Adrenals

Thin echogenic medulla surrounded by hypoechoic cortex.

  • Adrenal cortex (‘GFR’)- Outer zona Glomerulosa (mineralocorticoids esp aldosterone stimulated by the RAS renin-angiotensin system), zona Fasciculata (thickest, glucocorticoids esp cortisol stimulated by ACTH) and inner zona Reticularis (androgens stimulated by ACTH).
  • Adrenal medulla – Neural crest cells (neuroendocrine, chromaffin cells) with supporting sustentacular cells. Produces catecholamines (epinephrine, norepinephrine). Extra-adrenal paraganglia include branchiomeric (associated with arterial vessels including aorticopulmonary, pulmonary and coronary), intravagal (along vagus nerve), aortico-sympathetic (sympathetic trunk and ganglia along aorta, including organs of Zuckerkandl close to the bifurcation), visceral-autonomic (visceral organs eg heart, other blood vessels). Tumours include pheochromocytoma/paraganglioma (chromaffin cells) and neuroblastic tumours (neuronal cells).

Endocrine Syndromes

Cushing Syndrome

(Hypercorticolism). Excessive glucocorticoids causing truncal obesity, moon facies, buffalo hump (fat accumulation in posterior neck and back), proximal muscle atrophy, DM, loss of collagen (easy to bruise, thin skin), osteoporosis, increased risk of infection, mental disturbances, hirsutism, oligomenorrhoea, nephrolithiasis. Causes include:

  • Exogenous glucocorticoids (iatrogenic Cushing syndrome) – Most, causing bilateral cortical atrophy.
  • ACTH-dependent – Bilateral diffuse cortical hyperplasia with thickening, variably nodular, vacuolated lipid-rich zona fasciculata. Most hyperplasia is ACTH dependent; primary cortical hyperplasia is uncommon.
    • Cushing disease (70%) – ACTH-secreting pituitary adenoma.
    • ACTH-secreting non-pituitary tumours (10%) – SCLC, bronchial carcinoid, medullary thyroid carcinoma, neuroendocrine tumours (may produce ectopic CRH stimulating the pituitary).
  • ACTH-independent – Elevated serum cortisol with reduced ACTH.
    • Adrenal adenoma (10%)
    • Adrenal carcinoma (5%) – Generally more marked hypercortisolism than adenomas or hyperplasia.
    • Macronodular hyperplasia – Usually sporadic. Includes McCune-Albright syndrome (precocious puberty, polyostotic fibrous dysplasia and Cafe-au-lait spots). Prominent nodules up to 30mm.

Hyperaldosteronism

Elevated aldosterone causing HTN, persistent hypokalaemia, raised serum and urine aldosterone, reduced plasma renin activity.

  • Primary hyperaldosteronism – Adrenal venous sampling may confirm site of aldosterone secretion and differentiate adenoma from hyperplasia.
    • Bilateral idiopathic hyperaldosteronism (IHA, 60%) – Bilateral adrenal nodular hyperplasia. Older, less severe HTN. Unknown aetiology. Tx medical.
    • Adrenal adenoma (80%, Conn syndrome) – 30-40yo, F:M 2:1. Almost all are solitary, <20mm, L>R, may be buried in the gland. Tx resection.
    • Adrenal carcinoma (rare)
    • Glucocorticoid-remediable hyperaldosteronism (uncommon) – Familial, under influence of ACTH.
  • Secondary hyperaldosteronism – Activated renin-angiotensin system (increased plasma renin).
    • Reduced renal perfusion – Arteriolar nephrosclerosis, renal artery stenosis.
    • Arterial hypovolaemia and oedema – CHF, cirrhosis, nephrotic syndrome.
    • Pregnancy – Oestrogen-induced.

Adrenogenital Syndrome

(Virilisation syndromes). Androgens secreted include dehydroepiandrosterone (DHEA) and androstenedione (Andro), regulated by ACTH.

  • Excess ACTH – May cause pure syndrome or asociated with Cushing disease.
  • Androgen-secreting adrenal carcinomas – More common than adenomas. May be asociated with hypercorticolism (mixed syndrome).
  • Congenital adrenal hyperplasia (CAH) – Group of AR enzyme deficiency (esp 21-hydroxylase) with lack of cortisol and/or aldosterone (salt-wasting) production. May be associated with genital ambiguity. Excess precursors are channeled to other pathways including androgen production. Increased ACTH causes marked adrenal hyperplasia.

Adrenocortical Insufficiency

Progressive weakness, fatigue, hyperkalaemia, hyponatraemia, hypovolaemia/hypotension, hypoglycaemia.

  • Primary hypoadrenalism – Hyperpigmentation due to elevated pro-opiomelanocortin (POMC, precursor for ACTH and melanocyte-stimulating hormone MSH)
    • Acute primary adrenocortical insufficiency (adrenal crisis) – Intractable vomiting, abdominal pain, hypotension, coma, hypotension, imminent death. Tx corticosteroids.
      • Crisis in those with chronic adrenocortical insufficincy – Any stress requiring increase in steroids (infection, trauma, surgery), but glands are incapable of doing so.
      • Rapid withdrawal of exogenous corticosteroids, or failure to increase in periods of acute stress.
      • Massive adrenal haemorrhage damaging the adrenal cortex – Newborns in difficult labour (deficient prothrombin), anticoagulation, postsurgical DIC with haemorrhagic infarcts. Waterhouse-Friderichsen syndrome is from bacteraemic infection (esp N.meningitidis, Pseudomonas, pneumococci, H.influenzae, staph) with rapidly progressing hypotension, DIC, bilateral adrenal haemorrhage; more common in children.
    • Chronic primary adrenocortical insufficiency (Addison disease) – When 90% of cortex is destroyed. Causes include:
      • Autoimmue adrenalitis (60-70%) – Autoantibodies to steriodogenic enzyes. Isolated or part of autoimmune polyendocrine syndroem type 1 (APS1, autoimmune polyendocrinopath) associated with hypoparathyroidism, hypogonadism, pernicious anaemia; or APS2 associated with type 1 DM or thyroiditis.
      • Infection – TB adrenalitis (previously most common cause), fungi including histoplasmosis, coccidioides, AIDS (CMV, MAI, Kaposi sarcoma). Calcifications suggest previous TB or histoplasmosis.
      • Metastases – Usually enough tissue is preserved to avoid insufficiency, but can occur.
      • Amyloidosis, sarcoidosos, haemochromatosis.
      • Congenital – Congenital adrenal hypoplasia, adrenoleukodystrophy.
  • Secondary hypoadrenalism – Deficiency of ACTH from pituitary/hypothalamic axis with tumour, infection, infarction, radiotherapy, long-term exogenous steroids or neoplastic production. Usually as a component of panhypopituitarism.

Benign Adrenal Lesions

Adrenocortical Hyperplasia

50% will appear anatomically normal, 50% are diffusely enlarged (>50mm long, >10mm thick, maintaining normal shape), occasionlly nodular mimicing adenomas. Occasional loss of signal on out-of-phase MR (microscopic fat). DDx metastases, infection (TB, histoplasmosis, CMV), lymphoma.

Adrenocortical Adenoma

F>M, peak 30-50yo. Nonhyperfunctional or functional (radiologically and histologically similar); more commonly hyperaldosteronism or Cushing syndrome. If functional the contralateral adrenal cortex may be atrophic. Incidental in 3-5% of population. Yellow-brown due to lipid. Typically small <40mm, well-defined, smooth, round, homogeneous, 70% are lipid-rich (functioning adrenal tissue concentrates cholesterol as precursor of hormones) with unenhanced CT <10HU or loss of signal on out-of-phase (cf in-phase) chemical shift MRI. Homogeneous enhancement with rapid washout on delayed 10-15min scan. Absolute percentage washout (APW) >60% being (PV-delayed)/(PV-unenhanced). Relative percentage washout (RPW) >40% being (PV-delayed)/PV. Histogram analysis with >10% negative pixel percentage. Lesions still indeterminate require follow-up or biopsy.

Adrenal Myelolipoma

Rare, nonfunctioning tumours from haematopoietic cells mixed with adipocytes, no malignant potential. Up to 300mm, commonly heterogeneous with mixed marrow fat and haemopoietic tissue, calcification in 20%. Macroscopic fat makes diagnosis difinitive with HU < -30, fat-sat MRI shows loss of signal. On US extremely echogenic, may blend in with retroperitoneal fat.

Adrenal Haemorrhage

Most common in newborn, induced by hypoxia, birth trauma, septicemia; most bilateral. In children may be from child abuse. In adults from trauma, infection; R>L. Bilateral may cause adrenal insufficiency. Hypodense, periadrenal fat stranding, thickening of adjacent fascia. Reduces in size over time, may calcify, causes adrenal pseudocyst.

Adrenal Calcifications

Most commonly from adrenal haemorrhage. TB and histoplasmosis may cause diffuse calcification and Addison disease. Tumours that calcify include neuroblastoma, ganglioneuroma, adrenal carcinoma, pheochromocytoma. Wolman disease – rare autosomal recessive lipid disorder with enalrged calcified adrenals, hepatosplenomegaly.

Adrenal Cysts

Rare, usually incidental, F>M, any age. True cysts are lined with endothelium/epithelium, tend to be multilocular with septal calcification. Pseudocysts have fibrous wall, usually from haemorrhage or infarction, usually unilocular with calcification in wall. May be necrosis or cystic degeneration of a cortical/medullary neoplasm. Parasitic cysts are usually echinococcal. Benign and uncomplicated when have thin walls, internal water density without debris, <50-60mm, no internal enhancement, homogeneous high T2. Calcification in wall and septa are common. Complicated cysts may be from haemorrhage or tumour, should be resected.

Malignant Adrenal Lesions

Adrenal Metastases

In 25% of those with malignancy, 4th most common site of metastases after lung, liver and bone. Most commonly lung, breast, melanoma, GI, renal. Small <30-40mm lesions tend to be homogeneous, well-defined, difficult to distinguish from adenomas. Larger >40mm lesions tend to be heterogeneous, thick irregular border invading adjacent structures.

Adrenocortical Carcinoma

Uncommon, lethal. Carcinomas are more common than adenomas in children. Increased risk with Li-Fraumeni syndrome, Beckwith-Wiedermann sydnrome. Most large and invasive at presentation. 50% are hyperfunctioning (more than adenomas) causing virilisation (more common), Cushing syndrome, or feminisation. Typically 40-200mm with central necrosis and haemorrahge, cystic change, irregular enhancment, delayed washout, calcification in 30%. Rarely contains fat. Commonly invades adrenal/renal vein, IVC, lymphatics with para-aortic nodes, metastases to liver, lung etc. Bone metastases are unusual. Any tumours >40-50mm should be resected due to risk of carcinoma. Mean survival ~2yrs. Metastatic carcinomas may be histologically difficult to distinguish from primary adrenal carcinoma.

Adrenal Lymphoma

May be indistinguishable from metastases. 50% bilateral. May be intrinsic to the adrenal preserving the overall shape (adreniform), or invade from the retroperitoneum. Associated with retroperitoneal nodes.

Phaeochromocytoma

Rare tumour of chromaffin cells causing excess catecholamines with HTN, HA, tremor, paroxysmal attacks (abrupt HTN, tachycardia, palpitations, HA, sweating, tremor, apprehension). Catecholamine cardiomyopathy is acute CHF, pulmonary oedema, MI, VF or CVA. Some also secrete other hormones including ACTH, somatostatin. Increased urinary free catecholamines and metabolites (vanillymanmdelic acid, metanephrines). Rule of 10’s:

  • 10% bilateral (of sporadic tumours), up to 50% in syndromes.
  • 10% extra-adrenal (ie 90% from adrenal medulla), others are termed paragalngiomas.
  • 10% of adrenal lesions are malignant – Defined by presence of metastases (LN, liver, lung, bone). Histology unreliable for benignity, even capsular/vascular invasion may be benign. 30% of extra-adrenal paragangliomas are malignant. 30% of familial lesions are malignant.
  • 10% not associated with hypertension.
  • 25% are familial (previously thought to be 10%) – Younger age, more likely multifocal/bilateral, 30% of these are malignant. Mutations include MEN-2A, MEN-2B, NF1, VHL, familial paraganglioma 1,2&3, TS, Struge-Weber.

Traditionally advised against IV contrat due to risk of adrenergic crisis, but recent studies show it is safe with nonionic contrast. Most are >20mm, vary from purely solid to complex to predominantly cystic, calcification rare but usually eggshell or stippled, poor contrast washout, commonly atypical appearance, most common adrenal tumour to spontaneously haemorrhage. If no lesion is seen, scan chest to pelvis with extra-adrenal sites including organ of Zuckerkandl (near aortic bifurcation), bladder, para-aortic sympathetic chain; may be best with MR. Very bright T2, moderate enhancement, no chemical shift, bright on MIBG.

Multiple Endocrine Neoplasia (MEN) Syndromes

Proliferative lesions of multiple endocrine organs including hyperplasia, adenomas, carcinomas. Occur at younger ages, synchronous or metachronous, multifocal, tend to be more aggressive with higher recurrence rates.

  • MEN-1 (Wermer syndrome) – Rare AD, MEN1 tumour suppressor gene on chromosome 11 (encodes menin). Involves the Parathyroids (primary hyperparathyroidism in 90%, hyperplasia and adenomas), Pancreas (pancreatic endocrine tumours, most commonly Pancreatic Polypeptide, next gastrinomas, insulinomas), Pituitary (Prolactinoma, occasionally somatotrophin-secreting tumour), duodenal gastrinoma. NOT associated with pheochromocytomas.
  • MEN-2
    • MEN-2A (Sipple syndrome) – RET gene on chromosone 10. Pheochromocytoma, thyroid medullary carcinoma, parathyroid hyperplasia.
    • MEN-2B – RET gene. Medullary thyroid carcinomas, pheochromocytomas, neuromas/ganglioneuromas (skin, oral mucosa, eyes, respiratory/GI tract), marfanoid skeleton.
    • Familial medullary thyroid cancer – Variant of MEN-2A, with predisposition to medullary thyroid cancer.

Genetic screening is more beneficial in MEN-2 due to life-threatening medullary thyroid carcinoma. All those with RET mutations should be offered prophylactic thyroidectomy.