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{{Growth hormone deficiency}}
{{Growth hormone deficiency}}


{{CMG}}; {{AE}}
{{CMG}}; {{AE}} {{MAD}}
==Overview==
==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.
Isolated GH deficiency is the most common hormone deficiency of pituitary gland. There are three types of GH deficiency: [[congenital]], [[Acquired disorder|acquired]], and [[idiopathic]]. Congenital causes include [[genetic mutations]] in POU1F1, [[PROP1|PROP-1]], and GH-1 genes. Structural causes of GH deficiency includes [[optic nerve hypoplasia]], [[Agenesis of the corpus callosum|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|somatotroph cells]] of the anterior pituitary gland produce growth hormone. During the development of the [[Anterior pituitary gland|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 molecule|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 [[Laron syndrome|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 rate|mortality rates]] than normal subjects. [[Prognosis]] is generally good with treatment. Measurement of a random serum [[Growth hormone|GH]] level alone is not helpful. Measurement of [[Insulin-like growth factor 1|Insulin-like growth factor I]] (IGF-I) and [[Insulin-like growth factor binding protein 3|Insulin-like growth factor binding protein-3]] ([[IGFBP3|IGFBP-3]]) is more helpful than GH level alone. GH stimulation tests are indicated for most patients suspected to have GHD. [[Growth hormone|Growth hormone (GH)]] is indicated for children with [[Growth hormone|GH]] deficiency whose [[Epiphysis|epiphyses]] are open. Serum levels of [[Insulin-like growth factor 1|insulin-like growth factor I]] ([[IGF-I]]) should be measured several weeks after beginning [[Growth hormone|GH]] treatment or making a dose adjustment. [[Growth hormone|GH]] side effects include [[Headache|headaches]], [[Idiopathic intracranial hypertension]], [[Slipped capital femoral epiphysis]], worsening of existing [[scoliosis]], [[Pancreatitis]], and [[Gynecomastia]].


==Historical Perspective==
==Historical Perspective==
In the mid 1940s, Li and Evans were the first to purify [[Growth hormone|bovine GH.]] In 1981, Genentech developed the first [[Recombinant DNA|recombinant]] human [[Growth hormone|GH]]. In 1981, Genentech developed the first [[Recombinant DNA|recombinant]] human GH for the therapy of severe childhood GHD. By 1985, GH extracted from human [[Pituitary gland|pituitary glands]] were used to treat growth hormone deficiency.


==Classification==
==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==
==Pathophysiology==
The [[Somatotrophs|somatotroph cells]] of the [[Anterior pituitary gland|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==
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 the corpus callosum|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 ((Page name)) from Other Diseases==
==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]], [[Short stature|familial short stature]], growth hormone resistance, [[Noonan syndrome]], [[panhypopituitarism]], [[Hypothyroidism|pediatric hypothyroidism]], Short stature accompanying systemic disease, psychosocial Short Stature, [[Silver-Russell Syndrome]], [[Turner syndrome]], and [[idiopathic short stature]].


==Epidemiology and Demographics==
==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 [[Tumor|tumors]] and [[Radiation therapy|radiation,]] in which no gender bias should be present, there was still 62% male.


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


==Screening==
==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==
==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 DNA–derived growth hormone have become to be had, most children with growth hormone deficiency attain normal adult stature.
==Diagnosis==


==Diagnosis==
=== Diagnostic criteria ===
===Diagnostic Criteria===


===History and Symptoms===
===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 [[Body mass|lean body mass]], [[fractures]] of the [[lumbar spine]], and [[osteopenia]].


===Physical Examination===
===Physical Examination===
Patients with growth hormone deficiency usually look tired and less energetic than normal subjects. Extremities show [[Clubbing]], [[muscle atrophy]], [[neonatal jaundice]], [[Cyanosis|neonatal cyanosis]]. Head may show infantile facies, [[Dentition|delayed dentition]], and brittle hair. Children may show [[hyporeflexia]] and [[delayed puberty]].


===Laboratory Findings===
===Laboratory Findings===
 
An immediate investigation should be started in severe [[short stature]] defined as a short child more than 3 [[standard deviation]]<nowiki/>s below the mean of children at the same age. Measurement of a random serum [[Growth hormone|GH]] level alone is not helpful. Measurement of [[Insulin-like growth factor 1|Insulin-like growth factor I]] (IGF-I) and [[Insulin-like growth factor binding protein 3|Insulin-like growth factor binding protein-3]] ([[IGFBP3|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 [[Growth hormone|GH]] testing reduces the chance of a [[false-positive]] result.
===Electrocardiogram===


===X-ray===
===X-ray===
An x-ray may be helpful in the diagnosis of delayed [[bone age]] associated with growth hormone deficiency.


===CT scan===
===CT scan===
[[Pituitary gland|Pituitary]] [[Computed tomography|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 (electromagnetic radiation)|attenuation]] similar to the [[brain]] and [[calcification]] is rarely found.


===MRI===
===MRI===
[[Brain]] [[Magnetic resonance imaging|MRI]] may be helpful in the diagnosis of growth hormone deficiency. On [[T1|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|anterior pituitary hypoplasia]], [[Pituitary stalk|pituitary stalk agenesis]], and [[Posterior pituitary|posterior pituitary ectopia]] can be diagnosed using [[Magnetic resonance imaging|MRI]].


===Ultrasound===
===Ultrasound===
There are no ultrasound findings associated with growth hormone deficiency.


===Other Imaging Findings===
===Other Imaging Findings===
There are no other imaging findings associated with growth hormone deficiency.


===Other Diagnostic Studies===
===Other Diagnostic Studies===
There are no other diagnostic studies associated with growth hormone deficiency.


==Treatment==
==Treatment==
===Medical Therapy===
===Medical Therapy===
[[Growth hormone|Growth hormone (GH)]] is indicated for children with [[Growth hormone|GH]] deficiency whose [[Epiphysis|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 1|insulin-like growth factor I]] (IGF-I) should be measured several weeks after beginning [[Growth hormone|GH]] treatment or making a dose adjustment. GH side effects include [[Headache|headaches]], [[Idiopathic intracranial hypertension]], [[Slipped capital femoral epiphysis]], worsening of existing [[scoliosis]], [[Pancreatitis]], and [[Gynecomastia]]. There is a possible role for [[Growth hormone|GH]] in cancer risk.


===Surgery===
===Surgery===
Surgical intervention is not recommended for the management of growth hormone deficiency.


===Primary Prevention===
===Primary Prevention===
There are no established measures for the primary prevention of growth hormone deficiency.


===Secondary Prevention===
===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|growth rate]] more than expected should be investigated to exclude other causes such as [[hypothyroidism]] or [[inflammatory bowel disease]].


==References==
==References==

Latest revision as of 14:02, 30 October 2017

Growth hormone deficiency Microchapters

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Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Growth hormone deficiency from other Diseases

Epidemiology and Demographics

Risk Factors

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Natural History, Complications and Prognosis

Diagnosis

Diagnostic Criteria

History and Symptoms

Physical Examination

Laboratory Findings

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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

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 hypoplasiaagenesis of corpus callosumsepto-optic dysplasiaempty sella syndrome, and holoprosencephaly. Acquired causes of growth hormone deficiency include brain surgeryradiation therapy for brain tumorscentral nervous system infectioncraniopharyngioma, 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 osteopeniadyslipidemiadelayed 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 headachesIdiopathic intracranial hypertensionSlipped capital femoral epiphysis, worsening of existing scoliosisPancreatitis, 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 failureneonatal 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 DNA–derived 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 asphyxiahypoglycemia, and jaundice. Adults symptoms include increased lean body massfractures of the lumbar spine, and osteopenia.

Physical Examination

Patients with growth hormone deficiency usually look tired and less energetic than normal subjects. Extremities show Clubbingmuscle atrophyneonatal jaundiceneonatal 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 clonidineglucagonarginine, 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 hypoplasiapituitary 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 headachesIdiopathic intracranial hypertensionSlipped capital femoral epiphysis, worsening of existing scoliosisPancreatitis, 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.

References


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