Growth Hormone Deficiency

Growth Hormone Deficiency in Both Children and Adults

Alicia M. Held, MSW

 

Growth Hormone Deficiency (GHD) is exactly what it sounds like, a deficiency of the body’s natural growth hormone. Growth hormone is one of the hormones secreted by the pituitary gland. GHD occurs in both children and adults, but oftentimes the causes and especially the symptoms are vastly different. In order to begin to understand GHD we will take a more in-depth look at the pituitary gland, we will also explore the differences between GHD in children and adults, and then look at the different methods available for testing and why they are necessary, and finally we will discuss the main treatment options available.

The Pituitary Gland

The pituitary gland is a very small gland, about the size of a pea, that sits at the base of the skull. It is often called the “master gland” as it is responsible for the production and secretion of  hormones that are essential for proper functioning of the human body, and those then hormones regulate other endocrine glands like the thyroid, adrenal glands, and reproductive glands (Emerson, 2015). The pituitary gland is also unique in that it is separated into two parts: the anterior pituitary (adenohypophysis) and the posterior pituitary (neurohypophysis). For our purposes, we will focus on the anterior pituitary, however, the posterior pituitary does produce two hormones, vasopressin (VP), also called antidiuretic hormone (ADH), which helps control the body’s fluid balance, and also oxytocin (OXT), which is responsible for beginning labor in women (Corenblum, 2016).

The anterior pituitary gland is our focus, as that is where growth hormone is both made and released. In addition to growth hormone the anterior pituitary produces other hormones:

  • Corticotropin, or adrenocorticotropic hormone (ACTH)-regulates the activity of the adrenal glands, mainly the release of cortisol from the adrenal cortex
  • Gonadotropins, which are the two hormones luteinizing hormone (LH) and follicle stimulating hormone (FSH)-these hormones regulate the gonads, or sex glands
  • Prolactin-initiates and sustains lactation
  • Somatotropin, or growth hormone (GH)-stimulates the growth of essentially all tissues of the body
  • Thyrotropin, or thyroid stimulating hormone (TSH)-aids in the release of thyroid hormones (T3 and T4) from the thyroid gland

Each of these hormones is produced by a specific cell in the anterior pituitary gland. Growth hormone is produced by somatotrophs which make up approximately 40% of the anterior pituitary gland and can secrete between one and two milligrams of GH every day (Emerson). GH is vital to the normal growth of children. Levels of GH are highest during childhood, peak during puberty, and begin to fall off in early adulthood (Utiger, 2010). Problems with the level of GH can lead to disorders such as acromegaly when there is an excess of GH, or growth hormone deficiency when there is not enough.

Growth Hormone Deficiency in Childhood

The causes for growth hormone deficiency are generally classified into two different types, “organic”-tumors, radiation damage due to a tumor, genetic syndromes, etc. which counts for approximately 20% of cases; or “idiopathic”, meaning that there is no physical finding that results in growth hormone deficiency which makes up about 80% of GHD in children (Hardin, 2008). However, what generally brings children to be referred to an endocrinologist for growth hormone testing is the appearance of “short stature” noticed by parents and caregivers (Stanley, 2012). In the US approximately 2.5% of children have the appearance of short stature, however, only between 1 in 10,000 to 1 in 40,000 is diagnosed with growth hormone deficiency (Stanley). The diagnosis of GHD, however, is very difficult during childhood, and adulthood for that matter, due to the lack of a true gold standard and the relatively poor performance of currently available diagnostic testing (Stanley).

In children the main symptom of GHD is “progressive slowing of growth, [including] delayed skeletal maturation and delayed puberty (Ismail et al., 2013)”. While GH has been shown to have effects on many body systems, in children a slowing of physical growth is by far the main symptom, and the reason people seek out diagnosis and treatment. Treatment is especially critical to start as early as possible in children, because children with GHD who do not receive any GH generally end up with an adult height approximately 6 SD (standard deviations) below the average adult height; and children who do not start treatment until adolescence have an adult height approximately 4 SD below average (Burns et al., 1981).

Growth Hormone Deficiency in Adults

Growth hormone deficiency in adults is generally represented by two distinct clinical manifestations: children with GHD that have grown into adulthood, and GHD acquired in adulthood. GHD acquired in adulthood can again either be organic, such as pituitary tumors and the subsequent radiological and surgical damage, which is the number one cause of adult growth hormone deficiency (AGHD) or idiopathic-no known cause (Gupta, 2011). The clinical features of AGHD, however, separate it distinctly from GHD in childhood, in which the only main feature was a slowing of physical growth. The list of possible symptoms for AGHD is:

  • Changes in cognition such as: memory, processing speed, or attention
  • Lack of well being
  • Depression
  • Anxiety
  • Social isolation
  • Fatigue
  • Lack of strength, muscle weakness
  • Fibromyalgia syndrome
  • Neuromuscular dysfunction
  • Centralized fat deposits
  • Decreased muscle mass
  • Decreased bone density
  • Impaired cardiac function
  • Decreased insulin sensitivity
  • Increased blood clotting
  • Decreased sweating and body temperature regulation
    • (Gupta, 2011)

Patients with AGHD frequently complain of low levels of energy, mental difficulties, emotional problems, and an overall low-quality of life (Gupta). In adults the symptoms of GHD are multi-systemic and varied, and can be associated with multiple other conditions, which, in addition to the difficulties mentioned earlier, can make diagnosis of AGHD extremely difficult.

Diagnosis and Testing

There is no gold standard for testing in the diagnosis of growth hormone deficiency. And although the diagnostic tools used for testing for GHD in both children and adults are the same, the process is often much different, as are the requirements for diagnosis. In children, x-rays to determine bone age, measurement of insulin-like growth factor 1 (IGF-1) and IGF binding protein, growth hormone (GH) testing, brain magnetic resonance imaging (MRI), and, in certain cases, genetic testing are how doctors would progress in ruling out different conditions that could be causing the main symptom of short stature in children (Stanley). In adults, often dynamic testing of GH is the first step; although IGF-1 may be tested, a normal level does not rule out the possibility of GHD (Gupta).

In both children and adults in order for insurance companies to pay for expensive GH treatment, deficiency must be proven through dynamic testing and GH levels must be below a certain cutoff, generally 5μg/L (5ng/mL), with 3μg/L (3ng/mL) representing severe GHD. There are multiple testing options available in order to test for GHD, however, there is much variance among endocrinologists as to which test is the best. The top diagnostic tests are as follows:

  • Insulin tolerance test (ITT)-considered by some the “gold standard” for diagnosing GHD in adults, however, it is contraindicated in some populations, mainly the elderly and those with cardiac issues (Yuen, 2011). The test uses insulin to induce hypoglycemia, which is a potent stimulator for GH. GH levels are measured every 15-30 minutes over 2 hours (Glynn and Agha, 2012). This test is uncomfortable, and difficult for many people to tolerate.
  • Glucagon stimulation test (GST)-this is a reliable and safe alternative to the ITT, and gaining popularity among endocrinologists. Similarly to the ITT, glucagon is administered and then blood levels of GH are sampled between 90 and 240 minutes after administration. The mechanism for why glucagon stimulates GH release is not really known (Glynn and Agha).
  • Combined growth hormone releasing hormone (GHRH) and the arginine test- This test has been found in some studies to have 95% sensitivity and 91% specificity at a GH cutoff of 4.1 μg/L, and is gaining acceptance among endocrinologists as an alternative to ITT, however, it can be greatly influenced by BMI (Glynn and Agha).
  • Other tests with much lower rates of use are stimulation tests that use arginine only, levodopa, arginine plus levodopa, clonidine, or growth-hormone-releasing peptide 2 (Gupta).

Amongst all the dynamic tests, the insulin tolerance test (ITT) and combined GHRH and arginine test have the best sensitivity and specificity (Gupta).

Treatment

There is really only one treatment for growth hormone deficiency in both children and adults, and that is the artificial replacement of growth hormone, although the level of replacement does differ based on age, gender, and sometimes weight. Previously children were provided GH supplementation up until the closure of the epiphyseal plates (growth plates) in their bones, however, more recent studies have suggested that there are benefits to lifelong GH supplementation in persons with GHD such as benefits for bone mineralization and lean mass, improving cardiac risk factors, especially decreasing fatty tissue around the organs and improving lipid profiles (Hardin).

Somatotropin made of recombinant DNA, the current treatment for GHD, has been commercially available since 1985. It replaced GH derived from human pituitary glands which was withdrawn from the market due to safety concerns (Hardin). Currently there are many brands available to patients: Genotropin by Pfizer, Humatrope by Eli Lily, Nordotropin by Novo Nordisk, Nutropin by Genetech, and Saizen by EMD Serono to name a few. But it is important to note that there is a lot of information on the internet about GHD and the use of GH supplements (pills, sprays, etc.) to promote overall health and anti-aging. However, for persons with a diagnosed growth hormone deficiency the only way to get treatment that will alleviate the symptoms of GHD is to get a prescription from a licensed physician.

Conclusion

Growth hormone deficiency is a rare disorder that can be present in childhood due to genetic conditions, tumors, or for unknown reasons, and can also present in adulthood as well. Although there are multiple tests available for diagnosing growth hormone deficiency there is a lot of debate among doctors as to the best option for testing and also who should be tested. This makes receiving a diagnosis of GHD, especially as an adult, extremely difficult. Once you are diagnosed with GHD the treatment is straightforward, however, working with your insurance and managing the excessive cost of the medication is often a significant barrier to treatment for many people. Growth hormone deficiency in most cases, and especially in adults, causes a significant portion of people to report a low quality of life due to managing the prolific and myriad symptoms of the disease. And although it may seem overwhelming between the symptoms, the difficulties of testing, and the excessive barriers to treatment; know that you are not alone. There are many people traveling the same path as you, and there is help available in getting a diagnosis, and managing your GHD in your daily life.

**If you are having trouble paying for your GH treatment there are programs available through many of the pharmaceutical manufacturers, plus there are organizations which offer grants to help offset the cost of the medication. Please send a message to our On-Staff Social Worker, Alicia Held, MSW and she will attempt to help to the best of her ability.

Alicia can be reached via e mail at alicia@epictogether.org or phone at 888-862-5554 Ext. 704 Toll Free

 

References

 

  1. Burns, E. C., Tanner, J. M., Preece, M. A., Cameron, N. (1981) Final height and pubertal development in 55 children with idiopathic growth hormone deficiency, treated for between 2 and 15 years with human growth hormone. European Journal of Pediatrics. Retrieved from: http://link.springer.com/article/10.1007/BF00441309
  2. Corenblum, B. MD, FRCPC. (2016) Hypopituitarism (Panhypopituitarism). Retrieved from: http://emedicine.medscape.com/article/122287-overview
  3. Emerson, C. H. (2015) Pituitary gland. In Encyclopedia Britannica. Retrieved from: https://www.britannica.com/science/pituitary-gland
  4. Glynn, N, Agha, A. (2012). Diagnosing growth hormone deficiency in adults. International Journal of Endocrinology. Retrieved from: https://www.hindawi.com/journals/ije/2012/972617/
  5. Gupta, V. (2011). Adult growth hormone deficiency. Indian Journal of Endocrinology and Metabolism. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3183535/
  6. Hadin, D. (2008). Treatment of short stature and growth hormone deficiency in children with somatotropin (rDNA origin). Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2727887/
  7. Ismail, N. A., Metwaly, N. S. E., El-Moguy, F. A., Hafez, M. H., Abd El Dayem, S. M., Farid, T. M. (2013). Children with isolated growth hormone deficiency: Empty sella versus normal sella. Indian Journal of Human Genetics. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3758716/
  8. Stanley, T. (2013). Diagnosis of growth hormone deficiency in childhood. Current Opinions in Endocrinology, Diabetes, and Obesity. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3279941/
  9. Utiger, R. D. (2010) Growth hormone (GH). In Encyclopedia Britannica. Retrieved from: https://www.britannica.com/science/growth-hormone
  10. Yuen, K. C. J. (2011) Glucagon stimulation testing in assessing for adult growth hormone deficiency: Current Status and future perspectives. ISRN Endocrinology. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3262627/