Cushing syndrome (CS), a fatal disease, is suspected in many thousands of patients each year, but confirmed in only a fraction of these. This project seeks to identify accurately which patients have Cushing syndrome, to define the etiology of their disease, and to treat it optimally. A major initiative in the past year has been to examine the potential role of vasopressin in the pathogenesis of Cushing's disease. Vasopressin (VP) is known to induce ACTH secretion, and thus might stimulate corticotropes to form tumors. We measured vasopressin concentrations in the petrosal sinuses of patients with Cushing's syndrome and normal volunteers. Unexpectedly, regardless of diagnostic group, nearly all subjects showed a """"""""dominant"""""""" petrosal sinus on basal sampling, so that one of the petrosal sinuses had greater levels of both ACTH and VP than the contralateral sinus. However, the absolute concentration of VP was greater in patients with CS than in normal volunteers, and was similar in patients with various causes of CS. Petrosal sinus VP levels in the dominant petrosal sinus increased further after CRH administration. The similarity of petrosal VP levels in CS suggests that VP is not involved in the etiology of Cushing's disease. Other studies during this reporting period focussed on diagnostic and treatment approaches for patients with adrenal masses. We examined the role of surgery in management of pheochromocytoma, demonstrating that bilateral adrenalectomy should not be performed in the setting of ACTH secretion from the tumor.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Intramural Research (Z01)
Project #
1Z01HD000638-03
Application #
2575638
Study Section
Special Emphasis Panel (DEB)
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
1996
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code
Raff, Hershel; Sharma, Susmeeta T; Nieman, Lynnette K (2014) Physiological basis for the etiology, diagnosis, and treatment of adrenal disorders: Cushing's syndrome, adrenal insufficiency, and congenital adrenal hyperplasia. Compr Physiol 4:739-69
Sharma, S T; Nieman, L K (2013) Is prolactin measurement of value during inferior petrosal sinus sampling in patients with adrenocorticotropic hormone-dependent Cushing's Syndrome? J Endocrinol Invest 36:1112-6
Sharma, S T; Nieman, L K (2012) Prolonged remission after long-term treatment with steroidogenesis inhibitors in Cushing's syndrome caused by ectopic ACTH secretion. Eur J Endocrinol 166:531-6
Baid, Smita K; Rubino, Domenica; Sinaii, Ninet et al. (2009) Specificity of screening tests for Cushing's syndrome in an overweight and obese population. J Clin Endocrinol Metab 94:3857-64
Nieman, Lynnette K; Biller, Beverly M K; Findling, James W et al. (2008) The diagnosis of Cushing's syndrome: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 93:1526-40
Nieman, Lynnette (2007) Editorial: The dexamethasone-suppressed corticotropin-releasing hormone test for the diagnosis of Cushing's syndrome: what have we learned in 14 years? J Clin Endocrinol Metab 92:2876-8
Baid, Smita K; Sinaii, Ninet; Wade, Matt et al. (2007) Radioimmunoassay and tandem mass spectrometry measurement of bedtime salivary cortisol levels: a comparison of assays to establish hypercortisolism. J Clin Endocrinol Metab 92:3102-7
Nieman, Lynnette K (2007) Screening for reversible osteoporosis: is cortisol a culprit? Ann Intern Med 147:582-4
Newell-Price, John; Bertagna, Xavier; Grossman, Ashley B et al. (2006) Cushing's syndrome. Lancet 367:1605-17
Weil, Robert J; Vortmeyer, Alexander O; Nieman, Lynnette K et al. (2006) Surgical remission of pituitary adenomas confined to the neurohypophysis in Cushing's disease. J Clin Endocrinol Metab 91:2656-64

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