Growth hormone deficiency overview
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Differentiating Growth hormone deficiency from other Diseases |
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Diagnosis |
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mohammed Abdelwahed M.D[2]
Overview
Growth hormone deficiency (GHD) is a rare disorder characterized by the inadequate secretion of growth hormone (GH) from the anterior pituitary gland, a small gland located at the base of the brain that is responsible for the production of several hormones. GHD can be present from birth (congenital), resulting from genetic mutations or from structural defects in the brain. It can also be acquired later in life as a result of trauma, infection, radiation therapy, or tumor growth within the brain. A third category has no known or diagnosable cause (idiopathic). Childhood-onset GHD may be all three: congenital, acquired, or idiopathic. It results in growth retardation, short stature, and maturation delays reflected by the delay of lengthening of the bones of the extremities that is inappropriate to the chronological age of the child. Adult-onset GHD is most often is acquired from a pituitary tumor or trauma to the brain but may also be idiopathic. It is characterized by a number of variable symptoms including reduced energy levels, altered body composition, osteoporosis (reduced bone mineral density), reduced muscle strength, lipid abnormalities such as increased LDL cholesterol, insulin resistance, and impaired cardiac function. Treatment for GHD requires daily injections of recombinant human growth hormone. Patients with GHD that have no known cause are diagnosed as having idiopathic GHD. Genetic tests may reveal a congenital anomaly, but are often considered unnecessary after confirmation of GHD since they will have no effect on treatment. However, it is recommended that children be retested for GHD when they transition from pediatric to adult care since GH levels may normalize upon reaching adulthood. The level of GH considered normal for an adult is much lower than that for a child, especially one undergoing the pubertal growth spurt.
Historical Perspective
In the mid-1940s, bovine GH has been purified for the first time then, growth hormone was isolated from the human pituitary gland in 1956. 7700 children in the United States and 27,000 children worldwide were given GH extracted from human pituitary glands. In 1981, Genentech developed the first recombinant human GH.
Classification
Growth hormone deficiency can be classified by nature 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.
Pathophysiology
The somatotroph cells of the anterior pituitary gland produce growth hormone. GH best-known effect is increasing body mass. GH causes epiphyseal plate widening and cartilage growth. GH deficiency results in alterations in the physiology of different systems of the body, manifesting as altered lipid metabolism, increased subcutaneous visceral fat, decreased muscle mass. Genetic basis of congenital growth hormone deficiency depends on many genes, for example, POU1F1 gene mutations are the most common known genetic cause of combined pituitary hormone deficiency. Gene deletions, frameshift mutations, and nonsense mutations of GH1 gene have been described as causes of familial GHD.
Causes
Causes of growth hormone deficiency could be congenital or acquired. Congenital causes include genetic mutations in POU1F1, PROP-1, and GH-1 genes. Structural causes can cause growth hormone deficiency such as optic nerve hypoplasia, agenesis of corpus callosum, septo-optic dysplasia, empty sella syndrome, and holoprosencephaly. Acquired causes can cause growth hormone deficiency such as GHD following brain surgery and radiation therapy for brain tumors, central nervous system infection, craniopharyngioma, pituitary adenoma.
Differentiating ((Page name)) 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, psychosocial short stature, short stature accompanying systemic disease, short stature from abuse and neglect, Silver-Russell Syndrome, and Turner Syndrome.
Epidemiology and Demographics
Risk Factors
There are no established risk factors for growth hormone deficiency.
Screening
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
Electrocardiogram
X-ray
CT scan
Pituitary CT scan may be helpful in the diagnosis of growth hormone deficiency if an MRI is not available.
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.