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Endocrine problems after treatment for cancer Abby S. Hollander, MD Associate Professor of Pediatrics Pediatric Endocrinology and Diabetes Washington University School of Medicine and St. Louis Children’s Hospital The glands controlled by the hypothalamus and pituitary The hypothalamus directs the actions of the pituitary gland. The pituitary produces vasopressin, a hormone for water balance, growth hormone, and several other signal hormones. Pituitary signals The pituitary produces TSH which signals the thyroid gland, ACTH which signals the adrenal gland, and FSH and LH which signal the gonads (ovaries or testes). The hypothalamus and pituitary are at risk to be damaged by surgery or radiation. Radiation damage is generally dose-dependent, but may not occur until several years after the radiation was given. Deficiencies can occur in all or just some of the hormones produced by the hypothalamus and pituitary. Below a dose of 1800 Gy, it is unusual to have deficiencies. Above a dose of 3500 Gy, there are almost always deficiencies, and in between doses are quite variable. The most common hormone that becomes deficient is growth hormone. The dose of radiation that is important is the dose that touches the hypothalamus and pituitary, not necessarily the dose directed toward the tumor bed. Causes of growth problems after treatment for cancer Growth hormone deficiency Thyroid hormone deficiency Radiation of the spine Early timing of puberty causing growth to end early Poor nutrition High dose steroid treatment Thyroid deficiency or hypothyroidism Causes: Surgical removal of thyroid (thyroid cancer), radiation of the thyroid (spinal irradiation), chemotherapy (pazopanib), loss of TSH due to hypothalamic/pituitary damage Symptoms: Fatigue, feeling cold, constipation, dry skin, poor growth, excessive menstrual bleeding, irregular menses Treatment: levothyroxine (Synthroid, Levoxyl, Unithroid, etc) Common blood tests: free T4, TSH Cortisol is a stress hormone made by the adrenal glands when they are signalled by pituitary ACTH. Low cortisol levels occur due to ACTH deficiency after cranial irradiation. Low cortisol levels can also be a temporary problem after taking high dose steroids for an extended period. Symptoms of low cortisol: fatigue, weakness, frequent vomiting, dizziness, risk of severe low blood pressure (shock) Treatment: hydrocortisone, prednisone Test: cortisol levels after Cortrosyn stimulation The testes will not produce testosterone or sperm if there are deficiencies of FSH and LH from the pituitary. The ovaries can stop functioning due to hypothalamic/pituitary damage, or they can be injured directly from radiation or chemotherapy. Symptoms: no periods (or no breast development), hot flashes Treatment: estrogen and progesterone (pill, patch) The testes are also very susceptible to damage by radiation or chemotherapy. Sperm production is usually affected, but testosterone production may remain normal. Other endocrine-related problems that develop after cancer treatment Hyperlipidemia After some chemotherapy With growth hormone deficiency Obesity After brain tumor treatment After cranial irradiation Due to high dose steroids Decreased bone density With growth hormone deficiency With sex hormone deficiency Due to high dose steroids Conclusions Several hormone deficiencies are possible after treatment for cancer. Deficiencies due to radiation damage may not be evident until several years after treatment is complete. Patients who are at high risk to develop endocrine problems should see an endocrinologist 6-12 months after completion of therapy, and they should be monitored closely. As children reach adulthood, they should be aware of the symptoms that could indicate possible hormone problems (excessive fatigue, weight gain, loss of libido, irregular periods, infertility) so they will be evaluated by an appropriate specialist if needed.