Panhypopituitarism in Children

Panhypopituitarism is a condition in which the production and secretion of all hormones by the pituitary gland is reduced. The pituitary gland, also called the “master gland of the body”, is a pea-sized organ located in the center of the brain. It produces and regulates the release of many different chemicals, or hormones, that control growth, sexual development and function, metabolism, and the body’s response to stress.

Some examples of pituitary hormones are:

• Growth hormone (GH): helps children grow in height and helps adults optimize fat and muscle development. This hormone also plays a role in the development and maintenance of bone strength.
• Thyroid stimulating hormone (TSH): Directs the thyroid gland in the neck to produce thyroid hormone, which is important for an infant’s cognitive development, a child’s height growth, and metabolic functions of the body.
• Adrenocorticotropin hormone (ACTH): Directs the adrenal gland to produce cortisol that helps regulate the body’s response to stress.
• Luteinizing hormone (LH) and follicle stimulating hormone (FSH): Puberty hormones that direct the gonads (ovaries and testes) to make sex steroids such as estrogen and testosterone.  
• Vasopressin or anti-diuretic hormone (ADH): Controls water balance in the body and in the kidneys.

When the production and release of some of these hormones is reduced, the condition is called hypopituitarism. When the production or release of all hormones is reduced, it is considered panhypopituitarism.

Effects of panhypopituitarism may be gradual, or sudden and dramatic.

Pituitary hormone production is regulated by the hypothalamus the area just above the pituitary that helps regulate hormone release from the gland. Reduced hormone output could be due to a problem with either the hypothalamus or the pituitary gland. Those problems, in turn, may be caused by:

• A tumor, or cyst, on or near the pituitary gland or hypothalamus
• Underdeveloped or poorly formed pituitary gland
• Birth trauma or other injury
• Infection
• Autoimmune reaction
• Pressure from hydrocephalus
• Surgery
• Radiation treatment

Sometimes, no exact cause of panhypopituitarism can be determined.

Symptoms of panhypopituitarism vary widely, depending on the degree to which hormone production is reduced. Symptoms in infants, children or adolescents may include:

• Abnormal slowing of growth
• Delayed puberty
• Excessive thirst and excessive urination
• Less frequent menstrual periods
• Low blood sugar (hypoglycemia)
• Prolonged jaundice in infants
• Sensitivity to cold
• Poor appetite
• Weight loss or weight gain
• Unusually dry skin
• Nausea or dizziness Fatigue or drowsiness
• Small penis in males

These symptoms may resemble other conditions or medical problems. Always consult your doctor for a diagnosis.

Your doctor will usually ask a series of questions, including any symptoms you may have noticed, then assess your child’s growth and weight gain, and examine your child. If signs indicate concern for panhypopituitarism, additional testing and evaluation may include:

• Neurological exam to check mental status, coordination, reflexes and muscle function
• Eye test to check for loss of vision, including narrowing field of vision
• Blood and urine tests to check hormone levels; the blood tests, or venous sampling, involve taking blood from peripheral veins in the arms that will look at hormone levels originating from the pituitary gland in the brain
• Magnetic resonance imaging (MRI) or computerized tomography (CT) scan to get visual images of the pituitary gland, brain and spinal cord
• X-ray of the left hand and wrist to determine “bone age,” another marker of growth

Treatment of hypopituitarism depends on its cause. The goal of treatment is to restore normal levels of hormones in the body.

• Drug therapy may be used to replace hormones that are being under-produced.
• If there is a tumor, surgery may be performed to remove it if medications have not successfully decreased the tumor size, or the tumor is putting pressure on the optic nerve or surrounding brain tissue. Surgeons may reach the tumor through an incision in the upper lip or at the bottom of the nose, or by cutting through the skull.
• Radiation therapy may be used to kill tumor cells or to keep them from growing. Radiation therapy for a pituitary tumor must be narrowly targeted to minimize damage to nearby brain tissue.

For most children and adolescents with panhypopituitarism, treatment with hormone replacement therapy is effective in restoring normal hormone levels. Hormone replacement therapy substitutes medically administered hormones for those normally produced by the pituitary gland. Even if the underlying cause of panhypopituitarism cannot be found or addressed, hormone replacement therapy works to return the body to a healthy rate of development and to normal metabolic function.

When the cause is found to be a tumor, this can usually be controlled with surgery, medications or a combination of the two. Radiation therapy is sometimes used.

Regular office visits with specialists are necessary to make sure medications are working and children are growing and developing as expected. When medication is needed to supplement hormone production, periodic follow-up tests are needed to ensure that the treatment continues to work effectively. Dosage levels and the combination of medications may need to be adjusted over time.

Sometimes repeat imaging tests or additional blood tests may be recommended. If the treatment has eliminated or decreased the size of a tumor, follow-up tests and imaging will be needed periodically to make sure the tumor has not returned.

Children with panhypopituitarism often require care from many pediatric specialties.

The Neuroendocrine Center at Children’s Hospital of Philadelphia offers families a coordinated and multidisciplinary approach to treatment for neuroendocrine disorders. Our team combines the expertise of pediatric endocrinologists, neuro-oncologists, neuro-surgeons, neuro-ophthalmologists, neuro-radiologists, and pathologists.

All our team members have vast experience in the treatment of complex neuroendocrine conditions like panhypopituitarism.