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 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, pituitary adenoma.'' | |||
==Causes== | ==Causes== | ||
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==== Genetic causes ==== | ==== 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 ''GH-1:'' | 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 ''GH-1:'' | ||
* The ''POU1F1'' gene is responsible for pituitary-specific transcription of genes for GH, prolactin, thyrotropin, and the growth hormone releasing hormone (GHRH) receptor | * The ''POU1F1'' gene 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> ''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> | ||
* | * Mutations of ''GH1 which is'' the gene encoding GH.<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> | ||
* Gene deletions, frameshift mutations, and nonsense mutations of ''GH1'' have been described as causes of familial GHD. | |||
==== '''Structural causes''' ==== | ==== '''Structural causes''' ==== | ||
It is associated with midline craniofacial anomalies causing agenesis of the hypothalamic-pituitary stalk. | * GHD is highly likely to be permanent in these patients | ||
* It is associated with midline craniofacial anomalies causing agenesis of the hypothalamic-pituitary stalk:<ref name="pmid21602453">{{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 | |||
* Agenesis of corpus callosum | * Agenesis of corpus callosum | ||
* Arachnoid cyst | |||
* Holoprosencephaly | |||
* Septo-optic dysplasia | * Septo-optic dysplasia | ||
* Encephalocele | |||
* Empty sella syndrome | * Empty sella syndrome | ||
* | * Single central incisor | ||
* Hydrocephalus | * Hydrocephalus | ||
=== '''Acquired growth hormone deficiency''' === | === '''Acquired growth hormone deficiency'''<ref name="pmid21602453" /> === | ||
* GHD following brain surgery and radiation therapy for brain tumors. Permanent GHD is highly likely to be permanent in infants or young children. | * GHD following brain surgery and radiation therapy for brain tumors. Permanent GHD is highly likely to be permanent in infants or young children.<ref name="pmid3092668">{{cite journal| author=Snyder PJ, Fowble BF, Schatz NJ, Savino PJ, Gennarelli TA| title=Hypopituitarism following radiation therapy of pituitary adenomas. | journal=Am J Med | year= 1986 | volume= 81 | issue= 3 | pages= 457-62 | pmid=3092668 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3092668 }}</ref> | ||
* Central nervous system infection | * Central nervous system infection | ||
* Tumors of hypothalamus or pituitary | * Tumors of hypothalamus or pituitary | ||
| Line 42: | Line 44: | ||
* Sarcoidosis | * Sarcoidosis | ||
* Tuberculosis | * Tuberculosis | ||
* Hypophysitis | * Hypophysitis<ref name="pmid11238484">{{cite journal| author=Cheung CC, Ezzat S, Smyth HS, Asa SL| title=The spectrum and significance of primary hypophysitis. | journal=J Clin Endocrinol Metab | year= 2001 | volume= 86 | issue= 3 | pages= 1048-53 | pmid=11238484 | doi=10.1210/jcem.86.3.7265 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11238484 }}</ref> | ||
* Surgery of the pituitary or hypothalamus | * Surgery of the pituitary or hypothalamus | ||
* Infarction | * Infarction | ||
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:
Overview
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, 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 GH-1:
- 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]
- Mutations of GH1 which is the gene encoding GH.[3]
- Gene deletions, frameshift mutations, and nonsense mutations of GH1 have been described as causes of familial GHD.
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:[4]
- Optic nerve hypoplasia
- Midline facial defects
- Agenesis of corpus callosum
- Arachnoid cyst
- Holoprosencephaly
- Septo-optic dysplasia
- Encephalocele
- Empty sella syndrome
- Single central incisor
- Hydrocephalus
Acquired growth hormone deficiency[4]
- GHD following brain surgery and radiation therapy for brain tumors. Permanent GHD is highly likely to be permanent in infants or young children.[5]
- Central nervous system infection
- Tumors of hypothalamus or pituitary
- Pituitary adenoma
- Craniopharyngioma
- Rathke’s cleft cyst
- Glioma/astrocytoma
- Germinoma
- Infiltrative/granulomatous disease:
- Langerhans cell histiocytosis
- Sarcoidosis
- Tuberculosis
- Hypophysitis[6]
- Surgery of the pituitary or hypothalamus
- Infarction
- Spontaneous
- Sheehan’s syndrome
- Idiopathic
Laron syndrome
- Growth hormone insensitivity is a reduction in or absence of the biological effects of growth hormone despite normal or above normal production and secretion of GH.
- These disorders are characterized by growth failure and normal or increased circulating levels of GH, in contrast with GH deficiency.
- It is the most common known cause of genetically-mediated GHI.
- is characterized by severe postnatal growth failure.
- It is caused by homozygous or compounds heterozygous mutations in the growth hormone (GH) receptor gene; a variety of mutations have been identified, most of which affect the extracellular GH-binding region of the receptor.
- reflected by IGF-I and insulin-like growth factor-binding protein 3 (IGFBP-3) levels.
- Adult height does not correlate with genotype or with measures of height in family members.
- hyperlipidemia and episodes of hypoglycemia Data are conflicting on the risk of insulin resistance.
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.
- ↑ 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.
- ↑ 4.0 4.1 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.
- ↑ 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.