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Pituitary hormone deficiency, combined, 6(CPHD6)

MedGen UID:
462790
Concept ID:
C3151440
Disease or Syndrome
Synonym: OTX2-Related Combined Pituitary Hormone Deficiency
 
Gene (location): OTX2 (14q22.3)
 
Monarch Initiative: MONDO:0013518
OMIM®: 613986

Definition

Any combined pituitary hormone deficiencies, genetic form in which the cause of the disease is a mutation in the OTX2 gene. [from MONDO]

Clinical features

From HPO
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Feeding difficulties
MedGen UID:
65429
Concept ID:
C0232466
Finding
Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Ectopic posterior pituitary
MedGen UID:
481201
Concept ID:
C3279571
Finding
An abnormal anatomical location of the posterior lobe of the hypophysis, also known as the neurohypophysis. The posterior pituitary is normally present in the dorsal portion of the sella turcica, but when ectopic is usually near the median eminence. This defect is likely to be due to abnormal migration during embryogenesis.
Posterior pituitary hypoplasia
MedGen UID:
868797
Concept ID:
C4023202
Anatomical Abnormality
Underdevelopment of the neurohypophysis.
Hypoglycemia
MedGen UID:
6979
Concept ID:
C0020615
Disease or Syndrome
A decreased concentration of glucose in the blood.
Neonatal hypoglycemia
MedGen UID:
57646
Concept ID:
C0158986
Finding
Blood glucose concentration below the lower limit of established reference ranges in a newborn.
Hyperbilirubinemia
MedGen UID:
86321
Concept ID:
C0311468
Finding
An increased amount of bilirubin in the blood.
Decreased thyroid-stimulating hormone level
MedGen UID:
717708
Concept ID:
C1295607
Finding
Reduced amount of the thyroid-stimulating hormone (TSH), which is produced by the anterior pituitary gland and stimulates the function of the thyroid gland.
Decreased circulating follicle stimulating hormone concentration
MedGen UID:
892977
Concept ID:
C4072889
Finding
A reduction of the circulating level of follicle-stimulating hormone (FSH).
Decreased circulating luteinizing hormone level
MedGen UID:
893008
Concept ID:
C4072890
Finding
A reduction in the circulating level of luteinizing hormone (LH).
Reduced circulating growth hormone concentration
MedGen UID:
1815075
Concept ID:
C5706169
Finding
Concentration of growth hormone in the blood circulation below normal limits.
Decreased circulating ACTH concentration
MedGen UID:
1841520
Concept ID:
C5826343
Finding
The concentration of corticotropin, also known as adrenocorticotropic hormone (ACTH), is below the lower limit of normal in the blood circulation.

Professional guidelines

PubMed

Atila C, Loughrey PB, Garrahy A, Winzeler B, Refardt J, Gildroy P, Hamza M, Pal A, Verbalis JG, Thompson CJ, Hemkens LG, Hunter SJ, Sherlock M, Levy MJ, Karavitaki N, Newell-Price J, Wass JAH, Christ-Crain M
Lancet Diabetes Endocrinol 2022 Oct;10(10):700-709. Epub 2022 Aug 22 doi: 10.1016/S2213-8587(22)00219-4. PMID: 36007536
Falsetti L, Gambera A, Platto C, Legrenzi L
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Recent clinical studies

Etiology

Scherdel P, Matczak S, Léger J, Martinez-Vinson C, Goulet O, Brauner R, Nicklaus S, Resche-Rigon M, Chalumeau M, Heude B
J Clin Endocrinol Metab 2019 Feb 1;104(2):241-249. doi: 10.1210/jc.2018-00723. PMID: 30137417
Ali ZS, Lang SS, Kamat AR, Adappa ND, Palmer JN, Storm PB, Lee JY
Childs Nerv Syst 2013 Nov;29(11):2065-70. Epub 2013 May 24 doi: 10.1007/s00381-013-2153-1. PMID: 23702738
Lin-Su K, Harbison MD, Lekarev O, Vogiatzi MG, New MI
J Clin Endocrinol Metab 2011 Jun;96(6):1710-7. Epub 2011 Mar 30 doi: 10.1210/jc.2010-2699. PMID: 21450983Free PMC Article
Honke K, Taniguchi N
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Abayomi OK, Sadeghi-Nejad A
Int J Radiat Oncol Biol Phys 1986 Jun;12(6):945-8. doi: 10.1016/0360-3016(86)90390-1. PMID: 3721935

Diagnosis

Atila C, Loughrey PB, Garrahy A, Winzeler B, Refardt J, Gildroy P, Hamza M, Pal A, Verbalis JG, Thompson CJ, Hemkens LG, Hunter SJ, Sherlock M, Levy MJ, Karavitaki N, Newell-Price J, Wass JAH, Christ-Crain M
Lancet Diabetes Endocrinol 2022 Oct;10(10):700-709. Epub 2022 Aug 22 doi: 10.1016/S2213-8587(22)00219-4. PMID: 36007536
Gohil J, Gowda A, George T, Easwer HV, George A, Nair P
Pituitary 2021 Dec;24(6):854-858. Epub 2021 May 21 doi: 10.1007/s11102-021-01156-1. PMID: 34021443Free PMC Article
Chiovato L, Magri F, Carlé A
Adv Ther 2019 Sep;36(Suppl 2):47-58. Epub 2019 Sep 4 doi: 10.1007/s12325-019-01080-8. PMID: 31485975Free PMC Article
Hirai Y, Asahata S, Ainoda Y, Fujita T, Miura H, Hizuka N, Kikuchi K
Mycopathologia 2015 Aug;180(1-2):111-6. Epub 2015 Apr 8 doi: 10.1007/s11046-015-9884-3. PMID: 25851027
Hoes MJ
Med Hypotheses 1980 Oct;6(10):1063-75. doi: 10.1016/0306-9877(80)90019-5. PMID: 7001193

Therapy

Atila C, Loughrey PB, Garrahy A, Winzeler B, Refardt J, Gildroy P, Hamza M, Pal A, Verbalis JG, Thompson CJ, Hemkens LG, Hunter SJ, Sherlock M, Levy MJ, Karavitaki N, Newell-Price J, Wass JAH, Christ-Crain M
Lancet Diabetes Endocrinol 2022 Oct;10(10):700-709. Epub 2022 Aug 22 doi: 10.1016/S2213-8587(22)00219-4. PMID: 36007536
Chiovato L, Magri F, Carlé A
Adv Ther 2019 Sep;36(Suppl 2):47-58. Epub 2019 Sep 4 doi: 10.1007/s12325-019-01080-8. PMID: 31485975Free PMC Article
Wit JM, Balen HV, Kamp GA, Oostdijk W
Eur J Endocrinol 2004 Aug;151 Suppl 1:S41-5. doi: 10.1530/eje.0.151s041. PMID: 15339243
Weltman A, Weltman JY, Veldhuis JD, Hartman ML
Eat Weight Disord 2001 Sep;6(3 Suppl):28-37. PMID: 11706505
Hermens WA, Belder CW, Merkus JM, Hooymans PM, Verhoef J, Merkus FW
Eur J Obstet Gynecol Reprod Biol 1991 Jun 5;40(1):35-41. doi: 10.1016/0028-2243(91)90042-j. PMID: 1906815

Prognosis

Hirai Y, Asahata S, Ainoda Y, Fujita T, Miura H, Hizuka N, Kikuchi K
Mycopathologia 2015 Aug;180(1-2):111-6. Epub 2015 Apr 8 doi: 10.1007/s11046-015-9884-3. PMID: 25851027
Lin-Su K, Harbison MD, Lekarev O, Vogiatzi MG, New MI
J Clin Endocrinol Metab 2011 Jun;96(6):1710-7. Epub 2011 Mar 30 doi: 10.1210/jc.2010-2699. PMID: 21450983Free PMC Article
Delemarre EM, Felius B, Delemarre-van de Waal HA
Eur J Endocrinol 2008 Dec;159 Suppl 1:S9-15. Epub 2008 Sep 16 doi: 10.1530/EJE-08-0314. PMID: 18796540
Wit JM, Balen HV, Kamp GA, Oostdijk W
Eur J Endocrinol 2004 Aug;151 Suppl 1:S41-5. doi: 10.1530/eje.0.151s041. PMID: 15339243
Abayomi OK, Sadeghi-Nejad A
Int J Radiat Oncol Biol Phys 1986 Jun;12(6):945-8. doi: 10.1016/0360-3016(86)90390-1. PMID: 3721935

Clinical prediction guides

Tosetto A, Castaman G
Blood 2015 Feb 5;125(6):907-14. Epub 2014 Dec 4 doi: 10.1182/blood-2014-08-551960. PMID: 25477497
Shioda Y, Adachi S, Imashuku S, Kudo K, Imamura T, Morimoto A
Int J Hematol 2011 Dec;94(6):545-51. Epub 2011 Nov 17 doi: 10.1007/s12185-011-0965-x. PMID: 22139588
Lin-Su K, Harbison MD, Lekarev O, Vogiatzi MG, New MI
J Clin Endocrinol Metab 2011 Jun;96(6):1710-7. Epub 2011 Mar 30 doi: 10.1210/jc.2010-2699. PMID: 21450983Free PMC Article
Carel JC, Coste J, Gendrel C, Chaussain JL
Growth Horm IGF Res 1998 Feb;8 Suppl A:1-8. doi: 10.1016/s1096-6374(98)80001-4. PMID: 10993583
Kliesch S, Behre HM, Nieschlag E
Fertil Steril 1995 Jun;63(6):1326-8. doi: 10.1016/s0015-0282(16)57619-5. PMID: 7750608

Recent systematic reviews

Wang F, Shi X, Yu X, Yang Y
Front Endocrinol (Lausanne) 2024;15:1326684. Epub 2024 Jan 22 doi: 10.3389/fendo.2024.1326684. PMID: 38318292Free PMC Article
Jadhav S, Diwaker C, Lila AR, Gada JV, Kale S, Sarathi V, Thadani PM, Arya S, Patil VA, Shah NS, Bandgar TR
Pituitary 2021 Oct;24(5):657-669. Epub 2021 Mar 20 doi: 10.1007/s11102-021-01140-9. PMID: 33742319
De Rienzo F, Mellone S, Bellone S, Babu D, Fusco I, Prodam F, Petri A, Muniswamy R, De Luca F, Salerno M, Momigliano-Richardi P, Bona G, Giordano M; Italian Study Group on Genetics of CPHD
Clin Endocrinol (Oxf) 2015 Dec;83(6):849-60. Epub 2015 Aug 6 doi: 10.1111/cen.12849. PMID: 26147833
Kreitschmann-Andermahr I, Siegel S, Weber Carneiro R, Maubach JM, Harbeck B, Brabant G
Clin Endocrinol (Oxf) 2013 Dec;79(6):760-9. Epub 2013 Sep 20 doi: 10.1111/cen.12314. PMID: 23941570
Davidson P, Milne R, Chase D, Cooper C
Clin Endocrinol (Oxf) 2004 Jan;60(1):92-8. doi: 10.1111/j.1365-2265.2004.01935.x. PMID: 14678294

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