Abstract
We studied the hormonal background of the fluid derangements and arterial hypertension associated with adrenocorticotrophic hormone (ACTH) treatment for infantile spasms in ten infants aged 5–22 months. They received a 6 week course of (carboxymethyl-cellulose-)ACTH: 80IU at 0800 hours daily in weeks 1–3, then tapering, and termination at the end of week 6. The infants showed large, variable increases in 24 h urine cortisol during treatment. The mean plasma cortisol concentration (24 h after ACTH injection) was not significantly increased, but was correlated with the relative dose of ACTH. The mean plasma aldosterone concentration decreased. No significant change occurred in plasma renin activity (PRA), or in the concentrations of renin substrate (RS) or arginine vasopressin (AVP). Seven infants developed arterial hypertension, which was severe in three. This severe hypertension was associated with the highest relative ACTH doses and the highest plasma RS and cortisol concentrations. In the group as a whole, systolic blood pressure correlated with plasma RS and cortisol concentrations, but not with the other parameters. At the end of treatment urine and plasma cortisol dropped below the pretreatment levels and stayed low for >2 weeks. There was a sharp peak in PRA and plasma aldosterone concentration, and a decrease in plasma RS. Plasma AVP levels dropped markedly. The mean body weight increased sharply and urine flow decreased. Mean plasma electrolyte levels remained unaltered. The danger at termination of ACTH treatment appears to be associated with a sudden transition from hypercortisolism to hypocortisolism, activation of the renin-angiotensin-aldosterone axis, and suppression of AVP secretion.
Similar content being viewed by others
Abbreviations
- ACTH:
-
adrenocorticotrophic hormone
- AVP:
-
arginine vasopressin
- PRA:
-
plasma renin activity
- RS:
-
renin substrate
- 17-KGS:
-
17-ketogenic steroids
References
Abraham GE, Manlimos FS, Garza R (1977) Radioimmunoassay of steroids. In: Abraham GE (ed) Handbook of radioimmunoassay. Dekker, New York, pp 551–610
Aicardi J (1980) Seizures and epilepsy in children under 2 years of age. In: Tyrer JH (ed) The treatment of epilepsy. MTP, Lancaster, pp 222–230
Baxter JD, Perloff D, Hsueh W, Biglieri EG (1987) The endocrinology of hypertension. In: Felig P, Baxter JD, Broadus AE, Frohman LA (eds) Endocrinology and metabolism, 2nd edn, McGraw-Hill, New York, pp 693–788
Dixon WJ (1981) BMDP statistical software. University of California Press, Berkeley
Few JD (1961) A method for the analysis of urinary 17-hydroxycorticosteroids. J Endocrinol 22:31–46
Fyhrquist F, Soveri P, Puutula L, Stenman U-H (1976) Radioimmunoassay of plasma renin activity. Clin Chem 22:250–256
Fyhrquist F, Wallenius FM, Hollemans HJC (1976) Radioimmunoassay of vasopressin in unextracted plasma. Scand J Clin Lab Invest 36:841–850
Gould AB, Green D (1971) Kinetics of the human renin and human renin substrate reaction. Cardiovasc Res 5:58–89
Immonen I, Fyhrqvist F, Pohjavuori M, Simell O (1981) Age dependence of human plasma renin substrate. Scand J Clin Lab Invest 41:167–170
Lacy JR, Penry JK (1976) Infantile Spasms. Raven Press, New York
Lombrosco C (1983) A prospective study of infantile spasms: clinical and therapeutic correlations. Epilepsia 24:135–157
Newton MA, Sealey JE, Ledingham JGG, Laragh JH (1968) High blood pressure and oral contraceptives. Am J Obstet Gynecol 101:1037–1045
O'Donohoe N (1976) A 15-year follow-up of 100 children with infantile spasms. Ir J Med Sci 145:138–145
Perheentupa J, Riikonen R, Dunkel L, Simell O (1986) Adrenocortical hyporesponsiveness after ACTH therapy of infantile spasms. Arch Dis Child 61:750–753
Reid IA, Morris BJ, Ganong W (1978) The renin-angiotensin system. Ann Rev Physiol 40:366–410
Riikonen R, Donner M (1980) ACTH therapy in infantile spasms: Side effects. Arch Dis Child 55:664–672
Rosset E, Scherrer JR, Veyrat R (1973) Increased plasma renin substrate concentrations in human malignant hypertension. Clin Sci Mol Med 45:291–294
Saruta T, Suzuki H, Handa M, Igarashi Y, Kondo K, Senba S (1986) Multiple factors contribute to the pathogenesis of hypertension in Cushing's syndrome. J Clin Endocrinol Metab 62:275–279
Shinebourne EA (1972) Growth and development of the cardiovascular system. In: Davis JA, Dobbing J (eds) Scientific foundations of paediatrics. Heineman, London, pp 198–213
Skinner SL, Lumbers ER, Symonds EM (1969) Alteration by oral contraceptives of normal menstrual changes in plasma renin activity, concentration and substrate. Clin Sci 36:67–76
Sorel L (1972) 196 cases of infantile myoclonic encephalopathy with hypsarrhythmia IMEH: West syndrome, treated with ACTH. Electroencephalogr Clin Neurophysiol 32:567A
Suzuki H, Handa M, Kondo K, Saruta T (1982) Role of renin-angiotensin system in glucocorticoid hypertension in rats. Am J Physiol 243 (Endocrinol Metab 6):E48-E51
Tyrrell JB, Baxter JD (1987) Glucocorticoid therapy. In: Felig P, Baxter JD, Broadus AE, Frohman LA (eds) Endocrinology and metabolism, 2nd edn, McGraw-Hill, New York, pp 788–817
Author information
Authors and Affiliations
Additional information
Dedicated to Professor Walter Teller on the occasion of his 60th birthday
Rights and permissions
About this article
Cite this article
Riikonen, R., Simell, O., Dunkel, L. et al. Hormonal background of the hypertension and fluid derangements associated with adrenocorticotrophic hormone treatment of infants. Eur J Pediatr 148, 737–741 (1989). https://doi.org/10.1007/BF00443098
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00443098