LETTERS
Letters that report new clinical or laboratory observations, cases of unusual importance, and new developments in medical care will be considered for publication in this section. Manuscripts must be typed double-spaced. Text length must not exceed 750 words', no more than five references and one figure or table can be used. See "Information for Authors" on page 1-6 for form of references. Manuscripts should include an abstract of length not exceeding 50 words. Letters will be reviewed by consultants when, in the opinion of the editors, such review is needed. The Editor reserves the right to shorten letters and to make changes that accord with our style. Water Intoxication and Thioridazine (Mellaril®) T H E OCCURRENCE of water intoxication in patients who have the ability to dilute urine normally is very unusual (1). Normal adults can excrete between 10 and 14 ml/ min of solute-free water, and it is an unusual circumstance which results in the ingestion of sufficiently more water than this so that significant dilutional hyponatremia develops. We wish to report two cases of patients we have recently observed, both of whom had a psychiatric background and who were being treated with thioridazine (Mellaril®) at the time of the water intoxication. The first patient was a 51-year-old man admitted to the hospital because of disorientation and confusion. He had been treated with 100 mg of thioridazine twice a day because of schizophrenia. At the time of admission his serum sodium concentration was 116 meq/ litre, plasma osmolality was 268 mosmol/kg H 2 0 , and urine osmolality was 66. The patient improved on fluid restriction and by the next day the serum sodium was 134, plasma osmolality was 281, and urine osmolality was 665. Several days after admission and after the discontinuation of the thioridazine, the patient was given a 20 ml/kg waterload, and his urine osmolality decreased to 69. The second patient was a 42-year-old female who was admitted because of seizures and disorientation. Because of mental retardation and a seizure disorder she had been treated with barbital, 100 mg twice a day; diphenylhydantoin, 100 mg twice a day; oxazepam, 15 mg twice a day; and thioridazine, 250 mg daily. At the time of admission she was responsive only to painful stimuli, and there was gross distension of the urinary bladder. Serum sodium was 111 meq/litre, whereas plasma osmolality was 250 mosmol/kg H 2 0 and urine osmolality was 73. Four litres of urine were obtained by catheterization. She was allowed no fluids, and on the first day her urine output was 10.3 litres. During the first 24 hours of hospitalization her sensorium markedly improved, and the serum sodium concentration increased by 131 meq/litre. At 48 hours after admission the serum sodium was 140 meq/ litre, plasma osmolality was 285, and urine osmolality was 490. Water intoxication in the presence of normal urinary diluting capacity has been reported only in patients with severe psychiatric disorders. The fluid has usually been Annals of Interna! Medicine 82:61-63, 1975
Downloaded from https://annals.org by Tulane University user on 01/12/2019
water administered by mouth, but water enemas (2) and beer drinking (3) have also been reported to cause this problem. The presence of a markedly hypotonic urine in these two patients at the time of the water intoxication and hyponatremia eliminates the possibility that thioridazine produced the syndrome of inappropriate antidiuretic hormone secretion, as has been observed with drugs such as chlorpropamide and vincristine (4, 5 ) . The phenothiazine group of drugs is known to have marked parasympathetic effects and may cause dryness of the mouth, which may aggravate tendencies toward compulsive water drinking. Another possibility is that thioridazine and perhaps other phenothiazines may stimulate the hypothalamic thirst center directly. The urinary retention in our second patient may have also been a side effect of the thioridazine. Regardless of mechanism, we believe that the medical profession should be alerted to the fact that certain drugs may possibly promote water intake and lead to water intoxication. We believe that the association of water intoxication and thioridazine therapy in these two patients may not be coincidence. K. J. RAO, M.D. MYRON MILLER, M.D. ARNOLD MOSES, M.D.
Veterans Administration Hospital Irving Avenue and University Place Syracuse, New York 13210 Department of Medicine State University of New York Upstate Medical Center Syracuse, New York 13210 REFERENCES
1. LANGGARD H, SMITH WO: Self-induced water intoxication without predisposing illness. N Engl J Med 266:378-381, 1962 2. NIELSEN J: Water intoxication and psychosis (letter). Ann InternMed 80:280-281, 1974 3. DEMANET JC, BONNYNS M, BLEIBERG H, et al: Coma due to
water intoxication in beer drinkers. Lancet 2:1115-1117, 1971 4. GARCIA M, MILLER M, MOSES AM:
Chlorpropamide-induced
water retention in patients with diabetes mellitus. Ann Intern Med 75:549-554, 1971 5. ROSENTHAL S, KAUFMAN S: Vincristine neurotoxicity. Ann In-
tern Med 80:733-737, 1974 Raw Diet and Insulin Requirements D I E T control has been and is a mainstay of the therapeutic regime used to treat diabetes mellitus. It is generally recognized that overweight diabetic patients on oral antidiabetic agents can sometimes have their oral agents discontinued if they lose weight and adhere closely to an anti-diabetic diet. It is not usually accepted that a patient on insulin may have his insulin requirement reduced without significant reduction of his weight. In the cases reported here one patient had his insulin requirement reduced from 60 units per day to 15 units per day by
61
Table 1. Insulin Requirem*ants of Two Patients After Modi flcations in Their Diets* Diet Raw
Cooked
_ Patient 1 30 July 1970 4 August 1970 31 December 1971 17 March 1971 21 May 1971 9 June 1971 18 June 1971 27 July 1972 20 March 1973 21 May 1974 Patient 2 13 February 1973 2 Marc^i 1973 11 April 1973 8 May 1973 24 May 1973 11 July 1973 23 November 1973 7 February 1974 23 April 1974 23 May 1974
Insulin
Blood Sugai
Weight
Fasting
•Other units
mg/100 ml
kg
5 10 10 80 90 90 95 30 50 50
95 90 90 20 10 10 5 70 50 50
63.5 64.4 ? 63.0 61.6 ? 62.1 62.1 62.5 61.4
94 118
118 173 108
5 60 60 80 80 20 50 50 60
95 40 40 20 20 80 50 50 40
86.1 87.0 86.6 83.4 ? 84.1 86.8 ? 84.3
193 157 208 168 125 220 167 218 192
60
40
83.2
185
90 f 901 103 50 248§
40 NPH/20 lente 40 NPH 40 NPH 35 NPH 25 NPH 20 NPH 0 15 NPH 18 NPH 30 NPH 70 NPH 60 NPH 30 NPH 0 0 15 NPH Diabinese, 250/day Diabinese, 250 twice a day Diabinese, 250 three times a day Diabinese, 250 three times a day and phenformin hydrochloride, 50/day
* N P H = neutral protamiiie Hagedorn insulin. t Measured by Dextrostix imethod. X Random measurement. § Measured one hour post cibum.
dietary management alone, and another had his insulin requirement reduced from 70 units per day to oral agents alone. Both of these changes were accomplished by increasing the percentage of raw food in their diets. My rationale was that since early man lived entirely on raw food, perhaps such a diet would be less stressful to the human system in general and less diabetogenic than a cooked food diet. I recommended raw foods such as vegetables, seeds, nuts, berries, melons, fruits, eggs (yolks only), honey, oils, and goat's milk. Fruits, melons, and honey were not to be eaten in large quantities, and nuts and salads were to be made the main part of the raw-food diet. Raw meats and fish were not suggested because of the parasite infestation problem. I recommended raw goat's milk because there is much less risk of brucellosis or tuberculosis from it than, from raw cow's milk*. Raw egg white was not advised because it may contain a biotinblocking factor.
control is adequate so long as he maintains an 80% raw diet (Table 1). The mechanism whereby this salutory effect on diabetes was obtained is unknown. It may have to do with the interaction of the non-inactivated enzymes that are present in raw items or with the fast transit time that is inherent in a raw diet (1, 2 ) . The observed effect seems to merit a formal study with more patients, with better documentation of diet and patients' adherence to diet.
Patient 1 is an elderly Euro-American man who was comparatively comfortable with his insulin dosage but did not like taking insulin twice a day. His diet was first brought more toward the recommended diabetic diet and then modified toward an uncooked diet. As of 21 May 1974 he was on 30 units of insulin and on an approximately 50% raw diet (Table 1). Patient 2 is a young Mexican-American man who complained so bitterly about the pain associated with taking insulin that he insisted that he would rather die than take "shots." At present his diabetes is controlled on oral agents alone. His
1. POTTENGER FM JR: The effect of heat processed foods and metabolized vitamin D milk on the dentofacial structures of experimental animals. Am J Orthodont Oral Surg 32:467-485, 1946
* UNITED STATES DEPARTMENT OF AGRICULTURE: Personal communica-
tion. 52
JOHN M. DOUGLASS, M.D.
Department of Internal Medicine Southern California Permanente Medical Group and Kaiser Foundation Hospital 1526 North Edgemont St. Los Angeles, California 90027 REFERENCES
2. BURKITT DP, WALKER ARP, PAINTER NS: Dietary fiber and dis-
ease. JAMA 229:1068-1074, 1974
Cyclic Laryngeal Edema with Aphonia IN JULY 1974 we saw Mrs. B. for the first time. This 24year-old woman complained of aphonia of 5 to 7 days' duration, which was followed by several days of hoarseness. Such episodes had occurred with each of her menstrual periods through the previous 8 months.
January 1975 • Annals of Internal Medicine • Volume 82 • Number 1
Downloaded from https://annals.org by Tulane University user on 01/12/2019
Her menarche had been at age 14, and her menses were regular ever since. Five years ago she became pregnant, but miscarried in the third month of pregnancy. She never became pregnant again. A year ago a diagnosis of left-sided ovarian cyst was made and the cyst was removed surgically. The pelvic organs were examined carefully during surgery and were normal. A year ago, the patient took a birth-control medication for 3 months. She stopped its use because of muscle aches. Eight months before admission, the patient had aphonia for the first time. This occurred on the second menstrual day, was not accompanied by cough or fever, and lasted for 7 days. Since then the aphonia has occurred with each of her menstrual periods. Occasionally slight hoarseness and some "wheezing" developed in the middle of the menstrual cycle accompanied by some abdominal "bloating," stiffness of the neck, and temporary premenstrual weight gain up to 2.2 kg [5 lbs]. She had occasional headaches. The past medical history was unremarkable. Two members of her family have been treated for diabetes mellitus. The patient weighed 49.6 kg [109^ lbs] and was 1.67 metres [5 feet 6 inches] tall. Her blood pressure was 110/70 mm Hg, pulse 72/min and regular. She was afebrile. Her breasts were slightly tender to palpation, and she had no galactorrhea. The external genitalia, pelvic organs, and secondary sex characteristics were normal. The basal temperature chart indicated normal ovulatory cycles. Neurologic findings were normal. The laryngoscopy examination showed diffuse swelling of the vocal cords during the episode of aphonia and normal findings during remission. Normal laboratory data included urinanalysis findings; complete blood count; multichannel (12) biochemical data; protein electrophoresis; measurement of serum thyroxine, T3 resin uptake, and thyroid stimulating hormone; and glucose tolerance test. Serum creatinine and creatinine clearance were normal. Total 24-hour urinary estrogens were 18.0 fig in midcycle (minimum normal range 7 to 23 /*g, ovulation peak 44 to 93). Premenstrual serum estradiol was 24.6 ng/100 ml (normal, luteal phase, 10 to 30 ng/100 ml), serum estrone was 15.7 ng/100 ml (normal 5 to 20), and serum progesterone 3.225 /tg/100 ml (normal, 0 to 1.6). Midcycle serum follicle stimu-
lating hormone and luteinizing hormone were normal, 20 and 34 mlU/ml respectively. Serum electrolytes were normal: sodium, 143 meq/litre, potassium 4.6 meq/litre, chlorine 108 meq/litre. Urinary electrolytes were also normal: sodium, 194 meq/24 h, potassium 39 meq/24 h and chlorine, 199 meq/24 h. Plasma renin was 1.3 ng/ml-h (normal, 0.73 to 4.90 ng/ml-h), and aldosterone secretion rate 20 fig/24 h urine (normal, 2 to 26). The aphonia was interpreted as due to vocal cord swelling after premenstrual fluid retention. The patient was advised to restrict her salt intake and was given spironolactone (Aldactone®) and hydrochlorothiazide (Hydrodiuril®). With the beginning of this therapy she had a moderate weight loss 0.9 to 1.3 kg [2 to 3 lbs] and the episodes of aphonia disappeared as did all other associated symptoms. I believe that increased local capillary permeability and resulting edema of the vocal cords were the reason for this syndrome. It may belong in the obviously heterogenous diagnostic group of idiopathic cyclic edema, in which patients with protein rich edema may have abnormal carbohydrate metabolism, capillary membrane thickening, increased capillary permeability, and secondary hyperaldosteronism ( 1 , 2 ) . The significance of the high serum progesterone in our case remains to be elucidated. LUBOMIR J. VALENTA, M.D.
Department of Medicine, College of Human Medicine B220 Life Sciences I Michigan State University East Lansing, Michigan 48824 REFERENCES
1. COLEMAN M, HORWTTH M, BROWN JL: Idiopathic edema. Studies
demonstrating protein leaking angiopathy. Am J Med 49:106112, 1970 2. ROVNER DR: The enigma of idiopathic cyclic edema. Hosp Tract 7:103-110, 1972
Letters
Downloaded from https://annals.org by Tulane University user on 01/12/2019
63
Letters that report new clinical or laboratory observations, cases of unusual importance, and new developments in medical care will be considered for publication in this section. Manuscripts must be typed double-spaced. Text length must not exceed 750 words', no more than five references and one figure or table can be used. See "Information for Authors" on page 1-6 for form of references. Manuscripts should include an abstract of length not exceeding 50 words. Letters will be reviewed by consultants when, in the opinion of the editors, such review is needed. The Editor reserves the right to shorten letters and to make changes that accord with our style. Water Intoxication and Thioridazine (Mellaril®) T H E OCCURRENCE of water intoxication in patients who have the ability to dilute urine normally is very unusual (1). Normal adults can excrete between 10 and 14 ml/ min of solute-free water, and it is an unusual circumstance which results in the ingestion of sufficiently more water than this so that significant dilutional hyponatremia develops. We wish to report two cases of patients we have recently observed, both of whom had a psychiatric background and who were being treated with thioridazine (Mellaril®) at the time of the water intoxication. The first patient was a 51-year-old man admitted to the hospital because of disorientation and confusion. He had been treated with 100 mg of thioridazine twice a day because of schizophrenia. At the time of admission his serum sodium concentration was 116 meq/ litre, plasma osmolality was 268 mosmol/kg H 2 0 , and urine osmolality was 66. The patient improved on fluid restriction and by the next day the serum sodium was 134, plasma osmolality was 281, and urine osmolality was 665. Several days after admission and after the discontinuation of the thioridazine, the patient was given a 20 ml/kg waterload, and his urine osmolality decreased to 69. The second patient was a 42-year-old female who was admitted because of seizures and disorientation. Because of mental retardation and a seizure disorder she had been treated with barbital, 100 mg twice a day; diphenylhydantoin, 100 mg twice a day; oxazepam, 15 mg twice a day; and thioridazine, 250 mg daily. At the time of admission she was responsive only to painful stimuli, and there was gross distension of the urinary bladder. Serum sodium was 111 meq/litre, whereas plasma osmolality was 250 mosmol/kg H 2 0 and urine osmolality was 73. Four litres of urine were obtained by catheterization. She was allowed no fluids, and on the first day her urine output was 10.3 litres. During the first 24 hours of hospitalization her sensorium markedly improved, and the serum sodium concentration increased by 131 meq/litre. At 48 hours after admission the serum sodium was 140 meq/ litre, plasma osmolality was 285, and urine osmolality was 490. Water intoxication in the presence of normal urinary diluting capacity has been reported only in patients with severe psychiatric disorders. The fluid has usually been Annals of Interna! Medicine 82:61-63, 1975
Downloaded from https://annals.org by Tulane University user on 01/12/2019
water administered by mouth, but water enemas (2) and beer drinking (3) have also been reported to cause this problem. The presence of a markedly hypotonic urine in these two patients at the time of the water intoxication and hyponatremia eliminates the possibility that thioridazine produced the syndrome of inappropriate antidiuretic hormone secretion, as has been observed with drugs such as chlorpropamide and vincristine (4, 5 ) . The phenothiazine group of drugs is known to have marked parasympathetic effects and may cause dryness of the mouth, which may aggravate tendencies toward compulsive water drinking. Another possibility is that thioridazine and perhaps other phenothiazines may stimulate the hypothalamic thirst center directly. The urinary retention in our second patient may have also been a side effect of the thioridazine. Regardless of mechanism, we believe that the medical profession should be alerted to the fact that certain drugs may possibly promote water intake and lead to water intoxication. We believe that the association of water intoxication and thioridazine therapy in these two patients may not be coincidence. K. J. RAO, M.D. MYRON MILLER, M.D. ARNOLD MOSES, M.D.
Veterans Administration Hospital Irving Avenue and University Place Syracuse, New York 13210 Department of Medicine State University of New York Upstate Medical Center Syracuse, New York 13210 REFERENCES
1. LANGGARD H, SMITH WO: Self-induced water intoxication without predisposing illness. N Engl J Med 266:378-381, 1962 2. NIELSEN J: Water intoxication and psychosis (letter). Ann InternMed 80:280-281, 1974 3. DEMANET JC, BONNYNS M, BLEIBERG H, et al: Coma due to
water intoxication in beer drinkers. Lancet 2:1115-1117, 1971 4. GARCIA M, MILLER M, MOSES AM:
Chlorpropamide-induced
water retention in patients with diabetes mellitus. Ann Intern Med 75:549-554, 1971 5. ROSENTHAL S, KAUFMAN S: Vincristine neurotoxicity. Ann In-
tern Med 80:733-737, 1974 Raw Diet and Insulin Requirements D I E T control has been and is a mainstay of the therapeutic regime used to treat diabetes mellitus. It is generally recognized that overweight diabetic patients on oral antidiabetic agents can sometimes have their oral agents discontinued if they lose weight and adhere closely to an anti-diabetic diet. It is not usually accepted that a patient on insulin may have his insulin requirement reduced without significant reduction of his weight. In the cases reported here one patient had his insulin requirement reduced from 60 units per day to 15 units per day by
61
Table 1. Insulin Requirem*ants of Two Patients After Modi flcations in Their Diets* Diet Raw
Cooked
_ Patient 1 30 July 1970 4 August 1970 31 December 1971 17 March 1971 21 May 1971 9 June 1971 18 June 1971 27 July 1972 20 March 1973 21 May 1974 Patient 2 13 February 1973 2 Marc^i 1973 11 April 1973 8 May 1973 24 May 1973 11 July 1973 23 November 1973 7 February 1974 23 April 1974 23 May 1974
Insulin
Blood Sugai
Weight
Fasting
•Other units
mg/100 ml
kg
5 10 10 80 90 90 95 30 50 50
95 90 90 20 10 10 5 70 50 50
63.5 64.4 ? 63.0 61.6 ? 62.1 62.1 62.5 61.4
94 118
118 173 108
5 60 60 80 80 20 50 50 60
95 40 40 20 20 80 50 50 40
86.1 87.0 86.6 83.4 ? 84.1 86.8 ? 84.3
193 157 208 168 125 220 167 218 192
60
40
83.2
185
90 f 901 103 50 248§
40 NPH/20 lente 40 NPH 40 NPH 35 NPH 25 NPH 20 NPH 0 15 NPH 18 NPH 30 NPH 70 NPH 60 NPH 30 NPH 0 0 15 NPH Diabinese, 250/day Diabinese, 250 twice a day Diabinese, 250 three times a day Diabinese, 250 three times a day and phenformin hydrochloride, 50/day
* N P H = neutral protamiiie Hagedorn insulin. t Measured by Dextrostix imethod. X Random measurement. § Measured one hour post cibum.
dietary management alone, and another had his insulin requirement reduced from 70 units per day to oral agents alone. Both of these changes were accomplished by increasing the percentage of raw food in their diets. My rationale was that since early man lived entirely on raw food, perhaps such a diet would be less stressful to the human system in general and less diabetogenic than a cooked food diet. I recommended raw foods such as vegetables, seeds, nuts, berries, melons, fruits, eggs (yolks only), honey, oils, and goat's milk. Fruits, melons, and honey were not to be eaten in large quantities, and nuts and salads were to be made the main part of the raw-food diet. Raw meats and fish were not suggested because of the parasite infestation problem. I recommended raw goat's milk because there is much less risk of brucellosis or tuberculosis from it than, from raw cow's milk*. Raw egg white was not advised because it may contain a biotinblocking factor.
control is adequate so long as he maintains an 80% raw diet (Table 1). The mechanism whereby this salutory effect on diabetes was obtained is unknown. It may have to do with the interaction of the non-inactivated enzymes that are present in raw items or with the fast transit time that is inherent in a raw diet (1, 2 ) . The observed effect seems to merit a formal study with more patients, with better documentation of diet and patients' adherence to diet.
Patient 1 is an elderly Euro-American man who was comparatively comfortable with his insulin dosage but did not like taking insulin twice a day. His diet was first brought more toward the recommended diabetic diet and then modified toward an uncooked diet. As of 21 May 1974 he was on 30 units of insulin and on an approximately 50% raw diet (Table 1). Patient 2 is a young Mexican-American man who complained so bitterly about the pain associated with taking insulin that he insisted that he would rather die than take "shots." At present his diabetes is controlled on oral agents alone. His
1. POTTENGER FM JR: The effect of heat processed foods and metabolized vitamin D milk on the dentofacial structures of experimental animals. Am J Orthodont Oral Surg 32:467-485, 1946
* UNITED STATES DEPARTMENT OF AGRICULTURE: Personal communica-
tion. 52
JOHN M. DOUGLASS, M.D.
Department of Internal Medicine Southern California Permanente Medical Group and Kaiser Foundation Hospital 1526 North Edgemont St. Los Angeles, California 90027 REFERENCES
2. BURKITT DP, WALKER ARP, PAINTER NS: Dietary fiber and dis-
ease. JAMA 229:1068-1074, 1974
Cyclic Laryngeal Edema with Aphonia IN JULY 1974 we saw Mrs. B. for the first time. This 24year-old woman complained of aphonia of 5 to 7 days' duration, which was followed by several days of hoarseness. Such episodes had occurred with each of her menstrual periods through the previous 8 months.
January 1975 • Annals of Internal Medicine • Volume 82 • Number 1
Downloaded from https://annals.org by Tulane University user on 01/12/2019
Her menarche had been at age 14, and her menses were regular ever since. Five years ago she became pregnant, but miscarried in the third month of pregnancy. She never became pregnant again. A year ago a diagnosis of left-sided ovarian cyst was made and the cyst was removed surgically. The pelvic organs were examined carefully during surgery and were normal. A year ago, the patient took a birth-control medication for 3 months. She stopped its use because of muscle aches. Eight months before admission, the patient had aphonia for the first time. This occurred on the second menstrual day, was not accompanied by cough or fever, and lasted for 7 days. Since then the aphonia has occurred with each of her menstrual periods. Occasionally slight hoarseness and some "wheezing" developed in the middle of the menstrual cycle accompanied by some abdominal "bloating," stiffness of the neck, and temporary premenstrual weight gain up to 2.2 kg [5 lbs]. She had occasional headaches. The past medical history was unremarkable. Two members of her family have been treated for diabetes mellitus. The patient weighed 49.6 kg [109^ lbs] and was 1.67 metres [5 feet 6 inches] tall. Her blood pressure was 110/70 mm Hg, pulse 72/min and regular. She was afebrile. Her breasts were slightly tender to palpation, and she had no galactorrhea. The external genitalia, pelvic organs, and secondary sex characteristics were normal. The basal temperature chart indicated normal ovulatory cycles. Neurologic findings were normal. The laryngoscopy examination showed diffuse swelling of the vocal cords during the episode of aphonia and normal findings during remission. Normal laboratory data included urinanalysis findings; complete blood count; multichannel (12) biochemical data; protein electrophoresis; measurement of serum thyroxine, T3 resin uptake, and thyroid stimulating hormone; and glucose tolerance test. Serum creatinine and creatinine clearance were normal. Total 24-hour urinary estrogens were 18.0 fig in midcycle (minimum normal range 7 to 23 /*g, ovulation peak 44 to 93). Premenstrual serum estradiol was 24.6 ng/100 ml (normal, luteal phase, 10 to 30 ng/100 ml), serum estrone was 15.7 ng/100 ml (normal 5 to 20), and serum progesterone 3.225 /tg/100 ml (normal, 0 to 1.6). Midcycle serum follicle stimu-
lating hormone and luteinizing hormone were normal, 20 and 34 mlU/ml respectively. Serum electrolytes were normal: sodium, 143 meq/litre, potassium 4.6 meq/litre, chlorine 108 meq/litre. Urinary electrolytes were also normal: sodium, 194 meq/24 h, potassium 39 meq/24 h and chlorine, 199 meq/24 h. Plasma renin was 1.3 ng/ml-h (normal, 0.73 to 4.90 ng/ml-h), and aldosterone secretion rate 20 fig/24 h urine (normal, 2 to 26). The aphonia was interpreted as due to vocal cord swelling after premenstrual fluid retention. The patient was advised to restrict her salt intake and was given spironolactone (Aldactone®) and hydrochlorothiazide (Hydrodiuril®). With the beginning of this therapy she had a moderate weight loss 0.9 to 1.3 kg [2 to 3 lbs] and the episodes of aphonia disappeared as did all other associated symptoms. I believe that increased local capillary permeability and resulting edema of the vocal cords were the reason for this syndrome. It may belong in the obviously heterogenous diagnostic group of idiopathic cyclic edema, in which patients with protein rich edema may have abnormal carbohydrate metabolism, capillary membrane thickening, increased capillary permeability, and secondary hyperaldosteronism ( 1 , 2 ) . The significance of the high serum progesterone in our case remains to be elucidated. LUBOMIR J. VALENTA, M.D.
Department of Medicine, College of Human Medicine B220 Life Sciences I Michigan State University East Lansing, Michigan 48824 REFERENCES
1. COLEMAN M, HORWTTH M, BROWN JL: Idiopathic edema. Studies
demonstrating protein leaking angiopathy. Am J Med 49:106112, 1970 2. ROVNER DR: The enigma of idiopathic cyclic edema. Hosp Tract 7:103-110, 1972
Letters
Downloaded from https://annals.org by Tulane University user on 01/12/2019
63
