What is GH (Growth hormone)?

GH is a hormone produced from the pituitary gland. It is secreted under the influence of GHRH (GH releasing hormone) which is released from the hypothalamus. Just like any other hormone it is also secreted in a pulsatile manner. GH secretion is affected by a lot of factors (age, weight, sex, thyroid hormones, sex hormones, nutrition, stress, etc.).

What are the functions of GH?

GH is required for the growth of a child (till all the bones are fused). It has an important role in regulating carbohydrate, fat and protein metabolism. It is also an anabolic hormone and affects body composition.

What are the problems associated with GH deficiency (lack of GH)?

Lack of GH in child can lead to short stature. Lack of GH in an adult can result in altered body composition (decreased muscle mass and increased abdominal fat) leading to abdominal obesity and metabolic syndrome.

What are the reasons for GH deficiency (GHD)?

It can be congenital (deficiency since birth) or acquired (deficiency after birth).

Congenital:
(a) Isolated GH deficiency: GH1 gene mutation, GHRHR gene mutation, etc.
(b) Combined pituitary hormone deficiency: Pit1 gene mutation, PROP1 gene mutation, HESX1 gene mutation, etc.

Acquired:
(a) Tumors of the pituitary gland (adenoma/metastasis/lymphoma)
(b) Trauma to pituitary gland
(c) Infections of the pituitary gland (Tuberculosis, abscess, etc.)
(d) Infiltration of the pituitary gland (Langerhans cell histiocytosis, etc.)
(e) After radiotherapy/pituitary surgery
(f) Damage to the hypothalamus or stalk
(g) Inflammation of pituitary gland (hypophysitis)

How to diagnose GHD in a child?

(a) Short stature or decline in growth velocity
(b) Rule out other causes of short stature (malabsorption, malnutrition, chronic medical illness, skeletal dysplasia, syndromic short stature, rickets, renal tubular acidosis, pseudohypoparathyroidism, hypothyroidism, etc.)
(c) Peak GH level < 7 ng/ml on GH stimulation test (d) Low/low normal IGF1/IGFBP3 level (e) Delayed bone age

What is GH stimulation test?

GH is a hormone, which is secreted in pulsatile fashion. Hence, a single random value of low GH level is not sufficient to diagnose GHD. GH level should be checked after stimulation with medicines (Clonidine, Glucagone, GHRH, Insulin, etc.). This test is done in fasting. It may require repeated blood sampling (every 30 minutes) for 2-4 hours. You may be asked to take Estrogen tablets for 3 days prior to the test (for GH priming). GH level > 7 ng/ml after stimulation almost rules out GHD. Checking GH level by 2 different stimulation tests may be required to increase the specificity.

What is the importance of bone age in GHD?

X ray left hand is required for bone age estimation. It is useful for the diagnosis as well as management/monitoring. GHD is associated with delayed bone age. If the bones are fused then GH therapy is of no use for height gain.

What is the treatment of GHD?

GHD is treated with Growth hormone (GH). GH is given as a subcutaneous injection at bedtime daily. GH can be easily injected by yourself or by parents. Daily dose of GH is based on weight. So, the dose needs adjustment at regular interval.

What are the side effects of GH therapy?

GH Therapy in a patient with GHD is not associated with any major adverse events. Rare side effects are: injection site reactions, gynecomastia, fluid retention, impaired glucose tolerance, etc. These side effects are usually seen in those patients where GH therapy is started for the reasons other than GHD (e.g. idiopathic short stature, turner syndrome, etc.) or GH is prescribed in a higher dose. IGF1 levels can be monitored at least once in 6 months to keep IGF1 level in upper normal range (to avoid overdose of GH).

What is the usual height gain with GH therapy in a patient with GHD?

First year: 10-12 cm, second year: 8-10 cm, thereafter: ~ 5-6 cm/year.