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Revision as of 18:00, 27 September 2017

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, 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]
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.^[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^[5]

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
Pituitary adenoma^[7]
Craniopharyngioma
Rathke’s cleft cyst
Glioma/astrocytoma
Germinoma
Infiltrative/granulomatous disease:^[8]
Langerhans cell histiocytosis
Sarcoidosis^[9]
Tuberculosis
Hypophysitis^[10]
Surgery of the pituitary or hypothalamus^[11]
Sheehan’s syndrome^[12]
Idiopathic

Laron syndrome

It is the most common known cause of genetically-mediated 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.
↑ 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.
↑ 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.
↑ ^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.

[pmid1977085-1] 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.

[pmid22024773-2] 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.

[pmid9462743-3] 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.

[pmid8768831-4] 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.

[pmid216024532-5] 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.

[pmid3092668-6] 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.

[pmid26252454-7] 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.

[pmid6794282-8] 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.

[pmid112384842-9] 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.

[pmid11238484-10] 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.

[pmid262524542-11] 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.

[pmid2750772-12] Barkan AL (1989). "Pituitary atrophy in patients with Sheehan's syndrome". Am J Med Sci. 298 (1): 38–40. PMID 2750772.

[pmid26062520-13] 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.

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@@ Line 4: / Line 4: @@
 ==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 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]], [[pituitary adenoma]].''
+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]].''
 ==Causes==
@@ Line 11: / Line 11: @@
 ==== 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 ''GH1:''
-* 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>
+* 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>
-* 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>
+* [[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.<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>
+* [[Gene deletion|Gene deletions]], [[Frameshift mutation|frameshift mutations]], and [[nonsense mutations]] of ''GH1'' 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>
-==== '''Structural causes''' ====
+==== '''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]]:<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]]
-* [[Midline facial defects]]
+* Midline facial defects
 * [[Agenesis of the corpus callosum|Agenesis of corpus callosum]]
 * [[Arachnoid cyst]]
@@ Line 31: / Line 31: @@
 === '''Acquired growth hormone deficiency'''<ref name="pmid216024532" /> ===
-* 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>
+* 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]]
 * [[Pituitary adenoma]]<ref name="pmid26252454">{{cite journal| author=Jahangiri A, Wagner JR, Han SW, Tran MT, Miller LM, Chen R et al.| title=Improved versus worsened endocrine function after transsphenoidal surgery for nonfunctional pituitary adenomas: rate, time course, and radiological analysis. | journal=J Neurosurg | year= 2016 | volume= 124 | issue= 3 | pages= 589-95 | pmid=26252454 | doi=10.3171/2015.1.JNS141543 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26252454  }}</ref>
 * [[Craniopharyngioma]]
-* [[Rathke’s cleft|Rathke’s cleft cyst]]
+* [[Rathke’s pouch|Rathke’s]] cleft [[cyst]]
 * [[Glioma]]/[[astrocytoma]]
 * [[Germinoma]]
-* Infiltrative/[[Granulomatous|granulomatous disease]]:<ref name="pmid6794282">{{cite journal| author=Charbonnel B, Chupin M, Le Grand A, Guillon J| title=Pituitary function in idiopathic haemochromatosis: hormonal study in 36 male patients. | journal=Acta Endocrinol (Copenh) | year= 1981 | volume= 98 | issue= 2 | pages= 178-83 | pmid=6794282 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6794282  }}</ref>
+* [[Infiltrative and Metabolic Diseases Affecting the Liver|Infiltrative]]/[[Granulomatous|granulomatous disease]]:<ref name="pmid6794282">{{cite journal| author=Charbonnel B, Chupin M, Le Grand A, Guillon J| title=Pituitary function in idiopathic haemochromatosis: hormonal study in 36 male patients. | journal=Acta Endocrinol (Copenh) | year= 1981 | volume= 98 | issue= 2 | pages= 178-83 | pmid=6794282 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6794282  }}</ref>
 * [[Langerhans cell histiocytosis]]
 * [[Sarcoidosis]]<ref name="pmid112384842">{{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>
@@ Line 47: / Line 47: @@
 * [[Idiopathic]]
-==== '''[[Laron syndrome]]'''<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> ====
+==== '''[[Laron syndrome]]''' ====
-* It is the most common known cause of genetically-mediated GHI.
+* It is the most common known cause of genetically-mediated 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 biological 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]].
-* In contrast with GH deficiency, [[Laron syndrome]] is characterized by growth failure and normal levels of GH.
+* [[Laron syndrome]] is characterized by [[growth failure]] and normal levels of [[Growth hormone|GH]].
-* It is caused by mutations in the growth hormone (GH) receptor gene which affects the extracellular GH-binding of the receptor.
+* 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 1|insulin-like growth factor-binding protein]] 3 ([[IGFBP-3]]) levels.
 == References ==
 {{Reflist|2}}