Growth hormone deficiency overview
|
Growth hormone deficiency Microchapters |
|
Differentiating Growth hormone deficiency from other Diseases |
|---|
|
Diagnosis |
|
Treatment |
|
Case Studies |
|
Growth hormone deficiency overview On the Web |
|
American Roentgen Ray Society Images of Growth hormone deficiency overview |
|
Risk calculators and risk factors for Growth hormone deficiency overview |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mohammed Abdelwahed M.D[2]
Overview
Isolated GH deficiency is the most common hormone deficiency of pituitary gland. There are three types of GH deficiency congenital, acquired, and idiopathic. Congenital causes include genetic mutations in POU1F1, PROP-1, and GH-1 genes. Structural causes of GH deficiency includes optic nerve hypoplasia, agenesis of corpus callosum, septo-optic dysplasia, empty sella syndrome, and holoprosencephaly. Acquired causes include GHD from brain surgery, radiation therapy for brain tumors, central nervous system infection, craniopharyngioma, and pituitary adenoma. The somatotroph cells of the anterior pituitary gland produce growth hormone. During the development of the anterior pituitary gland, the temporal and spatial expression of early (Hesx1, Sox2, Sox3, Lhx3, Lhx4, Ptx1, Ptx2, and Otx2) and late (Prop1 and Pou1f1) transcription factors and signaling molecules has a major role in the pathogenesis of GH deficiency. Growth hormone deficiency in children must be differentiated from other diseases that cause short stature in children such as Achondroplasia, constitutional growth delay, familial short stature, and growth hormone resistance. Prevalence and incidence data of growth hormone deficiency vary widely due to the lack of standard diagnostic criteria. Genetic screening of growth hormone deficiency(GHD) is indicated for patients with early and severe symptoms. Common complications of growth hormone deficiency include osteopenia, dyslipidemia, delayed puberty, and higher mortality rates than normal subjects. Prognosis is generally good with treatment. Measurement of a random serum GH level alone is not helpful. Measurement of Insulin-like growth factor I (IGF-I) and Insulin-like growth factor binding protein-3 (IGFBP-3) is more helpful than GH level alone. GH stimulation tests are indicated for most patients suspected to have GHD. Growth hormone (GH) is indicated for children with GH deficiency whose epiphyses are open. Serum levels of insulin-like growth factor I (IGF-I) should be measured several weeks after beginning GH treatment or making a dose adjustment. GH side effects include headaches, Idiopathic intracranial hypertension, Slipped capital femoral epiphysis, worsening of existing scoliosis, Pancreatitis, and Gynecomastia.
Historical Perspective
In the mid-1940s, Li and Evans were the first to clean cow-like GH. By 1985, GH extricated from human pituitary organs were utilized to treat development hormone insufficiency. In 1981, Genentech built up the main recombinant human GH. In 1981, Genentech built up the main recombinant human GH for the treatment of serious GHD.
Classification
Growth hormone deficiency can be classified by cause into congenital type in which infants show symptoms such as hypoglycemia, neonatal growth failure, neonatal jaundice, and asphyxia or acquired type presents with severe growth failure, delayed bone age, delayed puberty, or Idiopathic growth hormone deficiency which defined as having a height significantly shorter than the normal population with no detectable cause for short stature.
Pathophysiology
The somatotroph cells of the anterior pituitary organ create development hormone (GH). GH best-known impact is expanding weight. GH causes epiphyseal plate broadening and ligament development. GH inadequacy brings about changes in the physiology of various frameworks of the body, showing as modified lipid digestion, expanded subcutaneous instinctive fat, diminished bulk. The hereditary premise of inborn development hormone insufficiency relies upon numerous qualities, for instance, POU1F1 quality transformations are the most widely recognized known hereditary reason for the joined pituitary hormone lack. Quality erasures, frameshift transformations, and jabber changes of GH1 quality have been portrayed as reasons for familial GHD.
Causes
Causes for development hormone insufficiency could be congenital or acquired. Congenital causes incorporate hereditary transformations in POU1F1, PROP-1, and GH-1 qualities. Basic causes include development hormone inadequacy, for example, optic nerve hypoplasia, agenesis of corpus callosum, septo-optic dysplasia, empty sella disorder, and holoprosencephaly. Procured causes include the development of hormone inadequacy, for example, GHD following brain surgery and radiation treatment for brain tumors, central nervous system disease, craniopharyngioma, and pituitary adenoma.
Differentiating growth hormone deficiency from Other Diseases
Growth hormone deficiency in children must be differentiated from other diseases that cause short stature in children such as: Achondroplasia, constitutional growth delay, familial short stature, growth hormone resistance, Noonan Syndrome, Panhypopituitarism, pediatric hypothyroidism, Short stature accompanying systemic disease, psychosocial Short Stature, Silver-Russell Syndrome, Turner Syndrome, and idiopathic short stature.
Epidemiology and Demographics
Prevalence and incidence data of growth hormone deficiency vary widely due to the lack of standard diagnostic criteria. Diagnosis of growth hormone deficiency is made during 2 broad age peaks; the first age peak occurs at 5 years, a time when children begin school. The second age peak occurs in girls aged 10-13 years and boys aged 12-16 years. There is no apparent racial difference in the incidence of GHD. Seventy-three percent of patients with idiopathic GHD in were males due to societies that concern more about males short stature than the females. Patients with GHD from organic causes such as tumors and radiation, in which no gender bias should be present, were still 62% male.
Risk Factors
There are no established risk factors for growth hormone deficiency.
Screening
Genetic screening of growth hormone deficiency(GHD) is indicated for patients with early and severe symptoms. GHD patients have been screened for mutations in the GH1 and GHRH gene. Understanding of genetic contributions to GHD opens the possibility for a more reasonable approach to the diagnosis and management of GHD.
Natural History, Complications, and Prognosis
If left untreated, patients with growth hormone deficiency may progress to develop delayed postnatal growth, delayed bone age, delayed puberty, infantile fat distribution, and infantile voice. Common complications of growth hormone deficiency include osteopenia, dyslipidemia, delayed puberty, and higher mortality rates than normal subjects. Prognosis is generally good with treatment. GH treatment can improve GH-deficient adults symptoms. Since recombinant DNA–derived growth hormone became available, most children with growth hormone deficiency reach normal adult stature.
Diagnosis
Diagnostic criteria
History and Symptoms
The hallmark of growth hormone deficiency is growth failure. The most common symptoms of GHD in infants are delayed Bone age, perinatal asphyxia, hypoglycemia, and jaundice. Adults symptoms include increased lean body mass, fractures of the lumbar spine, and osteopenia.
Physical Examination
Patients with growth hormone deficiency usually look tired and less energetic than normal subjects. Extremities show Clubbing, muscle atrophy, neonatal jaundice, neonatal cyanosis. Head may show infantile facies, delayed dentition, and brittle hair. Children may show hyporeflexia and delayed puberty.
Laboratory Findings
An immediate investigation should be started in severe short stature defined as a short child more than 3 standard deviations below the mean of children at the same age. Measurement of a random serum GH level alone is not helpful. Measurement of Insulin-like growth factor I (IGF-I) and Insulin-like growth factor binding protein-3 (IGFBP-3) is more helpful than GH level alone. GH stimulation tests are indicated for most patients suspected to have GHD. If the clinical and other laboratory criteria are sufficient to make the diagnosis of GHD, there is no need to perform the test. Pharmacologic stimuli include clonidine, glucagon, arginine, and insulin-induced hypoglycemia. Administration of sex steroids for a few days prior to the provocative GH testing reduces the chance of a false-positive result.
X-ray
An x-ray may be helpful in the diagnosis of delayed bone age associated with growth hormone deficiency.
CT scan
Pituitary CT scan may be helpful in the diagnosis of growth hormone deficiency if an MRI is not available. Brain CT of pituitary apoplexy is insensitive to the diagnosis of apoplexy unless intracranial hemorrhage is present. Brain CT of adrenal adenoma shows typically has attenuation similar to the brain and calcification is rarely found.
MRI
Brain MRI may be helpful in the diagnosis of growth hormone deficiency. On T1-weighted imaging, a clear demarcation can be made between the adenohypophysis and the neurohypophysis, which appears as hyperintense. Other pituitary abnormalities such as anterior pituitary hypoplasia, pituitary stalk agenesis, and posterior pituitary ectopia can be diagnosed using MRI.
Ultrasound
There are no ultrasound findings associated with growth hormone deficiency.
Other Imaging Findings
There are no other imaging findings associated with growth hormone deficiency.
Other Diagnostic Studies
There are no other diagnostic studies associated with growth hormone deficiency.
Treatment
Medical Therapy
Growth hormone (GH) is indicated for children with GH deficiency whose epiphyses are open. The dose for children is between 0.16 and 0.24 mg/kg/week, divided into once daily injections. Serum levels of insulin-like growth factor I (IGF-I) should be measured several weeks after beginning GH treatment or making a dose adjustment. GH side effects include headaches, Idiopathic intracranial hypertension, Slipped capital femoral epiphysis, worsening of existing scoliosis, Pancreatitis, and Gynecomastia. There is a possible role for GH in cancer risk.
Surgery
Surgical intervention is not recommended for the management of growth hormone deficiency.
Primary Prevention
There are no established measures for the primary prevention of growth hormone deficiency.
Secondary Prevention
Patients who are receiving growth hormone therapy should be followed up 2-4 times per year. Growth rate usually increases during the first year of treatment, with an average increase of 8-10 cm/y. A slow growth rate more than expected should be investigated to exclude other causes such as hypothyroidism or inflammatory bowel disease.