Co-Existent Diabetes Mellitus and Diabetes Insipidus, a Familial Disease VED V. GOSSAIN,1 MASAHIRO SUGAWARA, AND GARRETT A. HAGEN The Veterans Administration Hospital and the Department University School of Medicine, St. Louis, Missouri ABSTRACT. Three male siblings with diabetes mellitus are described, two of whom also had coexistent diabetes insipidus. The co-existence of diabetes mellitus and insipidus appears to represent a single genetic abnormality and may or may not be
T
HE co-existence of diabetes mellitus and diabetes insipidus in one individual is a rare occurrence. Only about 50 cases have been described (1-11). The simultaneous occurrence of the two disorders has been considered fortuitous except in a case described by Natelson (2) in which a hyperfunctioning eosinophilic adenoma of the pituitary caused the onset of both diabetes mellitus and diabetes insipidus. More recently, however, this association has been considered to represent a single genetic disorder which may be expressed as diabetes mellitus, diabetes insipitus, optic atrophy, or any combination of these (9,10). This report describes a family in which three brothers had diabetes mellitus, two of whom also had co-existent diabetes insipidus. Case Reports
Patient A. A 45-year-old white man was first admitted to the Medical Service of the St. Louis Veterans Administration Hospital (Jefferson Barracks Division) in June, 1974 for management of uncontrolled diabetes mellitus. Although the patient had been aware of this diagnosis for about 15 years, no dietary or other Received May 13, 1975. Supported in part by a gift from Pfizer Laboratories, Chicago, IL. Medical Research Information System Number 3168. 1 Present address: Department of Medicine, College of Human Medicine, Michigan State University, East Lansing, Mi. 48824. Reprints: G. A. Hagen, M.D. (111C-JB), Unit III Medical Service, V.A. Hospital, St. Louis, Mo. 63125.
of Internal Medicine, St. Louis
accompanied by primary optic atrophy. Chlorpropamide was effective in controlling the symptoms of diabetes mellitus and diabetes insipidus. (J Clin Endocrinol Metab 41: 1020, 1975)
therapy had been instituted. A fasting blood sugar one month before admission was 340 mg/100 ml. During hospitalization, fasting blood sugars ranged from 157 to 350 mg/100 ml, and several urine samples contained glucose and acetone. Hyperglycemia and glycosuria were readily controlled on a 1200-calorie diabetic diet with 20 units of NPH and 5 units of regular insulin administered each moning. The patient was discharged on this regimen, and did well until August 1974 when he was re-admitted to the hospital with hypoglycemia. The insulin dosage was gradually reduced and finally discontinued, the diabetes remaining well controlled, with no glycosuria, and blood glucose levels ranging between 74-160 mg/100 ml. However, the patient was noted to have significant polyuria and polydipsia. Water intake and urine output averaged about 12 liters per day. Further questioning revealed polyuria and polydipsia to have been present since 1969. Fluid intake consisted of large quantities of water, beer, and iced tea. The patient also had a long psychiatric history of depression. He received electroshock therapy in 1970 and since then had continued to be under psychiatric care, receiving chlorpromazine, thioridazine, diazepam, and doxepin at various times. He was also receiving colchicine and allopurinol for gout. A mild hypertension of about 10 years duration had not been treated since July 1973. A maternal grandmother and the patient's two brothers had diabetes mellitus. The patient's three childlren did not have polyuria or polydipsia. The systemic review was negative except for symptoms of intermittent vertigo. Physical examination. The patient was a moderately obese white male whose height was 173 cm and weight 110 kg. The pulse was 76/min
1020
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CO-EXISTENT DIABETES MELLITUS AND INSIPIDUS and the blood pressure 160/90 mm mercury. The hearing was decreased on the left side. Funduscopic examination revealed minimal arteriolar tortuosity. There were no exudates or hemorrhages and the optic discs appeared normal. The thyroid gland was palpable but not enlarged. The liver edge was palpable 3 cm below the right costal margin and had a span of 12 cm to percussion. The rest of the physical examination was unremarkable. Laboratory data. The hemoglobin was 13.5 gm/ 100 ml and hematocrit 48%. The white blood cell count was 3700/mm3 with a normal differential count. Urinalysis revealed a specific gravity of 1.001, pH 6.0, and no glucose or albumin. Microscopic examination of the urinary sediment was negative. A fasting blood sugar level was 126 mg/100 ml. The serum Na concentration was 138, K 4.2, Cl 100, and CO2 26 mEq/L. The blood urea nitrogen was 9 mg/100 ml and creatinine 1.3 mg/100 ml. The serum uric acid level was 9.1 mg/100 ml. Roentgenographic studies of the chest and skull were normal. EKG, brain scan following administration of 99 Tc intravenously, and EEG were all within normal limits. Several randomly obtained urine osmolalties on an unlimited water intake varied between 72-114 mOsm/kg, and serum osmolalities between 282-325 mOsm/kg. Results of other endocrinological tests were also within normal limits and are summarized in Table 1. A dehydration test was performed according to the method of Miller and Moses (12), the results of which are shown in Fig. 1. Maximum urinary osmolality (475 mOsm) was achieved after 13.5 hours of dehydration; it then declined to 366 and 316 mOsm/kg at 14.5 and 15.5 hours, respectively. Administration of 5 U aqueous vasopressin intramuscularly resulted in an increase of urine osmolality to 666 mOsm/kg two hours after the injection. During dehydration, the patient lost 3.5 kg (3% of body weight). Plasma osmolality increased from 282 mOsm to 315 mOsm/kg and decreased to 302 mOsm at the end of the test. The clinical course of this patient is summarized in Fig. 2. Administration of long-acting vasopressin resulted in reduction of the water intake and output to about 4 liters/ day, and the patient was able to concentrate his urine to a maximum osmolality of 688 mOsm. When vasopressin was discontinued and chlorpropamide 500 mg daily was administered, the patient's water intake remained relatively un-
1021
TABLE 1. Endocrine function tests in two brothers with diabetes mellitus and insipidus Test
Patient A
24 Hour 17 Hydroxysteroids
10.2 21.3'
Patient B
Normal range
Urine (4-14 mg/24h) (Two-fold or greater rise from basal levels)
Plasma 7.7
(5.5-11.5/ig/100 ml)
Tri-iodothyronine
97.5
(70-200 ng/100 ml)
Cortisol—8 AM
27
(5-25 *ig/100 ml)
Thyroxine
Thyrotropin
2.9 7.81
2.7 22f
(7.5-29 /xU/ml)
Growth hormone
4.8
1.7 28
3 0 0 -
-500
O
T
HE co-existence of diabetes mellitus and diabetes insipidus in one individual is a rare occurrence. Only about 50 cases have been described (1-11). The simultaneous occurrence of the two disorders has been considered fortuitous except in a case described by Natelson (2) in which a hyperfunctioning eosinophilic adenoma of the pituitary caused the onset of both diabetes mellitus and diabetes insipidus. More recently, however, this association has been considered to represent a single genetic disorder which may be expressed as diabetes mellitus, diabetes insipitus, optic atrophy, or any combination of these (9,10). This report describes a family in which three brothers had diabetes mellitus, two of whom also had co-existent diabetes insipidus. Case Reports
Patient A. A 45-year-old white man was first admitted to the Medical Service of the St. Louis Veterans Administration Hospital (Jefferson Barracks Division) in June, 1974 for management of uncontrolled diabetes mellitus. Although the patient had been aware of this diagnosis for about 15 years, no dietary or other Received May 13, 1975. Supported in part by a gift from Pfizer Laboratories, Chicago, IL. Medical Research Information System Number 3168. 1 Present address: Department of Medicine, College of Human Medicine, Michigan State University, East Lansing, Mi. 48824. Reprints: G. A. Hagen, M.D. (111C-JB), Unit III Medical Service, V.A. Hospital, St. Louis, Mo. 63125.
of Internal Medicine, St. Louis
accompanied by primary optic atrophy. Chlorpropamide was effective in controlling the symptoms of diabetes mellitus and diabetes insipidus. (J Clin Endocrinol Metab 41: 1020, 1975)
therapy had been instituted. A fasting blood sugar one month before admission was 340 mg/100 ml. During hospitalization, fasting blood sugars ranged from 157 to 350 mg/100 ml, and several urine samples contained glucose and acetone. Hyperglycemia and glycosuria were readily controlled on a 1200-calorie diabetic diet with 20 units of NPH and 5 units of regular insulin administered each moning. The patient was discharged on this regimen, and did well until August 1974 when he was re-admitted to the hospital with hypoglycemia. The insulin dosage was gradually reduced and finally discontinued, the diabetes remaining well controlled, with no glycosuria, and blood glucose levels ranging between 74-160 mg/100 ml. However, the patient was noted to have significant polyuria and polydipsia. Water intake and urine output averaged about 12 liters per day. Further questioning revealed polyuria and polydipsia to have been present since 1969. Fluid intake consisted of large quantities of water, beer, and iced tea. The patient also had a long psychiatric history of depression. He received electroshock therapy in 1970 and since then had continued to be under psychiatric care, receiving chlorpromazine, thioridazine, diazepam, and doxepin at various times. He was also receiving colchicine and allopurinol for gout. A mild hypertension of about 10 years duration had not been treated since July 1973. A maternal grandmother and the patient's two brothers had diabetes mellitus. The patient's three childlren did not have polyuria or polydipsia. The systemic review was negative except for symptoms of intermittent vertigo. Physical examination. The patient was a moderately obese white male whose height was 173 cm and weight 110 kg. The pulse was 76/min
1020
The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 04 August 2016. at 07:57 For personal use only. No other uses without permission. . All rights reserved.
CO-EXISTENT DIABETES MELLITUS AND INSIPIDUS and the blood pressure 160/90 mm mercury. The hearing was decreased on the left side. Funduscopic examination revealed minimal arteriolar tortuosity. There were no exudates or hemorrhages and the optic discs appeared normal. The thyroid gland was palpable but not enlarged. The liver edge was palpable 3 cm below the right costal margin and had a span of 12 cm to percussion. The rest of the physical examination was unremarkable. Laboratory data. The hemoglobin was 13.5 gm/ 100 ml and hematocrit 48%. The white blood cell count was 3700/mm3 with a normal differential count. Urinalysis revealed a specific gravity of 1.001, pH 6.0, and no glucose or albumin. Microscopic examination of the urinary sediment was negative. A fasting blood sugar level was 126 mg/100 ml. The serum Na concentration was 138, K 4.2, Cl 100, and CO2 26 mEq/L. The blood urea nitrogen was 9 mg/100 ml and creatinine 1.3 mg/100 ml. The serum uric acid level was 9.1 mg/100 ml. Roentgenographic studies of the chest and skull were normal. EKG, brain scan following administration of 99 Tc intravenously, and EEG were all within normal limits. Several randomly obtained urine osmolalties on an unlimited water intake varied between 72-114 mOsm/kg, and serum osmolalities between 282-325 mOsm/kg. Results of other endocrinological tests were also within normal limits and are summarized in Table 1. A dehydration test was performed according to the method of Miller and Moses (12), the results of which are shown in Fig. 1. Maximum urinary osmolality (475 mOsm) was achieved after 13.5 hours of dehydration; it then declined to 366 and 316 mOsm/kg at 14.5 and 15.5 hours, respectively. Administration of 5 U aqueous vasopressin intramuscularly resulted in an increase of urine osmolality to 666 mOsm/kg two hours after the injection. During dehydration, the patient lost 3.5 kg (3% of body weight). Plasma osmolality increased from 282 mOsm to 315 mOsm/kg and decreased to 302 mOsm at the end of the test. The clinical course of this patient is summarized in Fig. 2. Administration of long-acting vasopressin resulted in reduction of the water intake and output to about 4 liters/ day, and the patient was able to concentrate his urine to a maximum osmolality of 688 mOsm. When vasopressin was discontinued and chlorpropamide 500 mg daily was administered, the patient's water intake remained relatively un-
1021
TABLE 1. Endocrine function tests in two brothers with diabetes mellitus and insipidus Test
Patient A
24 Hour 17 Hydroxysteroids
10.2 21.3'
Patient B
Normal range
Urine (4-14 mg/24h) (Two-fold or greater rise from basal levels)
Plasma 7.7
(5.5-11.5/ig/100 ml)
Tri-iodothyronine
97.5
(70-200 ng/100 ml)
Cortisol—8 AM
27
(5-25 *ig/100 ml)
Thyroxine
Thyrotropin
2.9 7.81
2.7 22f
(7.5-29 /xU/ml)
Growth hormone
4.8
1.7 28
3 0 0 -
-500
O
