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Growth hormone deficiency
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Growth hormone deficiency
Synonyms
Pituitary dwarfism
Growth hormone
Specialty
Endocrinology
Symptoms
Short height[1]
Complications
Low blood sugar, high cholesterol levels, poor bone density[1][2]
Types
Congenital, acquired[1]
Causes
Not enough growth hormone[3]
Risk factors
Genetics, trauma, infections, tumors, radiation therapy[2]
Diagnostic method
Blood tests for growth hormone[2]
Differential diagnosis
Small for gestational age, Turner syndrome, Noonan syndrome, Prader-Willi syndrome[2]
Treatment
Growth hormone replacement[1]
Frequency
Unclear[2]
Growth hormone deficiency (GHD) is a medical condition due to not enough growth hormone (GH).[3] Generally the most noticeable symptom is a short height.[1] In newborns there may be low blood sugar or a small penis.[2] In adults there may be decreased muscle mass, high cholesterol levels, or poor bone density.[1]
GHD can be present at birth or develop later in life.[1] Causes may include genetics, trauma, infections, tumors, or radiation therapy.[2] Genes that may be involved include GH1, GHRHR, or BTK.[3] In a third of cases no cause is apparent.[2] The underlying mechanism generally involves problems with the pituitary gland.[2] Some cases are associated with a lack of other pituitary hormones, in which case it is known as combined pituitary hormone deficiency.[4] Diagnosis involves blood tests to measure growth hormone levels.[2]
Treatment is by growth hormone replacement.[1] The frequency of the condition is unclear.[2] Most cases are initially noticed in children.[1] The genetic forms are estimates to affect about 1 in 7,000 people.[3] Most types occur equally in males and females though males are more often diagnosed.[2]
Contents
[hide]
1 Signs and symptoms
1.1 Child
1.2 Adults
2 Causes
3 Pathophysiology
4 Diagnosis
4.1 Classification
5 Treatment
5.1 Child
5.2 Adults
5.3 Side effects
6 Prognosis
6.1 Child
6.2 Adults
7 Epidemiology
8 History
9 See also
10 References
11 External links
Signs and symptoms[edit]
Child[edit]
Severe prenatal deficiency of GH, as occurs in congenital hypopituitarism, has little effect on fetal growth. However, prenatal and congenital deficiency can reduce the size of a male's penis, especially when gonadotropins are also deficient. Besides micropenis in males, additional consequences of severe deficiency in the first days of life can include hypoglycemia and exaggerated jaundice (both direct and indirect hyperbilirubinemia).
Even congenital GH deficiency does not usually impair length growth until after the first few months of life. From late in the first year until mid teens, poor growth and/or shortness is the hallmark of childhood GH deficiency. Growth is not as severely affected in GH deficiency as in untreated hypothyroidism, but growth at about half the usual velocity for age is typical. It tends to be accompanied by delayed physical maturation so that bone maturation and puberty may be several years delayed. When severe GH deficiency is present from birth and never treated, adult heights can be as short as 48-65 inches (122–165 cm).
Severe GH deficiency in early childhood also results in slower muscular development, so that gross motor milestones such as standing, walking, and jumping may be delayed. Body composition (i.e., the relative amounts of bone, muscle, and fat) is affected in many children with severe deficiency, so that mild to moderate chubbiness is common (though GH deficiency alone rarely causes severe obesity). Some severely GH-deficient children have recognizable, cherubic facial features characterized by maxillary hypoplasia and forehead prominence (said to resemble a kewpie doll).
Other side effects in children include sparse hair growth and frontal recession, and pili torti and trichorrhexis nodosa are also sometimes present.[5]:501
Adults[edit]
Recognised effects include:[6][better source needed]
Increased 5-alpha-reductase
Reduced sex hormone-binding globulin (SHBG)
Reduced muscle mass and strength
Baldness in men
Reduced bone mass and osteoporosis
Reduced energy
Impaired concentration and memory loss
Increased body fat, particularly around the waistline
Lipid abnormalities, particularly raised LDL cholesterol
Increased levels of fibrinogen and plasminogen activator inhibitor
Cardiac dysfunction, including a thickened intima media
Causes[edit]
Growth hormone deficiency in childhood commonly has no identifiable cause (idiopathic), and adult-onset GHD is commonly due to pituitary tumours and their treatment or to cranial irradiation.[7] A more complete list of causes includes:
mutations of specific genes (e.g., GHRHR, GH1)
congenital diseases such as Prader-Willi syndrome, Turner syndrome,[8] or short stature homeobox gene (SHOX) deficiency[9]
congenital malformations involving the pituitary (e.g., septo-optic dysplasia, posterior pituitary ectopia)
chronic renal insufficiency[10]
intracranial tumors in or near the sella turcica, especially craniopharyngioma
damage to the pituitary from radiation therapy to the head (e.g. for leukemia or brain tumors), from surgery, from trauma, or from intracranial disease (e.g. hydrocephalus)
autoimmune inflammation (hypophysitis)
ischemic or hemorrhagic infarction from low blood pressure (Sheehan syndrome) or hemorrhage pituitary apoplexy
There are a variety of rare diseases which resemble GH deficiency, including the childhood growth failure, facial appearance, delayed bone age, and low IGF levels. However, GH testing elicits normal or high levels of GH in the blood, demonstrating that the problem is not due to a deficiency of GH but rather to a reduced sensitivity to its action. Insensitivity to GH is traditionally termed Laron dwarfism, but over the last 15 years many different types of GH resistance have been identified, primarily involving mutations of the GH binding protein or receptors.
Pathophysiology[edit]
As an adult ages, it is normal for the pituitary to produce diminishing amounts of GH and many other hormones, particularly the sex steroids. Physicians therefore distinguish between the natural reduction in GH levels which comes with age, and the much lower levels of "true" deficiency. Such deficiency almost always has an identifiable cause, with adult-onset GHD without a definable cause ("idiopathic GH deficiency") extremely rare.[11] GH does function in adulthood to maintain muscle and bone mass and strength, and has poorly understood effects on cognition and mood.
Diagnosis[edit]
Although GH can be readily measured in a blood sample, testing for GH deficiency is constrained by the fact that levels are nearly undetectable for most of the day. This makes simple measurement of GH in a single blood sample useless for detecting deficiency. Physicians therefore use a combination of indirect and direct criteria in assessing GHD, including:
Auxologic criteria (defined by body measurements)
Indirect hormonal criteria (IGF levels from a single blood sample)
Direct hormonal criteria (measurement of GH in multiple blood samples to determine secretory patterns or responses to provocative testing), in particular:
Subnormal frequency and amplitude of GH secretory peaks when sampled over several hours
Subnormal GH secretion in response to at least two provocative stimuli
Increased IGF1 levels after a few days of GH treatment
Response to GH treatment
Corroborative evidence of pituitary dysfunction
"Provocative tests" involve giving a dose of an agent that will normally provoke a pituitary to release a burst of growth hormone. An intravenous line is established, the agent is given, and small amounts of blood are drawn at 15 minute intervals over the next hour to determine if a rise of GH was provoked. Agents which have been used clinically to stimulate and assess GH secretion are arginine,[12] levodopa, clonidine, epinephrine and propranolol, glucagon and insulin. An insulin tolerance test has been shown to be reproducible, age-independent, and able to distinguish between GHD and normal adults,[12] and so is the test of choice.
Severe GH deficiency in childhood additionally has the following measurable characteristics:
Proportional stature well below that expected for family heights, although this characteristic may not be present in the case of familial-linked GH deficiency
Below-normal velocity of growth
Delayed physical maturation
Delayed bone age
Low levels of IGF1, IGF2, IGF binding protein 3
Increased growth velocity after a few months of GH treatment
In childhood and adulthood, the diagnosing doctor will look for these features accompanied by corroboratory evidence of hypopituitarism such as deficiency of other pituitary hormones, a structurally abnormal pituitary, or a history of damage to the pituitary. This would confirm the diagnosis; in the absence of pituitary pathology, further testing would be required.
Classification[edit]
Growth hormone deficiency can be congenital or acquired in childhood or adult life. It can be partial or complete. It is usually permanent, but sometimes transient. It may be an isolated deficiency or occur in association with deficiencies of other pituitary hormones.
The term hypopituitarism is often used interchangeably with GH deficiency but more often denotes GH deficiency plus deficiency of at least one other anterior pituitary hormone. When GH deficiency (usually with other anterior pituitary deficiencies) is associated with posterior pituitary hormone deficiency (usually diabetes insipidus), the condition is termed panhypopituitarism.
Treatment[edit]
Main article: Growth hormone treatment
GH deficiency is treated by replacing GH with daily injections under the skin or into muscle. Until 1985, growth hormone for treatment was obtained by extraction from human pituitary glands collected at autopsy. Since 1985, recombinant human growth hormone (rHGH) is a recombinant form of human GH produced by genetically engineered bacteria, manufactured by recombinant DNA technology. In both children and adults, costs of treatment in terms of money, effort, and the impact on day-to-day life, are substantial.
Child[edit]
GH treatment is not recommended for children who are not growing despite having normal levels of growth hormone, and in the UK it is not licensed for this use.[13] Children requiring treatment usually receive daily injections of growth hormone. Most pediatric endocrinologists monitor growth and adjust dose every 3–6 months and many of these visits involve blood tests and x-rays. Treatment is usually extended as long as the child is growing, and lifelong continuation may be recommended for those most severely deficient. Nearly painless insulin syringes, pen injectors, or a needle-free delivery system reduce the discomfort. Injection sites include the biceps, thigh, buttocks, and stomach. Injection sites should be rotated daily to avoid lipoatrophy. Treatment is expensive, costing as much as US $10,000 to $40,000 a year in the USA.
Adults[edit]
GH supplementation is not recommended medically for the physiologic age-related decline in GH/IGF secretion.[7][11] It may be appropriate in diagnosed adult-onset deficiency, where a weekly dose approximately 25% of that given to children is given. Lower doses again are called for in the elderly to reduce the incidence of side effects and maintain age-dependent normal levels of IGF-1.[14]
In many countries, including the UK, the majority view among endocrinologists is that the failure of treatment to provide any demonstrable, measurable benefits in terms of outcomes means treatment is not recommended for all adults with severe GHD,[15] and national guidelines in the UK as set out by NICE suggest three criteria which all need to be met for treatment to be indicated:
Severe GH deficiency, defined as a peak GH response of <9mU/litre during an insulin tolerance test
Perceived impairment of quality of life, as assessed by questionnaire
They are already treated for other pituitary hormone disorders
Where treatment is indicated, duration is dependent upon indication.
Cost of adult treatment in the UK is 3000-4000 GBP annually.[15]
Side effects[edit]
Headaches
Joint pain and muscle pain
Fluid retention, and carpal tunnel syndrome
Mild hypertension
Visual problems
Nausea and vomiting
Paraesthesiae
Antibody formation
Reactions at the injection site
Rarely, benign intracranial hypertension.[7]
Prognosis[edit]
Child[edit]
When treated with GH, a severely deficient child will begin to grow faster within months. In the first year of treatment, the rate of growth may increase from half as fast as other children are growing to twice as fast (e.g., from 1 inch a year to 4 inches, or 2.5 cm to 10). Growth typically slows in subsequent years, but usually remains above normal so that over several years a child who had fallen far behind in his height may grow into the normal height range. Excess adipose tissue may be reduced.
Adults[edit]
GH treatment can confer a number of measurable benefits to severely GH-deficient adults, such as enhanced energy and strength, and improved bone density. Muscle mass may increase at the expense of adipose tissue. Although adults with hypopituitarism have been shown to have a reduced life expectancy, and a cardiovascular mortality rate more than double controls,[15] treatment has not been shown to improve mortality, although blood lipid levels do improve. Similarly, although measurements of bone density improve with treatment, rates of fractures have not been shown to improve.[15]
Effects on quality of life are unproven, with a number of studies finding that adults with GHD had near-normal indicators of QoL at baseline (giving little scope for improvement), and many using outdated dosing strategies. However, it may be that those adults with poor QoL at the start of treatment do benefit.[7]
Epidemiology[edit]
The incidence of idiopathic GHD in infants is about 1 in every 3800 live births,[16] and rates in older children are rising as more children survive childhood cancers which are treated with radiotherapy, although exact rates are hard to obtain.[8]
The incidence of genuine adult-onset GHD, normally due to pituitary tumours, is estimated at 10 per million.[15]
History[edit]
Like many other 19th century medical terms which lost precise meaning as they gained wider currency, "midget" as a term for someone with severe proportional shortness acquired pejorative connotations and is no longer used in a medical context.
Notable modern pop cultural figures with growth hormone deficiency include actor and comedian Andy Milonakis, who has the appearance and voice of an adolescent boy despite being in his early 40s.[17][18]
See also[edit]
Hypothalamic–pituitary–somatic axis
References[edit]
^ Jump up to: a b c d e f g h i "Growth hormone deficiency". Genetic and Rare Diseases Information Center (GARD) – an NCATS Program. 2016. Retrieved 12 December 2017.
^ Jump up to: a b c d e f g h i j k l "Growth Hormone Deficiency". NORD (National Organization for Rare Disorders). 2016. Retrieved 12 December 2017.
^ Jump up to: a b c d "isolated growth hormone deficiency". Genetics Home Reference. February 2012. Retrieved 12 December 2017.
Jump up ^ "Combined pituitary hormone deficiency". Genetics Home Reference. August 2010. Retrieved 13 December 2017.
Jump up ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0.
Jump up ^ "Human Growth Hormone Deficiency". HGH. Retrieved 20 January 2012.
^ Jump up to: a b c d "Human growth hormone (somatropin) in adults with growth hormone deficiency" (PDF). National Institute for Clinical Excellence. 2006-07-01. Retrieved 2009-01-16.
^ Jump up to: a b "Growth failure (in children) - human growth hormone (HGH)" (PDF). National Institute for Clinical Excellence. 2008-09-25. Archived from the original (pdf) on 2011-10-26. Retrieved 2009-01-16.
Jump up ^ Rappold GA, Fukami M, Niesler B, et al. (March 2002). "Deletions of the homeobox gene SHOX (short stature homeobox) are an important cause of growth failure in children with short stature". J. Clin. Endocrinol. Metab. 87 (3): 1402–6. doi:10.1210/jc.87.3.1402. PMID 11889216.
Jump up ^ Saborio P, Hahn S, Hisano S, Latta K, Scheinman JI, Chan JC (October 1998). "Chronic renal failure: an overview from a pediatric perspective". Nephron. 80 (2): 134–48. doi:10.1159/000045157. PMID 9736810.
^ Jump up to: a b Molitch ME, Clemmons DR, Malozowski S, et al. (May 2006). "Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society Clinical Practice Guideline". J. Clin. Endocrinol. Metab. 91 (5): 1621–34. doi:10.1210/jc.2005-2227. PMID 16636129.
^ Jump up to: a b Aimaretti G, Corneli G, Razzore P, et al. (May 1998). "Comparison between insulin-induced hypoglycemia and growth hormone (GH)-releasing hormone + arginine as provocative tests for the diagnosis of GH deficiency in adults". J. Clin. Endocrinol. Metab. 83 (5): 1615–8. doi:10.1210/jc.83.5.1615. PMID 9589665. Retrieved 2008-07-23.
Jump up ^ "Guidance on the use of human growth hormone (somatropin) in children with growth failure" (pdf). National Institute for Clinical Excellence. 2002-05-01. Retrieved 2009-01-16.
Jump up ^ "Consensus Guidelines for Adult Growth Hormone Deficiency 2007".
^ Jump up to: a b c d e "The Use of Growth Hormone Replacement in Adult Patients with Severe Growth Hormone Deficiency" (pdf). The Society for Endocrinology. 2000-10-01. Retrieved 2009-01-18.
Jump up ^ "Growth Hormone Deficiency". UK Child Growth Foundation. Retrieved 2009-01-16.
Jump up ^ TV.com (1976-01-30). "Andy Milonakis". TV.com. Retrieved 2017-03-28.
Jump up ^ Maureen Ryan (2005-07-31). "Andy Milonakis, 12 going on ageless". Articles.chicagotribune.com. Retrieved 2017-03-28.
External links[edit]
Classification
D
ICD-10: E23.0
ICD-9-CM: 253.3
OMIM: 262400
MeSH: D004393
DiseasesDB: 5447
External resources
MedlinePlus: 001176
eMedicine: med/930

Growth Hormone Deficiency In Adults The Pituitary Foundation supporting pituitary patients, their families, friends and carers
Am Assoc Clinical Endocrinologists - practice guidelines and recommendations for diagnosis and treatment of GH deficiency, reflecting standard practice among U.S. endocrinologists
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Diseases of the endocrine system (E00–E35, 240–259)
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Pod Save America
From Wikipedia, the free encyclopedia
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Pod Save America
"A no-bullshit conversation about politics."
Presentation
Hosted by
Jon Favreau, Dan Pfeiffer, Jon Lovett, Tommy Vietor
Genre
Political commentary, interview
Format
Twice weekly (Tuesday and Friday)
Language
English
Length
41–82 minutes
Production
Preceded by
Keepin' it 1600
Publication
Original release
January 2017 – present
Provider
Crooked Media
Related shows
Pod Save the People, Lovett or Leave It, With Friends Like These, Pod Save the World, Crooked Conversations, Majority 54, Keep It, Hysteria, The Wilderness
Website
Pod Save America
Pod Save America is an American progressive political podcast produced and distributed by Crooked Media. The podcast debuted in January 2017 and airs twice weekly, with the Tuesday edition hosted by former Barack Obama staffers Jon Favreau, Tommy Vietor and Jon Lovett, and the Thursday edition by Favreau and Dan Pfeiffer.[1][2][3][4]
It is the flagship podcast of Crooked Media, the progressive media company founded by Favreau, Vietor and Lovett.[5] The show averages more than 1.5 million listeners an episode, and had been downloaded more than 120 million times by November 2017.[6]
Four Pod Save America one-hour HBO TV specials are planned to air in fall 2018 to cover the upcoming U.S. midterm elections.[7][8]
Contents
1 History
2 Tour
3 Content
4 Reception
5 References
6 External links
History[edit]
The podcast debuted in January 2017 as a successor to Keepin' it 1600, a political podcast produced by Bill Simmons' The Ringer and hosted by Favreau, Vietor, Lovett and Pfeiffer which ran from March to December 2016. Pod Save America maintained the basic format of its predecessor.[9]
In an interview with Recode's Kara Swisher, the hosts have stated that, rather than continue the previous podcast, the election of Donald Trump as President of the United States spurred them to create a new, progressive media company with a network of podcasts. Their goal is to inform, entertain, and inspire action or activism.[10]
Tour[edit]
Crooked Media took the podcast on its first live tour, Pod Tours America, in the fall of 2017. Live shows were recorded and released as podcasts.[11] An international tour, Pod Tours the World, was announced for 2018, with live shows in Stockholm, Oslo, Amsterdam and London.[12]
Content[edit]
The podcast typically covers recent news items relating to politics, including the Trump administration, the US government and the Democratic Party, as well as leftwing grassroots activism.[13]
The show typically features interviews with politicians, activists and journalists, including Obama's last interview as president.[14] Other guests have included Hillary Clinton[15] and senators Elizabeth Warren, Cory Booker, Kamala Harris and Chris Murphy. Guests are often referred to as "friends of the pod".[16]
Favreau, Vietor, and guest Seth Meyers at a live taping at Radio City Music Hall
Reception[edit]
The show averages more than 1.5 million listeners an episode, and had been downloaded more than 120 million times by November 2017.[6]
The New York Times described the podcast as "one of the big breakout hits of the nascent resistance movement",[2] and "the left’s answer to conservative talk radio... with a shoestring budget and no organizational backing, its hosts seem to have created something that liberals have spent almost two decades, and hundreds of millions of dollars, futilely searching for".[6]
The San Francisco Chronicle called it "one of the nation’s most popular podcasts".[17] GQ called it one of the "most popular strategies for coping with the looming death of the republic".[18]
Newsweek wrote that the show's hosts "do something far more rare [than political analysis], which is to make politics entertaining and even fun, without ever downplaying what they see as the threat posed to American democracy by the man elected to defend it."[19]
References[edit]
Jump up ^ Gillies, Craille Maguire (January 18, 2017). "Pod save America: 12 podcasts to get you through the Trump presidency". The Guardian.
^ Jump up to: a b Rutenberg, Jim (March 20, 2017). "Opposition and a Shave: Former Obama Aides Counter Trump". The New York Times. ISSN 0362-4331. Retrieved March 22, 2017.
Jump up ^ Willis, Jay (April 6, 2017). "The Pod Save America Guys Have Some Ideas About What President Obama Should Do Next". GQ. Retrieved June 11, 2017.
Jump up ^ "CROOKED MEDIA FIGHTS TRUMP WITH "POD SAVE AMERICA"". Newsweek. March 26, 2017. Retrieved June 11, 2017.
Jump up ^ Wilstein, Matt (January 9, 2017). "The 'Keepin' It 1600' Guys Launch Crooked Media to Counter Trump". The Daily Beast. Retrieved January 3, 2018.
^ Jump up to: a b c Zengerle, Jason. "The Voices in Blue America's Head". Retrieved November 22, 2017.
Jump up ^ "- HBO Announces Pod Save America Podcast Specials". HBO.
Jump up ^ "'Pod Save America' Getting HBO Treatment With Election Specials". hollywoodreporter.com.
Jump up ^ "'Keeping It 1600' Podcast's Obama Alums Launch New Show and 'Crooked Media' Company". The Hollywood Reporter. Retrieved January 3, 2018.
Jump up ^ "Live @ SXSW: Crooked Media and Kara Swisher". Crooked Media. Retrieved March 23, 2017.
Jump up ^ "Pod Save America announces nationwide tour". Consequence of Sound. August 16, 2017. Retrieved January 3, 2018.
Jump up ^ "Pod Save America and Lovett or Leave It are coming to London in January, here's how to get tickets". The List. December 1, 2017. Retrieved January 3, 2018.
Jump up ^ Sawyer, Miranda (March 19, 2017). "The week in radio: Pod Save America; The Long View". The Observer. ISSN 0029-7712. Retrieved January 3, 2018.
Jump up ^ Verdier, Hannah (January 26, 2017). "Pod Save America – the podcast that won Obama's last interview". The Guardian. ISSN 0261-3077. Retrieved January 3, 2018.
Jump up ^ "Hillary Clinton says Donald Trump 'is a clear and present danger to America'". The Independent. September 12, 2017. Retrieved January 3, 2018.
Jump up ^ "Podcasts are becoming the left's right-wing talk radio". VICE News. Retrieved January 3, 2018.
Jump up ^ "'Pod Save America' about to take its next step". San Francisco Chronicle. Retrieved January 3, 2018.
Jump up ^ Willis, Jay (April 6, 2017). "The 'Pod Save America' Guys Gave Donald Trump His Best, Weirdest Nickname Yet". GQ. Retrieved January 3, 2018.
Jump up ^ "How the Crooked Media trio is taking on Donald Trump with "Pod Save America"". Newsweek. March 26, 2017. Retrieved January 3, 2018.
External links[edit]
Twitter page
Podcast website
Retrieved from "https://en.wikipedia.org/w/index.php?title=Pod_Save_America&oldid=861671229"
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2017 podcast debuts
Audio podcasts
English-language podcasts
Political podcasts
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