Pituitary tumors are relatively uncommon pediatric brain tumors, accounting for only 2 to 6% of tumors in children, adolescents, and young adults under the age of 20.1 The incidence increases throughout childhood, from 0.5% during the first decade of life, to 10% during the second decade, finally peaking during the third decade.2 The overwhelming majority of intrasellar tumors are benign, despite their ability to spread locally. Craniopharyngiomas account for roughly 80 to 90% of neoplasms arising in the sellar/suprasellar region; however, only approximately 25% of craniopharyngiomas are truly intrasellar lesions.3 Pituitary adenomas account for approximately 90% of intrasellar lesions. Other neoplasms that may infiltrate the pituitary include meningiomas, germinomas, hamartomas, lipomas, and teratomas. Dysembryogenic lesions, such as Rathke cleft cysts and dermoid/epidermoid cysts, also occur in the pediatric population. Finally, immunologic and infectious conditions involving the sella include histiocytosis X, tuberculosis, and sarcoidosis. Metastatic lesions to the pituitary gland are exceedingly uncommon in the pediatric population. Fortunately, pituitary apoplexy in a child is a rare event ( Table 21.1 ).
There are few historical reports of pediatric pituitary surgery. From The Pituitary Body and Its Disorders, we know that Cushing4 successfully utilized a sublabial transsphenoidal re-section for a few children with sellar lesions, most of whom had no definitive pathological diagnosis, but surely these lesions included pituitary adenomas and craniopharyngiomas.
The current methods of endoscopic endonasal approaches are used less frequently in the pediatric population, perhaps related to perceived unfavorable challenges, including small nostrils, narrow nasal cavities, and poor pneumatization of the sphenoid sinus; outcomes, however, are comparable to those performed through the traditional sublabial microscopic approach.5–7 Recovery ordinarily is quite rapid following pituitary surgery, and the child often leaves the hospital within a few days and is back to school and normal activities within 2 to 4 weeks. Long-term follow-up with a specialized team including a neurosurgeon and an endocrinologist are crucial for optimal outcomes.
Pituitary adenomas are the most common cause of pituitary disease in adults but rarely present during childhood (although the incidence increases during adolescence).8,9 Only 3.5 to 8.5% of all pituitary tumors are diagnosed by the age of 20 and only 25% of those present before the age of 12 (primarily corticotropinomas). Pituitary adenomas constitute less than 3% of supratentorial tumors in children.10 Although they are often sporadic, they can occur in the context of multiple endocrine neoplasia type 1 (MEN-1), McCune-Albright syndrome, Carney complex, or familial isolated pituitary adenomas (FIPA).11
A review of all published case series of transsphenoidal surgery for pediatric pituitary adenomas ( Table 21.2 ) demonstrates that prolactinomas are the most frequent adenoma subtype in children, followed by the corticotropin-secreting tumors and the somatotropinomas.6,9,12–24 Nonfunctioning pituitary adenomas are less common and account for only 3 to 10% of all pediatric pituitary tumors.13 Females are more likely to be diagnosed with pituitary adenomas (prolactin [PRL]- and adrenocorticotropic hormone [ACTH]-secreting adenomas), and males are more likely to be diagnosed with nonfunctioning macroadenomas.8
Signs and Symptoms
Presenting signs and symptoms are generally related to endocrine dysfunction, but vary with gender and maturity. Prepubertal children and pubescent boys typically present with headaches, visual complaints, and growth delay. Pubescent girls present with pubertal arrest and hypogonadism with or without galactorrhea.
Prolactinomas generally present at the time of or after puberty, with primary or secondary amenorrhea in girls.25,26 They are the most common pituitary tumor, comprising nearly 50% of pituitary tumors in children. The classic signs are headaches, visual complaints, growth delay, and pubertal delay/failure. Boys more frequently have macroprolactinomas, which are associated with a higher incidence of neurologic and ophthalmologic signs11 ( Table 21.3 ).
Corticotropinomas (Cushing disease) typically appear in prepubescent children between 11 and 15 years of age and are a frequent cause of adrenal hyperfunction in this age group.15,20,27 Weight gain is the common hallmark, accompanied by growth failure; premature puberty; facial plethora; atrophic striae in the abdomen, legs, and arms; muscular weakness; hypertension; and osteoporosis. Children may also have impaired carbohydrate tolerance (although frank diabetes mellitus is uncommon). Increases in adrenal androgens may cause acne and excessive hair growth.
Somatotropinomas (acromegaly) are rare in children (only 5 to 15% of pituitary tumors) but are notable for causing gigantism before growth plate fusion, diabetes, visual disturbances, or headaches.9 These tumors may occasionally co-secrete prolactin and thyroid hormone, resulting in symptoms of those tumors as well. They may be associated with McCune-Albright syndrome or Carney complex as a result of somatotroph hyperplasia.11
Rathke cleft cyst
Thyrotropinomas are extremely rare but usually present as macroadenomas with mass effect symptoms such as headache and visual disturbance, together with various symptoms and signs of hyperthyroidism.28,29
Nonsecreting adenomas are uncommon in childhood, as they are slow growing and often take decades before signs of pituitary insufficiency and mass effect are evident.13
All patients with suspected pituitary tumors should undergo pituitary magnetic resonance imaging (MRI) before and after the administration of gadolinium contrast ( Table 21.4 ). The anterior pituitary is isointense compared with the rest of the brain, but pituitary adenomas often appear hypointense as they are slower to take up contrast. Microadenomas (especially ACTH-secreting pituitary adenomas) may not be visible on even high-quality pituitary MRI. Other imaging signs of a pituitary adenoma include deviation of the pituitary stalk or asymmetry of the gland on a coronal image. Of note, pediatric pituitary adenomas may be more aggressive, larger, and more invasive than in adults. Indeed, they may be a more biologically aggressive disease.1,12,17,30
Pubertal changes (precocious/delay)
Excessive acne/hair growth
Hypointense on contrast study
Deviation of pituitary stalk
Gland asymmetry (coronal view)
Prolactinomas are usually diagnosed at the time of puberty or in the postpubertal period ( Fig. 21.1). The diagnosis is confirmed by measuring the serum PRL. Values greater than 250 ng/mL are usually diagnostic of a prolactinoma.31,32
Corticotropinomas are diagnosed through the measurement of basal and stimulated levels of cortisol and ACTH ( Fig. 21.2 ). Cushing syndrome must first be confirmed on the basis of an elevated 24-hour urinary free cortisol (corrected for the child′s body surface area) or serial 11 pm salivary cortisol measurements. Administration of a low dose of dexamethasone at midnight (15 µg/kg) does not induce suppression of morning serum cortisol concentrations in patients with Cushing syndrome. Cushing disease must then be distinguished from ectopic ACTH-producing lesions. Suppression of cortisol by more than 50% after administration of high-dose dexamethasone given at midnight (120 µg/kg) will confirm that hypercortisolism is due to an ACTH-secreting pituitary adenoma.33 In many cases in which neuroimaging is not diagnostic, inferior petrosal sinus sampling can have a high specificity for diagnosing both a pituitary location of ACTH production (sensitivity of 97%) and laterality (in 75% of cases), but it carries a high rate of false-positive results. If a patient without anomalous venous drainage patterns exhibits a lateralizing ACTH gradient of 2:1 or greater, removal of the appropriate half of the anterior pituitary gland can be curative in up to 80% of cases.34–36 Experience with this test in prepubertal children is (appropriately) quite limited.
Somatotropinomas are usually diagnosed clinically but are confirmed by measuring circulating insulin-like growth factor–1 (IGF-1) concentrations that correlate with the integrated 24-hour growth hormone (GH) secretion levels ( Fig. 21.3 ). Further evaluation includes an oral glucose tolerance test associated with failure of GH suppression or a paradoxical increase in GH production in patients with a GH-secreting pituitary lesion.37 In addition, these tumors may co-secrete prolactin and thyroid hormone, which should be measured. Radiographs may be obtained to assess bone age and closure of the epiphyseal plates.
Thyrotropinomas are confirmed through thyroid function tests. A failure to respond to a thyrotropin-releasing hormone (TRH) stimulation test distinguishes a thyrotropinoma from central thyroxine (T4) resistance. An elevated α-subunit level relative to thyroid-stimulating hormone (TSH) may also be useful.28,29
Nonfunctioning pituitary adenomas are generally macroadenomas; apoplexy is more common in the nonfunctioning macroadenomas than in the hormone-secreting adenomas (up to 21%). Cystic formation aside from hemorrhage may occur in up to 17%.13
Surgical Pearls and Pitfalls
Prior to surgery, review the sphenoid sinus anatomy. Note whether the sphenoid sinus is conchal, presellar, or a sellar type configuration. Pediatric patients more often have a conchal-type sphenoid sinus. In patients with conchal- or presellar-type sphenoid sinuses, it is advisable to use image guidance.
In the patient with a conchal or incompletely pneumatized sphenoid sinus, the bony face of the sphenoid is cortical bone, which may be opened with a chisel or drill. The face of the sella is also a thin layer of cortical bone. The central sphenoid sinus in these cases is composed of soft medullary bone that is readily removed with a small bone curette, exposing the face of the sella.
The bony sellar exposure should extend from cavernous sinus to cavernous sinus, and from the superior intercavernous sinus to the sellar floor.
Prior to opening the dura, re-review the preoperative MRI and be cognizant of the intercarotid distance. Liberal use of the micro-Doppler ultrasound probe is recommended.
During the dural opening, an attempt should be made to preserve the tumor and pituitary pseudocapsule. After dural opening, a subdural plane should be developed between the dura and the tumor.
Pituitary macroadenomas should be removed in a sequential fashion: first the inferior portions of the tumor, followed by the lateral extensions, and finally the superior portions. Early removal of the superior portions of the tumor will cause early descent of the diaphragm and increase the likelihood of incomplete tumor removal.
A common location for residual tumor is at the junction of the cavernous sinus wall and the diaphragm. This location should be carefully inspected prior to closure.
Pituitary microadenomas are best removed in one piece using an extracapsular technique when possible. It is often prudent (Cushing disease, acromegaly, prolactinoma) to resect a thin rim of adjacent pituitary gland, which may be invaded by tumor cells.