PEDIATRICS Vol. 10 No. 5 November 1952, pp. 543-566
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ADRENOCORTICOTROPHIC HORMONE (ACTH) THERAPY OF THE NEPHROTIC SYNDROME IN CHILDREN

JACK METCOFF M.D.1, CHARLES P. RANCE M.D.1, WESTON M. KELSEY M.D.1, NOBUYUKI NAKASONE M.D.1, and CHARLES A. JANEWAY M.D.1

1 The Department of Pediatrics, Harvard Medical School, and the Medical Department, Children's Medical Center, Boston.

The clinical and physiologic features characterizing the administration of 56 courses of ACTH therapy to 45 children with the nephrotic syndrome have been reviewed.

The intramuscular administration of ACTH in daily doses of 150 to 200 mg./sq.m./ 24 hours for at least 8 and usually 10 days resulted in complete diuresis in 38 of 47 (81%) such courses, in 68% of all courses, and in 34 of 45 (75%) patients treated. Approximately 50% of the patients undergoing diuresis have maintained clinical remissions of three months or longer. Twelve of 16 such patients have been in clinical remission for over 6 months; 6 of these, for over 12 months. Induced diuresis and remission were associated with considerable improvement in renal function, particularly glomerular filtration rate and filtration fraction. Some diminution of proteinuria and increased serum protein levels were observed after diuresis, and serum cholesterol fell toward normal levels. Rather consistent but minimal changes in serum electrolyte patterns were noted. An increase of 2 to 4 mM/1. in Na, slight alkalosis and a fall in serum K were usual responses.

ACTH therapy of the nephrotic syndrome in children may be hazardous. Four patients died as a result of complications associated with therapy. The principal complications were infection, severe hypertension and hypotonicity of the extracellular fluid. Prompt recognition and treatment of these disorders with immediate withdrawal of ACTH therapy required constant vigilance and careful supervision. For this reason, this method of treatment is not considered to he a safe outpatient procedure.

The mechanisms responsible for diuresis and remission induced by ACTH therapy are not yet clear. Adequate dosage, normal diet without salt restriction but without added or excessive salt, and possibly a limited period of reduced renal function appear to favor diuresis. Neither the age of the patient nor the (chronologic) duration of disease appear to influence the outcome in children.

Although ACTH therapy may not effect a cure, it does appear to alter the course favorably in a relatively significant number of patients treated, and therefore at the present time appears to be the treatment of choice for the active phase of the nephrotic syndrome in children. A preventive or curative agent is still to be found.

Submitted on March 21, 1952




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