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Clonidine Growth Hormone Stimulation Test

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How Is Growth Hormone Deficiency In Adults Tested And Diagnosed

Growth Hormone Stimulation Test

If you are an adult over 40, and are exhibiting any number of the above symptoms, your doctor will likely want to have you tested for a growth hormone deficiency. There are a number of ways to test for growth hormone deficiency in adults, however, they all start with drawing blood.

Since HGH levels in your blood rise and fall during the day, and vary from day to day, a test that simply measures the presence of HGH in your blood is not adequate enough to achieve a diagnosis of growth hormone deficiency. More sophisticated testing is required.

The way we test for growth hormone deficiency in adults is to use what are known as stimulation tests. Rather than testing for the presence or level of HGH in your blood at any given time, HGH stimulation tests introduce a medication that is supposed to stimulate your pituitary gland to release growth hormone. Similarly, a test that stimulates the release of another hormone, related to HGH, IGF-1, may also be used.

These growth hormone stimulation tests may be used alone or in combination. In any case, once the stimulant is introduced, your blood will be drawn and evaluated for adequate production and release of growth hormone.

Rather than testing for the presence or level of HGH in your blood at any given time, HGH stimulation tests introduce a medication that is designed to stimulate your pituitary gland to release growth hormone.

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What Kind Of Results Could I Expect From Growth Hormone Therapy

If you have had your HGH levels tested, and you have received a diagnosis of adult growth hormone deficiency, you can expect to see many benefits from growth hormone therapy, such as increased muscle mass, loss of fat, and renewed energy.

For men and women who have been diagnosed with age-related GHD, growth hormone injections have been found to:

  • Improve fat metabolism, resulting in lower body mass index
  • Increase energy and stamina
  • Improve memory and other cognitive functions
  • Increase libido and improve sexual performance
  • Strengthen bones, and fight osteoporosis

In addition, HGH injections can also improve heart health by helping to reduce cholesterol, and open blood vessels that have been clogged with arterial plaque.

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Establishing The Maintenance Gh Dose

When the indication for GH-replacement has been ascertained, the patient is usually on a low initial dose , but dependent on age, since adolescents during transition may benefit from higher initial doses, as will also women on estrogen therapy a higher dose may be employed . The dose titration is monitored by IGF-I concentrations , and a number of end organ end responses, which may act as biomarkers of the treatment effects .

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How Adults Can Prepare

Your doctor will typically ask you to take more than one kind of test.

You may need the stimulation test, as well as some of these other tests:

  • The IGF-1 and IGFBP-3 tests, which check the amount of a different but related hormones
  • Tests to check for issues with other hormones, including cortisol, prolactin, and testosterone

Children will also typically get a combination of these tests.

If you need to take a growth hormone stimulation test, you may need to:

Fast: Some medical experts recommend up to 12 hours without food before the test. Talk to your doctor about this beforehand to find out what you should do in your case.

Avoid certain medications: These include insulin, birth control pills, and the herb St. Johnâs wort. If you take these or any other medicines, talk to your doctor to see what you need to do.

Donât exercise: Workouts 10 hours or less before the test can throw off resting hormone levels.

Testing takes up to 3 hours, so you should also dress comfortably and bring a book or some entertainment.

Low blood sugar and obesity may skew results, so talk with your doctor if you have these conditions.

The Night Before The Test

Hematuria as an adverse outcome following provocative growth hormone ...
  • Your child should NOT have anything to eat or drink after midnight the night before the test, except tap water. This means NO breakfast, breath mints, chewing gum, flavored or bottled water.
  • Your child should not take any medicine before the test unless the health care provider tells you they can have it. You may bring their medicine with you to the test so it may be given after the test is over.
  • Tell the health care provider if your child has recently or is currently taking steroids.
  • Tell the health care provider if your child has had any allergies or reactions to medicine, food preservatives or dyes in the past. Signs of a reaction can be a rash, hives, itching, shortness of breath, wheezing, coughing and swelling of face, lips, tongue or throat.
  • Your child should go to bed at their usual time.

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Standardization Of Gh Assays

Accurate measurement of GH levels is critical for establishing the diagnosis of adult GHD because the analytical method influences the results of GH stimulation tests, which is dependent on specific GH cut-point levels. However, circulating GH is present in several different isoforms and isomers, including the most common variant of 22 kDa, and other smaller molecules, such as the 20 kDa GH variant. Monoclonal antibodies binding to a specific molecular form of GH are used to limit detection to the 22 kDa GH, but will not detect other GH isoforms. Other molecules similar to GH could potentially cross-react and affect the measurement of GH levels. Growth hormone binding protein, to which approximately 50% of circulating GH is bound, can also cause interference in a GH assay. Furthermore, substantial heterogeneity exists among currently utilized assays due to the use of different standard preparations for calibration of GH immunoassays, and lack of harmonization between various GH assays makes it difficult to directly compare diagnostic cut-points across different published studies. Another source of confusion when interpreting data of GH stimulation tests was that some laboratories reported GH levels in activity , whereas others used mass units .

Diagnosis Of Adult Gh Deficiency

Adult GHD is a heterogeneous disorder that commonly results from a variety of organic causes, including hypothalamic-pituitary tumors and/or their treatment, head trauma, and infiltrative diseases . This condition is characterized by decreased lean body mass and increased fat mass, dyslipidemia, cardiac dysfunction, decreased fibrinolysis and premature atherosclerosis, decreased muscle strength and exercise capacity, decreased bone mineral density, increased insulin resistance, and impaired quality of life . Treatment with GH replacement improves most of these abnormalities . However, due to the high cost of GH replacement and concerns of potential long-term risks, particularly the development of diabetes mellitus, cancer and tumor recurrence, it is imperative that the correct diagnosis is established so that appropriate GH replacement is offered to adults who are truly GH-deficient, and not for anti-aging and sporting enhancement .

All GH stimulation tests are based on the concept that a pharmacological agent acutely stimulates pituitary GH secretion, and peak serum GH levels detected by sequential blood sampling of serum GH levels after administration of the GH provocative agent. The desired criteria of an ideal GH stimulation test should include the following: the ability to accurately and reliably differentiate adults with GHD from GH-sufficient individuals, high reproducibility, safe with minimal side-effects, affordable, short test duration, and simple to perform.

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What Type Of Medication Will My Child Be Given During A Growth Hormone Stimulation Test

Your child’s Pediatric Endocrinologist will determine which medication is best for your child and then explain to you why that choice was made. Some of the options include:

All of these potential and rare side effects are temporary and should pass quickly. Your child’s endocrinologist will discuss with you in further detail about the minor and uncommon side effects to these medications.

New Models For Diagnosis

What is a growth hormone stimulation test?

Basal, oscillating, and pulsatile GH inputs and the wide range of intrasubject and intersubject variance in GH pharmacokinetics negate the assumption of a uniform relationship between GH secretion and serum GH concentration. Because of this, peak GH concentration is an oversimplified outcome of GH testing. Bright and colleagues postulated that serum GH concentrations reflect multiple components of GH input and that a composite pharmacokinetic model that accounts for pulsatile , basal, and oscillatory components is required to accurately estimate each individual’s pharmacokinetic parameters. Ongoing research may aid in applying these complex mathematical models to daily practice.

References
  • Asa SL, Kovacs K. Functional morphology of the human fetal pituitary. Pathol Annu. 1984. 19 Pt 1:275-315. .

  • Cogan JD, Phillips JA 3rd, Sakati N, Frisch H, Schober E, Milner RD. Heterogeneous growth hormone gene mutations in familial GH deficiency. J Clin Endocrinol Metab. 1993 May. 76:1224-8. .

  • Goth MI, Lyons CE, Canny BJ, Thorner MO. Pituitary adenylate cyclase activating polypeptide, growth hormone -releasing peptide and GH-releasing hormone stimulate GH release through distinct pituitary receptors. Endocrinology. 1992 Feb. 130:939-44. .

  • Ikeda H, Suzuki J, Sasano N, Niizuma H. The development and morphogenesis of the human pituitary gland. Anat Embryol . 1988. 178:327-36. .

  • Lee MM. Clinical practice. Idiopathic short stature. N Engl J Med. 2006 Jun 15. 354:2576-82. .

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    High Growth Hormone Levels

    High growth hormone levels associated with high IGF-1 concentrations and normal GH and IGF-1 receptors, seen in the following conditions, cause gigantism in children and acromegaly in adults:

    • Pituitary gland tumor

    • Multiple endocrine neoplasia type I

    • Ectopic production – Some tumors located in the lungs, adrenal glands, pancreas, or elsewhere can secrete either GH or GH-releasing hormone the latter can stimulate the production of GH by the pituitary gland

    • McCune-Albright syndrome – An early postzygotic genetic disease resulting from activating mutations in the alpha subunit of the G protein it can cause constitutional activation of the post-GHRH receptor pathway and increase GH production from the pituitary gland

    High GH concentrations not associated with high IGF-1 levels are seen in the following conditions:

    • Uncontrolled diabetes mellitus

    • Inherited resistance to GH

    High GH levels associated with high IGF-1 concentrations are seen in the following condition:

    • Dwarfism due to IGF-1 resistance because of inactivating mutations in the IGF-1 receptor

    Patients Transitioning From Pediatric To Adult Care

    Laboratory retesting for GHD is also appropriate to determine if GHD is persistent in patients transitioning from pediatric to adult care who have been off GH treatment for at least 1 month with:

    • Suspected hypothalamic GHD
    • Organic GHD with deficiency of two or fewer pituitary hormones in addition to GH

    Testing for GHD is also appropriate in transition patients after radiation treatment.

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    Exercise Capacity And Performance

    Increased exercise capacity, as measured by maximal oxygen uptake, power output, and isometric muscle strength, has been observed during GH replacement in GH deficient adults . A meta-analysis concluded that evidence from short-term controlled studies failed to support a benefit on muscle strength of GH replacement in GH deficient patients, which is likely to occur over a longer time-course, as seen in open-label studies .

    The impact of these changes for individual patients is variable and dependent on age and previous exercise requirements. It is intuitively probable that the improvements depend at least in part on improvements in lean body mass. However, restoration of normal circulating volume may also play a positive role . In addition, improvement in psychological well-being might be expected to enhance physical activity whilst the latter may have a reciprocal beneficial effect on well-being.

    Gh Stimulation In Adults

    Table 1.

    The insulin-induced hypoglycemia test is considered to be the test of choice for diagnosing GH deficiency in adults.4 Since this test involves some risk to the patient , the GHRH + arginine test has been proposed as an equally sensitive alternative.5 Most normal adults will produce a GH concentration > 5 ng/mL after either of these stimulation protocols. Severe GH deficiency has been defined as the inability to produce GH levels > 3 ng/mL during these tests.4,5

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    What Is Growth Hormone

    Growth hormone is one of several hormones produced by the pituitary gland in your brain. Its also known as human growth hormone or somatotropin.

    GH plays a crucial role in human growth and development, especially in children and adolescents. GH levels that are higher or lower than they should be can lead to health problems in both children and adults.

    If your doctor suspects that your body may be producing too much or too little GH, theyll typically start by ordering tests to measure the levels of GH in your blood. Identifying any issues related to GH will help your doctor make a diagnosis and determine the best course of treatment for you.

    Side Effects Of Medicines

    • L-Arginine: This medicine can cause low blood sugar, which can make your child lightheaded or nauseated. Side effects from L-Arginine are rare and usually pass by the time your child goes home.
    • Clonidine: Clonidine lowers blood pressure. The most common side effect is feeling dizzy and lightheaded. Your child should get up slowly after sitting or lying down and be extra careful climbing stairs. They should not go to school and should not play any sports, swim or exercise for the rest of the day. Activities that require them to be alert or have clear vision should be avoided. They may also feel very sleepy for a few hours or have dry mouth, dry eyes or blurry vision. These side effects can last up to 24 hours. Your child should be fine the following day after a good nights sleep.
    • Glucagon: This medicine can cause low blood sugar, which can lead to nausea and vomiting. After the test is done, a snack or meal will help make your child feel better.
    • Cortrosyn: Although rare, Cortrosyn can cause a flushing, warm feeling in the face and a metallic taste in the mouth.

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    Diagnostic Criteria For Hyposomatotropism

    Random testing of serum GH concentrations is of no use in establishing the diagnosis of GHD. Provocative GH testing is not the current criteria standard. Current diagnostic criteria include the following:

    • Growth-velocity Z score below -2, evidence of certain genetic mutations

    • Predicted adult height

    • Serum-free or total IGF-1 Z score below -2

    About Gh Stimulation Testing

    Growth Hormone Stimulation Test | Human Growth Hormone |

    A GH stimulation test is done to find out if your pituitary gland is releasing the right amount of GH.

    During your GH stimulation test, youll take medications to make your pituitary gland release GH. The medications used for your GH stimulation testing are clonidine and L-arginine. Next, your nurse will take blood samples and measure the amount of GH in your blood. Because GH is released in bursts, the level of GH in a single blood sample is likely to be very low. To get the most accurate results, your nurse will take several blood samples over several hours.

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    How Is Growth Hormone Deficiency Treated

    Treatment for growth hormone deficiency in both children and adults involves synthetic growth hormone injections given at home. People with GHD most often need a daily shot.

    Synthetic growth hormone treatment is long-term, often lasting for several years. Its essential to see your healthcare provider regularly to make sure the treatment is working and to see if you need to adjust your dose of medication.

    If you or your child have deficiencies in other pituitary hormones, you or they will also need treatment to correct those deficiencies.

    Side effects of growth hormone deficiency treatment

    Mild to moderate side effects of growth hormone injections for the treatment of growth hormone deficiency are uncommon. They include:

    • Mildly underactive thyroid gland .
    • Swelling of your hands and feet.
    • Progression of spine curvature in people with scoliosis.

    Rare but serious side effects of GHD treatment include:

    • Severe headache with vision problems.

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    What Happens During A Growth Hormone Test

    Your provider may order a GH stimulation or a GH suppression test, depending on whether symptoms show a possible GH deficiency or a GH excess .

    A GH stimulation test is used to check for a GH deficiency. During the test:

    • A health care professional will take a blood sample from a vein in your arm, using a small needle.
    • After the needle is inserted, a small amount of blood will be collected into a test tube or vial.
    • Your child will be given a medicine through an IV line that stimulates the pituitary gland to make GH.
    • More blood samples will be taken over the course of about two hours.
    • Each sample will be tested to see if GH levels have increased.

    A GH suppression test is used to check for a GH excess. During the test:

    • A health care professional will take a blood sample from a vein in your arm, using a small needle.
    • After the needle is inserted, a small amount of blood will be collected into a test tube or vial.
    • You or your child will drink a solution that contains water and glucose .
    • Two more blood samples will be taken within one to two hours after drinking the solution.
    • The blood samples will be tested to see if GH levels have decreased.

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    Causes Of Gh Deficiency

    GH deficiency is when you dont have enough GH. Its usually caused by damage to your pituitary gland. This damage can be caused by:

    • Cancer treatments, such as radiation or surgery to your head or brain
    • A tumor in or near your pituitary gland

    GH deficiency can be total or partial. With total GH deficiency, no GH is made. With partial GH deficiency, some GH is made, but not enough to support normal growth.

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