Post-Radiation Endocrinopathies

Overview

Post-radiation endocrinopathies are hormone-related disorders that develop as a complication of undergoing radiation therapy, particularly to the head and neck, brain, chest, or pelvis.

Endocrine tissues in these regions, like the pituitary gland, hypothalamus, and thyroid gland in the head and neck, are susceptible to radiation. This means that radiation therapy can damage these tissues over time and, in turn, disrupt hormone production, hormone regulation, or hormone signaling.

Doctors categorize the different types of post-radiation endocrinopathies by the endocrine system that’s affected. They include:

• Hypothalamic-pituitary dysfunction: This is the most common form of post-radiation endocrinopathy, especially in people who have received radiation to the head. The hypothalamus is more radiosensitive than the pituitary gland, so damage here can lead to hypopituitarism—the underproduction of one or more of the following pituitary hormones:
  • Growth hormone (GH) deficiency: This is typically the earliest and most common hormone deficiency, especially in children, and leads to poor growth, fatigue, and changes in body composition.
  • Gonadotropin deficiency: This hormone deficiency leads to delayed puberty or hypogonadism, a condition where the body doesn’t make enough sex hormones. 
  • Thyrotropin (TSH) deficiency: This hormone deficiency leads to hypothyroidism, a condition where the thyroid doesn’t make enough thyroid hormone. 
  • Hyperprolactinemia: Damage to the hypothalamus can lead to abnormally high levels of the hormone prolactin, which is responsible for stimulating and maintaining lactation in breastfeeding women. 
  • Adrenocorticotropic hormone (ACTH) deficiency: Although uncommon, this hormone deficiency is most serious because it affects cortisol production and can cause life-threatening adrenal insufficiency. 
• Hypothyroidism: This form of post-radiation endocrinopathy is due to direct damage to the thyroid gland, typically after radiation therapy treating head and neck cancer or Hodgkin lymphoma. 
• Arginine–vasopressin deficiency (AVD): This condition, formerly known as diabetes insipidus, occurs when the posterior pituitary gland or hypothalamus is damaged, affecting the secretion of antidiuretic hormone (ADH). 

Many post-radiation endocrinopathies don’t appear immediately after radiation. They may not emerge for years or even decades after treatment. The risk for post-radiation endocrinopathies increases over time, so lifelong monitoring for those who have undergone radiation therapy is essential. 

What causes post-radiation endocrinopathies?

Post-radiation endocrinopathies are triggered by radiation-induced cellular damage to endocrine glands, hormone-secreting tissues, or the structures that regulate them. This damage can occur immediately or evolve gradually over time.

That said, the severity and type of the post-radiation endocrinopathy will depend on numerous factors, including radiation dose, the part of the body that received treatment, age at exposure, and the cumulative dose of radiation over time.

If you or someone you know has a post-radiation endocrinopathy, you may experience some combination of the following symptoms:

• If there’s a growth hormone (GH) deficiency: Symptoms can include fatigue, poor concentration and memory, an increase in fat, especially around the abdomen, a decrease in muscle mass and strength, as well as bone density, and, in children, slowed growth or shorter stature.
• If there’s a thyroid-stimulating hormone (TSH) deficiency: Symptoms can include a persistent feeling of fatigue, weight gain, cold intolerance, a new or sudden onset of depression, dry skin, slowed heart rate, and constipation. 
• If there’s thyroid dysfunction: Hypothyroidism, or an underactive thyroid gland that isn’t producing enough T3 and T4 thyroid hormones. Symptoms like fatigue, weight gain, hair thinning or hair loss, dry or coarse skin, cold intolerance, depression, memory problems, and menstrual irregularities in women can develop. 
• If there is a gonadotropin deficiency: Also known as hypogonadism, a gonadotropin deficiency shows up as irregular or absent periods, a decreased libido, vaginal dryness, and infertility in women; in men, it presents as erectile dysfunction, a decrease in libido and muscle mass, breast enlargement, and infertility. In both sexes, it can lead to mood changes, like irritability or depression.
• If there is an adrenocorticotropic hormone (ACTH) deficiency: Symptoms can include chronic fatigue and weakness, low blood pressure, nausea and vomiting, weight loss, salt cravings, electrolyte imbalances, and dizziness or fainting.
• If there’s a prolactin deficiency: Known as hypoprolactinemia, symptoms can include a milky discharge from the breasts not related to pregnancy or breastfeeding, known as galactorrhea, and irregular or complete absence of menstrual periods in women. In men, it can include a decreased libido, erectile dysfunction, and infertility.
• If there’s an arginine-vasopressin deficiency (AVD): Formerly known as diabetes insipidus, symptoms of AVD can include excessive thirst, frequent urination, dehydration, muscle cramps or weakness, nausea and vomiting, and confusion or irritability. 
• If there’s an adrenal insufficiency: Symptoms can include fatigue, weakness, a loss of appetite, nausea and vomiting, low blood pressure, dizziness or fainting, joint or abdominal pain, and increased skin pigmentation. 
• Symptoms specific to children can include: Delayed puberty or early (precocious) puberty, poor bone development, short stature, and emotional and/or social difficulties may occur in pediatric cases of post-radiation endocrinopathies.

What’s more, some people with post-radiation endocrinopathies can experience vague or overlapping symptoms, like chronic fatigue, poor stress tolerance, cognitive issues, and anxiety or depression. And because these symptoms develop gradually, they can be attributed to aging, stress, or cancer recovery, which ultimately leads to delayed diagnosis. 

As such, long-term follow-up with regular hormone testing is essential for individuals who’ve undergone radiation involving the brain, neck, chest, or midsection.

Post-Radiation Endocrinopathies Diagnosis

Physicians most often diagnose post-radiation endocrinopathies through detailed patient evaluation, hormonal testing, and occasionally imaging scans. Ultimately, diagnosis requires a high degree of clinical suspicion—especially if you’re a cancer survivor who has received radiation to the sensitive endocrine regions of your body—because post-radiation endocrinopathies can develop months or years after receiving radiation therapy.

Doctors might use the following exams, tests, and imaging tests to diagnose post-radiation endocrinopathies:

• Clinical history and risk assessment: Radiation exposure history is crucial in diagnosing post-radiation endocrinopathies. Your healthcare provider will consider the site of radiation, the radiation dose, the age at which you received radiation, and the time that has elapsed since you received radiation therapy. 
• Physical and neurological exam: Your healthcare provider will next ask about your symptoms. Subtle or nonspecific complaints like fatigue, weight changes, menstrual changes, or decreased libido will likely prompt further evaluation. Neurological function will also be assessed, including reflexes, coordination, strength, and sensation.
• Blood tests: These tests are crucial in determining which hormones are low based on the suspected deficiencies. Standard blood tests include LH, FSH, estradiol, testosterone, TSH, free T4, IGF-1, prolactin, ACTH, electrolytes, glucose, and sodium.
• Water deprivation test: If arginine-vasopressin deficiency (AVD) is suspected, your care team will perform a water deprivation test that involves not drinking any liquid for several hours to monitor how your body responds. Close supervision will ensure dehydration doesn’t occur. 
• Magnetic Resonance Imaging (MRI): Imaging studies are crucial in visualizing the brain and identifying abnormalities, and an MRI is considered the gold standard. An MRI of the brain and pituitary region can be helpful to look for structural changes in the pituitary or hypothalamus region, or tumor recurrence if you’re a cancer survivor.
• Pediatric-specific evaluations: For children, a growth chart review, X-rays to assess skeletal development, a calculation of height velocity, and Tanner staging—a system used to evaluate the physical development of children and adolescents during puberty—will be crucial. 

Because post-radiation endocrinopathy symptoms appear over time, individuals who receive radiation that’s deemed “high risk” should undergo yearly hormone, fertility, and sexual function assessments. Regular growth monitoring will also be necessary for children. 

Early recognition is critical to start the appropriate hormone replacement therapy and to improve long-term health outcomes.

Nonsurgical Treatments

The cornerstone of treatment for post-radiation endocrinopathies is hormone replacement therapy (HRT), tailored to the specific hormone or hormones that are deficient. While hormone replacement therapy is generally lifelong, it is highly effective.

Hormone replacement therapy for post-radiation endocrinopathies includes: 

• Thyroid hormone replacement: In the case of hypothyroidism or an underactive thyroid, synthetic levothyroxine can restore normal metabolic function, resolve fatigue, improve temperature regulation, and manage weight. 
• Glucocorticoid replacement: Endocrinologists prescribe hydrocortisone or prednisone for adrenal insufficiency caused by an ACTH deficiency. Patients with this deficiency are also educated on temporary dose increases during illness or stress to prevent adrenal crisis.
• Sex hormone replacement: In females, doctors prescribe estrogen and progesterone to regulate menstruation, support cardiovascular health, and preserve bone density and sexual function. In males, testosterone can be prescribed and administered as a gel, patch, or injection to help maintain muscle mass, body composition, bone density, and sexual function.
• Fertility treatments: For those who wish to conceive but are experiencing gonadal failure, where the ovaries or the testes produce little to no sex hormones, assisted reproductive technologies like IVF and egg or sperm retrieval may be considered. Your care team may also use gonadotropins or GnRH therapy to help stimulate fertility. 
• Growth hormone (GH) replacement: GH therapy in the form of recombinant growth hormone injections is used in children—and in some cases, adults—to promote normal growth and improve energy, body composition, and bone health.
• Desmopressin (DDAVP): In cases of arginine-vasopressin deficiency (AVD), synthetic antidiuretic hormone is used to help control excessive urination and prevent dehydration.

In addition to hormone therapy, lifestyle modifications, nutritional support, and emotional and social support are often integrated into care. 

To best manage post-radiation endocrinopathies, diligent coordination between endocrinologists, oncologists, and primary care providers is required. Regular endocrine assessments, laboratory monitoring, and patient education will be crucial for long-term care. 

Surgical Treatments

Surgery is not a standard treatment for post-radiation endocrinopathies, but may prove helpful in certain circumstances, such as: 

• Residual or recurrent tumors: If a pituitary tumor, craniopharyngioma, or another type of tumor continues to grow or cause compression of surrounding structures after radiation therapy, neurosurgical removal may be necessary.
• Hydrocephalus or mass effect symptoms: Tumors or cysts near the hypothalamic-pituitary region that cause symptoms like vision loss or persistent headaches may require surgery for decompression to relieve pressure on nerves.
• Thyroid nodules or cancer: In patients who develop thyroid nodules after neck radiation, doctors may perform a biopsy to evaluate for malignancy. If thyroid cancer is confirmed, a partial or total thyroidectomy may be performed.

These surgical approaches generally address structural issues rather than hormonal imbalances. Even after surgery, most patients with post-radiation endocrine damage will still require ongoing hormone replacement therapy. 

One Central Location with Multiple Treatment Options

At Barrow Neurological Institute’s renowned Pituitary Center, we treat people with pituitary tumors and disorders in one robust location. And because our doctors and nurses treat more people with pituitary disorders than any other team in the Southwest U.S., you can rest assured that you’ll be in very experienced hands.