A clinically silent invasive adrenocortical

tumour: charting steroid excretion before

tumour removal, and after mitotane therapy
and repeat surgery

Mrs L Ghataore1

Taylor, NF1. Schulte, K-M2. Aylwin, SJB2

Departments of Clinical Biochemistry1, Surgery and Medicine2,

King’s College Hospital
 25 year old male

 September 2008
 10-day left sided abdominal pain
 2-day history of dry cough

 Past medical Hx - asthma as a child

 Examination:
 Large firm mass in the left upper abdomen
 Some reduced breath sounds in the left lung base
 Radiology [CT - Abdomen (coronal)]

Right lung
lesion

Mass
15 x 19 x
18 cm
 Radiology [CT - Chest (axial)]

Right lung
lesions
 Radiology [CT - Abdomen (axial)]

Lymph node
involvement
paraaortic
&
Blood
periportal
vessels

Mass
15 x 19 x
18 cm
 Biochemical investigations
Tests
Renal, Liver, Bone profiles
24 hr urine CATS (x2)
Aldosterone/Renin
24 hr urine cortisol:
Cortisol (DST=0.5, 48 hr):
ACTH
17OH progesterone
DHEAS
Progesterone:
Androstenedione:
Results
Normal
Normal
Normal
164 (30-250nmol/D)
178 (<30 nmol/L)
34ng/L (<50 ng/L, 9am)
12.8 (<19.6nmol/L)
14.7 (7.6-17.4umol/L)
10 (<5nmol/L)
24.1 (2.4-12.6nmol/L)
 Urine Steroid Profiling (USP)

Cholesterol DP3

20,22-lyase

Pregnenolone 17-Hydroxypregnenolone DHA Dihydrotestosterone

17,20-lyase
17-OHase
3-HSD/4,5 isomerase
3-HSD/4,5 isomerase
3-HSD/4,5 isomerase X X 5-reductase

Progesterone 17-Hydroxyprogesterone Androstenedione Testosterone

17-OHase 17,20-lyase 17-HSD
aromatase
aromatase
21-hydroxylase 21-hydroxylase

Oestrone Oestradiol
11-Deoxycorticosterone 11-Deoxycortisol 17-HSD

11-hydroxylase
11-hydroxylase

Corticosterone
THS X
Aldosterone synthase

Cortisol
Aldosterone
 Normal vs abnormal USP

GARRARD Neil 14-09-2008

Normal Adult
gallacher edward 17-9 Scan EI+
100 AAA18.34 TIC
8.23e8

28.64
18.77

29.93
30.22
%
22.52 24.61
DP3 S CB
38.14
DHA21.47 25.67
30.50 34.72
24.22 THS
19.14 28.24
32.08
33.78
0
garrard neil 14-09 1: Scan EI+
100
Patient 25y TIC
A 3.99e9

DHA
19.84 DP3
% THS 28.36
18.84
26.38
20.22 30.05
18.39 25.77
23.55
30.32
22.14
32.17
S
34.83 CB
38.18
0 Time
18.00 23.00 28.00 33.00 38.00
 USP: Pre & Post Dexamethasone

GARRARD Neil 14-09-2008

Patient 14-9-8 baseline
garrard neil 14-09 1: Scan EI+
100 TIC
3.99e9

DHA DP3
19.84

% THS 28.36
18.84
26.38
20.22 30.05
A18.39 23.55
25.77
30.32
22.14 S CB
32.17 34.83 38.18
0
garrard neill 17-9 Scan EI+
Patient 17-9-8
18.84
Post Dex TIC
100
2.42e9
DP3
DHA THS 28.34

25.76
19.80

% A18.38 20.19 24.69

23.55
23.37 30.01
CB
21.47 30.58 S
34.79
38.17
32.12
39.82
0 Time
18.00 23.00 28.00 33.00 38.00
 Surgery

 Sept 08: Radical L adrenalectomy & retroperitonial

en-bloc evisceration

 Feb 09: R thoracotomy & metastasectomy

 April 09: L thoracotomy & metastasectomy

 Histology

 Sep 08: High grade ACC invading the peri-adrenal soft

tissue. No involvement of the kidney, spleen,
pancreas, bowel, stomach or diaphragm.

 Feb 09: Morphology in keeping with metastatic ACC.

Vascular invasion is noted.

 Apr 09: Features are those of metastatic ACC.

Tumour infiltrates into, but not through the pleura.
 USP: Pre & Post Surgery

GARRARD Neil 14-09-2008

Patient 14-9-8 Pre
garrard neil 14-09 1: Scan EI+
100 TIC
3.99e9

DHA
19.84
DP3
% THS 28.36
18.84
26.38
20.22 30.05
18.39 25.77
A 23.55
30.32
22.14 S
34.83
CB
32.17 38.18
0
garrard neill 3-12 Scan EI+
Patient 03-12-8
100
18.77 Post TIC
A 1.46e9

28.55 29.79

24.55 25.61
DP3 30.39 S
DHA 34.64 CB
38.06
19.08 22.49
23.44
THS
28.16
31.07
26.26

0 Time
18.00 23.00 28.00 33.00 38.00
 Pharmacotherapy

 Sept 08 (post surgery): hydrocortisone 20mg,10mg

 Dec 08: Mitotane (dose 4g/daily increased to 6g daily)

 Mitotane effects

GARRARD Neill 03-12-2008

Patient 3-12-08 Pre
garrard neill 3-12 Scan EI+
TIC
100 A 18.77 1.46e9

28.55 29.79

%
5α
24.55 25.61 30.39
S
34.64 CB
28.16 38.06
19.08 22.49
23.44 26.26
20β
31.07

0
garrard neill 9-1 Scan EI+
100 Patient 9-1-10 Post 29.79 TIC
2.58e9

A16.69
19.90

%
5α
28.53
An 20β
30.38
21.47
18.75
27.85
S
34.64
CB
38.09
25.58 31.87

0 Time
18.00 23.00 28.00 33.00 38.00
 USP: Follow-up

100000

10000
Excretion (ug/24h)

1000

pregnenetriol
THS
100
DHA + DHA metabs

10

Primary R & L metastasis

mass
 Current status

 No radiological evidence of disease recurrence

 Working part time

 Medications: Mitotane, Hydrocortisone, Nandrolone,

Ondansetron

 Mild gynaecomastia

 Reduced lung function

 Adrenocortical carcinoma (I)

 Rare malignancy (0.2% of all cancers)

 Incidence 1-2 cases per million annually

 F>M (ratio about 1.5)

 Bimodal age distribution

 Prognosis: 5-year survival rate of 20-35%

Fassnacht M and Allolio B. Best practice & Research Clinical Endocrinology &
Metabolism. 2009; 23: 273-289
 Adrenocortical carcinoma (II)

 Functioning tumours (60%)

 May secrete: glucocorticoids (Cushing’s syndrome),
mineralocorticoids (hypertension), androgens
(virilization), oestrogens in men (gynaecomastia)
 Non functioning tumours
 Local symptoms: abdominal pain or fullness,
gastrointestinal complaints due to mass effect
 Pre-operative endocrine assessment:
 steroid excess and pattern
(adrenocortical origin of tumour)
 tumour markers for monitoring tumour recurrence
 USP: Adrenocortical carcinoma

 USP examines the steroids excreted in greatest amount

 Some 200 adrenal tumours have been investigated.

Steroid excretion patterns show considerable variety

 In tumour recurrences, the steroid pattern tends to be

found again
 Summary

 ACC is a rare malignancy with a 5 year prognosis

<30%

 Frequently clinically silent with increase of steroid

hormone precursors

 USP: identification of tumour markers for

recurrence monitoring

 USP can still be used during hydrocortisone and

mitotane treatment
 Acknowledgements

Endo-NET MDM

 Mr M Marrinan (Surgical Consultant)

 Dr D Lewis (Radiologist)
 Dr R Vincent (Consultant Chemical Pathologist)

P649735