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Combined pituitary hormone deficiencies, genetic form

MedGen UID:
906592
Concept ID:
C4273747
Disease or Syndrome
Synonym: Pituitary hormone deficiency, combined
SNOMED CT: Familial congenital hypopituitarism (718182008); Combined pituitary hormone deficiency genetic form (718182008); Multiple pituitary hormone deficiency genetic form (718182008)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
X-linked recessive inheritance
MedGen UID:
375779
Concept ID:
C1845977
Finding
Source: Orphanet
A mode of inheritance that is observed for recessive traits related to a gene encoded on the X chromosome. In the context of medical genetics, X-linked recessive disorders manifest in males (who have one copy of the X chromosome and are thus hemizygotes), but generally not in female heterozygotes who have one mutant and one normal allele.
 
Related genes: LHX4, LHX3, PROP1, POU1F1, OTX2
 
Monarch Initiative: MONDO:0013099
OMIM® Phenotypic series: PS613038
Orphanet: ORPHA95494

Definition

Combined pituitary hormone deficiency is a condition that causes a shortage (deficiency) of several hormones produced by the pituitary gland, which is located at the base of the brain. A lack of these hormones may affect the development of many parts of the body. The first signs of this condition include a failure to grow at the expected rate and short stature that usually becomes apparent in early childhood.

People with combined pituitary hormone deficiency may have hypothyroidism, which is underactivity of the butterfly-shaped thyroid gland in the lower neck. Hypothyroidism can cause many symptoms, including weight gain and fatigue. Other features of combined pituitary hormone deficiency include delayed or absent puberty and lack the ability to have biological children (infertility). The condition can also be associated with a deficiency of the hormone cortisol. Cortisol deficiency can impair the body's immune system, causing individuals to be more susceptible to infection.

Rarely, people with combined pituitary hormone deficiency have intellectual disability; a short, stiff neck; or underdeveloped optic nerves, which carry visual information from the eyes to the brain. [from MedlinePlus Genetics]

Professional guidelines

PubMed

Castets S, Albarel F, Bachelot A, Brun G, Bouligand J, Briet C, Bui Quoc E, Cazabat L, Chabbert-Buffet N, Christin-Maitre S, Courtillot C, Cuny T, De Filippo G, Donadille B, Illouz F, Pellegrini I, Reznik Y, Saveanu A, Teissier N, Touraine P, Vantyghem MC, Vergier J, Léger J, Brue T, Reynaud R
Ann Endocrinol (Paris) 2024 Jul;85(4):327-339. Epub 2024 Mar 5 doi: 10.1016/j.ando.2024.03.001. PMID: 38452869
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Eur J Endocrinol 2010 May;162(5):835-51. Epub 2010 Mar 5 doi: 10.1530/EJE-10-0083. PMID: 20207726
Bachega TA, Billerbeck AE, Marcondes JA, Madureira G, Arnhold IJ, Mendonca BB
Clin Endocrinol (Oxf) 2000 May;52(5):601-7. doi: 10.1046/j.1365-2265.2000.00995.x. PMID: 10792340

Recent clinical studies

Etiology

Castets S, Albarel F, Bachelot A, Brun G, Bouligand J, Briet C, Bui Quoc E, Cazabat L, Chabbert-Buffet N, Christin-Maitre S, Courtillot C, Cuny T, De Filippo G, Donadille B, Illouz F, Pellegrini I, Reznik Y, Saveanu A, Teissier N, Touraine P, Vantyghem MC, Vergier J, Léger J, Brue T, Reynaud R
Ann Endocrinol (Paris) 2024 Jul;85(4):327-339. Epub 2024 Mar 5 doi: 10.1016/j.ando.2024.03.001. PMID: 38452869
Lee SC, Baranowski ES, Sakremath R, Saraff V, Mohamed Z
Front Endocrinol (Lausanne) 2023;14:1198519. Epub 2023 Nov 20 doi: 10.3389/fendo.2023.1198519. PMID: 38053731Free PMC Article
Bonomi M, Libri DV, Guizzardi F, Guarducci E, Maiolo E, Pignatti E, Asci R, Persani L; Idiopathic Central Hypogonadism Study Group of the Italian Societies of Endocrinology and Pediatric Endocrinology and Diabetes
Asian J Androl 2012 Jan;14(1):49-56. Epub 2011 Dec 5 doi: 10.1038/aja.2011.68. PMID: 22138902Free PMC Article
Tenenbaum-Rakover Y, Sobrier ML, Amselem S
Clin Endocrinol (Oxf) 2011 Aug;75(2):214-9. doi: 10.1111/j.1365-2265.2011.04028.x. PMID: 21521297
Libber SM, Migeon CJ, Bias WB
J Clin Endocrinol Metab 1985 Apr;60(4):727-30. doi: 10.1210/jcem-60-4-727. PMID: 3871788

Diagnosis

Castets S, Albarel F, Bachelot A, Brun G, Bouligand J, Briet C, Bui Quoc E, Cazabat L, Chabbert-Buffet N, Christin-Maitre S, Courtillot C, Cuny T, De Filippo G, Donadille B, Illouz F, Pellegrini I, Reznik Y, Saveanu A, Teissier N, Touraine P, Vantyghem MC, Vergier J, Léger J, Brue T, Reynaud R
Ann Endocrinol (Paris) 2024 Jul;85(4):327-339. Epub 2024 Mar 5 doi: 10.1016/j.ando.2024.03.001. PMID: 38452869
Lee SC, Baranowski ES, Sakremath R, Saraff V, Mohamed Z
Front Endocrinol (Lausanne) 2023;14:1198519. Epub 2023 Nov 20 doi: 10.3389/fendo.2023.1198519. PMID: 38053731Free 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
Wit JM, Oostdijk W, Losekoot M, van Duyvenvoorde HA, Ruivenkamp CA, Kant SG
Eur J Endocrinol 2016 Apr;174(4):R145-73. Epub 2015 Nov 17 doi: 10.1530/EJE-15-0937. PMID: 26578640
Pfäffle R, Kim C, Otten B, Wit JM, Eiholzer U, Heimann G, Parks J
Horm Res 1996;45 Suppl 1:25-8. doi: 10.1159/000184824. PMID: 8805025

Therapy

Lee SC, Baranowski ES, Sakremath R, Saraff V, Mohamed Z
Front Endocrinol (Lausanne) 2023;14:1198519. Epub 2023 Nov 20 doi: 10.3389/fendo.2023.1198519. PMID: 38053731Free PMC Article
Yanus GA, Akhapkina TA, Whitehead AJ, Bizin IV, Iyevleva AG, Kuligina ES, Aleksakhina SN, Anisimova MO, Holmatov MM, Romanko AA, Zaitseva OA, Yatsuk OS, Zagorodnev KA, Matsneva MA, Koloskov AV, Togo AV, Suspitsin EN, Imyanitov EN
Eur J Med Genet 2019 Jul;62(7):103656. Epub 2019 Apr 24 doi: 10.1016/j.ejmg.2019.04.013. PMID: 31028847
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
Concolino D, Muzzi G, Rapsomaniki M, Moricca MT, Pascale MG, Strisciuglio P
J Inherit Metab Dis 2008 Dec;31 Suppl 2:S193-7. Epub 2008 Apr 15 doi: 10.1007/s10545-007-0788-3. PMID: 18425437
Shoham Z, Homburg R, Jacobs HS
Baillieres Clin Obstet Gynaecol 1990 Sep;4(3):589-608. doi: 10.1016/s0950-3552(05)80312-8. PMID: 2282743

Prognosis

Almatrafi AM, Hibshi AM, Basit S
Medicina (Kaunas) 2023 Feb 27;59(3) doi: 10.3390/medicina59030474. PMID: 36984475Free PMC Article
Cangiano B, Swee DS, Quinton R, Bonomi M
Hum Genet 2021 Jan;140(1):77-111. Epub 2020 Mar 21 doi: 10.1007/s00439-020-02147-1. PMID: 32200437
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
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
Rosenfeld RG, Kofoed E, Little B, Woods K, Buckway C, Pratt K, Hwa V
Growth Horm IGF Res 2004 Jun;14 Suppl A:S35-8. doi: 10.1016/j.ghir.2004.03.009. PMID: 15135774

Clinical prediction guides

Almatrafi AM, Hibshi AM, Basit S
Medicina (Kaunas) 2023 Feb 27;59(3) doi: 10.3390/medicina59030474. PMID: 36984475Free PMC Article
Voutetakis A
Handb Clin Neurol 2021;181:9-27. doi: 10.1016/B978-0-12-820683-6.00002-6. PMID: 34238482
Cangiano B, Swee DS, Quinton R, Bonomi M
Hum Genet 2021 Jan;140(1):77-111. Epub 2020 Mar 21 doi: 10.1007/s00439-020-02147-1. PMID: 32200437
Bonomi M, Libri DV, Guizzardi F, Guarducci E, Maiolo E, Pignatti E, Asci R, Persani L; Idiopathic Central Hypogonadism Study Group of the Italian Societies of Endocrinology and Pediatric Endocrinology and Diabetes
Asian J Androl 2012 Jan;14(1):49-56. Epub 2011 Dec 5 doi: 10.1038/aja.2011.68. PMID: 22138902Free PMC Article
Pfaeffle RW, Hunter CS, Savage JJ, Duran-Prado M, Mullen RD, Neeb ZP, Eiholzer U, Hesse V, Haddad NG, Stobbe HM, Blum WF, Weigel JF, Rhodes SJ
J Clin Endocrinol Metab 2008 Mar;93(3):1062-71. Epub 2007 Dec 11 doi: 10.1210/jc.2007-1525. PMID: 18073311Free PMC Article

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