2. • Adrenocortical tumors are rare
(incidence 1-2 per 1 million) (1)
• They present in a variety of ways and
carry a poor prognosis
• 5 cases of adrenocortical tumors and
their outcomes
1. B. Allolio & M. Fassnacht. Clinical Review. Adrenocortical Carcinoma: Clinical update. JCEM June 2006. 91(6):2027-2037
4. Case 1: LB, 64 ♀
• Jan 2013: Presented with incidental 9cm right adrenal
mass on US after investigation of fever and pain
• Jan – May : further images and endocrinology DELAY in
investigation
• 2 May 2013: discussed at MDT
• 5 June 2013: open R adrenalectomy and nephrectomy
• 5 July 2013: Mitotane started (histology: high mitotic
activity, capsular rupture).
• Oct 2013: unable to tolerate therapeutic levels of
Mitotane (tremors and nausea). No evidence of
metastases
5.
6. Case 2: TB, 38 ♀
• Nov 2012: Presented to DGH with abdominal pain. CT
20cm left adrenal mass and probable lung nodules
• 13 Dec 2012: Transferred to tertiary centre – L
adrenalectomy. Not thought clinically cushingoid but no
secretory studies pre or post operatively. Not seen by
endocrinology. Histology showed high mitotic rate, Ki67
index and capsular invasion
• 17 Jan 2013: Admitted SOB with tumour in R ventricle
and IVC. Mitotane started DELAY from surgery
• Etoposide, Doxorubicin and Cisplatin discussed but RIP 4
Feb 2013
7. Case 3: KG, 39 ♂
• Feb 2012: 6M history in features of Cushings DELAY in
presentation
• 17 Feb 2012: seen by endocrinology and discussed at
MDT. Referred to tertiary oncology centre due to
invasion of IVC (and noted to have pulmonary nodules)
• 24 May 2012: R adrenalectomy, IVC thrombectomy and
para-aortic lymphadenectomy
• Surgery at tertiary centre delayed to control Cushings
and enable 3 surgeons to operate together DELAY in
surgery
• June 2012: started Mitotane (achieved therapeutic
levels) and declined chemotherapy
• RIP May 2013
8.
9. Case 4: RH, 78 ♀
• 12 months history of Cushings and repeated GP visits –
self diagnosis DELAY in referral
• 1 March 2012: Private referral (geographically far) DELAY
in local referral
• 19 April 2012: R adrenalectomy (noted probable lung
metastases)
• 29 May 2012: 2nd opinion from tertiary cancer centre but
opted for local care
• June 2012: Mitotane initiated (unable to tolerate
therapeutic levels) and declined chemotherapy
• RIP Feb 2013
10.
11. Case 5: SB, 54 ♀
• 6 month history of vague abdominal ache (declined US
abdo by GP) DELAY by patient to investigate symptoms
• 3 April 2013: incidental finding after admission for PE
(11cm adrenal mass invading IVC with liver and lung
mets). Cortisol secreting
• 8 April 2013: referred to tertiary hospital MDT for
discussion of whether resection an option
• 10 April 2013: Mitotane started
• 15 April 2013: Readmitted
• 18 April 2013: MDT felt inoperable DELAY of ?2 weeks
for MDT decision (whilst patient was inpatient)
• 26 April 2013: rapid decline with hepatic obstruction RIP
12.
13. Age
First
presentation
Biochemistry
Imaging
First MDT
Surgery
Mitotane
Post-op
Steroid Rx
Other Rx
Outcome
64♀ LB
Jan 2013
Secondary care
(incidental)
Secretory
(A4 28.3nmol/l
(0.8-11.9),
ODST 9am Cortisol 147nmol/l)
8.5cm R adrenal
tumor
(Stage 3)
22/05/13
DELAY
05/06/13
(Open)
Adrenal surgeon
Y
Y
None
Alive
+
Mitotane Rx
38♀ TB
Nov 2012
Secondary care
(mass symptoms)
Secretory
(cortisol secreting post op,
30min Cortisol 875nmol/l)
DELAY
20cm L adrenal
tumor & lung
metastasis
(Stage 4)
15/01/13
13/12/12
(Open)
Urologist
Y
DELAY
Y
Palliative RTX
RIP
04/02/13
39♂
KG
Feb 2012
Secondary care
(secretory
symptoms)
Secretory
(24 hr Ur Cortisol 2308, 3495,
3868 nmol/l (10-147))
8cm R adrenal
tumor, IVC & lung
metastasis
(Stage 4)
17/02/12
24/05/12
(Open)
Cancer centre (joint
approach)
DELAY
Y
therapeutic
Y
Ketoconazole
Metyrapone
RIP
07/05/13
76♀
RH
Sep 2011
Private
(secretory
symptoms)
DELAY
Secretory
(24 hr Ur Cort
426, 173, 299 nmol/l (10-147))
13cm L adrenal
tumor & lung
metastasis
(Stage 4)
N/A
19/04/12
(Open)
Urologist
DELAY
Y
Y
Ketoconazole
Metyrapone
RIP
18/02/13
54♀ SB
April 2013
Secondary care
(mass symptoms)
DELAY
Secretory
(24 hr Ur Cortisol 229, 172,
220umol/l (10-147),
A4 63.2nmol/l(0.8-11.9), DHEAS
27.1umol/l (0.5-5.56), )
11cm R adrenal
tumor, cardiac,lung
& liver metastasis
(Stage 4)
11/04/13
DELAY
Unstable for
surgery
Y
Y
Metyrapone
RIP
26/04/13
14. Summary…
• All patients had delay in their pathway of
adrenocortical cancer
• There was no one point of delay and all
patients with invasion of IVC were
discussed at tertiary cancer centres
15. Summary…
• Delays
– Presentation and referral to secondary care
– Referral for surgery, decision by MDTs, operation
date and small delays in starting mitotane
• Mitotane started in all patients: only 1 able to
tolerated therapeutic levels, 2 managed
subtherapeutic and 2 died prior to therapeutic
levels
• Chemo offered to 4 patients with progressive
disease: all declined
16. unanswered questions:
•What could have been done better in terms of
diagnosis and intervention planning via MDT?
•Does multiple opinions improve outcomes and
survival including virtual MDTs?
•How do you increase the awareness of urgent
referrals to endocrinology from primary care?
Hinweis der Redaktion
CT TAP- 8.8x8.7x8.7 cm heterogenous mass R adrenal gland region. A 4.1cm low attenuation area in th emidpoint of right kidney 20-25HU presumably cyct or hemorrhage within the cyst. No metastasis.Pl Normetanephrines 592 (120-1180), Pl Metanephrines 231 (80-510),
Testosterone 2.29
Random Cortisol 377 (@13:10), ODST 147(<50)
Androstenedione 28.3 (0-3.5) DHEAS 18.1 (0.5-5.56)
Miscroscopy – tumor showed nuclear pleomorphism, high mitotic activity (2-3/10 HPF) Confluent tumor necrosis seen. Proliferation index (MIB-1) 10-20%
1.894 kg 20x17x19 cm Left adrenal tumor with lung nodules.
Microscopy (14/12/2012) showing multiple areas of coagulative and hemorrhagic necrosis. High mitotic rate 8-10/10HPF. Capsular invasion seen. Ki67 labelling index ~30%.
CTPA (17/01/2013) extensive pericardial metastasis and a large pericardial effusion probably tamponade.Probable pulmonary metastasis present.
Referred by GP with cushoingoid appearance. Seen in endocrine clinic Feb 2012
24 HOUR Ur Corticol 2308, 3495, 3868 (10-147)
Referred to Royal Marsdon 27/02/12 by AG due to invasion to IVC requiring combined approach from cardiothoracic, urology and surgeon.
Admitted to Royal Brompton 26/03/13 – 04/04/2012 for further assessment. He had MRI Abdo (27/03/12), CT Cor angio (27/03/12) and Fluroscopy of diaphragm (29/03/12)
Surgery (24/05/2013) involving general, urology and cardiothoracic surgeon. Median sternotomy and laprotomy
Histology- 13.5x7.5x8.5 cm L adrenal mass weighing 452gms. Mitotic count 5/10HPFmultiple foci of tumor necrosis seen. MIB1 proliferation index upto 40%
Started Mitotane due to cortisol oversecretion with regular hormone check and rescannings.
A CT scan (22/03/2013) showed progression of lung secondaries and R retroperitonium.
Pt declined chemo as he previously had SEs with mitotane especially nausea and vomitting.
He continued Mitotane till recently he passed away.
Had seen a neurologist privately 24/10/11 as she had ongoing postural dizziness since returning from India in March. A random cortisol was done in addition to other routine investigations.
9am Cortisol 856 (171-536) 09/11/11, 24 hour Ur Cortisol 426, (10-147) 21/11/11
MRI adrenals (01/02/12) showed a large 6.3x12.8x8.4cm R adrenal mass with a regional lymphadenopathy and lung metastasis
First letter about R adrenal carcinoma 01/03/12 Nuffield. Attended privately for non-specific symptoms. Random Cortisol was found elevated. CT adrenals showed R adrenal mass. She was immediately referred to Derriford.
R adrenalectomy (palliative) 19/04/12
(19/04/12) 340gm adrenal mass histology showed high mitotic rate (9/10 HPF) with extensive tumor necrosis.
Second opinion regarding recurrance of metastatic R adrenal carcinoma from Royal Marsden MDT 30/05/12 confirming recurrence with lung metastasis bilaterally referred back locally for Mitotane therapy
MDT RD&E 05/07/12. To continue Mitotane, not keen for chemo and agrreeable for local followup
Commenced Ketoconazole and Metyrapone 06/12/12 eventually for persistant hypercortisolemia
Admitted with new PE 03/04/13-08/04/13, also found to have large R adrenal carcinoma with lung and possible liver mets.
05/04/13 - Androstenedione 63.2 (0.8-11.9), Cortisol 988 (171-536), DHEAS >27.1 (0.51-5.56), Testosterone 11.6 (0.1-1.5)
08/04/13 24 hour Ur Cortisol 229, 172, 220 (10-147)
LDDST Cortisol 908
CT TAP (04/04/13) after CTPA which showed pulmonary mets in addition to PEs for ongoing SoB & wt gain, showed 9x11cm R adrenal mass invading IVC, possible liver metastasis and left lung matastasis.
MDT11/04/13 – AG review next week to initiate Mitotane.
Refrral letter to QEH, Birmingham 08/04/13 for surgery
Readmitted 09/04/13 with fever, cough and hemoptysis. D/C home on 10/04/13 and commenced on Mitotane.
Admitted on 15/04/13 with poor urine output and dehydration, 18/04/13 Decision was taken by oncologist via Birmingham that she was too unfit and risky for surgery and not for chemo either. Afterwards she was commenced on LCP. She progressively deteriorated and died on 26/04/13.
