Incidentaloma natural history, complications and prognosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mohammed Abdelwahed M.D[2]

Overview

If left untreated, patients with adrenal incidentaloma may progress to develop Dyslipidemia, Osteoporosis, Hyperglycemia, Malignant hypertension, Intracranial hemorrhage, Acute coronary syndrome, Aortic dissection, malignant transformation, and metastasis. Prognosis is usually good in benign adrenal incidentalomas, death is not directly related to the adrenal mass, but to cardiovascular accidents, malignancy, and chronic disorders, as observed in the general population. Adrenocortical carcinoma (ACC) carries a poor prognosis and is unlike most tumours of the adrenal cortex, which are benign (adenomas) and only occasionally cause Cushing's syndrome.

Natural History, Complications, and Prognosis

Natural History

• The symptoms of adrenal incidentaloma usually develop in the first/ second/ third decade of life, and start with symptoms such as weight loss, anorexia. diabetes, high incidence of vertebral fractures, dyslipidemia, impaired glucose tolerance or type 2 diabetes mellitus, and evidence of atherosclerosis, paroxysmal attacks of hypertension, palpitation, diaphoresis, headache, pallor, and tremor, hypertension and hypokalemia.
• If left untreated, patients with adrenal incidentaloma may progress to develop Dyslipidemia, Osteoporosis, Hyperglycemia, Malignant hypertension, Intracranial hemorrhage, Acute coronary syndrome, Aortic dissection, malignant transformation, and metastasis.
• It seems that the majority of masses, classified as benign and non-hypersecreting at diagnosis, subsequently remains hormonally and morphologically unchanged.

• In a percentage which varies in different series, some cases develop mass enlargement and/or adrenal hyperfunction.
• Nine precent of cases showed mass enlargement greater than 1 cm and/or the appearance of another mass in the contralateral adrenal gland.
• Mass enlargement was generally limited to 1–2 cm increase in diameter over a period of 1–3 years.
• The likelihood of malignant transformation at longterm follow-up for masses considered as benign at diagnosis is therefore minimal, and is estimated at one case per 1000 incidentalomas.
• Reduction or even disappearance of the adrenal mass have been reported in up to 40% (mean, 3.6%) of adrenal incidentalomas, most often in the case of cystic lesions, hematomas, or adrenal pseudotumors.

Complications

• Common complications of adrenal incidentaloma include:
  • Hypertension
  • Glucose intolerance
  • Diabetes mellitus
  • Obesity
  • Dyslipidemia
  • Osteoporosis
  • Hyperglycemia due to opposition of insulin effect by high doses of adrenaline secreted by the tumor.
  • Malignant hypertension that may cause cerebrovascular accidents such as:
    • Intracranial hemorrhage
    • Acute coronary syndrome
    • Aortic dissection
    • Heart failure
  • Metastasis to:
  • Lymph nodes
  • Bones
  • Lungs
  • Liver

Prognosis

• In the vast majority of patients with apparently benign adrenal incidentalomas, death is not directly related to the adrenal mass, but to cardiovascular accidents, malignancy, and chronic disorders, as observed in the general population.
• Cardiac disease in 43%, malignancy in 22%, chronic obstructive pulmonary diseases in 11%, Alzheimer’s disease in 6%, cerebrovascular accident in 4%, pneumonia or sepsis in 4%, ruptured abdominal aortic aneurysm in 2.5%, diabetic renal failure in 2.5%, and other causes in 5%. Also in the series reported by Siren et al., including 21 patients with adrenal incidentaloma.
• Adrenocortical carcinoma (ACC) carries a poor prognosis and is unlike most tumours of the adrenal cortex, which are benign (adenomas) and only occasionally cause Cushing's syndrome.
• Five-year disease-free survival for a complete resection of a stage I–III ACC is approximately 30%.
• The most important prognostic factors are age of the patient, stage of the tumor, mitotic activity, venous invasion, weight of 50g, and diameter of 6.5 cm.
• The most common causes of death were related to cardiovascular diseases (acute myocardial infarction, ventricular arrhythmia, cardiac failure, multi-infarct dementia, and acute cerebrovascular infarct), which occurred in seven out of nine deaths, whereas pulmonary embolism secondary to deep vein thrombosis and lung cancer occurred in two.
• Mean age at death was 72.8 years.
• Whether the relatively high rate of mortality due to cardiovascular disease is related to hypercortisolism was not investigated.