Medical Articles

Adrenal Carcinoma

Case study: Miss JW

  • 32 year old female
  • Presented to Endocrinology @ TBH 12/2006 with severe virilisation
  • Obese (110Kg)
  • Other complaints:
    • Depression
    • Menstrual irregularity
  • No past history of note

Examination

  • Obese patient with Cushingoid habitus and severe virilisation
  • Hypertensive with BP 155/94
  • Abdomen: Striae, no masses palpable
  • Systemic examination otherwise unremarkable

Workup

Biochemistry:

  • U+E - Normal
  • FBC - Normal
  • LFT - Normal
  • 24h U-Cortisol - 1380 nmol/24h (152-789)
  • ACTH - Low
  • DHEAS - 23.2 umol/l (2.7-9.2)
  • Testosterone - 11nmol/l (0.5-2.6)
  • Suppressed FSH and LH
  • Metanephrines and VMA normal
  • Aldosterone renin ratio normal

Imaging

  • Contrasted CT abdomen
    • 5cm heterogeneous mass of the right adrenal with microcalcification. No evidence of invasion of surrounding structures.
    • Four liver metastasis less than 2cm (Segment 2,4B, 5 and 6)
  • Norchol scan (NP59)
    • Adrenal primary with liver metastasis

Options

Conservattiive

  • Surgery
  • Debullking for symptom relief
  • Chemotherapy
  • Mitotane
  • Mitotane with Cisplattin/Etoposide

Procedure - Palliation

  • Performed at TBH on 25/1/2007
  • Laparoscopic right adrenalectomy
  • Laparoscopic sonar guided Radiofrequency ablation of liver metastasis
  • Uncomplicated course with discharge on day 3 on stteroid replacement

Histology

  • Adrenocortical cancer with areas in keeping with pigmented miicronodular hyperplasia. Tumour to within 1mm of the resection margin.
  • Functional (Glucocorticoid and androgen producing) ACC

Follow up

  • 07/2007 (Endocrinology TBH)
    • Virilisation resolved (Voice change persistent)
    • Weight 96Kg
    • Biochemistry
      • Testosterone 1.3 (0.5-2.6)
      • DHEAS 0.2 (2.7-9.2)
      • 24h U-Cortisol 93 (152-789)
    • Imaging
      • CT – No recurrence
      • Norchol scan – No hot spots

Follow up

  • 15/1/2008 (Endocrinology TBH)
    • Virilisation resolved (Voice unchanged)
    • Weight 89Kg
    • Biochemistry
      • Testosterone 2.1 (0.5-2.6)
      • DHEAS 0.1 (2.7-9.2)
      • 24h U-Cortisol 240 (152-789)
    • Imaging
      • CT – No change from 2007 scan

ACC – An overviiew

  • 1% of all adrenal tumours (1/million/year in USA)
  • Median age 40–50 years
  • 1:1 male to female ratio
  • 60-80% functional
    • 30% Cortisol
    • 20% androgen
    • 10% estrogen
    • 35% mixed (High index of suspicion in adrenal lesions producing more than one hormone)

ACC - Staging

  • Stage I
    • Disease confined to the adrenal gland and <5 cm in diameter (approx 20%)
  • Stage II
    • Diisease conffiined tto tthe adrenall glland and >5 cm iin diiametter (approx 20%)
  • Stage III
    • Local invasion that does not involve adjacentt organs or regional lymph nodes (approx 20%)
  • Stage IV
    • Distant mettasttases or invasion into adjacentt organs plus regional lymph nodes (approx 40%)

ACC – An overview

  • Imaging
    • CT – Hettrogenous mass
    • MRII – Rapiid conttrastt washoutt iin adenoma and persiisttence in malignant tumours

ACC – An overviiew

  • Treatment
    • Complete en bloc resection
    • Local disease 40 – 60% 5 year survival
    • Local invasiion 20 – 30% 5 year survival
    • Metastatic diisease <10% one year survival
  • Recurrence after resection
    • 65% llocalllly or iin draiiniing llymph nodes
    • Distant recurences – Lung, Liiver, Bone

ACC – Surgery

Adrenal Carcinoma

Complete surgical resection is the primary treatment modality

ACC - Surgery

  • MSKCC: 47 patients with recurrent/metastatic disease

Complete second resection - mediian surviivall of 74 montths (5-year survival, 57%)

Incomplete second resection - median survival of 16 months (5-year survival, 0%).

Prognostic factors

  • Review of 46 patients at MSKCC - 3 histologic factors correlated with survival
    • Tumour >12cm
    • Six or more mitotic figures /10hpf
    • Presence off hiisttollogiic eviidence off iinttrattumourall hemorrhage
    • 5 year surviivalls::
      • 0 factors: 83%
      • 1 factor: 42%
      • 2 factors: 33%

ACC – Systemic therapy

  • Mitotane
  • Pesticide analogue (DDT) – direct adrenolytic agent
  • Remission rate 20-35%
  • Symptom palliation 60 - 80%
  • Trials evaluating combination Tx with Cisplatin/Etoposide ongoing.

Adjuvant Mitotane

Adrenal Carcinoma

Italian series: No survival difference between two groups of completely resected patients

Effect of adjuvant mitotane (n = 11) compared with no treatment (n = 15) on the disease-free interval in patients with localized or regional adrenocortical carcinoma.

Summary

  • Adrenocortical carcinoma is a rare disease that often presents late
  • Priimary curattiive ttherapy iis surgiicall
  • No rolle ffor adjjuvantt chemottherapy has been demonsttratted tto datte
  • Palliative therapy with mitotane may be useful; its palliative effect may be entirely due to adrenollytic effect
  • Reoperation appears to be the only long term curative option in recurent cases
  • Cytotoxic chemotherapy in the advanced/ metastatic setting has nott been definitively demonstrated to be useful in controlled trials