This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Faggiano, A. Articles by Colao, A. Search for Related Content PubMed PubMed Citation Articles by Faggiano, A. Articles by Colao, A.

Nephrolithiasis in Cushing’s Disease: Prevalence, Etiopathogenesis, and Modification after Disease Cure

Departments of Molecular and Clinical Endocrinology and Oncology (A.F., R.P., M.F., M.C.D.M, C.D.S., G.L., A.C.), Pediatrics (D.M.), and Internal Medicine (M.P.), "Federico II" University, Naples, Italy

Address all correspondence and requests for reprints to: Annamaria Colao, M.D., Ph.D., Department of Molecular and Clinical Endocrinology and Oncology, "Federico II" University of Naples, Via Sergio Pansini 5, 80131 Naples, Italy. E-mail: colao{at}unina.it.

The pathogenesis of nephrolithiasis in Cushing’s syndrome is still not completely clarified. The current study aimed at investigating prevalence of nephrolithiasis and role of different lithogenic factors in Cushing’s disease (CD). Forty-six CD patients (24 with active and 22 with cured disease) and 46 sex- and age-matched controls entered the study. Body mass index, blood pressure, fasting glucose and insulin, serum and urinary creatinine, urea, uric acid, electrolytes, and cystine, urinary volume, pH, oxalate, and citrate levels, and renal ultrasonography (US) were performed in all patients and controls. Nephrolithiasis was found in 50% of active patients, 27.3% of cured patients, and 6.5% of controls (P < 0.001). Compared with controls, patients with active disease had a significantly increased prevalence of obesity, arterial hypertension, diabetes mellitus, hypercalciuria, hypocitraturia, and hyperuricosuria, significantly higher levels of serum and urinary cystine, urinary creatinine, urea, uric acid, potassium, calcium, phosphorus, and oxalate, significantly lower levels of urinary citrate levels. Compared with controls, patients cured from CD had a significantly increased prevalence of obesity, systemic arterial hypertension, and diabetes mellitus, whereas urinary citrate was significantly decreased. At multivariate analysis, a significantly increased risk to develop kidney stones was independently associated with urinary excretion of uric acid (odds ratio = 1.6, confidence interval = 1.0–2.5) and systemic arterial blood pressure (odds ratio = 2.6, confidence interval = 1.1–6.6).

In conclusion, patients with active CD have an increased prevalence of nephrolithiasis compared with general population, which decreases but not disappears in patients successfully cured from the disease. This complication is likely caused by the synergic effect of different hypercortisolism-dependent metabolic and hemodynamic abnormalities, among which systemic arterial hypertension and excessive urinary uric acid excretion seem to play a pivotal role.

Abbreviations: BMI, Body mass index; CD, Cushing’s disease; DBP, diastolic blood pressure; SBP, systolic blood pressure; US, ultrasonography.

This article has been cited by other articles:

				P. Anagnostis, V. G. Athyros, K. Tziomalos, A. Karagiannis, and D. P. Mikhailidis The Pathogenetic Role of Cortisol in the Metabolic Syndrome: A Hypothesis J. Clin. Endocrinol. Metab., August 1, 2009; 94(8): 2692 - 2701. [Abstract] [Full Text] [PDF]

				P Haentjens, L De Meirleir, R Abs, J Verhelst, K Poppe, and B Velkeniers Glomerular filtration rate in patients with Cushing's disease: a matched case-control study Eur. J. Endocrinol., December 1, 2005; 153(6): 819 - 829. [Abstract] [Full Text] [PDF]

				A. Faggiano, D. Melis, R. Alfieri, M. De Martino, M. Filippella, F. Milone, G. Lombardi, A. Colao, and R. Pivonello Sulfur Amino Acids in Cushing's Disease: Insight in Homocysteine and Taurine Levels in Patients with Active and Cured Disease J. Clin. Endocrinol. Metab., December 1, 2005; 90(12): 6616 - 6622. [Abstract] [Full Text] [PDF]