Cushing disease

General Information (adopted from Orphanet):

Synonyms, Signs: CUSHING DISEASE, PITUITARY
Pituitary dependent Cushing syndrome
Pituitary corticotroph micro-adenoma
Corticotroph pituitary adenoma
Number of Symptoms 112
OrphanetNr: 96253
OMIM Id: 219090
ICD-10: E24.0
UMLs: C0221406
MeSH: D047748
MedDRA: 10035109
Snomed: 190502001

Prevalence, inheritance and age of onset:

Prevalence: 4 [Orphanet]
Inheritance:
[Orphanet]
Age of onset: Adult
[Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases: ACTH-dependent Cushing syndrome
 -Rare endocrine disease
Functioning pituitary adenoma
 -Rare endocrine disease
 -Rare genetic disease
 -Rare oncologic disease

Comment:

Symptom Information: Sort by abundance 

1
 (HPO:0000876) Oligomenorrhea 13 / 7739
2
 (HPO:0000789) Infertility Frequent [Orphanet] 74 / 7739
3
 (HPO:0000869) Secondary amenorrhea Occasional [Orphanet] 42 / 7739
4
 (HPO:0100608) Metrorrhagia Frequent [Orphanet] 5 / 7739
5
 (HPO:0100805) Precocious menopause Occasional [Orphanet] 4 / 7739
6
 (HPO:0000144) Decreased fertility Frequent [Orphanet] 11 / 7739
7
 (HPO:0100607) Dysmenorrhea Frequent [Orphanet] 8 / 7739
8
 (HPO:0000132) Menorrhagia Frequent [Orphanet] 40 / 7739
9
 (HPO:0000787) Nephrolithiasis Frequent [Orphanet] 78 / 7739
10
 (HPO:0000311) Round face Very frequent [Orphanet] 104 / 7739
11
 (HPO:0000572) Visual loss Occasional [Orphanet] 272 / 7739
12
 (HPO:0000618) Blindness Occasional [Orphanet] 124 / 7739
13
 (HPO:0000646) Amblyopia Occasional [Orphanet] 42 / 7739
14
 (HPO:0000518) Cataract Occasional [Orphanet] 454 / 7739
15
 (HPO:0000505) Visual impairment Occasional [Orphanet] 297 / 7739
16
 (HPO:0002076) Migraine Occasional [Orphanet] 41 / 7739
17
 (HPO:0000709) Psychosis Occasional [Orphanet] 61 / 7739
18
 (HPO:0100852) Abnormal fear/anxiety-related behavior 2 / 7739
19
 (HPO:0000716) Depression Frequent [Orphanet] 99 / 7739
20
 (HPO:0000737) Irritability Frequent [Orphanet] 93 / 7739
21
 (HPO:0001289) Confusion Occasional [Orphanet] 36 / 7739
22
 (HPO:0001254) Lethargy Occasional [Orphanet] 104 / 7739
23
 (HPO:0000739) Anxiety Frequent [Orphanet] 67 / 7739
24
 (HPO:0007302) Bipolar affective disorder Occasional [Orphanet] 15 / 7739
25
 (HPO:0001259) Coma Occasional [Orphanet] 65 / 7739
26
 (HPO:0002360) Sleep disturbance Occasional [Orphanet] 113 / 7739
27
 (HPO:0004372) Reduced consciousness/confusion Occasional [Orphanet] 73 / 7739
28
 (HPO:0000741) Apathy Frequent [Orphanet] 42 / 7739
29
 (HPO:0001345) Psychotic mentation 2 / 7739
30
 (HPO:0003473) Fatigable weakness Frequent [Orphanet] 39 / 7739
31
 (HPO:0002315) Headache Occasional [Orphanet] 175 / 7739
32
 (HPO:0100753) Schizophrenia Occasional [Orphanet] 20 / 7739
33
 (HPO:0002329) Drowsiness Occasional [Orphanet] 19 / 7739
34
 (HPO:0008221) Adrenal hyperplasia Very frequent [Orphanet] 24 / 7739
35
 (HPO:0001578) Hypercortisolism Very frequent [Orphanet] 17 / 7739
36
 (HPO:0100568) Neoplasm of the endocrine system Very frequent [Orphanet] 2 / 7739
37
 (HPO:0000819) Diabetes mellitus Frequent [Orphanet] 131 / 7739
38
 (HPO:0003154) Increased circulating ACTH level 8 / 7739
39
 (HPO:0002748) Rickets Frequent [Orphanet] 41 / 7739
40
 (HPO:0000939) Osteoporosis Frequent [Orphanet] 129 / 7739
41
 (HPO:0002749) Osteomalacia Frequent [Orphanet] 24 / 7739
42
 (HPO:0002659) Increased susceptibility to fractures Frequent [Orphanet] 110 / 7739
43
 (HPO:0002953) Vertebral compression fractures 14 / 7739
44
 (HPO:0002757) Recurrent fractures Frequent [Orphanet] 47 / 7739
45
 (HPO:0004349) Reduced bone mineral density Frequent [Orphanet] 165 / 7739
46
 (HPO:0004586) Biconcave vertebral bodies 15 / 7739
47
 (HPO:0000938) Osteopenia Frequent [Orphanet] 138 / 7739
48
 (HPO:0002808) Kyphosis 289 / 7739
49
 (HPO:0010885) Aseptic necrosis Occasional [Orphanet] 24 / 7739
50
 (HPO:0006462) Generalized bone demineralization Frequent [Orphanet] 11 / 7739
51
 (HPO:0002027) Abdominal pain Occasional [Orphanet] 184 / 7739
52
 (HPO:0011848) Abdominal colic Occasional [Orphanet] 8 / 7739
53
 (HPO:0002588) Duodenal ulcer Occasional [Orphanet] 15 / 7739
54
 (HPO:0004295) Abnormality of the gastric mucosa Occasional [Orphanet] 4 / 7739
55
 (HPO:0002592) Gastric ulcer Occasional [Orphanet] 39 / 7739
56
 (HPO:0005263) Gastritis Occasional [Orphanet] 9 / 7739
57
 (HPO:0011968) Feeding difficulties Very frequent [Orphanet] 240 / 7739
58
 (HPO:0001956) Truncal obesity Very frequent [Orphanet] 39 / 7739
59
 (HPO:0001508) Failure to thrive Very frequent [Orphanet] 454 / 7739
60
 (HPO:0001513) Obesity 172 / 7739
61
 (HPO:0001510) Growth delay Very frequent [Orphanet] 295 / 7739
62
 (HPO:0000963) Thin skin Very frequent [Orphanet] 96 / 7739
63
 (HPO:0100585) Telangiectasia of the skin Occasional [Orphanet] 66 / 7739
64
 (HPO:0007552) Abnormal subcutaneous fat tissue distribution Very frequent [Orphanet] 12 / 7739
65
 (HPO:0001058) Poor wound healing 9 / 7739
66
 (HPO:0001061) Acne Frequent [Orphanet] 33 / 7739
67
 (HPO:0007440) Generalized hyperpigmentation Occasional [Orphanet] 11 / 7739
68
 (HPO:0001007) Hirsutism Frequent [Orphanet] typical [HPO] 91 / 7739
69
 (HPO:0001009) Telangiectasia Occasional [Orphanet] occasional [HPO] 46 / 7739
70
 (HPO:0004554) Generalized hypertrichosis Frequent [Orphanet] typical [HPO] 30 / 7739
71
 (HPO:0001065) Striae distensae 26 / 7739
72
 (HPO:0001581) Recurrent skin infections Occasional [Orphanet] 9 / 7739
73
 (HPO:0000953) Hyperpigmentation of the skin Occasional [Orphanet] occasional [HPO] 75 / 7739
74
 (HPO:0000998) Hypertrichosis Frequent [Orphanet] 52 / 7739
75
 (HPO:0000978) Bruising susceptibility Frequent [Orphanet] 123 / 7739
76
 (HPO:0000979) Purpura 27 / 7739
77
 (HPO:0001818) Paronychia Occasional [Orphanet] 6 / 7739
78
 (HPO:0200042) Skin ulcer Occasional [Orphanet] 138 / 7739
79
 (HPO:0001041) Facial erythema 8 / 7739
80
 (HPO:0002230) Generalized hirsutism Frequent [Orphanet] typical [HPO] 32 / 7739
81
 (HPO:0000822) Hypertension Frequent [Orphanet] 224 / 7739
82
 (HPO:0001644) Dilated cardiomyopathy Occasional [Orphanet] 141 / 7739
83
 (HPO:0001639) Hypertrophic cardiomyopathy Occasional [Orphanet] 137 / 7739
84
 (HPO:0002625) Deep venous thrombosis Occasional [Orphanet] occasional [HPO] 10 / 7739
85
 (HPO:0004936) Venous thrombosis Occasional [Orphanet] occasional [HPO] 41 / 7739
86
 (HPO:0004418) Thrombophlebitis Occasional [Orphanet] 1 / 7739
87
 (HPO:0000969) Edema 117 / 7739
88
 (HPO:0002900) Hypokalemia Frequent [Orphanet] 45 / 7739
89
 (HPO:0000833) Glucose intolerance 20 / 7739
90
 (HPO:0001948) Alkalosis 4 / 7739
91
 (HPO:0010978) Abnormality of immune system physiology Frequent [Orphanet] 148 / 7739
92
 (HPO:0002721) Immunodeficiency Frequent [Orphanet] 97 / 7739
93
 (HPO:0002718) Recurrent bacterial infections Frequent [Orphanet] 75 / 7739
94
 (HPO:0002719) Recurrent infections Frequent [Orphanet] 107 / 7739
95
 (HPO:0003700) Generalized amyotrophy 39 / 7739
96
 (HPO:0100295) Muscle fiber atrophy 22 / 7739
97
 (HPO:0003202) Skeletal muscle atrophy 281 / 7739
98
 (HPO:0003198) Myopathy Occasional [Orphanet] 151 / 7739
99
 (HPO:0009064) Generalized lipodystrophy Very frequent [Orphanet] 17 / 7739
100
 (HPO:0009125) Lipodystrophy Very frequent [Orphanet] 54 / 7739
101
 (HPO:0009124) Abnormality of adipose tissue Very frequent [Orphanet] 5 / 7739
102
 (OMIM) Thin 2 / 7739
103
 (OMIM) Elevated plasma ACTH 3 / 7739
104
 (OMIM) Elevated plasma cortisol 1 / 7739
105
 (MedDRA:10035104) Pituitary tumour Very frequent [Orphanet] 1 / 7739
106
 (MedDRA:10061538) Pituitary tumour benign Very frequent [Orphanet] 1 / 7739
107
 (OMIM) Dexamethasone suppression 1 / 7739
108
 (OMIM) Elevated urinary 17-hydroxycorticosteroids 1 / 7739
109
 (OMIM) Oligomnenorrhea 1 / 7739
110
 (OMIM) Ruddy face and neck 1 / 7739
111
 (OMIM) Hypochloremic alkalosis 1 / 7739
112
 (MedDRA:10026672) Malignant pituitary tumour Very frequent [Orphanet] 1 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) Cushing 'disease' is a condition associated with increased blood cortisol resulting from adrenocorticotropic hormone (ACTH)-producing pituitary tumors that are resistant to glucocorticoid negative feedback (Bilodeau et al., 2006). ACTH is formed as a precursor from the POMC gene ...
Clinical Description OMIM Swinburn and Holdaway (1988) described 2 teenaged sisters with pituitary-based Cushing syndrome. In 1 patient, the disorder was cured by pituitary radiation; in the other, biopsy showed pituitary adenoma. Swinburn and Holdaway (1988) granted that 'despite the negative ...
Molecular genetics OMIM In a 26-year-old Polish patient with Cushing disease due to an ACTH-secreting pituitary adenoma, Georgitsi et al. (2007) identified a heterozygous mutation in the AIP gene (605555.0008).

- Somatic Mutations

In a series of ...