• Credits

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

• Q. Enlist the uses of Growth hormone (GH) in children?

  • GH deficiency
  • Idiopathic short stature
  • Small for gestational age
  • Turner’s syndrome
  • CRF
  • Prader Willi
  • Noonan’s syndrome
  • Short stature with SHOX deficiency

• Q. What is the effect of GH and insulin on Fatty acid?

  • They have opposite actions
  • Insulin promotes Free fatty acid synthesis
  • GH mobilizes fatty acid from the periphery

• #Clinicalpearl

  • GH increases protein and muscles mass
  • Reduces fat mass

• Q. What is the effect of GH on cartilage?

  • It enhances cartilage growth

• Q. What type of GH is used in therapy at present?

  • Aqueous solution of recombinant human growth hormone injected subcutaneously

• Q. Is it effective if given on alternate days?

  • Daily therapy is more effective than alternate day therapy, even if the same weekly dose is used

• Q. Is sustained-release preparation given weekly effective?

  • It is as effective as daily preparation

• **Use of growth hormone **

• Q. When is the best age to start treatment?

  • As young as possible

• Q. What is the starting dose in children?

  • Norditropin recommends 25-35 ug/kg/day in children (same dose recommended by guidelines)
  • However, uptodate recommends a starting dose of 40 mcg/kg/day
  • A lower dose can be used in children with severe GH deficiency since they are more sensitive to GH (20 ug/kg/day)

• Q. Which patients require a higher dose?

  • Turner and CRF patient
  • They have  a degree of GH deficiency
  • During puberty

• Q. What are the doses during puberty?

  • Doses as high as 100 ug/kg/day may be required during puberty

#Keypoints

-3 IU = 1 mg (dose conversion)
- Dose in children – 25-35 ug/kg/day (0.07-0.1 iu/kg/day)
- Turner’s = 50 ug/kg/day
- In adults- 0.15- 0.3 mg/day

• Q. What is the best time to administer GH?

  • Traditionally given in the evening or at bedtime
  • But no evidence that that is better

• Q.  How to monitor therapy and titrate dose?

  • Repeat IGF1 -4-6 week after starting GH
  • Keep IGF1 about 1 SD above the mean
  • If IGF1 is low, increase the dose and vice versa
  • Monitor GH after six month – then that is considered an important parameter
  • Note
    • The IGF1 based dosing is not recommended by guidelines (This is the idea of Cohen et al.)
    • They recommend doing IGF1 once  a year
    • IGF1 based dosing is controversial; however, Cohen’s studies show they are not only safe and effective but also efficient in terms of the dose of GH required

• Q. What to do if IGF1 is high, but GV is good?

  • Lower the dose slightly by 20%

• Q. Is IGF1 used for monitoring therapy in children with Idiopathic short stature also?

  • Yes
  • But ISS require a slightly higher dose to maintain the same IGF1 than GH deficient children

• Q. What is defined as a good response to therapy based on Growth velocity?

  • See the GV, 6 months after starting treatment. Two approaches are useful
    • If GV charts for children with GH deficiency are available – then keep the GV 1SD above the mean
    • If they are not available, use GV  charts of normal children  and try and get the GV, above the 75th percentile

• Q. Summarize the follow up investigations ?

  • IGF1 – 4-6 weeks after starting treatment
  • GV calculated 6 months after starting treatment
  • IGF1 – repeat 6-12 monthly
  • GV- check every 6 months

• Q. How , when and why is thyroid function checked ?

  • Check thyroid function 1 year after starting therapy
  • Treatment with GH can lead to treatment-related hypothyroidism- though this is rare
  • Hypothyroidism is central hence T4 must also be measured

• Q. What are the causes of poor response to treatment ?

  • Poor compliance
  • GH insensitivity
  • GH antibody (rare)
  • Concurrent glucocorticoid use
  • Incorrect dosing
  • Incorrect diagnosis
  • Concurrent hypothyroidism – untreated

• Q. Which patients develop GH antibody ?

  • Patients with GH 1A deficiency typically develop GH antibodies

• Q. When to suspect GH antibody ?

  • Patient having an initially good response to GH but then the response to GH suddenly stops
  • Check the anti-GH antibody and also mutation analysis for GH1 mutation

• **Expected response to GH therapy **

• Q. Is the increase in growth rate with GH therapy proportional to the dose ?

  • No
  • Different people have different response to GH

• Q. Which databases have provided information on response to GH therapy ?

  • Pfizer international growth database (previously called KIGS)
  • National childhood growth study (NCGS) in North America

• Q. Which factors influenced better response to GH therapy according to KIGS database ?

  • Younger age
  • Birth weight
  • Lower peak GH value on GH stimulation
  • Bodyweight
  • GH dose
  • More difference between height of child and MPH
  • All this predicts response to therapy in the first year of therapy

• Q. Is there any evidence of giving a higher dose during puberty improves final height ?

  • Yes
  • In one study, GH was at the dose of 70 ug/kg was compared to standard dose in puberty and children given higher dose had 3.6 cm gain in final adult height
  • Children not achieving expected GV at puberty may benefit with higher dose up to 100 ug/kg during puberty

• Q. What happens when GH therapy is not initiated until puberty ?

  • In such cases response to GH in any case may not be very good because epiphysis would have started to close

• Q. Does giving GnRH agonist therapy to halt puberty along with GH in children diagnosed with GH deficiency during puberty any helpful ?

  • Some studies have shown benefit of this approach
  • However, the benefit must be judged against the potential risks
  • The risks include
  • Less bone accrual during puberty
  • Psychological issues with delayed puberty

• Q. Will adding aromatase inhibitor to GH therapy in boys be helpful ?

  • Yes
  • One study has shown that adding anastoazole to GH therapy in boys with GH deficiency helped the final adult height
  • However, safety of this approach may have issues

• Q. Does GH therapy in childhood improve peak bone mass in adulthood ?

  • Yes
  • Hence continuing GH therapy in transition to adulthood may help in improving the peak bone mass

• CONTRAINDICATIONS

• Q. Can GH be used in presence of retinopathy ?

  • Proliferative or severe NPDR – contraindications

• Q. What about active malignancy ?

  • Malignancy
  • Ongoing active malignancy is a contraindication
  • If malignancy is treated it is not a contraindication

• Q. Does GH improve outcomes in critically ill patients ?

  • No it in fact, increases mortality
  • So it is contraindicated

• Q. What about Prader Willi?

  • It is per se not a contraindication for Prader Willi
  • It is contraindicated in PWS  in the following cases
    • Severe obesity
    • Upper respiratory tract obstruction
    • Untreated sleep apnea
    • Lung infection

• **Adverse effects  **

• Q. Which is the commonest side effect of GH therapy ?

  • It is headache

• Q. Enlist some common side effects in children ?

  • Headache
  • Idiopathic intracranial tension
  • Increase intraocular pressure
  • Worsening of scoliosis
  • Puberty gynecomastia
  • Slipped capital femoral epiphysis
  • Growth of nevi

• Q. How does GH affect cortisol metabolism ?

  • GH inhibits conversion of cortisone to cortisol by blocking 11 beta HSD1

• Q. When does IIH occur after starting treatment ?

  • Generally within 8 weeks after starting therapy
  • It generally resolves on stopping the medications

• Q. Which ADR are common in adults but rare in children ?

  • Arthralgia
  • Edema
  • Carpal tunnel syndrome

• Q. Does GH increase blood sugar ?

  • Yes
  • However incidence of new-onset diabetes and/OR IGT is rare

• Q. Does GH therapy increase the risk of cancer ?

  • No

• Q. Does it lead to secondary malignancy in children who are cancer survivors ?

  • No

• Q. Which benign cancer is probably increased in certain kids ?

  • Meningioma in kids with brain tumors treated with radiotherapy

• Q. What is SAGhe study ?

  • Study done in Europe done to find side effects of GH therapy
  • Found slightly high CV mortality in long term with children treated with GH
  • However, because of flaws in the study, it has been a bit discredited

• Q. Does it cause Creutzfeldt Jacob disease ?

  • Older prerpration from Pituitary extract had this risk
  • Not newer preparations

• **Duration of therapy  **

• Q. Till when should treatment for GH supplementation be continued ?

  • It should be continued till  final height is achieved defined by :
  • Growth velocity <1 cm /year (uptodate say 2-2.5 cm / year)
  • Fusion of long bone of epiphysis has taken place

• **Once weekly GH **

• Q. How much GV is typically seen with both once weekly and daily injection?

  • About 11 cm /year in the first year

• Q. What is the dose of once-weekly Eutropin?

  • 0.5 mg/kg/week

• Q. When is IGF1 measured after GH injection

  • The timing of IGF1 measurement actually does not matter, however, measure if 12 hours after the last dose and day 4 of once-weekly injection according to Khadilkar’s study

• #Updates **Notes from Endosessions **

• #Clinicalpearl

  • IGF1 based approach is actually new in pediatrics while it is a standard in adult endocrine
  • In adult endocrine – GH therapy – IGF1 is target to the normal range
  • While in children , traditionally, growth is used as a parameter
  • IGF1 correlates with the growth in children too, and hence IGF1 based approach may be a good idea for children as well

• Q. Who grows more with the same IGF1 on GH therapy – ISS or GH deficient?

  • GH deficient patients have a better response to GH despite having the same IGF1 compared to ISS patients
  • ISS patients have some degree of GH and IGF1 insensitivity

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