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ACTH-independent macronodular adrenal hyperplasia


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Other Names:
AIMAH; Massive macronodular adrenocortical disease; MMAD; AIMAH; Massive macronodular adrenocortical disease; MMAD; Adrenocorticotropic hormone-independent macronodular adrenal hyperplasia; Corticotropin-independent macronodular adrenal hyperplasia; ACTH-independent macronodular adrenocortical hyperplasia; Primary macronodular adrenal hyperplasia See More
Categories:
Congenital and Genetic Diseases; Endocrine Diseases; Female Reproductive Diseases; Congenital and Genetic Diseases; Endocrine Diseases; Female Reproductive Diseases; Male Reproductive Diseases See More

Summary Summary


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The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
orphanet

Orpha Number: 189427

Definition
A rare cause of Cushing syndrome (CS) characterized by nodular enlargement of both adrenal glands (multiple nodules above 1 cm in diameter) that produce excess cortisol and features of adrenocorticotropic hormone (ACTH) independent CS.

Epidemiology
Prevalence of endogenous CS is estimated at 1/26,000 and Cushing syndrome due to macronodular adrenal hyperplasia (CSMAH) represents less than 1% of the cases.

Clinical description
The disease presents a bimodal age distribution with a rare subset presenting in the first years of life, particularly associated to McCune-Albright syndrome (MAS; see this term). Most patients present in their 5th or 6th decade and the disease might be more prevalent in females. CSMAH most frequently presents as clinical or subclinical CS and signs usually become apparent only after several decades of life. However, in some patients the adrenal lesions are found incidentally, in the process of radiological investigation of another disease. The adrenal glands can be massively enlarged bilaterally with the presence of numerous macronodules; however diffuse adrenal enlargement without nodules has been described.

Etiology
The exact etiology is unknown but the adrenal overgrowth seen in CSMAH may be due to the expression of aberrant membrane receptors found in the adrenal cortex that regulate cortisol secretion and which are stimulated by gastric inhibitory polypeptide (GIP), vasopressin, serotonin, catecholamines and luteinizing hormone (LH).

Diagnostic methods
Diagnosis is based on the clinical picture of CS, the demonstration of ACTH-independent hypercortisolism (decreased levels of ACTH in plasma, non suppressible cortisol level after dexamethasone administration), and bilateral adrenal nodular enlargement on radiological imaging. Diagnosis is often difficult because hypercortisolism usually develops slowly over years, may be cyclical and is often associated with subtle CS. Radiological imaging is helpful, but occasionally nodularity is indistinguishable from that in normal elderly persons. Diagnosis can be confirmed by histological examination. Hormonal investigations can demonstrate aberrant receptor expression with abnormal stimulation of cortisol secretion by various hormones such as GIP in cases of food-dependent CS and gonadotropin-releasing hormone (GnRH) in cases of LH-dependent CS.

Differential diagnosis
Differential diagnoses include other causes of ACTH-independent CS (adrenal adenoma and carcinoma), ACTH-dependent CS including pituitary (Cushing disease) or extra-pituitary tumors (ectopic ACTH secretion; see these terms), polycystic ovary syndrome and metabolic syndrome.

Genetic counseling
CSMAH is most often reported as sporadic but there are increasing reports of familial cases with autosomal dominant transmission. As the genetics of this disease are largely unknown genetic counseling is not yet possible.

Management and treatment
Treatment can be medical if aberrant adrenal receptors are identified and can be blocked (i.e. with propranolol, somatostatin or GnRH analogs). If the blockade is not possible, treatment will be chosen depending on the level of steroid excess. Unilateral adrenalectomy can be proposed for patients with a moderate increase in hormone production, while bilateral adrenalectomy is recommended for patients with significant overproduction. After bilateral adrenalectomy, glucocorticoid and mineralocorticoid replacement is required.

Prognosis
Prognosis after treatment is good but quality of life may be affected due to the long-term effects of hypercortisolemia. Without treatment the disease is life-threatening as in the case of manifest hypercortisolism. In cases of moderate hypercortisolism, long-term morbidity is due to the increased cardiovascular and metabolic risk factors associated with mild CS.

Visit the Orphanet disease page for more resources.
Last updated: 9/1/2012

Symptoms Symptoms


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This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Showing of 31 |
Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Failure to thrive
Faltering weight
Weight faltering
[ more ]
0001508
Macronodular adrenal hyperplasia 0008231
Round face
Circular face
Round facial appearance
Round facial shape
[ more ]
0000311
Thin skin 0000963
Truncal obesity 0001956
30%-79% of people have these symptoms
Bruising susceptibility
Bruise easily
Easy bruisability
Easy bruising
[ more ]
0000978
Depressivity
Depression
0000716
Diabetes mellitus 0000819
Fatigue
Tired
Tiredness
[ more ]
0012378
Generalized hirsutism
Excessive hairiness over body
0002230
Hypertension 0000822
Menometrorrhagia 0400008
Muscle weakness
Muscular weakness
0001324
Nephrolithiasis
Kidney stones
0000787
Osteoporosis 0000939
5%-29% of people have these symptoms
Meningioma 0002858
Percent of people who have these symptoms is not available through HPO
Adult onset
Symptoms begin in adulthood
0003581
Agitation 0000713
Anxiety
Excessive, persistent worry and fear
0000739
Decreased circulating ACTH level 0002920
Kyphosis
Hunched back
Round back
[ more ]
0002808
Mental deterioration
Cognitive decline
Cognitive decline, progressive
Intellectual deterioration
Progressive cognitive decline
[ more ]
0001268
Mood changes
Moody
0001575
Neoplasm 0002664
Osteopenia 0000938
Primary hypercortisolism 0001579
Psychosis 0000709
Skeletal muscle atrophy
Muscle degeneration
Muscle wasting
[ more ]
0003202
Somatic mutation 0001428
Sporadic
No previous family history
0003745
Striae distensae
Stretch marks
0001065
Showing of 31 |
Do you have more information about symptoms of this disease? We want to hear from you.
Last updated: 1/1/2021
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Find a Specialist Find a Specialist


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If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

  • To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Learn More Learn More


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These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • Genetics Home Reference (GHR) contains information on ACTH-independent macronodular adrenal hyperplasia. This website is maintained by the National Library of Medicine.

In-Depth Information

  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.

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Have a question? Contact a GARD Information Specialist.
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