Craniopharyngiomas are slow-growing tumors thus are usually diagnosed late when the patient develops symptoms from intracranial pressure including headaches and vision changes. The endocrinopathy may be reported for several years. On initial presentation,  most children will be found to have sub-normal growth, obesity, and delayed puberty.[2][3]

1. Headaches: Headaches are reported in approximately 50 % of patients. Headaches may be due to increased intracranial pressure (ICP) with associated nausea and vomiting or meningeal irritation from the cystic fluid.
2. Visual symptoms:  62% to 84% of craniopharyngiomas patients will present with visual symptoms. The most common visual disturbance encountered is temporal hemianopsia due to optic chiasm compression. The dysfunction of the optic pathway is present in 50-75% of patients. Unfortunately, children rarely are aware of the vision changes, and consequently, they develop permanent loss of vision. Severe cases may manifest with optic nerve atrophy, papilledema, and visual field deficits.
3. Behavioral and cognitive dysfunction: Visual and olfactory hallucination has been reported in children with craniopharyngioma. Monoplegia and hemiplegia have been observed in some cases. Seizures and unsteady gain have been reported in about 10% of cases.
4. Hormonal deficiency: Approximately 80-90% of patients present with at least one hormonal deficit on the initial presentation. However, only 15% of children will present with endocrine symptoms leading to the evaluation of craniopharyngioma.

• Growth Hormone (GH) deficiency: Short stature is the common reason for the evaluation of the pituitary axis in children. It is present in 75% of pediatric craniopharyngioma.
• Gonadotropin deficiency: 85 % of children will have gonadotropin deficiency leading to delayed puberty. Delayed puberty is the lack of sexual development at a certain time, which is the absence of breast development by age 12 years in girls and the absence of testicular growth in 14 years old boys.  
• Thyroid-stimulating hormone (TSH) deficiency: It is present in 2-25%  of pediatric craniopharyngioma.  The symptoms of hypothyroidism include weight gain, fatigue, dry skin, cold intolerance, constipation, and failure to thrive.
• Adrenocortical hormone (ACTH) deficiency: This is present in 25-70% of patients on the initial presentation. The symptoms may be subtle, but weight loss, fatigue, dizziness, anorexia, and hypoglycemia may be present.
• Vasopressin deficiency, also known as diabetes insipidus( DI), is reported in approximately 9-38% of patients presenting with symptoms of increased thirst and urination.

The evaluation of craniopharyngioma required a multi-disciplinary approach with evaluation by an endocrinologist, neuro-opthalmologist, and neurosurgeon.[3]

Imaging: Craniopharyngioma is diagnosed with computerized tomography (CT) and or magnetic resonance imaging (MRI) during the evaluation of visual symptoms. MRI is the standard of care in identifying craniopharyngiomas or any other pituitary tumors as it provides better information on the tumor, its location, and association to the surrounding structure.  The cystic area is visible on both modalities but calcification is primarily seen with CT imaging. Craniopharyngioma is heterogeneous in texture; the combination of solid, cystic, and calcification components is a clue to its diagnosis on imaging modalities. ACP is primarily large irregular with 90% calcification and a cystic area, while PCP is mostly solid, and rarely with cysts and calcifications. 

Visual Exam: A complete visual exam, including acuity and visual field, should be done by a neuro-opthalmologist in patients with visual disturbances.

Endocrine Evaluation:

• GH deficiency: Initial laboratory evaluation includes checking insulin-like growth factor-1 ( IGF-1), insulin-like growth factor-binding protein -3, and bone age X-ray. Checking plasma GH level add limited value as it is secreted in a pulsatile fashion. If insulin-like growth factor 1 (IGF-1) is normal in patients with craniopharyngioma, then provocative tests using pharmacologic agents to stimulate GH secretion should be performed. The pharmacologic agents are glucagon, levodopa, arginine, or insulin.  The use and interpretation of these agents should be done cautiously for e.g stimulation of GH secretion with insulin is not the right choice in a patient with a history of seizures disorder as hypoglycemia can further precipitate the seizures. 
• Gonadotropin deficiency: This is diagnosed by observation of a lack of pubertal growth in adolescents. Checking gonadotropins, estradiol or testosterone may not aid in diagnosis.
• TSH deficiency: Checking Free T4 is the key to diagnose central hypothyroidism. TSH level will be inappropriately normal to the low free T4 level.
• ACTH deficiency: A baseline morning cortisol with a low ACTH level can give a pretty good assessment of the hypothalamic-pituitary-adrenal axis. AM cortisol of > 18 ugs/dl rules out adrenal insufficiency. Dynamic testing like a cosyntropin stim test can be done in selected patients where AM cortisol is equivocal or indeterminate
• Vasopressin deficiency: The diagnosis is established by documenting fluid intake and output along with checking plasma sodium, plasma, and urine osmolarity. The urine is diluted due to the lack of vasopressin. A water deprivation test can be done to confirm the diagnosis.

The treatment for craniopharyngiomas is challenging because of their location, invasiveness, and proximity to adjacent neurovascular structures. Multiple modalities can be implemented in the management of craniopharyngioma, including surgery, radiotherapy, and intracystic therapy. The choice of treatment, surgery type, and extent should be individualized for each patient. The patient's age, underlying medical co-morbidities, tumor location, type and invasiveness, and ultimately neurosurgeon experience should be considered while deciding the treatment strategy.  There is no consensus on the best treatment regimen.[4][5][6][7][8][9]

Neurosurgery

Surgical intervention is indicated to confirm the diagnosis, tumors causing neurologic deficits, pituitary dysfunction, and hydrocephalus. The most common surgical approaches are endoscopic endonasal transsphenoidal (EET) or transcranial depending on the location of craniopharyngioma. Extension of resection is a matter of debate. Gross total resection has been associated with an increased incidence of post-surgical deficits, with no change in the recurrence rates.

Several grading systems have been developed based on the location of craniopharyngioma and relation to surrounding structures to help decide on the best modality for surgery. Kassam et al had a classification system based on the infundibulum to strategize the surgical approach.  Type I tumors are pre-infundibular which are subchiastmatic tumors displacing the optic chiasm superiorly and posteriorly. Type II tumors are trans-infundibular which can extend into the third ventricle. Type III is retro-infundibular which can either extend superiorly into the third ventricle or inferiorly into the pontine cisterns. Type IV tumors are primarily located in the third ventricles. ETT can be done in all types except Type IV. The isolated third ventral tumors are better approached with craniotomy and transcallosal, transcortical, or trans-ventricular approaches. ETT should be avoided in very large tumors, mostly solid with calcification and vascular invasiveness.

In cases of cystic tumors, the surgeon can introduce an intracystic catheter into the tumor and connect it to a reservoir, called the Ommaya reservoir. The reservoir then permits frequent aspiration of the cyst thus helping to avoid aggressive surgeries and further radiotherapy in children.

Radiotherapy

Radiation therapy includes various modalities: conventional external radiotherapy, proton beam therapy, stereotactic radiotherapy, radiosurgery, and brachytherapy. The goal of radiotherapy is to decrease tumor burden while protecting essential neural structures. Specific Gy doses have been designated for every radiation modality. Multiple reports have suggested decreased mortality with slightly reduced morbidity following radiation therapy. Despite this, radiation therapy has not been proven to reduce the recurrence rate. Therefore, it continues to be an adjuvant modality to neurosurgical intervention.

Intracystic Therapy

Inttacystic therapy is primarily used for purely cystic craniopharyngioma. Toxic substances like radioactive isotopes, bleomycin, interferon-alpha are used in intracystic therapy to produce tumor fibrosis and sclerosis. This method has been reported to produce significant cyst shrinkage, but there is limited data on its use and support. A disadvantage of this option is that severe neurotoxicity can occur in some cases due to cystic leakage of the sclerosing substance

Hormonal Treatment

GH deficiency: Most children will receive GH replacement after 6 months to 1 year after documenting a cure from craniopharyngioma.  Most of the patients requiring GH treatment have persistent GH deficiency and have not achieved their normal height velocity. Interestingly some patients swill attain normal height postoperatively without replacement. The period after surgery without any treatment is essential to identify the patients who will benefit from GH treatment.  Even though GH treatment is relatively safe, there are some concerns of growth in residual tumors, thus patients should be monitored closely when treating them with growth hormones.

Gonadotropin deficiency: The hormone replacement should be individualized depending on the age and growth of patients. Earlier treatment with sex steroids can lead to cessation of growth. In girls, a combination of estrogen and progesterone is given to induce puberty. The treatment usually starts with a very low dose of estrogen with a gradual increase over time with periodic progesterone treatment to prevent uterine hyperplasia.  In boys, testosterone treatment is started at age 12-15 years depending on their growth. Usually, patients are started on a smaller dose and gradually increased to the full adult dose. The current testosterone replacements available are intramuscular testosterone, given every 2 weeks and gel preparation that is used daily. 

TSH deficiency: The thyroid function test should be monitored postoperatively as 29-85% of patients can develop hypothyroidism following surgery or radiation treatment. The ideal way of replacement is by giving synthetic LT4, Levothyroxine, as an oral tablet daily. It is important to make sure the adrenal axis is intact before starting treatment as thyroid hormone replacement can increase the metabolic clearance of glucocorticoids thus may cause an adrenal crisis.

ACTH deficiency: Patients should be monitored post-operatively by checking AM cortisol as > 50 % of children can be diagnosed with adrenal insufficiency later after surgery or radiation treatment. Children are usually treated with prednisone or hydrocortisone. The glucocorticoid replacement dose is 6-9 mg/m2  with dose adjustment with increasing age and weight.                 

Vasopressin deficiency: DI can develop in 70 % of craniopharyngioma patients after surgery. Postoperatively it is important to monitor patient urine output and check plasma sodium and urine osmolality and specific gravity. Desmopressin acetate-DDAVP- is the primary treatment in the form of an oral tablet or nasal spray.

The differential diagnosis for craniopharyngioma include[10]:

• Inflammatory conditions: Pituitary abscess, lymphocytic hypophysitis, infundibulitis, histiocytosis, sarcoidosis, tuberculosis, and syphilis
• Other congenital conditions: Rathke's cleft cyst and arachnoid cysts
• Other tumors: Pituitary adenomas, primitive neuroectodermal tumors, hypothalamic hamartoma, germ cell tumor, epidermoid or dermoid tumor, meningioma, medulloblastoma, brainstem glioma and lymphoma
• Vascular malformations: Giant suprasellar carotid aneurysm, cavernous sinus hemangioma, and carotid-cavernous fistula

The outcomes for microadenomas are excellent but patients with macroadenomas may be left with residual visual, metabolic, or neurological deficits following treatment.[9][8][11][12] 

• Visual field disturbance and loss of vision
• Diabetes insipidus and hypernatremia
• Hydrocephalus
• Seizures
• Pituitary hormone disturbances
• Hypothalamic obesity
• Death

The patients should be educated regarding the likely complications and a detailed discussion should be done if a surgery is being planned. The patient should be made aware of the likely complications that can occur following any type of intervention.

The management of craniopharyngioma is complex and usually requires an interprofessional team that includes a neurosurgeon, radiologist, radiotherapy specialist, neurologist, ophthalmologist, and an endocrinologist. The patient requires long term follow up with endocrinologist for evaluation and management of hormonal deficiency.