Friday, August 19, 2022

Growth Hormone Stimulation Test Protocol

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Parent Information For Crossroads Registration

What is a growth hormone stimulation test?
  • Crossroads Registration is located on the main level near the Crossroads Welcome Desk, between the Crossroads elevators and the Tower elevators. Follow the Blue Path to the Crossroads lobby where the Green Path meets the Blue Path.
  • The Infusion Clinic can be accessed from the Tower elevators . Take the Tower elevators to level 4 and turn right into Suite D.

Parking Options:

  • Hospital Garage on Childrens Drive. Once inside, turn right and follow the Blue Path. It meets the Green Path at the Crossroads Registration Area.
  • Outpatient Care Garage on 18th Street. Enter the hospital and follow the Blue Path. It meets the Green Path at the Crossroads Registration Area.
  • Valet parking on Childrens Drive or 18th Street. Enter the hospital and follow the Blue Path. It meets the Green Path at the Crossroads Registration Area.

If you have any questions, contact your childs health care provider in the endocrinology department.

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.

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

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Clinical And Biochemical Parameters Of Patients With Ghd Or Iss

Values are presented as mean±standard deviation . GHD: growth hormone deficiency, ISS: idiopathic short stature, CA: chronological age, BA: bone age, SDS: standard deviation score, MPH: midparental height, BMI: body mass index, IGF-1: insulin-like growth factor-1, IGFBP-3: IGF binding protein-3, Peak GH-L: L-dopa, Peak GH-I: insulin.

TABLE 2

What Is Growth Hormone

Results of pharmacological growth hormone stimulation tests in our ...

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.

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Evidence And Science Behind The Test

A lack of growth hormone in children leads to short stature and other growth problems. In adults, it affects body composition and can decrease quality of life.

Growth hormone releasing hormone is found in the hypothalamus of the brain and its secretion increases when the body is exposed to stress . GHRH stimulates the release of growth hormone.

Somatostatin prevents GHRH and GH secretion and arginine inhibits somatostatin release, allowing growth hormone levels to increase. One 2006 study showed that subjects who received a 30 g administration of arginine before exercising were able to demonstrate a larger release of growth hormone, when compared to those subjects who just exercised.

Diagnosing growth hormone deficiency in adults requires growth hormone secretion to be stimulated in the body. Although the insulin tolerance test is one way to stimulate a growth hormone response, the GHRH+Arg test is becoming popular. Not only does it have similar results to the ITT test, results can be reproduced and patients tolerate the testing better.

A recent validation study showed that the GHRH+Arg test and ITT had similar results although the ITT was more sensitive. Subjects who underwent the GHRH+Arg test reported fewer adverse events during the testing.

Obesity in both men and women is linked with decreased levels of growth hormone release. One study confirmed a significant inverse relationship between growth hormone response and body mass index .

How Is It Done

It is important not to exercise before the test and fasting is usually required. If undergoing hormone treatments, these may need stopping before the test. In a typical test, an IV catheter is inserted into the arm and left for a while, allowing the patient to relax. A blood sample is then taken for baseline measurements. The doctor or nurse wi. Oral arginine attenuates the growth hormone response to resistance exercise. Journal of Applied Physiology. Vol. 101 no. 3 848-852

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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 .

What Happens During The Test

Growth Hormone Stimulation Test | Human Growth Hormone |

For your child, the test begins with a technician placing an IV line in their arm or hand.

After giving a blood sample, your child will get a dose of medicine or medicines to stimulate the pituitary gland to release growth hormone. The most common medicines chosen are clonidine , arginine or glucagon. Insulin is less commonly used now because of safety concerns with children.

During all of this, the assistant will probably take a blood sample around every 30 minutes. The samples are not large — perhaps a couple of teaspoons, total, over the course of the day.

At the end of the test, your child can eat. They should rest afterwards.

Itâs a similar process for adults who get the GH stimulation test. Adults have the option of a medicine called macimorelin which is given as a liquid to drink. Insulin is less often used now because of unpleasant side effects and safety concerns due to low blood sugars.

Both children and adult blood samples can also be checked for IGF-1 and IGFBP-3 alongside the stimulation test.

If you take the GH suppression test, youâll drink a glucose solution in the first 5 minutes, and get your blood checked every 30 minutes for 2 hours.

Growth hormone tests arenât likely to cause any complications, though some people may feel faint. Bruising is possible where the IV line went into your vein.

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Limitations And Caveats When Interpreting Gh Stimulation Tests

The responses to all GH stimulation tests show intra-individual variability, and the GH cut-points vary depending on the test used. For the ITT and GST, the cut-points advocated by previous consensus guidelines were 3-5 g/L and 2.5-3g/L, respectively . Other GH stimulatory agents such as clonidine, L-DOPA, and arginine are weaker GH secretagogues, and would require very low GH cut-points with utilization of sensitive GH assays to achieve adequate specificity . Hence, these tests are generally not recommended in the United States . Other limitations include the relative lack of validated normative data based on age, gender, BMI, glycemic status, and the paucity of data for specific etiologies of adult GHD that have recently been described, such as traumatic brain injury, subarachnoid hemorrhage, ischemic stroke, and central nervous system infections .

Growth Hormone Stimulation Test

A growth hormone stimulation test is done to find out if the pituitary gland is releasing growth hormone into the bloodstream in the right amounts. The pituitary is a small gland in the brain.

For this test, your child will get medicines to stimulate the pituitary gland to release growth hormone. The medicines used are L-arginine and:

  • Clonidine or
  • Glucagon

Your provider may also use a medicine called CortrosynTM to know about cortisol, a stress hormone, in the blood.

Samples of blood are then taken and sent to the laboratory to measure the amount of growth hormone.

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When To Get Tested

When a child has slow growth, short stature, and delayed motor development or sometimes when an adult has decreased bone density and/or muscle strength and elevated blood lipid levels that could be related to growth hormone deficiency when a child or adult has signs and symptoms suggestive of growth hormone excess, which can cause two rare conditions, gigantism and acromegaly, respectively when a pituitary disorder is suspected and other pituitary hormone levels are abnormal

What Is Being Tested

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Growth hormone is a hormone that is essential for normal growth and development in children. It promotes proper linear bone growth from birth through puberty. In both children and adults, growth hormone helps regulate the rate at which the body both produces energy from food and makes lipids, proteins, and glucose . It also helps regulate the production of red blood cells and muscle mass.

Growth hormone is produced by the pituitary gland, a small gland located at the base of the brain behind the bridge of the nose. It is normally released into the blood in pulses throughout the day and night with peaks that occur mostly during the night. Because of this, a single measurement of the level of GH in blood is difficult to interpret and not usually clinically useful. The value will be higher if the sample is taken during a pulse and lower if it is taken during a period between pulses.

Therefore, procedures called growth hormone stimulation and suppression tests are most often used to diagnose conditions caused by growth hormone deficiency or excess. These procedures are used in conjunction with signs and symptoms and growth factor levels and insulin-like growth factor binding protein 3). See How is the test used? under Common Questions for more detail.

GH deficiency

GH excess

Excess GH is most often due to a pituitary tumor that produces GH.

How is the sample collected for testing?

Is any test preparation needed to ensure the quality of the sample?

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How The Test Is Done

The test will be done in the Infusion Clinic. This test may take up to 6 hours. Parents are asked to stay with their child during the test. Since there is limited seating, other family members may be asked to sit in the waiting room.

  • The nurse will start an intravenous line . The nurse may offer to put lidocaine-prilocaine cream on your childs arm before starting the IV. The cream takes about 20 minutes to numb the skin where the IV will go.
  • The IV will be used to draw blood samples, to give L-Arginine and, if ordered, Cortrosyn .
  • Your child will then get either Clonidine or Glucagon. Clonidine is a pill that is swallowed. Glucagon is given by injection under the skin in the upper arm and not in the IV.
  • Blood samples will be drawn for growth hormone studies every 30 minutes for up to 4 hours. Your child should not feel any pain since the blood will be drawn from the IV. The total amount of blood drawn is small .

Gh Test Protocol And Types

There are several different types of GH tests, and the specific testing protocol varies depending on which test your doctor orders.

As with all medical tests, its important to follow all of the preparation instructions from your healthcare team. In general, for GH tests, your doctor will ask you to:

  • fast for a specific period of time before the test
  • stop taking the vitamin biotin, or B7, at least 12 hours before the test
  • stop taking certain prescription medications a few days before the test, if they might interfere with the test results

For some tests, your doctor may provide additional preparation instructions.

Its uncommon for people to have GH levels outside the typical range, so GH tests arent performed routinely. If your doctor thinks the levels of GH in your body may be abnormal, theyll likely order one or more of the following tests.

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Growth Hormone Stimulation Test: What To Expect

    Your child is scheduled to have a growth hormone stimulation test. Learn how to prepare for the test and learn what to expect on the day of the test.

    • If your child is sick, you need to cancel and reschedule the test. Please call the PICU at 617-724-4350.
    • If your child is not sick, but you need to reschedule the test, please call the Pediatric Endocrinology nurse line at 617-726-7424.

    Growth Hormone Stimulation Testing: To Test Or Not To Test That Is One Of The Questions

    Which medications are used for a growth hormone stimulation test?
    • Division of Pediatric Endocrine and Diabetes, Mount Sinai Kravis Childrens Hospital, New York, NY, United States

    The evaluation of children with short stature includes monitoring over a prolonged period to establish a growth pattern as well as the exclusion of chronic medical conditions that affect growth. After a period of monitoring, evaluation, and screening, growth hormone stimulation testing is considered when the diagnosis of growth hormone deficiency is entertained. Though flawed, growth hormone stimulation tests remain part of the comprehensive evaluation of growth and are essential for the diagnosis of growth hormone deficiency. Variables including testing length, growth hormone assay and diagnostic cut off affect results. Beyond the intrinsic issues of testing, results of GH stimulation testing can be influenced by patient characteristics. Various factors including age, gender, puberty, nutritional status and body weight modulate the secretion of GH.

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    Gh Stimulation In Children

    The exercise stimulation test is often used as an initial screen for GH deficiency, but combinations of other tests have been advocated by various institutions. A subnormal response from a single provocative test is not diagnostic for GH deficiency and should be confirmed with a second provocative test. These tests produce an increase in plasma GH to > 7 ng/mL in individuals with appropriate GH production.1-3 Some institutions use 10 ng/mL as a cutoff for normal GH response.1,3

    The insulin-induced hypoglycemia and the GHRH tests provide additional information beyond establishing GH deficiency. The insulin-induced hypoglycemia test allows the assessment of the entire hypothalamic-pituitary-adrenal axis. A normal GH response to GHRH in a patient proven to be GH deficient by previous stimulation testing suggests that the GH deficiency is due to insufficient GHRH production by the hypothalamus.

    Due to low baseline levels of GH, prepubertal children should be primed prior to performing the stimulation tests by one of the following:3

  • 5 mg Premarin® PO the night before and the morning of the test, or
  • 50100 g/day of ethinyl estradiol for three consecutive days prior to testing, or
  • 100 mg/day depot testosterone for three consecutive days prior to testing
  • Comparison Of The Two Tests

    There was a strong correlation between the GH response to the ITT and to the GHRH/GHRP test .

    There is no absolute definition for the criteria of severe GHD. Recent consensus guidelines define severe GHD as a peak GH response to hypoglycemia of less than 9 mU/L, provided the GH assays use polyclonal competitive RIAs calibrated against a specific pituitary-derived preparation IRP 80/505. Using this criterion as the basis for our diagnosis of severe GHD , 28 of our 36 patients were severely GH deficient . The other eight patients had a mean peak GH response of 35.5 mU/L . Using the ITT data to classify our patients, we grouped our GHRH/GHRP results according to the ITT diagnosis. On this basis, the GHD patients showed a mean peak GH response of 10.0 mU/L and the other patients showed a mean peak GH response of 74.05 mU/L to the GHRH/GHRP test.

    If instead of looking for peak response to GHRH/GHRP we only look at the result at 30 min and define severe GHD with the same criteria as that used for peak responses to GHRH/GHRP , there is 100% concurrence in diagnosis for all our subjects. If, on the other hand, the ITT is considered to be the reference test, then the GHRH/GHRP test has 78.6% sensitivity and 100% specificity even when the 30-min datum point alone is used.

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