Zahrae Sandouk1, Philip Johnston2, Dustin Bunch3, Sihe Wang4, James Bena5, Amir Hamrahian6, Laurence Kennedy7. 1. Division of Metabolism, Endocrinology, and Diabetes, Department of Medicine, University of Michigan, Ann Arbor, Michigan. 2. Regional Centre for Endocrinology and Diabetes, Royal Victoria Hospital, Belfast, Northern Ireland. 3. Department of Pathology, Yale School of Medicine, New Haven, Connecticut. 4. Department of Clinical Pathology, Cleveland Clinic, Cleveland, Ohio. 5. Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio. 6. Department of Endocrinology, Medical Subspecialties Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates. 7. Department of Endocrinology, Diabetes and Metabolism, Cleveland Clinic, Cleveland, Ohio.
Abstract
Background: The frequency of variable hormonogenesis in patients with Cushing disease (CD) but without cyclical symptoms is unclear. Aim: To assess the frequency of variable hormonogenesis in patients presenting with CD. Methods: Over a 6-month period, patients with confirmed or suspected CD provided late-night salivary samples for up to 42 consecutive nights. Results: Of 19 patients confirmed to have CD, 16 provided at least 7 consecutive salivary samples, and 13 provided at least 21; these 16 patients are the subjects of this report. Twelve patients had at least three peak and two trough levels of late-night salivary cortisol (LNSC) but in only two patients were strict criteria for cyclical hormonogenesis fulfilled; variation was assessed as random in the others. Eight patients had de novo CD, and eight had recurrent/persistent disease. All patients with recurrent/persistent CD had two or more normal results, and in four of these patients, >50% of LNSC were normal. In six patients with de novo disease with at least one normal LNSC level, the maximum levels ranged from 1.55 to 15.5 times the upper limit of normal. Conclusions: Extreme fluctuations of cortisol production, measured by sequential LNSC, are common in CD. In newly diagnosed disease, this may only occasionally impair diagnostic ability, whereas in most patients with recurrent/persistent disease after pituitary surgery, LNSC is frequently within the reference range, with potential to cause diagnostic problems.
Background: The frequency of variable hormonogenesis in patients with Cushing disease (CD) but without cyclical symptoms is unclear. Aim: To assess the frequency of variable hormonogenesis in patients presenting with CD. Methods: Over a 6-month period, patients with confirmed or suspected CD provided late-night salivary samples for up to 42 consecutive nights. Results: Of 19 patients confirmed to have CD, 16 provided at least 7 consecutive salivary samples, and 13 provided at least 21; these 16 patients are the subjects of this report. Twelve patients had at least three peak and two trough levels of late-night salivary cortisol (LNSC) but in only two patients were strict criteria for cyclical hormonogenesis fulfilled; variation was assessed as random in the others. Eight patients had de novo CD, and eight had recurrent/persistent disease. All patients with recurrent/persistent CD had two or more normal results, and in four of these patients, >50% of LNSC were normal. In six patients with de novo disease with at least one normal LNSC level, the maximum levels ranged from 1.55 to 15.5 times the upper limit of normal. Conclusions: Extreme fluctuations of cortisol production, measured by sequential LNSC, are common in CD. In newly diagnosed disease, this may only occasionally impair diagnostic ability, whereas in most patients with recurrent/persistent disease after pituitary surgery, LNSC is frequently within the reference range, with potential to cause diagnostic problems.
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