Intracranial Calcification in Nephrogenic Diabetes Insipidus
| Title: | Intracranial Calcification in Nephrogenic Diabetes Insipidus |
|---|---|
| Authors: | Bagga, MD, Arvind; Kumar, Amit; Bajaj, MD, Geeta; Gupta, MD, Arun; Srivastava, MD, R.N. |
| Publisher: | Clinical Pediatrics |
| Date Published: | January 01, 1996 |
| Reference Number: | 39 |
Introduction
Congenital nephrogenic diabetes insipidus (NDI), characterized by insensitivity of the distal nephron to antidiuretic hormone, is usually inherited as an X-linked disorder. A rare form of this condition is associated with intracranial calcification.1-4 We report a 5-month-old girl and a 2-year-old boy presenting with fever of unknown origin and polyuria, respectively, who were diagnosed with this condition. Despite adequate treatment, the calcification process progressed to involve the subcortical regions of the frontal lobe in the first patient; this complication has not been previously reported in NDI.
Patient Reports
Patient I
A 5-month-old girl was admitted with a 3-month history of unexplained fever that ranged from 37ÉC-39.6ÉC. She was born at term after an uncomplicated pregnancy and normal delivery. Her weight at birth was 3,200 g. There was no family history of renal disease or parental consanguinity. She had continued to feed normally but failed to thrive. Social smile appeared at 4 months, but she was unable to hold her head up or turn from prone to supine position. On examination she was alert and did not appear ill. Weight was 4,200 g, length 56 cm, and head circumference 37 cm (all at the 50th percentile for age 2 months). A detailed physical examination disclosed no significant abnormality.
An infectious cause to explain her high fever was excluded by appropriate laboratory tests. Cultures of blood, urine, and cerebrospinal fluid for bacteria and fungi were sterile. Her hemoglobin was 11.5 g/dL, with blood smear showing features of iron deficiency anemia. Blood levels of urea, creatinine, calcium, inorganic phosphate, alkaline phosphatase, and tests of liver function were all within the normal range. A tuberculin test was negative and a chest radiograph showed no abnormality.
 Figure 1. Noncontrast cranial CT in Patient 1 shows symmetrically distributed calcification in both basal ganglia. |
Serum levels of sodium ranged from 156-181 mmol/L and potassium from 3.2-3.5 mmol/L. Blood pH was 7.3 and bicarbonate was 22 mmol/L. Plasma osmolality ranged between 298 and 320 mOsm/kg and urine osmolality between 110 and 244 mOsm/kg. Following a subcutaneous injection of 5U of vasopressin, plasma and urine osmolalities were 314 mOsm/kg and 165 mOsm/kg, respectively. There was no abnormal urinary excretion of glucose, protein, calcium, and phosphorus. Creatinine clearance was 94 mL/min/1.73 m2, and tubular reabsorption of phosphate was 94%.
A diagnosis of NDI was made. Ultrasonography of the abdomen showed normal kidneys with no calcification. A 99Tc dimercaptosuccinic acid scan showed normal-sized kidneys with no scarring. Cranial computed tomography (CT) showed symmetrical calcification of the basal ganglia (Figure 1).
The patient was treated with hydrochlorothiazide 2 mg/kg/day and indomethacin I mg/kg/day. The parents were instructed to add no salt to her diet; to give her at least a liter of fluid daily, chiefly water and milk; and to supplement her diet with cereals, vegetables, and fruits. Within 1 week of treatment, she became afebrile, and her urine output was 1.8-2.2 mL/kg/hr. There were no further episodes of hypernatremic dehydration.
At the age of 22 months, her weight was 8.6 kg (third percentile), height 79 cm (10th-25th percentile), and the head circumference 43 cm (fifth percentile). Developmental assessment showed a motor age of 13 months and a mental age of 14 months, indicating moderate retardation. A repeat CT scan 17 months after the initial study showed persistence of the basal ganglia calcification and appearance of new lesions in the subcortical white matter of the frontal lobes (Figure 2).
Patient 2
A 2-year-old boy was referred for evaluation of polyuria of 1-year duration. He was born at term after an uncomplicated pregnancy; there was no parental consanguinity. An elder male sibling had died at the age of 3 years with similar complaints; detailed evaluation was not carried out. This child's weight was 8.7 kg (50th percentile for 1 year) and height 78 cm (50th percentile for 14 months). Developmental assessment showed a motor and mental age of 14 months. Systemic examination revealed no abnormality.
Blood levels of urea, creatinine, calcium, phosphate, and uric acid were normal. Serum sodium level ranged from 138-149 mmol/L and potassium 4-4.6 mmol/L. Blood pH was 7.35 and bicarbonate 21 mmol/L. Plasma and urine osmolalities ranged from 296-306 mOsm/kg and 129-144 mOsm/kg, respectively. Following a subcutaneous injection of 5U of vasopressin, the plasma and urine osmolalities were 302 mOsm/kg and 150 mOsm/kg, respectively. There was no abnormal urinary excretion of sodium, glucose, protein, calcium, phosphorus, or amino acids. Ultrasound examination of the abdomen showed normal kidneys.
A diagnosis of NDI was made and the patient treated with hydrochlorothiazide and indomethacin. Within the next 2 weeks, his urine output reduced. At the age of 4 years 8 months, his weight was 16 kg and height 101 cm; both were at the 50th percentile. His development was normal for his age. A CT scan showed bilateral frontal lobe and basal ganglia calcification (Figure 3).
Discussion
Both patients had characteristic features of NDI. Various conditions causing NDI, such as nephrocalcinosis, hypercalcemia, hypokalemia, obstructive nephropathy, and polycystic disease of the kidney, were excluded, and the disorder was diagnosed as renal tubular resistance to antidiuretic hormone.
Intracranial calcification is a rare, unexplained association of NDI. Only seven such patients have been previously reported.1-4 The calcification was detected early in our first patient; in only one of the previously reported patients it was observed at the age of 5 months.1 All of these patients had delayed psychomotor development, and five of the seven had seizures. Intracranial calcification in these patients was symmetrically distributed in the basal ganglia, and in the frontal, parietal, temporal, and occipital lobes.1-4
Calcification of the basal ganglia may be caused by hypoparathyroidism, pseudohypoparathyroidism, intrauterine infections, and certain rare degenerative conditions.5 These disorders were excluded in our two patients. In the previously reported patients, the cause of the intracranial calcification could not be found.
Infants with hypernatremic dehydration are known to develop multiple petechial hemorrhages in the cortex and subcortical white matter.6 Multiple foci of necrosis with calcification have also been reported in such cases.7,8 In an autopsied case of NDI with intracranial calcification, calcium was observed in or around the capillaries in the cortex and the basal ganglia, and the neurons were not affected.3 It has, therefore, been suggested that recurrent hypernatremic dehydration may damage endothelial and other cells and initiate dystrophic calcification within or around vessel walls.3,9 However, such calcification is only rarely associated with NDI, and it is likely that other undefined mechanisms are operative. It is, however, also possible that the rarity of reported brain calcification in NDI is due to the fact that it is not carefully looked for.
Both of our patients were treated with hydrochlorothiazide and indomethacin. Despite improvement of symptoms, the calcification process progressed in the first patient. This suggests that intracranial calcification in these patients can develop postnatally, possibly secondary to episodes of hypernatremic dehydration causing brain damage and dystrophic calcifications. Early diagnosis and prevention of episodes of hypernatremic dehydration are important to prevent brain damage and associated complications in these patients.
REFERENCES
- Miura J, Tachi N, Okabe M, Sogawa H. Two cases of nephrogenic diabetes insipidus associated with intracranial calcification. Acta Paediatr Jpn. 1983;87:934-938.
- Kanzaki S, Omura T, Miyake M, et al. Intracranial calcification in nephrogenic diabetes insipidus. JAMA. 1985; 254:3349-3350.
- Schofer 0, Beetz R, Kruse K, et al. Nephrogenic diabetes insipidus and intracerebral calcification. Arch Dis Child. 1990;65:885-887.
- Nozue T, Uemasu F, Endoh H, et al. Intracranial calcifications associated with nephrogenic diabetes insipidus. Pediatr Nephrol 1993;7:74-76.
- Patel PJ. Some rare causes of intracranial calcification in children: computed tomographic findings. Eur J Pediatr. I987;146:177-180.
- Conley SB. Hypernatremia. Pediatr Clin North Am. 1990;37:365-372.
- Macaulay D, Watson M. Hypernatremia in infants as a cause of brain damage. Arch Dis Child. 1967;42:485-491.
- Hammond DN, Moll GW, Robertson GL, Chelmicka-Schorr E. Hypodipsic hypernatremia with normal osmoregulation of vasopressin. N Engl J Med. 1986;315:433-436.
- Russell RGG, Caswell AM, Hearn PR, Sharrard RM. Calcium in mineralised tissues and pathologic calcifications. Br Med Bull 1986;42:435-446.
Departments of Pediatrics and Radiodiagnosis, All India Institute of Medical Sciences, New Delhi, India. Address correspondence to: R.N. Srivastava, F.R.C.P., Department of Pediatrics, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110 029, India.
This translation by the NDI Foundation is to assist the lay reader. To provide a clear, accessible interpretation of the original article, we eliminated or simplified some technical detail and complicated scientific language. We concentrated our translation on those aspects of the article dealing directly with NDI. The NDI Foundation thanks the researchers for their work toward understanding and more effectively treating this disorder.
© Copyright NDI Foundation 2007 (JC)
The 5-month-old girl was diagnosed with NDI after extensive laboratory tests ruled out other causes for her symptoms (a high fever and developmentally delayed motor functions). A scan of her cranium using a method called computed tomography (CT) showed symmetrical calcification in a select grouping of nerve cell bodies called the basal ganglia.
The infant girl was treated with hydrochlorothiazide and indomethacin. She was placed on a diet excluding salt and including at least a liter of fluid a day, chiefly water and milk, and supplemented with cereals, vegetables and fruits. Within a week, the infant's symptoms began to improve. However, when she was 22-months-old a developmental assessment indicated she was moderately retarded. And a scanning of her cranium revealed a persistence of the calcification of her basal ganglia along with the appearance of new lesions in the frontal lobe area of her brain.
The 2-year-old boy was diagnosed with NDI and treated with hydrochlorothiazide and indomethacin. Within 2 weeks his urine output reduced. Whereas at 2 years of age, the boy's developmental assessment showed a motor and mental age equivalent of 14 months, at age 4 years and 8 months, a developmental assessment indicated normal development for his age. Nonetheless, a scan of his cranium at this time showed calcification in his bilateral frontal lobe and basal ganglia.
Discussion: Intracranial calcification can occur through thyroid malfunctions, intrauterine infections and certain rare degenerative conditions. Whether it can occur through NDI is unclear. Presently, NDI is viewed as a rare, as yet unexplained association with intracranial calcification. Previous to the authors' work, only seven NDI patients were reported to also have calcification of select brain tissues; however, this low number may be due to the fact that NDI patients are not routinely checked for brain calcification.
It is known that infants suffering from dehydration due to excessive amounts of sodium in the blood can develop calcification in specific areas of the brain. The authors noted that although their two patients experienced improvement of their NDI symptoms after medical treatment, the calcification process progressed in the girl. (It was not stated whether the boy was scanned with a CT when he was first seen by the authors at age 2.) This suggested to the authors that intracranial calcification in patients can develop postnatally, possibly after episodes of excessive amounts of sodium in the blood cause dehydration (hypernatremic dehydration) which in turn causes brain damage and calcification within the brain. They state that early diagnosis and prevention of episodes of hypernatremic dehydration are important to help prevent brain damage and associated complications from occurring.