Growth Hormone Deficiency: Symptoms, Types, Causes and Treatment

Growth hormone deficiency (GHD) is a complex medical condition that can affect both children and adults, influencing not only physical growth but also overall metabolic health, psychological wellbeing, and quality of life. Understanding its symptoms, types, causes, and treatment options is essential for timely diagnosis and effective management. In this article, we synthesize current research findings to provide a comprehensive and accessible guide to GHD.

Symptoms of Growth Hormone Deficiency

Growth hormone deficiency manifests differently depending on age, but its impact on the body and mind is substantial. For children, the most recognizable symptom is impaired growth, but adults experience a broader range of issues that may be less obvious at first glance. Recognizing these symptoms is crucial for early diagnosis and intervention.

Symptom	Description	Age Group	Source(s)
Short stature	Height below expected for age and sex	Children	1 6 14
Slow growth	Reduced linear growth velocity	Children	1 6
Increased fat	Truncal/central adiposity, reduced lean mass	Both	1 3 4
Low bone density	Decreased bone mineral density, fracture risk	Both	1 3 4
Hypoglycemia	Fasting low blood sugar	Children	1
Fatigue	Low energy, reduced vitality	Adults	2 3 4
Psychological	Low mood, poor wellbeing, social isolation	Adults	2 3 4

Table 1: Key Symptoms of Growth Hormone Deficiency

Growth-Related Symptoms

Children

• Short Stature and Slow Growth: The hallmark of GHD in children is a significantly slower growth rate than peers, leading to short stature with normal body proportions. Growth charts often reveal a child falling below the third percentile for height relative to age and sex 1 6 14.
• Delayed Bone Age: Bone maturation is delayed, which can be confirmed via radiological assessment 1 6.

Adults

• Loss of Muscle Mass and Increased Fat: Adults experience increased fat, especially around the abdomen (truncal adiposity), and a loss of lean muscle mass and strength 1 3 4.
• Reduced Bone Mineral Density: Both children and adults with GHD have lower bone density, increasing the risk of osteoporosis and fractures 1 3 4.

Metabolic and Psychological Symptoms

• Hypoglycemia: In children, GHD can lead to low blood sugar episodes, particularly during fasting 1.
• Fatigue and Low Energy: Adults often report persistent fatigue and reduced exercise capacity 2 3 4.
• Mood and Cognitive Changes: Symptoms such as depression, social withdrawal, poor concentration, and overall reduced psychological wellbeing are increasingly recognized in adults 2 3 4.

Additional Physical Changes

• Abnormal Lipid Profile: Increased LDL cholesterol and reduced insulin sensitivity are common findings, contributing to cardiovascular risk 4.
• Other: Decreased extracellular fluid volume, reduced physical performance, and abnormal body composition may also occur 3 4.

Types of Growth Hormone Deficiency

Not all cases of GHD are the same. The condition can be classified based on when it develops, its underlying cause, and whether it occurs alone or with other hormonal deficiencies. Knowing the type of GHD helps guide diagnosis, monitoring, and treatment.

Type	Key Features	Prevalence/Onset	Source(s)
Isolated GHD	Only GH is deficient; can be congenital/acquired	Most common	5 6 9 10
Multiple Pituitary Hormone Deficiency (MPHD)	GH + other pituitary hormones deficient	Often congenital	6 9 11
Congenital	Present from birth; due to genetic or structural anomalies	Childhood	5 6 8 9 10
Acquired	Develops after birth due to injury, tumor, etc.	More common in adults	6 7
Familial	Runs in families, with genetic mutations	Variable	5 8 9 10

Table 2: Types of Growth Hormone Deficiency

Isolated Growth Hormone Deficiency (IGHD)

• Definition: Only GH is lacking; other pituitary hormones are normal.
• Causes: May be congenital (often genetic) or acquired later in life.
• Genetics: Mutations in the GH1 or GHRHR genes are common culprits 5 6 9 10.
• Forms: Can be sporadic or familial, with different inheritance patterns (autosomal dominant, recessive) 5 8 10.

Multiple Pituitary Hormone Deficiency (MPHD)

• Definition: Deficiency of GH along with one or more other pituitary hormones (such as ACTH, TSH, LH/FSH).
• Causes: Often due to mutations in pituitary transcription factors (e.g., POU1F1, PROP1), structural defects, or acquired damage 6 9 11.

Congenital vs. Acquired GHD

• Congenital GHD: Present from birth. Causes include genetic mutations, developmental brain anomalies, or syndromes affecting pituitary formation 5 6 8 9 10 12.
• Acquired GHD: Develops after birth. Common triggers are head trauma, pituitary tumors, surgery, radiation, or other insults to the hypothalamic-pituitary axis 6 7.

Familial GHD

• Genetic Inheritance: Familial forms may be inherited as autosomal dominant or recessive traits and may show variable severity and risk of additional hormone deficiencies over time 5 8 9 10.

Causes of Growth Hormone Deficiency

The underlying causes of GHD are diverse, spanning genetic mutations, structural abnormalities, and acquired injuries. A clear understanding of these factors is essential for accurate diagnosis and personalized management.

Cause	Description	Typical Age/Onset	Source(s)
Genetic Mutations	Mutations in GH1, GHRHR, POU1F1, PROP1, others	Congenital/child	5 6 8 9 10 11
Structural Abnormalities	Pituitary/hypothalamic malformations	Congenital/child	6 12
Pituitary Tumors	Mass effect or treatment causing pituitary damage	Any age	2 4 7
Cranial Irradiation	Radiation for tumors or other conditions	Any age	2 4 7
Head Trauma	Injury to pituitary region	Any age	7
Idiopathic	No identifiable cause	Any age	6 10

Table 3: Causes of Growth Hormone Deficiency

Genetic Causes

• Mutations in GH1 and GHRHR: These account for many congenital and familial cases of IGHD. Mutations can disrupt hormone production, secretion, or action 5 6 8 9 10.
• Transcription Factor Genes: Mutations in genes controlling pituitary development (e.g., POU1F1, PROP1) often cause MPHD but may first present with isolated GHD 9 11.
• Inheritance Patterns: Autosomal dominant, autosomal recessive, and sporadic forms all exist, with varying severity 5 8 9.

Structural Malformations

• Congenital Brain/Pituitary Anomalies: MRI may reveal pituitary hypoplasia, ectopic posterior pituitary, or pituitary stalk interruption, often associated with GHD 6 12.

Acquired Causes

• Pituitary Tumors and Treatment: Tumors can compress or destroy hormone-secreting cells; surgery or radiotherapy can exacerbate deficiency 2 4 7.
• Cranial Irradiation: Used for cancer treatment, can damage hypothalamic-pituitary tissue 2 4 7.
• Trauma or Infections: Head injuries and certain infections can disrupt pituitary function 7.

Idiopathic

• Unknown Cause: In a significant percentage of cases, no clear cause is found, even after genetic and imaging studies 6 10.

Treatment of Growth Hormone Deficiency

Effective management of GHD aims to restore normal growth in children and improve body composition, bone health, and quality of life in adults. Treatment is tailored to the individual's age, severity, and underlying cause.

Treatment	Overview	Special Considerations	Source(s)
rhGH Therapy	Recombinant human GH injection	Dosage individualized	13 14 16
GHRH Analogues	Stimulates body’s own GH production	Limited to select cases	13
Monitoring	IGF-1 levels, growth rate, bone age	Adjust dose as needed	14 16
Lifelong Care	Transition to adult care, monitor comorbidities	Necessary for persistent GHD	6 16
Address Other Deficiencies	Replace additional hormones if needed	Especially MPHD	14 16

Table 4: Treatment Approaches for Growth Hormone Deficiency

Recombinant Human Growth Hormone (rhGH) Therapy

• Mainstay of Treatment: rhGH is administered via daily subcutaneous injection. Early initiation in children maximizes growth potential and helps achieve adult height within the normal range 14 16.
• Dose Individualization: Dosing is based on body weight and titrated according to response, with regular monitoring of IGF-1 levels, growth velocity, and bone age 14 16.
• Adults: In adults, rhGH therapy improves body composition (reducing fat, increasing lean mass), bone mineral density, lipid profile, and quality of life 15 17. Subcutaneous injections remain the standard, but long-acting formulations are being developed to enhance convenience 17.

Growth Hormone-Releasing Hormone (GHRH) Analogues

• Alternative Option: For select pediatric patients, GHRH analogues can stimulate endogenous GH release, though not all patients respond equally. This approach remains less common than rhGH therapy 13.

Monitoring and Safety

• Regular Assessment: Monitoring growth rate, serum IGF-1, and bone age is essential to optimize therapy and minimize the risk of over- or under-treatment 14 16.
• Side Effects: rhGH therapy is generally safe, but patients should be monitored for rare complications such as glucose intolerance, edema, or development of neutralizing antibodies 14 17.
• Transition of Care: Adolescents with persistent GHD require careful transition to adult care to maintain metabolic health and quality of life 6 16.

Management of Multiple Hormone Deficiencies

• Comprehensive Replacement: In MPHD, other deficient hormones (thyroid, adrenal, gonadal) must be replaced alongside GH for full metabolic and developmental benefits 14 16.

Long-term Considerations

• Lifelong Follow-Up: Patients, especially those with genetic forms, may develop additional hormone deficiencies over time and need regular reassessment 5 10 16.
• Quality of Life: Psychological and social wellbeing are important targets for therapy, particularly in adults where symptoms can be subtle but impactful 4 17.

Conclusion

Growth hormone deficiency is a multi-faceted disorder with significant implications for growth, metabolism, and overall quality of life. Early recognition and tailored treatment can dramatically improve outcomes.

Key Takeaways:

• Symptoms are age-dependent, with growth failure in children and metabolic, psychological, and physical changes in adults 1 2 3 4 6.
• Types include isolated GHD and MPHD, with both congenital and acquired forms influenced by genetic and structural factors 5 6 9 10 11.
• Causes vary widely, from genetic mutations to pituitary tumors and idiopathic cases 2 5 6 7 8 9 10 11 12.
• Treatment is centered on rhGH replacement therapy, adjusted individually and requiring ongoing monitoring and multidisciplinary care 13 14 15 16 17.
• Comprehensive management improves not just growth but also bone health, metabolism, and psychological wellbeing 3 4 15 17.

Understanding and addressing GHD requires a holistic, lifelong approach—empowering patients to achieve their full health potential at every stage of life.