Pituitary gigantism is a rare hormonal disorder characterized by excessive growth hormone production. This condition begins in childhood, before the skeletal growth plates in the bones have fused, leading to disproportionate and rapid overgrowth. It represents a unique challenge in pediatric endocrinology due to its potential for significant physical and health complications if left unaddressed.
What Pituitary Gigantism Is
Pituitary gigantism results from the overproduction of growth hormone (GH) by the pituitary gland, a small, pea-sized gland located at the base of the brain. Normally, the pituitary gland produces GH, which then signals the liver to produce insulin-like growth factor 1 (IGF-1). IGF-1 is the primary driver of bone and tissue growth throughout the body.
Excessive GH production leads to high IGF-1 levels. This occurs before the epiphyseal growth plates at the ends of long bones have fused. Since these growth plates are still open, the excess GH and IGF-1 stimulate continued linear bone growth, resulting in significantly increased height and overall body size. This distinguishes it from acromegaly, a similar condition where GH overproduction occurs after growth plate fusion, leading to thickening of bones and soft tissues rather than increased height.
Identifying the Indicators
Individuals with pituitary gigantism exhibit several signs and symptoms. The most noticeable indicator is rapid and excessive height growth, often placing the child above the 97th percentile for their age. This accelerated growth is usually accompanied by disproportionately large hands and feet, often described as spade-shaped.
Facial features can also become coarser, with a prominent jaw and forehead, an enlarged nose, lips, and tongue, and gaps between the teeth. Individuals may experience frequent headaches. Visual disturbances, such as double vision or difficulty with peripheral vision, can occur if the pituitary tumor presses on the optic nerves. Other common symptoms include excessive sweating, joint pain due to enlarged joints, muscle weakness, and, in some cases, delayed puberty.
Causes and Underlying Mechanisms
Excessive growth hormone production in pituitary gigantism is primarily caused by a benign tumor on the pituitary gland, known as a pituitary adenoma. These tumors, particularly macroadenomas (larger than 10 millimeters in diameter), directly produce or stimulate the pituitary gland to release an excess of growth hormone. In some instances, the pituitary gland itself may be enlarged without a distinct tumor, a condition called pituitary hyperplasia.
Genetic factors also play a role, with nearly 50% of pituitary gigantism cases having an identifiable genetic cause. Mutations or deletions in the AIP gene are the most common genetic link, accounting for approximately 29% of cases. Other rare genetic conditions, such as Multiple Endocrine Neoplasia Type 1 (MEN1), Carney complex, and McCune-Albright syndrome, can also predispose individuals to developing growth hormone-secreting pituitary adenomas. These genetic alterations lead to uncontrolled growth of pituitary cells and overproduction of growth hormone.
Diagnosis and Confirmation
Diagnosis involves medical tests to confirm excessive growth hormone production and identify its cause. The initial screening often begins with blood tests to measure levels of insulin-like growth factor 1 (IGF-1). Elevated IGF-1 levels are a strong indicator of growth hormone excess because IGF-1 levels remain relatively stable throughout the day, unlike growth hormone which fluctuates.
To confirm the diagnosis, an oral glucose tolerance test (OGTT) is performed. During this test, the individual drinks a sugary liquid, and growth hormone levels are measured before and after glucose intake. In healthy individuals, glucose intake suppresses growth hormone levels; however, in those with gigantism, growth hormone levels will remain high. Following biochemical confirmation, imaging techniques are employed to locate any pituitary tumors. Magnetic Resonance Imaging (MRI) of the pituitary gland is the preferred imaging modality as it can pinpoint the size and location of an adenoma. If visual disturbances are reported, a visual field exam may also be conducted to assess potential pressure on the optic nerves from the tumor.
Management and Treatment Options
The management of pituitary gigantism aims to normalize growth hormone and insulin-like growth factor 1 levels, ultimately halting excessive growth and alleviating associated symptoms. Surgical removal of the pituitary adenoma is the primary treatment approach. Transsphenoidal surgery, a procedure performed through the nose and sphenoid sinus, allows for the removal of the tumor while minimizing invasiveness. This surgical intervention can lead to rapid reductions in growth hormone levels and prevent further mass effects from tumor growth.
When surgery is not fully successful in normalizing hormone levels or is not feasible, medical therapies are employed. Somatostatin analogs, such as octreotide and lanreotide, are often used as a first-line medical treatment after surgery. These medications mimic natural somatostatin, a brain hormone that inhibits growth hormone secretion, and can also lead to tumor shrinkage in some cases. Dopamine agonists, including cabergoline, may also be used to help lower growth hormone and IGF-1 levels, though they are less effective at normalizing these hormones compared to somatostatin analogs.
A growth hormone receptor antagonist, pegvisomant, directly blocks the action of growth hormone on the body’s tissues, leading to a decrease in IGF-1 levels. This medication does not affect tumor size but is highly effective at normalizing IGF-1 levels. Radiation therapy may be considered as a secondary or adjuvant treatment option if surgery and medical therapies do not achieve adequate control, especially for residual tumor tissue. The overall goal of these combined treatments is to normalize hormone levels, preserve pituitary function, and prevent long-term complications associated with sustained growth hormone excess.