IllnessCushing syndrome, adrenal hyperplasia; differential diagnosis

NGS +

Cushing disease is caused by elevated cortisol levels and results in a variety of symptoms that usually appear between the ages of 20 and 50; children can also be affected. The first signs of the disease are often weight gain, then striae, bruises and abnormal fat deposits appear. Later, patients may exhibit muscle weakness, fatigue and osteoporosis with a weakened immune system or mood disorders, hypertension, diabetes and hirsuitism in women. Affected children typically grow slowly. Most often, Cushing disease occurs in isolation, less commonly as a symptom of genetic syndromes with pituitary adenomas, such as multiple endocrine neoplasia 1 (MEN1) or familial isolated pituitary adenoma. Pituitary adenomas cause the vast majority of cases of Cushing disease, but adenomas in the adrenal gland can also cause the condition. Most cases of Cushing disease occur sporadically and are due to somatic mutations. The different syndromes that have M. Cushing as a feature may have different inheritance patterns. Most of these disorders are inherited in an autosomal dominant manner. A negative test result from germline DNA does not exclude the clinical diagnosis.

Reference: https://link.springer.com/article/10.1007/s11102-022-01253-9

• Alias: ACTH-independent macronodular adrenocortical hyperplasia
• Alias: Adrenal Cushing syndrome due to AIMAH
• Alias: Adrenocorticotropic hormone-independent macronodular adrenal hyperplasia
• Alias: Corticotropin-independent macronodular adrenal hyperplasia
• Alias: Primary bilateral macronodular adrenal hyperplasia
• Allelic: Acrodysostosis 1, +/- hormone resistance (PRKAR1A)
• Allelic: Adenomatous polyposis coli (APC)
• Allelic: Brain tumor-polyposis syndrome 2 (APC)
• Allelic: Carcinoid tumor of lung (MEN1)
• Allelic: Cardioacrofacial dysplasia 1 (PRKACA)
• Allelic: Carney complex, type 1 (PRKAR1A)
• Allelic: Congenital Adrenal Hypoplasia (MC2R)
• Allelic: Desmoid disease, hereditary (APC)
• Allelic: Fumarase deficiency (FH)
• Allelic: Gardner syndrome (APC)
• Allelic: Gastric adenocarcinoma + proximal polyposis of the stomach (APC)
• Allelic: Glucocorticoid deficiency, due to ACTH unresponsiveness (MC2R)
• Allelic: Ideopathic Primary Adrenal Failure (MC2R)
• Allelic: Leiomyomatosis + renal cell cancer (FH)
• Allelic: McCune-Albright syndrome, somatic, mosaic (GNAS)
• Allelic: Multiple endocrine neoplasia 1 (MEN1)
• Allelic: Myxoma, intracardiac (PRKAR1A)
• Allelic: Osseous heteroplasia, progressive (GNAS)
• Allelic: Pituitary adenoma 3, multiple types, somatic (GNAS)
• Allelic: Pseudohypoparathyroidism Ia (GNAS)
• Allelic: Pseudohypoparathyroidism Ib (GNAS)
• Allelic: Pseudohypoparathyroidism Ic (GNAS)
• Allelic: Pseudopseudohypoparathyroidism (GNAS)
• Allelic: Striatal degeneration, AD (PDE8B)
• ACTH-independent macronodular adrenal hyperplasia (GNAS)
• ACTH-independent macronodular adrenal hyperplasia 2 (ARMC5)
• Bilateral adrenal hyperplasia (APC, FH, MC2R, MEN1)
• Cushing syndrome, ACTH-independent adrenal, somatic (PRKACA)
• Isolated micronodular adrenal hyperplasia (PDE11B, PDE8B)
• Macronodular adrenal hyperplasia (GNAS)
• Pigmented nodular adrenocortical disease, primary, 1 (PRKAR1A)
• Pigmented nodular adrenocortical disease, primary, 2 (PDE11A)
• Pigmented nodular adrenocortical disease, primary, 3 (PDE8B)
• Primary bilateral macronodular adrenal hyperplasia (APC, ARMC5, MEN1, MC2R, PRKACA)
• Primary pigmented micronodular adrenal dysplasia (PRKAR1A)