Testing 101: Testing Growth Hormone Levels in Adults

Ok...what's the big deal, anyhow? Why would anyone need to have their growth hormone levels evaluated? I'm going to stick to adults today because low growth hormone (GH) is a whole 'nuther ballgame with children.

As a review, growth hormone is secreted by the pituitary gland. Some pituitary tumors secrete too much GH which causes gigantism in children and acromegaly in adults. However, on the flip side, some tumors suppress the pituitary and too little is secreted. Even if the tumor does not do that, surgery to remove a tumor may cause the pituitary to quit or lessen it's secretion of GH. Radiation is also used on pituitary tumors that cannot be totally removed or if there is hyperplasia, and it, too, can damage the pituitary.

Adult Growth Hormone Deficiency (GHD) is a very real problem. GH maintains a healthy balance of muscle, bones, and fat and if an adult is deficient, her body composition changes. The body has less muscle, visceral fat is deposited around the abdomen, and bones weaken. Other fats in the body are affected. "Good" cholesterol (HDL) decreases but "bad" cholesterol (LDL) increases. This is very hard on the cardiovascular system (remember, the heart is a muscle) and the cerebrovascular system.

In Diagnosis of adult GH deficiency [V. Gasco, et al, Pituitary (2008) 11:121–128], the authors state:

Adults with growth hormone deficiency (GHD) have impaired health, which improves with GH replacement. GHD in adults leads to impairment in body composition and function, as well as to deranged lipoprotein and carbohydrate metabolism and increased cardiovascular morbidity. Based on evidence that GHD in adults is a
new syndrome which may benefit from GH replacement, health authorities in many countries have approved the therapeutic use of GH in hypopituitaric patients with severe GHD.

Not only is the physical health of a GHD adult affected. Social isolation, excessive tiredness, anxiety, depression, and apathy are also symptoms of GHD.

Ok, all of that to get to the testing part! Whew!

Growth hormone secretion is pulsatile which means random measurements of GH levels are not helpful or diagnostic. Since insulin-like growth factor-1(IGF-1) is stimulated by GH but does not fluctuate during the day like GH, it is useful in monitoring GH levels. Low levels are an excellent indication of a GHD problem. However, normal levels do not mean there is no deficiency.

The Growth Hormone Research Society met in 2007 in Australia and penned a consensus statement about the problems, testing, and treatments associated with adult GHD. In their consensus statement, they write:

...the patient with objective evidence of hypothalamic–pituitary disease (e.g., on imaging or after irradiation), who may present with organic isolated GHD as the first hormonal deficiency...may account for up to 25% of cases of GHD in the adult.

Consensus guidelines for the diagnosis and treatment of adults with GH deficiency II[European Journal of Endocrinology (2007) 157 695–700]

In this same consensus statement, they say:

Not all patients suspected of having GHD,however, require a GH stimulation test for diagnosis.Patients with three or more pituitary hormone deficiencies and an IGF-I level below the reference range have >97% chance of being GHD, and therefore do not need a GH stimulation test.

The Insulin Tolerance Test has, in the past, been the "gold-standard" for measuring true GHD. However, there have been some problems with its reproducibility and specificity.

In Clinical Presentation and Diagnosis: Growth Hormone Deficiency in Adults the American Journal of Managed Care [Volume 10:S424-S430 , October 2004 , Number 13 Suppl ] states:

Numerous pharmacologic agents can be used to assess GH production and secretion
by the pituitary in adults (Table 3). These include insulin, arginine, levodopa
(L-dopa), arginine plus L-dopa, arginine plus GHRH, and the glucagon test. None
display perfect sensitivity and specificity; however, the insulin tolerance test
(ITT) and arginine-GHRH are excellent tests.

The arginine-GHRH test is being used by major pituitary centers around the world. It is less stressful with less risk for the patient but yields reproducible and accurate results.

What are the differences in these two tests? In the ITT, the pituitary is provoked to produce GH by causing hypoglycemia in the patient with insulin. With the A-GHRH test, arginine is a somatostatin antagonist which essentially does the same thing. Combined with GHRH (to stimulate GH production), it is now the test of choice (see article linked above).

I had the arginine-GHRH stimulation test done this past spring at the University of North Carolina. There aren't many places to have this done on the east coast, yet. An IV was placed in my veins (after many attempts....I'm such a hard "stick") prior to the test. I had GHRH injected via an IV push, then Arginine was infused over a period of 30 minutes. My blood was drawn every 30 minutes afterwards for 3 hours and sent to Mayo Clinic labs to be tested. I received the following email a couple of weeks later, and my results were sent to my endocrinologist.

"You are definitely growth hormone deficient. Your starting GH value was 0.02ng/ml and your peak value was 0.13ng/ml."

I wasn't surprised. Neither was my endo.