Growth is one of the most important indicators of health and vitality, particularly in children. When the body fails to produce enough growth hormones, an essential factor in development and metabolism, it might indicate a more serious medical condition known as Growth Hormone Deficiency (GHD).
But what causes this vital hormone deficiency? Growth Hormone Deficiency causes range from hidden genetic abnormalities and birth difficulties to tumors and severe traumas, and they are all severe. Understanding these root causes is essential for early detection, successful treatment, and better long-term results.
Read this article to explore the common causes of GHD.
Growth Hormone Deficiency causes
Growth Hormone Deficiency (GHD) is a health condition where the pituitary gland fails to generate sufficient growth hormone, resulting in poor development in children and several health issues in adults. The causes of GHD are diverse and can be classified as congenital (existing at birth) or acquired (developing later in life).
Now, let’s look at the causes of Growth Hormone Deficiency in detail.
Congenital causes of GHD
Congenital GHD occurs at birth and can be caused by several factors that disturb the pituitary gland’s normal development and function, which is the primary site of GH production. These factors include genetic mutations, structural abnormalities, and perinatal (time around childbirth) injury.
Genetic mutations
Congenital GHD can be genetic and caused by inherited or spontaneous gene mutations involved in pituitary gland development, GH synthesis, or GH action. The following gene mutations have been related to isolated or combined pituitary hormone deficiencies:
- Mutations in the GH1 gene affect the generation of growth hormone itself.
- GHRHR gene mutations affect the growth hormone-releasing hormone receptor, which disrupts GH synthesis.
PROP1, POU1F1, LHX3, and LHX4 are the transcription factors that control pituitary development and can result in combined pituitary hormone deficits. As per the review published by The Journal of Clinical Research in Pediatric Endocrinology in 2010, a mutation in the PROP1 gene is a leading cause of Combined Pituitary Hormone Deficiency (CPHD).
Structural abnormalities
Brain abnormalities, particularly those affecting the hypothalamus or pituitary gland, might limit growth hormone production. These often include:
- Pituitary Aplasia or Hypoplasia: Incomplete development or absence of the pituitary gland.
- Septo-optic Dysplasia: Underdevelopment of the optic nerve, midline brain regions, and pituitary gland.
Perinatal injury
Birth trauma, Asphyxia, or Hypoglycemia in newborns may damage the hypothalamus or pituitary gland, affecting GH production. This, in turn, can lead to congenital GHD. As per a review published in 2023 by the journal Frontiers in Endocrinology, GHD and Asphyxia are found to be related.
Hypoglycemia is a medical problem where the blood sugar level is below the normal range, between 70 mg/dL (3.9 mmol/L) and 100 mg/dL (5.6 mmol/L).
Acquired causes of GHD
Acquired GHD arises later in life due to injury or malfunction in the hypothalamus or pituitary glands. Several factors, such as pituitary tumors, brain injury, CNS infections, radiation therapy, and pituitary infarction, may contribute to this.
Pituitary tumors
Benign tumors of the pituitary gland (adenomas) or tumors in the surrounding hypothalamus, such as craniopharyngiomas, are the most common cause of Growth Hormone Deficiency acquired later in life. These tumors can directly destroy GH-producing cells or disrupt the signals that control GH release. Treatment for these tumors, including surgery and radiation therapy, can result in GHD.
Brain injury
Traumatic Brain Injury (TBI), especially prebirth or postbirth head injury, can damage the pituitary gland or hypothalamus, causing GHD.
CNS infections
Central nervous system infections, including Meningitis or Encephalitis, can occasionally compromise pituitary function and contribute to GHD.
Radiation therapy
Radiation to the brain or pituitary gland, which is commonly used to treat brain tumors or other types of Cancer, can destroy GH-producing cells, resulting in GHD. The radiation dosage and treatment area determine GHD risk and severity.
According to a recent review published by the medical journal Endocrine-Related Cancer in 2024, radiation involving the hypothalamic-pituitary axis can lead to GHD.
Pituitary infarction
A deficiency of blood flow to the pituitary gland (infarction) can damage it and cause hormonal deficits such as GHD. This can happen in cases like Sheehan’s syndrome (postpartum pituitary Necrosis).
Besides all these causes, sometimes the reason behind the symptoms of Growth Hormone Deficiency is idiopathic or unknown.
Conclusion
Growth Hormone Deficiency causes are varied and complex, ranging from genetic abnormalities and congenital brain abnormalities to acquired conditions such as tumors, trauma, infections, and radiation therapy.
Sometimes, the cause is idiopathic, meaning no specific reason can be found, while in other situations, it is connected to genetic disorders or pituitary gland injury.
Understanding the various causes of GHD is essential for accurate diagnosis and treatment, especially during critical development stages in children. Advances in imaging, genetic testing, and endocrinology have enabled healthcare experts to pinpoint individual triggers and customize therapies. This can significantly impact a patient’s development, general health, and quality of life.
Frequently Asked Questions
How rare is it to have Growth Hormone Deficiency?
GHD is considered rare, affecting about 1 in 4,000 to 10,000 children. Adult-onset GHD is even less common and usually results from pituitary tumors or injuries. Its rarity often leads to delayed diagnosis.
Can Growth Hormone Deficiency cause ADHD?
Yes. While Growth Hormone Deficiency doesn’t directly cause Attention-deficit/hyperactivity Disorder (ADHD), some children with GHD may show attention, memory, or behavioral issues that mimic ADHD. These symptoms may result from hormonal imbalances affecting brain development and can improve with appropriate GH treatment.
How does Growth Hormone Deficiency cause Hypoglycemia?
GHD can cause Hypoglycemia because growth hormones typically help maintain blood glucose levels by promoting glycogen breakdown and reducing insulin sensitivity. Without enough GH, glucose production drops, and insulin effects increase, leading to low blood sugar, especially in children.
Are there environmental toxins that cause GHD?
Yes. While rare, exposure to certain toxins, such as heavy metals or endocrine-disrupting chemicals, could potentially affect pituitary function, though direct links to GHD in humans remain under investigation and are not yet well-established.
Can emotional trauma cause Growth Hormone Deficiency?
Yes, severe emotional neglect or chronic stress in children can lead to psychosocial dwarfism, where growth hormone secretion is suppressed. Preventing the child from emotional distress often reverses the deficiency and resumes normal growth.
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