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ACTH-independent macronodular adrenal hyperplasia 1(AIMAH1)

MedGen UID:
347456
Concept ID:
C1857451
Disease or Syndrome
Synonyms: ACTH-INDEPENDENT MACRONODULAR ADRENAL HYPERPLASIA; ACTH-INDEPENDENT MACRONODULAR ADRENOCORTICAL HYPERPLASIA; ADRENOCORTICOTROPIC HORMONE-INDEPENDENT MACRONODULAR ADRENAL HYPERPLASIA; AIMAH1; CORTICOTROPIN-INDEPENDENT MACRONODULAR ADRENAL HYPERPLASIA; CUSHING SYNDROME, ADRENAL, DUE TO AIMAH
 
Gene (location): GNAS (20q13.32)
 
Monarch Initiative: MONDO:0020735
OMIM®: 219080

Definition

ACTH-independent macronodular adrenal hyperplasia (AIMAH) is an endogenous form of adrenal Cushing syndrome characterized by multiple bilateral adrenocortical nodules that cause a striking enlargement of the adrenal glands. Although some familial cases have been reported, the vast majority of AIMAH cases are sporadic. Patients typically present in the fifth and sixth decades of life, approximately 10 years later than most patients with other causes of Cushing syndrome (Swain et al., 1998; Christopoulos et al., 2005). Approximately 10 to 15% of adrenal Cushing syndrome is due to primary bilateral ACTH-independent adrenocortical pathology. The 2 main subtypes are AIMAH and primary pigmented nodular adrenocortical disease (PPNAD, see 610489), which is often a component of the Carney complex (160980) and associated with mutations in the PRKAR1A gene (188830) on chromosome 17q23-q24. AIMAH is rare, representing less than 1% of endogenous causes of Cushing syndrome (Swain et al., 1998; Christopoulos et al., 2005). See also ACTH-independent Cushing syndrome (615830) due to somatic mutation in the PRKACA gene (601639). Cushing 'disease' (219090) is an ACTH-dependent disorder caused in most cases by pituitary adenomas that secrete excessive ACTH. Genetic Heterogeneity of ACTH-Independent Macronodular Adrenal Hyperplasia AIMAH2 (615954) is caused by germline mutation of 1 allele of the ARMC5 gene (615549) coupled with a somatic mutation in the other allele. [from OMIM]

Clinical features

From HPO
Neoplasm
MedGen UID:
10294
Concept ID:
C0027651
Neoplastic Process
An organ or organ-system abnormality that consists of uncontrolled autonomous cell-proliferation which can occur in any part of the body as a benign or malignant neoplasm (tumor).
Hypertensive disorder
MedGen UID:
6969
Concept ID:
C0020538
Disease or Syndrome
The presence of chronic increased pressure in the systemic arterial system.
Truncal obesity
MedGen UID:
1637490
Concept ID:
C4551560
Finding
Obesity located preferentially in the trunk of the body as opposed to the extremities.
Anxiety
MedGen UID:
1613
Concept ID:
C0003467
Finding
Intense feelings of nervousness, tension, or panic often arise in response to interpersonal stresses. There is worry about the negative effects of past unpleasant experiences and future negative possibilities. Individuals may feel fearful, apprehensive, or threatened by uncertainty, and they may also have fears of falling apart or losing control.
Depression
MedGen UID:
4229
Concept ID:
C0011581
Mental or Behavioral Dysfunction
Frequently experiencing feelings of being down, miserable, and/or hopeless; struggling to recover from these moods; having a pessimistic outlook on the future; feeling a pervasive sense of shame; having a low self-worth; experiencing thoughts of suicide and engaging in suicidal behavior.
Psychotic disorder
MedGen UID:
19568
Concept ID:
C0033975
Mental or Behavioral Dysfunction
A condition characterized by changes in personality and thought patterns, often accompanied by hallucinations and delusional beliefs, is known as psychosis.
Agitation
MedGen UID:
88447
Concept ID:
C0085631
Sign or Symptom
A state of extreme restlessness and excessive motor activity is associated with mental distress or a feeling of inner tension.
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.
Mental deterioration
MedGen UID:
66713
Concept ID:
C0234985
Mental or Behavioral Dysfunction
Loss of previously present mental abilities, generally in adults.
Kyphosis
MedGen UID:
44042
Concept ID:
C0022821
Anatomical Abnormality
Exaggerated anterior convexity of the thoracic vertebral column.
Osteopenia
MedGen UID:
18222
Concept ID:
C0029453
Disease or Syndrome
Osteopenia is a term to define bone density that is not normal but also not as low as osteoporosis. By definition from the World Health Organization osteopenia is defined by bone densitometry as a T score -1 to -2.5.
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).
Muscular atrophy
MedGen UID:
892680
Concept ID:
C0541794
Pathologic Function
The presence of skeletal muscular atrophy (which is also known as amyotrophy).
Round face
MedGen UID:
116087
Concept ID:
C0239479
Finding
The facial appearance is more circular than usual as viewed from the front.
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.
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.
Macronodular adrenal hyperplasia
MedGen UID:
137971
Concept ID:
C0342495
Finding
Adrenal hyperfunction associated with multiple bilateral adrenal nodules, usually more than one centimeter in diameter.
Adrenal hyperplasia
MedGen UID:
301220
Concept ID:
C1621895
Disease or Syndrome
Enlargement of the adrenal gland.
Increased circulating cortisol level
MedGen UID:
871175
Concept ID:
C4025651
Finding
Overproduction of the hormone of cortisol by the adrenal cortex, resulting in a characteristic combination of clinical symptoms termed Cushing syndrome, with truncal obesity, a round, full face, striae atrophicae and acne, muscle weakness, and other features.
Primary hypercortisolism
MedGen UID:
892570
Concept ID:
C4025760
Disease or Syndrome
Hypercortisolemia associated with a primary defect of the adrenal gland leading to overproduction of cortisol.
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

Sheikh-Ahmad M, Dickstein G, Matter I, Shechner C, Bejar J, Reut M, Sroka G, Laniado M, Saiegh L
Exp Clin Endocrinol Diabetes 2020 Dec;128(12):827-834. Epub 2019 Oct 21 doi: 10.1055/a-0998-7884. PMID: 31634962
Vassiliadi DA, Tsagarakis S
Endocr Relat Cancer 2019 Oct 1;26(10):R567-R581. doi: 10.1530/ERC-19-0240. PMID: 32053747
Sonino N, Boscaro M, Fallo F
Treat Endocrinol 2005;4(2):87-94. doi: 10.2165/00024677-200504020-00003. PMID: 15783246

Recent clinical studies

Etiology

Gosavi V, Lila A, Memon SS, Sarathi V, Thakkar K, Dalvi A, Malhotra G, Prakash G, Patil V, Shah NS, Bandgar T
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Acharya R, Dhir M, Bandi R, Yip L, Challinor S
World J Surg 2019 Feb;43(2):527-533. doi: 10.1007/s00268-018-4788-2. PMID: 30232569
Faucz FR, Zilbermint M, Lodish MB, Szarek E, Trivellin G, Sinaii N, Berthon A, Libé R, Assié G, Espiard S, Drougat L, Ragazzon B, Bertherat J, Stratakis CA
J Clin Endocrinol Metab 2014 Jun;99(6):E1113-9. Epub 2014 Mar 6 doi: 10.1210/jc.2013-4280. PMID: 24601692Free PMC Article
Rockall AG, Babar SA, Sohaib SA, Isidori AM, Diaz-Cano S, Monson JP, Grossman AB, Reznek RH
Radiographics 2004 Mar-Apr;24(2):435-52. doi: 10.1148/rg.242035092. PMID: 15026592
Swain JM, Grant CS, Schlinkert RT, Thompson GB, vanHeerden JA, Lloyd RV, Young WF
Arch Surg 1998 May;133(5):541-5; discussion 545-6. doi: 10.1001/archsurg.133.5.541. PMID: 9605918

Diagnosis

Ferri J, Perelló E, Lorente RI, Argente C, Rossetti P, Pedro T, Martinez-Hervas S, Real JT
Endocrinol Diabetes Nutr (Engl Ed) 2020 Apr;67(4):245-252. Epub 2019 Oct 28 doi: 10.1016/j.endinu.2019.07.005. PMID: 31672533
Vassiliadi DA, Tsagarakis S
Endocr Relat Cancer 2019 Oct 1;26(10):R567-R581. doi: 10.1530/ERC-19-0240. PMID: 32053747
Gagliardi L, Hotu C, Casey G, Braund WJ, Ling KH, Dodd T, Manavis J, Devitt PG, Cutfield R, Rudzki Z, Scott HS, Torpy DJ
Clin Endocrinol (Oxf) 2009 Jun;70(6):883-91. Epub 2008 Nov 5 doi: 10.1111/j.1365-2265.2008.03471.x. PMID: 19018784
Costa MH, Lacroix A
Arq Bras Endocrinol Metabol 2007 Nov;51(8):1226-37. doi: 10.1590/s0004-27302007000800008. PMID: 18209860
Rockall AG, Babar SA, Sohaib SA, Isidori AM, Diaz-Cano S, Monson JP, Grossman AB, Reznek RH
Radiographics 2004 Mar-Apr;24(2):435-52. doi: 10.1148/rg.242035092. PMID: 15026592

Therapy

Tan XG, Zhu J, Cui L
BMC Endocr Disord 2022 Jan 5;22(1):11. doi: 10.1186/s12902-021-00910-7. PMID: 34986816Free PMC Article
Vassiliadi DA, Tsagarakis S
Endocr Relat Cancer 2019 Oct 1;26(10):R567-R581. doi: 10.1530/ERC-19-0240. PMID: 32053747
Zieleniewski W, Michalak R
Gynecol Endocrinol 2017 May;33(5):349-352. Epub 2017 Feb 26 doi: 10.1080/09513590.2017.1290070. PMID: 28277127
Oki K, Yamane K, Nakanishi S, Nakashima R, Jitsuiki K, Kohno N
Endocrine 2009 Dec;36(3):372-6. Epub 2009 Oct 8 doi: 10.1007/s12020-009-9246-3. PMID: 19813002
Sonino N, Boscaro M, Fallo F
Treat Endocrinol 2005;4(2):87-94. doi: 10.2165/00024677-200504020-00003. PMID: 15783246

Prognosis

Wang W, Wei F
BMC Endocr Disord 2022 Aug 22;22(1):211. doi: 10.1186/s12902-022-01128-x. PMID: 35996143Free PMC Article
Tan XG, Zhu J, Cui L
BMC Endocr Disord 2022 Jan 5;22(1):11. doi: 10.1186/s12902-021-00910-7. PMID: 34986816Free PMC Article
Morita N, Hosaka T, Yamazaki Y, Takahashi K, Sasano H, Ishida H
J Int Med Res 2019 Jul;47(7):3360-3370. Epub 2019 Jul 1 doi: 10.1177/0300060519855179. PMID: 31256733Free PMC Article
Faucz FR, Zilbermint M, Lodish MB, Szarek E, Trivellin G, Sinaii N, Berthon A, Libé R, Assié G, Espiard S, Drougat L, Ragazzon B, Bertherat J, Stratakis CA
J Clin Endocrinol Metab 2014 Jun;99(6):E1113-9. Epub 2014 Mar 6 doi: 10.1210/jc.2013-4280. PMID: 24601692Free PMC Article
Xu Y, Rui W, Qi Y, Zhang C, Zhao J, Wang X, Wu Y, Zhu Q, Shen Z, Ning G, Zhu Y
World J Surg 2013 Jul;37(7):1626-32. doi: 10.1007/s00268-013-2059-9. PMID: 23592061

Clinical prediction guides

Wang W, Wei F
BMC Endocr Disord 2022 Aug 22;22(1):211. doi: 10.1186/s12902-022-01128-x. PMID: 35996143Free PMC Article
Gosavi V, Lila A, Memon SS, Sarathi V, Thakkar K, Dalvi A, Malhotra G, Prakash G, Patil V, Shah NS, Bandgar T
Horm Metab Res 2022 Feb;54(2):57-66. Epub 2022 Feb 7 doi: 10.1055/a-1735-3232. PMID: 35130566
Tan XG, Zhu J, Cui L
BMC Endocr Disord 2022 Jan 5;22(1):11. doi: 10.1186/s12902-021-00910-7. PMID: 34986816Free PMC Article
Ferri J, Perelló E, Lorente RI, Argente C, Rossetti P, Pedro T, Martinez-Hervas S, Real JT
Endocrinol Diabetes Nutr (Engl Ed) 2020 Apr;67(4):245-252. Epub 2019 Oct 28 doi: 10.1016/j.endinu.2019.07.005. PMID: 31672533
Faucz FR, Zilbermint M, Lodish MB, Szarek E, Trivellin G, Sinaii N, Berthon A, Libé R, Assié G, Espiard S, Drougat L, Ragazzon B, Bertherat J, Stratakis CA
J Clin Endocrinol Metab 2014 Jun;99(6):E1113-9. Epub 2014 Mar 6 doi: 10.1210/jc.2013-4280. PMID: 24601692Free PMC Article

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