Adrenal tumours and nodules

• Adrenal incidentalomas affect 3% of people aged >50, and 10% aged >80
• The adrenal medulla produces catecholamines
• The adrenal cortex produces aldosterone, cortisol and androgens

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Differential of an adrenal nodule

• 80% benign (20% of these secrete hormones). These include adenomas, cysts, haematomas, myelolipomas, nodular hyperplasia, ganglioneuromas
• 8% represent cancer
• 2% are adrenal carcinoma
• 7% are phaeochomocytoma
• 5% are metastases
  • • Especially from the lung, breast, bowel, pancreas
    • Adrenal metastases are uncommon if there’s no known history of cancer
• Functional tumours (14%) may secrete cortisol, aldosterone or catecholamines
  • • MACS – mild autonomous cortisol secretion
    • PA – primary hyperaldosteronism
    • Both are associated with CV risk
    • Conshing syndrome – tumours which secrete aldosterone and cortisol, very rare

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Initial assessment

• Usually only investigate nodules if
  • • > 1cm
    • Risk factors for malignancy
    • Age <40
    • Relevant symptoms
• Only investigate nodules <1cm if there are clinical signs – especially of phaeochomocytoma or malignancy
• Always discuss with endocrinology
  • • The can be subtle hormone excess or malignancy
    • If referring – include detailed drug history (which can interfere with endocrine tests)
• Ask about
  • • Weight loss / gain and fatigue (malignancy, Cushing’s)
    • Menstruation
    • Proximal myopathy
    • Hirsutism in women
    • Symptoms suggesting phaeochromocytoma like headaches and palpitations
• Check
  • • Blood pressure, CBG, HbA1C
    • Examine for striae, buffalo hump, moon face, proximal myopathy
    • If bulky bilateral lesions – check for hormone deficiency (there may be a postural drop, weight loss, low Na)
• Red flags for malignancy – though note that cancer and benign adrenal tumours can co-exist
  • • Older age
    • Previous cancer
    • Size > 4cm
    • Heterogenous density
    • Growth at follow up

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Imaging

• Consider CT (plain, non-con) or MRI (good if young, but more subjective and has less diagnostic value) of adrenals
• Appearances can help distinguish type on CT
  • • Especially helpful for diagnosing lipid-rich adenomas and myelolipomas, which have a low Hounsfield Unit score
    • Problem is – not adrenal masses picked up on different types of scan ie contrast scans, CTPAs etc, not a plain CT of adrenals, so interpretation is difficult
• Hounsfield Units 
  • • One has a Hounsfield unit of 1000, air of -1000. Liver is about 50, brain 45, blood 40, kidney 30, muscle 25, water 0, fat -75.
    • If HU of <10 – no need for further assessment
    • If HU >10, ask for contrast CT of adrenals
    • If lesion if homogenous, and of any size (even if >4cm), and HU<10 – no further imaging or follow up required
    • If HU 10-20, <4cm, homogenous
      • • Probably fine if no history of previous cancer
        • Could do 12-month surveillance scan or consider further imaging (PET, MRI, contrast CT)
        • If HU <20 and lesion <4cm – positive predictive value for benign disease is 99.4 (if no previous cancer)
    • If >20 HU, and either heterogenous or >4cm
      • • Up to 50% risk of cancer if both are true
        • Needs MDT discussion
        • Consider surgery or immediate additional imaging
    • If HU 11-20 and >4cm, or HU >20 and <4cm, or heterogenous and <4cm
      • • Likely benign if no history of cancer, but needs MDT discussion and PET-CT if available (if not – consider follow up CT/MRI)
• Consider functional imaging
  • • FDG PET for malignancy, or for indeterminate masses
    • MIBG SPECT for phaeochromocytoma
    • C-metomidate PET for Primary Hyperaldosteronism

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Hormonal assessment

• Often done later in the endocrinology clinic
• Consider functional hormone testing in all adrenal adenomas – even if thought to be metastatic
• Phaeochromocytoma
  • • Can often be excluded on imaging alone (often high density, vascular, heterogenous)
    • If not – plasma metanephrines
    • Beware of false positives (medications like amitriptyline/TCAs can raise metanephrine levels)
• Hyperaldosteronism – can check aldosterone-renin ratio off interfering drugs and once K+ corrected
• Sometimes check plasma androgens
• Cortisol excess
  • • Often lesions of 2-3cm do slightly overproduce cortisol in the absence of Cushing’s, so a more tricky hormone to test for
    • Consider an overnight dexamethasone suppression test – take 1mg dexamethasone at bedtime, measure cortisol next morning
      • • Cortisol suppressed to <50 excludes it
        • If >50 and signs of Cushing’s = Cushing’s
        • If >50 and no signs of CS, likely MACS (mild autonomous cortisol secretion)
    • MACS
      • • In this case check for comorbidities eg DM, HTN, dyslipidaemia, osteoporosis, and check ACTH.
        • Likely that ACTH is low, and urinary free cortisol is low
        • Management controversial and no consensus
        • Risk of progression to overt Cushing’s is <1%
        • Usually no need for monitoring
        • Occasionally surgery considered, especially if comorbidities, unilateral mass, good general health, patient preference
        • Can help BP control especially, and to some extent glycaemic control

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Adrenal biopsy

• Often not required
• If concern over adrenal carcinoma – best to resect (unless it’s very advanced cancer, or patient unfit for surgery)
• Always ensure metanephrines normal first (phaeochromocytomas can look like adrenal carcinomas)
• Only do if histology will change management (histology may suggest appropriate immunotherapy for instance)
• Sometimes done if indeterminate mass in someone with extra-adrenal cancer, or if there’s a possibility of infiltrative disease (lymphoma, TB)

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Notes on specific conditions

• Primary aldosteronism
  • • Work up is complex
    • Elevated aldosterone, low renin
    • Unilateral disease treated surgically, bilateral disease, medically (lifelong spironolactone). Consider adrenal venous sampling to distinguish
    • Hypertension common, hypokalamia affects up to half
    • Check aldosterone/renin ratio (rectify hypokalaemia first, and check medications don’t interfere)
    • For a more detailed review, see hypertension – secondary causes
• Adrenal carcinoma
  • • Aggressive
    • Can produce cortisol (Cushings syndrome) or no hormones
    • Often large when diagnosed
    • Treat with surgery, mitotane and irradiation
• Adrenal metastases
  • • Common from a variety of tumours – especially kidney, lung, melanoma, breast, gastric, NET, HCC
    • Often do not respond well to immunotherapy
    • Usually a bad sign, especially in lung cancer or melanoma
    • Adrenalectomy can be considered, but often not beneficial, and high rate of complications. There is evidence of benefit in renal cancer in particular however