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Not All Growth Disorders Reflect Hormone Deficit

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Not All Growth Disorders Reflect Hormone Deficit November 15, 2005 • www.familypracticenews.com Metabolic Disorders 21 Not All Growth Disorders Reflect Hormone Deficit BY HEIDI SPLETE problems when the growth rate is less than corticoids might contribute to delayed bolic profile, complete blood count, thy- Senior Writer 5 cm/yr from age 3 years to 12 years, Dr. growth. Long-term data on the impact of roid function test, and celiac screen. Plotnick advised. In addition, consider the other medications—including stimulants, A definitive diagnosis of growth hor- B ALTIMORE — Consider a wide range possibility of a growth disorder when a antidepressants, antiseizure medications, mone deficiency requires at least two tests of causes when evaluating a child for a child’s height is below the 5th percentile or and antipsychotics—on growth delay re- that indicate a growth hormone level of growth disorder, Leslie Plotnick, M.D., said when height drops across percentiles over main inconclusive as well. less than 10 ng/mL, including arginine, L- at a meeting on pediatric endocrinology time. Another sign is when a child’s height Carefully monitor height and weight dopa, clonidine, glucagon, and insulin-in- sponsored by Johns Hopkins University. is more than two standard deviations below patterns in children who take these med- duced hypoglycemia. If a child appears to Although growth hormone treatment is the average height of the biologic parents. ications, Dr. Plotnick said. Changes from have growth hormone deficiency, con- approved by the Food and Drug Adminis- Causes of short stature or poor linear established pretreatment growth patterns duct a brain MRI and test other pituitary tration for some conditions, not all chil- growth include major organ system dis- suggest a medication effect and may re- axis hormones, she added. dren with growth problems are growth eases that are cardiac, pulmonary, renal, quire further evaluation. Growth hormone deficiency can be con- hormone deficient, and a thorough eval- gastrointestinal, nutritional, hematolog- Endocrine-related causes of short genital or genetic, or it can be acquired as uation is important, including a complete ic, or CNS-related. In addition, chromo- stature include hypothyroidism, cortisol a result of brain tumors, infiltrative dis- history and physical examination. somal disorders such as Turner’s syn- excess, pseudohypoparathyroidism, poor- eases, head trauma, infection, central ner- “A child with normal growth will track drome; intrauterine growth retardation; ly controlled diabetes mellitus, and growth vous system surgery, or central nervous along a percentile line,” said Dr. Plotnick, endocrine disorders; or, simply, familial hormone deficiency. Features associated system irradiation to treat a tumor. a pediatric endocrinologist at Johns Hop- short stature or constitutional growth de- with these conditions include goiter, dry For more specific information about kins University. Growth velocity normal- lay can cause a child to grow at a slower skin, midline defects, micropenis in boys, growth patterns in children and to down- ly decreases prior to puberty, until the ado- than average rate. and an especially round, cherubic face. load the current growth charts from the lescent growth spurt begins. Although evidence of any association The screening work-up for short stature Centers for Disease Control and Preven- Consider evaluating children for growth remains uncertain, oral or inhaled gluco- is extensive and includes a complete meta- tion, visit www.cdc.gov/growthcharts. ■ Dosing Growth Hormones to ICMA Gonadotropin Test Called IGF-1 Levels More Effective The Best Lab Evidence of Puberty BY BETSY BATES justable doses of growth hormone Los Angeles Bureau based on IGF-1 levels at 3-month check- BY DOUG BRUNK evidence of breast development by age 13 ups. San Diego Bureau years or a boy who has no evidence of tes- S AN D IEGO — Short children grew One group received growth hor- ticular enlargement by age 14 years. The fol- far taller when their growth hormone mone in amounts necessary to Y OSEMITE, CALIF. — The best laborato- lowing are general possibilities in this differ- doses were adjusted according to their achieve normal IGF-1 levels, and in- ry evidence of puberty is a test for luteinizing ential diagnosis: insulin-like growth factor 1 levels cluded 70 children. The other group, hormone and follicle-stimulating hormone Ǡ Constitutional delay in growth. Most rather than to their weight, according which numbered 68 children, received done by immunochemiluminometric assay, children seen for concerns about delayed pu- to randomized study results. enough growth hormone to drive Stephen M. Rosenthal, M.D., said at a pediatric berty will fit this category. “IGF-1 levels do matter,” said Pin- their IGF-1 levels two standard devi- conference sponsored by Symposia Medicus. “This is one of those interesting scenarios chas Cohen, M.D., professor and di- ations above the norm. Two labs that run the tests are Esoterix Inc. where it appears that people not only grow rector of research and training in the The three groups achieved mean and Quest Diagnostics Inc., said Dr. Rosenthal, more slowly and reach puberty more slowly, division of endocrinology at the Uni- IGF-1 levels of +0.4, +0.4, and +2.0 professor of pediatrics it’s like there’s some- versity of California, Los Angeles, standard deviation scores in the first 9 at the University of Cal- Some ‘people thing in their biological School of Medicine. months of the study, and doses of 41 ifornia, San Francisco. not only grow clock that makes them The notion of targeting dosing in mcg/kg per day, 33 mcg/kg per day, “If you ever order more slowly and age more slowly,” Dr. order to maximize height in children and 110 mcg/kg per day were required tests for LH and FSH, it’s reach puberty Rosenthal noted. “They of short stature is somewhat new and to sustain these levels, said Dr. Cohen. very important that you more slowly ... ultimately reach a nor- had been thought clinically impracti- Only a small, nonsignificant differ- order them by immuno- [they] age more mal adult height and full cal, Dr. Cohen said at a clinical sym- ence was seen in children receiving chemiluminometric as- slowly.’ pubertal development; posium during the annual meeting of standard growth hormone doses ac- say (ICMA), because [the it just takes them longer the Endocrine Society. cording to weight and those receiving tests] are able to distin- DR. ROSENTHAL to get there. This often However, it was “possible and doses targeted at a normal IGF-1. guish between someone runs in families. Is it pos- doable” to adjust doses according to The big difference in height was seen who’s prepubertal and the different Tanner sible that these kids actually age more slowly a simple IGF-1–based algorithm. This in children who received growth hor- stages,” he said. as they grow older, even as adults?” he asked. approach resulted in “significant, mone at a dose aimed at raising their If you get results that are difficult to inter- “Is there something to be learned here to give quite dramatic improvement in IGF-1 levels to two standard deviations pret, Dr. Rosenthal recommended doing a us some insight? We don’t know the answer to height” for some children enrolled in greater than the norm. In this group, GnRH stimulation test, which is also called a that yet because there are so many variables the 2-year, multicenter trial. children with growth hormone defi- luteinizing hormone releasing factor (LRF) as we get older that affect longevity.” In all, 172 children diagnosed with ciency grew 45% more, and children stimulation test. This involves giving a syn- Ǡ Hypogonadotropic hypogonadism. In growth hormone deficiency or idio- with idiopathic short stature grew 58% thetic bolus of GnRH and then measuring this condition, the defect is located in the hy- pathic short stature were enrolled in more than children in the other groups. the patient’s levels of LH, FSH, and either pothalamus or in the pituitary gland. The the trial sponsored by Novo Nordisk Side effects and adverse events were estradiol or testosterone. cause could be Kallmann syndrome or could Inc., a manufacturer of human growth similar in all three groups. Dr. Rosenthal noted that there have been be associated with other conditions including hormone, and the Lucile Packard Interestingly, a huge variability was availability problems with GnRH. If GnRH cleft palate; congenital deafness; the X-linked Foundation for Children’s Health. seen in the amount of growth hor- is not available, a similar test can be done with form of congenital adrenal hypoplasia; Prad- The children were aged 3-15 years mone required to maintain targeted leuprolide acetate, a GnRH agonist. Guide- er-Willi syndrome; Laurence-Moon-Biedl and significantly below normal height IGF-1 levels among individual pa- lines for carrying out the latter test are de- syndrome; central nervous system disease; for their age, with a mean standard tients: 9-114 mcg/kg per day in the scribed in the following reference: J. Clin. En- and a variety of other conditions such as hy- deviation score of –2.63. They also first targeted group and 20-346 docrinol. Metab. 1994;78:30-5. pothyroidism, poorly controlled diabetes, had low levels of IGF-1, the core me- mcg/kg per day in the second. “If you give an injection of synthetic and anorexia nervosa. diator of growth hormone action on Dr. Cohen serves as a consultant or GnRH [or agonist] to somebody who’s in pu- Ǡ Hypergonadotropic hypogonadism. In linear growth. advisory board member or receives berty, their own pituitary gland has been this condition, the defect is in the testes or The complex study design featured research support from a number of primed by their own GnRH; so when you ovaries.
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