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Safety Considerations For Growth Hormone Deficiency

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How We Diagnose Growth Hormone Deficiency

Diagnosis, Treatment and Safety of Growth Hormone Therapy in Adults

The first step in treating your child is forming an accurate and complete diagnosis. Before a growth hormone deficiency diagnosis can be made, your child’s physician may have to rule out other disorders first, including genetic short stature , inadequate caloric intake, thyroid hormone deficiency, and other illnesses, including gastrointestinal problems.

In addition to learning your child’s complete medical history, gathering information about the heights and any health problems of your relatives, and conducting a physical examination, your child’s doctor may:

  • monitor your child’s growth over a period of time
  • review the mother’s pregnancy, labor, and delivery
  • draw a small amount of blood to look for evidence of other diseases
  • arrange for an x-ray of your child’s hand and wrist
  • measure amounts of insulin-like growth factor-1 and insulin-like growth factor binding protein-3 in the blood, which are produced when the liver and other tissues are stimulated by growth hormone

Since growth hormone is produced in bursts, it is unlikely that any single blood sample will provide a definitive diagnosis.

If growth hormone deficiency is suspected, your physician may use a stimulant of growth hormone secretion , and measure the growth hormone release over time.

If growth hormone deficiency is diagnosed, your physician may order an MRI of the brain to look at the hypothalamus and pituitary gland.

The Importance Of Growth Hormone Therapy For Pws

Early diagnosis and optimal clinical care can improve outcomes for people with PWS, and one proven intervention is growth hormone therapy. This treatment was approved by the US Food and Drug Administration for children with PWS in June 2000. Since then, several benefits have been reported, and growth hormone therapy for PWS has become an important step after an initial diagnosis.

Treatment Of Ghd In Children

Patients with proven GHD should be treated with recombinant hGH as soon as possible after the diagnosis is made. The primary objectives of the therapy of GHD are normalization of height during childhood and attainment of normal adult height. Normally growing patients with craniopharyngioma and GHD should be considered for therapy with GH for metabolic and body composition benefits and for enhancement of pubertal growth. Insufficient data regarding the utility of GHRH, GH secretagogues, and depot GH are currently available to formulate recommendations regarding their use in GHD.

Dosing of GH. GH should be administered sc in the evening on a daily basis, and the dosage of GH should be expressed in milligrams per kg/day, although consideration should be given to dosing in micrograms per m2/day in patients with obesity. GH is routinely used in the range of 2550 g/kg/day. A dose-response relationship in terms of height velocity in the first 2 yr of treatment has been clearly demonstrated within this range. Under special circumstances, higher doses may be required. Prediction models of growth response might be useful for determination of the optimal individual dose and are currently being investigated, but need further evaluation.

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What Is Human Growth Hormone

Growth hormone is a small protein made in part of the brain called the pituitary gland. It travels in the bloodstream to all tissues in the body to stimulate growth.

Lack of HGH can cause slow growth in children and also problems with fitness and health in adults.

A very high level of HGH can cause children to be abnormally tall. In adults, it can cause overgrowth of bone that disfigures the hands, feet and face a condition called acromegaly.

Until the mid-1980s, the growth hormone used to treat humans was extracted from the donated brains of dead people. However a small number of people treated with such HGH developed Creutzfeld-Jakob Disease , a brain disease that causes muscle wasting and dementia.

Today synthetic HGH is used. There is no risk now of CJD.

Transitional Care After Childhood Gh Treatment


5.1. We recommend that patients with multiple pituitary hormone deficiencies regardless of etiology, or GHD with a documented causal genetic mutation or specific pituitary/hypothalamic structural defect except ectopic posterior pituitary, be diagnosed with persistent GHD.

5.2. We recommend re-evaluation of the somatotropic axis for persistent GHD in persons with GHD and deficiency of only one additional pituitary hormone, idiopathic isolated GHD , IGHD with or without a small pituitary/ectopic posterior pituitary, and in patients after irradiation.

Technical Remark: Testing can be performed after a trial of at least 1 month off GH treatment.

5.2.1. We suggest that measurement of the serum IGF-I concentration be the initial test of the somatotropic axis if re-evaluation of the somatotropic axis is clinically indicated.

5.2.2. We recommend GH provocative testing to evaluate the function of the somatotropic axis in the transition period if indicated by a low IGF-I level.

5.3. We suggest that GH treatment be offered to individuals with persistent GHD in the transition period. There is evidence of benefit however, the specifics of the patient population that benefits, the optimal time to re-initiate treatment, and the optimal dose are not clear.

Technical Remark: The transition period is the time from late puberty to establishment of adult muscle and bone composition, and encompasses attainment of AH.

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Are There Any Specific Side Effects That May Occur After Short

Key statement: Some side effects related to GH replacement in children occur more frequently among cancer survivors, such as increased intracranial pressure, slipped capital femoral epiphysis, and worsening of scoliosis. In adults, there are no data to suggest a different side-effect profile.

After starting GH replacement, re-testing for central hypothyroidism and adrenal insufficiency may be needed, and in those already on treatment for these deficiencies, dose adjustment may be required as reviewed and stated in previous guidelines .

There are no data in adults to indicate that side effects of GH replacement differ from those seen in patients without a history of cancer. In children, however, increased intracranial pressure, slipped capital femoral epiphysis, and worsening of scoliosis may be more frequent among cancer survivors . In children who have received spinal irradiation, disproportionate growth may be exaggerated with GH therapy, as the spine may grow proportionally less than the limbs .

Other Treatments For Growth Hormone Deficiency

In addition to growth hormone therapy, you may need other treatments for growth hormone deficiency.

For example, being very short can affect a childs self-esteem: Classmates can tease a child to the point of tears. Thats why mental and emotional therapy is often an important part of treatment. A mental health counselor or psychologist can talk you through your feelings and teach you how to cope with growth hormone deficiency.

Getting enough sleep, eating a balanced diet, and regularly exercising are also important parts of an overall growth hormone deficiency treatment plan. Your doctor can teach you how to incorporate growth hormone injections into a healthy lifestyle.

More on this topic

Adult growth hormone deficiency. Cedars-Sinai Medical Center Web site. . Accessed May 16, 2011.

Growth hormone deficiency. Health Guide. New York Times Web site. . Published September 13, 2009. Accessed May 16, 2011.

Growth hormone deficiency – children. MedlinePlus Web site. . Update July 26, 2010. Accessed May 16, 2011.


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Experimental Evidence For The Role Of Gh

The effects of GH in stimulating mitosis, cell differentiation and growth has been known since the early years of the twentieth century . In the 1950s, it was shown that GH action in peripheral tissues could be mediated by insulin-like growth factor I , and since then, novel components of the GH-IGF-I signaling system and their roles on normal and abnormal cell growth and metabolism have been progressively unraveled .

Fig. 1

Cumulative data obtained from natural or genetically modified animals exhibiting normal or disrupted GH production or action, have also brought a wealth of evidence linking GH axis and carcinogenesis . The repression of the GH-IGF signaling system in many of these models has been associated with significant reductions in cancer rates and increased longevity. In contrast, transgenic mice with excessive circulating levels of GH or tissue overexpression of IGF-I exhibit an increased risk for hyperplasia and tumor formation .

Symptoms Of Deficiency Of Growth Hormone

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Any three of the below mentioned problems in the body are a reason for possible deficiency of growth hormone and one should get it checked by a good doctor:

  • Thinning of Skin and premature wrinkling
  • Currently receiving one or more other hormone preparations
  • Increased Fat around the Waistline
  • Loss of muscle mass or decreased strength
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    Gh Treatment In Cancer Survivors In Childhood

    The growth of children who have undergone cancer treatment should be assessed every 612 months, and lifelong assessment may be necessary to screen for the development of GHD. It is recommended to measure standing and sitting height in children treated with spinal radiotherapy, i.e., total body irradiation, craniospinal irradiation, as well as radiation to the chest, abdomen, or pelvis . GHD should be suspected when growth deceleration is observed with a deflection of at least 0.3 SDS/year or height deviates from the familial background . The measurement of serum IGF-I levels is not recommended as a biomarker for the diagnosis of GHD in CCS, especially among those exposed to hypothalamic-pituitary irradiation . Normal serum IGF-I levels have been observed in CCS who failed in GH dynamic testing, especially those treated with low doses of radiotherapy. In survivors of childhood ALL treated with cranial radiotherapy, IGF-I levels< 2 SDS showed a sensitivity of only 17.86% sensitivity of IGF-I as a diagnostic tool was even lower in subjects treated with 14.4 Gy total body irradiation before bone marrow transplantation. The use of IGF-I as a screening tool should be restricted to patients treated with high cranial radiation doses . Similarly, serum IGFBP3 do not aid in the diagnosis of GHD in CCS children .

    Table 3 Current recommendations related to clinical evaluation and growth hormone treatment in cancer suvivors during childhood

    Growth Hormone Therapy Cost

    Before a few years, the cost of growth hormone therapy was too much at about $1000 per month. This price has now come down to $500 per month and that too depending upon the dosage. This hormone is required in fewer doses in men than in women. Many insurance schemes cover the cost of growth hormone completely.

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    What Is The Role Of Gh

    Key statement: Epidemiological studies have shown an association between serum IGF-I levels in the higher normal reference range and an increased risk of certain cancer types, but it is not clear that markedly excessive GH levels in acromegaly are independently associated with increased cancer occurrence.

    Several epidemiological studies and systematic reviews with meta-analyses have drawn attention to a possible association between serum IGF-I levels in the higher normal reference range with the presence of breast, colorectal, and prostate cancer in the general population . Nevertheless, a causal relationship is difficult to determine from these studies due to the presence of multiple confounders, such as age, body weight and height, nutritional status, insulin resistance, heterogeneity of IGF-I assays, and serum IGFBP3 levels . In addition, it has not been possible to translate results of epidemiological studies into clinical practice in order to establish a âsafeâ IGF-I level.

    Is Gh Replacement Associated With A Higher Risk Of A Secondary Neoplasm

    Human Growth Hormone and The Magic Zone

    Key statement: The specific effect of GH replacement on secondary neoplasia risk is minor in comparison to host- and tumour treatment-related factors.

    A significant association between GH replacement and a higher risk for secondary neoplasia has been reported in some , but not all , studies investigating health outcomes in childhood cancer survivors, as well as a meta-analysis from the Endocrine Society . Host- and treatment-related factors, such as radiotherapy, are the primary drivers of secondary neoplasia risk in this population .

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    Questions To Ask Your Doctor

    You and your family are key players in your childs medical care. Its important that you share your observations and ideas with your childs health care provider and that you understand your providers recommendations.

    If your child is experiencing symptoms of growth hormone deficiency and youve set up an appointment, you probably already have some ideas and questions on your mind. But at the appointment, it can be easy to forget the questions you wanted to ask. Its often helpful to jot them down ahead of time so that you can leave the appointment feeling like you have the information you need.

    If your child is old enough, you may want to suggest that she write down what she wants to ask her health care provider, too.

    Some of the questions you may want to ask include:

    • Whats causing my childs growth hormone deficiency?
    • Will you be prescribing growth hormone replacement therapy?
    • Are there any side effects or potentially dangerous risks to treatment?
    • How long will my child have to remain on medication?
    • How much can I expect my child to grow?

    What Causes Growth Hormone Deficiency

    GHD that isnt present at birth may be caused by a tumor in the brain. These tumors are normally located at the site of the pituitary gland or the nearby hypothalamus region of the brain.

    In children and adults, serious head injuries, infections, and radiation treatments can also cause GHD. This is called acquired growth hormone deficiency .

    Most cases of GHD are idiopathic, meaning that no cause has yet been found.

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    Safety Of Hgh Replacement In Children

    Safety issues during GH replacement may be related to the medical substance itself, may be due to the formulation of the drug , be the result of the genuine effects they may be due to inappropriate dosages or a genuine incompatibility with the patient being treated . During the pit-hGH era, when relatively crude GH material were applied in low doses, local effects were occasionally observed . Due to the transmission of prions through some pit-hGH preparations, which caused the deadly Creutzfelt-Jakob disease, this era ended .

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    • 1Barrow Pituitary Center, Barrow Neurological Institute, Departments of Neuroendocrinology and Neurosurgery, University of Arizona College of Medicine and Creighton School of Medicine, Phoenix, AZ, United States
    • 2Division of Pediatric Endocrinology, Department of Pediatrics, University of Minnesota, Minneapolis, MN, United States
    • 3SEMPR, Serviço de Endocrinologia e Metabologia, Departamento de Clínica Médica, Hospital de Clínicas da Universidade Federal do Paraná, Curitiba, Brazil
    • 4Department of Medicine, VA Palo Alto Health Care System and Stanford University School of Medicine, Palo Alto, CA, United States

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    What Tests Will Be Done To Diagnose Growth Hormone Deficiency

    Healthcare providers use different tests to diagnose growth hormone deficiency depending on if youre a child or adult.

    GHD diagnostic tests for children

    Your childs healthcare provider will review their medical history and growth charts to look for signs of impaired growth, risk factors for growth hormone deficiency and other conditions that can affect growth.

    Other health conditions that can affect and prevent growth include:

    Since growth hormone levels in your blood normally vary greatly throughout the day, a simple blood test cant determine a GH deficiency. Because of this, your childs provider may order the following tests to help diagnose GHD and/or to rule out other conditions that affect growth:

    GHD diagnostic tests for adults

    One of the most common tests for diagnosing growth hormone deficiency in adults is the insulin tolerance test. Insulin is a natural hormone your pancreas makes.

    During this test, your provider will give you an injection of synthetic insulin to lower your blood sugar level. They will then take blood samples and send them to a lab for testing in order to measure the amount of growth hormone in your blood.

    When your body experiences low blood sugar , it normally releases growth hormone. If your blood tests reveal lower-than-normal levels of growth hormone than whats expected for an insulin tolerance test, it confirms growth hormone deficiency.

    Other tests may include:

    When Should I See My Healthcare Provider About Growth Hormone Deficiency

    There are many reasons for slow growth and below-average height in children. At times, slow growth is normal and temporary, such as right before puberty starts. If youre concerned about your childs rate of growth, see a pediatric endocrinologist or healthcare provider. They can help find out if your childs rate of growth is cause for concern.

    If youre an adult and are experiencing symptoms of growth hormone deficiency , talk to your healthcare provider.

    If you or your child have been diagnosed with GHD, youll need to see your healthcare provider regularly to make sure your treatment is working properly.

    A note from Cleveland Clinic

    If youre noticing a lack of growth in your child, its important to talk to their healthcare provider as soon as possible. While it may be unlikely that growth hormone deficiency is the cause, any concerning changes are worth evaluating. People with GHD who are diagnosed early have the best outlook and usually lead healthy lives. If you have any questions about what to expect with your childs growth, dont be afraid to reach out to their provider. Theyre there to help.

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    Measures Of Carbohydrate Metabolism

    Fasting blood glucose and HbA1c/GHb.

    Average fasting blood glucose values measured on an annual basis were similar among the five treatment groups across the two ISS studies. Values were not significantly changed with GH treatment, and no GH dose effect was detected . Rare, sporadic elevated blood glucose values were observed for individual patients, probably due to inadequate fasting. As would be expected from the lack of GH effect on fasting blood glucose, no significant changes were observed in HbA1c or GHb .

    Fasting insulin and indices of insulin sensitivity.

    Analyses of insulin sensitivity were performed only in study ISS1. There were no significant differences in mean fasting insulin between the GH- and placebo-treated groups throughout the study . Nevertheless, because fasting glucose and insulin concentrations may fail to reveal subtle changes in insulin sensitivity, an analysis of the QUICKI, a validated measure of insulin sensitivity, was performed. In this analysis, higher values reflect greater insulin sensitivity. As shown in , there was marked interindividual variation in the pattern of QUICKI changes from baseline to last visit in both treatment groups. Overall, there was no systematic difference between the treatment groups for the pattern of these changes. Furthermore, by analysis of covariance accounting for a slight imbalance in baseline QUICKI values, there was no significant GH effect on the change in QUICKI values from baseline to last visit.

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