Endocrine

Question 1

Definition of adrenal incidentaloma

Answer 1

Tumour identified during investigation of an unrelated
condition

Question 2

Aetiology of adrenal incidentaloma

Answer 2

o Non-functional adrenal tumours
o Functional adrenal tumours (15%)
▪ Cortisol-producing adenoma
▪ Aldosterone producing adenoma
▪ pheochromocytoma
o Adrenocortical carcinoma (5-10%)
o Phaeochromocytoma (5-10%)
o Metastases (2.5%)
▪ Lung, breast, ovary, kidney, melanoma
o Others
▪ Myelolipoma, haemorrhage, adrenal cortical cyst
▪ Ganglioneuroma, neuroblastoma, lymphoma
▪ Congenital adrenal hyperplasia
▪ Haemangioma
▪ Granulomatous disease

Question 3

Key parts in history and exam of functional adrenal incidentaloma

Answer 3

o Cortisol – Cushing’s syndrome
▪ History
* Weight gain
* Fatigue, depression, emotional or cognitive changes
* Sleep disturbance, menstrual irregularity
* High blood pressure, glucose intolerance
* Easy bruising

▪ Examination
* Hypertension
* Central obesity, supraclavicular fat accumulation, buffalo hump
* Facial plethora, thin skin, purple striae, acne, bruising
* Hirsutism
* Proximal myopathy

o Aldosterone – Conn’s syndrome
▪ History
* Nocturia, polyuria
* Muscle cramps, palpitations
* Hypertension – difficult to control

▪ Examination
* Hypertension

o Pheochromocytoma
▪ History
* Episodic or paroxysmal headache, palpitations, diaphoresis
* Tremor, anxiety

▪ Examination
* Hypertension
* Orthostatic hypotension
* Pallor, retinopathy

Question 4

Biochemical evaluation of functional adrenal incidentaloma

Answer 4

o Screening
▪ Plasma aldosterone : renin ratio >20
* EUCs – hypokalaemia
▪ 24h urine catecholamines OR plasma metanephrines
* Urine metanephrine >1800mcg = diagnostic
* Plasma >3-4x upper limit normal is diagnostic
o Plasma test has high sensitivity. If positive, confirm with urine test
▪ 1mg dexamethasone suppression test (taken at midnight), plasma cortisol at 8am the next morning
* >138nmol/L is diagnostic
▪ Serum DHEAS and 17-hydroxyprogesterone

o Confirmation
▪ Midnight salivary cortisol, ACTH levels, 24h urine cortisol, 2 day dexamethasone suppression test
* 24h urine cortisol could be pituitary/adrenal/ectopic
* ACTH elevated means ACTH dependent cushing’s (pituitary or ectopic)
o High dose dexamethasone test will suppress pituitary but not ectopic
* ACTH independent Cushing’s → adrenal
▪ Plasma aldosterone >15ng/dL, aldosterone suppression test using saline infusion, 24h urinary aldosterone while on high sodium diet
* Consider adrenal venous sampling if bilateral CT abnormalities and >40y to avoid operating on bilateral adrenal hyperplasia

Question 5

Imaging required for adrenal incidentaloma

Answer 5

o Adrenal protocol CT
▪ IV contrast enhanced
* Delayed phases at 10 and 15 minutes
▪ Aims to determine benign vs malignant vs phaeochromocytoma
* Benign –
o CT attenuation <10 hounsfield units on non contrast CT
o Washout >50% at 10 minutes

• Suspicious
  o CT attenuation >10 hounsfield units on non contrast CT
  o Washout <50% at 10 minutes
• Phaeochromocytoma
• > 10HU
  o Enhancement with contrast >100HU
• Size
  o >4cm is suspicious and should be offered OT (>6cm = 35-98% chance ACC, vs <1/10000
  if <6cm)

o MRI
▪ Good alternative to CT with high resolution (useful in children and pregnancy)
▪ Phaeo
* Intensity similar on T1 to liver
* Hyperintense on T2

o MIBG scan (Iodine-123 meta-iodobenzylguanidine)
▪ Best localisation scan for phaeochromocytoma

• 18 FDG PET scan (can consider PET DOTATATE)

Question 6

Indication of adrenal biopsy

Answer 6

Has a role in suspected metastastses to adrenal
▪ Need to exclude phaeo before biopsy
▪ Otherwise no role

Question 7

Management of non functioning adrenal tumour

Answer 7

o >6cm – adrenalectomy; (4-6cm – individualised decision)
o <4cm – biochemical and imaging surveillance annually

Question 8

Management of pheochromocytoma

Answer 8

o Medical management preoperatively (usually inpatient workup)
▪ Phenoxybenzamine
* Non selective alpha blocker
* 20mg BD, increasing in 10mg increments until postural hypotension occurs
o 2-4 weeks as outpatient
* Side effects
o Headache, nasal stuffiness, somnolence, reflex tachycardia
▪ Add beta blocker after alpha blockade complete – propranolol
* Counteracts reflex tachycardia

o Adrenalectomy
▪ Avoid handling tumour
▪ Clip vein early
▪ Intraoperative hypertension management
* IV sodium nitroprusside
* Nicardipine, Phentolamine, Beta blockers
▪ Reactive hypotension after tumour devascularisation
* May need volume replacement/inotropes

o Post op
▪ HDU, regular glucose monitoring

o Malignant phaeochromocytoma
▪ Higher risk in
* larger phaeo or extra adrenal paraganglioma
* SDHB mutation
▪ Diagnosed based on metastatic disease
* Lymph nodes, liver, bone, lung
▪ Treatment
* Tumour debulking
* Alpha and beta blockade
* Radiotherapy, Chemotherapy, Transcatheter arterial embolization

o Phaeochromocytoma in pregnancy
▪ Adrenalectomy after delivery
* Alpha blockade
* Elective c-section in 3rd trimester
* Early adrenalectomy after haemodynamics of pregnancy

Question 9

Management of Cushing’s disease

Answer 9

o Adrenalectomy
▪ Be aware patients will be high risk of infection, fractures, hyperglycaemia post operatively
o Post operative steroid replacement (remaining adrenal gland is usually suppressed)
▪ Synacthen test before withdrawal of steroid supplementation (up to 1 year later)

Question 10

Management of primary hyperaldosteronism

Answer 10

o Preoperative
▪ Correct hypertension and hypokalaemia
o Adrenalectomy
o Post operative
▪ Hypotension resolves completely in 50%, others will continue to need medical management
o Unfit for surgery → spironolactone
o Bilateral adrenal hyperplasia → medical management

Question 11

Adrenocortical carcinoma

Answer 11

• Epidemiology
  o Incidence 1-2/million/year
  o Majority sporadic
  ▪ Associated with some rare syndromes
• MEN1
• Beckwith Wiedemann syndrome (exophthalmos, macroglossia, nephromegaly)
• Li-Fraumeni syndrome (breast carcinoma, osteosarcoma, brain tumours)
• Clinical
  o Majority (60%) are hormonally functional, usually multiple hormones
  ▪ Primary hyperaldosteronism
  ▪ Virilisation or feminisation
  ▪ 57% functional, 48% cushing’s, 6% virilisation, 3% feminisation, 18% cushing + virilisation, 43% non
  functional
  o Incidental finding
  o Abdominal discomfort
• Workup – biochemistry
  o Hormone profile as above
  ▪ Plasma metanephrines
  ▪ Dexamethasone suppression test
  ▪ Plasma aldosterone/renin ratio
  ▪ DHEAS
• Imaging
  o Adrenal protocol CT
  ▪ >10 Hounsfield units on non-enhanced CT
  ▪ Delayed washout of contrast <50% after 10 minutes
  ▪ Irregular margin
  ▪ Local invasion
  ▪ Distant metastases
  ▪ Size
• Risk 2% <4cm, 6% 4-6cm, 25% >6cm

o MRI
▪ Hyperintense T2
▪ Heterogeneous enhancement
▪ Delayed washout with gadolinium contrast

• Biopsy
  o Not recommended (risk of seeding, difficult to interpret)
• Treatment
  o Adrenalectomy
  ▪ Access
• Laparoscopy in expert hands
• Open surgery recommended
  ▪ En bloc resection of perinephric fat, regional lymph nodes, adjacent organs if required (kidney,
  pancreas, liver, spleen)

o Debulking
▪ Consider in functional, unresectable disease

o Medical treatments
▪ Mitotane
* Originally an insecticide
* Induces necrosis by mitochondrial degeneration
▪ Radiotherapy to tumour bed if involved margins or high risk patient
▪ Chemotherapy agents are under investigation
* Prognosis
o 5YS 16-38%, median survival in metastatic disease or R1 resection <12 months