Growth hormone deficiency

Definitions & Key takeaways

Growth hormone (GH) is a peptide hormone that stimulates growth, cell reproduction, and regeneration. Growth hormone deficiency is a medical condition in which the body does not produce enough growth hormone. Growth hormone deficiency can cause failure to grow, delayed puberty, short stature, and other health problems.

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Introduction0:00–0:28

Growth hormone deficiency is a condition that occurs when the pituitary gland fails to release enough growth hormone. Growth hormone, also known as somatotropin, helps promote overall growth of the body, muscle mass development, protein synthesis, and carbohydrate and lipid metabolism.
So a deficiency in growth hormone, which can occur in kids and adults, results in problems in all of these areas. Growth hormone is released by the pituitary which is a pea sized gland that is connected by a stalk to a part of the brain called the hypothalamus.

Physiology0:28–3:43

The hypothalamus secretes growth hormone releasing hormone which travels through a network of capillaries called the hypophyseal portal system.
Releasing hormone eventually reaches the anterior pituitary and triggers it to secrete growth hormone. Growth hormone then travels via the blood to various target tissues in the body to stimulate growth.
This is called the hypothalamic pituitary axis. Normally, growth hormone is released in a pulsatile manner, throughout the day and peaks one hour after you fall asleep, but it is also secreted in response to various forms of internal and external stimuli.
For example, the hypothalamus senses when there’s hypoglycemia, or low blood sugar, and in response it secretes growth hormone releasing hormone.
Exercise causes the adrenal glands to secrete epinephrine and that stimulates the hypothalamus to react in the same way.
Estrogen and testosterone which are produced in high levels during puberty, stimulate the hypothalamus to release growth hormone releasing hormone as well.
The hypothalamic pituitary axis, however, is also regulated by three negative feedback loops which can prevent the release of additional growth hormone.
First off, high levels of growth hormone and growth hormone releasing hormone in the blood can signal the hypothalamus to stop secreting more growth hormone releasing hormone.
Second, it also signals the hypothalamus to produce somatostatin, which is a hormone that directly inhibits the anterior pituitary from releasing growth hormone.
Third, growth hormone secretion from the anterior pituitary is inhibited by a somatomedin called insulin-like growth factor 1, which also stimulates somatostatin release from the pituitary.
Somatomedins are produced in the liver and have many of the same growth-promoting effects on target tissues as growth hormone.
It mediates these effects by binding to insulin-like growth factor 1 receptors as well as insulin receptors, which are present on almost all tissue types.
Growth hormone can stimulate growth in most organs in the body. In the muscles, it stimulates amino acid uptake into the muscle cells, which helps with protein production and muscle growth.
Similarly, growth hormone stimulates the activity of osteoblasts in the bones and chondrocytes in the cartilage, which helps boost growth, particularly during the growth spurts of puberty.
Growth hormone also has many metabolic functions. In adipose tissue, it causes lipolysis, which is the breakdown of fats, and gluconeogenesis in the liver, which is the production of glucose.
To increase glucose levels, growth hormone causes insulin resistance, which decreases insulin's ability to move glucose into the cells.
Growth hormone also triggers the steady release of insulin like growth factor from the liver, and once it’s released into the bloodstream, insulin like growth factor functions has many of the same effects as growth hormone.

Pathophysiology3:43–5:03

Most cases of growth hormone deficiency have no identifiable cause, but sometimes there is a specific genetic or physiologic cause.
One genetic cause is a mutation in the receptor for growth hormone releasing hormone, leaving the growth hormone releasing hormone with nowhere to bind.
More broadly, there are genetic syndromes associated with growth hormone deficiency, like Prader-Willi syndrome, which is a defect in the paternal copy of chromosome 15, and Turner's syndrome, where a female is missing one of her two X chromosomes.
There are also acquired causes of growth hormone deficiency like brain trauma, infections, and radiation therapy - all of which can cause damage to the hypothalamus and pituitary gland.
The most common cause of acquired growth hormone deficiency, is a pituitary tumor which can cause compression of the gland.
This tumor-induced compression cuts off the blood supply to the pituitary gland and can prevent the release of a number of other pituitary hormones, like sex hormones, a condition called hypopituitarism.
Since sex hormones normally stimulate growth hormone release, conditions like hypopituitarism and delayed puberty where there is a deficiency in sex hormones, can also lead to growth hormone deficiency.

Symptoms5:03–6:20

Growth hormone deficiency can cause a variety of symptoms and vary in children and adults. Decreased growth hormone results in low blood glucose levels and that can lead to severe hypoglycemia, especially in infants.
In children, chronic growth hormone deficiency can cause an under stimulation of osteoblasts resulting in short stature, and in severe cases may cause dwarfism.
Sometimes that under-stimulation of osteoblasts means that the growth plates of the bones don’t fully fuse, and therefore bone growth of a child with growth hormone deficiency will be significantly slower than the average child of the same age.
This is referred to as delayed bone age. Additionally, decreased muscle development can cause children to have delayed developmental milestones in gross motor function like standing, walking, and jumping.
Delayed milestones, delayed puberty, and short stature are the most common complaints of parents with children that have a deficiency of growth hormone.
In adults, decreased growth hormone can cause muscles to weaken over time and a lower bone density with bones that are prone to fractures.
Psychological symptoms include poor memory, social withdrawal, and depression. Diagnosis typically begins by measuring growth hormone in the blood, but because growth hormone levels fluctuate throughout the day, the testing is usually done after giving a person a stimulatory agent like epinephrine or insulin.

Diagnosis and treatment6:20–6:53

It’s also helpful to measure insulin-like growth factor levels which are relatively stable throughout the day. In children, X-rays of the hand can also reveal a delayed bone age.
Growth hormone deficiency is treated by growth hormone therapy which usually involves regular injections of recombinant human growth hormone.
All right, as a quick recap: Growth hormone is an endocrine hormone secreted by the anterior pituitary and possess a variety of functions including stimulation of growth of all tissue, especially muscle and bone, and it also promotes gluconeogenesis, and protein and fat breakdown.

Review6:53–7:27

Most of these functions are mediated via the somatomedin, insulin-like growth factor 1. In children growth hormone deficiency manifests as a failure to grow and is associated with delayed puberty, whereas adults experience more generalized symptoms.