4 16
Brief clinical and laboratory observations
may signal the invasiveness of an amp-R strain that previously was carried only in the nasopharynx. Whether it would prove useful to monitor throat or nasopharyngeal cultures obtained from patients with H. influenzae type b meningius prior to initiating antibiotic therapy is unknown In the laboratory the presence of a heterogeneous population ofH. influenzae type b creates the potential for reports of false sensitivity to ampicillin. When the KirbyBauer disc method is utilized, agar plates must be inspected carefully for the presence of "breakthrough" colonies within the 20-mm zone of inhibition.1 It also seems possible that. on rare occasions, only amp-S colonies could be subcultured from the original culture to sensitivity plates or utilized for the beta-lactamase assay. Furthermore. if the clinical isolate contains a small percentage of amp-R colonies, the color change may not be easily observed in the one-minute beta-lactamase test. since this reqmres greater than 97 units of penicillinase. 7 REFERENCES
The Journal of Pediatrics September 1979
2.
3.
4.
5.
6.
7.
Haemophilus influenzae, Antimicrob Agents Chemother 11:1021, 1977. YogevR. Lander HB. and Davis AT: Effect of Tmp-Smx on nasopharyngeal carriage of ampicillin-sensitive and ampicillin-resistant Hemophilus influenzae type b, J PEDIATR 93:394. 1978. Thornsberry C. and Kirven LA: Antimicrobial susceptibility of Haemophilus influenzae, Antimicrob Agents Chemother 6:620. 1974 Thornsberry C. and Kirven LA: Ampicillin resistance in Haemophilus influenzae as determined by a rapid test for t%lactamase production. Antimicrob Agents Chemother 6:653. 1974. SmithAL. Scheifel DW. Syriopoulou V, and Daum R: In Vivo segregation of plasmid mediated ampicillin resistance in Haemophilus influenzae. Seventeenth Interscience Conference on Antimicrobial Agents and Chemotherapy, New York. October. 1977. Delage (3, DeClerck Y. Lescop J. Dery P, and Shareck F: Hemophilus influenzae, type b infections: Recurrent disease due to ampicillin-resistant strains, J PEDIATR90:319, 1977. Escamilla J: Susceptibility of Haemophilus influenzae to ampicillin as determined by use of a modified, one-minute beta-lactamase test. Antimicrob Agents Chemother 9:196, 1976.
1. Gray BM, Hubbell CA, and Dillon HD: Manner and meaning of susceptibility testing of ampicillin resistant
Serum concentrations of 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D in patients with cystic fibrosis Yosef Weisman, Edward Reiter, Robert C. Stern, and Allen Root,* Tampa and St. Petersburg, Fla.,
and Cleveland, Ohio
prevalent gastrointestinal m a n i f e s t a of cystic fibrosis. Although deficiencies of vitamins A, E, and K have been described in patients with this disease, 1-~ vitamin D deficiency and r rickets have rarely been reported. The major form of vitamin D, cholecalcifero ! (vitamin D3), is produced by ultraviolet irradiation of 7-dehydrocholesterol in the skin. Ergocalciferol (vitamin S T E A T O R R H E A is a
tion
From the Departments of Pediatrics, University of South Florida College of Medicine; and Case Western Reserve University School of Medicine," Ed Wright Pediatric Endocrinology Researc h Laboratory, All Children's Hospital," and Rainbow Babies and Children's Hospital. Supported by National Foundation-March of Dimes Grants C-199, 1-632, Grants AM08305 and HL 13885 from the United States Public Health Service, and by grants from the National Cystic Fibrosis Foundation: *Reprint address: All Children's Hospital, 801 Sixth St. South, St. Petersburg, FL 33701.
D2) is a product of p l a n t ergosterol. We studied the vitamin D status of patients with cystic fibrosis by measurement of the serum concentrations of the major circulating metabolit~es of Vitamin D: 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D. The liver is the site of synthesis of 25OHD, whereas 24,25(OH)2Dis synthesized primarily in the kidney. Abbreviations used 25OHD: 25-hydroxyvitamin D 24,25(OH)~D: 24,25-dihydroxyvitamin D 25OHDa: 25-hydroxycholecalciferol SUBJECTS
AND
METHODS
After seParation of vitamin D metabolites by gel chromatography, the serum concentrations of 25OHD (N = 23) and of 24,25(OH)~D (N = 10) were determined by competitive protein-binding radioassays employing rat serum-binding protein6 in children and adolescents with
0022:~3476/79/090416+03500.30/0 9 1979 The C. V. Mosby Co.
Volume 95 Number 3
Brief clinical and laboratory observations
4 17
Table. Concentrations of vitamin D metabolites in children with cystic fibrosis and control subjects
Control subjects (9) Mean _+ SD Range Cystic fibrosis patients (23) Mean + SD Range
250HD
250HD~
250HDJ250HD
27.7* _+9.9 11.3-44.6
25.0* _+4.9 19.8-34.6
0.860 _+0.119 0.769-1.112
2.6* _+1.3 1.0-4.9
25.5 _+8.4 14.6-55.4
21.6 _+7.5 8.8-36.3
0.837 _+0.169 0.392-1.097
2.2 _+0.6 1.6-3.6 (10)
I
24,25(OH)2D
*ng/ml. cystic fibrosis attending the Rainbow Babies and Children's Hospital, Cleveland, 7 and from nine normal children. All sera were collected in early summer, and shipped frozen to St. Petersburg for assay. Additionally, an assay which employed chick serum as the binding protein (which preferentially binds 25OHD~ rather than 25OHD~) was utilized for direct measurement of 25OHD~ levels in these patients? The diagnosis of cystic fibrosis was established by the presence of elevated sweat electrolytes, typical chronic pulmonary disease, and pancreatic insufficiency.' The patients were receiving 800 units of vitamin D~ daily in a water-soluble preparation. RESULTS The mean serum concentrations of total 25OHD, 25OHD3, and 24,25(OH)2D and 25OHD3/25OHD ratios in patients with cystic fibrosis were similar to values recorded in control subjects (Table). In one patient the concentration of 25OHD3 and in five patients the 2 5 O H D J 2 5 O H D ratios were below the ranges recorded in normal subjects. DISCUSSION The present study demonstrates that the serum concentrations of the major metabolites of vitamin D in patients with cystic fibrosis are similar to those in healthy subjects, and that 25OHD3 is the major circulating moiety of 25OHD in patients and control subjects. Endogenous vitamin D~ (cholecalciferol) produced by sunlight irradiation of cutaneous stores of 7-dehydrocholesterol is the principal form of the vitamin in the normal population) O u r data indicate that cutaneous production of D~ is normal in patients with cystic fibrosis and similar to that in healthy subjects. Recently two papers have appeared with data on serum levels of 25OHD in patients with cystic fibrosis. 1~ ~ Hubbard et aP 1 reported that the mean concentration of 25OHD was normal in these patients, but in four of 17
subjects the levels were below the range of normal. Hahn et alI~ reported that the mean serum concentrations of 25OHD and total calcium were significantly decreased, and that the mean concentration of immunoreactive parathyroid hormone was significantly increased in patients with cystic fibrosis when compared to values in matched controls. Furthermore, there was an associated decrease in bone mineralization in affected patients. Hubbard and co-workers 11 employed a nonchromatographic (and less specific) method for their measurements, whereas Hahn et al 1~ utilized silicic acid chromatography to separate individual vitamin D metabolites. The discrepancies between the observations of Hahn et al 1~ and those of Hubbard et aP 1 and our own may, in part, b e due to differences among assay methods, but more likely reflect the different seasons in which the specimens were obtained. We collected specimens in June and July, Hubbard et aP 1 during the summer and early fall, and Hahn et aP ~ in late winter and early spring. Thus in the last group exposure to sunlight had probably been minimal prior to specimen collection, whereas in the other two groups, there had been increased exposure to sunlight and hence greater synthesis of endogenous vitamin D3. The data suggest that there is a subtle deficiency of vitamin D in patients with cystic fibrosis deprived of sunlight and endogenous vitamin D3 production, even though they may be ingesting seemingly adequate amounts of supplemental vitamin D; exposure to light is sufficient to protect the majority of patients from the clinical manifestations of overt vitamin D deficiency, and adequate sunlight can maintain total 25OHD and 24,25(OH)2D values within the normal range. REFERENCES
1. diSant'Agnese PA, and Davis PB: Research in cystic fibrosis, N Engl J Med 295:597, 1976. 2. Kopel FB: Gastrointestinal manifestations of cystic fibrosis, Gastroenterology 62:483, 1972. 3. Farrel! PM, Bieri JG, Fratantoni JF, Wood RE, and
4 18
Brief clinical and laboratory observations
diSant'Agnese PA: The occurrence and effects of human vitamin E deficiency. A study in patients with cystic-fibrosis, J Clin Invest 60:233, 1977. 4. Torstenson OL, Humphrey GB, Edson JR, et al: Cystic fibrosis presenting with severe hemorrhage due to vitamin K malabsorption: A report of three cases, Pediatrics 45:857, 1970. 5. Keating JP, and Feigin RD: Increased intracranial pressure associated with probable vitamin A deficiency in cystic fibrosis, Pediatrics 46:41, 1970. 6. Weisman Y, Reiter E, and Root A: Measurement of 24,25 dihydroxyvitamin D in sera of neonates and children, J PEDIATR 91:904, 1977. 7. Stern RC, Boat TF, Doershuk CF, Tucker AS, Primiano FP Jr, and Matthews LW: Course of cystic fibrosis in 95 patients, J PEDIATR 89:406, 1976.
The Journal of Pediatrics September 1979
8.
Preece MA, Tomlinson S, Ribot CA, Pietrek J, Korn HT, Davies DM, Ford JA, Dunnigan MG, and O'Riordan JLH: Studies of vitamin D deficiency in man, Q J Med 44:575, 1975. 9. Haddad JG, and Hahn TJ: Natural and synthetic sources of circulating 25 hydroxyvitamin D in man, Nature 244:515, 1973. 10. Hahn TJ, Squires AE, Halstead LR, and Strominger DB: Reduced serum 25 hydroxyvitamin D concentration and disordered mineral metabolism in patients with cystic fibrosis, J PEDIATR 94:38, 1979. 11. Hubbard VS, Farrell PM, and diSant'Agnese PA: 25Hydroxycholecalciferol levels in patients with cystic fibrosis, J PBDIATR94:84, 1979.
Female pseudohermaphroditism caused by maternal congenital adrenal hyperplasia Hiroshi Kai, M.D.,* Osamu Nose, M.D., Yoshihiko Iida, M.D., Jiro Ono, M.D., Tokuzo Harada, M.D., and Hyakuji Yabuuchi, M.D., Osaka, Japan
FEMALE P S E U D O H E R M A P H R O D I T I S M is usually caused by exposure to exogenous a n d e n d o g e n o u s a n d r o g e n s d u r i n g the p e r i o d o f organogenesis o f the f e m a l e fetus. T h i s p a p e r reports the first example of female p s e u d o h e r m a p h r o d i t i s m caused by a n d r o g e n o f m a t e r n a l origin, the m o t h e r h a v i n g h a d congenital adrenal hyperplasia. CASE REPORT Patient. A girl of 6 years and 2 months was admitted to our hospital with clitoral enlargement. She had weighed 2,770 gm at birth and her mother had noticed her clitoral enlargement immediately after birth. Her mental and physical development had been normal. On admission she was a healthy-appearing girl of 119 cm height (seventy-fifth to ninetieth percentile) and 21 kg weight (seventy-fifth to ninetieth p6rcentile). The only abnormal finding was clitoral enlargement (2.5 cm in length and 0.8 cm in diameter); she had normal vaginal and urethral openings and no labioscrotal fusion. Her blood 9pressure was normal. Her skeletal age was 64/1~years. The karyotype was 46XX. Serum electrolyte values were within the normal range. An intravenous pyelogram showed no abnormality. The results of steroid tests on the patient (Table) were within normal limits. Subsequently she underwent clitorectomy. Mother. The patient's mother was 43 years of age and 145 cm in height. She had had a masculine habitus with clitoral enlarge-
From the Department of Pediatrics, University of Osaka, School of Medicine. *Reprint address: Department of Pediatrics, Osaka University Hospital, Fukushima-ku, Osaka, Japan.
ment since childhood. At the time of PUberty she had a deep voice and hirsutism, and her breasts were not developed. At 29 years of age she complained of amenorrhea and was diagnosed as having CAH because urinary 17-KS values were elevated. She accordingly underwent clitorectomy and was given betamethasone orally. Thereafter her menstrual periods started and became regular, and she married. One year later, she became pregnant but had a spontaneous abortion after four months of pregnancy. Two years later she discontinued betamethasone therapy but her menstrual periods continued regularly until the age of 42 years. After discontinuation of corticosteroid therapy, she delivered vaginally a healthy male infant (elder brother of this patient) and then this patient. Her karyotype was 46XX, her serum electrolyte values were normal, and her blood pressure was normal. r
Abbreviations used CAH: Congenital adrenal hyperplasia 17-KS: 17-ketosteroids T: testosterone Steroid tests showed that urinary excretion of 17-KS was slightly elevated, and urinary excretion of pregnanetriol and the plasma T level were very high. However, the plasma ACTH level was not elevated and there was a circadian rhythm in the plasma cortisol leVel. After injections of 20 units of ACTH on three consecutive days, urinary excretion of 17-KS and of pregnanetriol, and the plasma T level were greatly increased (Table). After oral administration of 4 m g of dexamethasone for seven days, urinary excretion of 17-KS and pregnanetriol and the plasma T level were decreased. After human chorionic gonado-
0022-3476/79/090418+03500.30/0 9 1979 The C. V. Mosby Co.
Brief clinical and laboratory observations
may signal the invasiveness of an amp-R strain that previously was carried only in the nasopharynx. Whether it would prove useful to monitor throat or nasopharyngeal cultures obtained from patients with H. influenzae type b meningius prior to initiating antibiotic therapy is unknown In the laboratory the presence of a heterogeneous population ofH. influenzae type b creates the potential for reports of false sensitivity to ampicillin. When the KirbyBauer disc method is utilized, agar plates must be inspected carefully for the presence of "breakthrough" colonies within the 20-mm zone of inhibition.1 It also seems possible that. on rare occasions, only amp-S colonies could be subcultured from the original culture to sensitivity plates or utilized for the beta-lactamase assay. Furthermore. if the clinical isolate contains a small percentage of amp-R colonies, the color change may not be easily observed in the one-minute beta-lactamase test. since this reqmres greater than 97 units of penicillinase. 7 REFERENCES
The Journal of Pediatrics September 1979
2.
3.
4.
5.
6.
7.
Haemophilus influenzae, Antimicrob Agents Chemother 11:1021, 1977. YogevR. Lander HB. and Davis AT: Effect of Tmp-Smx on nasopharyngeal carriage of ampicillin-sensitive and ampicillin-resistant Hemophilus influenzae type b, J PEDIATR 93:394. 1978. Thornsberry C. and Kirven LA: Antimicrobial susceptibility of Haemophilus influenzae, Antimicrob Agents Chemother 6:620. 1974 Thornsberry C. and Kirven LA: Ampicillin resistance in Haemophilus influenzae as determined by a rapid test for t%lactamase production. Antimicrob Agents Chemother 6:653. 1974. SmithAL. Scheifel DW. Syriopoulou V, and Daum R: In Vivo segregation of plasmid mediated ampicillin resistance in Haemophilus influenzae. Seventeenth Interscience Conference on Antimicrobial Agents and Chemotherapy, New York. October. 1977. Delage (3, DeClerck Y. Lescop J. Dery P, and Shareck F: Hemophilus influenzae, type b infections: Recurrent disease due to ampicillin-resistant strains, J PEDIATR90:319, 1977. Escamilla J: Susceptibility of Haemophilus influenzae to ampicillin as determined by use of a modified, one-minute beta-lactamase test. Antimicrob Agents Chemother 9:196, 1976.
1. Gray BM, Hubbell CA, and Dillon HD: Manner and meaning of susceptibility testing of ampicillin resistant
Serum concentrations of 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D in patients with cystic fibrosis Yosef Weisman, Edward Reiter, Robert C. Stern, and Allen Root,* Tampa and St. Petersburg, Fla.,
and Cleveland, Ohio
prevalent gastrointestinal m a n i f e s t a of cystic fibrosis. Although deficiencies of vitamins A, E, and K have been described in patients with this disease, 1-~ vitamin D deficiency and r rickets have rarely been reported. The major form of vitamin D, cholecalcifero ! (vitamin D3), is produced by ultraviolet irradiation of 7-dehydrocholesterol in the skin. Ergocalciferol (vitamin S T E A T O R R H E A is a
tion
From the Departments of Pediatrics, University of South Florida College of Medicine; and Case Western Reserve University School of Medicine," Ed Wright Pediatric Endocrinology Researc h Laboratory, All Children's Hospital," and Rainbow Babies and Children's Hospital. Supported by National Foundation-March of Dimes Grants C-199, 1-632, Grants AM08305 and HL 13885 from the United States Public Health Service, and by grants from the National Cystic Fibrosis Foundation: *Reprint address: All Children's Hospital, 801 Sixth St. South, St. Petersburg, FL 33701.
D2) is a product of p l a n t ergosterol. We studied the vitamin D status of patients with cystic fibrosis by measurement of the serum concentrations of the major circulating metabolit~es of Vitamin D: 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D. The liver is the site of synthesis of 25OHD, whereas 24,25(OH)2Dis synthesized primarily in the kidney. Abbreviations used 25OHD: 25-hydroxyvitamin D 24,25(OH)~D: 24,25-dihydroxyvitamin D 25OHDa: 25-hydroxycholecalciferol SUBJECTS
AND
METHODS
After seParation of vitamin D metabolites by gel chromatography, the serum concentrations of 25OHD (N = 23) and of 24,25(OH)~D (N = 10) were determined by competitive protein-binding radioassays employing rat serum-binding protein6 in children and adolescents with
0022:~3476/79/090416+03500.30/0 9 1979 The C. V. Mosby Co.
Volume 95 Number 3
Brief clinical and laboratory observations
4 17
Table. Concentrations of vitamin D metabolites in children with cystic fibrosis and control subjects
Control subjects (9) Mean _+ SD Range Cystic fibrosis patients (23) Mean + SD Range
250HD
250HD~
250HDJ250HD
27.7* _+9.9 11.3-44.6
25.0* _+4.9 19.8-34.6
0.860 _+0.119 0.769-1.112
2.6* _+1.3 1.0-4.9
25.5 _+8.4 14.6-55.4
21.6 _+7.5 8.8-36.3
0.837 _+0.169 0.392-1.097
2.2 _+0.6 1.6-3.6 (10)
I
24,25(OH)2D
*ng/ml. cystic fibrosis attending the Rainbow Babies and Children's Hospital, Cleveland, 7 and from nine normal children. All sera were collected in early summer, and shipped frozen to St. Petersburg for assay. Additionally, an assay which employed chick serum as the binding protein (which preferentially binds 25OHD~ rather than 25OHD~) was utilized for direct measurement of 25OHD~ levels in these patients? The diagnosis of cystic fibrosis was established by the presence of elevated sweat electrolytes, typical chronic pulmonary disease, and pancreatic insufficiency.' The patients were receiving 800 units of vitamin D~ daily in a water-soluble preparation. RESULTS The mean serum concentrations of total 25OHD, 25OHD3, and 24,25(OH)2D and 25OHD3/25OHD ratios in patients with cystic fibrosis were similar to values recorded in control subjects (Table). In one patient the concentration of 25OHD3 and in five patients the 2 5 O H D J 2 5 O H D ratios were below the ranges recorded in normal subjects. DISCUSSION The present study demonstrates that the serum concentrations of the major metabolites of vitamin D in patients with cystic fibrosis are similar to those in healthy subjects, and that 25OHD3 is the major circulating moiety of 25OHD in patients and control subjects. Endogenous vitamin D~ (cholecalciferol) produced by sunlight irradiation of cutaneous stores of 7-dehydrocholesterol is the principal form of the vitamin in the normal population) O u r data indicate that cutaneous production of D~ is normal in patients with cystic fibrosis and similar to that in healthy subjects. Recently two papers have appeared with data on serum levels of 25OHD in patients with cystic fibrosis. 1~ ~ Hubbard et aP 1 reported that the mean concentration of 25OHD was normal in these patients, but in four of 17
subjects the levels were below the range of normal. Hahn et alI~ reported that the mean serum concentrations of 25OHD and total calcium were significantly decreased, and that the mean concentration of immunoreactive parathyroid hormone was significantly increased in patients with cystic fibrosis when compared to values in matched controls. Furthermore, there was an associated decrease in bone mineralization in affected patients. Hubbard and co-workers 11 employed a nonchromatographic (and less specific) method for their measurements, whereas Hahn et al 1~ utilized silicic acid chromatography to separate individual vitamin D metabolites. The discrepancies between the observations of Hahn et al 1~ and those of Hubbard et aP 1 and our own may, in part, b e due to differences among assay methods, but more likely reflect the different seasons in which the specimens were obtained. We collected specimens in June and July, Hubbard et aP 1 during the summer and early fall, and Hahn et aP ~ in late winter and early spring. Thus in the last group exposure to sunlight had probably been minimal prior to specimen collection, whereas in the other two groups, there had been increased exposure to sunlight and hence greater synthesis of endogenous vitamin D3. The data suggest that there is a subtle deficiency of vitamin D in patients with cystic fibrosis deprived of sunlight and endogenous vitamin D3 production, even though they may be ingesting seemingly adequate amounts of supplemental vitamin D; exposure to light is sufficient to protect the majority of patients from the clinical manifestations of overt vitamin D deficiency, and adequate sunlight can maintain total 25OHD and 24,25(OH)2D values within the normal range. REFERENCES
1. diSant'Agnese PA, and Davis PB: Research in cystic fibrosis, N Engl J Med 295:597, 1976. 2. Kopel FB: Gastrointestinal manifestations of cystic fibrosis, Gastroenterology 62:483, 1972. 3. Farrel! PM, Bieri JG, Fratantoni JF, Wood RE, and
4 18
Brief clinical and laboratory observations
diSant'Agnese PA: The occurrence and effects of human vitamin E deficiency. A study in patients with cystic-fibrosis, J Clin Invest 60:233, 1977. 4. Torstenson OL, Humphrey GB, Edson JR, et al: Cystic fibrosis presenting with severe hemorrhage due to vitamin K malabsorption: A report of three cases, Pediatrics 45:857, 1970. 5. Keating JP, and Feigin RD: Increased intracranial pressure associated with probable vitamin A deficiency in cystic fibrosis, Pediatrics 46:41, 1970. 6. Weisman Y, Reiter E, and Root A: Measurement of 24,25 dihydroxyvitamin D in sera of neonates and children, J PEDIATR 91:904, 1977. 7. Stern RC, Boat TF, Doershuk CF, Tucker AS, Primiano FP Jr, and Matthews LW: Course of cystic fibrosis in 95 patients, J PEDIATR 89:406, 1976.
The Journal of Pediatrics September 1979
8.
Preece MA, Tomlinson S, Ribot CA, Pietrek J, Korn HT, Davies DM, Ford JA, Dunnigan MG, and O'Riordan JLH: Studies of vitamin D deficiency in man, Q J Med 44:575, 1975. 9. Haddad JG, and Hahn TJ: Natural and synthetic sources of circulating 25 hydroxyvitamin D in man, Nature 244:515, 1973. 10. Hahn TJ, Squires AE, Halstead LR, and Strominger DB: Reduced serum 25 hydroxyvitamin D concentration and disordered mineral metabolism in patients with cystic fibrosis, J PEDIATR 94:38, 1979. 11. Hubbard VS, Farrell PM, and diSant'Agnese PA: 25Hydroxycholecalciferol levels in patients with cystic fibrosis, J PBDIATR94:84, 1979.
Female pseudohermaphroditism caused by maternal congenital adrenal hyperplasia Hiroshi Kai, M.D.,* Osamu Nose, M.D., Yoshihiko Iida, M.D., Jiro Ono, M.D., Tokuzo Harada, M.D., and Hyakuji Yabuuchi, M.D., Osaka, Japan
FEMALE P S E U D O H E R M A P H R O D I T I S M is usually caused by exposure to exogenous a n d e n d o g e n o u s a n d r o g e n s d u r i n g the p e r i o d o f organogenesis o f the f e m a l e fetus. T h i s p a p e r reports the first example of female p s e u d o h e r m a p h r o d i t i s m caused by a n d r o g e n o f m a t e r n a l origin, the m o t h e r h a v i n g h a d congenital adrenal hyperplasia. CASE REPORT Patient. A girl of 6 years and 2 months was admitted to our hospital with clitoral enlargement. She had weighed 2,770 gm at birth and her mother had noticed her clitoral enlargement immediately after birth. Her mental and physical development had been normal. On admission she was a healthy-appearing girl of 119 cm height (seventy-fifth to ninetieth percentile) and 21 kg weight (seventy-fifth to ninetieth p6rcentile). The only abnormal finding was clitoral enlargement (2.5 cm in length and 0.8 cm in diameter); she had normal vaginal and urethral openings and no labioscrotal fusion. Her blood 9pressure was normal. Her skeletal age was 64/1~years. The karyotype was 46XX. Serum electrolyte values were within the normal range. An intravenous pyelogram showed no abnormality. The results of steroid tests on the patient (Table) were within normal limits. Subsequently she underwent clitorectomy. Mother. The patient's mother was 43 years of age and 145 cm in height. She had had a masculine habitus with clitoral enlarge-
From the Department of Pediatrics, University of Osaka, School of Medicine. *Reprint address: Department of Pediatrics, Osaka University Hospital, Fukushima-ku, Osaka, Japan.
ment since childhood. At the time of PUberty she had a deep voice and hirsutism, and her breasts were not developed. At 29 years of age she complained of amenorrhea and was diagnosed as having CAH because urinary 17-KS values were elevated. She accordingly underwent clitorectomy and was given betamethasone orally. Thereafter her menstrual periods started and became regular, and she married. One year later, she became pregnant but had a spontaneous abortion after four months of pregnancy. Two years later she discontinued betamethasone therapy but her menstrual periods continued regularly until the age of 42 years. After discontinuation of corticosteroid therapy, she delivered vaginally a healthy male infant (elder brother of this patient) and then this patient. Her karyotype was 46XX, her serum electrolyte values were normal, and her blood pressure was normal. r
Abbreviations used CAH: Congenital adrenal hyperplasia 17-KS: 17-ketosteroids T: testosterone Steroid tests showed that urinary excretion of 17-KS was slightly elevated, and urinary excretion of pregnanetriol and the plasma T level were very high. However, the plasma ACTH level was not elevated and there was a circadian rhythm in the plasma cortisol leVel. After injections of 20 units of ACTH on three consecutive days, urinary excretion of 17-KS and of pregnanetriol, and the plasma T level were greatly increased (Table). After oral administration of 4 m g of dexamethasone for seven days, urinary excretion of 17-KS and pregnanetriol and the plasma T level were decreased. After human chorionic gonado-
0022-3476/79/090418+03500.30/0 9 1979 The C. V. Mosby Co.
