15th September 2024

Growth hormone deficiency

GH, also referred to as somatropin, is released from somatotroph cells, which make up 45-50% of the anterior pituitary. GH release is positively regulated by growth hormone-releasing hormone and negatively regulated by IGF-1 and somatostatin. The target organs for GH include the liver, cartilage, muscle, fat, and skin. GH influences linear and somatic growth and metabolism, including the metabolism of lipids, proteins, and carbohydrates.

Causes of GH deficiency

Clinical features

Typical symptoms and signs related to body composition include increased body fat, particularly central adiposity, decreased muscle mass and decreased muscle function.

Features related to cardiovascular and metabolic health include poor thermoregulation, decreased insulin sensitivity, increased total and LDL cholesterol and Apo B, decreased HDL cholesterol, accelerated atherogenesis, impaired cardiac function and decreased exercise capacity.

Growth hormone deficiency can cause decreased bone mineral density, which is associated with an increased risk of fractures. Quality of life can also be affected, resulting in depressed mood, reduced concentration, increased anxiety, fatigue and low self-esteem.

Investigations

Both insulin and glucagon stimulate GH and tests have derived from giving these hormones and measuring a lack of GH level rise. The insulin stress test and glucagon stimulation test are widely used methods to assess GH reserves, unless there are contraindications to insulin or glucagon use such as epilepsy, ischemic heart disease, untreated hypothyroidism or basal cortisol levels below 100 nmol/l. The growth hormone-releasing hormone test, also known as the arginine stimulation test, serves as a 2nd line option for those where the insulin tolerance and glucagon tests are contraindicated.

Low IGF-1 levels support the diagnosis of GH deficiency, but normal IGF-1 levels do not exclude it. A pituitary MRI should be performed to rule out a pituitary tumour that could be compressing GH-producing cells and causing GH deficiency.

Management

All patients with GH deficiency should be considered for growth hormone replacement therapy, especially those who are symptomatic with impaired quality of life, reduced mineral density, adverse cardiovascular risk profile, and reduced exercise capacity.

IGF-1 level is monitored to avoid over replacement, aiming to keep the values within the age-matched reference range. GH treatment is associated with impairment of insulin sensitivity, lipid metabolism and bone density. Therefore, these should be monitored at regular intervals. It can be useful to monitor quality of life using the adult growth hormone deficiency assessment (AGHDA) questionnaire.

Adverse effects of growth hormone replacement include sodium and water retention, weight gain, carpal tunnel syndrome, hyperinsulinemia, arthralgia (possibly due to intra-articular cartilage swelling), myalgia and benign intracranial hypertension which resolves on stopping treatment.

References

• Cook D, Yuen K , Miller B et al Guidelines for use of growth hormone in clinical practice, Ncbi.nlm.nih.gov, OHST-Endocrinology by Kalhan
• Feldt-Rasmussen U, Klose M. Adult Growth Hormone Deficiency- Clinical Management. [Updated 2022 May 23]. In: Feingold KR, Anawalt B, Blackman MR, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK425701/