- 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 ---- Please consider donating to *"Notes in Endocrinology"* to keep us going. Please visit our [[DONATION]] page to know more