Neuroendocrine Case 1

James is 5 years old and has had worsening headaches for several weeks. He awakens with repeated vomiting. His parents rush him to the emergency room where he has a generalized seizure. A computerized tomography (CT) scan shows a posterior fossa tumor and hydrocephalus. He is admitted to the hospital and an emergency ventriculoperitoneal shunt is placed. Magnetic resonance imaging (MRI) confirms a likely medulloblastoma. In discussion with oncology, parents ask about future effects of treatment for the tumor.

Question 1

What empiric endocrine treatment should be started prior to the patient's craniotomy to remove the tumor?

A. Thyroid hormone
B. Glucocorticoids
C. Gonadotropin-releasing hormone agonist (GnRH-a)
D. All of the above
E. No hormone treatment since he has not yet been identified with any deficiencies
Incorrect!
Correct!
Correct Answer
B. Glucocorticoids

Patients with a brain tumor have a high risk for various neuroendocrinopathies. Late-endocrine effects of cancer therapies can cause significant morbidity. Increased intracranial pressure from the tumor itself can alter hypothalamic-pituitary function and anatomy, including secondary empty sella.

Neurosurgery itself can add to the risk for pituitary deficiencies as a result of mechanical traction. Because most intracranial resections of tumors involve significant recovery, often with prolonged hospitalizations, glucocorticoids, such as oral dexamethasone or hydrocortisone, given in stress dose quantities (50-100 mg/m2/day of hydrocortisone equivalency), are recommended as a precaution in the event of corticotrophin-releasing hormone (CRH) and/or adrenocorticotropic hormone (ACTH) deficiency that may result from the tumor or its resection, collectively called central adrenal insufficiency (AI). Rapid clinical decompensation may occur in the setting of central AI unless exogenous glucocorticoids are provided. Mineralocorticoid replacement is not required in central AI as the renin-angiotensin-aldosterone system is not impacted.

Thyrotropin-releasing hormone (TRH) or thyroid-stimulating hormone (TSH) deficiency can occur as a result of tumor mass effect, cranial radiation, and/or injury to the hypothalamus or pituitary glands. However, little data is available to support the empiric use of thyroid hormone prior to craniotomy, in the absence of direct evidence of abnormal thyroid hormone function testing. GnRH agonist treatment may be indicated in the setting of precocious puberty caused by a primary brain tumor or its treatment but is not used in the acute setting of craniotomy. As time goes on after acute management of the brain tumor, at least yearly monitoring of growth and endocrine function should be performed. Radiation therapy can lead to gradual decline (over 6 to 10 years) in hypothalamic messages to the pituitary gland. Chemotherapy can augment the late endocrine effects of irradiation or occasionally cause hypopituitarism. In addition, chemotherapy can cause gonadotoxicity and primary hypogonadism and contributes to development of osteopenia. Growth hormone (GH) deficiency and hypothyroidism (central and primary taken together) are common following radiation doses as low as 15-20 Gy. Precocious or rapid puberty can occur in association with optic gliomas and after cranial irradiation. Late ACTH deficiency can develop after radiation doses greater than 25 Gy, and gonadotropin deficiency can develop after doses above 30 Gy.

Patients with a brain tumor have a high risk for various neuroendocrinopathies. Late-endocrine effects of cancer therapies can cause significant morbidity. Increased intracranial pressure from the tumor itself can alter hypothalamic-pituitary function and anatomy, including secondary empty sella.

Neurosurgery itself can add to the risk for pituitary deficiencies as a result of mechanical traction. Because most intracranial resections of tumors involve significant recovery, often with prolonged hospitalizations, glucocorticoids, such as oral dexamethasone or hydrocortisone, given in stress dose quantities (50-100 mg/m2/day of hydrocortisone equivalency), are recommended as a precaution in the event of corticotrophin-releasing hormone (CRH) and/or adrenocorticotropic hormone (ACTH) deficiency that may result from the tumor or its resection, collectively called central adrenal insufficiency (AI). Rapid clinical decompensation may occur in the setting of central AI unless exogenous glucocorticoids are provided. Mineralocorticoid replacement is not required in central AI as the renin-angiotensin-aldosterone system is not impacted.

Thyrotropin-releasing hormone (TRH) or thyroid-stimulating hormone (TSH) deficiency can occur as a result of tumor mass effect, cranial radiation, and/or injury to the hypothalamus or pituitary glands. However, little data is available to support the empiric use of thyroid hormone prior to craniotomy, in the absence of direct evidence of abnormal thyroid hormone function testing. GnRH agonist treatment may be indicated in the setting of precocious puberty caused by a primary brain tumor or its treatment but is not used in the acute setting of craniotomy. As time goes on after acute management of the brain tumor, at least yearly monitoring of growth and endocrine function should be performed. Radiation therapy can lead to gradual decline (over 6 to 10 years) in hypothalamic messages to the pituitary gland. Chemotherapy can augment the late endocrine effects of irradiation or occasionally cause hypopituitarism. In addition, chemotherapy can cause gonadotoxicity and primary hypogonadism and contributes to development of osteopenia. Growth hormone (GH) deficiency and hypothyroidism (central and primary taken together) are common following radiation doses as low as 15-20 Gy. Precocious or rapid puberty can occur in association with optic gliomas and after cranial irradiation. Late ACTH deficiency can develop after radiation doses greater than 25 Gy, and gonadotropin deficiency can develop after doses above 30 Gy.