DISORDERS OF GROWTH HORMONE:CAUSES,

DIAGNOSIS AND TREATMENT.

ABSTRACT: Growth hormone (GH) is synthesised and

secreted by the somatotroph cells of the anterior lobe of
the pituitary gland. Its actions involve multiple organs and
systems, affecting postnatal longitudinal growth as well as
protein, lipid, and carbohydrate metabolism. GH
hypersecretion results in gigantism or acromegaly, a
condition associated with significant morbidity and
mortality, while GH deficiency results in growth
retardation in children and the GH deficiency syndrome in
adults.
Growth hormone (GH) is an anabolic hormone that is
synthesised and secreted by the somatotroph cells of the
anterior lobe of the pituitary gland. It is a member of the
GH gene family, which includes prolactin and the
placental lactogens. Using x ray crystallography, the three
dimensional structure of human GH has been shown to
consist of two disulfide bridges, four α‐helices arranged in
an “up‐up‐down‐down” topology, and three shorter
connective helices. GH exerts its biological effects by
binding to the extracellular domain of the GH receptor, a
single pass protein that also contains transmembrane and
intracellular regions. A single GH molecule binds to two
GH receptor molecules, resulting in dimerisation of the
receptor. This GH induced GH receptor dimerisation is
thought to be the first step in the signal pathway that
ultimately results in the various biological effects
associated with GH.

The somatomedin hypothesis postulated that the observed

effects of GH are mediated via a growth factor, initially
labelled “somatomedin” and subsequently identified as
insulin‐like growth factor (IGF) 1. However, recent
evidence suggests that not all actions of GH are mediated
by IGF1 and many factors other than GH contribute to the
expression of serum IGF1 including nutritional state, liver
function, serum protease activity, IGF1 binding proteins,
and sex hormones. binding proteins, and sex hormones.
GH secretion is regulated by the hypothalamus and the
mediators of GH actions. Regulatory factors include GH
releasing hormone (GHRH), somatostatin, GH releasing
peptide (ghrelin), and IGF1. Disorders of the GH/IGF1
system result either from GH hypersecretion (gigantism,
acromegaly) or GH deficiency.

DEFINITION OF HORMONES
Hormones are chemical messengers produced by glands
in the endocrine system. They travel through the
bloodstream, regulating various physiological processes
and maintaining homeostasis in the body.

DEFINITION OF GROWTH HORMONE

Growth hormone (GH) is a peptide hormone that
stimulates growth, cell reproduction, and regeneration in
humans and other animals. It plays a crucial role in the
development and maintenance of tissues and organs
throughout the body.

ROLE OF GROWTH HORMONE

The growth hormone (GH) has several important roles in

the body:

1. **Stimulating Growth:** GH promotes the growth of

bones and tissues, especially during childhood and
adolescence. It stimulates the elongation of bones and
increases the number and size of cells.

2. **Metabolism Regulation:** GH influences

metabolism by promoting the breakdown of fats and
encouraging the use of fats for energy. It also helps spare
glucose for essential functions by reducing glucose uptake
in certain tissues.

3. **Muscle Growth:** GH contributes to muscle growth

by promoting protein synthesis and inhibiting protein
breakdown. This is important for overall muscle
development and maintenance.

4. **Organ Function:** GH supports the proper

functioning of various organs, including the heart,
kidneys, and immune system.

5. **Bone Density:** It enhances the mineralization of

bone, contributing to increased bone density and strength.

6. **Regulation of Body Composition:** GH helps

maintain a healthy balance of muscle and fat in the body.

7. **Regulation of Insulin Sensitivity:** GH has an

impact on insulin sensitivity and glucose metabolism,
affecting how the body uses and stores carbohydrates.
These roles highlight the diverse effects of growth
hormone on the body's growth, metabolism, and overall
physiological balance.

METABOLIC EFFECT OF GROWTH HORMONE

The metabolic effects of Growth Hormone (GH) include:

1. **Lipolysis:** GH stimulates the breakdown of fats

(lipolysis) in adipose tissue, releasing fatty acids into the
bloodstream. This helps provide an alternative energy
source.

2. **Protein Synthesis:** GH enhances protein synthesis

in various tissues, promoting the growth and maintenance
of lean body mass, particularly in muscles.

3. **Glucose Regulation:** GH reduces glucose uptake

in certain tissues, such as muscle and adipose tissue, and
promotes the production of glucose by the liver
(gluconeogenesis). This helps spare glucose for essential
functions and contributes to maintaining blood glucose
levels.
4. **Insulin Sensitivity:** GH influences insulin
sensitivity, affecting how cells respond to insulin. It can
have both insulin-sensitizing and insulin-antagonistic
effects in different tissues.

5. **Retention of Nitrogen:** GH helps the body retain

nitrogen, an essential component of proteins, which
contributes to the positive impact on protein synthesis and
muscle growth.

Overall, these metabolic effects of Growth Hormone play

a crucial role in maintaining energy balance, regulating
glucose levels, and supporting the growth and
maintenance of various tissues in the body.

IMPORTANCE OF BALANCED HORMONAL

LEVELS

Balanced hormone levels are crucial for several reasons:

1. **Homeostasis:** Hormones help maintain internal

stability and balance (homeostasis) by regulating various
physiological processes, including metabolism, growth,
and reproduction.
2. **Health and Well-being:** Proper hormone balance is
essential for overall health and well-being. Imbalances
can lead to a range of health issues, affecting physical and
mental aspects of an individual's life.

3. **Reproductive Health:** Hormones play a pivotal

role in reproductive processes, influencing fertility,
menstrual cycles, and the development of secondary
sexual characteristics. Balanced hormone levels are vital
for reproductive health.

4. **Metabolism:** Hormones like insulin and thyroid

hormones regulate metabolism. Balanced levels
contribute to efficient energy utilization, weight
management, and overall metabolic health.

5. **Bone Health:** Hormones such as estrogen and

testosterone are critical for maintaining bone density.
Imbalances can lead to conditions like osteoporosis.

6. **Mood and Emotions:** Hormones have a significant

impact on mood and emotions. Imbalances, especially in
hormones like serotonin and cortisol, can contribute to
mood disorders and stress.
7. **Immune Function:** Hormones influence immune
system function. Balanced hormone levels support a
robust immune response, helping the body defend against
infections and diseases.

8. **Cognitive Function:** Hormones play a role in

cognitive function and brain health. Imbalances can affect
memory, concentration, and overall cognitive
performance.

In summary, balanced hormone levels are essential for the

proper functioning of the body, influencing a wide range
of physiological processes that contribute to overall health
and quality of life. Hormone imbalances can lead to
various health issues, emphasizing the importance of
maintaining equilibrium in hormonal regulation.

DEFINITION OF GROWTH HORMONE DISORDERS

Growth hormone disorders refer to medical conditions

characterized by an imbalance or dysfunction in the
production, release, or response to growth hormone (GH).
These disorders can manifest as either excessive or
deficient levels of GH and may impact normal growth and
development, metabolism, and various physiological
functions. Conditions such as gigantism, acromegaly, and
growth hormone deficiency are examples of growth
hormone disorders. Gigantism and acromegaly result
from excess GH, leading to abnormal growth, while
growth hormone deficiency is characterized by
insufficient GH production, affecting normal growth in
children and various metabolic functions in adults.

TYPES OF GROWTH HORMONE DISORDERS

There are two main types of growth hormone disorders:

1. **Excess Growth Hormone Disorders:**

- **Gigantism:** Occurs when there is an
overproduction of growth hormone before the closure of
the growth plates in the long bones. This condition leads
to excessive growth in height, often resulting in
individuals being much taller than average.
- **Acromegaly:** Typically develops in adulthood
due to an overproduction of growth hormone. Unlike
gigantism, acromegaly doesn't cause significant height
increase but leads to the enlargement of bones, tissues,
and organs, resulting in characteristic changes in facial
features and other body parts.
2. **Deficient Growth Hormone Disorders:**
- **Growth Hormone Deficiency (GHD):** This
condition arises when the pituitary gland fails to produce
sufficient growth hormone. In children, GHD can result in
stunted growth and delayed development. In adults, it
may contribute to various metabolic issues, reduced bone
density, and altered body composition.

These growth hormone disorders can have different

underlying causes, including tumors affecting the
pituitary gland, genetic factors, or other medical
conditions influencing the endocrine system. Treatment
approaches vary depending on the specific disorder and
may involve hormone replacement therapy, surgery, or
other interventions to restore hormonal balance.

CAUSES OF GROWTH HORMONE DISORDERS

The causes of growth hormone disorders can vary and

may include:

1. **Tumors:** Tumors, particularly those affecting the

pituitary gland, can disrupt the normal production and
release of growth hormone. Tumors may lead to either
excessive (resulting in gigantism or acromegaly) or
insufficient (causing growth hormone deficiency)
hormone levels.

2. **Genetic Factors:** Some individuals may inherit

genetic mutations that affect the synthesis, secretion, or
action of growth hormone. Genetic factors can contribute
to conditions such as familial short stature or specific
syndromes associated with growth disorders.

3. **Brain Injury or Trauma:** Damage to the

hypothalamus or pituitary gland, often due to head
injuries or trauma, can interfere with the regulation and
secretion of growth hormone, leading to disorders.

4. **Infections:** Infections affecting the central nervous

system, particularly the hypothalamus and pituitary gland,
can disrupt the normal functioning of the endocrine
system, including growth hormone regulation.

5. **Autoimmune Conditions:** Autoimmune disorders

that target the pituitary gland can impair its ability to
produce and release growth hormone.
6. **Radiation Therapy:** Exposure to radiation,
especially in the head and neck region, as part of cancer
treatment, can damage the pituitary gland and affect
growth hormone production.

7. **Idiopathic Causes:** In some cases, the exact cause

of a growth hormone disorder may not be identified, and
it is classified as idiopathic.

Understanding the specific cause of a growth hormone

disorder is crucial for developing an appropriate treatment
plan. Medical professionals may use a combination of
clinical evaluations, imaging studies, and hormonal tests
to diagnose and determine the underlying cause of the
disorder.

SYMPTOMS AND COMPLICATIONS OF GROWTH

HORMONE DISORDERS

**Symptoms of Excess Growth Hormone (Gigantism or

Acromegaly):**
1. **Gigantism:**
- Rapid and excessive growth in height during
childhood or adolescence.
 - Delayed puberty.
- Enlarged hands and feet.
- Facial features may appear coarse.

2. **Acromegaly:**
- Enlargement of hands, feet, and facial bones.
- Thickening of the skin.
- Changes in facial features, such as a protruding jaw or
enlarged nose.
- Joint pain and stiffness.
- Organ enlargement, potentially leading to
complications.

**Symptoms of Growth Hormone Deficiency (GHD):**

1. **In Children:**
- Short stature and slow growth.
- Delayed puberty.
- Delayed development of teeth.
- Delayed motor development.

2. **In Adults:**
 - Decreased muscle mass and strength.
- Increased body fat, especially around the waist.
- Decreased bone density, potentially leading to
osteoporosis.
- Fatigue and reduced exercise tolerance.
- Changes in mood and cognitive function.

**Complications:**
1. **Cardiovascular Issues:** Excess growth hormone
can contribute to cardiovascular problems, including
hypertension and an increased risk of heart disease.

2. **Joint and Bone Complications:** Both excess and

deficiency of growth hormone can affect bone health.
Excess GH may lead to joint pain and arthritis, while
GHD can result in decreased bone density.

3. **Metabolic Effects:** Growth hormone plays a role

in glucose metabolism. Excess GH can lead to insulin
resistance and diabetes, while GHD may contribute to
abnormal lipid profiles.
4. **Organ Enlargement:** In acromegaly, the
enlargement of organs such as the heart, liver, and spleen
can lead to complications and reduced organ function.

5. **Psychological Impact:** Growth hormone disorders

can have psychological effects due to changes in physical
appearance and the impact on overall well-being.

Management and treatment of growth hormone disorders

often involve hormone replacement therapy, surgery to
address tumors, or other targeted interventions based on
the specific disorder and its underlying cause. Regular
medical monitoring is essential to manage symptoms and
prevent complications.

DIAGNOSIS OF GROWTH HORMONE DISORDERS

The diagnosis of growth hormone (GH) disorders

involves a combination of clinical evaluations, medical
history assessments, and laboratory tests. Here's an
overview of the diagnostic process:

1. **Clinical Evaluation:**
 - **Physical Examination:** A healthcare provider will
assess growth patterns, physical features, and overall
development. Specific attention is given to height, weight,
and proportional growth.
- **Medical History:** Gathering information about the
patient's medical history, growth milestones, and family
history of growth-related issues is crucial.

2. **Hormonal Testing:**
- **GH Stimulation Test:** This is a key diagnostic test
where the patient is given a substance (such as arginine or
insulin) to stimulate GH release, and blood samples are
taken to measure the GH response.
- **IGF-1 (Insulin-like Growth Factor-1) Test:** IGF-1
is a hormone produced in response to GH. Elevated or
low levels can indicate GH excess or deficiency,
respectively.
- **GH Suppression Test:** In some cases, a GH
suppression test may be performed to evaluate the ability
of the body to suppress GH release under certain
conditions.

3. **Imaging Studies:**
 - **MRI or CT Scan:** Imaging studies, such as
magnetic resonance imaging (MRI) or computed
tomography (CT) scans, may be conducted to visualize
the pituitary gland and identify any tumors or
abnormalities.

4. **Bone Age Assessment:**

- **X-rays of Hand and Wrist:** A bone age X-ray can
help assess skeletal maturity and compare it to
chronological age, aiding in the diagnosis of growth
disorders.

5. **Genetic Testing:**
- **Genetic Analysis:** Genetic testing may be
considered, especially if there is a suspicion of a genetic
disorder affecting GH production or action.

6. **Other Endocrine Assessments:**

- **Thyroid Function Tests:** Thyroid hormones play a
role in growth, so assessing thyroid function is important.
- **Adrenal Function Tests:** Adrenal hormones can
also impact growth, so testing adrenal function may be
part of the evaluation.
Accurate diagnosis is essential for determining the
specific type and cause of the growth hormone disorder,
allowing healthcare professionals to tailor appropriate
treatment plans. The diagnostic process is often
collaborative, involving endocrinologists, pediatricians, or
other specialists depending on the age and specific
symptoms of the individual.

TREATMENT OF GROWTH HORMONE DISORDERS

The treatment of growth hormone (GH) disorders depends

on the specific type of disorder and its underlying cause.
Here are common approaches:

1. **Excess Growth Hormone (Gigantism or

Acromegaly):**
- **Surgery:** If the excess GH is due to a pituitary
tumor, surgical removal of the tumor may be
recommended.
- **Radiation Therapy:** In some cases, radiation
therapy may be used to shrink or control pituitary tumors.
- **Medications:** Somatostatin analogs or growth
hormone receptor antagonists can be prescribed to reduce
GH levels.
2. **Growth Hormone Deficiency (GHD):**
- **Growth Hormone Replacement Therapy:** The
mainstay of treatment for GHD involves daily injections
of synthetic growth hormone. This helps promote growth
in children and addresses metabolic and other issues in
adults with GHD.
- **Monitoring and Adjustment:** Patients undergoing
growth hormone replacement therapy require regular
monitoring to adjust the dosage and assess treatment
effectiveness.

3. **Supportive Therapies:**
- **Physical Therapy:** For individuals with growth
hormone disorders affecting mobility or joint function,
physical therapy may be recommended.
- **Nutritional Support:** A balanced diet and
nutritional guidance may be part of the overall
management, especially in cases where there are
associated metabolic issues.

4. **Treatment for Underlying Causes:**

 - If the GH disorder is secondary to another medical
condition (e.g., genetic disorders, tumors), addressing the
underlying cause is a key part of the treatment plan.

5. **Lifelong Monitoring:**
- Individuals with growth hormone disorders require
ongoing monitoring to assess treatment response, adjust
medication dosages, and manage any potential side
effects.

6. **Psychological Support:**
- Psychological support may be beneficial, especially
for individuals with acromegaly or other growth hormone
disorders that impact physical appearance and well-being.

Treatment plans are individualized based on the specific

diagnosis and may involve a multidisciplinary team,
including endocrinologists, pediatricians, neurosurgeons,
and other specialists. Regular follow-up appointments are
essential to ensure the effectiveness of treatment and
address any emerging concerns or complications.

PROGNOSIS AND LONG TERM MANAGEMENT OF

GROWTH HORMONE DISORDERS
**Prognosis:**

1. **Excess Growth Hormone Disorders (Gigantism or

Acromegaly):**
- Early diagnosis and appropriate treatment, often
involving surgery or medication, can improve symptoms
and quality of life.
- Prognosis is generally favorable with timely
intervention, but long-term monitoring is essential to
manage potential complications.

2. **Growth Hormone Deficiency (GHD):**

- Growth hormone replacement therapy in children with
GHD can lead to improved growth and development.
- In adults with GHD, hormone replacement can help
manage metabolic issues, improve quality of life, and
reduce the risk of complications.

**Long-Term Management:**

1. **Regular Monitoring:**
 - Ongoing monitoring of growth, development, and
hormonal levels is crucial to assess treatment
effectiveness and make necessary adjustments.

2. **Lifestyle Management:**
- Maintaining a healthy lifestyle, including a balanced
diet and regular exercise, is important for individuals with
growth hormone disorders.

3. **Psychosocial Support:**
- Addressing the psychosocial aspects of living with a
growth hormone disorder is vital. Support groups,
counseling, or mental health professionals can help
individuals cope with challenges related to appearance
and well-being.

4. **Bone Health:**
- Monitoring bone density and addressing any issues
related to bone health is important, especially in cases
where growth hormone disorders impact skeletal
development.

5. **Adherence to Treatment:**
 - Adherence to prescribed treatments, such as growth
hormone replacement therapy, is crucial for optimal
outcomes. Regular follow-up appointments help ensure
compliance.

6. **Transition of Care:**
- For individuals with pediatric-onset growth hormone
disorders, transitioning to adult care involves continued
monitoring and addressing specific needs related to
adulthood and aging.

7. **Addressing Underlying Causes:**

- If the growth hormone disorder is secondary to an
underlying condition, long-term management involves
addressing and managing that condition.

8. **Education and Empowerment:**

- Educating individuals and their families about the
condition, treatment options, and self-management is key
to empowering them in their healthcare journey.

Long-term management requires a collaborative approach

involving endocrinologists, primary care physicians, and
other specialists as needed. Adjustments to treatment
plans and strategies may be made based on the
individual's changing needs and life stages. Regular
medical check-ups and open communication with
healthcare providers contribute to effective long-term
management of growth hormone disorders.

RESEARCH AND ADVANCEMENT OF GROWTH

HORMONE DISORDERS

Advancements in the understanding and treatment of

growth hormone disorders continue to be a focus of
medical research. Some key areas of research and
innovation include:

1. **Genetic Studies:**
- Identifying specific genes associated with growth
hormone disorders provides insights into the genetic basis
of these conditions. This knowledge can contribute to
improved diagnostics and personalized treatment
approaches.

2. **Molecular and Cellular Research:**

- Investigating the molecular and cellular mechanisms
involved in growth hormone regulation helps researchers
understand how the hormone functions and how
disruptions lead to disorders. This knowledge may lead to
targeted therapies.

3. **Treatment Modalities:**
- Ongoing research explores novel treatment modalities,
including alternative medications and delivery methods
for growth hormone replacement therapy, aiming to
improve efficacy and patient convenience.

4. **Biomarkers:**
- Identifying reliable biomarkers associated with growth
hormone disorders can aid in early diagnosis and
monitoring of treatment response. This may involve the
use of advanced imaging techniques or blood markers.

5. **Neuroendocrine Research:**
- Understanding the intricate interplay between the
hypothalamus, pituitary gland, and peripheral tissues in
the regulation of growth hormone is a focus of research.
This knowledge contributes to a deeper understanding of
the neuroendocrine control of growth.

6. **Improved Imaging Technology:**

 - Advancements in imaging technologies, such as high-
resolution magnetic resonance imaging (MRI) and
positron emission tomography (PET), contribute to more
accurate diagnosis and monitoring of pituitary tumors
associated with growth hormone disorders.

7. **Patient Outcomes and Quality of Life Studies:**

- Research assessing long-term outcomes, quality of
life, and psychosocial aspects of individuals with growth
hormone disorders helps inform holistic care approaches
and improve patient well-being.

8. **Precision Medicine:**
- The concept of precision medicine involves tailoring
treatment plans based on an individual's genetic,
molecular, and clinical profile. This approach is gaining
attention in the management of growth hormone disorders
for personalized and effective interventions.

Collaborative efforts between clinicians, researchers, and

pharmaceutical companies drive progress in the field.
Clinical trials exploring new therapeutic agents, treatment
protocols, and diagnostic tools are crucial for advancing
the understanding and management of growth hormone
disorders. As research continues, it holds the potential to
enhance diagnostic accuracy, optimize treatment
strategies, and ultimately improve outcomes for
individuals affected by these disorders.

CONCLUSION

In conclusion, disorders of the growth hormone (GH) play

a significant role in impacting both pediatric and adult
populations. From excess GH leading to gigantism or
acromegaly to GH deficiency causing growth issues in
children and metabolic disturbances in adults, these
disorders pose complex challenges.

Advancements in medical research have contributed to a

deeper understanding of the underlying causes, diagnostic
methods, and treatment options for GH disorders. The
integration of genetic studies, molecular research, and
advanced imaging technologies has allowed for more
precise diagnoses and personalized treatment approaches.

Treatment strategies, whether involving surgery,

medications, or hormone replacement therapy, aim not
only to address the immediate symptoms but also to
improve long-term outcomes and the overall quality of
life for affected individuals. Ongoing research continues
to explore innovative avenues, such as precision medicine
and novel therapeutic modalities, promising a more
nuanced and effective management of GH disorders in the
future.

As medical knowledge evolves, it is essential to

emphasize the importance of multidisciplinary care,
regular monitoring, and psychosocial support in managing
individuals with GH disorders. The collaboration between
healthcare professionals, researchers, and patients is
crucial in navigating the complexities of these disorders
and ensuring the best possible outcomes for those
affected.