• Credits

  • Section Writer: Dr. Om J Lakhani
  • Section Editor: [[Dr. Om J Lakhani]

• Q. How common are endocrinopathies in chilhood cancer survivors ?

  • Very common
  • They are found in 40-60% of childhood cancer survivors
  • They are one of the most common late manifestations of these survivors

• Q. What are the potential reasons for endocrinopathies in them ?

  • Alkylating agents
  • Radiotherapy

• Q. Which are the most common endocrine manifestations of childhood cancer survivors ?

  • Hypopitutarism
  • Thyroid dysfunction
  • Gonadal dysfunction

• **Hypothalamo-pituitary dysfunction **

• Q. Enlist the problems in Hypothalamopituitary region in chilhood cancer survivors ?

  • Growth hormone deficiency
  • Central hypothyroidism
  • Central hypoadrenalism
  • Diabetes insipidus
  • Pubertal disorder
    • Precocious puberty
    • Delayed puberty
    • Pubertal arrest

• Q. Which cancer patients develop Hypothalamo-Pituitary dysfunction  ?

  • Surgery of sellar region
  • Cranial radiotherapy

• Q. What radiation exposure produces various pituitary defects ?

  • Radiation >18 Gy- GH deficiency and Precocious puberty
  • Radiation >30 Gy- LH,FSH, TSH and ACTH deficiency
  • Sequence of loss is GH, FSH/LH, TSH and ACTH

• Q. Does radiotherapy produce DI ?

  • No
  • It is seen with surgical intervention of sellar region

• Q. Which anticancer drug can produce DI ?

  • Temozolomide

• Q. Which is the most common Endocrinopathy following radiotherapy ?

  • Growth hormone deficiency

• Q. Is testicular volume a reliable indicator of puberty in childhood cancer survivors ?

  • No
  • Because cytotoxic drugs can cause damage to the seminiferous tubules leading to smaller size of testis

• Q. What are the pubertal issues in cancer patients ?

  • Delayed puberty
  • Precocious puberty
  • Arrest of puberty (Hypogonadotropuc hypogonadism)

• Q. Define early menarche ?

  • Menarche before age of 10 years
    #Clinicalpearl
    • Radiation dose >18 Gy- produces precocious puberty
    • Radiation dose > 30 Gy produces delayed puberty

• #Clinicalpearl

  • All these pituitary dysfunction can occur any time even years after the radiotherapy
  • Hence lifelong screening is advised

• Q. How long to screen for potential ACTH deficiency ?

  • Screening to be done with 8:00 am cortisol for upto 15 years after initial treatment in patients with childhood cancer

• **Growth disorder **

• Q. What are the causes of short stature in cancer patients ?

  • Spinal radiation – leading to damage to growth plate in spinal vertebra  spinal dysplasia
  • GH deficiency
  • Precocious puberty
  • Central hypothyroidism
  • Primary hypothyroidism
  • Use of glucocorticoids with chemotherapy

• Thyroid disorders

• Q. What are causes of primary hypothyroidism in cancer treated patients ?

  • Surgery of thyroid gland (thyroid cancer)
  • Radiation – to neck, mantle, total body radiation
  • Tyrosine kinase inhibitors
  • Use of I-123 MIBG or other iodine labelled compounds
  • Stem cell transplant with high dose chemotherapy like buslphan or cyclophosphomide

• #Clinicalpearl

  • Hypothyrodism may occur as late at 25 years after initial treatment
  • Hence lifelong suvelliance is required

• Q. Can they develop hyperthyroidism ?

  • Yes but it is rare
  • Radiation >35 Gy to neck region can lead to hyperthyroidism due to radiation thyroiditis

• Q. What radiation dose produces risk of thyroid cancer ?

  • Risk of thyroid cancer is seen in following :
  • Radiation therapy to children <10 years and/or
  • Radiation dose of 20-29 Gy to neck
  • Radiation dose <20 Gy with alklayting agent

• Q. What about radiation dose >30 Gy ?

  • This dose generally does not produce thyroid cancer  because thyroid cells are killed by this dose

• #Clinicalpearl

  • Routine use of ultrasound for screening may cause issues because of unnecessary thyroid nodules being detected

• Q. Summarize the thyroid dysfunctions ?

  • Central hypothyroidism
  • Primary hypothyroidism
  • Hyperthyroidism
  • Thyroid cancers

• Gonadal dysfunction  (males)

• #Clinicalpearl

  • Germ cells – produce sperm
  • Sertoli cells- support germ cell function
  • Leydig cell – produce testosterone
  • Seminiferous tubules – combination of germ cell and Sertoli cells

• Q. What radiation dose produces Germ cell dysfunction leading to Oligo/azoospermia ?

  • Radiation dose as low as 0.15 Gy can lead to germ cell dysfunction
  • Almost all males with total body radiation develop this

• Q. Which chemotherapy agents produce germ cell dysfunction ?

  • Cyclophosphamide
  • Busulphan
  • Cisplatin

• Q. What dose of radiation produces Leydig cell dysfunction ?

  • Compared to germ cell dysfunction, leydig cell dysfunction requires considerably higher dose of radiation
  • It also depends on age- younger age- more likely to develop leydig cell dysfunction
  • In prepubertal males- dose of >24 Gy – can lead to leydig cell dysfunction

• Q. Do chemotherapeutic agents produce Leydig cell dysfunction ?

  • Generally no
  • It is very rare
  • May produce subclinical leydig cell dysfunction

• #Clinicalpearl

  • Small dose of radiotherapy and chemotherapy- can produce Germ cell dysfunction
  • Only high dose of radiotherapy produces Leydig cell dysfunction

• Gonadal dysfunction (females)

• Q. What dose of radiation can produce ovarian dysfunction ?

  • Radiation >10 Gy can lead to ovarian dysfunction

• **Effect on bones **

• Q. Why are these patients at a risk of Low BMD ?

  • Malignant infiltration of bones
  • GH deficiency
  • Hypogonadism
  • Sedentary life
  • Drugs – glucocorticoids and methotrextate

• **Overweight , obesity and diabetes **

• Q. What is the cause for obesity in these patients ?

  • Hypothalamic obesity- due to surgery in hypothalamic region
  • GH deficiency
  • Hypogonadism
  • Sedentary lifestyle
  • Use of glucocorticoids

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