What are the causes of growth hormone deficiency in children. How is growth hormone deficiency diagnosed. What are the treatment options for growth hormone deficiency. What are the long-term effects of untreated growth hormone deficiency. How can parents support a child with growth hormone deficiency.

Understanding Growth Hormone Deficiency in Children

Growth hormone deficiency (GHD) is a medical condition that occurs when the pituitary gland fails to produce sufficient amounts of growth hormone to stimulate proper body growth. This condition can result in noticeably short stature in children and may have other long-term health implications.

GHD can be categorized as partial, where the pituitary gland produces insufficient amounts of growth hormone, or total, where no growth hormone is produced at all. The condition may manifest during infancy or later in childhood, affecting approximately one in 4,000 to 10,000 children.

Prevalence and Early Detection

How common is growth hormone deficiency in children? While not extremely prevalent, it affects a significant number of children worldwide. Early detection and treatment are crucial, as many affected children can reach a normal height with appropriate interventions.

Recognizing the Symptoms of Growth Hormone Deficiency

Identifying the symptoms of growth hormone deficiency can be challenging, as growth occurs over an extended period and varies among children. However, there are several key indicators to watch for:

• Noticeably slow growth with normal body proportions
• Immature appearance compared to peers
• A chubby body build
• A prominent forehead
• An underdeveloped bridge of the nose

It’s important to note that growth hormone deficiency does not affect a child’s intelligence. However, these symptoms may resemble other conditions, so consulting a physician for an accurate diagnosis is crucial.

Defining Normal Growth in Children

To better understand growth hormone deficiency, it’s essential to have a baseline for normal growth rates in children. While growth rates can vary considerably, average “normal” growth is often described as follows:

• 0-12 months: about 10 inches a year
• 1-2 years: about 5 inches a year
• 2-3 years: about 3½ inches a year
• 3 years to puberty: about 2 to 2½ inches a year

When should parents be concerned about their child’s growth? If a child’s height falls below the third percentile for their age, it may be a red flag for growth hormone deficiency and warrant further investigation.

Exploring the Causes of Growth Hormone Deficiency

Growth hormone deficiency can result from various factors affecting the pituitary gland or hypothalamus. These causes can be categorized as congenital (present at birth) or acquired (occurring during or after birth).

Congenital Causes

Congenital growth hormone deficiency may occur due to:

• Mutations in genes crucial for pituitary gland development
• Abnormalities in receptors and factors along the growth hormone pathway
• Unknown factors (the cause of most cases remains unidentified)

Acquired Causes

Acquired growth hormone deficiency can result from:

• Brain tumors in the hypothalamus or pituitary
• Head trauma
• Radiation therapy for cancers affecting the hypothalamus and pituitary
• Infiltrative diseases such as histiocytosis
• Autoimmune conditions like lymphocytic hypophysitis

Why is it important to identify the underlying cause of growth hormone deficiency? Understanding the root cause can guide treatment decisions and help predict potential long-term outcomes for affected children.

Complications Associated with Growth Hormone Deficiency

While short stature is the most obvious consequence of growth hormone deficiency, research suggests that there may be additional complications associated with this condition:

• Decreased bone mineral density
• Increased cardiovascular risk factors
• Decreased energy levels

How do these complications impact a child’s overall health and well-being? The effects of growth hormone deficiency extend beyond physical stature, potentially influencing bone health, cardiovascular function, and overall energy levels. This underscores the importance of early detection and comprehensive treatment approaches.

Diagnosing Growth Hormone Deficiency

Accurate diagnosis of growth hormone deficiency is crucial for appropriate treatment. The diagnostic process typically involves several steps:

1. Medical history review
2. Physical examination
3. Growth chart analysis
4. Blood tests to measure growth hormone levels
5. Stimulation tests to assess the pituitary gland’s response
6. Imaging studies (e.g., MRI) to examine the pituitary gland and hypothalamus

Why is a comprehensive diagnostic approach necessary? Growth hormone deficiency can be challenging to diagnose definitively, and other conditions may present with similar symptoms. A thorough evaluation helps ensure accurate diagnosis and appropriate treatment planning.

Treatment Options for Growth Hormone Deficiency

The primary treatment for growth hormone deficiency is growth hormone replacement therapy. This involves regular injections of synthetic growth hormone to supplement the body’s insufficient production.

Growth Hormone Replacement Therapy

How does growth hormone replacement therapy work? Synthetic growth hormone is administered through subcutaneous injections, typically given daily. The dosage is carefully calculated based on the child’s weight, growth response, and other factors.

What are the potential benefits and risks of growth hormone therapy? Benefits may include improved growth rates, increased bone density, and enhanced overall well-being. However, potential side effects should be discussed with a healthcare provider, as they may include headaches, joint pain, or rarely, more serious complications.

Monitoring and Adjusting Treatment

Regular follow-up appointments are essential to monitor growth progress and adjust treatment as needed. This may involve:

• Periodic height and weight measurements
• Blood tests to assess hormone levels and overall health
• Bone age X-rays to evaluate skeletal maturation
• Adjustments to medication dosage based on growth response

Supporting Children with Growth Hormone Deficiency

Parents and caregivers play a crucial role in supporting children with growth hormone deficiency. Here are some ways to provide support:

• Educate yourself about the condition and treatment options
• Maintain open communication with healthcare providers
• Encourage adherence to treatment regimens
• Provide emotional support and boost self-esteem
• Foster a healthy lifestyle with proper nutrition and exercise
• Connect with support groups or other families facing similar challenges

How can parents help their child cope with the emotional aspects of growth hormone deficiency? Open communication, positive reinforcement, and focusing on the child’s strengths and abilities can help build resilience and self-confidence.

Long-term Outlook and Management

With early detection and appropriate treatment, many children with growth hormone deficiency can achieve normal or near-normal height. However, long-term management may be necessary, particularly during the transition to adulthood.

Transitioning to Adult Care

As children with growth hormone deficiency approach adulthood, they may need to transition to adult endocrinology care. This process involves:

• Re-evaluation of growth hormone status
• Assessment of the need for ongoing treatment
• Education about potential adult-onset complications
• Guidance on lifestyle factors and overall health maintenance

Why is ongoing care important for individuals with growth hormone deficiency? Even after achieving final adult height, some individuals may benefit from continued growth hormone therapy to maintain optimal bone density, muscle mass, and metabolic health.

Future Directions in Research and Treatment

Ongoing research in the field of growth hormone deficiency aims to improve diagnosis, treatment, and long-term outcomes for affected individuals. Some areas of focus include:

• Development of long-acting growth hormone formulations
• Improved diagnostic techniques for early detection
• Gene therapy approaches for congenital forms of GHD
• Better understanding of the long-term effects of growth hormone therapy

How might future advancements impact the management of growth hormone deficiency? Continued research and innovation hold the promise of more personalized, effective, and convenient treatment options for individuals with growth hormone deficiency.

In conclusion, growth hormone deficiency is a complex condition that requires careful diagnosis, comprehensive treatment, and ongoing support. With appropriate medical care and a supportive environment, children with growth hormone deficiency can achieve optimal growth and overall health outcomes. As research continues to advance, the future holds promise for even better management strategies and improved quality of life for those affected by this condition.

Growth Hormone Deficiency | Boston Children’s Hospital

As the name implies, growth hormone deficiency results when the pituitary gland doesn’t produce enough growth hormone to stimulate the body to grow. This can result in noticeably short stature in children.

• Growth hormone deficiency may be partial (the pituitary gland produces insufficient amounts of growth hormone) or total (the pituitary gland produces no growth hormone).
• Growth hormone deficiency may occur during infancy or later in childhood.
• About one in 4,000 to 10,000 children have growth hormone deficiency.
• With early detection and treatment, many of these children can reach a normal height.

What are the symptoms of growth hormone deficiency?

Since growth takes place over many years and since children grow at different rates, symptoms of growth hormone deficiency may be hard to identify. In addition to noticeably slow growth with normal body proportions, signs may include:

• immature appearance, compared to peers
• a chubby body build
• a prominent forehead
• an underdeveloped bridge of the nose

Growth hormone deficiency has no effect on a child’s intelligence.

These symptoms may resemble other conditions, so be sure to always consult your child’s physician for a diagnosis.

How do you define ‘normal’ growth?

Growth rates vary considerably from child to child. But measured in height, average “normal” growth is often described as:

• 0-12 months: about 10 inches a year
• 1-2 years: about 5 inches a year
• 2-3 years: about 3½ inches a year
• 3 years to puberty: about 2 to 2½ inches a year

If your child is less than the third percentile in height for a child of his age, that can be a red flag for growth hormone deficiency.

What causes growth hormone deficiency?

Damage to the pituitary gland or hypothalamus may be the result of an abnormal formation that occurred before your child was born (congenital) or something that occurred during or after birth (acquired).

Congenital growth hormone deficiency can occur if there are mutations in genes for factors that are important in pituitary gland development, or in receptors and factors (including growth hormone) along the growth hormone pathway; to date, however, the cause of most of these cases is unknown.

Acquired causes of growth hormone deficiency include:

• a brain tumor in the hypothalamus or pituitary
• head trauma
• radiation therapy for cancers, if the treatment field includes the hypothalamus and pituitary
• diseases that infiltrate the hypothalamus or its connection to the pituitary gland, such as histiocytosis
• an autoimmune condition (lymphocytic hypophysitis)

It’s also important to remember that growth hormone deficiency is only one of many conditions that may affect your child’s growth. Your child’s short stature may be caused by other syndromes, and growth failure may be due to decreased nutritional intake, gastrointestinal disorders, diseases that have increased metabolic demand, or hypothyroidism.

What are complications of growth hormone deficiency?

Some research suggests that there are additional complications from growth hormone deficiency, including:

• decreased bone mineral density
• increased cardiovascular risk factors
• decreased energy level

Questions to ask your doctor

You and your family are key players in your child’s medical care. It’s important that you share your observations and ideas with your child’s health care provider and that you understand your provider’s recommendations.

If your child is experiencing symptoms of growth hormone deficiency and you’ve set up an appointment, you probably already have some ideas and questions on your mind. But at the appointment, it can be easy to forget the questions you wanted to ask. It’s often helpful to jot them down ahead of time so that you can leave the appointment feeling like you have the information you need.

If your child is old enough, you may want to suggest that she write down what she wants to ask her health care provider, too.

Some of the questions you may want to ask include:

• What’s causing my child’s growth hormone deficiency?
• Will you be prescribing growth hormone replacement therapy?
• Are there any side effects or potentially dangerous risks to treatment?
• How long will my child have to remain on medication?
• How much can I expect my child to grow?

How Boston Children’s Hospital approaches growth hormone deficiency

We view the diagnosis of growth hormone deficiency as an important first step to treatment — and, ultimately, to your child’s long-term health and continued growth. You can rest assured knowing your child is in capable hands.

Our compassionate staff includes physician specialists who are experienced in the evaluation, diagnosis, and treatment of growth hormone deficiency. And we are uniquely qualified to determine the best course of care for your child. Our child-centric approach ensures that we care for your child as a child, not just another patient.

Because the chain of events involved in growth hormone deficiency is so complex, our researchers are investigating the different events that can cause a child to have short stature. Not all of these individual defects are well understood or easy to detect with a test, making this research vital to treatment strategies.

Our Division of Endocrinology is one of the world’s leading centers dedicated to caring for children and adolescents with acute and chronic endocrine and metabolic disorders. For children who suffer from growth problems, our dedicated team of doctors, nurses, and other caregivers offer hope for a healthier future.

Growth Hormone Deficiency | Endocrine Society

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Growth hormone deficiency (GHD) is a rare condition in which the body does not make enough growth hormone (GH). Human growth hormone (GH) is a substance that controls children’s growth. Among children with short stature, GHD happens in approximately 1:4,000 to 1:10,000 cases.  

Endocrine Connection 

GH is made by the pituitary gland, a small organ at the base of the brain. In children, GH is essential for normal growth, muscle and bone strength, and distribution of body fat. It also helps control glucose (sugar) and lipid (fat) levels in the body. Without enough GH, a child is likely to grow slowly and be much shorter than other children of the same age and gender.  

GH works through a growth factor called insulin-like growth factor 1 (IGF-1). GH stimulates the liver to produce IGF-1 and release it into the circulation. IGF-1 then works at multiple tissues, like bone and cartilage, to promote growth. In addition, GH produces IGF-1 locally at tissues such as bone and cartilage.  

Some children are born with GHD (congenital), while others develop it after birth (acquired). Children with congenital GHD may lack additional hormones produced by the pituitary gland. Some children with congenital GHD are found to have mutations (errors in the genes) that involve the development of the pituitary gland or GH production and action. In certain instances, congenital GH deficiency also can be seen as part of a syndrome that may affect the development of the middle of the face.  

GHD may develop during childhood or adulthood (acquired GHD) after any process that can damage the pituitary gland or the surrounding brain area. Causes of acquired GHD include brain tumor, surgery, severe brain injury, or radiation of the area that is usually given for treatment of cancer. Rarely, acquired GHD can be the result of a chronic inflammation of the pituitary called hypophysitis, a condition that can be seen after treatment with certain cancer medications. In all these cases, the individual may have additional deficiencies of other pituitary hormones.   

Most children with childhood-onset GHD have no additional hormone deficiencies, and doctors cannot find any cause for GHD. These cases of acquired GHD are also called isolated or idiopathic and are not inherited. For some children, slow growth is not caused by GHD. There are many reasons for slow growth and below-average height in children. At times, slow growth is normal and temporary, such as right before puberty starts. A pediatric endocrinologist (children’s hormone specialist) or primary care doctor can help find out why a child is growing slowly. Most children with GHD grow less than two inches (5 centimeters) each year. 

The single most important clinical sign of GHD in children is growth failure. Children with GHD have severe short stature with normal proportions and appropriate body weight. Review of their growth chart usually shows a drop in height across two or more percentiles.    

Your doctor will review your child’s medical history and growth charts and look for signs of GHD and other conditions that affect growth. Your doctor may do tests to help find the cause of slow growth. These include: 

X-Ray: An X-ray of the hand and wrist, called bone ageto assess growth potential in children.  

Blood Tests: A doctor may order a blood test to rule out other conditions that affect growth.  

IGF-1 levels: Additional blood work testing for levels of growth factors, such as Insulin-like growth factor (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3), are helpful in diagnosing GHD.  

GH stimulation test: During this test, the child is given medicines that stimulate the pituitary to release GH. If GH levels in the blood don’t rise to a certain level, it can mean that the pituitary is not making enough GH. 

Magnetic resonance image (MRI): An MRI (imaging test) of the head is usually done in individuals with GHD to look for a problem with the pituitary or the brain.  

If IGF1 levels are low in the blood test, it may indicate that the person may have GHD. However, there are additional causes of low IGF1 levels, such as liver disease or low body weight. 

Common symptoms that are present with a diagnosis of growth hormone deficiency include: 

• Short stature and/or slowed growth in height in children.   
• Low blood glucose levels in infants and toddlers.
• Children with GHD and additional pituitary hormone deficiencies may have extra signs, such as a very small penis in newborn males or absence of puberty during teenage years.  
• Children with congenital GHD because of a syndrome may have additional symptoms such as blindness.  

Babies with severe congenital GHD usually have only a slightly reduced birth length and may not immediately show signs of slow growth. In these children, a low blood sugar can be the main sign of GHD.  

Adults with severe GHD may also experience: 

• An increase in body fat distribution with extra weight around the waist  
• A decrease in muscle bulk and strength  
• Low energy levels  
• Abnormalities in cholesterol levels  
• Increased risk for fractures 

Irradiation, surgery or injury to the pituitary area of the brain can increase the chance of developing acquired GHD. Untreated children with GHD reach a short adult height. Untreated GHD in adults may increase risk for heart disease and fractures.    

People with GHD receive treatment with daily injections of synthetic (manufactured) human GH, a prescription medicine. GH is given at home as an injection under the skin at bedtime. More recently, a sustained – release GH that is given as a weekly injection under the skin has become available.  

Individuals treated with GH need regular doctor check-ups. In children, your doctor usually monitors the growth response to GH and changes in IGF1 levels in the blood and bone age x ray.   

GH therapy is effective in improving growth and results in a normal adult height. The best results occur when GHD is diagnosed and treated early. In some children, GH can lead to four inches (10 centimeters) of growth during the first year of treatment. Therapy can continue until the child completes his/her growth and reaches adult height. At that point, the individual can be re-tested to see if he/she should continue GH therapy as an adult. Most of the childhood-onset cases of isolated GHD do not need therapy in adult life. 
 
In children, mild to moderate side effects are uncommon. They include: 

• Headaches 
• Muscle or joint pain 
• Mildly under active thyroid gland 
• Swelling of hands and feet 
• Worsening curvature of the spine (scoliosis) 

Rare but serious side effects include: 

• Severe headache with vision problems 
• A hip problem – when the top of the thigh bone slips out of place 
• Inflamed pancreas (pancreatitis) 
• Sleep apnea (i.e. blockage of upper airway during sleep) can happen in people with certain genetic conditions, such as Prader Will syndrome.  

For most children, the benefits of taking GH outweigh the risks. In adults, the GH side effects are also rare and can be swelling of hands and feet, joint pains and carpal tunnel syndrome. An increase risk for type II diabetes can happen in people with certain genetic predisposition such as Prader Will syndrome.   

Concerns have been raised about a possibility that GH may increase an individual’s cancer risk. Several studies so far point out that GH treatment for individuals with GHD does not increase the risk for leukemia or other cancers compared with age-matched healthy people.  

You can help your child get the best care for GHD by taking these steps: 

• Call the doctor if you have questions about treatment. 
• Follow directions carefully when giving GH and other prescription medicines to your child. 
• Tell all of your child’s doctors that your child takes GH. 
• Be sure your child gets frequent checkups. 

• What should my child’s height be at this age? 
• Why is my child growing slowly? 
  Does my child need treatment for GHD? 
• If so, how, and when do I give my child the shots? 
• Should we see a pediatric endocrinologist? 

Endocrine Library >>

Editor(s):
Alan Rogol, M.D., Henry Anhalt, DO, Melanie Schorr Haines, M. D., Maria George Vogiatzi, M.D.

Last Updated:
January 24, 2022

Isolated growth hormone deficiency | State Scientific Center of the Russian Federation Federal State Budgetary Institution “National Research Center for Endocrinology” of the Ministry of Health of Russia

Human growth begins from the moment of conception and goes through several stages in utero and then after the birth of a child. The growth process depends on both genetic and environmental factors, which together determine the final height of a person.

Stunting may be due to mutations in genes, acquired diseases and/or environmental factors.

Genetic factors influencing growth include factors involved in pituitary development (PROP1, POU1F1, HESX1, LHX3 and LHX4) as well as hypothalamic releasing hormone production (growth hormone releasing hormone (GHRH) or growth hormone (GH) , insulin-like growth factor-1 (IGF-1), insulin-like growth factor-2 (IGF-2), insulin (INS)) or regulating their receptors (GHRHR, GHSR, GHR, IGF1R, IGF2R and INSR), as well as factors transcriptions that control growth hormone signaling. With defects in the genes that regulate all of the above processes, it can be observed as Isolated growth hormone deficiency (Isolated Growth Hormone Deficiency, IGHD) or resistance to growth hormone, and multiple deficiency of other pituitary hormones (Multiple Pituitary Hormone Deficiency, MPHD).

Isolated growth hormone deficiency or isolated growth hormone deficiency , whose prevalence in the world is estimated from 1:4000 to 1:10000 newborns, while 5-30% of cases are congenital, most often the result of mutations in the growth hormone gene (gene Gh2) or in the growth hormone releasing hormone receptor gene (GHRHR gene).

Main clinical features of congenital isolated GH deficiency:

1. Short stature (below 3rd percentile or -2 SD)
2. Slow growth rate.
3. External signs: small facial features, large forehead, sunken bridge of the nose, bluish sclera
4. Special high timbre of voice (squeaky).
5. History may indicate hypoglycemic conditions (fatigue, loss of consciousness and a positive effect on the background of taking sweet food).
6. Uniform type of distribution of fatty tissue, it is loose; moderate diffuse pastosity.
7. Late teething or late change of milk teeth to permanent ones.

It is worth noting that a characteristic feature is manifestation after 1 year of life, as well as often burdened family history (siblings may have similar signs).

Main diagnostic criteria for diagnosis:

1. In blood: low level of IGF-1, low GH release on GH stimulation tests. The rest of the hormones (prolactin, cortisol, ACTH, TSH, free T4, free T3) are normal.
2. MRI of the brain: the pituitary may be of normal size or hypoplastic.
3. Bone age is more than 2 years behind the passport age.
4. When conducting a molecular genetic study, it is possible to detect mutations in genes.

The physician should always be aware that growth retardation or growth retardation may be the first signs of a brain mass.

The main treatment for isolated growth hormone deficiency is the administration of growth-stimulating therapy with recombinant growth hormone (rGH), which the child receives daily in the evening, until socially acceptable growth is achieved and until growth zones are closed.

Combination of growth hormone deficiency with deficiency of other pituitary hormones

Multiple pituitary hormone deficiency (or panhypopituitarism) is characterized by a deficiency of somatotropic hormone (STH), thyroid stimulating hormone (TSH) and adrenocorticotropic hormone (ACTH), as well as luteonizing hormone (LH) and follicle stimulating ( FSH) hormones and in some cases low prolactin levels.

Panhypopituitarism can be congenital (gene defect) or acquired.

Hereditary multiple pituitary hormone deficiency is caused by mutations in the POU1F1 (PIT-1), PROP-1, LHX-3, LHX-4, HESX-1, Pitx2 genes.

Main causes of acquired multiple deficiency of pituitary hormones:

1. Tumors of the hypothalamus and pituitary:

• craniopharyngioma;
• hamartomas;
• neurofibroma;
• germinoma;
• pituitary adenoma.

2. Tumors of other parts of the brain

3. Injuries:

• traumatic brain injury;
• surgical injury to the pituitary stalk.

4. Infections:

• encephalitis and meningitis;
• nonspecific (autoimmune) hypophysitis.

5. Suprasellar arachnoid cysts, hydrocephalus, empty sella symptom.

6. Pathology of cerebral vessels (hemorrhage)

7. Irradiation of the head and neck in oncological diseases

8. Toxic effects of chemotherapy.

9. Infiltrative diseases:

• histiocytosis;
• Sarcoidosis.

10. Transient:

• constitutional growth retardation and puberty;
• psychosocial (deprivation) nanism.

Important!

For children with growth hormone deficiency against the background of a volumetric formation in the brain (craniopharyngioma) or after a head injury, later periods of manifestation of growth deficiency are characteristic – after 5–6 years of age. In children with volumetric brain formation , the growth rate sharply decreases, polydipsia (drinks a lot) and polyuria (excretes a lot of urine), while emitting non-concentrated urine, may appear. Polyuria and polydipsia are characteristic signs of the development of central diabetes insipidus as a result of the development of the syndrome of compression of the pituitary stalk and impaired secretion of antidiuretic hormone.

In addition to growth deficiency, complaints such as headaches, blurred vision, and vomiting suggest intracranial pathology (craniopharyngioma).

In children with transient growth hormone deficiency (constitutional growth retardation and puberty), a family history in most cases allows us to identify similar cases of short stature and delayed sexual development in childhood and adolescence in one of the parents or close relatives.

Children with congenital multiple deficiency of pituitary hormones are characterized by a slowdown in growth dynamics from the first years of life. In children with GH deficiency, the growth rate does not exceed 4 cm per year, most often it is 1–2 cm per year.

In addition to examining the hormonal profile and assessing the bone age, the child undergoes MRI of the brain. In cases of suspected congenital nature of the disease, a molecular genetic study is indicated to search for mutations in the genes.

After a diagnosis of panhypopituitarism is made, treatment with recombinant growth hormone, levothyroxine preparations, and glucocorticoids is prescribed.