OVERVIEW: What every practitioner needs to know

Craniopharyngiomas are one of the most common pituitary tumors in childhood, accounting for approximately 50% of all sellar/suprasellar masses. They often cause diabetes insipidus and growth retardation as one of the earliest manifestations. Therefore, detection is key to preventing increased morbidity and mortality.

Rathke’s cleft cysts are less frequently seen than craniopharyngiomas. They are benign cysts that arise within the sella turcica and may be formed from remnants of Rathke’s pouch. These cysts are often undetected unless they cause compression of the surrounding structures.

Are you sure your patient has a Rathke cleft cyst? What are the typical findings for this disease?

  • Headache; nausea and vomiting; visual impairment; growth retardation.

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  • Polyuria and polydipsia; hypogonadism; weight gain.

What other disease/condition shares some of these symptoms?

Diseases which share some of these symptoms are other sellar or suprasellar masses including pituitary adenoma, epidermoid tumor, germinomas, Langerhans cell histiocytosis, arachnoid cyst, and suprasellar aneurysm.

What caused this disease to develop at this time?

  • Although the pathogenesis is unclear, craniopharyngiomas are thought to arise from either ectodermal tissues that are remnants from the Rathke’s cleft or residual, embryonal epithelium of the anterior pituitary gland and of the anterior infundibulum.

What laboratory studies should you request to help confirm the diagnosis? How should you interpret the results?

  • There are no laboratory studies that specifically indicate the presence of a craniopharyngioma; however, certain laboratory tests can diagnose the sequelae of disruption caused by the craniopharyngioma, specifically, single or multiple pituitary hormone deficiencies.

Screening for hypopituitarism should include:

  • IGF-1 and IGFBP-3 (to detect growth hormone deficiency)

  • if low, obtain growth hormone stimulation test.

  • first morning sodium, urinalysis, serum and urine osmolarity (to detect DI)

  • serum osmolarity>300mOsm/kg with urine osmolarity<300mOsm/kg is diagnostic of DI

  • 8am LH and FSH (only in pubertal children)

Would imaging studies be helpful? If so, which ones?

CT scan can usually detect greater than 90% of craniopharyngiomas, and should be the first imaging study. It is especially helpful in detecting calcifications, which are often present, and helps to differentiate between most childhood craniopharyngiomas and other sellar masses that often lack the presence of calcifications.

MRI with gadolinium can also be used to detect craniopharyngiomas, and can help with determining the structural content of the tumor. Solid portions of the tumor appear isointense on precontrast T1-weighted images and enhanced after gadolinium. Cystic components are usually hypointense on T1- and hyperintense on T2-weighted images. T1 images often demonstrate a peripheral thin rim-enhancing region encasing the tumor. Rathke’s cleft cysts, unlike craniopharyngiomas, have minimal enhancement of the cyst wall and lack calcifications or nodularity, and may be better detected via MRI.

Plain radiography, although of least expense, is less often used and provides little structural detail, with the exception of the presence of calcifications.

If you are able to confirm that the patient has a Rathke cleft cyst, what treatment should be initiated?

Consultation with a pediatric oncologist and neurosurgeon is recommended to determine the best method of treatment.

Treatment options include:

Complete or partial resection, depending upon the size, location, extent of calcification, tissue invasion, and experience of the neurosurgeon. These tumors often invade vital brain tissue structures, including neurovascular, hypothalamic and pituitary structures. Care is taken to salvage as much normal tissue as possible. However, complete resection is preferred when possible.

Irradiation. This is often used as adjunctive care for tumors that cannot be completely resected, and decreases recurrence rates.

Brachytherapy involves installation of radioactive beta-emitting isotopes directly into a cystic craniopharyngioma. The isotope often delivers higher doses of radiation than conventional methods and causes local destruction of neoplastic tissue.

Given that hypopituitarism can sometimes result from craniopharyngiomas, it is wise to do a screening evaluation before any surgical procedure is undertaken. Deficiencies such as ACTH, TSH, and vasopressin deficiency should be corrected before surgery.

Treatment for central deficiencies includes:

– Hypothyroidism- Levothyroxine (approximate oral dose)

  • neonates- 10-15 µg/kg/day

  • 1-5 years – 3-5 µg/kg/day

  • 6-12 years- 4 µg/kg/day

  • Adolescents- 2-3 µg/kg/day

  • -** if hypothyroidism is detected, it is important to determine if adrenal insufficiency is present before treatment is initiated, since this can precipitate an adrenal crisis.**

  • – IV dose is approximately 75% of oral dose.

  • -Adrenal insufficiency- Hydrocortisone at maintenance should be replaced orally with 6-10 mg/m2/day divided TID. Prior to and during any surgical procedure, these patients must be given stress doses of hydrocortisone, which should be decided with consultation by an endocrinologist.

  • -Diabetes Insipidus- This can be managed with DDAVP. If the thirst mechanism is intact, the patient is often allowed to drink as desired; however, fluid goals should be set if the thirst mechanism is not intact. Close monitoring of electrolytes and fluid status is warranted to prevent hyponatremia.

What are the adverse effects associated with each treatment option?

· Adverse effects

  • Resection can be associated with damage to vital brain tissue structures including the hypothalamus, pituitary, and optic nerves. This can lead to hyperphagia from loss of the satiety center and obesity, hypopituitarism causing growth retardation, polyuria, polydipsia, hypernatremia, hypotension, hypoglycemia, and vision loss.

  • Irradiation can often result in pituitary damage depending on the dose of radiation used. Typically, external beam radiation doses are set at 54 Gy. The growth hormone axis is most susceptible to damage, with isolated growth hormone deficiency seen with doses as low as 18 Gy. The frequency increases to 50%-100% within 3-5 years with doses as high as 30-50 Gy. Gonadotropin deficiency increases after receiving 30 Gy. About 3%-6% of patients will experience ACTH and TSH deficiency with doses between 30-50 Gy. Doses greater than 60 Gy increase the risk of all pituitary deficiencies.

What are the possible outcomes of a Rathke cleft cyst?

Survival rates ranges from 83%-98% at 10 years, depending upon the method of treatment. With recurrence, 10-year survival rates decrease to 20%-70%. The risk of recurrence is lowest with complete resection (0%-60%) and highest with incomplete resection without adjuvant radiation therapy (75%-90%).

What causes this disease and how frequent is it?

  • There are two main types of craniopharyngiomas: papillary and adamantinomatous. The adamantinomatous type is associated with pediatric craniopharyngiomas.

  • Peak occurrence is between ages 5-14 years.

  • It accounts for ~1%-5% of all pediatric intracranial tumors. It is extremely rare, with an incidence of 0.5-2 cases per million persons per year.

  • The etiology is unclear; however, pediatric craniopharyngiomas have been linked to mutations in exon 3 of the beta-catenin gene. This region encodes the degradation box of beta-catenin, and mutations result in its accumulation. Beta-catenin is a transcriptional activator of the Wnt signaling pathway. The Wnt pathway is important for regulation of cellular proliferation and development.

  • There are no clear predisposing factors.

How do these pathogens/genes/exposures cause the disease?


Other clinical manifestations that might help with diagnosis and management

Other clinical manifestations that may help with diagnosis and management include other signs of hypopituitarism in a child without predisposing risk factors, i.e., radiation. Therefore, patients with newly diagnosed pituitary hormone deficiencies (especially multiple) should have intracranial imaging.

What complications might you expect from the disease or treatment of the disease?

Unfortunately, even after treatment for craniopharyngioma, quality of life is negatively affected in most patients. Sequelae of disease, resulting from either primary tumor or therapeutic intervention, is present in the majority of patients. Most patients have resultant hyperphagia and hypothalamic dysregulation, causing severe obesity. Furthermore, neurological deficits and some degree of hypopituitarism (85%-95%) often result.

Are additional laboratory studies available; even some that are not widely available?


How can Rathke cleft cysts be prevented?

There are no known methods for prevention.

What is the evidence?

Karavitaki, N, Wass, JA. “Non-adenomatous pituitary tumours”. Best Pract Res Clin Endocrinol Metab. vol. 23. 2009. pp. 651-5.

Müller, HL. “Childhood craniopharyngioma–current concepts in diagnosis, therapy and follow-up”. Nat Rev Endocrinol. vol. 6. 2010. pp. 609-18.

Müller, HL. “Consequences of craniopharyngioma surgery in children”. J Clin Endocrinol Metab. vol. 96. 2011. pp. 1981-91.

Puget, S, Garnett, M, Wray, A. “Pediatric craniopharyngiomas: classification and treatment according to the degree of hypothalamic involvement”. J Neurosurg. vol. 106. 2007. pp. 3-12.

Ongoing controversies regarding etiology, diagnosis, treatment

There are ongoing controversies regarding etiology and treatment. There have not been any randomized placebo controlled trials to determine which treatment modality is best, with the exception of complete excision when possible.