Another Use of Androgens: Treatment of Anemia of. End-Stage Renal Diseasea. To the editor: I have read with great interest the excellent review by Bhasin and.
0021-972X/97/$03.00/0 Journal of Clinical Endocrinology and Metabolism Copyright © 1997 by The Endocrine Society
Vol. 82, No. 9 Printed in U.S.A.
LETTERS TO THE EDITOR Another Use of Androgens: Treatment of Anemia of End-Stage Renal Diseasea To the editor:
The Effect of Acute Administration of ACTH and Levothyroxine on Serum Carnitineb To the editor:
I have read with great interest the excellent review by Bhasin and Bremner (1) about androgen replacement therapy and their anabolic applications in wasting states. I would like to point another aspect of special interest in the androgen field: the use of these substances for the treatment of anemia in patients with end-stage renal disease. Anemia is a universal complication of renal insufficiency. Although its etiology is multifactorial, the main cause of anemia of renal disease is the deficient production of erythropoietin (EPO) by the kidneys. Since the last years of the 1980s, recombinant human EPO (rHuEPO) has become the standard therapy for renal anemia. However, this treatment has several limitations: the significant side effects, mainly hypertension, and the high cost. Androgens have been used as treatment for the anemia of end-stage renal disease since 1970 (2, 3); but with the easy availability of rHuEPO, the protocol treatments have completely changed, and androgens have been relegated to background. However, recent studies (4 – 6) have reported that androgens produced a significant improvement in anemia of hemodialysis patients, similar to that observed with the use of rHuEPO, with minimal secondary complications and with a lower economical cost. On the other hand, androgens have also demonstrated appreciable anabolic effects in these patients, with a significant increase of body weight and serum albumin concentration (6).
A single prior investigation of endocrine control of carnitine in humans indicated a dramatic effect of ACTH and thyroid hormone at 24 h (1). We attempted to duplicate those results and to assess the effect of a supraphysiologic thyroxine bolus on serum carnitine.
Materials and Methods Under Investigational Review Board approval, normal volunteers over age 18 yr and free of muscle or endocrine disease by interview and physical examination, were studied. Diet was unchanged, but a 12-h fast preceded each sample acquisition. One milligram synthetic ACTH was administered in the morning of the first day. Serum carnitine levels were determined at baseline (before injection) and 1, 2, and 3 days after ACTH administration. For the levothyroxine challenge, 300 mg levothyroxine were given orally in the morning, and serum carnitine levels were determined at baseline, and at 1, 2, and 3 days. Ten subjects were included in each challenge. If a subject did both challenges, two weeks elapsed between challenges. Serum free and total carnitine values were determined by radioenzymatic assay. Statistical analysis was done by ANOVA, with Tukey-Kramer significance level of 0.05.
Results
1. Bhasin S, Bremner WJ. 1997 Emerging issues in androgen replacement therapy. J Clin Endocrinol Metab. 82:3– 8. 2. DeGowin RL, Lavender AR, Forland M, Charleston D, Gottschalk A. 1970 Erythropoiesis and erythropoietin in patients with chronic renal failure treated with hemodialysis and testosterone. Ann Intern Med. 72:913–918. 3. Richardson Jr JR, Winstein MB. 1970 Erythropoietic response of dialyzed patients to testosterone administration. Ann Intern Med. 73:403– 407. 4. Teruel JL, Marce´n R, Navarro JF. 1995 Evolution of serum erythropoietin after androgen administration to hemodialysis patients: a prospective study. Nephron. 70:282–286. 5. Teruel JL, Aguilera A, Marce´n R, Navarro J, Garcı´a G, Ortun˜o J. 1996 Androgen therapy for anaemia of chronic renal failure. Scan J Urol Nephrol. 30:403– 408. 6. Teruel JL, Marce´n R, Navarro-Antolı´n J, Aguilera A, Ferna´ndez-Jua´rez G, Ortun˜o J. 1996 Androgen versus erythropoietin for the treatment of anemia in hemodialyzed patients: a prospective study. J Am Soc Nephrol. 7:140 –144.
Fourteen volunteer subjects were studied; 6 did both challenges. The average age for the ACTH challenge was 35.4, ranging between 29 and 49 yr. Three were female and 7 male. For the thyroxine challenge, the average age was 32.8, ranging from 24 to 49 yr, with 4 females and 6 males. The results of the 2 challenges are summarized in Table 1. The carnitine levels following ACTH and thyroxine stimulation were contrary to those obtained by Maebashi, et al. in 1977 (1), who determined serum carnitine levels following intramuscular injection of 1 mg ACTH in normal subjects and in patients with various endocrine deficiency states. In normals, there was a 50% rise in total serum carnitine levels within 24 h of injection that returned to baseline by the third day. Responses to ACTH were lacking or suppressed in patients with uncompensated thyroid or adrenal insufficiency. In hypothyroid or hypopituitary patients, substitution therapy restored the carnitine response to ACTH to normal. We are uncertain why our results did not duplicate these effects. Their subjects were on a “standard hospital diet,” which in Japan may differ from the unrestricted choice available to our subjects. The dose and route of ACTH administration was identical in both studies. Differences in the specificity of the carnitine assays should not influence relative changes after hormonal challenge. It is our observation that ACTH and levothyroxine boluses do not have a substantial short-term effect upon normal carnitine metabolism.
Received March 12, 1997. Address correspondence to: Juan F. Navarro, Department of Nephrology, Hosp. Ntra. Sra. de Candelaria, 38010 S/C de Tenerife, Spain.
James M. Gilchrist, MD, Manju Kandula, MD, and James V. Hennessey, MD Brown University School of Medicine, Rhode Island Hospital Providence, Rhode Island 02903
Juan F. Navarro Department of Nephrology, Hospital Ntra. Sra. de Candelaria 38010 S/C de Tenerife, Spain
References
Reference 1. Maebashi M, Kawamura N, Sato M, Imamura A, Yoshinaga K 1977 Urinary excretion of carnitine and serum concentrations of carnitine and lipids in patients with hypofunctional endocrine disease: involvement of adrenocorticoid and thyroid hormones in ACTH-induced augmentation of carnitine and lipid metabolism. Metabol Clin Exp. 26:357–361.
b Received May 29, 1997. Address correspondence to: Dr. James Gilchrist, 593 Eddy Street, APC 689, Providence, Rhode Island 02903.
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LETTERS TO THE EDITOR
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TABLE 1. Summary of results for ACTH and levothyroxine challenges in normal human subjects Hormone
Day
ACTH
0 1 3 0 1 3
Thyroxine
a
Total serum carnitine
Free serum carnitine
Average change from baseline
mean (SD) mM/L
mean (SD) mM/L
total %
free %
50.5 (10.2) 55.7 (12.1)a 48.6 (11.8)a 51.8 (13.1) 51.8 (11.2)a 51.8 (10.6)a
40.4 (9.5) 44.3 (9.4)a 40.6 (10.8)a 41.8 (11.8) 41.9 (10.5)a 41.6 (9.5)a
7.1a 4.4a
10.7a 0.1a
1.1a 5.0a
0.9a 1.5a
No significant difference at P , 0.05 level.
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