- Email: [email protected]
Anterior pituitary function in a neonate with craniofacial dysraphia
1 090
Letters to the Editor
2. Smith, D. W.: Recognizable patterns of h u m a n malformation, Philadelphia, 1970, W. B. Saunders Company, pp. 358 and 359 (Appendix). 3. Fleischer, N., Lorente, M., Kirkland, J., Kirkland, R., Clayton, G., and Calderon, M.: Synthetic thyrotropin releasing factor as a test of pituitary thyrotropin reserve, J. Clin. Endocrinol. 34: 617, 1972. 4. Haworth, J. D., Medovy, H., and Lewis, A. J.: Cebocephaly with endocrine dysgenesis, J. PEDIATR, 59: 726, 1961.
Anterior pituitary function in a neonate ~vith craniofacial dysraphia To the Editor: Hypofunction of the anterior pituitary gland has been observed in some patients with midline facial anomalies. 1, z In this report we describe a neonate with a midline facial cleft associated with a n anterior encephalomeningocele s in w h o m anterior pituitary function was normal.
From the Divisions o/Pediatrics and Surgery, Albert Einstein Medical Center, and Departments of Pediatrics and Surgery, Temple University School of Medicine. Supported by United States Public Health Service Grant HD 04840.
The Journal o/ Pediatrics December 1973
CASE REPORT Patient T. R. (AEMC No. 201358), a full-term female infant, was delivered vaginally to a 22-yearold gravida 3, para 2, woman following an uncomplicated gestation without maternal exposure to known teratogenic agents. Examination revealed a midline lobulated mass which divided vertically the upper portion of the face into two halves with widely spaced orbits and nares. Ventriculography demonstrated that the anterior facial mass communicated with the right lateral ventricle (Fig. 1). Minimal dilatation of the third ventricle was also observed. There were no anomalies of the cardiorespiratory, genitourinary, or gastrointestinal systems. The results of a complete blood count, urinalysis, serum calcium and electrolyte determinations and amino acid chromatography, as well as fasting blood glucose and blood urea nitrogen levels were normal. Chromosome constitution was 4 6 / X X . S e e r e l a t e d l e t t e r , p. 1088. EIectroencephalography demonstrated interhemispheric asymmetry with depression of normal rhythm over the left cerebral hemisphere and two independent foci of paroxysmal activity over the right. There was normal secretion of growth hormone, thyrotropin, and adrenocorticotropin (assessed indirectly by determination of plasma cortisol levels) (Table I). Serum insulin levels increased after glucose ingestion. The dural defect in the frontal fossa of the skull was closed at 2 weeks of age by application of a paracranial graft. The infant tolerated the pro-
VENTRICLE
Fig. 1. Patient T. R. at 4 days of age (left). The encephalocele is the pedunculated mass at the right corner of the mouth. T h e line drawing (right) depicts the relationship of the cerebral ventricular system and encephalocele to the craniofacial anomaly.
Volume 83 Number 6
Letters to the Editor
1 09 1
T a b l e I. A n t e r i o r p i t u i t a r y f u n c t i o n in a n e o n a t e w i t h c r a n i o f a c i a l d y s r a p h i a
Glucose tolerance test (1.75 Gm./Kg. by mouth--5 days) Glucose (mg./100 ml.) Insulin (~U/ml.) Growth hormone (ng./ml.)
Insulin tolerance test (0.1 U/Kg. intravenously-6 days) Glucose Cortisol (/zg/100 ml.) Growth hormone
Thyrotropin-releasing hormone (5 I~g/kg. intravenously-7 days) Thyrotropin (#U/ml.) Thyroxine (#g/100 ml.) Triiodothyronine (ng./100 ml.)
0
+15
55 20 8.1
95 42 6.8
-30
0
83 -20.5
73 42 22.2
-6
0
4.4 9.7 9O
6.4
I
+30 123 39 3.9
cedure but postoperatively developed seizures which were controlled with phenobarbital. At 8 weeks of age the major portion of the encephalocele was removed. Throughout the hospitalization the infant was nourished orally and by gavage, but at the time of discharge had gained but 7 ounces over birthweight. The patient was discharged at 10 weeks of age to be followed as an outpatient pending plastic surgical correction of the anomaly at a later date. DISCUSSION In the patient reported the anterior encephalomeningocele was associated with failure of midline facial fusion, cleft lip, and cleft palate. The chromosome karyotype was normal eliminating trisomy 13-15 as a cause of the anomaly. The facial anomaly may have been the result of a teratogenic influence early in gestation because development of this portion of the central nervous system is completed by 4 weeks. Although deficiency of growth hormone secretion and growth retardation have been documented in some patients'with failure of midline facial fusion, 1, 2 present data indicate that in the neonatal period the hypothalamic-anterior hypophyseal axis of this patient was intact. The resting levels of growth hormone were slightly elevated, a finding previously observed in neonates, 4 declined slightly during glucose administration" and increased during insulin-induced hypoglycemia. Plasma corti~ol levels were elevated in resting specimens, perhaps representing effects of preceding stress. Serum thyrotropin concentrations increased following administration
153 68 5.2
100 74 3.2
180
120
25 -34.2
38 50 29.1
65 -15.9
+15
Time (min.) 30 ] 60
17
36.5
55 -20.2
26
I 240
73 7 8.2
Time (min.) 60 ] 90
1+30
[
Time (min.) 60 T 12o
120 13.5
60 6 5.1
[
I 300 70 31 5.7
180 5.0
of thyrotropin-releasing hormone, 5 suggesting that the pituitary of the young infant is responsive to this hypothalamie peptide, as it is to gonadotropin-releasing hormoneY Pancreatic beta cell function during hyperglycemia was also appropriate. The authors thank Drs. H. Punnett and M. Kistenmacher for performing the karyotype analysis, and Dr. M. Anderson, Abbott Laboratories, for supplying synthetic thyrotropin-releasing hormone. Dr. R. Utiger kindly performed the determinations of thyrotropin, thyroxine and triiodothyronine. Mr. K. Goodman executed the schematic drawing. The technical assistance of G. Duckett and H. Kamali, and the secretarial assistance of Mrs. E. Morris is appreciatively acknowledged.
Rehka Yagnik, M.D. Rose Marie Reber, M.D. Richard Katz, M.D. Allen W. Root, M.D. Division of Pediatrics and Surgery Albert Einstein Medical Center Philadelphia, Pa. Departments of Pediatrics and Surgery Temple University School of Medicine Philadelphia, Pa.
REFERENCES
1. Laron, Z., Taube, E., and Kaplan, I.: Pituitary growth hormone insufficiency associated with cleft lip and palate. An embryonal developmental defect, Helv. Pediatr. Acta 24: 576, 1969.
1 09 2
Letters to the Editor
2. Hoyt, W. F., Kaplan, S. L., Grumbach, M. M., and Glaser, J. S.: Septo-optic dysplasia and pituitary dwarfism, Lancet 1: 893, 1970. 3. Matson, D. D.: Neurosurgery of infancy and childhood, ed. 2, Springfield, Ill., 1969, Charles C Thomas, Publisher, pp. 68-74. 4. Root, A. W.: Human pituitary growth hormone, Springfield, Ill., 1972, Charles C Thomas, Publisher, pp. 45-46. 5. Anderson, M. S., Bowers, C. Y., Kastin, A. J.,
The Journal o/ Pediatrics December 1973
Schalch, D. S., Schally, A. V., Snyder, P. J., Utiger, R. D., Wilber, J. F., and Wise, S. J.: Synthetic thyrotropin-releasing hormone. A potent stimulator of thyrotropin secretion in man, N. Engl. J. Med. 285: 1279, 1971. 6. Root, A. W., Smith, G. P,, Dhariwal, A. P. S., and McCann, S. M.: Luteinizing hormone releasing activity of crude ovine hypothalamic extract in man, Nature 221: 570, 1969.
Letters to the Editor
2. Smith, D. W.: Recognizable patterns of h u m a n malformation, Philadelphia, 1970, W. B. Saunders Company, pp. 358 and 359 (Appendix). 3. Fleischer, N., Lorente, M., Kirkland, J., Kirkland, R., Clayton, G., and Calderon, M.: Synthetic thyrotropin releasing factor as a test of pituitary thyrotropin reserve, J. Clin. Endocrinol. 34: 617, 1972. 4. Haworth, J. D., Medovy, H., and Lewis, A. J.: Cebocephaly with endocrine dysgenesis, J. PEDIATR, 59: 726, 1961.
Anterior pituitary function in a neonate ~vith craniofacial dysraphia To the Editor: Hypofunction of the anterior pituitary gland has been observed in some patients with midline facial anomalies. 1, z In this report we describe a neonate with a midline facial cleft associated with a n anterior encephalomeningocele s in w h o m anterior pituitary function was normal.
From the Divisions o/Pediatrics and Surgery, Albert Einstein Medical Center, and Departments of Pediatrics and Surgery, Temple University School of Medicine. Supported by United States Public Health Service Grant HD 04840.
The Journal o/ Pediatrics December 1973
CASE REPORT Patient T. R. (AEMC No. 201358), a full-term female infant, was delivered vaginally to a 22-yearold gravida 3, para 2, woman following an uncomplicated gestation without maternal exposure to known teratogenic agents. Examination revealed a midline lobulated mass which divided vertically the upper portion of the face into two halves with widely spaced orbits and nares. Ventriculography demonstrated that the anterior facial mass communicated with the right lateral ventricle (Fig. 1). Minimal dilatation of the third ventricle was also observed. There were no anomalies of the cardiorespiratory, genitourinary, or gastrointestinal systems. The results of a complete blood count, urinalysis, serum calcium and electrolyte determinations and amino acid chromatography, as well as fasting blood glucose and blood urea nitrogen levels were normal. Chromosome constitution was 4 6 / X X . S e e r e l a t e d l e t t e r , p. 1088. EIectroencephalography demonstrated interhemispheric asymmetry with depression of normal rhythm over the left cerebral hemisphere and two independent foci of paroxysmal activity over the right. There was normal secretion of growth hormone, thyrotropin, and adrenocorticotropin (assessed indirectly by determination of plasma cortisol levels) (Table I). Serum insulin levels increased after glucose ingestion. The dural defect in the frontal fossa of the skull was closed at 2 weeks of age by application of a paracranial graft. The infant tolerated the pro-
VENTRICLE
Fig. 1. Patient T. R. at 4 days of age (left). The encephalocele is the pedunculated mass at the right corner of the mouth. T h e line drawing (right) depicts the relationship of the cerebral ventricular system and encephalocele to the craniofacial anomaly.
Volume 83 Number 6
Letters to the Editor
1 09 1
T a b l e I. A n t e r i o r p i t u i t a r y f u n c t i o n in a n e o n a t e w i t h c r a n i o f a c i a l d y s r a p h i a
Glucose tolerance test (1.75 Gm./Kg. by mouth--5 days) Glucose (mg./100 ml.) Insulin (~U/ml.) Growth hormone (ng./ml.)
Insulin tolerance test (0.1 U/Kg. intravenously-6 days) Glucose Cortisol (/zg/100 ml.) Growth hormone
Thyrotropin-releasing hormone (5 I~g/kg. intravenously-7 days) Thyrotropin (#U/ml.) Thyroxine (#g/100 ml.) Triiodothyronine (ng./100 ml.)
0
+15
55 20 8.1
95 42 6.8
-30
0
83 -20.5
73 42 22.2
-6
0
4.4 9.7 9O
6.4
I
+30 123 39 3.9
cedure but postoperatively developed seizures which were controlled with phenobarbital. At 8 weeks of age the major portion of the encephalocele was removed. Throughout the hospitalization the infant was nourished orally and by gavage, but at the time of discharge had gained but 7 ounces over birthweight. The patient was discharged at 10 weeks of age to be followed as an outpatient pending plastic surgical correction of the anomaly at a later date. DISCUSSION In the patient reported the anterior encephalomeningocele was associated with failure of midline facial fusion, cleft lip, and cleft palate. The chromosome karyotype was normal eliminating trisomy 13-15 as a cause of the anomaly. The facial anomaly may have been the result of a teratogenic influence early in gestation because development of this portion of the central nervous system is completed by 4 weeks. Although deficiency of growth hormone secretion and growth retardation have been documented in some patients'with failure of midline facial fusion, 1, 2 present data indicate that in the neonatal period the hypothalamic-anterior hypophyseal axis of this patient was intact. The resting levels of growth hormone were slightly elevated, a finding previously observed in neonates, 4 declined slightly during glucose administration" and increased during insulin-induced hypoglycemia. Plasma corti~ol levels were elevated in resting specimens, perhaps representing effects of preceding stress. Serum thyrotropin concentrations increased following administration
153 68 5.2
100 74 3.2
180
120
25 -34.2
38 50 29.1
65 -15.9
+15
Time (min.) 30 ] 60
17
36.5
55 -20.2
26
I 240
73 7 8.2
Time (min.) 60 ] 90
1+30
[
Time (min.) 60 T 12o
120 13.5
60 6 5.1
[
I 300 70 31 5.7
180 5.0
of thyrotropin-releasing hormone, 5 suggesting that the pituitary of the young infant is responsive to this hypothalamie peptide, as it is to gonadotropin-releasing hormoneY Pancreatic beta cell function during hyperglycemia was also appropriate. The authors thank Drs. H. Punnett and M. Kistenmacher for performing the karyotype analysis, and Dr. M. Anderson, Abbott Laboratories, for supplying synthetic thyrotropin-releasing hormone. Dr. R. Utiger kindly performed the determinations of thyrotropin, thyroxine and triiodothyronine. Mr. K. Goodman executed the schematic drawing. The technical assistance of G. Duckett and H. Kamali, and the secretarial assistance of Mrs. E. Morris is appreciatively acknowledged.
Rehka Yagnik, M.D. Rose Marie Reber, M.D. Richard Katz, M.D. Allen W. Root, M.D. Division of Pediatrics and Surgery Albert Einstein Medical Center Philadelphia, Pa. Departments of Pediatrics and Surgery Temple University School of Medicine Philadelphia, Pa.
REFERENCES
1. Laron, Z., Taube, E., and Kaplan, I.: Pituitary growth hormone insufficiency associated with cleft lip and palate. An embryonal developmental defect, Helv. Pediatr. Acta 24: 576, 1969.
1 09 2
Letters to the Editor
2. Hoyt, W. F., Kaplan, S. L., Grumbach, M. M., and Glaser, J. S.: Septo-optic dysplasia and pituitary dwarfism, Lancet 1: 893, 1970. 3. Matson, D. D.: Neurosurgery of infancy and childhood, ed. 2, Springfield, Ill., 1969, Charles C Thomas, Publisher, pp. 68-74. 4. Root, A. W.: Human pituitary growth hormone, Springfield, Ill., 1972, Charles C Thomas, Publisher, pp. 45-46. 5. Anderson, M. S., Bowers, C. Y., Kastin, A. J.,
The Journal o/ Pediatrics December 1973
Schalch, D. S., Schally, A. V., Snyder, P. J., Utiger, R. D., Wilber, J. F., and Wise, S. J.: Synthetic thyrotropin-releasing hormone. A potent stimulator of thyrotropin secretion in man, N. Engl. J. Med. 285: 1279, 1971. 6. Root, A. W., Smith, G. P,, Dhariwal, A. P. S., and McCann, S. M.: Luteinizing hormone releasing activity of crude ovine hypothalamic extract in man, Nature 221: 570, 1969.