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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.
Reduced circulating growth hormone concentration
MedGen UID:
82880
Concept ID:
C0271561
Disease or Syndrome
Concentration of growth hormone in the blood circulation below normal limits.
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).
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
Binder G, Weber K, Rieflin N, Steinruck L, Blumenstock G, Janzen N, Franz AR
Clin Endocrinol (Oxf) 2020 Sep;93(3):305-311. Epub 2020 Jun 29 doi: 10.1111/cen.14264. PMID: 32521075
Falsetti L, Gambera A, Platto C, Legrenzi L
Am J Clin Dermatol 2000 Mar-Apr;1(2):89-99. doi: 10.2165/00128071-200001020-00003. PMID: 11702316

Recent clinical studies

Etiology

Jakobsen LK, Jensen RB, Birkebæk NH, Hansen D, Christensen AR, Bjerrum MC, Christesen HT
J Clin Endocrinol Metab 2023 Sep 18;108(10):2475-2485. doi: 10.1210/clinem/dgad198. PMID: 37043518Free PMC Article
Chanson P, Brochier S
J Endocrinol Invest 2005;28(11 Suppl International):93-9. PMID: 16625856
Honke K, Taniguchi N
Med Res Rev 2002 Nov;22(6):637-54. doi: 10.1002/med.10020. PMID: 12369092
Falsetti L, Gambera A, Platto C, Legrenzi L
Am J Clin Dermatol 2000 Mar-Apr;1(2):89-99. doi: 10.2165/00128071-200001020-00003. PMID: 11702316
Pombo M, Leal-Cerro A, Barreiro J, Peñalva A, Peino R, Mallo F, Dieguez C, Casanueva FF
J Pediatr Endocrinol Metab 1996 Jun;9 Suppl 3:333-8. PMID: 8887178

Diagnosis

Das L, Dutta P
Best Pract Res Clin Endocrinol Metab 2023 Dec;37(6):101820. Epub 2023 Aug 28 doi: 10.1016/j.beem.2023.101820. PMID: 37704550
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
Giordano M
Best Pract Res Clin Endocrinol Metab 2016 Dec;30(6):679-691. Epub 2016 Oct 15 doi: 10.1016/j.beem.2016.09.005. PMID: 27974184
Fang Q, George AS, Brinkmeier ML, Mortensen AH, Gergics P, Cheung LY, Daly AZ, Ajmal A, Pérez Millán MI, Ozel AB, Kitzman JO, Mills RE, Li JZ, Camper SA
Endocr Rev 2016 Dec;37(6):636-675. Epub 2016 Nov 9 doi: 10.1210/er.2016-1101. PMID: 27828722Free PMC Article

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
Eskes SA, Wiersinga WM
Best Pract Res Clin Endocrinol Metab 2009 Dec;23(6):735-51. doi: 10.1016/j.beem.2009.07.001. PMID: 19942150
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
Falsetti L, Gambera A, Platto C, Legrenzi L
Am J Clin Dermatol 2000 Mar-Apr;1(2):89-99. doi: 10.2165/00128071-200001020-00003. PMID: 11702316

Prognosis

Jakobsen LK, Jensen RB, Birkebæk NH, Hansen D, Christensen AR, Bjerrum MC, Christesen HT
J Clin Endocrinol Metab 2023 Sep 18;108(10):2475-2485. doi: 10.1210/clinem/dgad198. PMID: 37043518Free PMC Article
Di Iorgi N, Morana G, Allegri AE, Napoli F, Gastaldi R, Calcagno A, Patti G, Loche S, Maghnie M
Best Pract Res Clin Endocrinol Metab 2016 Dec;30(6):705-736. Epub 2016 Nov 24 doi: 10.1016/j.beem.2016.11.008. PMID: 27974186
Fang Q, George AS, Brinkmeier ML, Mortensen AH, Gergics P, Cheung LY, Daly AZ, Ajmal A, Pérez Millán MI, Ozel AB, Kitzman JO, Mills RE, Li JZ, Camper SA
Endocr Rev 2016 Dec;37(6):636-675. Epub 2016 Nov 9 doi: 10.1210/er.2016-1101. PMID: 27828722Free PMC Article
Vantyghem MC, Balavoine AS, Wémeau JL, Douillard C
Ann Endocrinol (Paris) 2011 Dec;72(6):500-12. Epub 2011 Nov 25 doi: 10.1016/j.ando.2011.10.001. PMID: 22119069
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

Clinical prediction guides

Jakobsen LK, Jensen RB, Birkebæk NH, Hansen D, Christensen AR, Bjerrum MC, Christesen HT
J Clin Endocrinol Metab 2023 Sep 18;108(10):2475-2485. doi: 10.1210/clinem/dgad198. PMID: 37043518Free PMC Article
Fang Q, George AS, Brinkmeier ML, Mortensen AH, Gergics P, Cheung LY, Daly AZ, Ajmal A, Pérez Millán MI, Ozel AB, Kitzman JO, Mills RE, Li JZ, Camper SA
Endocr Rev 2016 Dec;37(6):636-675. Epub 2016 Nov 9 doi: 10.1210/er.2016-1101. PMID: 27828722Free PMC Article
Spreafico M, Peyvandi F
Haemophilia 2008 Nov;14(6):1201-8. doi: 10.1111/j.1365-2516.2008.01845.x. PMID: 19141160
Chanson P, Brochier S
J Endocrinol Invest 2005;28(11 Suppl International):93-9. PMID: 16625856
Pombo M, Leal-Cerro A, Barreiro J, Peñalva A, Peino R, Mallo F, Dieguez C, Casanueva FF
J Pediatr Endocrinol Metab 1996 Jun;9 Suppl 3:333-8. PMID: 8887178

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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