Growth hormone deficiency (GHD) is a rare disorder characterised by the lack of growth hormone production or inadequate secretion of growth hormone (GH) from the anterior pituitary gland. It is located at the base of the brain and is responsible for the production of several hormones. GHD can be present from birth (congenital). The reason could be genetic mutations or structural defects in the human brain. It can also be acquired later in life as a result of infection, trauma, radiation therapy or tumour growth within the brain. There is also a third category that has no known or diagnosable cause is referred to as idiopathic.
Childhood-onset GHD can be all three: congenital acquired or idiopathic. It leads to growth retardation, short stature and delayed maturation such as delay in the lengthening of bones. It is one of the extremities that is inappropriate to the chronological age of the child.
In adults, GHD is often acquired from a trauma to the brain or pituitary tumour. It can also be idiopathic. It is characterised by numerous variable symptoms including reduced energy levels, reduced muscle strength, body composition, osteoporosis, increased LDL cholesterol etc,
Treatment for growth hormone deficiency requires daily injections of recombinant human growth hormone (rHGH). Patients with this type of disorder that have no known cause are diagnosed as having idiopathic GHD. Genetic tests may reveal a congenital anomaly, but these tests are often considered unnecessary after confirmation of GHD as they play no role in treatment.
However, children should be retested for GHD when they transition from pediatric to adult care. GH levels may normalise upon when they reach adulthood. The level of growth hormone considered normal for an adult is much lower than that for a child, especially one undergoing the pubertal growth spurt.
Congenital GHD is a result of genetic error and may be associated with defects in the structure of the or with midline facial defects such as a cleft palate or single central incisor.
GHD IA is an autosomal recessive condition and is characterised by retardation in growth in utero. The affected infant is small in relation to their siblings. The child usually has a normal response to the administration of hGH at first. However, at a later phase it develops antibodies to the hormone and grows into a very short adult.
Growth Hormone Deficiency IB is also an autosomal recessive and is similar to GHD IA. However, trace levels of GH is present in the child at birth and generally, the child continues to respond to HGH treatments.
GHD IIB and III are similar to IB, but IIB is autosomal dominant and III is X-linked.
Classic genetic diseases arise due to the interaction of two genes. One received from the father and the other from the mother.
Dominant genetic disorders are observed when a single copy of an abnormal gene is necessary to cause a specific disease. The abnormal gene is inherited from either parent or can be the result of a new mutation in the affected individual. The risk of passing the abnormal gene to the next generation is 50% during each pregnancy.
Recessive genetic disorders are observed when an individual inherits two copies of an abnormal gene for the same trait (one from each parent). If a person receives one normal gene and one abnormal gene for the disease, the person will be a carrier of the disease but will not show symptoms. The risk for two carrier parents to pass the defective genes and have an affected child is around 25% with each pregnancy. The risk to have a carrier child like the parents is around 50% with each pregnancy.
Offspring from parents who are close relatives have a higher chance of being affected than unrelated parents to both carry the same abnormal gene. This in turn increases the risk of having children with a recessive genetic disorder.
X-linked genetic disorders are conditions caused due to the presence of an abnormal gene on the X chromosome and it manifests mostly in males. Females who have a defective gene present on one of the X chromosomes are carriers. Carrier females generally do not show symptoms as females have two X chromosomes and only one carries the defective gene. Males have one X chromosome that is inherited from their mother and if a male inherits an X chromosome that contains a defective gene he will be affected by the disorder and show symptoms.
Acquired GHD could be a result of several causes including pre and postnatal brain trauma, central nervous system infection, tumours of the hypothalamus or pituitary such as
Rathke’s cleft cyst
Radiation Therapy, etc.
Teenagers who are diagnosed with GHD experience low self-esteem due to developmental delays such as short stature or a slow rate of maturing. For example, young men’s voices may not change at the same rate as their peers and young women may not develop breasts at the same rate.
Reduced bone strength is another symptom of AGHD. This may result in frequent fractures, especially in older adults. People with low GH levels may feel tired and lack stamina.
A range of psychological symptoms can be seen which includes:
Lack of concentration
Bouts of anxiety or emotional distress
Adults with GHD show high levels of cholesterol in the blood. Additional symptoms include an underdeveloped bridge of the nose, a distinguished forehead.etc.
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Testing is important in determining whether a child with growth retardation is suffering from a lack of growth hormone production. Several agents such as insulin, arginine, clonidine and l-dopa can indicate the presence of the disorder. The tests are meant to stimulate the pituitary to secrete growth hormone allowing for the testing of blood samples for the levels of GH at timed intervals.
Physicians also test for other hormone deficiencies that may be the primary reason behind a short stature. TSH, FreeT4, cortisol, celiac antibodies, etc. are measured to rule out underlying organic causes of stunted growth.
IGF-1, a protein produced primarily by the liver but present in all tissues in response to growth hormone stimulation. It can be measured to screen for GHD and later to titrate GH therapy.
GHD is treated by substituting growth hormones with daily injections of rHGH into the muscle or the skin. Growth hormone therapy is widely and commonly used treatment in both children and adults as discussed wherein the body is injected with artificially synthesised growth hormones. The hormone stimulates the function of the natural hormone which triggers the growth process and reproduction of cells in the body.
Daily doses rHGH is given depending on the severity of the condition. A patient diagnosed with GHD needs to visit the doctor every 1 to 2 months throughout the treatment for the condition and monitored for progress and blood tests are carried out to decide if more GH is required.
Also, regular examination of cholesterol levels, blood glucose levels, bone density will also take place during the ongoing therapy. Administration of rHGH influences the response of the body to insulin, the hormone is critical in regulating the blood glucose levels.
In the first year of this treatment, children who are administered with these injections typically grow around 4 inches or more. Over the next 2 years, they can grow up to three inches or more. Then the growth rate gradually slows down.
Q: What are the Parameters of a GHD Test?
Ans: It is a combination of direct and indirect parameters that are used to assess GHD tests, these are:
Auxologic Criteria – Body measurements are taken to be used as a defining factor.
Indirect Hormonal Criteria – IGF levels in a blood sample is measured.
Responsiveness of GH Treatment
Corroborative Evidence of Pituitary Dysfunction
Direct Hormonal Criteria – Growth hormone levels in several blood samples have measured the hormone to identity response to the provocative testing, precisely:
Increased IGF1 Levels in the Bloodstream After a Few Days of GH Treatment
Q: What are the Tests for GHD?
Ans: There are several tests to diagnose GHD
Blood test to
Measure growth hormone levels
Measure hormone levels pituitary gland produces
Test to Determine if Growth Issues Arise from the Pituitary Gland – Binding protein levels (IGF-I and IGFBP-3) blood test
Insulin Tolerance Test
Growth Hormone Stimulation Test