Adult growth hormone deficiency

Summary: Genotropin (somatropin, rbe) treatment in adult growth hormone deficiency has been shown to:

  • Reduce cardiovascular risk factors and mortality 1-3
  • Improve physical performance 4,5
  • Reverse unfavourable changes in body composition2
  • Increase bone mineral density (BMD) and bone mineral content (BMC) 6,7
  • Improve QoL and reduce healthcare consumption 8,9
  • Be of benefit in elderly patients (<65 years of age) with severe growth hormone deficiency.10

Normal growth hormone production

Growth hormone (GH) is produced by the anterior pituitary gland, and has a role in the regulation of protein, lipid and carbohydrate metabolism in addition to increasing growth in children.6

Growth hormone secretion is intermittent and is predominantly produced during deep sleep.  Peak growth hormone production is reached during adolescence, and production then declines by approximately 14% every decade.11

Causes of adult growth hormone deficiency (GHD)

Adult GHD can be a result of adult or childhood onset, and may occur as an isolated GH deficiency or as part of a multiple pituitary hormone deficiency.

Several possible aetiologies may underlie adult hormone deficiency (GHD). 11
 

Childhood-onset GH deficiency

  • Childhood-onset growth hormone deficiency is often idiopathic, and may continue into adult life.  11
  • Iatrogenic GHD may also occur in survivors of childhood malignancy as a result of previous cranial irradiation or chemotherapy. 11

Adult-onset growth hormone deficiency (GHD)

The Society for Endocrinology estimates that approximately 1 in 10,000 adults in the UK population will develop adult onset GHD. 11

In adult-onset, GHD is commonly due to:

  • Patients with signs and symptoms of hypothalamic-pituitary disease (endocrine, structural and / or genetic causes) 11
  • Irradiation or tumour treatment 11
  • Traumatic brain injury or subarachnoid haemorrhage 11

Untreated GHD in adults may be associated with:

  • A reduced quality of life and reduced energy levels 8,12
  • Altered body composition with increased fat mass around the trunk along with dyslipidaemia and hypertension are likely to contribute to increased cardiovascular mortality in GHD 6,8
  • Reduced bone mineral density, with increased risks of osteopenia and osteoporosis.  There is 2-5 fold increased risk of fractures in adults GHD vs. non GHD deficient populations 2
  • Reduced exercise capacity and a reduction in muscle strength 4,5
  • Increased cardiovascular risk as a result of
    • Increased thickness of the intima media of blood vessels11
    • Increased levels of fibrinogen and plasminogen activator inhibitor11
    • Lipid abnormalities, especially elevated LDL cholesterol11
    • Insulin resistance11
    • Impaired cardiac function11

Genotropin has proven benefits in adults with GHD

Genotropin therapy reduces cardiovascular risk and mortality 1,2,3,13,14

  • Therapy reduces vascular risk factors 1-3
  • Treatment has been shown to improve lipid parameters, decrease total and LDL cholesterol and increase HDL cholesterol 13
  • Mortality rates have been shown to be normalised with treatment in adult growth hormone deficiency. 14

Genotropin therapy improves physical performance 5,6,15

  • Improved muscle strength, approximately normalising muscle tone has been observed following 10 years of growth hormone (GH) therapy 5
  • Significantly improved exercise duration and capacity is associated with somatropin GH treatment 4,6,15
  • Therapy significantly improves left ventricular ejection fraction (LVEF0 at peak exercise) 4,15

Genotropin reverses unfavourable changes in body composition with treatment 2,8

  • Growth hormone therapy reduces fat mass and increases lean body mass.2
    • Decreases waist circumference. 8
    • Improves waist to hip ratio. 8

Genotropin therapy increases bone mineral density (BMD) and bone mineral content (BMC)1,6,7

  • Increase in BMC and net BMD with long-term growth hormone therapy 1,6
  • Sustained increase in BMC and BMD at weight bearing sites is stimulated by long-term somatropin therapy 6,7

Genotropin improves QoL and reduces healthcare consumption 8,9

  • Improved QoL during the first year of treatment with GH (maintained during 2nd year of treatment) 8,9
  • Reduced health care consumption, including number of days spent in hospital and number of doctor visits 8,9

In one study9, 2 years of growth hormone therapy resulted in:

  • A 63% reduction in the number of days of sick leave (p<0.0004);
  • An 83% reduction in the number of days in hospital (p<0.0001)
  • A reduction in the number of doctor visits (p<0.05)

Elderly patients with GHD

Elderly patients (>65 years of age) can benefit from GH treatment 10

  • Beneficial effects of growth hormone replacement are observed in elderly patients with severe organic growth deficiency. 16
  • In KIMS patients, 6 months of GH therapy resulted in improvements in waist circumference and waist to hip ratio, diastolic BP, Quality of Life, and total and LDL cholesterol levels.8,9

Treatment goals can be achieved using lower doses compared with doses required in younger adults, which is in line with the observed physiological decrease in GH secretion in adults >60 years of age.17

Indications for Genotropin therapy in adults with pronounced growth hormone deficiency.

Genotropin (somatropin) is indicated for patients with adult onset GHD who:

  • Have severe growth hormone deficiency associated with multiple hormone deficiencies as a result of known hypothalamic or pituitary pathology, and
  • Who have at least one known deficiency of a pituitary hormone other than prolactin.

Genotropin is indicated for childhood-onset patients who:-

  • were growth hormone deficient during childhood as a result of congenital, genetic, acquired, or idiopathic causes.
    • Patients with childhood onset GHD should be re-evaluated for growth hormone secretory capacity after completion of longitudinal growth.
    • In patients with a high likelihood for persistent GHD, i.e. a congenital cause or GHD secondary to a pituitary/hypothalamic disease or insult, an insulin-like growth factor-I (IGF-I) SDS < - 2 off growth hormone treatment for at least 4 weeks should be considered sufficient evidence of profound GHD.

Please refer to the Summary of Product Characteristics for full information

Genotropin Dosage in Deficient Adult patients

In patients who continue growth hormone therapy after childhood GHD, the recommended dose to restart is 0.2 – 0.5 mg per day. The dose should be gradually increased or decreased according to individual patient requirements as determined by the IGF-I concentration.

In patients with adult-onset GHD, therapy should start with a low dose, 0.15 – 0.3 mg per day. The dose should be gradually increased according to individual patient requirements as determined by the IGF-I concentration.

In patients above 60 years, therapy should start with a dose of 0.1 - 0.2 mg per day and should be slowly increased according to individual patient requirements. The minimum effective dose should be used. The maintenance dose in these patients seldom exceeds 0.5 mg per day.

Dose titration in adults >60 years of age

  • Dose titration in adults >60 starts at 0.1–0.2 mg/day and can be gradually increased based on patient requirements 10
  • Daily maintenance dose in these patients seldom exceeds 0.5 mg/day 6

Please refer to the Summary of Product Characteristics for full information

Adverse Events: Somatropin (rbe) Replacement Therapy in Adults with Growth Hormone Deficiency

Replacement somatropin (rbe) therapy in adults with Growth Hormone Deficiency

System Organ Class

Very Common

≥1/10

Common

≥1/100 to <1/10

Uncommon

≥1/1,000 to <1/100

Rare

≥1/10,000 to <1/1,000

Very Rare

<1/10,000

Not Known (cannot be estimated from available data)

Metabolism and Nutrition Disorders

 

 

 

 

 

Type 2 diabetes mellitus

Nervous System Disorders

 

Paraesthesia*

Carpal Tunnel Syndrome

 

 

 

Benign intracranial hypertension

Musculoskeletal, Connective Tissue and Bone Disorders

Arthralgia*

Myalgia*

Musculoskeletal stiffness*

 

 

 

 

General Disorders and Administration Site Conditions

Oedema peripheral*

 

 

 

 

Injection site reaction$

Investigations

 

 

 

 

 

Blood cortisol decreased

 

*In general, these adverse effects are mild to moderate, arise within the first months of treatment, and subside spontaneously or with dose-reduction. The incidence of these adverse effects is related to the administered dose, the age of the patients, and possibly inversely related to the age of the patients at the onset of growth hormone deficiency.

$ Transient injection site reactions in children have been reported.

‡ Clinical significance is unknown

References:
1. Molitch ME, et al. J Clin Endocrinol Metab 2006; 91(5): 1621–1634.

2. Maison P, et al. J Clin Endocrinol Metab 2004; 89(5): 2192–2199.

3. McCallum R, et al. Clin Endocrinol 2005; 62(4): 473–479. 

4. Widdowson WM & Gibney J. J Clin Endocrinol Metab 2008; 93: 4413–4417.

5. Götherström G, et al. Eur J Endocrinol 2007; 156(1): 55–64.

6. Genotropin Summary of Product Characteristics.

7. Bravenboer N, et al. J Bone Miner Res 2005; 20(10): 1778–1784.

8.Trainer P, Koltowska-Haagstrom M. KIMS Pfizer International Metabolic Database. Overview 2008 Number 11.

9. Saller B, et al. Eur J Endocrinol 2006; 154: 843–850

10. Monson J, et al. Clin Endocrinol 2000; 53: 281–289.

11.  NICE Guidance [TA64]. Human growth hormone (somatropin) in adults with growth hormone deficiency

12. Copinschi G,et al. Sleep disturbances, daytime sleepiness and quality of life with growth hormone deficiency. J Clin Endocrinol Metab 2010, 95(5):2195-202.

13. Verhelst J, et al. Clin Endocrinol 1997; 47: 485–494.

14. Thomas J & Monson J. Eur J Endocrinol 2009; 161: S97–S106

15. Colao A, et al. J Clin Endocrinol Metab 2001; 86: 1874–1881.

16. Drake W, et al.  Optimising Growth Hormone Replacement Therapy by Dose titration in Hypopituitary Adults.

17. Ho K, et al. Eur J Endocrinol 2007; 157: 695–700. 

Abbreviations: GH, growth hormone; GHD, growth hormone deficiency; LDL, low-density lipoprotein; HDL, high-density lipoprotein; BMD, bone mineral density; QoL, quality of life

 

PP-GEN-GBR-0465. July 2018