Growth hormone deficiency overview

# 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 of growth hormone deficiency include 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 growth hormone deficiency(GHD). 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 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 purify bovine GH. In 1981, Genentech developed the first recombinant human GH. In 1981, Genentech developed the first recombinant human GH for the therapy of severe childhood GHD. By 1985, GH extracted from human pituitary glands were used to treat growth hormone deficiency.

# 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). The most widely studied impact of growth hormone is increasing 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 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 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, and pituitary adenoma.

# Differentiating Growth Hormone deficiency from Other Diseases
Growth hormone deficiency in children must be differentiated from different infections that cause short stature in kids, for example, 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. 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. In seventy-three percent of patients with idiopathic GHD, 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, there was still 62% male.

# Risk Factors
There are no established risk factors for growth hormone deficiency.

# Screening
Genetic screening of increase hormone deficiency(GHD) is indicated for patients with early and severe signs. GHD patients have been screened for mutations within the GH1 and GHRH gene. understanding of genetic contributions to GHD opens the opportunity for a greater affordable technique to the diagnosis and management of GHD.

# Natural History, Complications, and Prognosis
If left untreated, patients with growth hormone deficiency can also development to develop delayed postnatal growth, delayed bone age, delayed puberty, infantile fat distribution, and infantile voice. common complications of growth hormone deficiency encompass osteopenia, dyslipidemia, delayed puberty, and higher mortality rates than regular subjects. prognosis is usually desirable with treatment. GH treatment can improve GH-deficient adults signs and symptoms. since recombinant DNAderived growth hormone have become to be had, most children with growth hormone deficiency attain 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.