Hypothalamic Growth Failure: Causes, Diagnosis, and Treatment

Introduction:

The hypothalamus helps keep the body in a balanced and stable state. It has the main connection between the endocrine and nervous systems. The hypothalamus functions to maintain body temperature, appetite, weight, childbirth, growth, breast milk secretion, sleep, sex drive, emotions, and behavior. Depending on the affected area of the hypothalamus show different symptoms. When a growth-related area is affected, growth failure occurs.

What Is the Structure of the Hypothalamus?

Hypothalamus has three regions namely; anterior, middle, and posterior regions. Each of them has different nuclei. Nuclei contain a group of neurons that play vital functions. The anterior region secretes many hormones which interact with the nearby pituitary gland to produce more hormones. This region regulates body temperature. The middle region is responsible for appetite and growth. The posterior region helps regulate body temperature

What Are Hypothalamus Disorders?

Hypothalamic dysfunction is responsible for the development of various conditions such as;

• Diabetes Insipidus: If the hypothalamus does not produce enough vasopressin, kidneys remove too much water and cause increased urination and thirst.

• Prader-Willi Syndrome: It is an inherited disease where the patient will have an increased urge to eat, which causes obesity.

• Hypopituitarism: When the pituitary gland cannot produce hormones, because of damage to the pituitary gland or due to damage to the hypothalamus.

• Gigantism: It is a condition in which excess growth hormone is produced by the pituitary gland. It is generally seen in children and adolescents. Tall stature, larger head, hands, and feet, any tumor in the pituitary gland, and hypothalamus disorder may cause this.

• Acromegaly: It is caused when excess growth hormone is produced by the pituitary gland. Acromegaly is similar to gigantism except that it occurs in adults. The height is not affected but the nose, lips, tongue, hands, and feet are affected.

• Syndrome of Inappropriate Antidiuretic Hormone: It can occur due to stroke, hemorrhage, infection, trauma, cancer, and certain medications that cause increased secretion of antidiuretic hormones.

• Central Hypothyroidism: Arare disease that occurs because of hypothalamic and pituitary dysfunction. The most common cause is a pituitary adenoma.

• Frohlich Syndrome: It is caused by trauma or tumors affecting the eating centers and the secretion of growth hormone-releasing hormone (GHRH) and gonadotropin-releasing hormone (GnRH) affecting eating habits and delayed puberty and stature which is short.

• Kallmann Syndrome: It causes delayed puberty by reduced secretion of gonadotropin-releasing hormone (GnRH).

What Are the Symptoms of Hypothalamus Dysfunction?

Symptoms of hypothalamus dysfunction depend on the hormones affected. These include;

• High blood pressure or low blood pressure.

• Water retention or dehydration.

• Weight loss or weight gain.

• Poor bone health.

• Delayed puberty.

• Muscle loss and weakness.

• Body temperature fluctuations.

• Trouble sleeping.

• Frequent urination.

• Short stature.

What Are the Causes of Hypothalamic Growth Failure?

Many acquired and congenital hypothalamic abnormalities cause growth failure. These include;

• CHARGE Syndrome: A epigenetic disease caused by heterozygous mutations in the gene acquire encoding CHD7, a chromatin remodeling protein, causing several malformations, life-threatening, hypothalamus dysfunction, and growth failure.

• Individuals With Genetically Isolated Severe Growth Hormone Deficiency (IGHD): A homozygous mutation in the GH-releasing hormone (GHRH) receptor gene. In this condition, we can notice a marked reduction of serum concentration of IGF-I, and an increase of IGF-II leading to growth failure. This IGHD may uncover the effects of GHRH, Pituitary GH and IGF-I, IGF-II, and local growth hormone (GH) and growth factors on the size and functions of the body.

• GHRH Resistance: Anterior pituitary hypoplasia and impairment of non-rapid eye movement (REM) sleep may be due to the resistance of GHRH.

• Stature: Short stature, doll facies, high pitched pre-pubertal voice, and reduced muscle mass are because of lack of combined effect of pituitary GH and IGF-I in bones and muscles.

• Central Adiposity: It occurs because of a lack of growth hormone (GH). The brain, eyes, and immune system involve IGF-II and local GH or growth factors.

• Growth Hormone Deficiency: It is known as pituitary dwarfism caused because of insufficient growth hormone in the body. Children with having deficiency of GH generally have short stature with normal body proportions. This condition may be from birth or later it may be acquired. This condition is because of less production of GH by the pituitary gland.

What Is the Treatment for Hypothalamic Dysfunction?

Treatments depend on the etiology of hypothalamic dysfunction and its symptoms.

• Surgery or radiation is required to treat tumors.

• In the case of hypothalamic gliomas observed first and biopsy is performed for those which are not involved in chiasm and tracts.

• In the case of hypothalamic hamartomas, surgery is recommended if symptomatic with uncontrolled seizures.

• Thermoablation and radiosurgery were also used.

• For hormonal deficiencies, therapeutic hormone replacement is done.

• Proper nutrition is suggested to regulate an individual’s appetite.

• Regular exercise, proper sleep, with the right food is suggested to treat this type of condition.

What Are the Conditions Similar to Hypothalamic Dysfunction?

Some of the conditions similar to hypothalamic dysfunction include;

• Pituitary gland lesions.

• Central hypothyroidism.

• Thyroid gland dysfunction.

• Increased appetite due to genetic abnormalities.

• Hyperthyroidism.

• Sleep disorders are due to a deficiency of hormones, and other reasons for sleep patterns.

What Is the Prognosis of Hypothalamic Dysfunction?

The prognosis depends on the condition of the patient. Generally, these can be treated well with hormonal therapies. If obesity is to be treated it needs an interdisciplinary approach.

What Are the Complications of Hypothalamic Dysfunction?

Some hormonal deficiencies may cause central hypothyroidism or adrenal insufficiency. This leads to complications such as;

• Heart problems.

• Elevated cholesterol.

• Low blood pressure.

• Electrolyte disturbances.

In case of deficiency of GHRH, complications include;

• Weakness.

• Short stature.

• Osteoporosis (weak and porous bones).

• High cholesterol.

In the case of structural causes of hypothalamic dysfunction, complications include;

• Increased intracranial pressure.

• Seizures.

• Blindness, or visual field defects.

Conclusion:

Hypothalamus is a coordinating center of the body. As it releases many hormones, it is involved in various bodily functions. It is challenging to diagnose diseases of the hypothalamus and it poses a diagnostic dilemma. Hypothalamic growth failure is associated with poor bone health, muscle weakness, delayed puberty, etc. It can be treated by hormone replacement therapy or by surgery. Identification of signs and symptoms at the earliest and with proper medical attention helps in the better outcome of the treatment.