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Pituitary dependent hypercortisolism(PITA4)

MedGen UID:
66381
Concept ID:
C0221406
Disease or Syndrome
Synonyms: Cushing disease due to pituitary adenoma; CUSHING DISEASE, PITUITARY; Pituitary ACTH Hypersecretion; PITUITARY ADENOMA 4, ACTH-SECRETING; Pituitary adenoma, acth-secreting, somatic
SNOMED CT: Pituitary dependent hypercortisolism (190502001); Pituitary-dependent Cushing's disease (190502001); Cushing disease (190502001); Pituitary Cushing syndrome (190502001); Pituitary dependent Cushing disease (190502001); Cushing basophilism (190502001); Pituitary hyperadrenal corticism (190502001); Cushing's disease (190502001)
Modes of inheritance:
Not genetically inherited
MedGen UID:
988794
Concept ID:
CN307044
Finding
Source: Orphanet
clinical entity without genetic inheritance.
 
Genes (locations): AIP (11q13.2); USP8 (15q21.2)
 
Monarch Initiative: MONDO:0009050
OMIM®: 219090
Orphanet: ORPHA96253

Disease characteristics

Excerpted from the GeneReview: AIP Familial Isolated Pituitary Adenomas
AIP familial isolated pituitary adenoma (AIP-FIPA) is defined as the presence of an AIP germline pathogenic variant in an individual with a pituitary adenoma (regardless of family history). The most commonly occurring pituitary adenomas in this disorder are growth hormone-secreting adenomas (somatotropinoma), followed by prolactin-secreting adenomas (prolactinoma), growth hormone and prolactin co-secreting adenomas (somatomammotropinoma), and nonfunctioning pituitary adenomas (NFPA). Rarely TSH-secreting adenomas (thyrotropinomas) are observed. Clinical findings result from excess hormone secretion, lack of hormone secretion, and/or mass effects (e.g., headaches, visual field loss). Within the same family, pituitary adenomas can be of the same or different type. Age of onset in AIP-FIPA is usually in the second or third decade. [from GeneReviews]
Authors:
Márta Korbonits  |  Ajith V Kumar   view full author information

Additional descriptions

From OMIM
Adrenocorticotropic hormone (ACTH) hypersecretion by corticotroph adenomas of the pituitary result in excess cortisol secretion, or Cushing disease. The clinical features of Cushing disease include central obesity, moon facies, 'buffalo hump,' diabetes, hypertension, fatigue, easy bruising, depression, and reproductive disorders. Cushing disease is associated with increased morbidity and mortality, mainly due to cardiovascular or cerebrovascular disease and infections (summary by Perez-Rivas et al., 2015). Mutations in the USP8 gene, leading to an upregulated epidermal growth factor receptor (EGFR; 131550) pathway, have been identified in about 36 to 62% of corticotroph adenomas (summary by Mete and Lopes, 2017).  http://www.omim.org/entry/219090
From MedlinePlus Genetics
Cushing disease is caused by elevated levels of a hormone called cortisol, which leads to a wide variety of signs and symptoms. This condition usually occurs in adults between the ages of 20 and 50; however, children may also be affected. The first sign of this condition is usually weight gain around the trunk and in the face. Affected individuals may get stretch marks (striae) on their thighs and abdomen and bruise easily. Individuals with Cushing disease can develop a hump on their upper back caused by abnormal deposits of fat. People with this condition can have muscle weakness, severe tiredness, and progressively thin and brittle bones that are prone to fracture (osteoporosis). They also have a weakened immune system and are at an increased risk of infections. Cushing disease can cause mood disorders such as anxiety, irritability, and depression. This condition can also affect a person's concentration and memory. People with Cushing disease have an increased chance of developing high blood pressure (hypertension) and diabetes. Women with Cushing disease may experience irregular menstruation and have excessive hair growth (hirsutism) on their face, abdomen, and legs. Men with Cushing disease may have erectile dysfunction. Children with Cushing disease typically experience slow growth.  https://medlineplus.gov/genetics/condition/cushing-disease

Clinical features

From HPO
Pituitary adenoma
MedGen UID:
45933
Concept ID:
C0032000
Neoplastic Process
A benign epithelial tumor derived from intrinsic cells of the adenohypophysis (anterior pituitary).
Oligomenorrhea
MedGen UID:
18159
Concept ID:
C0028949
Pathologic Function
Infrequent menses (less than 6 per year or more than 35 days between cycles).
Nephrolithiasis
MedGen UID:
98227
Concept ID:
C0392525
Disease or Syndrome
The presence of calculi (stones) in the kidneys.
Hypertensive disorder
MedGen UID:
6969
Concept ID:
C0020538
Disease or Syndrome
The presence of chronic increased pressure in the systemic arterial system.
Obesity
MedGen UID:
18127
Concept ID:
C0028754
Disease or Syndrome
Accumulation of substantial excess body fat.
Abdominal obesity
MedGen UID:
90229
Concept ID:
C0311277
Finding
Excessive fat around the stomach and abdomen.
Emotional lability
MedGen UID:
39319
Concept ID:
C0085633
Mental or Behavioral Dysfunction
Unstable emotional experiences and frequent mood changes; emotions that are easily aroused, intense, and/or disproportionate to events and circumstances.
Psychotic mentation
MedGen UID:
871301
Concept ID:
C4025789
Mental or Behavioral Dysfunction
A pattern of thinking and perceiving characterized by a loss of contact with reality, leading to significant changes in thoughts, perceptions, and behaviors.
Kyphosis
MedGen UID:
44042
Concept ID:
C0022821
Anatomical Abnormality
Exaggerated anterior convexity of the thoracic vertebral column.
Osteoporosis
MedGen UID:
14535
Concept ID:
C0029456
Disease or Syndrome
Osteoporosis is a systemic skeletal disease characterized by low bone density and microarchitectural deterioration of bone tissue with a consequent increase in bone fragility. According to the WHO criteria, osteoporosis is defined as a BMD that lies 2.5 standard deviations or more below the average value for young healthy adults (a T-score below -2.5 SD).
Vertebral compression fracture
MedGen UID:
75497
Concept ID:
C0262431
Finding
Muscular atrophy
MedGen UID:
892680
Concept ID:
C0541794
Pathologic Function
The presence of skeletal muscular atrophy (which is also known as amyotrophy).
Biconcave vertebral bodies
MedGen UID:
383834
Concept ID:
C1856087
Finding
Exaggerated concavity of the anterior or posterior surface of the vertebral body, i.e., the upper and lower vertebral endplates are hollowed inward.
Alkalosis
MedGen UID:
1410
Concept ID:
C0002063
Disease or Syndrome
Depletion of acid or accumulation base in the body fluids.
Edema
MedGen UID:
4451
Concept ID:
C0013604
Pathologic Function
An abnormal accumulation of fluid beneath the skin, or in one or more cavities of the body.
Hypokalemia
MedGen UID:
5712
Concept ID:
C0020621
Finding
An abnormally decreased potassium concentration in the blood.
Impaired glucose tolerance
MedGen UID:
852424
Concept ID:
C0151671
Finding
An abnormal resistance to glucose, i.e., a reduction in the ability to maintain glucose levels in the blood stream within normal limits following oral or intravenous administration of glucose.
Glucose intolerance
MedGen UID:
75760
Concept ID:
C0271650
Disease or Syndrome
Glucose intolerance (GI) can be defined as dysglycemia that comprises both prediabetes and diabetes. It includes the conditions of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) and diabetes mellitus (DM).
Ecchymosis
MedGen UID:
8524
Concept ID:
C0013491
Finding
A purpuric lesion that is larger than 1 cm in diameter.
Hirsutism
MedGen UID:
42461
Concept ID:
C0019572
Disease or Syndrome
Abnormally increased hair growth referring to a male pattern of body hair (androgenic hair).
Purpura
MedGen UID:
19584
Concept ID:
C0034150
Disease or Syndrome
Purpura (from Latin
Striae distensae
MedGen UID:
57541
Concept ID:
C0152459
Acquired Abnormality
Thinned, erythematous, depressed bands of atrophic skin. Initially, striae appear as flattened and thinned, pinkish linear regions of the skin. Striae tend to enlarge in length and become reddish or purplish. Later, striae tend to appear as white, depressed bands that are parallel to the lines of skin tension. Striae distensae occur most often in areas that have been subject to distension such as the lower back, buttocks, thighs, breast, abdomen, and shoulders.
Facial erythema
MedGen UID:
65986
Concept ID:
C0239488
Finding
Redness of the skin of the face, caused by hyperemia of the capillaries in the lower layers of the skin.
Thin skin
MedGen UID:
140848
Concept ID:
C0423757
Finding
Reduction in thickness of the skin, generally associated with a loss of suppleness and elasticity of the skin.
Bruising susceptibility
MedGen UID:
140849
Concept ID:
C0423798
Finding
An ecchymosis (bruise) refers to the skin discoloration caused by the escape of blood into the tissues from ruptured blood vessels. This term refers to an abnormally increased susceptibility to bruising. The corresponding phenotypic abnormality is generally elicited on medical history as a report of frequent ecchymoses or bruising without adequate trauma.
Poor wound healing
MedGen UID:
377525
Concept ID:
C1851789
Finding
A reduced ability to heal cutaneous wounds.
Increased circulating ACTH level
MedGen UID:
867375
Concept ID:
C4021740
Finding
An abnormal increased in the concentration of corticotropin, also known as adrenocorticotropic hormone (ACTH), in the blood.

Professional guidelines

PubMed

Mullan KR, Atkinson AB
Clin Endocrinol (Oxf) 2008 Mar;68(3):327-37. Epub 2007 Sep 14 doi: 10.1111/j.1365-2265.2007.03028.x. PMID: 17854395

Recent clinical studies

Etiology

Rapastella S, Morabito S, Sharman M, Benoit J, Schiavo L, Morris J, Dobson JM, Scudder CJ
J Vet Intern Med 2023 Jul-Aug;37(4):1331-1340. Epub 2023 May 22 doi: 10.1111/jvim.16724. PMID: 37218395Free PMC Article
Heaney AP, Hunter SJ, Sheridan B, Brew Atkinson A
Clin Endocrinol (Oxf) 1999 Sep;51(3):293-9. doi: 10.1046/j.1365-2265.1999.00766.x. PMID: 10469008
Chapuis Y, Pitre J, Conti F, Abboud B, Pras-Jude N, Luton JP
World J Surg 1996 Sep;20(7):775-9; discussion 779-80. doi: 10.1007/s002689900118. PMID: 8678950
Scott HW Jr, Liddle GW, Mulherin JL Jr, Mckenna TJ, Stroup SL, Rhamy RK
Ann Surg 1977 May;185(5):524-34. doi: 10.1097/00000658-197705000-00004. PMID: 857746Free PMC Article

Diagnosis

van Aken MO, Pereira AM, van Thiel SW, van den Berg G, Frölich M, Veldhuis JD, Romijn JA, Roelfsema F
J Clin Endocrinol Metab 2005 Mar;90(3):1570-7. Epub 2004 Dec 14 doi: 10.1210/jc.2004-1281. PMID: 15598691Free PMC Article
Heaney AP, Hunter SJ, Sheridan B, Brew Atkinson A
Clin Endocrinol (Oxf) 1999 Sep;51(3):293-9. doi: 10.1046/j.1365-2265.1999.00766.x. PMID: 10469008
Scott HW Jr, Liddle GW, Mulherin JL Jr, Mckenna TJ, Stroup SL, Rhamy RK
Ann Surg 1977 May;185(5):524-34. doi: 10.1097/00000658-197705000-00004. PMID: 857746Free PMC Article

Therapy

Chapuis Y, Pitre J, Conti F, Abboud B, Pras-Jude N, Luton JP
World J Surg 1996 Sep;20(7):775-9; discussion 779-80. doi: 10.1007/s002689900118. PMID: 8678950

Prognosis

Chapuis Y, Pitre J, Conti F, Abboud B, Pras-Jude N, Luton JP
World J Surg 1996 Sep;20(7):775-9; discussion 779-80. doi: 10.1007/s002689900118. PMID: 8678950
Scott HW Jr, Liddle GW, Mulherin JL Jr, Mckenna TJ, Stroup SL, Rhamy RK
Ann Surg 1977 May;185(5):524-34. doi: 10.1097/00000658-197705000-00004. PMID: 857746Free PMC Article

Clinical prediction guides

Chapuis Y, Pitre J, Conti F, Abboud B, Pras-Jude N, Luton JP
World J Surg 1996 Sep;20(7):775-9; discussion 779-80. doi: 10.1007/s002689900118. PMID: 8678950

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