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Late Effects





After radiation therapy (RT) to the hypothalamic-pituitary axis, growth hormone deficiency is the most common late effect. 

However, other pituitary deficiencies/effects can occur:

Gonadotrophin deficiency:

  • Second most common anterior pituitary deficit after GH deficiency in many series
  • Rare if the brain has been given less than 40 Gy
  • Increased incidence after doses greater than 50 Gy
  • Prevalence of gonadotrophin deficiency increases with time after therapy

Precocious (early) puberty:

  • Effect of RT on hypothalamic-pituitary-gonadal axis is RT dose dependent.
  • RT over 50 Gy leads to gonadotrophin deficiency
  • Low dose RT can lead to precocious puberty
  • Possibly due to disinhibition of cortical influences on hypothalamus
  • Low dose RT for prophylactic cranial RT in children with acute leukemia is associated with an increased incidence of precocious puberty
  • Girls more at risk than boys for low dose cranial RT
  • At higher doses (25 - 50 Gy) both girls and boys are affected

ACTH deficiency:

  • The hypothalamic-pituitary-adrenal axis appears to be relatively radioresistant (for children treated for non-pituitary brain tumors)
  • ACTH deficiency is common in survivors of pituitary tumors (eg. craniopharyngioma)
  • ACTH deficiency is uncommon in patients who have received less than 50 Gy of cranial RT
  • Incidence of ACTH deficiency increases if the dose of RT to the hypothalamus and pituitary is over 50 Gy
  • There is evidence to show that ACTH secretion may be measured at normal levels, but there is deficient secretion in times of stress
  • In the event of illness, such as infection, patients who had previous moderately high dose cranial RT may require steroid medication

TSH deficiency:

  • The incidence of TSH deficiency after cranial RT is dose dependent
  • The reported prevalence of secondary hypothyroidism (TSH deficiency) is about 3 - 6% in survivors of high dose cranial RT for pediatric brain tumors.
  • This problem is not seen after low dose prophylactic cranial RT or total body irradiation.
  • TSH deficiency is commonly seen in patients who have received over 50 Gy cranial RT
  • There can be an absence of nocturnal surge of TSH in patients who may not appear to be frankly deficient on testing. This is referred to as "hidden central hypothyroidism." There are abnormal secretory dynamics of TSH which would be missed by checking only the T4 and TSH levels. It is not clear how clinically relevant this problem is

Abnormalities in prolactin secretion:

  • Prolactin secretion is normally under the inhibitory control of the hypothalamic neurotransmitter dopamine
  • Damage to the hypothalamus may lead to loss of inhibition and to hyperprolactinemia
  • Hyperprolactinemia is commonest in adult females as a late effect of cranial RT, but may occur also male and younger survivors.
  • The risk is dose related and this problem is rare after low dose cranial RT, but may affect 20 - 50% of survivors who have received moderately high dose RT (over 40 Gy)
  • This problem tends to resolve gradually over time

Abnormalities in ADH secretion:

  • RT induced deficiency of antidiuretic hormone has never been reported.
  • This problem is usually seen in patients who had Langerhans cell histiocytosis (LCH) with involvement of the pituitary by disease


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