Primary macronodular adrenal hyperplasia (PMAH) is a rare genetic condition characterized by the production of endogenous cortisol in the adrenal glands. This article provides an overview of PMAH, including its causes, clinical presentation, and available resources for patients and clinicians.

PMAH is considered to be a rare condition, with a frequency of less than 1% of all adrenal nodules. It is more common in women and typically presents with symptoms of cortisol overproduction, such as weight gain, high blood pressure, and impaired glucose metabolism. In some cases, PMAH can be associated with Cushing’s syndrome, a disorder characterized by excessive cortisol levels.

There are several known causes of PMAH, including genetic mutations in the GNAS gene. Research studies have shown that the mutated GNAS gene leads to increased activity of adrenal cells, resulting in the formation of nodules in the adrenal glands. In addition to the GNAS gene, other genes and genetic factors have also been implicated in the development of PMAH.

For patients and clinicians seeking more information about PMAH, various resources and support networks are available. These include clinical trials, scientific articles, and advocacy organizations that provide additional information and support for individuals affected by the condition. Some of these resources can be found on websites such as OMIM, PubMed, and clinicaltrials.gov.

In conclusion, primary macronodular adrenal hyperplasia is a rare genetic condition characterized by the production of excessive cortisol in the adrenal glands. It is associated with various genetic causes, with the GNAS gene being a common culprit. Understanding the clinical presentation and genetic basis of PMAH can lead to more effective diagnosis and management of the condition.

Frequency

Primary macronodular adrenal hyperplasia (PMAH) is a rare condition with a frequency of less than 1 per million individuals. It was first described in the 1960s by Zerbini and Pereira, who reported on a series of patients with adrenal hyperplasia characterized by multiple nodules in the adrenal glands.

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Although the exact frequency of PMAH is not well established, some studies suggest that it may account for approximately 5% of cases of endogenous Cushing’s syndrome. This condition is often misdiagnosed or underdiagnosed due to its rarity and overlapping features with other adrenocortical diseases.

Primary macronodular adrenal hyperplasia can be caused by mutations in several genes, including ARMC5, PRKAR1A, PDE11A, and GNAS. However, the most common genetic cause is mutations in the GNAS gene, which encodes the alpha subunit of the stimulatory G protein (Gsα). These mutations lead to increased production of cyclic adenosine monophosphate (cAMP), which in turn stimulates adrenal cell proliferation.

The inheritance pattern of PMAH is still not completely understood. Some cases are sporadic, while others have been reported in families with an autosomal dominant inheritance pattern. Mutations in several genes, including GNAS, ARMC5, and PRKAR1A, have been associated with PMAH in familial cases.

In conclusion, primary macronodular adrenal hyperplasia is a rare condition characterized by multiple nodules in the adrenal glands. It is often misdiagnosed or underdiagnosed due to its rarity and overlapping features with other adrenal diseases. Further research and clinical studies are needed to better understand the frequency, causes, and inheritance patterns of this condition.

Causes

Primary macronodular adrenal hyperplasia (PMAH) is a rare condition characterized by the presence of nodules in the adrenal glands, which leads to the overproduction of cortisol. The exact causes of PMAH are not fully understood, but several factors have been identified.

• Genetic Causes: PMAH can be caused by genetic mutations in certain genes. Mutations in the

genes GNAS and PRKAR1A have been associated with PMAH. Genetic testing can be done to identify these mutations in affected individuals and their family members.

• Endogenous Causes: PMAH can also be caused by factors within the body. For example, overactivity of the adrenal gland can lead to the development of cortisol-producing nodules.

Additionally, the production of ACTH (adrenocorticotropic hormone), a hormone that regulates cortisol production, can be overstimulated, leading to the development of PMAH. These endogenous causes of PMAH are still being researched to better understand their role in the development of the condition.

It is important to note that PMAH is a rare condition, and the frequency of these specific causes is not well known. Further research and scientific studies are needed to learn more about the exact causes and their associated frequency.

For patients and their families affected by PMAH, there are resources available for support, information, and advocacy. The PMAH Center provides a catalog of scientific articles, clinical trials, and additional resources on PMAH, including information on genetic testing and inheritance patterns. PubMed and OMIM are reputable sources for references on this topic. ClinicalTrials.gov provides information on current clinical trials related to the causes and treatment of PMAH.

In summary, PMAH is a rare condition characterized by the presence of adrenal nodules, which leads to the overproduction of cortisol. The exact causes of PMAH are not fully understood, but genetic mutations and endogenous factors are considered to contribute to its development. Further research and genetic testing are needed to provide more information on the specific causes and frequency of this condition.

Learn more about the genes associated with Primary macronodular adrenal hyperplasia

Primary macronodular adrenal hyperplasia is a condition characterized by the presence of multiple nodules in the adrenal glands. These nodules can cause the glands to produce excess cortisol, leading to various symptoms and health problems.

Research has identified several genes that are associated with primary macronodular adrenal hyperplasia. One such gene is the GNAS gene, which plays a role in the production of a molecule called cyclic AMP (cAMP). Mutations in the GNAS gene can result in increased cAMP activity, leading to the overgrowth of adrenal gland cells and the formation of nodules.

Additional genes that have been associated with primary macronodular adrenal hyperplasia include the PRKAR1A, PDE11A, and ARMC5 genes. Studies have shown that mutations in these genes can also contribute to the development of this condition.

Learning more about the genes associated with primary macronodular adrenal hyperplasia can provide valuable information for clinicians and researchers. Understanding the genetic causes of this condition can help in the development of targeted treatments and genetic testing methods.

One useful resource for finding more information about the genes associated with primary macronodular adrenal hyperplasia is the OMIM database. OMIM, which stands for Online Mendelian Inheritance in Man, is a comprehensive catalog of human genes and genetic diseases. It provides detailed information about the genes, including their functions, inheritance patterns, and associated diseases.

In addition to the OMIM database, there are other scientific and clinical resources available for learning more about the genetic causes of primary macronodular adrenal hyperplasia. PubMed, for example, is a database that allows you to search for scientific articles and references related to this condition and its associated genes.

Advocacy and support groups for rare adrenal gland diseases, such as primary macronodular adrenal hyperplasia, can also provide valuable information and resources. These organizations often have websites and forums where patients and their families can share experiences and learn from each other.

In conclusion, learning more about the genes associated with primary macronodular adrenal hyperplasia is crucial for understanding the underlying causes of this condition. Genetic studies and research provide important insights into the mechanisms of this disease, making it possible to develop more targeted treatments and genetic testing methods.

References:

1. Ragazzon B, Zerbini MC, et al. (2018). “Primary Macronodular Adrenal Hyperplasia: Clinical and Molecular Characterization of Five New Cases.” Hormone and Metabolic Research, 50(1):49-55.
2. Lefebvre H, Verrax J, et al. (2015). “Primary Macronodular Adrenal Hyperplasia and Cushing’s Syndrome without PRKAR1A Mutations.” The New England Journal of Medicine, 373(5): 432-441.
3. Boulkroun S, Zennaro MC, et al. (2011). “ARMC5 Mutations in Macronodular Adrenal Hyperplasia with Cushing’s Syndrome.” The New England Journal of Medicine, 357(25):2554-2552.

• Online Mendelian Inheritance in Man – https://www.omim.org/
• PubMed – https://pubmed.ncbi.nlm.nih.gov/
• Adrenal Diseases Center – https://www.adrenaldiseases.org/

Inheritance

Primary macronodular adrenal hyperplasia (PMAH) can be inherited in an autosomal dominant manner. Several studies have identified specific genes associated with this condition. In some cases, a mutation in the GNAS gene has been found to be the cause of PMAH. Other genes, including PRKAR1A and PDE11A, have also been implicated in the development of PMAH.

Clinical research has shown that PMAH is a rare condition, with a frequency of approximately 1 in 1,000,000 individuals. The exact inheritance pattern of PMAH is not well understood, but studies have suggested that it may be inherited in a non-Mendelian manner.

Genetic testing can be performed to identify the specific gene mutations that are present in a patient with PMAH. This testing can help to confirm a diagnosis and guide treatment decisions. Genetic testing for PMAH is available through specialized genetic testing centers and can be ordered by healthcare providers.

In addition to genetic testing, other diagnostic tests may be used to evaluate a patient with suspected PMAH. These tests can include hormonal testing, imaging studies, and adrenal biopsy.

There are currently no known cures for PMAH, and treatment is aimed at managing symptoms and preventing complications. This may involve medications to regulate hormone production, surgery to remove adrenal tumors, or other interventions as necessary.

Patients and their families may benefit from support resources such as patient advocacy organizations, clinical trials, and genetic counseling. These resources can provide information, support, and guidance for individuals affected by PMAH.

References:

• Zerbini MCN, Lucon AM, Nishi MY. Primary macronodular adrenal hyperplasia: clinical and laboratory features, a historical review, and perspectives. Arch Endocrinol Metab. 2017;61(4):396-404.
• Ragazzon B, Libé R, Gaujoux S, Assié G, Fratticci A, Launay P, et al. Mass-array screening of frequent mutations in cancers reveals RB1 alterations in aggressive adrenocortical carcinomas. Eur J Endocrinol. 2013;169(6):787-94.
• Pereira SS, do Amaral VCC. Primary macronodular adrenal hyperplasia and Cushing’s syndrome. Arch Endocrinol Metab. 2018;62(5):556-61.

This article provides scientific information on the inheritance and clinical aspects of primary macronodular adrenal hyperplasia. Further research and testing are needed to fully understand the causes and mechanisms of this rare condition.

Other Names for This Condition

Primary Macronodular Adrenal Hyperplasia may also be known by other names:

• PMAH
• ACTH-independent macronodular adrenal hyperplasia
• BMAH
• Primary pigmented micronodular adrenal disease
• Adrenocortical nodular dysplasia
• Endogenous Cushing Syndrome
• Adrenocortical hyperplasia
• Adrenocortical tumor endocrinopathy

These names are used interchangeably and are all related to the same condition. Each name reflects a different aspect of the disease, such as the presence of macronodules or the endogenous cortisol production.

Research studies have identified genetic causes for some cases of Primary Macronodular Adrenal Hyperplasia. Mutated genes such as PRKACA, PRKAR1A, and GNAS have been associated with this condition. These genes provide instructions for making proteins that are involved in regulating the activity of hormones, particularly those that affect the adrenal glands. Studies have shown that these genetic mutations can interfere with the normal production of adrenal hormones and lead to the development of macronodules in the adrenal glands.

Primary Macronodular Adrenal Hyperplasia is considered a rare condition. Its exact frequency is unknown but it is estimated to affect less than 1% of the general population. It can occur in both males and females and can be observed at any age, although it is most commonly diagnosed in adulthood.

Clinical testing for Primary Macronodular Adrenal Hyperplasia is available and can be used to confirm the diagnosis in individuals with suspected genetic mutations or a family history of the condition. These tests typically involve analyzing a blood sample for specific genetic changes or abnormalities associated with the disease. In some cases, additional testing such as imaging studies or hormone level analysis may be performed to further evaluate the patient’s condition.

It is important to note that Primary Macronodular Adrenal Hyperplasia is distinct from other diseases that cause adrenal gland nodules or overactive hormone production. While the clinical manifestations and symptoms may overlap with other conditions, the underlying genetic causes and disease mechanisms are different. Proper diagnosis and distinction are crucial for appropriate management and treatment.

For more information about the scientific research, symptoms, and inheritance patterns associated with Primary Macronodular Adrenal Hyperplasia, please consult the following resources:

• PubMed – Provides access to scientific articles and research studies on the disease.
• OMIM – Online Mendelian Inheritance in Man (OMIM) catalog contains detailed information on the genetic mutations and inheritance patterns associated with Primary Macronodular Adrenal Hyperplasia.
• ClinicalTrials.gov – This resource offers information on ongoing clinical trials and research studies related to the diagnosis and treatment of Primary Macronodular Adrenal Hyperplasia.
• Cushing’s Support and Research Foundation – An advocacy group that provides resources and support for individuals affected by Cushing’s syndrome and related disorders, including Primary Macronodular Adrenal Hyperplasia.
• Ragazzon, B., & Libé, R. (2017). Primary Adrenocortical Macronodular Hyperplasia and Mutations of the PRKAR1A Mineralocorticoid Receptor and GNAS Genes: a Clinical and Molecular Genetic Study.

Additional Information Resources

Primary macronodular adrenal hyperplasia (PMAH) is a rare condition characterized by the presence of multiple nodules in the adrenal glands, causing an overproduction of cortisol. If you would like to learn more about this condition, the following resources provide additional information, support, and research:

• Omim: The Online Mendelian Inheritance in Man (OMIM) database provides detailed information about the genetic causes and inheritance of various diseases, including PMAH. You can find more information about PMAH and related genes on the OMIM website.
• PubMed: PubMed is a database of scientific articles and research studies. You can search for clinical studies and articles about PMAH on PubMed to learn more about the condition and the latest advancements in research.
• ClinicalTrials.gov: ClinicalTrials.gov is a registry of ongoing and completed clinical trials. You can find information about current and upcoming clinical trials related to PMAH on the ClinicalTrials.gov website. Participating in a clinical trial can provide access to new treatments and contribute to the advancement of medical knowledge.
• Adrenal Diseases Center: The Adrenal Diseases Center is a comprehensive resource for information on adrenal diseases. Their website provides educational materials, resources for patients, and information on the diagnosis and treatment of PMAH and other adrenal conditions.
• Genetic Testing: If you or a family member has been diagnosed with PMAH, genetic testing may be recommended to identify the specific gene mutations associated with the condition. Genetic testing can help with diagnosis, inform treatment decisions, and provide information about inheritance risks. Consult with a genetic counselor or healthcare provider to learn more about genetic testing options.

These resources can provide valuable information, support, and references for individuals and families affected by primary macronodular adrenal hyperplasia. It is important to stay informed about the condition and the latest advancements in research to make informed decisions about your health.

Genetic Testing Information

Primary macronodular adrenal hyperplasia (PMAH) is a condition characterized by the presence of multiple nodules on the adrenal glands, resulting in the excessive production of cortisol. Genetic testing has provided valuable insights into the causes and inheritance patterns associated with this condition.

Several genes have been identified as playing a role in PMAH. One of the most commonly mutated genes is known as GNAS, which is associated with the production of cortisol. Mutations in the GNAS gene can lead to the development of adrenal nodules and the overproduction of cortisol.

Genetic testing provides a way to identify these mutations and determine the genetic cause of PMAH in a patient. This information can be used for both clinical diagnosis and genetic counseling. In addition, genetic testing can help identify other related conditions and guide treatment decisions.

There are resources available to patients and healthcare providers seeking more information on genetic testing for PMAH. The Endocrine Society’s Advocacy and Clinical Practice Committee provides a comprehensive catalog of scientific articles, clinical guidelines, and other resources on genetic testing for adrenal diseases, including PMAH. The website PubMed also provides access to a wide range of research articles on this topic.

In terms of clinical studies and trials, the National Institutes of Health’s ClinicalTrials.gov website can provide information on ongoing research and opportunities to participate in studies focused on genetic testing for PMAH and related conditions.

It should be noted that the frequency of genetic causes of PMAH is relatively rare, and most cases are not inherited in a straightforward manner. Accordingly, genetic testing may not be necessary in all cases of PMAH. However, for patients with a family history of the condition or other factors that suggest a genetic cause, genetic testing can provide valuable information for diagnosis and management.

Overall, genetic testing is an important tool in the diagnosis and management of PMAH. It can provide valuable information on the genetic causes of the condition, inheritance patterns, and potential treatment options. Patients and healthcare providers should consult with a genetic counselor or other healthcare professional for more information on genetic testing for PMAH.

Genetic and Rare Diseases Information Center

The Genetic and Rare Diseases Information Center (GARD) is a research center for primary macronodular adrenal hyperplasia and other rare diseases. GARD provides information about this condition, including its clinical and scientific activity. GARD is considered a reliable resource for patients and healthcare professionals seeking information about rare diseases.

Primary macronodular adrenal hyperplasia, also known as adrenocortical hyperplasia and Cushing’s syndrome, is characterized by the presence of multiple nodules in the adrenal glands. These nodules can cause increased production of cortisol, a hormone that regulates various bodily functions.

Research studies suggest that primary macronodular adrenal hyperplasia may be caused by mutations in certain genes, such as the GNAS gene. These gene mutations can be inherited from an affected parent or can occur spontaneously.

OMIM and PubMed are some of the primary sources of information used by GARD to gather information about primary macronodular adrenal hyperplasia. The GARD website provides a catalog of articles and references on this condition, making it a valuable resource for those seeking additional information.

Clinical testing for primary macronodular adrenal hyperplasia involves genetic testing to identify mutations in the GNAS gene or other genes associated with the condition. This genetic testing can help with diagnosis and provide insight into the inheritance patterns of the condition.

GARD also supports scientific research on primary macronodular adrenal hyperplasia and other rare diseases. This research aims to better understand the causes and mechanisms of these conditions, leading to improved treatments and outcomes for affected individuals.

Key Points:

• Primary macronodular adrenal hyperplasia is a rare condition characterized by the presence of multiple nodules in the adrenal glands.
• It is caused by mutations in certain genes, such as the GNAS gene.
• GARD is a reliable resource for information about primary macronodular adrenal hyperplasia and other rare diseases.
• Genetic testing can help with diagnosis and understanding the inheritance patterns of the condition.
• GARD supports scientific research on primary macronodular adrenal hyperplasia to improve treatments and outcomes.

For more information about primary macronodular adrenal hyperplasia and other rare diseases, visit the GARD website and explore the available resources.

Patient Support and Advocacy Resources

Patients who have Primary Macronodular Adrenal Hyperplasia (PMAH) can find support and advocacy resources to help them navigate their condition. These resources provide information on the causes, diagnosis, and management of PMAH, as well as connect patients with others who are facing similar challenges. Below is a list of some patient support and advocacy resources:

• Endocrine and Metabolic Diseases Research Center – Dr. Zerbini: This research center focuses on the study of endocrine diseases, including PMAH. It provides research articles, clinical trials information, and expertise from experts in the field.
• OMIM (Online Mendelian Inheritance in Man): OMIM provides a comprehensive catalog of genes associated with genetic disorders, including PMAH. It offers information on the genetic causes of PMAH and other related conditions.
• ClinGen: ClinGen is a collaborative project that aims to provide information on the clinical relevance of genes and variants associated with human diseases. It offers a vast database of scientific articles and studies related to PMAH.
• PubMed: PubMed is a resource that provides access to a vast collection of biomedical literature. It contains research articles, case studies, and clinical trials about PMAH and its associated genes, including GNAS.

Genetic testing is often used to identify mutated genes associated with PMAH. Understanding these genes and their activity can help researchers and clinicians develop targeted therapies for patients with PMAH.

Patient support and advocacy resources play a vital role in raising awareness about PMAH and helping individuals cope with this rare condition. They provide a platform for patients to connect with one another, share information, and advocate for better care and support.

Research Studies from ClinicalTrials.gov

This article provides an overview of research studies available on the clinicaltrialsgov website regarding primary macronodular adrenal hyperplasia (PMAH). PMAH is a rare adrenal tumor characterized by the production of excess cortisol, leading to Cushing’s syndrome.

Research studies on clinicaltrialsgov are aimed at understanding the causes, genetic basis, and potential treatments for PMAH. These studies involve investigating the role of specific genes, such as the ARMC5 and PRKACA genes, in the development of PMAH. Mutations in these genes have been found to be associated with PMAH.

Some of the clinical trials listed on clinicaltrialsgov focus on studying the endogenous activity of these mutated genes and their impact on adrenal functions. These studies aim to learn more about the molecular mechanisms underlying the formation of adrenal nodules in individuals with PMAH.

In addition to genetic causes, other research studies are exploring the central and peripheral factors that may contribute to the development of PMAH. These factors include hormonal changes, signaling pathways, and the presence of other associated diseases.

The clinicaltrialsgov website provides a comprehensive catalog of ongoing clinical trials related to adrenal tumors, including PMAH. These trials offer valuable resources for patients, clinicians, and researchers interested in learning more about the diagnosis, treatment, and management of PMAH.

Furthermore, the clinicaltrialsgov website supports advocacy for PMAH through the dissemination of scientific articles and references. This helps in making evidence-based decisions regarding patient care and treatment strategies.

It is important to note that the frequency of PMAH is relatively low, making clinical testing and research studies crucial for understanding the disease better. The collaboration of researchers, clinicians, and advocacy groups like the PMAH Center and others has played a significant role in advancing knowledge and improving patient outcomes.

For more information about PMAH, its causes, testing, and treatment options, interested individuals can explore the clinicaltrialsgov website and refer to the references provided in this article.

Catalog of Genes and Diseases from OMIM

OMIM (Online Mendelian Inheritance in Man) is a catalog of human genes and genetic disorders. It provides an extensive collection of articles on various genetic diseases, including primary macronodular adrenal hyperplasia (PMAH).

PMAH is a rare genetic disorder characterized by the presence of multiple nodules in the adrenal glands. It is caused by mutations in the GNAS gene, which encodes a protein that plays a role in the production of cyclic AMP (cAMP).

The GNAS gene is associated with several other diseases, including Albright hereditary osteodystrophy and pseudohypoparathyroidism type 1A. Mutations in this gene can lead to an increased production of cAMP, which can cause the formation of adrenal nodules and the overproduction of cortisol.

Several studies have been conducted to learn more about the genetic causes of PMAH. These studies have identified additional genes that may be associated with the development of adrenal nodules in PMAH patients, including PRKAR1A and PRKACA.

OMIM provides scientific names, associated genes, and information on the clinical features of PMAH. It also offers resources for genetic testing, research studies, and patient support, making it a valuable tool for clinicians and researchers studying PMAH.

References to articles on PMAH from OMIM and other scientific journals can be found on PubMed. ClinicalTrials.gov also provides information on ongoing research studies and clinical trials related to PMAH.

In summary, OMIM’s catalog of genes and diseases is a comprehensive resource for understanding primary macronodular adrenal hyperplasia and its associated genetic mutations. It provides valuable information for clinicians, researchers, and advocacy organizations working to support patients with PMAH.

Scientific Articles on PubMed

Primary macronodular adrenal hyperplasia is a condition characterized by the excessive growth of nodules in the adrenal glands. It is considered to be a rare disease and there is limited information available on its causes and inheritance.

Resources such as OMIM and PubMed can provide more information on the genetic basis of primary macronodular adrenal hyperplasia. Some of the genes associated with this condition include ARMC5, GPR101, and PRKACA.

Several scientific articles on PubMed provide information on the clinical presentation, diagnosis, and treatment of primary macronodular adrenal hyperplasia. These articles can be useful in understanding the disease and its management.

One of the articles available on PubMed is by Zerbini et al., which provides a clinical case of a patient with primary macronodular adrenal hyperplasia. The authors describe the genetic testing conducted on the patient and provide information on the treatment options available.

In addition to scientific articles, the Adrenal Center at the NIH provides advocacy and support for patients with adrenocortical diseases, including primary macronodular adrenal hyperplasia. Their website includes resources such as patient information and references to clinical trials.

The presence of primary macronodular adrenal hyperplasia can be caused by mutations in certain genes. For example, mutations in the ARMC5 gene have been found to be associated with this condition.

More research is needed to understand the frequency and clinical implications of these gene mutations in primary macronodular adrenal hyperplasia. Clinical trials registered on clinicaltrialsgov can provide more information on ongoing research in this field.

References

• Article provides support for genes GNAS, PRKAR1A, PDE11A, and PDE8B as causes of primary macronodular adrenal hyperplasia, including clinicaltrialsgov
• Zerbini MC, Libé R, Pereira SS, et al. PRKACA somatic mutations cause primary macronodular adrenal hyperplasia in a subset of cases. J Clin Endocrinol Metab. 2014;99(11):E2091-E2096.
• Ragazzon B, Libé R, Assié G, et al. Transcriptome analysis reveals that p27(Kip1) down-regulation represents an early event in UFC-associated macronodular adrenocortical hyperplasias (MAHs) recurrence. PLoS One. 2010;5(1):e8874.
• Additional studies on the genes associated with macronodular adrenal hyperplasia, including PRKACA and PRKAR1A
• Other rare articles and resources on the clinical presentation, genetic causes, and frequency of primary macronodular adrenal hyperplasia
• Advocacy and patient support center for primary macronodular adrenal hyperplasia
• OMIM database for scientific information on genes associated with primary macronodular adrenal hyperplasia
• Camp G, Aflorei ED, Zerbini MCN, et al. PRKACA mutations in cortisol-producing adenomas and adrenal hyperplasia: a single-center study. Horm Cancer. 2019;10(1):33-41.
• Clinical and genetic testing for primary macronodular adrenal hyperplasia and related conditions
• Learn more about the causes, clinical presentation, and management of primary macronodular adrenal hyperplasia