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July 1966, Vol 15, No. 1 >
Article | July 1966

Neurogenic Hypernatremia

DAVID PLEASURE, MD; MARK GOLDBERG, PhD, MD
[+] Author Affiliations

Submitted for publication Dec 30, 1965; accepted Jan 9, 1966.

Reprint requests to Neurological Institute, 710 W 168th St, New York 10032 (Dr. Pleasure).


Arch Neurol. 1966;15(1):78-87. doi:10.1001/archneur.1966.00470130082009
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CENTRAL nervous system dysfunction has been implicated in disorders of water and osmolar balance, including diabetes insipidus, inappropriate secretion of antidiuretic hormone (ADH),1 hypodipsia,2,3 and neurogenic hypernatremia.4,5 The physiologic basis of diabetes insipidus is comparatively well understood, and hypodipsia and inappropriate secretion of ADH have been studied with the aid of experimental models.1,6-8 However, the existence of hypernatremia and hyperosmolarity due to hypothalamic disease and not attributable to diabetes insipidus or hypodipsia has been questioned.9,10 One difficulty in the recognition of this syndrome arises from the close proximity of the ADH secretion, thirst, and osmoreceptor centers in the anterior hypothalamus so that lesions in this area may produce various combinations of diabetes insipidus, hypodipsia, and hypernatremia.4,5

A clinical definition of primary neurogenic hypernatremia must distinguish this syndrome from the far more frequent hyperosmolarity of dehydration, resulting from diabetes insipidus, hypodipsia, and gastrointestinal or renal

REFERENCES

1 +
Goldberg, M.:  Hyponatremia and the Inappropriate Secretion of Antidiuretic Hormone, editorial , Amer J Med 35:293-298, 1963;.
2 +
Hays, R.M.; McHugh, P.R.; and Williams, H.E,:  Absence of Thirst in Association With Hydrocephalus , New Eng J Med 269:227-231, 1963;.
3 +
Bernard-Weil, E.; Dray, F.; and David, M.:  A propos d'un cas d'hypernatremie neurogene traite par l'extrait d'hypophyse posterieure étude de l'aldosteronurie , Ann Endocr 22:982-987, 1961;.
4 +
Avioli, L.V.; Earley, L.E.; and Kashima, H.K.:  Chronic and Sustained Hypernatremia, Absence of Thirst, Diabetes Insipidus, and Adrenocorticotrophin Insufficiency Resulting From Widespread Destruction of the Hypothalamus , Ann Intern Med 56:131-140, 1962;.
5 +
Kastin, A.J., et al:  Asymptomatic Hypernatremia , Amer J Med 38:306-315, 1965;.
6 +
Montemurro, D.G., and Stevenson, J.A.F.:  The Localization of Hypothalamic Structures in the Rat Influencing Water Consumption , Yale J Biol Med 28:396-403, 1955-1956;.
7 +
Andersson, B., and McCann, S.M.:  Drinking, Antidiuresis and Milk Ejection From Electrical Stimulation Within the Hypothalamus of the Goat , Acta Physiol Scand 35:191-201, 1955;.
8 +
Andersson, B., and McCann, S.M.:  The Effect of Hypothalamic Lesions on the Water Intake of the Dog , Acta Physiol Scand 35:312-320, 1955;.
9 +
Zierler, J.L.:  Hyperosmolarity in Adults: A Critical Review , J Chron Dis 7:1-23, 1958;.
10 +
Gilbert, G.J., and Glaser, G.H.:  On the Nervous System Integration of Water and Salt Metabolism , Arch Neurol 5:179-196, 1961;.
11 +
Jewell, P.A., and Verney, E.B.:  An Experimental Attempt to Determine the Site of the Neurohypophyseal Osmoreceptors in the Dog , Proc Roy Soc (Biol) 240:197-324, 1957;.
12 +
Roth, J., et al:  Hypoglycemia: A Potent Stimulus to Secretion of Growth Hormone , Science 140:987-988, 1963;.
13 +
Laragh, J.H.:  Aldosterone in Fluid and Electrolyte Disorders: Hyper- and Hypoaldosteronism , J Chronic Dis 11:292-318, 1960;.
14 +
Bradbury, M.W.B., et al:  The Distribution of Potassium, Sodium, Chloride and Urea Between Lumbar Cerebrospinal Fluid and Blood Serum in Human Subjects , Clin Sci 25:97-105, 1963;.
15 +
Downie, A.W.: " Studies in Nerve Conduction ," in Walton, J.N. (ed): Disorders of Voluntary Muscle , London: J. & A. Churchill, Ltd., 1964;, pp 511-535.
16 +
Shy, G.M., et al:  Studies in Familial Periodic Paralysis , Exp Neurol 3:53-121, 1961;.
17 +
Orloff, J.; Wagner, H.N.; and Davidson, D.G.:  The Effect of Variations in Solute Excretion and Vasopressin Dosage on the Excretion of Water in the Dog , J Clin Invest 37:458-464, 1958;.
18 +
Engel, F.L., and Jaeger, C.:  Dehydration With Hypernatremia, Hyperchloremia and Azotemia Complicating Nasogastric Tube Feeding , Amer J Med 17:196-204, 1954;.
19 +
Conn, J.W.; Knopf, R.F.; and Nesbit, R.M.:  Clinical Characteristics of Primary Aldosteronism From an Analysis of 145 Cases , Amer J Surg 107:159-172, 1964;.
20 +
Ferrebee, J.W., et al:  Certain Effects of Desoxycorticosterone: The Development of "Diabetes Insipidus" and the Replacement of Muscle Potassium by Sodium in Normal Dogs , Amer J Physiol 135:230-237, 1941-1942;.
21 +
Borst, J.G.G.:  The Cause of Hyperchloremia and Hyperazotemia in Patients With Recurrent Massive Hemorrhage From Peptic Ulcer , Acta Med Scand 97:68-88, 1938;.
22 +
Sonnenblick, E.H.; Cannon, P.J.; and Laragh, J.H.:  The Nature of the Action of Intravenous Aldosterone: Evidence for a Role of the Hormone in Urinary Dilution , J Clin Invest 40:903-913, 1961;.
23 +
Allott, E.N.:  Sodium and Chlorine Retention Without Renal Disease , Lancet 1:1035-1037, 1939;.
24 +
Taylor, W.H.:  Hypernatremia in Cerebral Disorders , J Clin Path 15:211-220, 1962;.
25 +
Kleeman, C.R.; Maxwell, M.H.; and Rockney, R.E.:  Mechanisms of Impaired Water Excretion in Adrenal and Pituitary Insufficiency: I. The Role of Altered Glomerular Filtration Rate and Solute Excretion , J Clin Invest 37:1799-1808, 1958;.
26 +
Martin, M.M.:  Combined Anterior Pituitary and Neurohypophyseal Insufficiency: Studies of Body Fluid Spaces and Renal Function , J Clin Invest 38:882-891, 1959;.
27 +
Crompton, M.R.:  Hypothalamic Lesions Following the Rupture of Cerebral Berry Aneurysms , Brain 86:301-314, 1963;.
28 +
Joynt, R.J.; Afifi, A.; and Harbison, J.:  Hyponatremia in Subarachnoid Hemorrhage , Arch Neurol 13:633-638, 1965;.
29 +
Perera, G.A.:  The Effect of Significant Weight Changes on the Predicted Plasma Volume , J Clin Invest 25:401-403, 1946;.
30 +
Weitzman, E.D., and Triedman, M.H.:  Hyperosmolarity Associated With a Hypothalamic Lesion , Neurology 10:584-590, 1960;.
31 +
Counihan, T.B.; Evans, B.M.; and Milne, M.D.:  Observations on the Pharmacology of the Carbonic Anhydrase Inhibitor "Diamox," Clin Sci 13:583-598, 1954;.
32 +
Laragh, J.H.:  The Mode of Action and Use of Chlorothiazide and Related Compounds , Circulation 26:121-132, 1962;.
33 +
Kamm, D.E., and Levinsky, N.G.:  Inhibition of the Renal Tubular Sodium Reabsorption by Hypernatremia , J Clin Invest 44:1144-1150, 1965;.
34 +
Dirks, J.H.; Cirksena, W.J.; and Berliner, R.W.:  The Effect of Saline Infusion on Sodium Reabsorption by the Proximal Tubule of the Dog , J Clin Invest 44:1160-1170, 1965;.
35 +
Koizumi, J.; Ishikawa, T.; and Brooks, C.McC.:  Control of Activity of Neurons in the Supraoptic Nucleus , J Neurophysiol 27:878-892, 1962;.
36 +
Lederis, K.: " The Distribution of Vasopressin and Oxytocin in Hypothalamic Nuclei ," in Heller, H., and Clark, R.B. (eds): Neurosecretion , New York: Academic Press, Inc., 1962;, pp 227-236.
37 +
Knowles, H.C., Jr.:  Hypernatremia , Metabolism 5:508-518, 1956;.
38 +
Epstein, A.N., and Teitelbaum, P.: " Severe and Persistent Deficits in Thirst Produced by Lateral Hypothalamic Damage ," in Wayner, M.J. (ed): Thirst , New York: Macmillan Co., 1964;, pp 395-406.
39 +
Milne, M.D.; Stanbury, S.W.; and Thomson, A.E.:  Observations on the Fanconi Syndrome and Renal Hyperchloraemic Acidosis in the Adult , Quart J Med 21:61-82, 1952;.

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1 +
Goldberg, M.:  Hyponatremia and the Inappropriate Secretion of Antidiuretic Hormone, editorial , Amer J Med 35:293-298, 1963;.
2 +
Hays, R.M.; McHugh, P.R.; and Williams, H.E,:  Absence of Thirst in Association With Hydrocephalus , New Eng J Med 269:227-231, 1963;.
3 +
Bernard-Weil, E.; Dray, F.; and David, M.:  A propos d'un cas d'hypernatremie neurogene traite par l'extrait d'hypophyse posterieure étude de l'aldosteronurie , Ann Endocr 22:982-987, 1961;.
4 +
Avioli, L.V.; Earley, L.E.; and Kashima, H.K.:  Chronic and Sustained Hypernatremia, Absence of Thirst, Diabetes Insipidus, and Adrenocorticotrophin Insufficiency Resulting From Widespread Destruction of the Hypothalamus , Ann Intern Med 56:131-140, 1962;.
5 +
Kastin, A.J., et al:  Asymptomatic Hypernatremia , Amer J Med 38:306-315, 1965;.
6 +
Montemurro, D.G., and Stevenson, J.A.F.:  The Localization of Hypothalamic Structures in the Rat Influencing Water Consumption , Yale J Biol Med 28:396-403, 1955-1956;.
7 +
Andersson, B., and McCann, S.M.:  Drinking, Antidiuresis and Milk Ejection From Electrical Stimulation Within the Hypothalamus of the Goat , Acta Physiol Scand 35:191-201, 1955;.
8 +
Andersson, B., and McCann, S.M.:  The Effect of Hypothalamic Lesions on the Water Intake of the Dog , Acta Physiol Scand 35:312-320, 1955;.
9 +
Zierler, J.L.:  Hyperosmolarity in Adults: A Critical Review , J Chron Dis 7:1-23, 1958;.
10 +
Gilbert, G.J., and Glaser, G.H.:  On the Nervous System Integration of Water and Salt Metabolism , Arch Neurol 5:179-196, 1961;.
11 +
Jewell, P.A., and Verney, E.B.:  An Experimental Attempt to Determine the Site of the Neurohypophyseal Osmoreceptors in the Dog , Proc Roy Soc (Biol) 240:197-324, 1957;.
12 +
Roth, J., et al:  Hypoglycemia: A Potent Stimulus to Secretion of Growth Hormone , Science 140:987-988, 1963;.
13 +
Laragh, J.H.:  Aldosterone in Fluid and Electrolyte Disorders: Hyper- and Hypoaldosteronism , J Chronic Dis 11:292-318, 1960;.
14 +
Bradbury, M.W.B., et al:  The Distribution of Potassium, Sodium, Chloride and Urea Between Lumbar Cerebrospinal Fluid and Blood Serum in Human Subjects , Clin Sci 25:97-105, 1963;.
15 +
Downie, A.W.: " Studies in Nerve Conduction ," in Walton, J.N. (ed): Disorders of Voluntary Muscle , London: J. & A. Churchill, Ltd., 1964;, pp 511-535.
16 +
Shy, G.M., et al:  Studies in Familial Periodic Paralysis , Exp Neurol 3:53-121, 1961;.
17 +
Orloff, J.; Wagner, H.N.; and Davidson, D.G.:  The Effect of Variations in Solute Excretion and Vasopressin Dosage on the Excretion of Water in the Dog , J Clin Invest 37:458-464, 1958;.
18 +
Engel, F.L., and Jaeger, C.:  Dehydration With Hypernatremia, Hyperchloremia and Azotemia Complicating Nasogastric Tube Feeding , Amer J Med 17:196-204, 1954;.
19 +
Conn, J.W.; Knopf, R.F.; and Nesbit, R.M.:  Clinical Characteristics of Primary Aldosteronism From an Analysis of 145 Cases , Amer J Surg 107:159-172, 1964;.
20 +
Ferrebee, J.W., et al:  Certain Effects of Desoxycorticosterone: The Development of "Diabetes Insipidus" and the Replacement of Muscle Potassium by Sodium in Normal Dogs , Amer J Physiol 135:230-237, 1941-1942;.
21 +
Borst, J.G.G.:  The Cause of Hyperchloremia and Hyperazotemia in Patients With Recurrent Massive Hemorrhage From Peptic Ulcer , Acta Med Scand 97:68-88, 1938;.
22 +
Sonnenblick, E.H.; Cannon, P.J.; and Laragh, J.H.:  The Nature of the Action of Intravenous Aldosterone: Evidence for a Role of the Hormone in Urinary Dilution , J Clin Invest 40:903-913, 1961;.
23 +
Allott, E.N.:  Sodium and Chlorine Retention Without Renal Disease , Lancet 1:1035-1037, 1939;.
24 +
Taylor, W.H.:  Hypernatremia in Cerebral Disorders , J Clin Path 15:211-220, 1962;.
25 +
Kleeman, C.R.; Maxwell, M.H.; and Rockney, R.E.:  Mechanisms of Impaired Water Excretion in Adrenal and Pituitary Insufficiency: I. The Role of Altered Glomerular Filtration Rate and Solute Excretion , J Clin Invest 37:1799-1808, 1958;.
26 +
Martin, M.M.:  Combined Anterior Pituitary and Neurohypophyseal Insufficiency: Studies of Body Fluid Spaces and Renal Function , J Clin Invest 38:882-891, 1959;.
27 +
Crompton, M.R.:  Hypothalamic Lesions Following the Rupture of Cerebral Berry Aneurysms , Brain 86:301-314, 1963;.
28 +
Joynt, R.J.; Afifi, A.; and Harbison, J.:  Hyponatremia in Subarachnoid Hemorrhage , Arch Neurol 13:633-638, 1965;.
29 +
Perera, G.A.:  The Effect of Significant Weight Changes on the Predicted Plasma Volume , J Clin Invest 25:401-403, 1946;.
30 +
Weitzman, E.D., and Triedman, M.H.:  Hyperosmolarity Associated With a Hypothalamic Lesion , Neurology 10:584-590, 1960;.
31 +
Counihan, T.B.; Evans, B.M.; and Milne, M.D.:  Observations on the Pharmacology of the Carbonic Anhydrase Inhibitor "Diamox," Clin Sci 13:583-598, 1954;.
32 +
Laragh, J.H.:  The Mode of Action and Use of Chlorothiazide and Related Compounds , Circulation 26:121-132, 1962;.
33 +
Kamm, D.E., and Levinsky, N.G.:  Inhibition of the Renal Tubular Sodium Reabsorption by Hypernatremia , J Clin Invest 44:1144-1150, 1965;.
34 +
Dirks, J.H.; Cirksena, W.J.; and Berliner, R.W.:  The Effect of Saline Infusion on Sodium Reabsorption by the Proximal Tubule of the Dog , J Clin Invest 44:1160-1170, 1965;.
35 +
Koizumi, J.; Ishikawa, T.; and Brooks, C.McC.:  Control of Activity of Neurons in the Supraoptic Nucleus , J Neurophysiol 27:878-892, 1962;.
36 +
Lederis, K.: " The Distribution of Vasopressin and Oxytocin in Hypothalamic Nuclei ," in Heller, H., and Clark, R.B. (eds): Neurosecretion , New York: Academic Press, Inc., 1962;, pp 227-236.
37 +
Knowles, H.C., Jr.:  Hypernatremia , Metabolism 5:508-518, 1956;.
38 +
Epstein, A.N., and Teitelbaum, P.: " Severe and Persistent Deficits in Thirst Produced by Lateral Hypothalamic Damage ," in Wayner, M.J. (ed): Thirst , New York: Macmillan Co., 1964;, pp 395-406.
39 +
Milne, M.D.; Stanbury, S.W.; and Thomson, A.E.:  Observations on the Fanconi Syndrome and Renal Hyperchloraemic Acidosis in the Adult , Quart J Med 21:61-82, 1952;.

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