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The Journal of Clinical Endocrinology & Metabolism 89(10):5271–5272 Copyright © 2004 by The Endocrine Society
LETTERS TO THE EDITOR Low Plasma Bicarbonate Level in Hyponatremia Related To Adrenocorticotropin Deficiencya To the editor: In the very interesting article by DeCaux et al. (1), a low serum bicarbonate is found to be a simple laboratory finding that can distinguish adrenocortical-induced hyponatremia from low sodium due to syndrome of inappropriate antidiuretic hormone. The low serum bicarbonate is postulated to be due to respiratory alkalosis. I disagree with this conclusion. Mineralocorticoids and, to some degree, glucocorticoids increase the exchange of sodium for potassium and hydrogen ion in the distal tubules of the kidneys. Adrenocortical deficiency results in the accumulation of hydrogen ion in the body, which is in turn neutralized by bicarbonate molecules. Therefore, the low serum bicarbonate in these patients is caused by consumption of bicarbonate molecules by excess hydrogen ions and not by increase in exhalation of carbonic acid (CO2) from the lungs. This situation causes very mild acidosis that is easily corrected by the body’s other buffering systems and the serum pH remains normal. The normal serum pH of 7.42 is a testimony to this notion. In true respiratory alkalosis of the magnitude to reduce the PCO2 to 30, as was the case in the patients in this article, the pH is much higher, even with compensation.
This hyperaldosteronism need requires the presence of cortisone as a cofactor (4). As discussed in our manuscript (2), in hyponatremia due to ACTH deficiency, we did not observe a metabolic alkalosis as seen in classical syndrome of inappropriate antidiuretic hormone. When these patients normalized their serum Na by water restriction (or urea therapy), but without cortisone administration, we observed a normalization of TCO2 (due to the correction of the respiratory alkalosis). The low TCO2 observed in hyponatremia related to ACTH deficiency could reflect compensated respiratory alkalosis and/or metabolic acidosis due to hypoaldosteronism. The respiratory alkalosis does not seem to be always secondary to the metabolic acidosis. Guy Decaux Department of Internal Medicine Research Unit for Study of Hydromineral Metabolism Brussels, 1070 Belgium
References 1. Zahedi T 2004 Low plasma bicarbonate level in hyponatremia related to adrenocorticotropin deficiency. J Clin Endocrinol Metab 89:5271 (Letter) 2. Decaux G, Musch W, Penninckx R, Soupart A 2003 Low plasma bicarbonate level in hyponatremia related to adrenocorticotropin deficiency. J Clin Endocrinol Metab 88:5255–5257 3. Decaux G, Crenier L, Namias B, Gervy C, Soupart A 1994 Normal acid-base equilibrium in acute hyponatremia and mixed alkalosis in chronic hyponatremia induced by arginine vasopressin or 1-deamino-8D-arginine vasopressin. J Lab Clin Med 123:892– 898 4. Decaux G, Crenier L, Namias B, Gervy C, Soupart A 1994 Restoration by corticosteroids of the hyperaldosteronism in hyponatraemic rats with panhypopituitarism. Clin Sci (Lond) 87:435– 439
Tooraj Zahedi Brookdale University Hospital and Medical Center Brookdale, New York 11212
Reference
doi: 10.1210/jc.2004-1278
1. DeCaux G, Musch W, Penninckx R, Soupart A 2003 Low plasma bicarbonate level in hyponatremia related to adrenocorticotropin deficiency. J Clin Endocrinol Metab 88:5255–5257 doi: 10.1210/jc.2004-0382
Author’s Response: Low Plasma Bicarbonate Level in Hyponatremia Related to Adrenocorticotropin Deficiencyb To the editor: We read with interest the comments made by Tooraj Zahedi (1) concerning our article (2) on the low TCO2 levels observed in hyponatremia related to ACTH deficiency. Unfortunately, interpretation of the acid-base equilibrium in this situation is not simple. The mean arterial blood value reported (pH 7.42; PCO2, 30 mm Hg; HCO3⫺, 20 mEq/liter; base excess, ⫺3.4 mEq/liter) is compatible with a mixed acid-base disturbance (respiratory alkalosis and metabolic acidosis). As mentioned in the manuscript, some patients presented with lower pH values (7.36 and 7.38), and, in those patients, the metabolic acidosis related to the hypoaldosteronism was probably the main factor for the low TCO2. In two other patients, the respiratory alkalosis was clearly the main factor (pH 7.47 and 7.52; despite hypoaldosteronism). In chronic severe hyponatremia with normal ACTH function, TCO2 is normal, but blood gases show a mixed respiratory and metabolic alkalosis (3), the latter condition due to development of a hyponatremia-related hyperaldosteronism (3). a Received February 26, 2004. Address correspondence to: Tooraj Zahedi, M.D., F.A.C.E., Clinical Associate Professor of Medicine, State University of New York in Brooklyn, One Brookdale Plaza, SSI/Room 101A, Brooklyn, New York 11212-3198. b Received July 1, 2004. Address correspondence to: Guy Decaux, M.D., Ph.D., Department of Internal Medicine, Research Unit for Study of Hydromineral Metabolism, 808 Route de Lennik, Brussels, 1070 Belgium. E-mail:
[email protected].
Is Growth Hormone Treatment in Young Children Safe for the Heart? To the editor: We read with great interest the paper by Shulman et al. (1). The authors report the beneficial effect of 1-yr recombinant human (rh) GH treatment on cardiac mass and function in children with classical GH deficiency (GHD). These findings have important clinical implications in the long-term follow-up because there is a well-established relationship between GHD and increased cardiovascular mortality in untreated adults (2). We would like, however, to make some comments. In the study, 10 young children with a relatively early onset of GHD at a median age of less than 5 yr were treated with rhGH at a dose of 0.3 mg/kg䡠wk for 12 months; seven had structural abnormalities of the hypothalamic-pituitary axis, a diagnosis compatible with permanent GHD. Their main findings consisted in increased left ventricular mass indexed by body surface area, height or height2.7 after 1 yr of rhGH therapy. The trophic effect of GH on the heart was confirmed, but the results raise questions about the long-term safety of subjects with childhood onset GHD treated at the above-mentioned dose. In a group of 14 GHD children treated with the same dosage (0.3 mg/kg䡠wk) for a mean period of 5 yr, we reported a significant increase in left ventricular (LV) mass, mass/volume ratio, and an alteration of LV diastolic function compared with a group of normal children (3). No differences in morphofunctional cardiac indices were shown between Received July 2, 2004. Address correspondence to: Dr. Giorgio Radetti, Department of Pediatrics, Regional Hospital of Bolzano, via L. Boehler no. 5, 39100 Bolzano, Italy. E-mail:
[email protected]; or Mohamad Maghnie, M.D., Ph.D, Department of Pediatrics, University of Pavia, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico S. Matteo, I-27100, Pavia, Italy. E:mail:
[email protected]. A response to this letter was invited, but the authors of the original article chose not to provide one.
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patients and controls after 1 yr of treatment (4). Moreover, in another study we carried out, no adverse effects on the heart were observed in a group of patients with Turner’s syndrome treated with the same rhGH dose for 1 yr (5). The discrepancy between our results and those reported by Shulman et al. (1) could be explained either by the duration of treatment or by a different tissue responsiveness to rhGH among patients. Indeed, tissue sensitivity is inversely correlated to serum GH levels (6). This would also explain the findings in Turner’s syndrome patients, who are not GH deficient and thus relatively resistant to the GH action. We think that the severity of GHD in the young patients of Shulman et al. (1) is indeed an important factor that should not be underestimated because these patients are probably more sensitive to GH action and, consequently, to its potential adverse effects on the heart in the long-term treatment. Furthermore, unlike our cohort of patients with isolated GHD (3), Shulman’s patients suffer from a combined pituitary hormone deficiency and thus from a more severe GH deficit that would make them even more sensitive to GH therapy. Indeed, this is supported by the negative correlation that Shulman found between the LV mass and the response to rhGH treatment. Hypothalamic-pituitary abnormalities in GHD are highly predictive of severe, “true,” and permanent GHD in adult life. We therefore believe that the amount of rhGH administered to children with severe GH deficit, as the one reported by Shulman et al., should be reduced to the lowest possible effective dosage to avoid a potential damage to cardiac mass and function later on in life.
Letters to the Editor
Giorgio Radetti and Mohamad Maghnie Department of Pediatrics (G.R.), Regional Hospital of Bolzano, 39100 Bolzano, Italy; and Department of Pediatrics (M.M.), University of Pavia, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico S. Matteo, 27100 Pavia, Italy
References 1. Shulman DI, Root AW, Diamond FB, Bercu BB, Martinez R, Boucek Jr RJ 2003 Effects of one year of recombinant human growth hormone (GH) therapy on cardiac mass and function in children with classical GH deficiency. J Clin Endocrinol Metab 88:4095– 4099 2. Rosen T, Bengtsson BA 1990 Premature mortality due to cardiovascular disease in hypopituitarism. Lancet 336:285–288 3. Radetti G, Crepaz R, Paganini C, Gentili L, Pitscheider W 1999 Medium-term cardiovascular effects of high-dose growth hormone treatment in growth hormone-deficient children. Horm Res 52:247–252 4. Crepaz R, Pitscheider W, Radetti G, Paganini C, Gentili L, Morini G, Braito E, Mengarda G 1995 Cardiovascular effects of high-dose growth hormone treatment in growth hormone-deficient children. Pediatr Cardiol 16:223–227 5. Radetti G, Crepaz R, Milanesi O, Paganini C, Cesaro A, Rigon F, Pitscheider W 2001 Cardiac performance in Turner’s syndrome patients on growth hormone therapy. Horm Res 55:240 –244 6. Martha Jr PM, Reiter EO, Davila N, Shaw MA, Holcombe JH, Baumann G 1992 Serum growth hormone (GH)-binding protein/receptor: an important determinant of GH responsiveness. J Clin Endocrinol Metab 75:1464 –1469 doi: 10.1210/jc.2004-1282
