Letters to the editors
Eur J Pediatr (1991) 150 : 599-600 0340619991001163
lntracranial calcifications and nephrogenic diabetes insipidius M. Di Rocco, P. Picco, P. Gandullia, and C. Borrone Second Paediatric Division, G Gaslini Institute, 1-16148 Genoa, Italy Sir: We have read with interest the paper of Schofer et al. on mental retardation, nephrogenic diabetes insipidus and intracerebral calcifications . We also have a 15-year-old boy with similar clinical and neuroradiotogical features (Fig. 1). He is the first child of unrelated parents; his mother shows a partial defect; his only sister is healthy; there are no other sibs. Subsequent family history is negative. Other patients with this condition have been reported [1, 3, 6]. Based on the above, we would like to make some comments: 1. It is impossible to exclude that either mental retardation or cerebral calcifications result from brain damage consistent with severe clinical and subclinical dehydratation in infancy. It is known that repeated severe bouts of hypernatraemia lead to mental impairement in survivors; further, loci of necrosis and calcifications are evident in brain tissue of patients who died of hypertonic encephalopathy . F o r these reasons is not infrequent that mental retardation accompanies this disorder. Severe dwarfism may also be a consequence of the chronic unbalanced disease .
2. In the family reported by Schofer et al.  there are no elements to exclude the diagnosis of "classic" nephrogenic diabetes insipidus. In our patient the demonstration of a partial defect in the m o t h e r is in accordance with the diagnosis of X-linked nephrogenic diabetes insipidus. We do not agree with Schofer et al. on the possibility of a new familial disease in the patients reported in his paper, but rather we think the localization of nephrogenic diabetes insipidus on the X chromosome may be another clue to explain the association of nephrogenic diabetes insipidus and mental retardation in some patients. Recently Kambouzis reported that the gene of nephrogenic diabetes insipidus is localized to Xq28 ; thus the study of possible microdeletions near X q28 in these families might help to clarify some of these problems.
References 1. Kanzaki S, Omura T, Miyaka M, Enomoto S, Mijata I, Ishimitsu H (1985) Intracranial calcification in nephrogenic diabetes insipidus. JAMA 254 : 3349-3350 2. Kambouzis M, Dlouhy SR, Trofatter JA, Conneally PM, Hooles ME (1988) Localization of the gene for X-linked nephrogenic diabetes insipidus to Xq28. Am J Med Genet 29 : 239-246 3. Miura J, Tachi N, Okabe M (1983) Two cases of nephrogenic diabetes insipidus associated with intracranic calcification. Acta Pediatr J 87: 934-938 4. Reeves WB, Andreoli TE (1989) Nephrogenic diabetes insipidus. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic basis of inherited disease. McGraw Hill, New York, p 1985-2011 5. Schofer O, Beetz R, Bohl J, Bornemann A, Oepen J, Spranger J (1990) Mental retardation syndrome with renal concentration deficiency and intercerebral calcification. Eur J Pediatr 149: 470-474 6. Schofer O, Beetz R, Kruse K, Rascher C, Schutz C, Bohl J (1990) Nephrogenic diabetes mellitus and intracranial calcification. Arch Dis Child 65 : 885-887
Reply O. Schofer, R. Beetz, and J. Spranger Department of Paediatrics, University Hospital, Langenbeckstrasse 1, D-6500 Mainz 1, Federal Republic of Germany Received January 21, 1991 / Accepted January 28, 1991
l~'g.I. Computed tomographic scan: symmetric calcification in the frontal and parietal lobes
Sir: We agree that classic nephrogenic diabetes insipidus cannot be ruled out in our patients . We also agree that intracerebral calcifications might be a consequence of severe dehydration during the course of nephrogenic diabetes insipidus, especially in infancy .
600 One of the two affected brothers, however, n e v e r had any proven episodes of dehydration necessitating hospital care and parental fluids. We took this as one argument against the above hypothesis that episodes of severe dehydration solely caused the massive intracerebral calcifications in our familial cases. Our second and stronger argument was the concurrence of several dysmorphic signs present in both affected boys, which are unusual for nephrogenic diabetes insipidus and which partly resembled those described for Cockayne syndrome. With the availability of a whole panel of genetic markers for the Xq28 region [1, 2] it is now possible to further investigate our patients at the molecular level. Such studies on our living patient are at presents under way.
References 1. Kambouris M, Dlouhy SR, Trofatter JA, Conneally PM, Hodes ME (1988) Localization of the gene for X-linked nephrogenic diabetes insipidus to Xq28. Am J Med Genet 29 : 239-246 2. Kenwrick S, Gitschier J (1989) A contiguous, 3-Mb physical map of Xq28 extending from the colorblindness locus to DXS15. Am J Hum Genet 45 : 873-882 3. Schofer O, Beetz R, Bohl J, Bornemann A, Oepen J, Spranger J (1990) Mental retardation syndrome with renal concentration deficiency and intracerebral calcification. Eur J Pediatr 149: 470-474 4. Schofer O, Beetz R, Kruse K, Rascher C, Schlitz C, Bohl J (1990) Nephrogenic diabetes insipidus and intracerebral calcification. Arch Dis Child 65 : 885-887
Magnetic resonance imaging in idiopathic hypopituitarism P. M. Doraiswamy 1, D . A . Axelson, P. R. Escalona, S. A. Shah, M. M. Husain, G. S. Figiei, and K. R. R. Krishnan 1Duke University Medical Center, Durham NC 27710, United States Washingon University School of Medicine, St. Louis, MO 63110, United States University of North Carolina School of Medicine, Chapel Hill, NC 27514, United States Received November 27, 1990 / Accepted February 7, 1991 Sir: We commend the investigation by Pellini et al.  into the role of magnetic resonance imaging (MRI) in the assessment of idiopathic hypopituitarism and growth hormone deficiency. Their findings are consistent with numerous studies supporting a relationship between pituitary size and adenohypophyseal activity. In addition their study demonstrates the clinical utility of quantitative MRI assessment of the pituitary in pediatric endocrinology. We would like to obtain clarification regarding the methodology used to obtain pituitary volumes and relate some of our experiences in this matter. The methods section of the article neglects to mention the technique by which hypophyseal and sellar volumes
were estimated. In addition, it is not reported whether two the identity of patient and control groups was known to the assessars and no mention was mede of their reliability. This information would considerably strengthen their findings. We would like to bring to attention two methods we have previously reported to estimate pituitary volumes [3, 4]. One is based on a formula for the volume of an ellipsoid [0.5 x height x length x width] and probably underestimates true pituitary volume. The other formula [cross-sectional midsagittal area • width] probably overestimates pituitary volume. Although both estimates appear to be valid for group comparisons [3, 4], it must be borne in mind that these are only estimates of pituitary volume and should not be directly compared with autopsy-obtained volumes. The second concern we have is that the patient and control groups may not have been adequately gender-matched. How were 15 controls age- and gender-matched with 30 patients? The age and gender of the patients in Table 1 as well as the malefemale composition of the control group is not reported by the authors. This is important since Elster et al.  and Suzuki et al.  have shown that gender differences in pituitary size are quite prominent in the 10- to 20-year age range. Lastly it must be stressed that correlations between clinical data and the neurohypophyseal "bright area" are to be interpreted with caution, since this signal can normally be absent or ectopic. The study by Pellini et al,  is an important contribution to the growing literature supporting a relationship between pituitary morphology and the neuro-endocrine milieu. Primary hypothyroidim (elevated thyrotropin releasing hormone?) , some forms of precocious puberty , normal adolescence  and affective illness (elevated corticotropin releasing hormone?)  have been associated with pituitary enlargement. Growth hormone deficiency , primary hypopituitarism , amenorrhea and anorexia nervosa (gonadotropin releasing hormone deficiency?)  and aging  have been associated with smaller pituitary size. With further technical refinement and the availability of normative data, quantitative MRI assessment of the pituitary will become an important tool in the pediatric endocrinologist's armentarium.
References 1. Doraiswamy PM, Krishnan KR, Figiel GS (1990) A brain MRI study of pituitary morphology in anorexia nervosa and bulimia. Biol Psychiatry 28:110-116 2. Elster A, Chen M, Williams D, Key L (1990) Pituitary gIand: MR imaging of physiologic hypertrophy in adolescence. Radiology 174: 681-685 3. Krishnan KRR, Doraiswamy PM, Lurie (1991) Pituitary size in major depression. J Clin Endocrinol Metab 72:256-259 4. Lurie SN, Doraiswamy PM, Husain MM (1990) In vivo assessment of pituitary volume with MRI: effect of age. J Clin Endocrinol Metab 71, 2:505-508 5. Pellini C, Natale B di, De Angelis R (1990) Growth hormone deficiency in children: role of magnetic resonance imaging in assessing aetiopathogenesis and prognosis in idiopathic hypopituitarism. Eur J Pediatr 149: 536-541 6. Suzuki M, Takashima T, Kadoya M (1990) Height of normal pituitary gland on MR imaging: age and sex differentiation. J Comput Assist Tomogr 14 : 36-39 7. Walmsley D, Messios N, O'Malley B, Rosentha] F (1987) Pituitary size in hypothyroidism as determined by computed tomography. Br J Radiol 60 : 935-936