Growth Hormone Therapy

Overview

Hormones regulate a wide range of bodily activities and processes, including growth and development, metabolism, sexual function and reproduction, and mood. Growth hormone (GH) is necessary for development, especially in youngsters, but it is also involved in many other bodily functions, such as bone density, muscular mass, and mood.

It aids in the processing of protein and enhances fat breakdown in order to give the energy required for tissue development. Growth hormone levels fluctuate throughout the day, and physical exercise has an impact.

Growth hormone (GH) therapy has transformed the treatment of children suffering from growth hormone deficiency (GHD). These children had a better height result, with ultimate heights falling inside the desired height range.

Background

Many European paintings, notably those of the Spanish Court, depict persons with unusually small height who may have suffered from a lack of growth hormone (GHD). General Tom Thumb and his wife, Lavinia Warren, exploited their tiny height as members of the Barnum and Bailey Circus in the 1800s. The pair may have had a growth hormone deficit, which was not diagnosed until the early 1900s.

Development hormone extracted from human and anthropoid ape pituitaries was found in the 1950s to boost growth in children with growth hormone insufficiency. From 1958 until 1985, a restricted quantity of cadaver-derived pituitary growth hormone was utilized to treat 8000 children in the United States who had growth hormone insufficiency. Because the preparation was in short supply, dosage was less than perfect, resulting in frequent medication vacations.

Potential receivers were needed to engage in a study procedure; in order to ration the cadaveric growth hormone, the patient had to have a specified peak growth hormone level in response to provoking stimuli. In response to a greater supply of cadaveric growth hormone, this demand steadily grew, first at 5 ng/mL, then 7 ng/mL, and eventually 10 ng/mL in the early 1980s.

Since 1985, recombinant DNA–produced human growth hormone has ensured a safe and limitless source for continuous treatment at levels sufficient to restore normal development. Growth hormone deficit can be alone or combined with other pituitary abnormalities. Multiple pituitary hormone deficit, which includes growth hormone deficiency, is caused by genetic deficiencies in pituitary stem cells or anatomic issues that might be congenital or acquired (eg, from tumor, trauma, radiation, infection).

Pathophysiology of Growth Hormone

Too little or too much growth hormone might lead to serious development issues. One of the primary reasons of low height and disorders like dwarfism is a lack of HGH. Some people use HGH because they believe it will help them gain muscle, boost their performance, or halt the aging process. The available information, however, does not support the use of HGH for these goals.

Exercise and other related activities might cause the levels to naturally rise. Growth hormone levels are also increased by sleep, stress, and low blood sugar levels. Even little variations in HGH levels have an impact on the body.

Growth hormone–releasing hormone (GHRH) from the hypothalamus and perhaps another signal, which may be activated by particular growth hormone–releasing peptides, increase pituitary growth hormone release (GHRPs). The GHRP receptors have been discovered, and the natural ligand for these receptors has been identified as ghrelin. The hypothalamic hormone somatostatin decreases growth hormone secretion.

Insulinlike growth factor 1 (IGF-1) is produced when growth hormone pulses are delivered into the systemic circulation, either locally or at the site of developing bone. Growth hormone circulates after attaching to a particular growth hormone–binding protein (GHBP). This GHBP is the growth hormone receptor's extracellular part. IGF-1 binds to one of numerous IGF-binding proteins and circulates almost exclusively in the bound form (>99 %). IGFBP-3 is responsible for the majority of IGF-I binding, and this binding protein is directly dependent on growth hormone.

A disturbance in the growth hormone axis in the upper brain, hypothalamus, or pituitary may result in growth hormone insufficiency. This disorder can be inherited or acquired.

Aside from growth hormone deficit, afflicted people have also experienced prolactin and varied thyroid-stimulating hormone (TSH) abnormalities. Pituitary imaging often indicates a hypoplastic or ectopic posterior pituitary gland.

Congenital growth hormone deficiency can be caused by a defective pituitary gland or as part of a disease such as septooptic dysplasia (SOD), which can include various pituitary deficits, optic nerve hypoplasia, and the lack of the septum pellucidum; it affects roughly 1 in 50,000 infants.

Trauma, infections (e.g., encephalitis, meningitis), cranial irradiation (somatotrophs appear to be the most radiation-sensitive cells in the pituitary), and other systemic disorders can all cause acquired growth hormone deficit (particularly histiocytosis). Although most cases of solitary growth hormone insufficiency are idiopathic, most cases of growth hormone deficit coupled with other pituitary abnormalities are caused by identifiable etiologies.

Growth hormone deficiency Symptoms

Children born with low amounts of growth hormone may or may not be smaller. Growth issues may arise over time, for example, if they are smaller than their classmates and grow fewer than 2 inches each year. Some children are born unable to manufacture growth hormone and continue to have low amounts throughout their lives.

Symptoms of growth hormone deficiency in children are:

Looking much younger than other children their age
Having a chubby body build
Impaired hair growth
Delayed puberty
Short stature

A lack of growth hormone is part of a hereditary issue in certain children, although the reason of the shortage is not always identified.

Pediatric Growth Hormone Deficiency

When the pituitary gland does not produce enough growth hormone, this is known as growth hormone deficit. GH is required to encourage bone and other tissue development. A child's IQ is unaffected by GH deficiency. Slow height development after a child's third birthday is the most obvious indicator of GH insufficiency.

Clinical Presentation

The following topics should be addressed in the history of patients with suspected growth hormone deficiency (GHD): Weight and length at birth: Intrauterine growth retardation is a differential diagnosis that should be obvious from the birth history.

Height of parents
Timing of puberty in parents
Previous growth points
General health of child: Exclusion of chronic disease as the cause of short stature is imperative.
Nutritional history: Malnutrition is the most common cause of short stature worldwide.

The following items should be targeted:

Height and weight measurement

Plotting the points on a growth chart is the greatest approach to examine height or weight data. A growth chart shows the child's growth through time, enables for height or weight comparisons with other children, and graphically indicates variations in growth or growth velocity.

Proportionality: Inspect the child for proportionality of limbs and trunk.
Pubertal status
Evidence of specific syndromes: Many syndromes include short stature as follows:

Turner syndrome
Noonan syndrome
Russell-Silver syndrome

Workup of growth hormone deficiency

Laboratory Studies

Laboratory studies in growth hormone deficiency (GHD) include the following:

Thyroxine and thyroid-stimulating hormone: Hypothyroidism should be ruled out as a cause of stunted development and small height.
Serum electrolytes: A low bicarbonate level might suggest renal tubular acidosis, which could lead to growth failure. Electrolytes that are abnormal may suggest renal failure.
CBC count and sedimentation rate: may be helpful if inflammatory bowel disease is suspected.
Insulinlike growth factor 1 (IGF-1) and IGF-binding protein 3

Imaging Studies

Bone age: A radiograph of the left hand and wrist is compared to standards to determine skeletal maturation.

Patients with growth hormone insufficiency should get a head MRI to rule out a brain tumor (eg, craniopharyngioma). A pituitary gland issue affects around 15% of people with growth hormone insufficiency (eg, ectopic bright spot, empty or small sella).

Growth Hormone Deficiency Management

Although growth hormone is naturally released in many peaks throughout the day and largely at night, a physiologic replacement can be achieved with a single daily injection of recombinant growth hormone. Other pituitary deficits must be corrected before growth hormone replacement can be successful. Sequential height measurements and bone age calculations are used to assess response to growth hormone treatment.

Newer, longer-acting GH formulations are currently being researched. Although none have yet been licensed in the United States, these medications that rely on multiple technologies to extend therapy duration look promise.

Getting and Giving GH Injections

Because GH injections are rapid and nearly painless, children as young as 10 years old may be able and frequently choose to administer their own shots. It is critical that a parent oversees the injection to ensure that the youngster administers the right amount each day. Younger children should be given the shots by their parents. Because natural growth hormone is mostly released during sleep in children, GH medication is more successful when administered before bedtime.

Learning how to give GH injections may seem scary at first, but after you and your child get used to it, it will become a routine. However, there are several things you should know before beginning GH therapy:

Storage

GH must be refrigerated at 36 to 42° F; letting it get too hot or too cold will decrease its effectiveness.
If left out overnight, you may place it back into the refrigerator and continue to use it.
When traveling, store it in the starter kit's cooler for up to 10 hours before putting it on ice. Avoid placing GH pens directly in ice and keep them separate by placing the pen in a Ziploc bag.

Time of Day

Give GH at night, ideally within an hour of going to bed. Try to administer it within an hour span, such as between 9 and 10 p.m. every night.
You may periodically adjust the time by a few hours sooner or later, but do not provide before 5 p.m. unless there are exceptional circumstances (such as leaving for a trip, a sleep-over, etc.)
Make up any missing shots.
Try not to miss more than once a month for optimum results.

Injection Sites

Use four of the eight potential injection sites, rotating them each time. The locations are the back of the arms, the top or outside of the thighs, the sides of the abdomen, and the outer quadrant of the buttocks.
On a calendar, record the site's use every night.
Keep a record of when you open a new cartridge to keep track of expiration dates and the number of injections utilized from each cartridge.

Finishing A Cartridge

Because GH is very expensive, you should use up all of the medication in every cartridge.

Pens will only enable you to dial to the remaining medicine. Use the last of it, then begin a fresh cartridge by injecting the quantity that is lacking a second time.
You may need to replace cartridges once a week or so. Do not administer another injection if there is less than 0.2 mg remaining in the old cartridge or if you are missing less than 0.2 mg from the previous injection.

What to Expect with Growth Hormone Treatment?

The essential thing to anticipate is progress. Although it may take 3 to 6 months to notice any height changes, the essential thing to remember is that your child will most likely grow 1 to 2 inches during the first 6 months of commencing therapy. Other things you may notice include:

Your child's shoes may swiftly outgrow them. Foot development can happen in 6 to 8 weeks; therefore, you may need to buy new shoes more frequently.
Your youngster may desire to consume more food. An increase in appetite is frequent, particularly if the patient had a low appetite before to therapy.
Once height growth begins, your child may appear skinnier for a period of time. GH therapy is commonly associated with an increase in lean body mass and a decrease in fat mass.

It may take years for your child to attain adult height, so you should be informed that GH therapy is frequently a long-term commitment. Regular appointments to the pediatric endocrinologist will be required, as will frequent blood tests and x-rays to check your child's therapy progress. Although the time of treatment varies, your kid will most likely need to continue receiving GH medication until he or she has:

Reached his or her full adult height
Reached full bone maturity
Grown less than 2 cm in the last year

Is Growth Hormone Therapy Safe?

Although growth hormone injections are reasonably safe and effective, they do have a few drawbacks. Fortunately, severe adverse effects are uncommon. The most frequent adverse effects include swelling, numbness, and joint and muscle aches and pains.

These adverse effects may occur if you receive more growth hormone than you require. If you have any of these symptoms, contact your doctor right once. He or she will change the dosage of the growth hormone you are taking. The symptoms should go away on their own once your doctor changes your dose.

Some patients, such as those with tumors or cancer, should not get growth hormone injections. People who are very ill, have many traumatic injuries, or have significant respiratory issues should not receive growth hormone injections.

Growth Hormone Deficiency Follow-up

Most pediatric endocrinologists see growth hormone treatment patients 2-4 times per year. The primary reasons for follow-up are to assess growth progress and alter growth hormone dose. The rate of growth normally rises the greatest during the first year of therapy, with an average increase of 8-10 cm/y.

Over the next few years, progressive development will decelerate (ie, waning effect). A slower-than-expected growth rate should trigger an examination for a medical explanation (e.g., hypothyroidism) or another diagnosis (eg, inflammatory bowel disease). Follow-up may also be required to ensure patient adherence to growth hormone injections.

Growth Hormone Therapy Complications

Although growth hormone treatment causes minimal adverse effects in individuals, the following problems have been identified:

Carbohydrate metabolism: Growth hormone has an anti-insulin action, and glucose metabolism has been examined in numerous growth hormone treatment clinical research. An examination of large databases encompassing over 35,000 kids on growth hormone and over 75,000 patients with years of exposure found no higher incidence of type 1 diabetes than would be predicted in an age-matched population of youngsters. One research indicating an increased prevalence of type 2 diabetes in children receiving growth hormone therapy and having diabetes risk factors implies that growth hormone may cause this illness to manifest sooner.
Benign intracranial hypertension (pseudotumor cerebri): There is a strong link between intracranial hypertension and growth hormone treatment. The probability looks to be around 0.001. (21 cases reported out of 19,000 patients receiving growth hormone, or 50,000 patient-years). During the first four months of treatment, severe headache symptoms (sometimes accompanied by vomiting) are common. This consequence was more common in children taking growth hormone for chronic renal insufficiency. In most cases, discontinuing growth hormone therapy corrected the intracranial hypertension; growth hormone may then be reintroduced at a reduced dose and gradually titrated back to the standard level.
Fluid homeostasis: Growth hormone disrupts fluid equilibrium, causing edema and even carpal tunnel syndrome. These issues are more frequent in individuals who are using growth hormone. When these instances become significant enough to warrant intervention, discontinuing the growth hormone provides a remedy. It is typically feasible to restart the growth hormone at a lower dose and gradually titrate it back to the regular amount.
Skeletal and joint problems: Children who get growth hormone therapy are more likely to have slipping capital femoral epiphysis (SCFE). Even without growth hormone treatment, children with GHD, hypothyroidism, or renal illness appear to be at greater risk for SCFE. When a kid taking growth hormone therapy complains of hip or knee pain, a thorough physical examination and, if necessary, hip radiography are required. Another skeletal-related consequence of growth hormone treatment is scoliosis advancement. Scoliosis is caused by fast development during therapy and is not a direct result of growth hormone. Patients with scoliosis who are receiving growth hormone treatment should have their scoliosis evaluated during treatment.
Prepubertal gynecomastia: Although teenage gynecomastia is prevalent, prepubertal gynecomastia is uncommon. Such instances have been documented in conjunction with growth hormone therapy, while it is unclear if the gynecomastia is due to the growth hormone. Prepubertal gynecomastia is a harmless disorder that disappears without complications.
Leukemia: In response to occasional reports of leukemia in individuals receiving growth hormone treatment, several global databases were analyzed. When patients with additional risk factors (for example, a history of leukemia, radiation, or chemotherapy) are eliminated, no higher risk of leukemia is seen. There is no indication that growth hormone treatment causes leukemia in otherwise healthy youngsters.

Conclusion

Children that are born tiny for their gestational age may experience ongoing growth retardation, resulting in permanent low stature. In most cases, this is associated with aberrant growth hormone release as well as abnormal insulin-like growth factor levels. Growth hormone treatment is a type of hormone therapy that involves the administration of growth hormone (GH) as a prescription drug.