Introduction

Adult GH deficiency most often occurs following pituitary surgery or radiation. Whenever pituitary surgery or radiation is performed, there is a risk that normal secretion of pituitary hormones will be affected. Of all of the pituitary hormones, secretion of GH appears to be the most easily impaired. If a patient is lacking normal secretion of three or four pituitary hormones, there is a 95% chance that the patient is GH deficient. In patients who have had pituitary surgery or radiation, there is a 25% chance that the patient will be GH deficient even if secretion of other pituitary hormones is normal. Thus, if pituitary surgery or radiation has been undertaken to cure Cushing’s disease, GH deficiency should be evaluated.

What is Growth Hormone?

Growth hormone (GH) is a protein hormone made by the pituitary gland. The pituitary gland not only produces GH, but releases (secretes) GH into the bloodstream. After entering the bloodstream, GH attaches to most tissues, especially bones, and results in height increase in children. In children, GH deficiency results in poor growth and resultant short stature. GH replacement restores normal growth in GH deficient children.

Over the last ten years, it has been discovered that adults need GH as well. Like children, adults can be given GH replacement if they are shown to be deficient. The approval by the FDA for adult GH replacement has been in place for the past 4 years. Since adults have already achieved their genetically determined height, loss of GH does not impact height, but it does affect the body in many other ways.

Growth Hormone Deficiency

The consequences of GH deficiency fall into three categories that include body changes, blood lipid (cholesterol and fat) changes, and psychological/cognitive changes. Because GH maintains muscle, bone, and fat, loss of this hormone results in a decrease in muscle, a decrease in bone density and an accumulation of fat. The decrease in muscle translates to poor muscle function and decreased exercise capacity. The decrease in bone density, can lead to osteoporosis and increased incidence of fractures. The increase in fat occurs under the skin, but also in the abdomen or, more specifically, inside the abdomen as occurs with Cushing’s Syndrome. This location is referred to as visceral fat. Medical science has discovered that visceral fat accumulation is especially dangerous because it is associated with an increase in the aging of blood vessels, referred to as atherosclerosis. The increased visceral fat leads to detrimental changes in the blood lipid levels. More specifically, there is an increase in the “bad” cholesterol (“LDL cholesterol”) and a decrease in the “good” cholesterol (“HDL cholesterol”). There is also an increase in blood triglycerides, another circulating fat, which is associated with premature blood vessel aging. GH also effects blood sugar regulation and unexplained hypoglycemia can be another clinical presentation.

The psychological changes associated with GH deficiency have been well studied. Patients who develop GH deficiency seem to lose energy. Loss of energy is often the guiding symptom that prompts further investigation. Many individuals who have undergone surgery or radiation to the pituitary, particularly those with other hormone deficiencies, realize that something is missing. Frequently, the missing component turns out to be GH. Many patients do not report feeling poorly, but the patient or their spouse usually notices a loss of interest in their usual hobbies or activities or a failure to resume normal activities following pituitary surgery or radiation. A decrease in sociability, referred to as social isolation, is another symptom. Patients suffering with this symptom do not like to go out and meet with their friends or social acquaintances. Patients with GH deficiency may also experience decreases in cognitive function, including memory difficulties, as well as mild depression and a decreased interest in sex. If GH deficiency is suspected, and there are no contraindications, testing for GH should be suggested.

Contraindications to GH therapy in adults include an actively growing tumor. There is no evidence that GH increases the rate of tumor growth, however, if not all of the tumor could be removed during surgery, it is recommended that the size of the tumor remain stable for a period of 1 year prior to starting GH replacement. Also, following successful pituitary surgery, testing for GH deficiency should be delayed 1 year to establish tumor removal or stability. GH does not cause cancer, but it is recommended that patients who have had cancer be cancer free for 5 years prior to beginning therapy. Another reason for not beginning therapy is proliferative retinopathy in diabetics. Also, GH hormone replacement can potentially aggravate carpal tunnel syndrome. Your individual physician can best determine if you are a candidate for GH replacement and testing.

Diagnosis of Adult GH Deficiency

Although GH circulates in the blood, it is released periodically and disappears rapidly from the bloodstream due to uptake by the tissues. Because of this, a random blood GH is usually low or undetectable in both normal and GH deficient patients. For this reason, endocrinologists use blood IGF-1 (insulin-like growth factor 1) measurements and a GH stimulation test to prove deficiency of this hormone. Patients with GH deficiency have low IGF-1 levels compared to normal age and sex matched controls. In patients with no pituitary function, low IGF-1 levels alone can be diagnostic, but in most cases a stimulation test will be required. Some patients may have normal IGF-1 and still be GH deficient.

There are a number of different GH stimulation tests. While these tests use different compounds or drugs, the common principle is that the pituitary gland is stimulated to secrete GH. Blood GH is then measured over a period of time, usually two hours, following stimulation. Your physician will pick one of the standard tests. The testing is done in the outpatient setting and you may be instructed not to eat or exercise prior to the test.

Treatment of GH Deficiency

Once a physician has proved GH deficiency, GH replacement therapy will be started. GH is given daily by injection by the patient or a family member using insulin needles and syringes. GH replacement should be started at a low dose and gradually increased until a final maintenance dose is reached. Slowly increasing the dose at 4-8 week intervals is required to avoid start up symptoms.

The symptoms associated with GH therapy fall into two categories; those associated with starting or raising the dose of GH and those associated with too much GH. Start-up symptoms consist of headache, blurred vision, and muscle and joint pain. These symptoms usually appear 7-10 days after starting GH or raising the dose and disappear by 14 days if transient. If these symptoms persist, the dose should be decreased. In my experience, very few patients elect to give up on treatment. If they do give up therapy, it is usually because they cannot get past the symptoms associated with beginning or advancing therapy.

Symptoms of excess GH are similar to start-up symptoms and consist of muscle or joint pain and/or carpal tunnel syndrome (numbness, tingling, or shooting pain in the thumb, index and middle finger). Growth hormone also increases water and salt retention and in excess, can cause swelling and potentially aggravate high blood pressure.

If you are a diabetic, your doctor will pay close attention to your blood sugar levels. Initially, GH replacement can aggravate diabetes, but later improves control. Diabetes is not a contraindication to therapy. GH will aggravate diabetes control initially and require a 20-30% increase in diabetic medication for the first 3-6 months. The need for increased medication usually subsides over the next 6 months.

Before beginning therapy, your physician will most likely collect some baseline information that can be tracked over a period of time. The items I usually track include bone density, body composition (percent fat and lean muscle mass ), blood lipid profiles, blood sugar, IGF-1 levels, height, weight, waist and hip circumference, blood pressure and answers to an easy to complete quality of life questionnaire. These are useful for showing improvements to patients as well as insurance companies. The starting dose I use for men, women not taking estrogen, or women on transdermal estrogen is 2 micrograms per kilogram of body weight per day (mcgs/kg/day). Women on oral estrogen are started at 4 mcgs/kg/day and both men and women over 60 years of age are started at no more than 100 micrograms total per day. In no case do I start a dose greater than 300 micrograms total per day.

Once the patient begins GH therapy, the patient will need to see their doctor every 4-8 weeks until the correct maintenance dose is established. To determine the proper dose, the physician will usually obtain a blood sample for measurement of IGF-1 levels and discuss how the patient is feeling. Low IGF-1 values generally indicate a need for a higher dose, while high IGF-1 values indicate that the dose is too high. In most cases, the maintenance dose is determined based on patient tolerance of therapy, rather than absolute IGF-1 concentrations. Depending on the patient, I generally increase the dose in increments of 1-2mcgs/kg/day except in those over 60 where the increment is a total of 50 micrograms per day. The number of dose changes at 4-8 week intervals needed to reach a maintenance dose is usually 2-4.

There is tremendous variability in GH dose requirements in adults, especially at the extremes of the age groups. In my experience, younger patients in their 20′s can require as much as 2000 micrograms per day, while older patients in their 70′s require as little as 80 micrograms per day. Most men and women in the middle age range require 200 – 800 micrograms per day.

Please note that the FDA approved, injectable GH that is prescribed by a physician is not the same as the health food store GH supplements. In general, health food store GH supplements are without any known benefit.

What should the Patient Expect?

Once the maintenance dose is reached, there is usually another 3-4 month period before the full benefits of GH therapy are realized. Why does this take so long? No one knows the answer to this question, but everyone agrees it takes 9-12 months before the individual experiences full benefits. This is not to say that some symptom improvement may not appear right away in 2-4 weeks. Most patients do feel better in this early time period. Often if the patient or physician asks a spouse how the patient is doing, the answer will be that the patient is returning to their usual self. The patient, however, is often not able to appreciate the subtle changes their body is going through. If the patient purposely or inadvertently misses a few doses, they will notice just what GH therapy has meant to them in their daily lives and quickly return to their daily GH injection. Generally, patients notice an increase in energy, less fatigue, an increased ability to exercise, improved cognitive function and a return to their normal social life. Weight loss may not be experienced, but there is an overall shift towards greater lean muscle mass and loss of abdominal fat with a resulting improvement in blood lipid levels. Bone density usually takes two years to improve. Improvements in the overall quality of life have been validated using pre and post treatment scores on quality of life questionnaires and the improvements are often dramatic. If you have had pituitary surgery or radiation and suspect that you may be GH deficient, complete the quality of life questionnaire inserted in this newsletter and take this article and the questionnaire to your endocrinologist. You may be pleasantly surprised.

Additional Information on Growth Hormone

The Pituitary Society

The Magic Foundation offers information and support services for patients with Growth Hormone deficiency.

Author: Dr. David Cook, MD (Winter, ’01)

Editor’s Note: Dr. Cook is Professor of Medicine at Oregon Health Sciences University in Portland, Oregon where he has been involved in the diagnosis and treatment of Cushing’s since 1969. Dr. Cook has also been extensively involved in the diagnosis and treatment of adult Growth Hormone deficiency. Some of the information in this article was previously published on the Pituitary Society web page and in the Magic Foundation Newsletter.