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Precocious puberty due to postmeningitic hydrocephalus
Precocious Puberty due to Postmeningitic Hydrocephalus Yuji Tomono, MD, Yutaka Maki, MD, Masami Ito, MD and Yoshitaka Nakada, MD A case of precocious puberty due to postmeningitic hydrocephalus was presented. Concentrations of serum gonadotropins and estradiol were found to be elevated, and the response of LH to LHRH was also high, similar to that in the late pubertal stage. CT scanning demonstrated marked dilatation of the third ventricle. It was considered that this was one of the factors which caused the precocious puberty. Tomono Y, Maki Y, Ito M, Nakada Y. Precocious puberty due to postmeningitic hydrocephalus. Brain Dev 1983;5:414-7
The most common pathological processes which cause precocious puberty of cerebral origin are hypothalamic hamartoma, astrocytoma, tumors of the pineal region , neurofibromatosis and suprasellar cysts. But the mechanisms that induce early sexual maturation remain unknown. Though hydrocephalus is also known as one of the causes, reports that described clinical features , endocrinological results or neuroradiological findings in detail are unexpectedly few. We present a case of precocious puberty probably due to postmeningitic hydrocephalus.
April 1982, she had vaginal bleeding. On admission, her height was 125.5 cm and her weight 28 kg, both in the standard ranges, but her head circumference was enlarged, 60.5 cm (normal: 51 .9 ± 1.5 cm), and her breast circumference was 72 cm (normal: 62.7 ± 4.8 cm). Her bone age was 13 years, four years ahead of her chronological age . The breasts were well developed into the Tanner stage 3 to 4, and mammary glands were also developed but no galactorrhea was noticed. Axillary hair was sparse but pubic hair was at
Case Report A nine-year-old girl was admitted to Tsukuba University Hospital in June 1982 with precocious puberty. She was born at full term by normal delivery. At the age of two months, she had meningitis, complicated by post-infectious hydrocephalus. In September 1972, a ventriculo-atrial shunt Was inserted at another neurosurgical unit. Although the shunt system was revised 8 times, her head circumference continued to increase till revision of the shunt system at our hospital in April 1978. At 7 years of age, her breasts began to develop, and in the following year, pubic hair began to grow. In
From the Department of Neurosurgery, Institute of Clinical Medicine, University of Tsukuba, Ibaraki. Received for publication: October 13, 1982. Accepted for publication : April 22,1983 .
Key words: Precocious puberty, meningitis, computed tomography.
hydrocephalus,
Correspondence address : Dr. Yuji Tomono, Institute of Clinical Medicine, University of Tsukuba, Sakuramura, Niihari-gun, Ibaraki 305, Japan.
Fig 1 Protograph of the girl at 9 years of age, showing enlargement of of the head, developed breasts and pubic hair.
B
A
ThelarChe
.
"I~;rml
\LZlI II ~t
(
60
zll
LH
PUDorCh ~
40
- LH
" enorc' U
... ,,"
4_
~
/
7
20
•••• 0
8
0
9
ieors
of
FSH ,,"--- --- ---
o'--...,.O--6:":O,----:,T20=-ml n .
Fig 2A Progress of sexual maturation alld elevation of serum gonadotro· pins. B: Serum gonadotropin levels after LHRH stimula· tion.
~
Fig 3 Coronal plane CT after con· trast demonstrating marked enlargement of the ven tricles. The structure of the bottom of the third ventricle cannot be recognized and is pressed against the pituitary gland. *: third ventricle, A : anterior horn, L : lateral horn of the lateral ventricle, P: pituitary gland, IC: internal carotid artery . CS: caver· nous sinus.
the Tanner stage 3. No palpable tumor was found in her abdomen (Fig 1). Her mental development was slightly retarded (6 years of mental age). Though the patient could walk alone, left spastic hemiparesis was present with left hyperactive deep tendon reflexes. Her visual acuity was preserved but the optic discs were pale and atrophic . The electroencephalogram showed diffuse dys·
rhythmic slowing with right-sided higher potential slow waves particularly in the temporal area. Laboratory findings on blood and urine were normal except for endocrinological studies. Endocrinological examinations revealed that serum gonadotropins were high (LH: 11.7 mIU/ml , FSH : 12.1 mIU/ml), which have gradually increased to the level of the late Tomono et al: Precocious puberty 415
pubertal stage during the last two years (Fig 2A). The response of gonadotropins, especially of LH , to LHRH was high, similar to that in pubertal age (Fig 2B). Serum estradiol was also high (51 pg/ml), but urinary chorionic gonadotropin was negative. Prolactin and other anterior pituitary hormones including thyroid hormones were within normal limits. The plain skull film showed a markedly enlarged skull, but the sella turcica was normal. Computed tomography demonstrated a marked panventricular dilatation, with an extremely thinned bifrontal and right temporal cerebral mantle. Past ventriculitis was suggested from the finding of a membranous projection in the lateral ventricle. On a coronal plane CT, the third ventricle was also seen to be dilated downward, being just adjacent to the hypophysis. The height of the hypophysis was 4 mm in normal range, but the structure of the ventral hypothalamus and the pituitary stalk could not be recognized in spite of thin-sliced and postcontrast CT examination. The shunt system was proved to be acting well by an RI-flowstudy. Discussion Though the mechanism of sexual maturation is very complicated, many investigators consider that the basic phenomenon, which occurs at the onset of puberty, is an increase of the threshold of the 'gonadostat' to the negative feedback of sex steroids [1]. That is to say, lowering of the sensitivity of the hypothalamus, which inhibits the release of LHRH, to sex steroids raises the levels of LHRH-gonadotropins-sex steroids. Moreover, it is said that elevation of gonadotropins during sleep [2] and appearance of positive feedback of estrogen in females [3] take part in sexual maturation processes. In many cases, including this case, precocious puberty of cerebral origin seems to be merely a phenomenon of premature activation of the 'normal' mechanism governing puberty. In precocious puberty with widespread intracranial lesions like hydrocephalus or inflammation, it is much more difficult to determine the responsible region in the central nervous system than in localized lesions like hamartomas. But recently, considerable numbers of cases of precocious puberty due to suprasellar cysts have been reported [4, 5]. 416 Brain & Development, Vol 5, No 4, 1983
Similarly in cases with hydrocephalus, it is likely that precocious puberty is due to the markedly enlarged third ventricle which has some influence on the hypothalamus in the same manner as suprasellar cysts. According to the questionnaire study in Japan [6], the proportion of hydrocephalus in the various causes of precocious puberty was 4 .9%. But reports with detailed clinical descriptions of the patients with hydrocephalus were unexpectedly few , and only eight cases were in conformity to this condition [7-11] . On reviewing these cases including the presented case, they were found to have some factors in common as follows: Eight of the 9 cases were female. This coincides with the evidence that idiopathic precocious puberty is more common in girls than in boys. Six children had a history of meningitis, and seven were not treated for hydrocephalus except for this girl whose shunt system had not functioned for a long time. In addition, optic atrophy was also observed in all of the cases. In conclusion, common factors in many of the cases are: (1) most are girls; (2) presence of cerebral damage by inflammation; and (3) presence of chronic intracranial hypertension due to untreated hydrocephalus. In addition to these factors, normal functioning of the anterior hypophysis may be needed to release sufficient quantities of hormones such as gonadotropins, growth hormones and so on. Precocious puberty cannot be induced by a destructive change of the hypothalamus. Though Dorff and Shapiro [8] reported an autopsy case with marked thinning of the base of the third ventricle, there has been no report in which detailed morphological changes were evaluated on CT. On the coronal CT in this case, the third ventricle was markedly dilated and the ventral hypothalamus was in paper-thin, while the appearance of the pituitary gland was preserved. So we conclude for this pathogenesis that the hypothalamic gonadostat was abolished by inflammatory change and by chronic pressure from the dilated third ventricle.
References 1. Grumbach MM, Roth Je, Kaplan SL, Kelch RP. Hypothalamic-pituitary regulation of puberty in man: Evidence and concepts derived from clinical research. In: Grumbach MM, Grave GD, Mayer
2.
3.
4.
5.
FE, eds. Control of the onset of puberty. New York: John Wiley and Sons, 1974: 115-66. Boyar R, Finkelstein J, Roffwarg H, Kapen S, Weitzman ED, Hellman 1. Synchronization of augmented luteinizing hormone secretion with sleep during puberty. N Engl J Med 1972;287: 582-6. Forest MG, De Peretti E, Bertrand J. Hypothalamic-pituitary-gonadal relationships in man from birth to puberty. Clin Endocrinol 1976;5: 551-69. Mori K, Hata K, Takaya K. Precocious puberty with fits of laughter and with a large cystic mass on the floor of the third ventricle (case report) (in Japanese). Clin Neurol (Tokyo) 1969;9: 254-60. Hung W, August GP, Brallier DR, Milhorat TH. Computerized tomography in the evaluation of isosexual precocity. Am J Dis Child 1980;134:
25-7 . 6. Hibi I. Central precocious puberty (in Japanese). Int Med (Tokyo) 1978 ;41:236-43. 7. Schlesinger B. Hydrocephalus with precocious puberty following post-basic meningitis. Proc Roy Soc Med 1935 ;28 :149. 8. Dorff GB, Shapiro LM. A clinicopathologic study of sexual precocity with hydrocephalus. Am J Dis Child 1937;53:481-99 . 9. Kahana L, Lebovitz H, Lusk W, et al. Endocrine manifestations of intracranial extrasellar lesions. J Clin Endocrinol Metab 1962;22:304-24. 10. Fideleff HL, Guitelman A, Mancini AM, et al. Puberte precoce vraie par hydrocephalie congenitale. Nouv Press Med 1975 ;4:2729. 11. Buonaguidi R, Ferdeghini M, Leoncini R, Tusini G. Hypothalamo-pituitary function in four cases of true precocious puberty. Child Brain 1982;9: 211-21.
Hemorrhagic Tendency as a Complication of Moxalactam Therapy in Bacterial Meningitis Wai-Ying Chan-Lui, MD, DCH, FRCPE, A.Barnard Stroebel, MB, ChB and Chap-Yung Yeung, MB, BS, DCH, FRCPE, FRCPG, FRCPC
Moxalactam penetrates cerebral spinal flUid (CSF) and subdural flUid well enough to be a promising antimicrobial for enteric bacterial meningitis in neonates and infants. Clinical trials in adults and children have found few adverse effects. Prolongation of prothrombin time (PT) and partial thromboplastin time (PTT) with or without bleeding was reported in adults. This paper reports this complication in two infants occurring at a time of clinical improvement following addition of Moxalactam to other antibiotics to which the meningitis had failed to respond. It is not certain if this complication was related to the underlying meningitis, the use of Moxalactam together with other antibiotics, or a combination of many factors. Further observation, close hemostatic monitoring, and timely vitamin K administration during its use are warranted. Chan-Lui WY, Stroebel AB, Yeung CY. Hemorrhagic tendency as a complication of Moxalactam therapy in bacterial meningitis. Brain Dev 1983;5:417-20
Moxalactam, a new parenteral l-oxa-~-lactam antibiotic, is highly effective in vitro against gram negative bacteria [1, 2], and produced
therapeutic results in experimental enteric bacillary meningitis [3] . Good penetration into CSF and subdural empyema was demonstrated
From the Department of Paediatrics, University of Hong Kong (WYC-L, CYY); Clinical Bacteriologist, Queen Mary Hospital, Hong Kong (ABS).
Key words: Parenteral Moxalactam, bacterial meningitis in infants.
Received for publication: March 1, 1983. Accepted for pUblication: July 18, 1983.
Correspondence address: Dr. W.Y. Chan-Lui, Department of Paediatrics, Queen Mary Hospital, Hong Kong.
The most common pathological processes which cause precocious puberty of cerebral origin are hypothalamic hamartoma, astrocytoma, tumors of the pineal region , neurofibromatosis and suprasellar cysts. But the mechanisms that induce early sexual maturation remain unknown. Though hydrocephalus is also known as one of the causes, reports that described clinical features , endocrinological results or neuroradiological findings in detail are unexpectedly few. We present a case of precocious puberty probably due to postmeningitic hydrocephalus.
April 1982, she had vaginal bleeding. On admission, her height was 125.5 cm and her weight 28 kg, both in the standard ranges, but her head circumference was enlarged, 60.5 cm (normal: 51 .9 ± 1.5 cm), and her breast circumference was 72 cm (normal: 62.7 ± 4.8 cm). Her bone age was 13 years, four years ahead of her chronological age . The breasts were well developed into the Tanner stage 3 to 4, and mammary glands were also developed but no galactorrhea was noticed. Axillary hair was sparse but pubic hair was at
Case Report A nine-year-old girl was admitted to Tsukuba University Hospital in June 1982 with precocious puberty. She was born at full term by normal delivery. At the age of two months, she had meningitis, complicated by post-infectious hydrocephalus. In September 1972, a ventriculo-atrial shunt Was inserted at another neurosurgical unit. Although the shunt system was revised 8 times, her head circumference continued to increase till revision of the shunt system at our hospital in April 1978. At 7 years of age, her breasts began to develop, and in the following year, pubic hair began to grow. In
From the Department of Neurosurgery, Institute of Clinical Medicine, University of Tsukuba, Ibaraki. Received for publication: October 13, 1982. Accepted for publication : April 22,1983 .
Key words: Precocious puberty, meningitis, computed tomography.
hydrocephalus,
Correspondence address : Dr. Yuji Tomono, Institute of Clinical Medicine, University of Tsukuba, Sakuramura, Niihari-gun, Ibaraki 305, Japan.
Fig 1 Protograph of the girl at 9 years of age, showing enlargement of of the head, developed breasts and pubic hair.
B
A
ThelarChe
.
"I~;rml
\LZlI II ~t
(
60
zll
LH
PUDorCh ~
40
- LH
" enorc' U
... ,,"
4_
~
/
7
20
•••• 0
8
0
9
ieors
of
FSH ,,"--- --- ---
o'--...,.O--6:":O,----:,T20=-ml n .
Fig 2A Progress of sexual maturation alld elevation of serum gonadotro· pins. B: Serum gonadotropin levels after LHRH stimula· tion.
~
Fig 3 Coronal plane CT after con· trast demonstrating marked enlargement of the ven tricles. The structure of the bottom of the third ventricle cannot be recognized and is pressed against the pituitary gland. *: third ventricle, A : anterior horn, L : lateral horn of the lateral ventricle, P: pituitary gland, IC: internal carotid artery . CS: caver· nous sinus.
the Tanner stage 3. No palpable tumor was found in her abdomen (Fig 1). Her mental development was slightly retarded (6 years of mental age). Though the patient could walk alone, left spastic hemiparesis was present with left hyperactive deep tendon reflexes. Her visual acuity was preserved but the optic discs were pale and atrophic . The electroencephalogram showed diffuse dys·
rhythmic slowing with right-sided higher potential slow waves particularly in the temporal area. Laboratory findings on blood and urine were normal except for endocrinological studies. Endocrinological examinations revealed that serum gonadotropins were high (LH: 11.7 mIU/ml , FSH : 12.1 mIU/ml), which have gradually increased to the level of the late Tomono et al: Precocious puberty 415
pubertal stage during the last two years (Fig 2A). The response of gonadotropins, especially of LH , to LHRH was high, similar to that in pubertal age (Fig 2B). Serum estradiol was also high (51 pg/ml), but urinary chorionic gonadotropin was negative. Prolactin and other anterior pituitary hormones including thyroid hormones were within normal limits. The plain skull film showed a markedly enlarged skull, but the sella turcica was normal. Computed tomography demonstrated a marked panventricular dilatation, with an extremely thinned bifrontal and right temporal cerebral mantle. Past ventriculitis was suggested from the finding of a membranous projection in the lateral ventricle. On a coronal plane CT, the third ventricle was also seen to be dilated downward, being just adjacent to the hypophysis. The height of the hypophysis was 4 mm in normal range, but the structure of the ventral hypothalamus and the pituitary stalk could not be recognized in spite of thin-sliced and postcontrast CT examination. The shunt system was proved to be acting well by an RI-flowstudy. Discussion Though the mechanism of sexual maturation is very complicated, many investigators consider that the basic phenomenon, which occurs at the onset of puberty, is an increase of the threshold of the 'gonadostat' to the negative feedback of sex steroids [1]. That is to say, lowering of the sensitivity of the hypothalamus, which inhibits the release of LHRH, to sex steroids raises the levels of LHRH-gonadotropins-sex steroids. Moreover, it is said that elevation of gonadotropins during sleep [2] and appearance of positive feedback of estrogen in females [3] take part in sexual maturation processes. In many cases, including this case, precocious puberty of cerebral origin seems to be merely a phenomenon of premature activation of the 'normal' mechanism governing puberty. In precocious puberty with widespread intracranial lesions like hydrocephalus or inflammation, it is much more difficult to determine the responsible region in the central nervous system than in localized lesions like hamartomas. But recently, considerable numbers of cases of precocious puberty due to suprasellar cysts have been reported [4, 5]. 416 Brain & Development, Vol 5, No 4, 1983
Similarly in cases with hydrocephalus, it is likely that precocious puberty is due to the markedly enlarged third ventricle which has some influence on the hypothalamus in the same manner as suprasellar cysts. According to the questionnaire study in Japan [6], the proportion of hydrocephalus in the various causes of precocious puberty was 4 .9%. But reports with detailed clinical descriptions of the patients with hydrocephalus were unexpectedly few , and only eight cases were in conformity to this condition [7-11] . On reviewing these cases including the presented case, they were found to have some factors in common as follows: Eight of the 9 cases were female. This coincides with the evidence that idiopathic precocious puberty is more common in girls than in boys. Six children had a history of meningitis, and seven were not treated for hydrocephalus except for this girl whose shunt system had not functioned for a long time. In addition, optic atrophy was also observed in all of the cases. In conclusion, common factors in many of the cases are: (1) most are girls; (2) presence of cerebral damage by inflammation; and (3) presence of chronic intracranial hypertension due to untreated hydrocephalus. In addition to these factors, normal functioning of the anterior hypophysis may be needed to release sufficient quantities of hormones such as gonadotropins, growth hormones and so on. Precocious puberty cannot be induced by a destructive change of the hypothalamus. Though Dorff and Shapiro [8] reported an autopsy case with marked thinning of the base of the third ventricle, there has been no report in which detailed morphological changes were evaluated on CT. On the coronal CT in this case, the third ventricle was markedly dilated and the ventral hypothalamus was in paper-thin, while the appearance of the pituitary gland was preserved. So we conclude for this pathogenesis that the hypothalamic gonadostat was abolished by inflammatory change and by chronic pressure from the dilated third ventricle.
References 1. Grumbach MM, Roth Je, Kaplan SL, Kelch RP. Hypothalamic-pituitary regulation of puberty in man: Evidence and concepts derived from clinical research. In: Grumbach MM, Grave GD, Mayer
2.
3.
4.
5.
FE, eds. Control of the onset of puberty. New York: John Wiley and Sons, 1974: 115-66. Boyar R, Finkelstein J, Roffwarg H, Kapen S, Weitzman ED, Hellman 1. Synchronization of augmented luteinizing hormone secretion with sleep during puberty. N Engl J Med 1972;287: 582-6. Forest MG, De Peretti E, Bertrand J. Hypothalamic-pituitary-gonadal relationships in man from birth to puberty. Clin Endocrinol 1976;5: 551-69. Mori K, Hata K, Takaya K. Precocious puberty with fits of laughter and with a large cystic mass on the floor of the third ventricle (case report) (in Japanese). Clin Neurol (Tokyo) 1969;9: 254-60. Hung W, August GP, Brallier DR, Milhorat TH. Computerized tomography in the evaluation of isosexual precocity. Am J Dis Child 1980;134:
25-7 . 6. Hibi I. Central precocious puberty (in Japanese). Int Med (Tokyo) 1978 ;41:236-43. 7. Schlesinger B. Hydrocephalus with precocious puberty following post-basic meningitis. Proc Roy Soc Med 1935 ;28 :149. 8. Dorff GB, Shapiro LM. A clinicopathologic study of sexual precocity with hydrocephalus. Am J Dis Child 1937;53:481-99 . 9. Kahana L, Lebovitz H, Lusk W, et al. Endocrine manifestations of intracranial extrasellar lesions. J Clin Endocrinol Metab 1962;22:304-24. 10. Fideleff HL, Guitelman A, Mancini AM, et al. Puberte precoce vraie par hydrocephalie congenitale. Nouv Press Med 1975 ;4:2729. 11. Buonaguidi R, Ferdeghini M, Leoncini R, Tusini G. Hypothalamo-pituitary function in four cases of true precocious puberty. Child Brain 1982;9: 211-21.
Hemorrhagic Tendency as a Complication of Moxalactam Therapy in Bacterial Meningitis Wai-Ying Chan-Lui, MD, DCH, FRCPE, A.Barnard Stroebel, MB, ChB and Chap-Yung Yeung, MB, BS, DCH, FRCPE, FRCPG, FRCPC
Moxalactam penetrates cerebral spinal flUid (CSF) and subdural flUid well enough to be a promising antimicrobial for enteric bacterial meningitis in neonates and infants. Clinical trials in adults and children have found few adverse effects. Prolongation of prothrombin time (PT) and partial thromboplastin time (PTT) with or without bleeding was reported in adults. This paper reports this complication in two infants occurring at a time of clinical improvement following addition of Moxalactam to other antibiotics to which the meningitis had failed to respond. It is not certain if this complication was related to the underlying meningitis, the use of Moxalactam together with other antibiotics, or a combination of many factors. Further observation, close hemostatic monitoring, and timely vitamin K administration during its use are warranted. Chan-Lui WY, Stroebel AB, Yeung CY. Hemorrhagic tendency as a complication of Moxalactam therapy in bacterial meningitis. Brain Dev 1983;5:417-20
Moxalactam, a new parenteral l-oxa-~-lactam antibiotic, is highly effective in vitro against gram negative bacteria [1, 2], and produced
therapeutic results in experimental enteric bacillary meningitis [3] . Good penetration into CSF and subdural empyema was demonstrated
From the Department of Paediatrics, University of Hong Kong (WYC-L, CYY); Clinical Bacteriologist, Queen Mary Hospital, Hong Kong (ABS).
Key words: Parenteral Moxalactam, bacterial meningitis in infants.
Received for publication: March 1, 1983. Accepted for pUblication: July 18, 1983.
Correspondence address: Dr. W.Y. Chan-Lui, Department of Paediatrics, Queen Mary Hospital, Hong Kong.