250
Brief clinical and laboratory observations
Intracranial human chorionic gonadotropinsecreting tumor with precocious puberty Carolyn A. Romshe, M.D.* and Juan F. Sotos,
M.D., Columbus, Ohio
PRECOCIOUS PUBERTY r e s u l t i n g f r o m i n t r a c r a n i a l tumors secreting h u m a n chorionic gonadotropin is rare. To date four cases t-4 h a v e b e e n reported and only in one was a specific r a d i o i m m u n o a s s a y for h u m a n chorionic gonadotropin performed. 4 T h e p r e s e n t report c o n c e r n s a 9-year-old boy in w h o m an H C G - s e c r e t i n g t u m o r of the third ventricle was responsible for rapid sexual dev e l o p m e n t and u n u s u a l h o r m o n a l features. T h e patient was treated with radiation therapy and subsequently all e n d o c r i n e abnormalities r e t u r n e d to normal. Observations o b t a i n e d indicate that specific R I A for H C G can be used to assess the effectiveness of t r e a t m e n t and may will indicate early e v i d e n c e of r e c u r r e n c e o f the tumor.
The Journal of Pediatrics February 1975
Laboratory data included a normal blood count and normal concentrations of blood urea nitrogen, blood glucose, serum electrolytes, calcium, inorganic phosphorous, and alkaline pbosphatase. The urinalysis was negative with a specific gravity of 1.018. The endocrine studies are discussed later. The bone age was 12 years and there was some widening of the cranial sutures with a normal sella turcica in a roentgenogram of the skull. A ventriculogram revealed a large mass located between the pineal recess and the aqueduct of Sylvius with moderate obstruction of the aqueduct. He was treated with dexamethasone and a ventriculojugular shunt was performed to relieve the increased intracranial pressure. Because of t~e size and location of the tumor, it was judged that radiation therapy (4,500 rads over a 5-week period) prior to surgical removal would be the safest therapeutic approach. Within 2 months of the beginning of radiation therapy, clinical improvement was noted, with lessening of the amount of facial hair, improvement of acne, and general well being. Surgery was not performed. The improvement of the clinical manifestations correlated with a decrease of the serum concentrations of testosterone. Abbreviations used HCG: human chorionic gonadotropin RIA: radioimmunoassay TSH: thyroid-stimulating hormone FSH: follicle-stimulating hormone LH: luteinizing hormone
CASE REPORT P. A,, a 9-year-old boy, who had been in good health was noted after returning from one month at summer camp to have deepening of the voice, pubic hair, and enlargement of the phallus. In the subsequent month after our initial observation he developed headaches, nausea, vomiting, and blurred vision. The father and three older siblings did not develop sexually until about 13 years of age. On physical examination he was lethargic, in some distress, and had paralysis of upward gaze. The height was 5689 inches (ninetieth percentile), weight 87 pounds (ninetieth percentile) and the blood pressure was 120/80 mm/Hg. The pupils were dilated and sluggish to light and there was bilateral papilledema. Early development of beard was present. There was 2+ pubic hair and the penis was enlarged measuring, 10 cm in length by 3 cm in width. The left testis measured 2.7 cm in length by 1.4 cm in width and the right testis 3 cm in length by 1.7 cm in width, each of which was small for the degree of sexual d e v e l o p m e n t . T h e r e was u n s u s t a i n e d clonus and moderately hyperactive reflexes bilaterally. The remainder of the physical examination was normal. From the Department of Pediatrics, College of Medicine, The Oh& State University, and Children's Hospital Research Foundation. Supported by the John W. Champion Center, Children's Hospital, Columbus, Ohio, and General Research Support R R-05504. *Reprint address: Children's Hospital, 561 S. 17th St., Columbus, Ohio 43205.
METHODS Plasma cortisol was m e a s u r e d by c o m p e t i t i v e protein b i n d i n g . T h e u r i n a r y 1 7 - h y d r o x y s t e r o i d s and 17ketosteroids were m e a s u r e d by a modification of the Porter-Silber and Sobel methods, respectively. 5 S e r u m t h y r o x i n e , t h y r o i d - s t i m u l a t i n g h o r m o n e , folliclestimulating hormone, luteinizing hormone, progesterone, and testosterone were m e a s u r e d by radioimmunoassay. Since the assay for LH cross-reacted with HCG and tumor gonadotropin, and since elevated values for LH m i g h t r e p r e s e n t the p r e s e n c e of H C G , a specific R I A for H C G was performed. T h e assay for H C G uses an antibody against HCG-/3 subunits, w h i c h permits the selective m e a s u r e m e n t o f H C G in the prese n c e of physiologic a m o u n t s o f LH. 6 RESULTS
OF ENDOCRINE
STUDIES
The s e r u m c o n c e n t r a t i o n of t h y r o x i n e was 6.6 ~ g / d l ( n o r m a l 4-11) and the value of TSH was less than 3.1 ~ U / m l ( n o r m a l less than 10). T h e values of 24 hour excretions o f urinary 17-hydroxysteroids (2 rag) and pregnanetriol (1.7 mg) were normal and were suppressed (0.2 and 0.5 mg, respectively) after two days of dexa m e t h a s o n e therapy at a dose of 2 mg/day. T h e plasma levels of cortisol were 19.8 ~ g / d l at 8AM and 9.5 ~ g / d l at 4 PM, w h i c h are within normal limits. T h e s e r u m con-
Volume 86 Number 2
Brief clinical and laboratory observations
251
Table I. Endocrine studies before and after radiation therapy
Date 8/21/73 9/28/73 10/5/73 10/9/73 10/11/73 10/19/73 10/22/73 11/7/73 11/8/73 12/4/73
FSH Normal*(2-12 mlU/ml)
LH (6-20 mlU/ml)
HCG (Undetectable)
Testosterone (21-34 ng/dl)
(0.8 (1.0 Radiation begun with 4,500 rads
>70 >70
4,825 mlU/ml
>2,000 >2,000
(1.0
>70 >70 109 66
1,000 920
Radiation completed 13.2 6.6
Undetectable Undetectable
50 (50
*Normal for age. c e n t r a t i o n of p r o g e s t e r o n e was 0.278 /zg/dl ( n o r m a l 0-1.6). The values of 24-hour excretion of urinary 17ketosteroids were 10.2 mg which are elevated for age, a n d were not s u p p r e s s e d ( 1 7 - k e t o s t e r o i d s - 12.4 mg) with d e x a m e t h a s o n e t h e r a p y . A p r e g n a n c y test on urine was negative. Marked interstitial cell hyperplasia and some hypertrophy were noted on a testicular biopsy. The seminiferous tubules were lined with a few Sertoli cells, spermatogonia, and spermatocytes but without spermatids or spermatozoa. Serum concentrations of LH, testosterone, and H C G were markedly elevated initially and returned to normal levels following radiation therapy. C o n c e n t r a t i o n of serum FSH was low initially but returned to a normal value after treatment. (Table I) DISCUSSION The rapid progression of virilization in our patient suggested a process other than idiopathic precocious puberty. The normal basal values and suppression with administration of dexamethasone of the urinary excretion of 17-hydroxysteroids and pregnanetriol, as well as the normal values of plasma cortisol and progesterone, indicated normal adrenal function. The advanced bone age and the elevated values of urinary 17-ketosteroids, whicJa were not suppressed with dexamethasone therapy, suggested that the source of excessive androgens was not likely under regulation of ACTH. The elevated serum levels of testosterone in conjunction with interstitial cell hyperplasia established the testes as the source of excessive androgens. Both the elevated serum levels of LH and the paralysis of upward gaze indicated a central cause of precocious puberty. The striking elevation of serum levels of testosterone, greatly exceeding those of normal adult males, conc o m i t a n t l y with i n c r e a s e d LH levels s u g g e s t e d an a u t o n o m o u s s e c r e t i o n of LH. The s e c r e t i o n of LH
could arise from the tumor itself or be mediated by the pressure of the tumor on the hypothalamic area, impairing the secretion of LH releasing factor inhibitor. The markedly elevated levels of H C G of 4,825 m l U , levels comparable to those observed in late pregnancy, clearly indicated a tumor-secreting chorionic gonadotropin, which could explain all of the clinical and laboratory findings. The serum levels of LH obtained could be the result of cross reactivity of HCG, since H C G levels were fifty to one hundred times those of LH. The low levels of FSH have been reported in other patients with H C G secreting tumors 7 and could be attributed to the suppressive effects of testosterone on the hypothalamus directly or indirectly by its peripheral c o n v e r s i o n to estradiol. 8 T h e lack of c o m p l e t e spermatogenesis in our patient, particularly in view of the brief clinical course, is not surprising, since in the absence of endogenous secretion of FSH, it is still questionable whether administration of HCG alone can induce tub ular development of spermatogenesis. 9 Of the four boys reported since 1945 with intracranial chorioepithelioma, three had an abnormal HCG-like substance present in a large amount in the urine or in the tumor itself) 3 and one had elevated plasma levels of H C G by radioimmunoassay. 4 Vaitukaifis 4 studied the sera of a number of patients with HCG-secreting tumors and found that intact HCG is the predominant form of the secreted hormone. The patients have, in addition, at least one of the H C G subunits ( H C G a or HCG/3) and other aberrant forms of HCG. The studies suggested that altered forms of H C G arise during synthesis. The radioimmunoassay of H C G has proved helpful in the detection of HCGsecreting tumors inducing precocious puberty, including hepatoblastomas, testicular choriocarcinoma, and teratomas.10 The observations indicate that radioimmunoassay of H C G is helpful in defining the nature of the tumor and
252
Brief clinical and laboratory observations
in assessing the effectiveness of therapy and hopefully may be used for the early detection of recurrence. Determination of serum concentrations of testosterone could be equally useful and easier to obtain for followup of such patients. Moreover, the findings indicate that intracranial chorioepitheliomas are radiosensitive and therefore radiation can be used to reduce the size of the tumor prior to surgery. It would appear worthwhile to measure HCG in children with precocious puberty with elevated LH or tumors. We are indebted to Dr. Vernon Stevens and Mr. John Powell, Department of Obstetrics and Gynecology, Ohio State University for performing the HCG assays and to Martin P. Sayers, M.D., Department of Surgery, Ohio State University for neurosurgical management.
REFERENCES 1. StowellRE, Sachs E, and Russel WO: Primary intracranial chorionephitheli6ma with metastases to the lungs, Am J Pathol 21:787, 1945. 2. Bruton OC, Martz DC, and Gerard ES: Precocious puberty due to secreting chorionephithioma (teratoma) of the brain, J PEDIATR59:719, 1961.
Leukocyte count differences in healthy white and black children I to 5years of age Elena Caramihai, M.D., Gungor Karayalcin, M.D.,* Arturo J. Aballi, M.D., and Philip Lanzkowsky, M.D., F.R.C.P., D,C.H., Jamaica, N. Y.
L E U K O P E N I A was r e p o r t e d i n b l a c k a d u l t s in Mississippi by Forbes and associates 1in 1941. Recently, Karayalcin and associates 2 also demonstrated neutropenia in healthy black adults in New York. The present prospective study a m o n g healthy black and white children 1 to 5 years of age in the same community revealed similar results. From the Division of Pediatric Hematology, Department of Pediatrics, Queens Hospital Center Affifiation and Long Island Jewish-Hillside Medical Center and the Department of Pediatrics of the Medical School of the Health Sciences Center of the State University of New York at Stony Brook. *Reprint address: QueensHospital Center, 82-68164th St., Jamaica, New York 11432
The Journal of Pediatrics February 1975
3. Hutchinson JSM, Brooks RV, Barratt TM, Newman CGH, and Prunty FTG: Sexual precocity due to intracranial tumor causing unusual testicular secretion of testosterone, Arch Dis Child 44:732, 1969. 4. Vaitukaitis JL: Immunologic and physical characterization of human chorionic gonadotropin (HCG) secreted by tumors, J Clin Endocrinol Metab 37:505, 1973. 5. Chattoraj SC: Endocrinology, in Tietz NW, editor: Fundamentals of clinical chemistry, Philadelphia, 1970, WB Saunders Company, p 501. 6. Vaitukaitis JL, Braunstein GD, and Ross GT: A radioimmunoassay which specifically measures human chorionic gonadotropin in the presence of human luteinizing hormone, Am J Obstet Gynecol 113:751, 1972. 7. Reiter EO, and Kulin HE: Suppressed follicle stimulating hormone in men with chorionic gonadotropin secreting testicular tumors, J Clin Endocrinol 33:957, 1971. 8. Sherins RJ, and Loriaux DL: Studies on the role of sex steroids in the feedback control of FSH concentrations in men, J Clin Endocrinol 36:886, 1973. 9. Paulsen CA, Espeland DH, and Michals EL: Effects of HCG, HMG, HLH and HGH administration on testicular function, in Rosenberg E, and Paulsen CA, editors: The human testis, New York, 1970, Plenum Press, p 552. 10. Omenn GS: Ectopic hormone syndrome associated with tumors in childhood, Pediatrics 47:613, 1971.
MATERIALS
AND METHODS
One hundred and fifty healthy black and 150 white children, 1 to 5 years of age, from the Queens Hospital Center Well Baby Clinics were investigated. Children with evidence of infection or those who had positive sickle cell preparations were excluded from the study. A n equal n u m b e r of children were studied in each age, race, and sex group. The following information was collected on each subject: age, race, sex, urinalysis, sickle cell preparation (metabisulfate method), hemoglobin concentration (cyanmethemoglobin method), microhematocrit values, leukocyte c o u n t ( C o u l t e r electronic counter, model S), and differential leukocyte count. Absolute granulocyte and lymphocyte counts were calculated. RESULTS There was no significant difference in the mean and range for hemoglobin and hematocrit values in black and white children (Table I). However, the mean total leukocyte counts in black children were significantly lower (p (0.01) than in the white children (7,877/mm 3 _+ 1,936 and 9,053/mm 3 + 1,843, respectively). The lower mean white blood cell count in black children compared to that in white children was due to a lower n u m b e r of neutrophils (2,509/mm3 ___ 1,176 and 3,392/
Brief clinical and laboratory observations
Intracranial human chorionic gonadotropinsecreting tumor with precocious puberty Carolyn A. Romshe, M.D.* and Juan F. Sotos,
M.D., Columbus, Ohio
PRECOCIOUS PUBERTY r e s u l t i n g f r o m i n t r a c r a n i a l tumors secreting h u m a n chorionic gonadotropin is rare. To date four cases t-4 h a v e b e e n reported and only in one was a specific r a d i o i m m u n o a s s a y for h u m a n chorionic gonadotropin performed. 4 T h e p r e s e n t report c o n c e r n s a 9-year-old boy in w h o m an H C G - s e c r e t i n g t u m o r of the third ventricle was responsible for rapid sexual dev e l o p m e n t and u n u s u a l h o r m o n a l features. T h e patient was treated with radiation therapy and subsequently all e n d o c r i n e abnormalities r e t u r n e d to normal. Observations o b t a i n e d indicate that specific R I A for H C G can be used to assess the effectiveness of t r e a t m e n t and may will indicate early e v i d e n c e of r e c u r r e n c e o f the tumor.
The Journal of Pediatrics February 1975
Laboratory data included a normal blood count and normal concentrations of blood urea nitrogen, blood glucose, serum electrolytes, calcium, inorganic phosphorous, and alkaline pbosphatase. The urinalysis was negative with a specific gravity of 1.018. The endocrine studies are discussed later. The bone age was 12 years and there was some widening of the cranial sutures with a normal sella turcica in a roentgenogram of the skull. A ventriculogram revealed a large mass located between the pineal recess and the aqueduct of Sylvius with moderate obstruction of the aqueduct. He was treated with dexamethasone and a ventriculojugular shunt was performed to relieve the increased intracranial pressure. Because of t~e size and location of the tumor, it was judged that radiation therapy (4,500 rads over a 5-week period) prior to surgical removal would be the safest therapeutic approach. Within 2 months of the beginning of radiation therapy, clinical improvement was noted, with lessening of the amount of facial hair, improvement of acne, and general well being. Surgery was not performed. The improvement of the clinical manifestations correlated with a decrease of the serum concentrations of testosterone. Abbreviations used HCG: human chorionic gonadotropin RIA: radioimmunoassay TSH: thyroid-stimulating hormone FSH: follicle-stimulating hormone LH: luteinizing hormone
CASE REPORT P. A,, a 9-year-old boy, who had been in good health was noted after returning from one month at summer camp to have deepening of the voice, pubic hair, and enlargement of the phallus. In the subsequent month after our initial observation he developed headaches, nausea, vomiting, and blurred vision. The father and three older siblings did not develop sexually until about 13 years of age. On physical examination he was lethargic, in some distress, and had paralysis of upward gaze. The height was 5689 inches (ninetieth percentile), weight 87 pounds (ninetieth percentile) and the blood pressure was 120/80 mm/Hg. The pupils were dilated and sluggish to light and there was bilateral papilledema. Early development of beard was present. There was 2+ pubic hair and the penis was enlarged measuring, 10 cm in length by 3 cm in width. The left testis measured 2.7 cm in length by 1.4 cm in width and the right testis 3 cm in length by 1.7 cm in width, each of which was small for the degree of sexual d e v e l o p m e n t . T h e r e was u n s u s t a i n e d clonus and moderately hyperactive reflexes bilaterally. The remainder of the physical examination was normal. From the Department of Pediatrics, College of Medicine, The Oh& State University, and Children's Hospital Research Foundation. Supported by the John W. Champion Center, Children's Hospital, Columbus, Ohio, and General Research Support R R-05504. *Reprint address: Children's Hospital, 561 S. 17th St., Columbus, Ohio 43205.
METHODS Plasma cortisol was m e a s u r e d by c o m p e t i t i v e protein b i n d i n g . T h e u r i n a r y 1 7 - h y d r o x y s t e r o i d s and 17ketosteroids were m e a s u r e d by a modification of the Porter-Silber and Sobel methods, respectively. 5 S e r u m t h y r o x i n e , t h y r o i d - s t i m u l a t i n g h o r m o n e , folliclestimulating hormone, luteinizing hormone, progesterone, and testosterone were m e a s u r e d by radioimmunoassay. Since the assay for LH cross-reacted with HCG and tumor gonadotropin, and since elevated values for LH m i g h t r e p r e s e n t the p r e s e n c e of H C G , a specific R I A for H C G was performed. T h e assay for H C G uses an antibody against HCG-/3 subunits, w h i c h permits the selective m e a s u r e m e n t o f H C G in the prese n c e of physiologic a m o u n t s o f LH. 6 RESULTS
OF ENDOCRINE
STUDIES
The s e r u m c o n c e n t r a t i o n of t h y r o x i n e was 6.6 ~ g / d l ( n o r m a l 4-11) and the value of TSH was less than 3.1 ~ U / m l ( n o r m a l less than 10). T h e values of 24 hour excretions o f urinary 17-hydroxysteroids (2 rag) and pregnanetriol (1.7 mg) were normal and were suppressed (0.2 and 0.5 mg, respectively) after two days of dexa m e t h a s o n e therapy at a dose of 2 mg/day. T h e plasma levels of cortisol were 19.8 ~ g / d l at 8AM and 9.5 ~ g / d l at 4 PM, w h i c h are within normal limits. T h e s e r u m con-
Volume 86 Number 2
Brief clinical and laboratory observations
251
Table I. Endocrine studies before and after radiation therapy
Date 8/21/73 9/28/73 10/5/73 10/9/73 10/11/73 10/19/73 10/22/73 11/7/73 11/8/73 12/4/73
FSH Normal*(2-12 mlU/ml)
LH (6-20 mlU/ml)
HCG (Undetectable)
Testosterone (21-34 ng/dl)
(0.8 (1.0 Radiation begun with 4,500 rads
>70 >70
4,825 mlU/ml
>2,000 >2,000
(1.0
>70 >70 109 66
1,000 920
Radiation completed 13.2 6.6
Undetectable Undetectable
50 (50
*Normal for age. c e n t r a t i o n of p r o g e s t e r o n e was 0.278 /zg/dl ( n o r m a l 0-1.6). The values of 24-hour excretion of urinary 17ketosteroids were 10.2 mg which are elevated for age, a n d were not s u p p r e s s e d ( 1 7 - k e t o s t e r o i d s - 12.4 mg) with d e x a m e t h a s o n e t h e r a p y . A p r e g n a n c y test on urine was negative. Marked interstitial cell hyperplasia and some hypertrophy were noted on a testicular biopsy. The seminiferous tubules were lined with a few Sertoli cells, spermatogonia, and spermatocytes but without spermatids or spermatozoa. Serum concentrations of LH, testosterone, and H C G were markedly elevated initially and returned to normal levels following radiation therapy. C o n c e n t r a t i o n of serum FSH was low initially but returned to a normal value after treatment. (Table I) DISCUSSION The rapid progression of virilization in our patient suggested a process other than idiopathic precocious puberty. The normal basal values and suppression with administration of dexamethasone of the urinary excretion of 17-hydroxysteroids and pregnanetriol, as well as the normal values of plasma cortisol and progesterone, indicated normal adrenal function. The advanced bone age and the elevated values of urinary 17-ketosteroids, whicJa were not suppressed with dexamethasone therapy, suggested that the source of excessive androgens was not likely under regulation of ACTH. The elevated serum levels of testosterone in conjunction with interstitial cell hyperplasia established the testes as the source of excessive androgens. Both the elevated serum levels of LH and the paralysis of upward gaze indicated a central cause of precocious puberty. The striking elevation of serum levels of testosterone, greatly exceeding those of normal adult males, conc o m i t a n t l y with i n c r e a s e d LH levels s u g g e s t e d an a u t o n o m o u s s e c r e t i o n of LH. The s e c r e t i o n of LH
could arise from the tumor itself or be mediated by the pressure of the tumor on the hypothalamic area, impairing the secretion of LH releasing factor inhibitor. The markedly elevated levels of H C G of 4,825 m l U , levels comparable to those observed in late pregnancy, clearly indicated a tumor-secreting chorionic gonadotropin, which could explain all of the clinical and laboratory findings. The serum levels of LH obtained could be the result of cross reactivity of HCG, since H C G levels were fifty to one hundred times those of LH. The low levels of FSH have been reported in other patients with H C G secreting tumors 7 and could be attributed to the suppressive effects of testosterone on the hypothalamus directly or indirectly by its peripheral c o n v e r s i o n to estradiol. 8 T h e lack of c o m p l e t e spermatogenesis in our patient, particularly in view of the brief clinical course, is not surprising, since in the absence of endogenous secretion of FSH, it is still questionable whether administration of HCG alone can induce tub ular development of spermatogenesis. 9 Of the four boys reported since 1945 with intracranial chorioepithelioma, three had an abnormal HCG-like substance present in a large amount in the urine or in the tumor itself) 3 and one had elevated plasma levels of H C G by radioimmunoassay. 4 Vaitukaifis 4 studied the sera of a number of patients with HCG-secreting tumors and found that intact HCG is the predominant form of the secreted hormone. The patients have, in addition, at least one of the H C G subunits ( H C G a or HCG/3) and other aberrant forms of HCG. The studies suggested that altered forms of H C G arise during synthesis. The radioimmunoassay of H C G has proved helpful in the detection of HCGsecreting tumors inducing precocious puberty, including hepatoblastomas, testicular choriocarcinoma, and teratomas.10 The observations indicate that radioimmunoassay of H C G is helpful in defining the nature of the tumor and
252
Brief clinical and laboratory observations
in assessing the effectiveness of therapy and hopefully may be used for the early detection of recurrence. Determination of serum concentrations of testosterone could be equally useful and easier to obtain for followup of such patients. Moreover, the findings indicate that intracranial chorioepitheliomas are radiosensitive and therefore radiation can be used to reduce the size of the tumor prior to surgery. It would appear worthwhile to measure HCG in children with precocious puberty with elevated LH or tumors. We are indebted to Dr. Vernon Stevens and Mr. John Powell, Department of Obstetrics and Gynecology, Ohio State University for performing the HCG assays and to Martin P. Sayers, M.D., Department of Surgery, Ohio State University for neurosurgical management.
REFERENCES 1. StowellRE, Sachs E, and Russel WO: Primary intracranial chorionephitheli6ma with metastases to the lungs, Am J Pathol 21:787, 1945. 2. Bruton OC, Martz DC, and Gerard ES: Precocious puberty due to secreting chorionephithioma (teratoma) of the brain, J PEDIATR59:719, 1961.
Leukocyte count differences in healthy white and black children I to 5years of age Elena Caramihai, M.D., Gungor Karayalcin, M.D.,* Arturo J. Aballi, M.D., and Philip Lanzkowsky, M.D., F.R.C.P., D,C.H., Jamaica, N. Y.
L E U K O P E N I A was r e p o r t e d i n b l a c k a d u l t s in Mississippi by Forbes and associates 1in 1941. Recently, Karayalcin and associates 2 also demonstrated neutropenia in healthy black adults in New York. The present prospective study a m o n g healthy black and white children 1 to 5 years of age in the same community revealed similar results. From the Division of Pediatric Hematology, Department of Pediatrics, Queens Hospital Center Affifiation and Long Island Jewish-Hillside Medical Center and the Department of Pediatrics of the Medical School of the Health Sciences Center of the State University of New York at Stony Brook. *Reprint address: QueensHospital Center, 82-68164th St., Jamaica, New York 11432
The Journal of Pediatrics February 1975
3. Hutchinson JSM, Brooks RV, Barratt TM, Newman CGH, and Prunty FTG: Sexual precocity due to intracranial tumor causing unusual testicular secretion of testosterone, Arch Dis Child 44:732, 1969. 4. Vaitukaitis JL: Immunologic and physical characterization of human chorionic gonadotropin (HCG) secreted by tumors, J Clin Endocrinol Metab 37:505, 1973. 5. Chattoraj SC: Endocrinology, in Tietz NW, editor: Fundamentals of clinical chemistry, Philadelphia, 1970, WB Saunders Company, p 501. 6. Vaitukaitis JL, Braunstein GD, and Ross GT: A radioimmunoassay which specifically measures human chorionic gonadotropin in the presence of human luteinizing hormone, Am J Obstet Gynecol 113:751, 1972. 7. Reiter EO, and Kulin HE: Suppressed follicle stimulating hormone in men with chorionic gonadotropin secreting testicular tumors, J Clin Endocrinol 33:957, 1971. 8. Sherins RJ, and Loriaux DL: Studies on the role of sex steroids in the feedback control of FSH concentrations in men, J Clin Endocrinol 36:886, 1973. 9. Paulsen CA, Espeland DH, and Michals EL: Effects of HCG, HMG, HLH and HGH administration on testicular function, in Rosenberg E, and Paulsen CA, editors: The human testis, New York, 1970, Plenum Press, p 552. 10. Omenn GS: Ectopic hormone syndrome associated with tumors in childhood, Pediatrics 47:613, 1971.
MATERIALS
AND METHODS
One hundred and fifty healthy black and 150 white children, 1 to 5 years of age, from the Queens Hospital Center Well Baby Clinics were investigated. Children with evidence of infection or those who had positive sickle cell preparations were excluded from the study. A n equal n u m b e r of children were studied in each age, race, and sex group. The following information was collected on each subject: age, race, sex, urinalysis, sickle cell preparation (metabisulfate method), hemoglobin concentration (cyanmethemoglobin method), microhematocrit values, leukocyte c o u n t ( C o u l t e r electronic counter, model S), and differential leukocyte count. Absolute granulocyte and lymphocyte counts were calculated. RESULTS There was no significant difference in the mean and range for hemoglobin and hematocrit values in black and white children (Table I). However, the mean total leukocyte counts in black children were significantly lower (p (0.01) than in the white children (7,877/mm 3 _+ 1,936 and 9,053/mm 3 + 1,843, respectively). The lower mean white blood cell count in black children compared to that in white children was due to a lower n u m b e r of neutrophils (2,509/mm3 ___ 1,176 and 3,392/
