Pituitary Dwarfism Causes, Symptoms, Diagnosis And Treatment
Pituitary dwarfism or dwarfism is a condition characterized by growth and development disorders caused by insufficient secretion of pituitary somatotrope hormone (growth hormone or GH). The condition begins in childhood, but becomes more evident during puberty. Dwarfism is a condition in which growth is very slowed or delayed. Pituitary dwarfism is a consequence of decreased function of the pituitary gland occurred early in childhood before the ossification of bone cartilages.
Pituitary Dwarfism Causes
Pituitary dwarfism is caused by various disorders of the pituitary gland function. The pituitary gland is an organ the size of a pea, located at the base of the brain, rests in a small, bony cavity called the Turkish saddle. This gland is divided into three lobes: anterior lobe (Adenohypophysis)?, intermediate and posterior (Neurohypophysis). The adenohypophysis produces the growth hormone (GH), adrenocorticotropin (ACTH), thyroid stimulating hormone (TSH), prolactin, follicle stimulating hormone (FSH), luteinizing hormone (LH). The neurohypophysis produce the antidiuretic hormone (vasopressin) and oxytocin.
The growth process starts in the hypothalamus. The hypothalamus provides a dual control role upon pituitary hormone secretion and autonomic nervous system activity.
The hypothalamus secretes GH-RH (growth hormone - releasing hormone) that stimulates growth hormone secretion from the adenohypophysis(GH). When growth hormone is released into the bloodstream it trigger secretion in the liver of a hormone called insulin-like growth factor-1 (IGF-1). In turn, IGF-1 directly stimulates bone and muscle development, causing growth of the long bones and increased protein synthesis in the muscles. Because growth is a complex phenomenon, it can be slowed or stopped by abnormalities that occur in any part of this process.
There are two types of pituitary dwarfism:
- Pituitary dwarfism due to low adenohypophysis production of hormones. When none of the previous pituitary hormones are properly produced, endocrine failure is manifested on pituitary hormone dependent lines. It is characterized by slow overall growth, and patients do not show signs of normal puberty.
- Pituitary dwarfism due to isolated growth hormone deficiency. A common form of dwarfism is caused by deficiency in the production of pituitary growth hormone (GH). Patients are developed proportionally, reach sexual maturity and can reproduce.
What causes pituitary dwarfism?
Pituitary dwarfism may be caused by:
- Genetic mutations – specific investigations are needed in order to determine the specific genetic mutations that can cause pituitary dwarfism occurrence.
- Trauma (including surgery) of the pituitary gland
- Tumors, trauma or irradiation of the central nervous system
- In most cases the cause of pituitary dwarfism is unknown – idiopathic.
Pituitary Dwarfism Symptoms
Children with pituitary have an abnormal slow growth rate, however the body proportions of children suffering from growth hormone deficiency are normal. Children with a pituitary dwarfism usually have a stature 20-25% lower than the normal average age stature. Smaller stature is evident from the age of 2-4 years. The cranial perimeter in children with growth hormone deficiency is usually normal.
Due to deficient degradation of fat, fat distribution in patients is much higher than in normal subjects of the same age, especially around the waist. Rarely excess fat deposits in the thighs, abdomen or in the mammary glands can occur.
In patients with pituitary dwarfism, protein synthesis is diminished and the muscle mass is proportionally decreased than in normal individuals of the same age. Studies show that in children with pituitary dwarfism, the skeletal muscle cells are less numerous than normal. Therefore, muscle strength, which can be measured in older children using different exercise tests, is decreased.
Sexual organs are not sufficiently developed, women have the uterus and vagina of reduced dimensions, the mammary glands are also underdeveloped. Amenorrhea is also present. In males the testicles are not descended into the scrotum, the penis and scrotum have infant sizes.
Patients may have a normal sex life but reproduction is quite rare and it usually takes place only in isolated deficiency of somatotropin cases.
Inadequate degradation of glycogen to glucose can lead to hypoglycemia and seizures in severe and untreated hypoglycemia cases.
Intelligence is mostly normal, but behavior remains childish and patients often present asthenic type disorders, depression, inferiority complex.
The head and limbs are too small, but proportionate, and this makes the overall appearance of the patient to be harmonic. The face is small, and due to the underdeveloped maxilla and mandible, the small teeth are intercalated. The nose is small, eyes very close to each other, but lively.
Pigmentation spots, freckles and fine wrinkles can be present on the facial skin. Due to these wrinkle, the patient gets an appearance of early aging. Hands and feet are small, often the skin is cyanotic.
Once puberty has passed, the patient retains the appearance of dwarf, skeleton and muscles remain undeveloped. Because the structure of the infant’s larynx, high-pitched voice in present also in adults.
In case of craniopharyngioma (a tumor located near the pituitary gland), children can have neurological symptoms such as headaches, vomiting, and vision problems (blurred vision, double vision).
Pituitary Dwarfism Diagnosis
Growth hormone deficiency is present at birth, but since the main symptom of pituitary dwarfism is growth at a reduced rate, the disease is not diagnosed until later in childhood. Growth charts by age will help determine a diagnosis. Another diagnostic technique using x-ray of the hand (fist) is used to determine bone age comparing it with the child’s chronological age. Bone age in children with pituitary dwarfism is usually 2 or more years delayed than the actual chronological age. This means that if a child with pituitary dwarfism is 10 years old, his bones will look like those of a child of 8 years.
Dosing the growth hormone and IGF-1 (somatomedin C) in blood is useful for diagnosis. Determination of growth hormone can be performed both in basal conditions and after stimulation (exercise, arginine, glucagon or insulin). Failure or inadequate response to stimulation tests is associated with hypopituitarism.
Radiography of the ”turkish saddle” (bone structure in which the pituitary gland rests) or more advanced imaging techniques such as magnetic resonance imaging (MRI) or computed tomography (CT) can help the doctor to highlight the presence of different tumors of the pituitary gland .
Pituitary Dwarfism Treatment
To limit growth disorders in children with pituitary dwarfism growth hormone therapy is recommended that is effective in a number of as long as the treatment is started during the growth process. Doses are given as daily subcutaneous injection until the child reaches an appropriate height.
To receive treatment based on growth hormone, a lack of secretion of this hormone that was diagnosed by repeated blood tests must be evidentiated .
Dwarfism can be seen in other cases, but that growth hormone is normal:
- Turner syndrome is a genetic disease that affects only girls. It is caused by complete or partial absence of a sex chromosome, leading to problems such as low height or reproductive difficulties.
- Children with renal failure, diabetes, tuberculosis, digestive disorders, heart disease and chronic infections
- Prader Willi syndrome is a chromosomal abnormality, due to gene deletions of the short arm of chromosome 15 of paternal origin or both chromosomes 15 with maternal origin. Syndrome traits are reduced fetal movements, obesity, hypotonia, mental retardation, short stature, hypogonadism, strabismus, small hands and feet. For these children, administration of growth hormone begins to show encouraging results.
A clear acceleration in the rate of growth of at least 4-7 cm / year indicates a positive response to treatment with growth hormone.
Between the 70′s and 80′s natural growth hormone was extracted from pituitary glands of cadavers. This hormone has been the source of transmission of a serious disease, Creutzfeld-Jacob. Today, synthetic growth hormone, genetically engineered is used fro treatment
If dwarfism is accompanied by sexual infantilism, treatment with sex hormones is added - estrogen and progesterone – in girls and testosterone – in boys. Testosterone and its derivatives have the advantage to stimulates protein anabolism, develops muscles mass and stature. Testosterone must be administered with caution in children due to its virilizing effect.
Other drugs that increase endogenous production of growth hormone include: clonidine, arginine, dopamine, propranolol. Anabolic substances such as fluoxinesterone, nandrolone and oxandrolone, stimulates protein synthesis, increase cartilage and bone growth.