Diagnosing and Treating Adult Growth Hormone Deficiency

December 28, 2018

Adults need growth hormones too!

Growth hormone (GH) is a protein hormone made by the pituitary, a gland located at the base of the skull. It was known for many years that growth hormone is needed for children to grow. The pituitary gland not only produces GH, but releases (secretes) GH into the bloodstream. Growth hormone is secreted in pulses and most of the time the pituitary does not secrete growth hormone. GH goes to the liver to release a large protein called insulin-like growth factor, IGF-1. This protein used to be called somatomedin C. IGF-1 goes to certain tissues, especially bones, and results in height increase in children.  Damage to the pituitary gland in children results in low GH secretion in children, resulting in poor growth and resultant short stature. In endocrinology, GH can be given to children to restore their normal growth and development.

Over the last 25 years, researchers in endocrinology have discovered that adults need GH too. Like children, adults can be given this hormone if deficient. 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. If adults have a deficiency of GH, major changes to the composition of the body results. These changes include loss of muscle, accumulation of fat, especially in the abdomen, and a decrease in the density (but not the length) of bones. Because GH is also necessary for normal brain function, adults without this hormone have psychological changes in addition. Patients with GH deficiency may have a lot of joint pain and many patients with fibromyalgia have been incorrectly diagnosed and are actually growth hormone deficient. Patients with growth hormone deficiency often have trouble sleeping, which can lead to daytime fatigue. This article will focus on describing the GH deficiency syndrome as it applies to adults, and how it is currently diagnosed and treated, including the clinical assessment that leads to a GHD diagnosis and the hormone therapies used for diagnosis and treatment.

Description of the Adult GH Deficiency Syndrome

There are three main components to the adult GH deficiency syndrome. These are body composition changes, blood lipid (cholesterol and fat) changes, and psychological changes.

Decrease in Muscle and Accumulation of Fat

Because GH maintains muscle and fat, loss of this hormone results in a decrease in muscle and in an accumulation of fat. The decrease in muscle translates to poor muscle function and decreased exercise capacity. The increase in fat occurs under the skin, but also in the abdomen or, more specifically, inside the abdomen. 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.

Blood Lipid Changes

The blood lipid changes reflect the fat deposit changes and are all in the wrong direction. 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 the blood triglycerides, another circulating fat, which is associated with blood vessel aging.

Psychological Changes

The psychological changes associated with GH deficiency have been extensively studied.  Patients who develop GH deficiency seem to lose energy. Loss of energy is often the guiding symptom which prompts further investigation. Many individuals with pituitary disease, especially those with other hormone deficiencies, realize that something is missing. Frequently, it turns out to be a deficiency of GH. Individuals with this problem, or their spouses, also notice a loss of interest in their usual hobbies or activities. 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 may also develop mild depression or decrease in sexual function.

Diagnosis of the Adult Growth Hormone Deficiency Syndrome

GH deficiency in adults occurs because of some type of injury to the pituitary gland. GH is the first hormone to be affected if the pituitary gland is injured. Injury usually can occur because of the presence of a pituitary tumor, or pituitary surgery or pituitary irradiation. It can also be caused by trauma to the gland or, very rarely, inflammation.

Incidentalomas

In 2008, Dr. Friedman and his colleagues published a paper showing that small pituitary tumors (called incidentalomas) may also cause growth hormone deficiency. As many physicians including endocrinologists, either do not know about adult growth hormone deficiency or “do not believe in it”, patients who suspect that they have growth hormone deficiency need to see an endocrinologists with expertise in this area who can make the proper diagnosis.

Risks of Improper GH Treatment

As GH can be damaging (including leading to an increased chance of cancers) if given to people who are not GH deficient, it is important to be properly diagnosed. Additionally, some physicians referred to as anti-aging physicians will often give GH to people who are not GH deficient, thus making it more important to be properly diagnosed.

Diagnostic Challenges and Testing Approaches for GH Deficiency

Because GH is secreted in pulses, GH is commonly undetectable in normal individuals as well as in GH deficient patients. A blood GH level taken randomly, in other words, is usually low and is not worth getting. For this reason, endocrinologists need to find another way to prove deficiency of this hormone. This is done by checking to see if stimulating the pituitary releases GH. There are various ways to stimulate the pituitary to release GH (called “GH stimulation tests”).

Imaging 

Imaging with a pituitary MRI is also helpful as patients with growth hormone deficiency may have a small pituitary, a pituitary tumor or have partial empty sella syndrome (ESS), which is a condition where the sella turcica, a bony structure that houses the pituitary gland, appears partially empty on imaging scans. In partial ESS, less than 50% of the sella is filled with cerebrospinal fluid (CSF), and the pituitary gland typically measures 3 to 7 millimeters (mm) thick. Sheehan’s syndrome, also known as postpartum hypopituitarism, is a condition that occurs when a woman experiences severe blood loss during childbirth, leading to damage to the pituitary gland. It is a common reason for growth hormone deficiency.

IGF-1 Screening

In patients whom Dr. Friedman suspects are growth hormone deficient, Dr. Friedman starts by measuring an IGF-1 level which is a standard blood test that can be done any time of the day by regular labs. The normal range is usually broad and is gender and age specific. The lab gives two values, the actual level and the Z score, which is the number of standard deviations a given result is above (positive score) or below (negative score) the age- and sex-adjusted population median.

Z scores are calculated using the measured IGF-1 concentration and parameters provided by the lab. Most results within the IGF-1 reference interval should have a Z score between -2.0 and +2.0. This is just a screening test, but it is useful. A patient with a + Z score (above the median) is unlikely to have growth hormone deficiency, while someone with a value with a Z score less than -2.0 will often be growth hormone deficient. The problem is many patients fall in the area with an IGF-1 in the bottom of the range (Z-score -2.0 to -1.0). Note that the range for IGF-1 is lower than it was several years ago as the assay is more specific. If these patients have symptoms of growth hormone deficiency (as discussed above) and have a pituitary problem, they should undergo Growth Hormone Stimulation Testing.

Growth Hormone Stimulation Testing

The testing for GH deficiency is done in the outpatient setting and usually takes about three to four hours. You should not eat prior to the test. This type of stimulation testing is not only necessary for medical diagnosis, but often for insurance purposes. The best test for GH deficiency is the glucagon stimulation test. This test has been used in thousands of patients, is very safe and is excellent at distinguishing between normals and growth hormone deficient subjects. Dr. Friedman performs this test in a clinic in West LA on Sundays. Dr. Friedman will often use the GH level of 5 ng/mL as a cutoff, although the Endocrine Society uses a cutoff of 3 ng/mL. Patients with mild GH deficiency may have a level between 3 and 5 ng/mL and are worthy of a trial of GH. Patients with GH less than 3 ng/mL are GH deficient and should be treated. Glucagon stimulates GH by several mechanisms. It causes a rise and then drop in glucose levels and the drop in glucose may signal an increase in GH. It may have metabolites that directly stimulate GH. It is also thought to stimulate GH via norepinephrine. While some endocrinologists use a lower cutoff in obese patients, Dr. Friedman is concerned that growth hormone deficiency can cause obesity and using a lower cut-off may miss people who are growth hormone deficient that caused their obesity. Dr. Friedman wants to avoid using the ITT, as hypoglycemia occurs during the test that can be both dangerous in patients with heart problems and unpleasant for the patient.  

Treatment with GH

Once Dr. Friedman has diagnosed GH deficiency, he or she will begin the patient on GH and if needed, the dose will be increased until a final maintenance dose is reached. Dr. Friedman begins with 0.2 mg a day for men and elderly patients and 0.4 mg for women. 

Estrogens decrease the effect of GH, which is thought to be the reason why females need more GH. The hormone is given daily by a subcutaneous injection (in the stomach), usually at night. Small needles and syringes are used. More recently, the weekly injection with Soroya is now available and recommended in some patients.

Dr. Friedman will evaluate the patient at four to eight-week intervals to ask how the patient is doing and to obtain a blood test which can help determine the correct dose. This test is the insulin-like growth factor test (“IGF-1 test”). It is a single blood test which reflects the amount of GH administered, although it is not GH itself. IGF-1 values which are low prompt giving a larger dose of growth hormone; values which are too high prompt a lower dose. 

Dr. Friedman likes to see the IGF-1 in the upper-normal range. Once a final dose is established, the blood tests will continue approximately every 4 to 6 months. The symptoms of GH excess include muscle or joint pain, retention of fluid (called edema) and carpal tunnel, which consists of pain and/or numbness in the hands. If these symptoms occur, it is likely that the dose is too high. In that case, Dr. Friedman will have you get an IGF-1 level, stop your GH for a few days, then restart at a lower dose. 

While a decade ago, there were about 8 companies that sold GH, now there only 3 companies that distribute growth hormone: Genotropin made by Pfizer, Omnitrope made by Sandoz Pharmaceuticals (and Ocean Breeze Pharmacy) and Norditropin made by Novo Nordisk. All companies require an extensive preauthorization process and have curtailed their patient assistance program. Some insurances have a high co-pay.

Treatment with Supplements that Raise IGF-1

Once the IGF-1 is measured and found to be low, but not below the range, Dr. Friedman will often prescribe supplements that help raise IGF-1. These are safe, but usually not as effective as growth hormone itself. 

O-Tropin

One is called O-tropin that helps restore your pituitary and raises your IGF-1 that you can get more information including seeing reviews at https://buyorenda.com/collections/best-sellers/products/orenda-o-tropin. It is a spray under your tongue that is given twice a day and is $48/month for subsribe and save or $60 for 1 month supplysupple. 

I advise patients to take it 30 min away from food or liquids for best absorption although it is not required. I recommend putting on nightstand and spraying 2 sprays on awakening and 4 sprays at bedtime. If over 200lbs 4 sprays in morning 4 sprays in evening. You can get a discount at https://buyorenda.com/collections/our-products/products/orenda-o-tropin?rfsn=7150732.af3182&utm_source=refersion&utm_medium=103903judysewell.

SeroVital

Another supplement that can be used to raise IGF-1 and help with growth hormone deficiency symptoms is SeroVital, that is advertised for its ability to boost growth hormone levels naturally. It is protected by 15 US and international patents, and the research behind it has been presented at conferences around the world. The website (SeroVital.com) claims it is the #1 anti-aging product for women (Dr. Friedman does not recommend it for anti-aging) with 4 clinical trials that were presented at meetings, but no peer-reviewed publications. 

SeroVital Advanced is advertised as more effective at reducing appetite and jumpstarting weight loss compared to SeroVital and can be purchased at SeroVital.com for $129 for a one-month order or $99 for monthly delivery. It can also be ordered on Amazon, CVS or at some Costco Pharmacies.

Medicines That Interfere with Growth Hormone.

Oral Estrogen

Oral estrogens, such as birth control pills, premarin and oral estrace all block the action of GH at the liver. This leads to high GH (which can cause diabetes) and low IGF-1, both of which are detrimental. 

External Estrogen

Estrogen applied to the skin (creams or patches) does not cause this effect. Patients on oral estrogens will often need two to three times the dose of GH. For these reasons, all patients taking GH should not take oral estrogens or birth control pills.

GH Reauthorization

Most insurances require a prior-authorization for GH yearly, although some require it every 6 months. For Dr. Friedman’s staff to obtain the reauthorization, patients need to get an IGF-1 and have a phone appointment to discuss the benefits and side effects of the GH. Dr. Friedman suggests this to be done 1-2 months before the authorization is set to expire. Dr. Friedman asks for $50 voluntary payment to help off-set Judy’s time in doing the prior-authorization that can be paid on PayPal.

Growth hormone on a cash basis. 

For those patients who are unable to do the growth hormone stimulation test or who fail the test, but insuranceinsurances still does notdo not cover the treatment, Dr. Friedman may prescribe growth hormone from pharmacies that offer GH on a cash basis. Depending on the dose prescribed by your doctor, growth hormone can be as low as $300 a month for the 0.2 mg dose, with the price increasing as the dose increases. Dr. Friedman often prescribes Omnitrope from Ocean Breeze Pharmacy. For some patients who have a high co-pay, this may be a good choice even though it is covered by insurance.

Summary 

Deficiency of GH in the adult is well established and treatment with GH for those patients deficient in GH is approved by the FDA. Most insurance will cover the cost of this medication if a patient failed their growth hormone stimulation test, provided proper documentation on the necessity of GH treatment. Alternatives are weekly growth hormone, cash-pay for growth hormone and supplements. Proper GH replacement therapy leads to improvement in most of the symptoms and body composition changes induced by this deficiency and about 90% of Dr. Friedman’s patients find GH helps with symptoms and is well-tolerated. GH replacement therapy for most GH-deficient adults is considered lifelong therapy care. 

To make an appointment to see Dr. Friedman or to schedule an appointment for a GH stimulation test or treatments for AGHD, visit Dr. Friedman’s website at goodhormonehealth.com. We are here to help you improve your quality of life (qol), contact us today to get your adult growth hormone treatment by a doctor who provides excellent care to all of his patients.