Journal of Neuro-Ophthalmology, June 1998, Volume 18, Issue 2

Pituitary Adenoma in Children

Pituitary adenoma is an uncommon intracranial tumor of children. The authors retrospectively reviewed the records of 10 patients younger than 17 years of age with pituitary adenoma. Five patients had visual loss at presentation. Four of these five patients with visual loss and extrasellar tumor extension were adolescents (12-15 years of age). Seven of 10 patients underwent neurosurgery. Of the five patients with visual loss, three patients experienced visual improvement, one patient was unchanged, and one patient did not have follow-up. The visual loss in these patients tended to be more severe and more likely to be associated with optic atrophy than adult patients. Although they are relatively uncommon, ophthalmologists should be aware that pituitary adenomas may occur in children and that these tumors when present in the pubertal period may be more likely to exhibit extrasellar extension or invasiveness.

Journal of Neuro- Ophthalmology 18( 2): 102- 105, 1998. © 1998 Lippincott- Raven Publishers, Philadelphia Pituitary Adenoma in Children Andrew G. Lee, M. D., Paul D. Sforza, M. D., Arman K. Fard, M. D., Michael X. Repka, M. D., David S. Baskin, M. D., and Robert C. Dauser, M. D. Pituitary adenoma is an uncommon intracranial tumor of chil­dren. The authors retrospectively reviewed the records of 10 patients younger than 17 years of age with pituitary adenoma. Five patients had visual loss at presentation. Four of these five patients with visual loss and extrasellar tumor extension were adolescents ( 12- 15 years of age). Seven of 10 patients under­went neurosurgery. Of the five patients with visual loss, three patients experienced visual improvement, one patient was un­changed, and one patient did not have follow- up. The visual loss in these patients tended to be more severe and more likely to be associated with optic atrophy than adult patients. Al­though they are relatively uncommon, ophthalmologists should be aware that pituitary adenomas may occur in children and that these tumors when present in the pubertal period may be more likely to exhibit extrasellar extension or invasiveness. Key Words: Pituitary adenoma- Pediatric. Pituitary adenoma is an uncommon intracranial tumor in children ( 1- 20). Although several reports on child­hood pituitary adenoma have appeared in the literature previously, to our knowledge, no series appear in the ophthalmologic literature. We present nine cases of pi­tuitary adenoma in childhood and review the English-language literature on pituitary adenomas in children younger than 17 years of age. METHODS The medical records of all patients younger than 17 years of age with the diagnosis of pituitary adenoma were retrospectively reviewed from the Baylor College of Medicine and the Texas Children's Hospital in Hous­ton, Texas, and the Wilmer Eye Institute, the Johns Hopkins Medical Institutions in Baltimore, Maryland, between the years 1989 and 1996. Chart information ob- Manuscript received July 22, 1997; accepted January 19, 1998. From the Departments of Ophthalmology ( A. G. L., P. D. S.), Neurol­ogy ( A. G. L.), and Neurosurgery ( A. G. L., D. S. B., R. C. D.), Baylor Col­lege of Medicine; the Division of Neurosurgery ( A. G. L.), M. D. Ander­son Cancer Center, the University of Texas, Houston, Texas, and the Department of Ophthalmology ( A. K. F., M. X. R.), the Wilmer Eye In­stitute, the Johns Hopkins Medical Institutions, Baltimore, Maryland, U. S. A. Address correspondence and reprint requests to Andrew G. Lee, M. D., Department of Ophthalmology, Baylor College of Medicine, 6565 Fannin St. NC- 205, Houston, TX 77030, U. S. A. tained included patient age, gender, initial ophthalmo­logic examination findings, initial signs and symptoms, endocrinologic findings, surgical, medical, and radiation therapy as applicable, and ophthalmologic examination at last follow- up visit. Patients 17 years of age or older were excluded. RESULTS Ten patient records with pituitary adenoma in child­hood were identified: four patients ( 40%) from Baylor College of Medicine, and 6 patients ( 60%) from the Johns Hopkins Medical Institutions ( Table 1). Patient age ranged from 2 to 16 years ( mean age, 12.3 years; median age, 14 years). Five patients ( 50%) had visual loss at initial presentation, whereas five patients ( 50%) had no visual loss. Four of the five patients with visual loss were adolescents ( ages 12, 15, 15, and 15 years) and one patient was 2 years, 4 months of age. Four of the five patients with visual loss ( 80%) had documented optic atrophy in both eyes at presentation. The visual field defect was a bitemporal or temporal hemianopia in the four patients with visual loss in whom formal visual fields were performed ( Cases 6, 7, 9, and 10). Visual acuity in the patients with visual loss ranged from 20/ 40 to light perception. Patients with visual loss had severe (< 20/ 100) loss of visual acuity in at least one eye. Seven of our 10 patients ( 70%) underwent surgery. The surgical approaches were two transfrontal cranioto­mies, two primary transsphenoidal approaches, one pri­mary craniotomy followed by a transsphenoidal resec­tion, one primary transsphenoidal followed by a repeat transsphenoidal resection, and one transsphenoidal resec­tion followed by craniotomy for further tumor debulking. One patient ( 10%) was treated medically, and two pa­tients ( 20%) did not undergo treatment. Two patients ( 20%) received postoperative radiation therapy ( Cases 6 and 9). Of the five patients with visual loss, three ( 60%) experienced visual improvement ( one patient had a re­turn of visual acuity to 20/ 20 with a normal visual field in both eyes- Case 7), one patient ( 20%) was unchanged ( Case 6), and one patient ( 20%) had worsening vision after primary transsphenoidal resection and has yet to return for follow- up after a craniotomy for further tumor resection ( Case 10). 102 PITUITARY ADENOMA IN CHILDREN 103 TABLE 1. Pituitary adenomas in childhood Case, age, gender 1. 2 4/ 12 years M 2. 15 7/ 12 years M 3. 13 1/ 12 years M 4. 7 7/ 12 years F 5. 13 1/ 12 years F 6. 12 years M 7. 15 years F 8. 15 years M 9. 15 years M 10. 15 3/ 12 years F M, male; F, female. VA, visual acuity. RE, right eye; LE, left GH, growth hormone; Preoperative symptoms and signs VA LP RE 6/ 30 LE Optic atrophy OU Height and weight gain Headaches Normal eye exam Incidental finding Normal eye exam Precocious puberty Normal eye exam Headaches, growth retardation Normal eye exam VA 20/ 70 RE 20/ 100 LE Complete bitemporal hemianopsia Optic atrophy OU VA 20/ 40 RE 20/ 100 LE Temporal hemianopia LE Optic atrophy OU Weight gain, acne, " buffalo hump" No visual symptoms VA HM RE 20/ 200 LE Nasal island only RE Temporal hemianopsia LE Optic atrophy OU Recurrent visual loss requiring a second surgery VA 20/ 20 RE, 20/ 300 LE Bitemporal hemianopia Headaches No optic atrophy eye; OU, both eyes. PRL, prolactin. Endocrine status High GH, PRL Normal Normal Not documented Low GH Hypothyroid High PRL Gushing's disease Normal Normal Treatment Craniotomy Transsphenoidal None None Medical treatment Craniotomy 2nd surgery via transsphenoidal Radiotherapy Bromocriptine Craniotomy Transsphenoidal Transsphenoidal 2nd transsphenoidal Radiotherapy Transsphenoidal, then craniotomy Postoperative results or comments LP RE 12/ 12 LE Normal Normal acuity after 26 months followup Unchanged visual acuity and visual field Normal visual acuity and normal visual field after 6 months Remission HM RE 20/ 20 LE Unchanged RE Improved LE 20/ 20 RE CF LE after trans­sphenoidal Endocrine status was abnormal in five patients ( 50%). The endocrine abnormalities included high growth hor­mone and elevated prolactin levels in one patient, el­evated prolactin in one patient, low growth hormone in one patient, hypothyroidism in one patient, and Cush-ing's disease in one patient. Four patients ( 40%) had normal endocrine status, and one patient ( 10%) did not have any documented endocrine evaluation. DISCUSSION Pituitary adenoma is an uncommon brain tumor in childhood. It accounts for only 1 % to 2% of all intracra­nial tumors in children ( 1- 18). Several authors ( 5,17) have suggested that pituitary adenoma may be more likely to be invasive and more often extrasellar in chil­dren than in adults. Other authors have not confirmed this finding ( 18). This discrepancy may be partially due to the lack of a defined age range for " pediatric" popu­lations in the various studies reported in the literature ( 1- 4,6,7,9- 18). Many of the studies in fact included pa­tients up to 20 years of age and older. These older pa­tients were postpubertal. The behavior of pituitary ade­nomas may be different for children of prepubertal or pubertal age compared with postpubertal patients ( 5). To minimize this confounding factor, we have defined ' ' pe­diatric" patients as patients being younger than 17 years of age at diagnosis. Although it is somewhat arbitrary, we believe that age 17 years is a reasonable demarcation for the " pediatric" age group. We recognize, however, that some patients may reach puberty before age 17 years. Visual symptoms and signs ( due to suprasellar exten­sion and compression of the optic nerve, chiasm, or tract) have been reported to be less frequent in children with pituitary adenoma than in adults. The most common pre­senting signs of pituitary adenoma in children since the advent of modern neuroimaging are endocrinologic de­ficiency, including failure of growth or sexual maturation ( 1,2,4- 13,15- 18). Most of the pituitary adenomas re­ported in childhood have been prolactin- secreting, adre­nocorticotropic hormone ( ACTH)- secreting, or growth hormone- secreting tumors ( 8,9,13). Maira et al. reported 52 cases treated with surgery before the age of 21 years and 52 cases treated after the age of 20 years but in whom the clinical history began before the age of 21 J Neuro- Ophlhalmol, Vol. 18, No. 2, 1998 104 A. G. LEE ET AL. years ( 13). Prolactinomas ( 65%) were thought to be the most common tumor in this series, followed by nonse-creting ( 18%), growth hormone- secreting ( 13%), and ACTH- secreting ( 4%) tumors ( 13). Laws et a), reviewed transsphenoidal microsurgical results in 1,400 pituitary adenomas treated at the Mayo Clinic between 1972 and 1986 ( 9). Approximately 6% of the tumors occurred in patients younger than 20 years old. Of these 76 cases, 43 ( 57%) had prolactinomas, 19 ( 25%) had Cushing's dis­ease, 3 ( 4%) had Nelson's syndrome, 9 ( 12%) had growth hormone- secreting tumors, 1 ( 1.3%) had a thy­roid- stimulating hormone adenoma, and 1 ( 1.3%) had a null- cell macroadenoma ( 9). Transsphenoidal surgery was " generally effective" in these patients with " suc­cessful tumor removal and preservation of normal func­tion in nearly every case." Preoperative visual loss, when present, improved in all patients and there were no operative mortalities. The indications for the transsphenoidal approach in children are thought to be similar to the indications for adult pituitary surgery ( 12). Transsphenoidal surgery for pituitary adenomas in children is relatively safe and ef­fective. Partington et al. reported 36 patients (< 17 years of age) who underwent transsphenoidal surgery. Signifi­cant operative morbidity included steroid- induced psy­chosis in one patient and diabetes insipidus in three pa­tients ( resolved in two patients) ( 19). Dyer et al. re­viewed transsphenoidal surgery in 66 children (< 16 years of age) and reported an overall cure rate of 78% for Cushing's disease, but only a 12% control rate for growth hormone tumors ( 20). Twelve of 18 ( 67%) pro-lactin- secreting tumors required additional treatment ( ei­ther medical or radiation therapy) for persistently el­evated prolactin levels. Eighteen percent of the children in this series required drilling of an incompletely pneu-matized sphenoid sinus to reach the sella, but these au­thors did not consider this a contraindication to trans­sphenoidal surgery. Radiation therapy is thought to be indicated for tumors with recurrent mass effect after pri­mary medical and surgical therapy ( 8). Ortiz- Suarez et al. reported 3 patients ( 2.6%) younger than 16 years of age of 115 total patients with pituitary adenomas ( 17). These authors believed that all ( 100%) of their adolescent patients had extracapsular tumor exten­sion ( all had oculomotor nerve palsies), compared with a 10% to 15% rate of extrasellar extension in their adult patients. Richmond and Wilson described nine patients younger than 17 years of age ( only one patient younger than 9 years of age) ( 18). Most patients were diagnosed during evaluations for delayed puberty. In addition to these 9 patients, these authors described 16 patients older than 17 years of age. Of the total 25 patients, 12 had optic atrophy and 16 patients had visual field defects ( 4 tem­poral unilateral, 8 bitemporal, and 4 homonymous hemi­anopsias). All 25 patients with preoperative visual field loss improved after surgery ( 23 transsphenoidal and 2 craniotomy and optic nerve decompression). Significant suprasellar extension or " invasiveness" was present in 36% of this series ( 18). Laws et al. reported 76 patients younger than 20 years of age, but only 5 patients were younger than 12 years of age. Macroadenomas were present in 49% of patients, and 10% were invasive ( 9). Haddad et al. reported 18 patients ( 5 with Cushing's disease and 13 prolactin- secreting tumors). Two of these patients had suprasellar extension with visual loss ( hom­onymous hemianopsia) requiring multiple surgeries and radiation therapy ( 8). Fraioli et al. reported nine patients with pituitary ad­enomas with presentation from 11 to 15 years of age. Seven tumors ( 77%) were thought to be " invasive" ( 5). These authors concluded that " pituitary adenomas aris­ing in puberty are or will become invasive." They ar­gued that the higher rate of ' ' invasive behavior'' in their series compared with the Richmond and Wilson series was related to their more precise definition of " pediat­ric" age. These authors reevaluated the 36% rate of " in­vasiveness" in the Richmond and Wilson series ( 18) and believed that these invasive cases occurred mainly in the nine patients who were in the postpubertal age group. Laws et al. believed that the incidence of macroad­enomas and invasive tumors was higher in children than adults ( 9). In our series, five patients ( 50%) had supra­sellar extension, of whom four were older than 12 years and one patient was younger than 12 years of age. We agree with previous authors ( 5,9,17) that pituitary ade­nomas with onset at puberty may be more likely to ex­hibit extrasellar extension and invasiveness than those tumors found in adults. Visual field and acuity loss in the report by Fraioli et al. occurred in eight ( 89%) of nine patients ( seven bitem­poral hemianopsias and one homonymous hemianopsia) and two patients ( 22%) had " ophthalmoplegia" ( 5). Seven of the eight ( 88%) patients with visual loss had improvement in vision after surgical ( transsphenoidal or subfrontal), medical ( bromocriptine in six patients), or radiation therapy. Mukai et al. reported five cases younger than 17 years of age ( 16). Four of these five patients ( 80%) had " visual defects," and three of these four ( 75%) patients had persistent " visual defects" after treatment with subtotal resection and radiation therapy ( 4,500- 5,700 cGy). Cook and Besser reported a 16- year-old boy with visual activity of counting fingers in the right eye and light perception in the left eye ( 3). Three months after surgical decompression of the optic chiasm, the visual acuity was 6/ 6 in the right eye and 6/ in the 9 left eye, with a residual left superior quadrantanopia. Grigsby et al. reported five patients younger than 17 years of age, of whom three had Cushing's disease, one had a chromophobe adenoma, and one Nelson's syn­drome. Of these five patients, four had no visual symp­toms, whereas one patient ( age 12 years) had " visual field loss" that improved after surgical decompression and radiation therapy ( 7). Laws et al. reported suprasellar extension with visual loss in three patients, all of whom had visual improvement after surgery ( 9). In our series, five patients had preoperative visual loss. After treatment, three patients ( 60%) experienced visual improvement, one patient ( 20%) was unchanged, and ./ Neiiro- Ophlllillinol, Vol. IS. No. 2, 199H PITUITARY ADENOMA IN CHILDREN 105 one patient ( 20%) worsened after transsphenoidal sur­gery and underwent a craniotomy. Follow- up is not available after the craniotomy in this last patient ( Case 10). From the results of our study and those reported in the literature, visual improvement after surgical decompres­sion for pituitary adenomas may not be as high for chil­dren as for adults, where postoperative improvement rates have been reported to be high as 70% to 90% ( 21,22). Vision loss in our patients at presentation tended to be more severe (< 20/ 100) and more likely to be asso­ciated with optic atrophy than in adults ( 22). These nega­tive visual prognostic indicators ( severe visual loss and optic atrophy) may account for the less successful visual results seen in children. It would be reasonable to suggest that children tend to report signs and symptoms ( includ­ing headache and visual loss) later in the course of dis­ease than adult patients. This delay in diagnosis and treatment may result in more permanent optic nerve damage and irreversible visual loss. Although they are relatively uncommon, ophthalmolo­gists should be aware that pituitary adenomas may occur in children and that these tumors when present in the pubertal period may be more likely to exhibit extrasellar extension or invasiveness. Acknowledgments: Supported in part by a grant from Re­search to Prevent Blindness, Inc., New York, New York, and the Koppelman Fund of the Neurological Research Foundation ( D. S. B.). 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