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Control of plasma aldosterone in diabetic patients with hyporeninemic hypoaldosteronism

Regulation der Aldosteronsekretion bei Patienten mit Diabetes mellitus und hyporeninämischem Hypoaldosteronismus

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Zusammenfassung

Bei drei Patienten mit Diabetes mellitus und hyporeninämischem Hypoaldosteronismus wurden Veränderungen der Plasmareninaktivität, des Plasmaaldosteron- und Plasmacortisolspiegels unter folgenden Bedingungen geprüft: Orthostase und intravenöse Furosemidapplikation, Infusion von synthetischem β1–24 ACTH an zwei aufeinanderfolgenden Tagen, Tag-Nacht-Rhythmus der basalen Hormonplasmaspiegel.

Alle Patienten zeigten eine nicht meßbare und durch Orthostase und Furosemid nicht stimulierbare Reninaktivität. Gleichzeitig wurden subnormale Aldosteronplasmakonzentrationen gemessen. Unter ACTH-Infusion zeigte nur ein Patient einen deutlichen Anstieg des Plasmaaldosterons, während das Plasmacortisol in allen drei Fällen normal stimulierbar war.

Die statistische Analyse der Tag-Nacht-Schwankungen von Plasmaaldosteron und Plasmacortisol zeigte in jedem der Fälle eine enge und statistisch signifikante Beziehung zwischen beiden Hormonen (p<0,05–<0,001). Es ist somit anzunehmen, daß Schwankungen des Plasmaaldosterons durch Veränderungen der hypophysären ACTH-Ausschüttung verursacht wurden. Jedoch war im Vergleich zu Normalpersonen die Rhythmik des basalen Plasmaaldosterons auf einem tieferen Niveau eingestellt. Unsere Ergebnisse lassen den Schluß zu, daß bei diesen Patienten nicht eine verminderte Sensitivität der Nebennierenrinde auf ACTH für die beobachteten subnormalen Aldosteronspiegel verantwortlich ist.

Ursache für den Hypoaldosteronismus scheint somit der Mangel an zirkulierendem Angiotensin II zu sein. Der genaue Mechanismus der nicht meßbaren Reninaktivität bei diesem Patienten bleibt unbekannt.

Summary

In three patients with diabetes and hyporeninemic hypoaldosteronism changes in renin activity, plasma aldosterone and cortisol were examined under various conditions: orthostasis and intravenous furosemide, infusion of synthetic β1–24 ACTH on two consecutive days and diurnal variations in basal hormone fluctuations.

Each patient showed unmeasurably low renin activity unresponsive to orthostasis and intravenous furosemide while plasma aldosterone was below normal range.

Under ACTH-infusion only marked increases in aldosterone were observed in one patient whereas cortisol responded normally in all diabetics tested.

Analysis of diurnal night day fluctuations (20.00–8.00) in plasma aldosterone and cortisol revealed a close and statistically significant relationship between both hormones in each of the three patients (p<0.05–<0.001). Variations in plasma aldosterone thus were mediated through changes in endogenous pituitary ACTH. Compared with normal controls however, diurnal aldosterone curves were set at a lower level.

Our results demonstrate that a reduced sensitivity of the adrenal gland to ACTH is not responsible for the observed subnormal plasma aldosterone levels in these patients. Therefore, the lack of circulating angiotensin II seems to be the causative reason of hypoaldosteronism.

The exact mechanism of undetectable renin activity in these patients remains unknown.

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References

  1. Adler, S.: An extrarenal action of aldosterone on mammalian skeletal muscle. Amer. J. Physiol.218, 616 (1970)

    Google Scholar 

  2. Alexander, E.A., Levinsky, N.G.: An extrarenal mechanism of potassium adaptation. J. clin. Invest47, 740 (1968)

    Google Scholar 

  3. Armbruster, H., Vetter, W., Beckerhoff, R., Nussberger, J., Vetter, H., Siegenthaler, W.: Diurnal variations of plasma aldosterone in supine man: relationship to plasma renin activity and plasma cortisol. Acta Endocrinol80, 95 (1975)

    Google Scholar 

  4. Beckerhoff, R., Nussberger, J., Vetter, W., Siegenthaler, W.: Problems connected with plasma renin activity measurements by angiotensin I radioimmunoassay. Horm. Metab. Res.7, 342 (1975)

    Google Scholar 

  5. Beigelman, P.M.: Severe diabetic ketoacidosis (diabetic “coma”): 482 episodes in 257 patients; experience of three years. Diabetes20, 490 (1971)

    Google Scholar 

  6. Brown, J.J., Chinn, R.H., Fraser, R., Lever, A.F., Morton, J.J., Robertson, J.I.S., Tree, M., Waite, M.A., Park, D.M.: Recurrent hyperkalemia due to selective aldosterone deficiency: correction by angiotensin infusion. Brit. Med. J.1, 650 (1973)

    Google Scholar 

  7. Campbell, I.W., Ewing, D.J., Anderton, J.L., Thompson, J.H., Horn, D.B., Clarke, B.F.: Plasma renin activity in diabetic autonomic neuropathy. Eur. J. clin. Invest.6, 381 (1976)

    Google Scholar 

  8. Carroll, H.J., Farber, S.J.: Hyperkalemia and hyperchloremic acidosis in chronic pyelonephritis. Metabolism13, 808 (1964)

    Google Scholar 

  9. Christensen, N.J.: Plasma catecholamines in long-term diabetics with and without neuropathy and in hypophysectomized subjects. J. clin. Invest51, 779 (1972)

    Google Scholar 

  10. Christlieb, A.R., Hickler, R.B., Lauler, D.P., Williams, G.H.: Hypertension with inappropriate aldosterone stimulation: a syndrome. New Engl. J. Med.281, 128 (1969)

    Google Scholar 

  11. Christlieb, A.R.: Diabetes and hypertensive vascular disease. Amer. J. Cardiol32, 592 (1973)

    Google Scholar 

  12. Christlieb, A.R., Munichoodappa, C., Braaten, J.T.: Decreased response of plasma renin activity to orthostasis in diabetic patients with orthostatic hypotension. Diabetes23, 835 (1974)

    Google Scholar 

  13. Christlieb, A.R., Assal, J.Ph., Katsilambros, N., Williams, G.H., Kozak, G.P., Suzuki, T.: Plasma renin activity and blood volume in uncontrolled diabetes. Diabetes24, 190 (1975)

    Google Scholar 

  14. Christlieb, A.R., Kaldany, A., D'Elia, J.A.: Plasma renin activity and hypertension in diabetes mellitus. Diabetes25, 969 (1976)

    Google Scholar 

  15. Cooke, C.R., Horvath, J.S., Moore, M.A., Bledsoe, T., Walker, W.G.: Modulation of plasma aldosterone concentration by plasma potassium in anephric man in the absence of a change in potassium balance. J. clin. Invest52, 3028 (1973)

    Google Scholar 

  16. David, R., Golan, S., Drucker, W.: Familial aldosterone deficiency: enzyme defect, diagnosis, and clinical course. Pediatrics41, 403 (1968)

    Google Scholar 

  17. Dawborn, J.K., Watson, L.: Effect of prolonged administration of aldosterone on potassium and magnesium metabolism in the rabbit. Med. J. Aust.2, 304 (1968)

    Google Scholar 

  18. Day, R.P., Luetscher, J.A., Gonzales, C.M.: Occurrence of big renin in human plasma, amniotic fluid, and kidney extracts. J. clin. Endocr. Metab.40, 1078 (1975)

    Google Scholar 

  19. De Leiva, A., Christlieb, A.R., Melby, J.C., Graham, C.A., Day, R.P., Luetscher, J.A., Zager, P.G.: Big renin and biosynthetic defect of aldosterone in diabetes mellitus. New Engl. J. Med.295, 639 (1976)

    Google Scholar 

  20. Dluhy, R.G., Axelrod, L., Underwood, R.H., Williams, G.H.: Studies of the control of plasma aldosterone concentration in normal man. II. Effect of dietary potassium and acute potassium infusion. J. clin. Invest51, 1950 (1972)

    Google Scholar 

  21. Ferrara, E., Werk, E., Hanenson, I., Privitera, P., Kenyon, C.: Selective hypoaldosteronism with blunted renin-activity responsiveness. Clin. Res.18, 602 (1970)

    Google Scholar 

  22. Gerstein, A.R., Kleeman, C.R., Gold, E.M., Franklin, S.S., Maxwell, M.H., Gonick, H.C., Feffer, M.L., Steinmann, T.I.: Aldosterone deficiency in chronic renal failure. Nephron5, 90 (1968)

    Google Scholar 

  23. Goldfarb, S., Strunk, B., Singer, I., Goldberg, M.: Paradoxical glucose-induced hyperkalemia. Combined aldosterone-insulin deficiency. Amer. J. Med.59, 744 (1975)

    Google Scholar 

  24. Goldfarb, S., Cox, M., Singer, I., Goldberg, M.: Acute hyperkalemia induced by hyperglycemia: hormonal mechanisms. Ann. Intern. Med.84, 426 (1976)

    Google Scholar 

  25. Gossain, V.V., Ferrara, E.V., Werk, E.E., Srivastava, I., Privitera, P.J., Hanenson, I.: Impaired renin responsiveness with secondary hypoaldosteronism. Arch. Intern. Med.132, 885 (1973)

    Google Scholar 

  26. Gossain, V.V., Werk, E.E., Sholiton, I.J., Srivastava, L., Knowles, H.C.: Plasma renin activity in juvenile diabetes mellitus and effects of diazoxide. Diabetes24, 833 (1975)

    Google Scholar 

  27. Hiatt, N., Yamakawa, T., Davidson, M.B.: Necessity for insulin in transfer of excess infused K to intracellular fluid. Metabolism23, 43 (1974)

    Google Scholar 

  28. Hudson, J.B., Chobanian, A.V., Relman, A.S.: Hypoaldosteronism: a clinical study of a patient with an isolated adrenal mineralocorticoid deficiency, resulting in hyperkalemia and Stokes-Adams attacks. New Engl. J. Med.257, 529 (1957)

    Google Scholar 

  29. Katz, F.H., Romth, P., Smith, J.A.: Diurnal variation of plasma aldosterone, cortisol and renin activity in supine man. J. clin. Endocr. Metab.40, 125 (1975)

    Google Scholar 

  30. Lambrew, C.T., Cawer, S.T., Peterson, R.E.: Hypoaldosteronism as a cause of hyperkalemia and syncopal attacks in a patient with complete heart block. Amer. J. Med.31, 81 (1961)

    Google Scholar 

  31. Lebel, M., Grose, J.H.: Selective hypoaldosteronism: a study of steroid biosynthetic pathways under adrenocorticotrophin and angiotensin II infusion. Clin. Sci. Mol. Med.51, 335s (1976)

  32. Lommer, D., Distler, A., Nast, H.P., Sinterhauf, K., Walter, U., Wolff, H.P.: Tagesprofile von Plasmaaldosteron, -Cortisol, -Renin, -Angiotensinogen und -Angiotensinasen bei Normalpersonen. Klin. Wschr.54, 123 (1976)

    Google Scholar 

  33. Marieb, N.J., Melby, J.C., Lyall, S.S.: Isolated hypoaldosteronism associated with idipathic hypoparathyroidism. Arch. Intern. Med.134, 424 (1974)

    Google Scholar 

  34. McGiff, J.C., Muzzarelli, R.E., Duffy, P.A.: Interrelationships of renin and aldosterone in a patient with hypoaldosteronism. Amer. J. Med.48, 247 (1970)

    Google Scholar 

  35. Mellinger, R.C., Petermann, F.L., Jurgenson, J.C.: Hyponatremia with low urinary aldosterone occurring in an old woman. J. clin. Endocr. Metab.34, 85 (1972)

    Google Scholar 

  36. Murphy, B.P., Engelberg, W., Pattee, C.J.: Simple method for the determination of plasma corticoids. J. clin. Endocr. Metab.30, 686 (1970)

    Google Scholar 

  37. Oh, M.S., Carroll, H.J., Clemmons, J.E.: A mechanism for hyporeninemic hypoaldosteronism in chronic renal disease. Metabolism23, 1157 (1974)

    Google Scholar 

  38. Perez, G., Siegel, I., Schreiner, G.F.: Selective hypoaldosteronism with hyperkalemia. Ann. Intern. Med.76, 757 (1972)

    Google Scholar 

  39. Perez, G.O., Oster, J.R., Vaamonde, C.A.: Renal acidosis and renal potassium handling in selective hypoaldosteronism. Amer. J. Med.57, 809 (1974)

    Google Scholar 

  40. Pettit, G.W., Vick, R.L.: Contribution of pancreatic insulin to extrarenal potassium homeostasis: a 2-compartment model. Amer. J. Physiol.226, 319 (1974)

    Google Scholar 

  41. Pettit, G.W., Vick, R.L., Swander, A.M.: Plasma K+ and insulin: changes during KCI infusion in normal and nephrectomized dogs. Amer. J. Physiol.228, 107 (1975)

    Google Scholar 

  42. Posner, J.B., Jacobs, D.R.: Isolated analdosteronism. I. Clinical entity, with manifestation of persistent hyperkalemia, periodic paralysis, salt-losing tendency and acidosis. Metabolism13, 513 (1964)

    Google Scholar 

  43. Reck, G., Beckerhoff, R., Vetter, W., Armbruster, H., Siegenthaler, W.: Control of plasma aldosterone in normal man during upright posture. Klin. Wschr.53, 955 (1975)

    Google Scholar 

  44. Roginsky, M., Abasamis, C., Asad, S.: The renin-angiotensinaldosterone system (RAAS) in the hypertensive diabetic (Abstract). Clin. Res.21, 501 (1973)

    Google Scholar 

  45. Schambelan, M., Stockigt, J.R., Biglieri, E.G.: Isolated hypoaldosteronism in adults. A renin-deficiency syndrome. New Engl. J. Med.287, 573 (1972)

    Google Scholar 

  46. Schambelan, M.: Isolated hypoaldosteronism. Calif. Med.118, 33 (1973)

    Google Scholar 

  47. Schindler, A.M., Sommers, S.C.: Diabetic sclerosis of the renal juxtaglomerular apparatus. Lab. Invest.15, 877 (1966)

    Google Scholar 

  48. Sebastian, A., McSherry, E., Schambelan, M.: Renal tubular acidosis (RTA) in patients with hypoaldosteronism caused by renin deficiency. Clin. Res.21, 706A (1973)

  49. Skanse, B., Hökfelt, B.: Hypoaldosteronism with otherwise intact adrenocortical function resulting in a characteristic clinical entity. Acta Endocrinol. (Kbh)28, 29 (1958)

    Google Scholar 

  50. Sparagana, M.: Hyporeninemic hypoaldosteronism associated with diabetic glomerulosclerosis. J. Steroid Biochem.5, 369 (1974)

    Google Scholar 

  51. Ueda, H., Yasuda, H., Takabatake, Y., Iizuka, M., Iizuka, T., Ihori, M., Sukamoto, Y.: Observations on the mechanisms of renin release by catecholamines. Circ. Res.26 and27 (Suppl. 2), 195 (1970)

    Google Scholar 

  52. Ulick, S., Gautier, E., Vetter, K.K., Markello, J.R., Yaffe, S., Lowe, C.U.: An aldosterone biosynthetic defect in a saltlosing disorder. J. clin. Endocr. Metab.24, 669 (1964)

    Google Scholar 

  53. Vagnucci, A.H.: Selective aldosterone deficiency. J. clin. Endocr. Metab.29, 279 (1969)

    Google Scholar 

  54. Vagnucci, A.H., McDonald, R.H., Drash, A.L., Wong, A.K.C.: Intradiem changes of plasma aldosterone, cortisol, corticosterone and growth hormone in sodium restriction. J. clin. Endocr. Metab.38, 761 (1974)

    Google Scholar 

  55. Vander, A.: Direct effects of potassium on renin secretion and renal funktion. Amer. J. Physiol.219, 455 (1970)

    Google Scholar 

  56. Vetter, W., Vetter, H., Siegenthaler, W.: Radioimmunoassay for aldosterone without chromatography. I. Determination of urinary 18-glucuronide excretion. Acta Endocrinol. (Kbh)74, 548 (1973)

    Google Scholar 

  57. Vetter, W., Vetter, H., Siegenthaler, W.: Radioimmunoassay for aldosterone without chromatography. 2. Determination of plasma aldosterone. Acta Endocrinol. (Kbh)74, 558 (1973)

    Google Scholar 

  58. Visser, H.K.A., Cost, W.S.: A new hereditary defect in the biosynthesis of aldosterone: urinary C21-corticosteroid pattern in three related patients with a salt-losing syndrome, suggesting an 18-oxidation defect. Acta Endocrinol. (Kbh)47, 589 (1964)

    Google Scholar 

  59. Weidmann, P., Reinhart, R., Maxwell, M.H., Rowe, P., Coburn, J.W., Massry, S.G.: Syndrome of hyporeninemic hypoaldosteronism and hyperkalemia in renal disease. J. clin. Endocr. Metab.36, 965 (1973)

    Google Scholar 

  60. Weinberger, H., Kem, C., Gomez-Sanchez, C., Kramer, J., Martin, T., Nugent, A.: The effect of dexamethasone on the control of plasma aldosterone concentration in normal recumbent man. J. Lab. Clin. Med.85, 957 (1975)

    Google Scholar 

  61. Wilson, I.D., Goetz, F.C.: Selective hypoaldosteronism after prolonged heparin administration. Amer. J. Med.36, 635 (1964)

    Google Scholar 

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  1. Department of Medicine Kantonsspital, University of Zürich, Switzerland

    U. Kuhlmann, W. Vetter, E. Fischer & W. Siegenthaler

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Kuhlmann, U., Vetter, W., Fischer, E. et al. Control of plasma aldosterone in diabetic patients with hyporeninemic hypoaldosteronism. Klin Wochenschr 56, 229–234 (1978). https://doi.org/10.1007/BF01477829

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