Growth hormone deficiency causes: Difference between revisions
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==Overview== | ==Overview== | ||
Causes of growth hormone deficiency could be congenital or acquired. Congenital causes | Causes of growth hormone deficiency could be congenital or acquired. Congenital causes can be genetic or structural. The genetic causes are due to [[genetic mutations]] in ''POU1F1'', ''PROP-1'', and ''GH-1 genes'' while the structural causes include [[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]] and [[radiation therapy]] for [[brain tumors]], [[central nervous system infection]], [[craniopharyngioma]], and [[pituitary adenoma]]. | ||
==Causes== | ==Causes== | ||
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* The ''POU1F1'' gene is responsible for [[Pituitary gland|pituitary]]-specific [[Transcription (genetics)|transcription of genes]] for [[Growth hormone|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> | * The ''POU1F1'' gene is responsible for [[Pituitary gland|pituitary]]-specific [[Transcription (genetics)|transcription of genes]] for [[Growth hormone|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> | ||
* ''[[PROP1]]'' [[mutations]] result in failure to activate ''POU1F1/Pit1'' [[gene expression]] and probably cause pituitary hypoplasia and [[familial]] multiple pituitary hormone deficiencies.<ref name="pmid22024773">{{cite journal| author=Obermannova B, Pfaeffle R, Zygmunt-Gorska A, Starzyk J, Verkauskiene R, Smetanina N et al.| title=Mutations and pituitary morphology in a series of 82 patients with PROP1 gene defects. | journal=Horm Res Paediatr | year= 2011 | volume= 76 | issue= 5 | pages= 348-54 | pmid=22024773 | doi=10.1159/000332693 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22024773 }}</ref> | * ''[[PROP1]]'' [[mutations]] result in failure to activate ''POU1F1/Pit1'' [[gene expression]] and probably cause pituitary hypoplasia and [[familial]] multiple pituitary hormone deficiencies.<ref name="pmid22024773">{{cite journal| author=Obermannova B, Pfaeffle R, Zygmunt-Gorska A, Starzyk J, Verkauskiene R, Smetanina N et al.| title=Mutations and pituitary morphology in a series of 82 patients with PROP1 gene defects. | journal=Horm Res Paediatr | year= 2011 | volume= 76 | issue= 5 | pages= 348-54 | pmid=22024773 | doi=10.1159/000332693 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22024773 }}</ref> | ||
* [[ | * [[Gene deletion|Gene deletions]], [[Frameshift mutation|frameshift mutations]], and [[nonsense mutations]] of ''GH1'' which codes for GH, have been described as causes of [[familial]] GHD.<ref name="pmid8768831">{{cite journal| author=Pellegrini-Bouiller I, Bélicar P, Barlier A, Gunz G, Charvet JP, Jaquet P et al.| title=A new mutation of the gene encoding the transcription factor Pit-1 is responsible for combined pituitary hormone deficiency. | journal=J Clin Endocrinol Metab | year= 1996 | volume= 81 | issue= 8 | pages= 2790-6 | pmid=8768831 | doi=10.1210/jcem.81.8.8768831 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8768831 }}</ref><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> | ||
==== '''Structural Causes''' ==== | ==== '''Structural Causes''' ==== | ||
* GHD is highly likely to be permanent in these patients | * GHD is highly likely to be permanent in these patients | ||
* It is associated with midline [[craniofacial]] anomalies causing agenesis of the [[Hypothalamic pituitary adrenal axis|hypothalamic-pituitary stalk]]:<ref name="pmid216024532">{{cite journal| author=Molitch ME, Clemmons DR, Malozowski S, Merriam GR, Vance ML, Endocrine Society| title=Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society clinical practice guideline. | journal=J Clin Endocrinol Metab | year= 2011 | volume= 96 | issue= 6 | pages= 1587-609 | pmid=21602453 | doi=10.1210/jc.2011-0179 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21602453 }}</ref> | * It is associated with midline [[craniofacial]] anomalies causing agenesis of the [[Hypothalamic pituitary adrenal axis|hypothalamic-pituitary stalk]]:<ref name="pmid216024532">{{cite journal| author=Molitch ME, Clemmons DR, Malozowski S, Merriam GR, Vance ML, Endocrine Society| title=Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society clinical practice guideline. | journal=J Clin Endocrinol Metab | year= 2011 | volume= 96 | issue= 6 | pages= 1587-609 | pmid=21602453 | doi=10.1210/jc.2011-0179 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21602453 }}</ref> | ||
**[[Optic nerve hypoplasia]] | |||
* [[Optic nerve hypoplasia]] | **Midline facial defects | ||
* Midline facial defects | **[[Agenesis of the corpus callosum|Agenesis of corpus callosum]] | ||
* [[Agenesis of the corpus callosum|Agenesis of corpus callosum]] | **[[Arachnoid cyst]] | ||
* [[Arachnoid cyst]] | **[[Holoprosencephaly]] | ||
* [[Holoprosencephaly]] | **[[Septo-optic dysplasia]] | ||
* [[Septo-optic dysplasia]] | **[[Encephalocele]] | ||
* [[Encephalocele]] | **[[Empty sella syndrome|Empty Sella syndrome]] | ||
* [[Empty sella syndrome|Empty Sella syndrome]] | **[[Hydrocephalus]] | ||
* [[Hydrocephalus]] | |||
=== '''Acquired growth hormone deficiency''' === | === '''Acquired growth hormone deficiency''' === | ||
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==== '''[[Laron syndrome]]''' ==== | ==== '''[[Laron syndrome]]''' ==== | ||
* | * This is the most common known cause of genetically-mediated growth hormone insensitivity (GHI).<ref name="pmid26062520">{{cite journal| author=Kurtoğlu S, Hatipoglu N| title=Growth hormone insensitivity: diagnostic and therapeutic approaches. | journal=J Endocrinol Invest | year= 2016 | volume= 39 | issue= 1 | pages= 19-28 | pmid=26062520 | doi=10.1007/s40618-015-0327-2 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26062520 }}</ref> | ||
* [[Growth hormone insensitivity syndrome|Growth hormone insensitivity]] is an absence of the effects of [[growth hormone]] despite a normal production of [[Growth hormone|GH]]. | * [[Growth hormone insensitivity syndrome|Growth hormone insensitivity]] is an absence of the effects of [[growth hormone]] despite a normal production of [[Growth hormone|GH]]. | ||
* [[Laron syndrome]] is characterized by [[growth failure]] and normal levels of [[Growth hormone|GH]]. | * [[Laron syndrome]] is characterized by [[growth failure]] and normal levels of [[Growth hormone|GH]]. | ||
Latest revision as of 14:07, 25 October 2017
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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
Causes of growth hormone deficiency could be congenital or acquired. Congenital causes can be genetic or structural. The genetic causes are due to genetic mutations in POU1F1, PROP-1, and GH-1 genes while the structural causes include optic nerve hypoplasia, agenesis of corpus callosum, septo-optic dysplasia, empty sella syndrome, and holoprosencephaly. Acquired causes of growth hormone deficiency include brain surgery and radiation therapy for brain tumors, central nervous system infection, craniopharyngioma, and pituitary adenoma.
Causes
Congenital growth hormone deficiency:
Genetic causes
It is usually recognized by the presence of affected relatives and confirmed by molecular testing for the causative genes, which include POU1F1, PROP-1, and GH1:
- The POU1F1 gene is responsible for pituitary-specific transcription of genes for GH, prolactin, thyrotropin, and the growth hormone-releasing hormone (GHRH) receptor.[1]
- PROP1 mutations result in failure to activate POU1F1/Pit1 gene expression and probably cause pituitary hypoplasia and familial multiple pituitary hormone deficiencies.[2]
- Gene deletions, frameshift mutations, and nonsense mutations of GH1 which codes for GH, have been described as causes of familial GHD.[3][4]
Structural Causes
- GHD is highly likely to be permanent in these patients
- It is associated with midline craniofacial anomalies causing agenesis of the hypothalamic-pituitary stalk:[5]
Acquired growth hormone deficiency
- GHD following brain surgery and radiation therapy for brain tumors. Permanent GHD is highly likely to be permanent in infants or young children[6]
- Central nervous system infection[5]
- Pituitary adenoma[7]
- Craniopharyngioma
- Rathke’s cleft cyst
- Glioma/astrocytoma
- Germinoma
- Infiltrative/granulomatous disease:[8]
- Surgery of the pituitary or hypothalamus[11]
- Sheehan’s syndrome[12]
- Idiopathic
Laron syndrome
- This is the most common known cause of genetically-mediated growth hormone insensitivity (GHI).[13]
- Growth hormone insensitivity is an absence of the effects of growth hormone despite a normal production of GH.
- Laron syndrome is characterized by growth failure and normal levels of GH.
- It is caused by mutations in the growth hormone receptor gene which affects the GH-binding of the receptor.
- Its severity correlates to IGF-I and insulin-like growth factor-binding protein 3 (IGFBP-3) levels.
References
- ↑ 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.
- ↑ Obermannova B, Pfaeffle R, Zygmunt-Gorska A, Starzyk J, Verkauskiene R, Smetanina N; et al. (2011). "Mutations and pituitary morphology in a series of 82 patients with PROP1 gene defects". Horm Res Paediatr. 76 (5): 348–54. doi:10.1159/000332693. PMID 22024773.
- ↑ Pellegrini-Bouiller I, Bélicar P, Barlier A, Gunz G, Charvet JP, Jaquet P; et al. (1996). "A new mutation of the gene encoding the transcription factor Pit-1 is responsible for combined pituitary hormone deficiency". J Clin Endocrinol Metab. 81 (8): 2790–6. doi:10.1210/jcem.81.8.8768831. PMID 8768831.
- ↑ 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.
- ↑ 5.0 5.1 Molitch ME, Clemmons DR, Malozowski S, Merriam GR, Vance ML, Endocrine Society (2011). "Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society clinical practice guideline". J Clin Endocrinol Metab. 96 (6): 1587–609. doi:10.1210/jc.2011-0179. PMID 21602453.
- ↑ Snyder PJ, Fowble BF, Schatz NJ, Savino PJ, Gennarelli TA (1986). "Hypopituitarism following radiation therapy of pituitary adenomas". Am J Med. 81 (3): 457–62. PMID 3092668.
- ↑ Jahangiri A, Wagner JR, Han SW, Tran MT, Miller LM, Chen R; et al. (2016). "Improved versus worsened endocrine function after transsphenoidal surgery for nonfunctional pituitary adenomas: rate, time course, and radiological analysis". J Neurosurg. 124 (3): 589–95. doi:10.3171/2015.1.JNS141543. PMID 26252454.
- ↑ Charbonnel B, Chupin M, Le Grand A, Guillon J (1981). "Pituitary function in idiopathic haemochromatosis: hormonal study in 36 male patients". Acta Endocrinol (Copenh). 98 (2): 178–83. PMID 6794282.
- ↑ Cheung CC, Ezzat S, Smyth HS, Asa SL (2001). "The spectrum and significance of primary hypophysitis". J Clin Endocrinol Metab. 86 (3): 1048–53. doi:10.1210/jcem.86.3.7265. PMID 11238484.
- ↑ Cheung CC, Ezzat S, Smyth HS, Asa SL (2001). "The spectrum and significance of primary hypophysitis". J Clin Endocrinol Metab. 86 (3): 1048–53. doi:10.1210/jcem.86.3.7265. PMID 11238484.
- ↑ Jahangiri A, Wagner JR, Han SW, Tran MT, Miller LM, Chen R; et al. (2016). "Improved versus worsened endocrine function after transsphenoidal surgery for nonfunctional pituitary adenomas: rate, time course, and radiological analysis". J Neurosurg. 124 (3): 589–95. doi:10.3171/2015.1.JNS141543. PMID 26252454.
- ↑ Barkan AL (1989). "Pituitary atrophy in patients with Sheehan's syndrome". Am J Med Sci. 298 (1): 38–40. PMID 2750772.
- ↑ Kurtoğlu S, Hatipoglu N (2016). "Growth hormone insensitivity: diagnostic and therapeutic approaches". J Endocrinol Invest. 39 (1): 19–28. doi:10.1007/s40618-015-0327-2. PMID 26062520.