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Late Effects of Cancer Treatment: Endocrine Effects

Late Effects of Cancer Treatment: Endocrine Effects. Thyroid Dysfunction Adrenal Insufficiency Gonadal Toxicity Growth Hormone Deficiency. Objectives . The learner will be able to: Describe the pathophysiology of endocrine dysfunction in patients due to cancer treatment.

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Late Effects of Cancer Treatment: Endocrine Effects

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  1. Late Effects of Cancer Treatment: Endocrine Effects Thyroid Dysfunction Adrenal Insufficiency Gonadal Toxicity Growth Hormone Deficiency

  2. Objectives The learner will be able to: • Describe the pathophysiology of endocrine dysfunction in patients due to cancer treatment. • Describe the manifestation, symptoms, and diagnostic workup of endocrine dysfunction in patients due to cancer treatment.

  3. Problem • Most common late effects are endocrine. • Highest rates in adult survivors of pediatric cancer • Up to 40% of cancer survivors • Toxic treatment: • Total dose received • Duration of exposure • Interval since the completion of therapy Stava, 2007

  4. Causes • Tumor invasion to hypothalamus region • Radiation therapy • Chemotherapy • Blood and marrow transplant • Pretreatment comorbidities Hypothalamus ↓ Pituitary • National Cancer Institute (http://www.cancer.gov)

  5. Pathophysiology Thyroid ↓ ↓ Triidodthyronine (T3) ↓ Thyroxin (T4) ↓ Hypothyroidism Thyroid Impairment Hypothalamus ↓ Pituitary ↓ Growth Hormone ↓ Delayed Growth and Development Testis and Ovaries ↓ ↓ Testosterone ↓ Estrogen ↓ Progesterone ↓ Ovarian Failure Early menopause Azoospermia Adrenal Glands ↓ ↓ Cortisol ↓ Aldosterone ↓ Adrenal Insufficiency

  6. Thyroid Dysfunction:Hypothalamus-Pituitary-Thyroid Axis • Subclinical hypothyroidism/thyroid impairment—most common – ↑ thyroid stimulating hormone (TSH) with normal T4 and T3 • Overt hypothyroidism – ↑ TSH with ↓T4 and/or T3 • Symptoms • Apathetic/sluggishRetarded bone age/short stature • Bradycardia ↓ growth rate • Constipation Delayed puberty • Menstrual irregularity  Infertility/spontaneous abortion

  7. Thyroid Dysfunction:Hypothalamus-Pituitary-Thyroid Axis • Screen with thyrotropin releasing hormone (TRH) stimulation test. • Thyroid ultrasound—Nodules/irregularity • Thyroid replacement therapy: Levothyroxine

  8. Secondary Adrenal Insufficiency:Hypothalamus-Pituitary-Adrenal Axis • Many chemotherapy and radiation regimens utilize glucocorticoids • Symptoms • Fatigue and weakness • Anorexia and weight loss • Abdominal pain • Nausea and vomiting • Male infertility • Adrenal crisis (critical cortisol levels) • Hypotension • Hypoglycemia

  9. Secondary Adrenal Insufficiency:Hypothalamus-Pituitary-Adrenal Axis • Lab testing • ACTH (serum) = < 9 • Cortisol (serum before 8 am); insufficiency = < 18 • Cortisol stimulation test • Treatment • Steroid 5 mg, 10 mg, 20 mg • If mineralocorticoid deficiency: • Low aldosterone • Also use fludrocortisone 0.05–0.2 mg/day oral in am.

  10. Gonadal Toxicity: Ovarian FailureHypothalamus-Pituitary-Gonadal Axis • Damage to oocytes and follicle support • Signs: • ↑ follicle stimulating hormone (FSH) Hot flashes • ↑ luteinizing hormone (LH)  Sleep/mood disturbance • ↓ estradiol  Musculoskeletal pain • Amenorrhea  Painful intercourse • Screening: • FSH • LH • Estradiol • Treatment: • Precancer treatment fertility counseling • Estrogen and cyclic progestin

  11. Gonadal Toxicity: Early Menopause/Infertility Hypothalamus-Pituitary-Gonadal Axis • Risks without treatment: • Early and extensive osteoporosis • Cardiovascular disease • Early dementia • Treatment • No menstruation post-treatment; consider hormone replacement therapy (HRT) • Pretreatment fertility counseling

  12. Gonadal Toxicity: Azoospermia/InfertilityHypothalamus-Pituitary-Gonadal Axis • Germinal epithelium responsible for spermatogenesis • Lydig cells responsible for testosterone production • Screen • Testosterone levels • Semen analysis • Treatment • Offer pretreatment sperm banking if treatment intensity is thought to produce sterility. • Testosterone gel or injections

  13. Growth Hormone Deficiency:Hypothalamus-Pituitary-Growth Hormone Axis • Deregulation of growth hormone (GH) • Signs • Short stature Delayed tooth development • Decreased growth velocity  Delayed onset of puberty • Increased fat around the waist • Screening post-treatment • Growth charts • Growth velocity • GH levels • If deficiency, follow with: • Provocation tests/GH stimulation test • Bone age tests. • Treatment • GH injections

  14. Nursing Implications • Endocrine late effects from cancer treatment can resolve or be permanent. • Understanding your patients’ history with cancer, including treatment and medical history, is key. • Adherence to follow-up screening and reporting of symptoms is important. • Endocrine dysfunction affects patients’ physical, emotional, behavioral, and social functioning.

  15. References Chemaitilly, W., & Sklar, C. (2010). Endocrine complications in long-term survivors of childhood cancers. Endocrine-Related Cancer, 17, R141R159. Stava, C.J., Jimenez, C., & Vassilopoulou-Sellin, R. (2007). Endocrine sequelae of cancer and cancer treatments. Journal of Cancer Survivorship, 1, 261274. Tauchmanovά, L., Selleri, C., De Rosa, G., Pagano, L., Orio, F., Lombardi, G., … Colao, A. (2002). High prevalence of endocrine dysfunction in long-term survivors after allogeneic bone marrow transplantation for hematologic diseases. Cancer, 95, 10761084.

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