MCID: PTT041
MIFTS: 47

Pituitary Stalk Interruption Syndrome

Categories: Rare diseases, Neuronal diseases, Endocrine diseases

Aliases & Classifications for Pituitary Stalk Interruption Syndrome

MalaCards integrated aliases for Pituitary Stalk Interruption Syndrome:

Name: Pituitary Stalk Interruption Syndrome 49 55 69
Ectopic Neurohypophysis 49 55
Psis 49 55

Characteristics:

Orphanet epidemiological data:

55
pituitary stalk interruption syndrome
Inheritance: Autosomal dominant,Autosomal recessive,Not applicable; Age of onset: Childhood; Age of death: early childhood;

HPO:

31
pituitary stalk interruption syndrome:
Mortality/Aging death in infancy


Classifications:

Orphanet: 55  
Rare endocrine diseases


Summaries for Pituitary Stalk Interruption Syndrome

NIH Rare Diseases : 49 Pituitary stalk interruption syndrome (PSIS) is a congenital abnormality of the pituitary gland  characterized by the triad of a very thin or interrupted pituitary stalk, a misplaced (ectopic) or absent posterior pituitary and a small or absent anterior pituitary, with permanent growth hormone (GH) deficit. Signs and symptoms in newborns include low blood sugar levels (hypoglycemia), jaundice, congenital abnormalities and small penis (micropenis) and/or testis that are not in the scrotal sac (cryptorchidism). Later in childhood, signs may include short stature, seizures, low arterial pressure (hypotension) and/or intellectual delay. Some people can also have vision problems (septooptic dysplasia) and Fanconi anemia. The cause of this condition is unknown.  Rare mutations in the HESX1, LHX4, OTX2, SOX3, and PROKR2 genes can be the cause in familial cases. The diagnosis is confirmed through MRI showing the characteristic findings. Treatment is based on replacement of deficient hormones, particularly GH, and should be started at birth to avoid hormone deficiencies and intellectual delay. Last updated: 1/28/2017

MalaCards based summary : Pituitary Stalk Interruption Syndrome, also known as ectopic neurohypophysis, is related to combined pituitary hormone deficiency and holoprosencephaly, and has symptoms including ectopic posterior pituitary, failure to thrive and short stature. An important gene associated with Pituitary Stalk Interruption Syndrome is LHX4 (LIM Homeobox 4), and among its related pathways/superpathways are Ectoderm Differentiation and Hedgehog Pathway. The drugs Testosterone and Benzocaine have been mentioned in the context of this disorder. Affiliated tissues include pituitary, testis and hypothalamus, and related phenotypes are behavior/neurological and growth/size/body region

Related Diseases for Pituitary Stalk Interruption Syndrome

Diseases related to Pituitary Stalk Interruption Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 57)
# Related Disease Score Top Affiliating Genes
1 combined pituitary hormone deficiency 30.2 HESX1 LHX4 POU1F1
2 holoprosencephaly 29.6 CDON SHH TGIF1
3 growth hormone deficiency 29.5 GH1 GHRHR HESX1 SOX3
4 pituitary hypoplasia 28.8 GHRHR HESX1 LHX4 POU1F1 PRL SOX3
5 pituitary hormone deficiency, combined, 2 28.7 GH1 HESX1 LHX4 POU1F1 PRL SOX3
6 hypopituitarism 28.7 GH1 HESX1 LHX4 POU1F1 PRL SOX3
7 central congenital hypothyroidism 11.2
8 isolated growth hormone deficiency, type iii 10.3 HESX1 SOX3
9 central nervous system organ benign neoplasm 10.3 HESX1 PRL
10 normosmic congenital hypogonadotropic hypogonadism 10.3 PROKR2 WDR11
11 hypothyroidism due to deficient transcription factors involved in pituitary development or function 10.2 HESX1 LHX4 POU1F1
12 combined pituitary hormone deficiencies, genetic forms 10.2 HESX1 LHX4 POU1F1
13 fibrous dysplasia/mccune-albright syndrome 10.1 GH1 PRL
14 tsh producing pituitary tumor 10.1 GH1 PRL
15 adenohypophysitis 10.1 GH1 PRL
16 pseudohypoparathyroidism, type ia 10.1 GH1 PRL
17 hypothalamic disease 10.1 GH1 PRL
18 growth hormone secreting pituitary adenoma 10.1 GHRHR PRL
19 pituitary adenoma 1, multiple types 10.1 GH1 PRL
20 kallmann syndrome 10.0 HESX1 PROKR2 WDR11
21 pneumonia 10.0
22 gigantism 10.0 GH1 PRL
23 empty sella syndrome 10.0 GH1 PRL
24 hyperpituitarism 10.0 GH1 PRL
25 insulin-like growth factor i 10.0
26 cholestasis 10.0
27 functioning pituitary adenoma 10.0 GH1 PRL
28 holoprosencephaly 4 9.9 SHH TGIF1
29 septooptic dysplasia 9.9 HESX1 LHX4 POU1F1 SOX3
30 borjeson-forssman-lehmann syndrome 9.9 HESX1 LHX4 POU1F1 SOX3
31 isolated growth hormone deficiency, type ib 9.9 GH1 GHRHR
32 tetrahydrobiopterin deficiency 9.9 GH1 PRL
33 chromophobe adenoma 9.8 GH1 PRL
34 septopreoptic holoprosencephaly 9.8 CDON SHH TGIF1
35 midline interhemispheric variant of holoprosencephaly 9.8 CDON SHH TGIF1
36 arthropathy 9.8
37 blood group, i system 9.8
38 esterase b 9.8
39 schizophrenia 9.8
40 lung cancer 9.8
41 leukemia 9.8
42 thrombocytopenia 9.8
43 immunoglobulin alpha deficiency 9.8
44 thrombocytopenia due to platelet alloimmunization 9.8
45 adenocarcinoma 9.8
46 microform holoprosencephaly 9.8 CDON SHH TGIF1
47 alobar holoprosencephaly 9.8 CDON SHH TGIF1
48 lobar holoprosencephaly 9.8 CDON SHH TGIF1
49 semilobar holoprosencephaly 9.8 CDON SHH TGIF1
50 hypothyroidism, congenital, nongoitrous, 4 9.8 GH1 POU1F1 PRL

Graphical network of the top 20 diseases related to Pituitary Stalk Interruption Syndrome:



Diseases related to Pituitary Stalk Interruption Syndrome

Symptoms & Phenotypes for Pituitary Stalk Interruption Syndrome

Human phenotypes related to Pituitary Stalk Interruption Syndrome:

55 31 (show all 17)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 ectopic posterior pituitary 55 31 obligate (100%) Obligate (100%) HP:0011755
2 failure to thrive 55 31 hallmark (90%) Very frequent (99-80%) HP:0001508
3 short stature 55 31 hallmark (90%) Very frequent (99-80%) HP:0004322
4 hypothyroidism 55 31 frequent (33%) Frequent (79-30%) HP:0000821
5 delayed puberty 55 31 frequent (33%) Frequent (79-30%) HP:0000823
6 hypoglycemia 55 31 frequent (33%) Frequent (79-30%) HP:0001943
7 hypoplasia of penis 55 31 frequent (33%) Frequent (79-30%) HP:0008736
8 cryptorchidism 55 31 occasional (7.5%) Occasional (29-5%) HP:0000028
9 primary amenorrhea 55 31 occasional (7.5%) Occasional (29-5%) HP:0000786
10 adrenal hypoplasia 55 31 occasional (7.5%) Occasional (29-5%) HP:0000835
11 diabetes insipidus 55 31 occasional (7.5%) Occasional (29-5%) HP:0000873
12 intellectual disability 55 31 occasional (7.5%) Occasional (29-5%) HP:0001249
13 seizures 55 31 occasional (7.5%) Occasional (29-5%) HP:0001250
14 global developmental delay 55 31 occasional (7.5%) Occasional (29-5%) HP:0001263
15 septo-optic dysplasia 55 31 occasional (7.5%) Occasional (29-5%) HP:0100842
16 abnormality of the hypothalamus-pituitary axis 55 Very frequent (99-80%)
17 death in infancy 55 Occasional (29-5%)

MGI Mouse Phenotypes related to Pituitary Stalk Interruption Syndrome:

43 (show all 11)
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 10.15 CDON GHRHR PRL GPR161 PROKR2 ROBO1
2 growth/size/body region MP:0005378 10.13 CDON POU1F1 GHRHR GPR161 PROKR2 HESX1
3 endocrine/exocrine gland MP:0005379 10.11 POU1F1 GHRHR PRL PROKR2 ROBO1 HESX1
4 nervous system MP:0003631 10.1 POU1F1 GHRHR PRL PROKR2 GPR161 ROBO1
5 craniofacial MP:0005382 10.08 POU1F1 GPR161 ROBO1 HESX1 CDON SHH
6 mortality/aging MP:0010768 10.07 CDON POU1F1 GPR161 PROKR2 HESX1 ROBO1
7 reproductive system MP:0005389 9.86 POU1F1 GHRHR PRL PROKR2 ROBO1 SHH
8 limbs/digits/tail MP:0005371 9.8 CDON GHRHR GPR161 SHH TGIF1
9 respiratory system MP:0005388 9.63 LHX4 CDON HESX1 SHH TGIF1 ROBO1
10 skeleton MP:0005390 9.5 CDON POU1F1 GHRHR SHH SOX3 TGIF1
11 taste/olfaction MP:0005394 8.8 HESX1 SHH TGIF1

Drugs & Therapeutics for Pituitary Stalk Interruption Syndrome

Drugs for Pituitary Stalk Interruption Syndrome (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 6)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Testosterone Approved, Investigational 58-22-0 6013
2
Benzocaine Approved, Investigational 1994-09-7, 94-09-7 2337
3 tannic acid Approved, Nutraceutical
4 Hormone Antagonists
5 Hormones
6 Hormones, Hormone Substitutes, and Hormone Antagonists

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Efficacy of Pulsatile GnRH Therapy on Male Patients With Pituitary Stalk Interruption Syndrome Unknown status NCT02705014 Gonadotropin-releasing Hormone

Search NIH Clinical Center for Pituitary Stalk Interruption Syndrome

Genetic Tests for Pituitary Stalk Interruption Syndrome

Anatomical Context for Pituitary Stalk Interruption Syndrome

MalaCards organs/tissues related to Pituitary Stalk Interruption Syndrome:

38
Pituitary, Testis, Hypothalamus

Publications for Pituitary Stalk Interruption Syndrome

Articles related to Pituitary Stalk Interruption Syndrome:

(show all 41)
# Title Authors Year
1
Vitamin D in children with growth hormone deficiency due to pituitary stalk interruption syndrome. ( 29368588 )
2018
2
Clues for Polygenic Inheritance of Pituitary Stalk Interruption Syndrome From Exome Sequencing in 20 Patients. ( 29165578 )
2018
3
Growth without growth hormone in combined pituitary hormone deficiency caused by pituitary stalk interruption syndrome. ( 28443260 )
2017
4
Multi-genic pattern found in rare type of hypopituitarism: a whole-exome sequencing study of Han Chinese with pituitary stalk interruption syndrome. ( 28707430 )
2017
5
Delayed diagnosis of pituitary stalk interruption syndrome with severe recurrent hyponatremia caused by adrenal insufficiency. ( 29025209 )
2017
6
Digenic Inheritance of PROKR2 and WDR11 Mutations in Pituitary Stalk Interruption Syndrome. ( 28453858 )
2017
7
Mutations in the Human ROBO1 Gene in Pituitary Stalk Interruption Syndrome. ( 28402530 )
2017
8
Pituitary stalk interruption syndrome: a rare and severe cause of pituitary deficiency Laboratory diagnosis of a newborn case. ( 28251898 )
2017
9
A case of pituitary stalk interruption syndrome with intermittent seizures as the first presentation. ( 28326739 )
2016
10
Pituitary Stalk Interruption Syndrome Presenting With Growth Retardation. ( 27238408 )
2016
11
Clinical Features of Pituitary Stalk Interruption Syndrome in 114 Cases. ( 27825409 )
2016
12
Growth Hormone Therapy Benefits Pituitary Stalk Interruption Syndrome Patients with Short Stature: A Retrospective Study of 75 Han Chinese. ( 27190512 )
2016
13
Pituitary stalk interruption syndrome: cause, clinical manifestations, diagnosis, and management. ( 27386973 )
2016
14
Correlation between Pituitary Stalk Interruption Syndrome and Prokineticin Receptor 2 and Prokineticin 2 Mutations. ( 26956854 )
2016
15
Pituitary stalk interruption syndrome: From clinical findings to pathogenesis. ( 27917547 )
2016
16
Cholestasis Reveals Severe Cortisol Deficiency in Neonatal Pituitary Stalk Interruption Syndrome. ( 26829045 )
2016
17
A nonsense mutation in the hedgehog receptor CDON associated with pituitary stalk interruption syndrome. ( 26529631 )
2015
18
Pituitary Stalk Interruption Syndrome from Infancy to Adulthood: Clinical, Hormonal, and Radiological Assessment According to the Initial Presentation. ( 26562670 )
2015
19
Relationship between pituitary stalk visibility and the severity of hormone deficiencies: Pituitary stalk interruption syndrome revisited. ( 25845766 )
2015
20
Whole exome sequencing identifies homozygous GPR161 mutation in a family with pituitary stalk interruption syndrome. ( 25322266 )
2014
21
Pituitary stalk interruption syndrome presenting as short stature: a case report. ( 25524465 )
2014
22
Pituitary stalk interruption syndrome: Case report of three cases with review of literature. ( 25250085 )
2014
23
Pituitary stalk interruption syndrome in 53 postpubertal patients: factors influencing the heterogeneity of its presentation. ( 23308160 )
2013
24
Pituitary stalk interruption syndrome in 58 Chinese patients: clinical features and genetic analysis. ( 23199197 )
2013
25
Pituitary stalk interruption syndrome and isolated pituitary hypoplasia may be caused by mutations in holoprosencephaly-related genes. ( 23476075 )
2013
26
Pituitary stalk interruption syndrome. ( 24617191 )
2013
27
Pituitary stalk interruption syndrome in Chinese people: clinical characteristic analysis of 55 cases. ( 23341953 )
2013
28
Pituitary stalk interruption syndrome in 59 children: the value of MRI in assessment of pituitary functions. ( 24257915 )
2013
29
Pituitary stalk interruption syndrome: diagnostic delay and sensitivity of the auxological criteria of the growth hormone research society. ( 21298012 )
2011
30
Pituitary stalk interruption syndrome in 83 patients: novel HESX1 mutation and severe hormonal prognosis in malformative forms. ( 21270112 )
2011
31
Magnetic resonance image of sellar region in pituitary stalk interruption syndrome in children and adolescents. ( 21375930 )
2011
32
17q21.31 microdeletion in a patient with pituitary stalk interruption syndrome. ( 21397059 )
2011
33
Pituitary stalk interruption syndrome: the role of MRI and review of the literature. ( 24148682 )
2010
34
The pituitary stalk interruption syndrome: endocrine features and benefits of growth hormone therapy. ( 20044069 )
2010
35
Diagnosis of growth hormone (GH) deficiency: comparison of pituitary stalk interruption syndrome and transient GH deficiency. ( 19419564 )
2009
36
Gonadotrophic status in adolescents with pituitary stalk interruption syndrome. ( 18088398 )
2008
37
Factors influencing the growth hormone peak and plasma insulin-like growth factor I in young adults with pituitary stalk interruption syndrome. ( 18620575 )
2008
38
Pituitary stalk interruption syndrome (PSIS). ( 17901685 )
2007
39
Long-term evolution of endocrine disorders and effect of GH therapy in 35 patients with pituitary stalk interruption syndrome. ( 16260897 )
2005
40
Growth hormone deficiency associated with pituitary stalk interruption syndrome. ( 9554478 )
1998
41
Pituitary stalk interruption syndrome: a clinical-biological-genetic assessment of its pathogenesis. ( 9329385 )
1997

Variations for Pituitary Stalk Interruption Syndrome

Expression for Pituitary Stalk Interruption Syndrome

Search GEO for disease gene expression data for Pituitary Stalk Interruption Syndrome.

Pathways for Pituitary Stalk Interruption Syndrome

GO Terms for Pituitary Stalk Interruption Syndrome

Cellular components related to Pituitary Stalk Interruption Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 endosome lumen GO:0031904 8.62 GH1 PRL

Biological processes related to Pituitary Stalk Interruption Syndrome according to GeneCards Suite gene sharing:

(show all 15)
# Name GO ID Score Top Affiliating Genes
1 negative regulation of transcription by RNA polymerase II GO:0000122 9.93 HESX1 POU1F1 SHH SOX3 TGIF1
2 multicellular organism development GO:0007275 9.91 GPR161 HESX1 ROBO1 SHH SOX3 TGIF1
3 positive regulation of JAK-STAT cascade GO:0046427 9.55 GH1 PRL
4 embryonic morphogenesis GO:0048598 9.52 CDON SHH
5 JAK-STAT cascade involved in growth hormone signaling pathway GO:0060397 9.51 GH1 PRL
6 determination of adult lifespan GO:0008340 9.49 GHRHR POU1F1
7 positive regulation of insulin-like growth factor receptor signaling pathway GO:0043568 9.48 GH1 GHRHR
8 striated muscle cell differentiation GO:0051146 9.46 CDON SHH
9 positive regulation of multicellular organism growth GO:0040018 9.43 GH1 GHRHR POU1F1
10 adenohypophysis development GO:0021984 9.4 GHRHR POU1F1
11 positive regulation of skeletal muscle tissue development GO:0048643 9.37 CDON SHH
12 pituitary gland development GO:0021983 9.33 HESX1 POU1F1 SOX3
13 regulation of insulin-like growth factor receptor signaling pathway GO:0043567 9.32 GHRHR POU1F1
14 somatotropin secreting cell development GO:0060133 8.96 GHRHR POU1F1
15 cell fate specification GO:0001708 8.8 CDON POU1F1 SHH

Molecular functions related to Pituitary Stalk Interruption Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 prolactin receptor binding GO:0005148 8.62 GH1 PRL

Sources for Pituitary Stalk Interruption Syndrome

3 CDC
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9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
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29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
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35 IUPHAR
36 KEGG
37 LifeMap
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41 MeSH
42 MESH via Orphanet
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50 NINDS
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54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
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67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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