Abstract
Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease and extrarenal manifestations may be observed in many organ systems. Hypothalamus-pituitary-adrenal axis was not evaluated extensively in patients with ADPKD. We aimed to evaluate this axis in these patients.
Methods: Twenty two patients with ADPKD and 27 healthy subjects were enrolled. Basal dehydroepiandrosterone sulfate (DHEAS) levels and cortisol and DHEA responses to low dose short adrenocorticotropin stimulation test were assessed. Correlation analyses of these parameters with glomerular filtration rates (GFR), renal volumes and pain characteristics in patients with ADPKD were performed.
Results: Patients with ADPKD had higher basal cortisol levels (12.1±3.4 vs. 9.6±4.3 μg/dL, p=0.033), and higher basal cortisol/DHEAS ratios (0.073±0.05 vs. 0.045±0.02, p=0.015) compared to controls. None of the subjects had inadequate response to adrenocorticotropin stimulation. Patients with ADPKD had lower delta cortisol (absolute increase between peak and basal) levels (10.3±2.8 vs. 12.6±4.2 μg/dL, p=0.026) compared to controls. Subgroup analysis showed that significant differences existed only between female patients and female controls. There was no significant correlation between cortisol levels and renal volumes or GFR. A significant correlation was found only between delta cortisol and pain frequency in female patients.
Conclusions: Patients with ADPKD had higher basal cortisol levels, higher basal cortisol/DHEAS ratios and lower delta cortisol levels compared to controls, indicating promptly stimulated zona fasciculata function. Further studies are needed to confirm these results and to investigate possible underlying mechanisms.
Key words
adrenal cortex function tests - adrenal functions - autosomal dominant polycystic kidney disease - flank pain - glomerular filtration rate - renal volume
References
-
1
Agwu JC, Spoudeas H, Hindmarsh PC. et al .
Tests of adrenal insufficiency.
Arch Dis Child.
1999;
80
((4))
330-333
-
2
Clodi M, Riedl M, Schmaldienst S. et al .
Adrenal function in patients with chronic renal failure.
Am J Kidney Dis.
1998;
32
((1))
52-55
-
3
Cockcroft DW, Gault MH.
Prediction of creatinine clearance from serum creatinine.
Nephron.
1976;
16
((1))
31-41
-
4
Crofford LJ.
The hypothalamic-pituitary-adrenal axis in the pathogenesis of rheumatic diseases.
Endocrinol Metab Clin North Am.
2002;
31
1-13
-
5
Cutolo M, Foppiani L, Minuto F.
Hypothalamic-pituitary-adrenal axis impairment in the pathogenesis of rheumatoid arthritis and polymyalgia rheumatica.
J Endocrinol Invest.
2002;
25
((10 Suppl))
19-23
-
6
Danby P, Harris KP, Williams B. et al .
Adrenal dysfunction in patients with renal amyloid.
Q J Med.
1990;
76
((281))
915-922
-
7
Demir H, Tanriverdi F, Ozogul N. et al .
Evaluation of the hypothalamic-pituitary-adrenal axis in untreated patients with polymyalgia rheumatica and healthy controls.
Scand J Rheumatol.
2006;
35
((3))
217-223
-
8
Dillon JS.
Dehydroepiandrosterone, dehydroepiandrosterone sulfate and related steroids: their role in inflammatory, allergic and immunological disorders.
Curr Drug Targets Inflamm Allergy.
2005;
4
((3))
377-385
-
9
Dorin RI, Qualls CR, Crapo LM.
Diagnosis of adrenal insufficiency.
Ann Intern Med.
2003;
139
((3))
194-204
-
10 Ecder T, Fick-Brosnahan GM, Schrier RW. Polycyctic kidney disease, in Schrier RW (ed) Disease of the Kidney and Urinary Tract (ed 8), chapter 18 Philadelphia, PA,: Lippincott Williams & Wilkins; 2007 pp 502-539
-
11
Ecder T, Schrier RW.
Hypertension in autosomal-dominant polycystic kidney disease: Early occurrence and unique aspects.
J Am Soc Nephrol.
2001;
12
194-200
-
12
Fick GM, Johnson AM, Hammond WS. et al .
Causes of death in autosomal dominant polycystic kidney disease.
J Am Soc Nephrol.
1995;
5
((12))
2048-2056
-
13
Fick-Brosnahan GM, Belz MM, McFann KK. et al .
Relationship Between Renal Volume Growth and Renal Function in Autosomal Dominant Polycystic Kidney Disease: A Longitudinal Study.
Am J Kidney Dis.
2002;
39
((6))
1127-1134
-
14
Gaillard RC.
Neuroendocrine-immune system interactions The immune-hypothalamo-pituitary-adrenal axis.
Trends Endocrinol Metab.
1994;
5
((7))
303-309
-
15
Gunduz Z, Kelestimur F, Durak AC. et al .
The hormonal and radiological evaluation of adrenal glands, and the determination of the usefulness of low dose ACTH test in patients with renal amyloidosis.
Ren Fail.
2001;
23
((2))
239-249
-
16
Jankord R, Turk JR, Schadt JC. et al .
Sex difference in link between interleukin-6 and stress.
Endocrinology.
2007;
148
((8))
3758-3764
-
17
Kelestimur F, Goktas Z, Gulmez I. et al .
Low dose (1 microg) adrenocorticotropin stimulation test in the evaluation of hypothalamo-pituitary-adrenal axis in patients with active pulmonary tuberculosis.
J Endocrinol Invest.
2000;
23
((4))
235-239
-
18
Kyrou I, Tsigos C.
Stress mechanisms and metabolic complications.
Horm Metab Res.
2007;
39
((6))
430-438
-
19
Laureti S, Candeloro P, Aglietti MC. et al .
Dehydroepiandrosterone, 17alpha-hydroxyprogesterone and aldosterone responses to the low-dose (1 microg) ACTH test in subjects with preclinical adrenal autoimmunity.
Clin Endocrinol (Oxf).
2002;
57
((5))
677-683
-
20
Levey AS, Bosch JP, Lewis JB. et al .
A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group.
Ann Intern Med.
1999;
130
((6))
461-470
-
21
Marin TJ, Martin TM, Blackwell E. et al .
Differentiating the impact of episodic and chronic stressors on hypothalamic-pituitary-adrenocortical axis regulation in young women.
Health Psychol.
2007;
26
((4))
447-455
-
22
McDonald WJ, Golper TA, Mass RD. et al .
Adrenocorticotropin-cortisol axis abnormalities in hemodialysis patients.
J Clin Endocrinol Metab..
1979;
48
((1))
92-95
-
23
McHorney CA, Ware Jr JE, Raczek AE.
The MOS 36-item short-form health survey (SF36): II. Phychometric and clinical tests of validity in measuring physical and mental health constructs.
Med Care.
1993;
31
((3))
247-263
-
24
Merta M, Tesar V, Zima T. et al .
Cytokine profile in autosomal dominant polycystic kidney disease.
Biochem Mol Biol Int.
1997;
41
((3))
619-624
-
25
Namli S, Oflaz H, Turgut F. et al .
Improvement of endothelial dysfunction with simvastatin in patients with autosomal dominant polycystic kidney disease.
Ren Fail.
2007;
29
((1))
55-59
-
26
National Kidney Foundation
.
K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification.
Am J Kidney Dis.
2002;
39
((Suppl 2))
S1-S266
-
27
Oguz Y, Oktenli C, Ozata M. et al .
The midnight-to-morning urinary cortisol increment method is not reliable for the assessment of hypothalamic-pituitary-adrenal insufficiency in patients with end-stage kidney disease.
J Endocrinol Invest.
2003;
26
((7))
609-615
-
28
Ramirez G, Gomez-Sanchez C, Meikle WA. et al .
Evaluation of the hypothalamic hypophyseal adrenal axis in patients receiving long-term hemodialysis.
Arch Intern Med.
1982;
142
((8))
1448-1452
-
29
Reimondo G, Bovio S, Allasino B. et al .
Secondary hypoadrenalism.
Pituitary.
2008;
11
((2))
147-154
-
30
Salek FS, Bigos KL, Kroboth PD.
The influence of hormones and pharmaceutical agents on DHEA and DHEA-S concentrations: a review of clinical studies.
J Clin Pharmacol.
2002;
42
((3))
247-266
-
31
Salvatori R.
Adrenal insufficiency.
JAMA.
2005;
294
((19))
2481-2488
-
32
Scott LV, Svec F, Dinan T.
A preliminary study of dehydroepiandrosterone response to low-dose ACTH in chronic fatigue syndrome and in healthy subjects.
Psychiatry Res.
2000;
97
((1))
21-28
-
33
Siamopoulos KC, Dardamanis M, Kyriaki D. et al .
Pituitary adrenal responsiveness to Corticotrophin-releasing hormone in chronic uremic patients.
Perit Dial Int.
1990;
10
((2))
153-156
-
34
Straub RH, Lehle K, Herfarth H. et al .
Dehydroepiandrosterone in relation to other adrenal hormones during an acute inflammatory stressful disease state compared with chronic inflammatory disease: Role of interleukin-6 and tumour necrosis factor.
Eur J Endocrinol.
2002;
146
((3))
365-374
-
35
Tanriverdi F, Karaca Z, Unluhizarci K. et al .
The hypothalamo-pituitary-adrenal axis in chronic fatigue syndrome and fibromyalgia syndrome.
Stress.
2007;
10
((1))
13-25
-
36
Wang Y, Moss J, Thisted R.
Predictors of body surface area.
J Clin Anesth.
1992;
4
((1))
4-10
-
37
Zietz B, Wengler I, Messmann H. et al .
Early shifts of adrenal steroid synthesis before and after relief of short-term cholestasis.
J Hepatol.
2001;
35
((3))
329-337
Correspondence
Dr. F. Tufan
Istanbul University
Istanbul Medical Faculty
Internal Medicine
Istanbul University Istanbul
Medical Faculty Department of Internal Medicine
34390 Istanbul
Turkey
Telefon: +902124142000
Fax: +902124142220
eMail: fatihtufan@gmail.com
