1 patient. In 2 of the 6 patients initially considered to have occult EAS, the source of the ACTH excess became apparent after adrenalectomy, whereas in the remaining 4 (25%) patients, it has remained occult. Of the 11 patients in whom resection of the NEN was attempted, 10 patients achieved an early remission (91%), but 4 (25%) of these patients had a recurrence during follow-up (biochemically and clinically silent in 2 patients). Three patients died (18.75%): the young woman with the mixed corticomedullary tumor, a man with a thymic NEN that evolved into a neuroendocrine (NE) carcinoma after 11 years of follow-up, and a woman with a bronchial NEN. Conclusion: The course of EAS varies according to tumor type and grade. Some patients have a protracted course, whereas others may evolve into neuroendocrine carcinomas. Abbreviations: ACTH = adrenocorticotropic hormone; CS = Cushing syndrome; CT = computed tomography; CV = coefficient of variation; EAS = ectopic ACTH syndrome; IQR = interquartile range; NEN = neuroendocrine neoplasm; SCCL = small cell carcinoma of the lung; TSS = transsphenoidal surgery; UFC = urinary free cortisol

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Adrenalectomy for Treatment of Cushing Syndrome: Results in 122 Patients and Long-Term Follow-up Studies

World Journal of Surgery ◽

10.1007/s002689900119 ◽

1996 ◽

Vol 20 (7) ◽

pp. 781-787 ◽

Cited By ~ 46

Author(s):

Tsuneo Imai ◽

Hiroomi Funahashi ◽

Yuji Tanaka ◽

Junichi Tobinaga ◽

Masaki Wada ◽

...

Keyword(s):

Cushing Syndrome ◽

Follow Up Studies ◽

Long Term Follow Up

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Adrenal Vein Cortisol to Metanephrine Ratio for Localizing ACTH-Independent Cortisol-Producing Adenoma: A Case Report

Journal of the Endocrine Society ◽

10.1210/jendso/bvab009 ◽

2021 ◽

Vol 5 (4) ◽

Author(s):

Rishi Raj ◽

Philip A Kern ◽

Neelima Ghanta ◽

Edilfavia M Uy ◽

Kamyar Asadipooya

Keyword(s):

Gold Standard ◽

Adrenocorticotropic Hormone ◽

Cushing Syndrome ◽

Emission Tomography ◽

Adrenal Vein ◽

Review Of The Literature ◽

Venous Sampling ◽

Positron Emission ◽

Subclinical Cushing Syndrome ◽

Subclinical Cushing

Abstract Context Finding the source of adrenocorticotropic hormone (ACTH)-independent cortisol-producing adenoma in the patients with subclinical Cushing syndrome (SCS) and bilateral adrenal nodules is sometimes challenging. Computed tomography (CT) and positron emission tomography are helpful, but adrenal venous sampling (AVS) is the gold standard approach. However, interpretation of AVS is important to improve the accuracy of decision-making for surgery. We report a case and review of the literature to assess the benefit of using adrenal vein cortisol to metanephrine ratio to determine the source of cortisol production in SCS and bilateral nodules. Evidence Acquisition Three authors searched PubMed for data on patients with SCS who had AVS procedure and measurements of cortisol and catecholamines. Case Description A 51-year-old woman with SCS and hypertension crisis presented to our clinic. Paraclinical investigations revealed that she had an ACTH-independent cortisol-producing adenoma and her CT scan showed bilateral adrenal nodules. After AVS, cortisol (high to low) lateralization ratio could not determine the source of cortisol production but the cortisol to metanephrine ratio localized the source to the left side, which included the larger nodule according to CT measurements. Left adrenalectomy led to clinical and paraclinical improvement. Conclusion There is a possibility of co-secretion of other steroids accompanied with cortisol in the setting of ACTH-independent SCS. Moreover, cortisol measurement alone and interpretation of AVS results based on cortisol values may not help lateralizing the source of cortisol production with bilateral adrenal nodules. Therefore, we suggest applying cortisol to metanephrine ratio with the same gradient (gradient > 2.3, highest to lowest concentration) when the source of cortisol production cannot be determined by cortisol lateralization ratio.

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Therapy and prevention for mental health: What if mental diseases are mostly not brain disorders?

Behavioral and Brain Sciences ◽

10.1017/s0140525x1800105x ◽

2019 ◽

Vol 42 ◽

Cited By ~ 2

Author(s):

John P. A. Ioannidis

Keyword(s):

Mental Health ◽

Mental Disease ◽

Brain Disorders ◽

Social Stressors ◽

Labor Education ◽

Mental Diseases ◽

Long Term Follow Up ◽

Political Decisions

AbstractNeurobiology-based interventions for mental diseases and searches for useful biomarkers of treatment response have largely failed. Clinical trials should assess interventions related to environmental and social stressors, with long-term follow-up; social rather than biological endpoints; personalized outcomes; and suitable cluster, adaptive, and n-of-1 designs. Labor, education, financial, and other social/political decisions should be evaluated for their impacts on mental disease.

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