Sub-section: Adrenal Section: Endocrine

Incidence and presentation

Rare – 1-2 per million per year
Almost all present between 40-50yrs
Minor peak in children < 5
M = F
Presentation = Late
- Tend to be large (mean 9-13cm) and spread beyond Adrenal Gland
Most are functioning (57%)
- 48% Cushing’s syndrome
- 18% Multiple (Cushing’s and Virilisation)
- 6% Pure virilisation
- 3% Feminisation
- Rarely hyperaldosteronism
- Non-functioning (43%)
34% Abdominal discomfort
9% Incidentaloma

Aetiology

Most sporadic
Can be associated with some syndromes
MEN 1 syndrome
Beckwith-Wiedemann Syndrome in childhood
- Exophthalmos, microglassia, nephromegaly
Li-Fraumeni syndrome

Unenhanced CT scan
- Usually large (> 90% are > 4cm)
- 4cm cut-off for malignancy
  - 93% sensitivity
  - 76% specificity
- Heterogenous +/- central necrosis
- Irregular margins
- Denser than adenomas (Hounsfield units > 10)
- If contrast added – delayed washout
MRI
- High intensity in T2 weighted images
- With gadolinium – heterogenous enhancement, delayed washout
FDG-PET
- If can’t characterise by CT/MRI
- 100% sensitivity, 88% specificity in differentiating malignant from benign lesions

Percutaneous biopsy not recommended
- Difficulty differentiating benign and malignant disease
- Tumour seeding
Only absolute criteria for malignancy:
- Invasion into local structures
- Distant metastatic disease

T category	T criteria
TX	Primary tumor cannot be assessed
T0	No evidence of primary tumor
T1	Tumor ≤5 cm in greatest dimension, no extra-adrenal invasion
T2	Tumor >5 cm, no extra-adrenal invasion
T3	Tumor of any size with local invasion but not invading adjacent organs
T4	Tumor of any size that invades adjacent organs (kidney, diaphragm, pancreas, spleen, or liver) or large blood vessels (renal vein or vena cava)
N1 and M1 - present

Differentiate adenomas from ACC
The Weiss score is currently the most widely used.
It is based on 9 criteria rated 0 or 1 each depending on their absence or presence
- (1) diffuse architecture >1/3 of the tumor surface
- (2) Tumor necrosis
- (3) ≤ 25% of clear cells of spongiocyte aspect
- (4) Führman nuclear grade III or IV
- (5) mitotic count > 5 mitoses / 50 fields x400
- (6) presence of atypical mitosis
- (7) capsular invasion
- (8) venous invasion
- (9) sinusoidal invasion
Tumors with a score ≥ 3 are considered to have metastatic potential and are diagnosed as ACC

Surgery offers only potential cure
Open Adrenalectomy +/- En-block resection of adjacent organs and regional lymphadenectomy
- Laparoscopy may increase risk of recurrence or carcinomatosis
Complete resection in 70%
- Incomplete resection has very poor prognosis (mean < 1yr)
Take care with right sided tumours > 9cm
- Potential IVC invasion (+/- right heart invasion)
- Should do these cases on cardiopulmonary bypass
  - Prevents risk of potentially fatal tumour embolism
Palliative surgery (esp. if functional)

Chemo with Mitotane
- Derivative of insecticide DDT
- Direct adrenocortical toxin
- Overall response usually poor
Indications
- High risk disease
  - Ki-67 >10
  - R1 resection
  - Tumour spillage
  - Vascular invasion
Dose dependent GI and neurotoxic side effects
- Narrow therapeutic window
- Adrenal insufficiency
  - Need to start glucocorticoid replacement
  - Also need to monitor for aldosterone deficiency
- Hepatic toxicity

Mitotane alone + addition of chemotherapy
Can consider ablation for small tumours (RFA) <5cm to provide short term local control

5yr survival 16-38% depending on stage at presentation
- Increasing with use of mitotane
Local recurrence and metastases common
- Typically occurs within 2yrs from surgery
Mean survival following non-curative surgery or metastatic disease
- < 12 months