Growth hormone deficiency pathophysiology: Difference between revisions

Jump to navigation Jump to search
No edit summary
No edit summary
Line 4: Line 4:


==Overview==
==Overview==
The [[Somatotroph|somatotroph cells]] of the anterior pituitary gland produce growth hormone (GH). 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 gland|pituitary]] hormone deficiency. Gene deletions, f[[Frameshift mutation|rameshift]] mutations, and [[nonsense mutations]] of ''GH1 gene'' have been described as causes of familial GHD.
The [[Somatotroph|somatotroph cells]] of the anterior pituitary gland produce growth hormone (GH). 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 the combined [[Pituitary gland|pituitary]] hormone deficiency. Gene deletions, f[[Frameshift mutation|rameshift]] mutations, and [[nonsense mutations]] of ''GH1 gene'' have been described as causes of familial GHD.


==Pathophysiology==
==Pathophysiology==
* The [[Somatotroph|somatotroph cells]] of the [[anterior pituitary]] gland produce growth hormone.<ref name="pmid8879986">{{cite journal| author=Cuttler L| title=The regulation of growth hormone secretion. | journal=Endocrinol Metab Clin North Am | year= 1996 | volume= 25 | issue= 3 | pages= 541-71 | pmid=8879986 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8879986  }}</ref>
* The [[Somatotroph|somatotroph cells]] of the [[anterior pituitary gland]] produce [[growth hormone]].<ref name="pmid8879986">{{cite journal| author=Cuttler L| title=The regulation of growth hormone secretion. | journal=Endocrinol Metab Clin North Am | year= 1996 | volume= 25 | issue= 3 | pages= 541-71 | pmid=8879986 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8879986  }}</ref>
* They are regulated by two [[Hypothalamus|hypothalamic]] hormones; [[GHRH|GH-releasing hormone]] ([[GHRH]]) stimulates and [[somatostatin]] inhibits them.  
* They are regulated by two [[Hypothalamus|hypothalamic]] hormones; [[GHRH|GH-releasing hormone]] ([[GHRH]]) stimulates and [[somatostatin]] inhibits them.  


* GH best-known effect is increasing body mass:  
* GH effect is increasing [[body mass]]:  
**GH increases total body [[protein]] content and is associated with an increase in [[amino acid]] incorporation into [[cartilage]] and [[bone]].<ref name="pmid13319878">{{cite journal| author=MURPHY WR, DAUGHADAY WH, HARTNETT C| title=The effect of hypophysectomy and growth hormone on the incorporation of labeled sulfate into tibial epiphyseal and nasal cartilage of the rat. | journal=J Lab Clin Med | year= 1956 | volume= 47 | issue= 5 | pages= 715-22 | pmid=13319878 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=13319878  }}</ref>  
**GH increases total body [[protein]] content and is associated with an increase in [[amino acid]] incorporation into [[cartilage]] and [[bone]].<ref name="pmid13319878">{{cite journal| author=MURPHY WR, DAUGHADAY WH, HARTNETT C| title=The effect of hypophysectomy and growth hormone on the incorporation of labeled sulfate into tibial epiphyseal and nasal cartilage of the rat. | journal=J Lab Clin Med | year= 1956 | volume= 47 | issue= 5 | pages= 715-22 | pmid=13319878 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=13319878  }}</ref>  
**GH stimulates l[[Lipolysis|ipolysis]] decreasing total body fat content.
**GH stimulates l[[Lipolysis|ipolysis]] decreasing total body [[fat]] content.
**GH also increases [[bone mass]] by stimulating skeletal [[insulin-like growth factor-I]] and causing [[hypertrophy]] of [[osteoblasts]], bone remodeling, and [[mineralization]].<ref name="pmid15689575">{{cite journal| author=Veldhuis JD, Roemmich JN, Richmond EJ, Rogol AD, Lovejoy JC, Sheffield-Moore M et al.| title=Endocrine control of body composition in infancy, childhood, and puberty. | journal=Endocr Rev | year= 2005 | volume= 26 | issue= 1 | pages= 114-46 | pmid=15689575 | doi=10.1210/er.2003-0038 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15689575  }}</ref>
**GH also increases [[bone mass]] by stimulating skeletal [[insulin-like growth factor-I]] and causing [[hypertrophy]] of [[osteoblasts]], bone remodeling, and [[mineralization]].<ref name="pmid15689575">{{cite journal| author=Veldhuis JD, Roemmich JN, Richmond EJ, Rogol AD, Lovejoy JC, Sheffield-Moore M et al.| title=Endocrine control of body composition in infancy, childhood, and puberty. | journal=Endocr Rev | year= 2005 | volume= 26 | issue= 1 | pages= 114-46 | pmid=15689575 | doi=10.1210/er.2003-0038 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15689575  }}</ref>
**GH causes [[epiphyseal plate]] widening and [[cartilage]] growth. 
**GH causes [[epiphyseal plate]] widening and [[cartilage]] growth. 


*[[Growth hormone|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, decreased [[bone density]], low exercise performance, and reduced quality of life.
*[[Growth hormone|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]], decreased [[bone density]], low exercise performance, and reduced quality of life.


==Genetics==
==Genetics==


==== ''[[POU1F1]]'' gene mutations ====
==== ''[[POU1F1]]'' gene mutations ====
* It is the most common known genetic cause of combined [[Pituitary gland|pituitary]] hormone deficiency.<ref name="pmid26608600">{{cite journal| author=Ziemnicka K, Budny B, Drobnik K, Baszko-Błaszyk D, Stajgis M, Katulska K et al.| title=Two coexisting heterozygous frameshift mutations in PROP1 are responsible for a different phenotype of combined pituitary hormone deficiency. | journal=J Appl Genet | year= 2016 | volume= 57 | issue= 3 | pages= 373-81 | pmid=26608600 | doi=10.1007/s13353-015-0328-z | pmc=4963446 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26608600  }}</ref>
* It is the most common known genetic cause of the combined [[Pituitary gland|pituitary]] hormone deficiency.<ref name="pmid26608600">{{cite journal| author=Ziemnicka K, Budny B, Drobnik K, Baszko-Błaszyk D, Stajgis M, Katulska K et al.| title=Two coexisting heterozygous frameshift mutations in PROP1 are responsible for a different phenotype of combined pituitary hormone deficiency. | journal=J Appl Genet | year= 2016 | volume= 57 | issue= 3 | pages= 373-81 | pmid=26608600 | doi=10.1007/s13353-015-0328-z | pmc=4963446 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26608600  }}</ref>
* It is responsible for pituitary-specific transcription of genes for GH, [[prolactin]], [[thyrotropin]], and the [[growth hormone releasing hormone]] (GHRH) receptor.<ref name="pmid1977085">{{cite journal| author=Li S, Crenshaw EB, Rawson EJ, Simmons DM, Swanson LW, Rosenfeld MG| title=Dwarf locus mutants lacking three pituitary cell types result from mutations in the POU-domain gene pit-1. | journal=Nature | year= 1990 | volume= 347 | issue= 6293 | pages= 528-33 | pmid=1977085 | doi=10.1038/347528a0 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1977085  }}</ref>
* It is responsible for [[Pituitary gland|pituitary]]-specific [[Transcription (genetics)|transcription]] of [[Gene|genes]] for GH, [[prolactin]], [[thyrotropin]], and the [[growth hormone releasing hormone|growth hormone-releasing hormone]] ([[GHRH]]) receptor.<ref name="pmid1977085">{{cite journal| author=Li S, Crenshaw EB, Rawson EJ, Simmons DM, Swanson LW, Rosenfeld MG| title=Dwarf locus mutants lacking three pituitary cell types result from mutations in the POU-domain gene pit-1. | journal=Nature | year= 1990 | volume= 347 | issue= 6293 | pages= 528-33 | pmid=1977085 | doi=10.1038/347528a0 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1977085  }}</ref>
* ''PROP1'' mutations result in failure to activate ''POU1F1/Pit1'' gene expression and probably cause pituitary hypoplasia.<ref name="pmid9462743">{{cite journal| author=Wu W, Cogan JD, Pfäffle RW, Dasen JS, Frisch H, O'Connell SM et al.| title=Mutations in PROP1 cause familial combined pituitary hormone deficiency. | journal=Nat Genet | year= 1998 | volume= 18 | issue= 2 | pages= 147-9 | pmid=9462743 | doi=10.1038/ng0298-147 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9462743  }}</ref>
* ''PROP1'' [[mutations]] result in failure to activate ''POU1F1/Pit1'' [[gene expression]] and probably cause [[Pituitary gland|pituitary]] hypoplasia.<ref name="pmid9462743">{{cite journal| author=Wu W, Cogan JD, Pfäffle RW, Dasen JS, Frisch H, O'Connell SM et al.| title=Mutations in PROP1 cause familial combined pituitary hormone deficiency. | journal=Nat Genet | year= 1998 | volume= 18 | issue= 2 | pages= 147-9 | pmid=9462743 | doi=10.1038/ng0298-147 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9462743  }}</ref>


==== [[GH1]] gene mutations ====
==== GH1 gene mutations ====
* It is ''GH1'' is the gene encoding GH, located on chromosome 17.
* It is ''GH1'' is the gene encoding GH, located on [[chromosome 17]].
* Gene deletions, f[[Frameshift mutation|rameshift]] mutations, and [[nonsense mutations]] of ''GH1'' have been described as causes of familial GHD.
* [[Gene deletion|Gene deletions]], f[[Frameshift mutation|rameshift]] mutations, and [[nonsense mutations]] of ''GH1'' have been described as causes of familial GHD.


==== Syndrome of bioinactive GH ====
==== Syndrome of bioinactive GH ====
Line 33: Line 33:


==== '''GH receptor signal [[transduction]]''' ====
==== '''GH receptor signal [[transduction]]''' ====
* It is essential for normal signaling of the GH receptor. Mutations in the gene encoding signal transducer decrease the response of receptors to GH.<ref name="pmid17389811">{{cite journal| author=Hwa V, Camacho-Hübner C, Little BM, David A, Metherell LA, El-Khatib N et al.| title=Growth hormone insensitivity and severe short stature in siblings: a novel mutation at the exon 13-intron 13 junction of the STAT5b gene. | journal=Horm Res | year= 2007 | volume= 68 | issue= 5 | pages= 218-24 | pmid=17389811 | doi=10.1159/000101334 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17389811  }}</ref>
* It is essential for normal signaling of the GH receptor. Mutations in the gene encoding signal transducer decrease the response of receptors to [[Growth hormone|GH]].<ref name="pmid17389811">{{cite journal| author=Hwa V, Camacho-Hübner C, Little BM, David A, Metherell LA, El-Khatib N et al.| title=Growth hormone insensitivity and severe short stature in siblings: a novel mutation at the exon 13-intron 13 junction of the STAT5b gene. | journal=Horm Res | year= 2007 | volume= 68 | issue= 5 | pages= 218-24 | pmid=17389811 | doi=10.1159/000101334 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17389811  }}</ref>


==== '''[[Insulin-like growth factor-I|IGF-I]] gene mutations''' ====
==== '''[[Insulin-like growth factor-I|IGF-I]] gene mutations''' ====
* Mutations in the gene encoding [[Insulin-like growth factor-I|IGF-I]] cause a unique syndrome of GHD.<ref name="pmid24243634">{{cite journal| author=Batey L, Moon JE, Yu Y, Wu B, Hirschhorn JN, Shen Y et al.| title=A novel deletion of IGF1 in a patient with idiopathic short stature provides insight Into IGF1 haploinsufficiency. | journal=J Clin Endocrinol Metab | year= 2014 | volume= 99 | issue= 1 | pages= E153-9 | pmid=24243634 | doi=10.1210/jc.2013-3106 | pmc=3879666 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24243634  }}</ref>
* Mutations in the gene encoding [[Insulin-like growth factor-I|IGF-I]] cause a unique syndrome of GHD.<ref name="pmid24243634">{{cite journal| author=Batey L, Moon JE, Yu Y, Wu B, Hirschhorn JN, Shen Y et al.| title=A novel deletion of IGF1 in a patient with idiopathic short stature provides insight Into IGF1 haploinsufficiency. | journal=J Clin Endocrinol Metab | year= 2014 | volume= 99 | issue= 1 | pages= E153-9 | pmid=24243634 | doi=10.1210/jc.2013-3106 | pmc=3879666 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24243634  }}</ref>
* Patients with [[Insulin-like growth factor-I|IGF-I]] gene mutations have prenatal growth failure, [[microcephaly]], significant neurocognitive deficits, and [[sensorineural hearing loss]].
* Patients with [[Insulin-like growth factor-I|IGF-I]] [[Gene mutation|gene mutations]] have prenatal growth failure, [[microcephaly]], significant [[Neurocognitive deficit|neurocognitive deficits]], and [[sensorineural hearing loss]].


==== '''Defective stabilization of circulating [[Insulin-like growth factor-I|IGF-I]]''' ====
==== '''Defective stabilization of circulating [[Insulin-like growth factor-I|IGF-I]]''' ====
* Acid-labile subunit is important for the stabilization of the [[Insulin-like growth factor-I|IGF-I]].
* Acid-labile subunit is important for the stabilization of the [[Insulin-like growth factor-I|IGF-I]].
* Mutations in the gene coding for it causes less stable and subsequently less effect.<ref name="pmid19729943">{{cite journal| author=Domené HM, Hwa V, Argente J, Wit JM, Wit JM, Camacho-Hübner C et al.| title=Human acid-labile subunit deficiency: clinical, endocrine and metabolic consequences. | journal=Horm Res | year= 2009 | volume= 72 | issue= 3 | pages= 129-41 | pmid=19729943 | doi=10.1159/000232486 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19729943  }}</ref>
* [[Mutations]] in the [[gene]] coding for it causes less stable and subsequently less effect.<ref name="pmid19729943">{{cite journal| author=Domené HM, Hwa V, Argente J, Wit JM, Wit JM, Camacho-Hübner C et al.| title=Human acid-labile subunit deficiency: clinical, endocrine and metabolic consequences. | journal=Horm Res | year= 2009 | volume= 72 | issue= 3 | pages= 129-41 | pmid=19729943 | doi=10.1159/000232486 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19729943  }}</ref>


==== '''[[Insulin-like growth factor-I|IGF-I]] receptor mutations''' ====
==== '''[[Insulin-like growth factor-I|IGF-I]] receptor mutations''' ====
* Mutations in the gene encoding the receptor for [[Insulin-like growth factor-I|IGF-I]] result in partial loss of function of the [[Insulin-like growth factor-I|IGF-I]] receptor.<ref name="pmid22309212">{{cite journal| author=Kawashima Y, Higaki K, Fukushima T, Hakuno F, Nagaishi J, Hanaki K et al.| title=Novel missense mutation in the IGF-I receptor L2 domain results in intrauterine and postnatal growth retardation. | journal=Clin Endocrinol (Oxf) | year= 2012 | volume= 77 | issue= 2 | pages= 246-54 | pmid=22309212 | doi=10.1111/j.1365-2265.2012.04357.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22309212  }}</ref>  
* [[Mutations]] in the [[gene]] encoding the receptor for the [[Insulin-like growth factor-I|IGF-I]] result in partial loss of function of the [[Insulin-like growth factor-I|IGF-I]] receptor.<ref name="pmid22309212">{{cite journal| author=Kawashima Y, Higaki K, Fukushima T, Hakuno F, Nagaishi J, Hanaki K et al.| title=Novel missense mutation in the IGF-I receptor L2 domain results in intrauterine and postnatal growth retardation. | journal=Clin Endocrinol (Oxf) | year= 2012 | volume= 77 | issue= 2 | pages= 246-54 | pmid=22309212 | doi=10.1111/j.1365-2265.2012.04357.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22309212  }}</ref>  


==References==
==References==
{{Reflist|2}}
{{Reflist|2}}

Revision as of 18:07, 27 September 2017

Growth hormone deficiency Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Growth hormone deficiency from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Criteria

History and Symptoms

Physical Examination

Laboratory Findings

X Ray

CT

MRI

Echocardiography or Ultrasound

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Growth hormone deficiency pathophysiology On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Growth hormone deficiency pathophysiology

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Growth hormone deficiency pathophysiology

CDC on Growth hormone deficiency pathophysiology

Growth hormone deficiency pathophysiology in the news

Blogs on Growth hormone deficiency pathophysiology

Directions to Hospitals Treating Growth hormone deficiency

Risk calculators and risk factors for Growth hormone deficiency pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mohammed Abdelwahed M.D[2]

Overview

The somatotroph cells of the anterior pituitary gland produce growth hormone (GH). 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 the combined pituitary hormone deficiency. Gene deletions, frameshift mutations, and nonsense mutations of GH1 gene have been described as causes of familial GHD.

Pathophysiology

  • 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, decreased bone density, low exercise performance, and reduced quality of life.

Genetics

POU1F1 gene mutations

GH1 gene mutations

Syndrome of bioinactive GH

GH receptor signal transduction

  • It is essential for normal signaling of the GH receptor. Mutations in the gene encoding signal transducer decrease the response of receptors to GH.[8]

IGF-I gene mutations

Defective stabilization of circulating IGF-I

  • Acid-labile subunit is important for the stabilization of the IGF-I.
  • Mutations in the gene coding for it causes less stable and subsequently less effect.[10]

IGF-I receptor mutations

References

  1. Cuttler L (1996). "The regulation of growth hormone secretion". Endocrinol Metab Clin North Am. 25 (3): 541–71. PMID 8879986.
  2. MURPHY WR, DAUGHADAY WH, HARTNETT C (1956). "The effect of hypophysectomy and growth hormone on the incorporation of labeled sulfate into tibial epiphyseal and nasal cartilage of the rat". J Lab Clin Med. 47 (5): 715–22. PMID 13319878.
  3. Veldhuis JD, Roemmich JN, Richmond EJ, Rogol AD, Lovejoy JC, Sheffield-Moore M; et al. (2005). "Endocrine control of body composition in infancy, childhood, and puberty". Endocr Rev. 26 (1): 114–46. doi:10.1210/er.2003-0038. PMID 15689575.
  4. Ziemnicka K, Budny B, Drobnik K, Baszko-Błaszyk D, Stajgis M, Katulska K; et al. (2016). "Two coexisting heterozygous frameshift mutations in PROP1 are responsible for a different phenotype of combined pituitary hormone deficiency". J Appl Genet. 57 (3): 373–81. doi:10.1007/s13353-015-0328-z. PMC 4963446. PMID 26608600.
  5. Li S, Crenshaw EB, Rawson EJ, Simmons DM, Swanson LW, Rosenfeld MG (1990). "Dwarf locus mutants lacking three pituitary cell types result from mutations in the POU-domain gene pit-1". Nature. 347 (6293): 528–33. doi:10.1038/347528a0. PMID 1977085.
  6. Wu W, Cogan JD, Pfäffle RW, Dasen JS, Frisch H, O'Connell SM; et al. (1998). "Mutations in PROP1 cause familial combined pituitary hormone deficiency". Nat Genet. 18 (2): 147–9. doi:10.1038/ng0298-147. PMID 9462743.
  7. Besson A, Salemi S, Deladoëy J, Vuissoz JM, Eblé A, Bidlingmaier M; et al. (2005). "Short stature caused by a biologically inactive mutant growth hormone (GH-C53S)". J Clin Endocrinol Metab. 90 (5): 2493–9. doi:10.1210/jc.2004-1838. PMID 15713716.
  8. Hwa V, Camacho-Hübner C, Little BM, David A, Metherell LA, El-Khatib N; et al. (2007). "Growth hormone insensitivity and severe short stature in siblings: a novel mutation at the exon 13-intron 13 junction of the STAT5b gene". Horm Res. 68 (5): 218–24. doi:10.1159/000101334. PMID 17389811.
  9. Batey L, Moon JE, Yu Y, Wu B, Hirschhorn JN, Shen Y; et al. (2014). "A novel deletion of IGF1 in a patient with idiopathic short stature provides insight Into IGF1 haploinsufficiency". J Clin Endocrinol Metab. 99 (1): E153–9. doi:10.1210/jc.2013-3106. PMC 3879666. PMID 24243634.
  10. Domené HM, Hwa V, Argente J, Wit JM, Wit JM, Camacho-Hübner C; et al. (2009). "Human acid-labile subunit deficiency: clinical, endocrine and metabolic consequences". Horm Res. 72 (3): 129–41. doi:10.1159/000232486. PMID 19729943.
  11. Kawashima Y, Higaki K, Fukushima T, Hakuno F, Nagaishi J, Hanaki K; et al. (2012). "Novel missense mutation in the IGF-I receptor L2 domain results in intrauterine and postnatal growth retardation". Clin Endocrinol (Oxf). 77 (2): 246–54. doi:10.1111/j.1365-2265.2012.04357.x. PMID 22309212.