Download Cushing's Disease

Endocrine Nurse’s
Conference
Cushing’s Disease
Veronica Kieffer MA BSc (Hons) RGN
Endocrine Nurse Specialist
Leicester Royal Infirmary, Leicester
History
October 1997
Miss A
 16 year old girl
 Moon face
 Hirsutism
 Central obesity
 Purple striae
 Proximal myopathy
 Primary amenorrhoea
Investigations
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Urea and Electrolytes (U&E)
Liver Function Test (LFT)
Thyroid function tests (TFTs)
LH/FSH
Oestrogen
Prolactin
Growth hormone
Cortisol
Adrenocorticotrophic hormone (ACTH)
24 hour Urinary Free Cortisol (UFC)
Results
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LFTs, U&Es, TFTs –all normal
LH
0.9iu/L
FSH
2.8iu/L
Prolactin 120iu/L ( 50-400 iu/L)
Oestradiol <50pmol/L
Cortisol
568nmol/L
UFC
257 nmol/24hours
(28-221nmol/24hrs)

ACTH
60ng/L (0-50ng/L)
Further Investigations
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Circadian rhythm cortisol
Midnight cortisol
Low dose Dexamethasone
suppression test
CRH test
MRI Pituitary gland
CT Adrenal glands
Petrosal Sinus Catheter
RESULTS
Circadian rhythm
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
0930 --- 556nmol/L
1200 --- 663nmol/L

1700 --- 635nmol/L
Mean --- 618nmol/L

Midnight cortisol --- 490nmol/L

Low Dose Dexamethasone Test
Dex 2+0 --- 568nmol/L
Dex 2+48--- 246nmol/L
Results
CRH Test
No change in cortisol levels so not
useful in diagnosing cause
MRI Pituitary
?Right Pituitary microadenoma
CT Adrenals
No lesion found
Petrosal Sinus Catheter
Sample
Right
Left
Peripheral
Gradient:
Gradient
Gradient
Right:Peri
Left:Peri
Right:Left
ACTH: Basal
98
68
87
1.1
0.8
1.4
ACTH: 5min
1,424
3,620
123
11.6
29.4
0.4
210
4,388
159
1.3
27.6
0.0
ACTH:
10min
Treatment
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Metyrapone
19/11/1997
Cortisol levels on Metyrapone 750mg stat
 0900 – 554nmol/l
 1200 – 79 nmol/l
 1700 – 107nmol/l
18/12/1997
Cortisol levels on Metyrapone 250mg t.d.s
 0900 – 120nmol/l
 1200 – 135nmol/l
 1430 – 89nmol/l
 1700 – 109nmol/l
 Mean 113nmol/l
Treatment
9th January 1998
0900 cortisol – 656 nmol/l
19/1/1998
Cortisol levels on Metyrapone 250mg nocte
 0900 – 514nmol/l
 1200 – 674nmol/l
 1430 – 620nmol/l
 1700 – 493nmol/l
 Mean -- 575nmol/l

Block and Replace

Metyrapone 250mg t.d.s /
Hydrocortisone10mg o.d.
Treatments for Cushing’s
Disease.
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Trans-sphenoidal removal of tumour.
 Remission
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External pituitary radiation
 Slow

acting. Effective in 50-60% cases.
Medical Therapy to reduce ACTH (Bromocriptine)
 Rarely

in 75-80% cases
effective
Bilateral Adrenalectomy
 Effective
last resort
Surgery
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Trans-sphenoidal hypophysectomy 10/03/1998
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18/03 - 0900 cortisol --- 768nmol/l
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19/03 - 0900 cortisol --- 992nmol/l
Trans-sphenoidal hypophysectomy 17/04/1998
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22/04 - 0900 cortisol --- 738nmol/l
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23/04- 0900 cortisol --- 624nmol/l
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25/04 -0900 cortisol --- 596nmol/l
Pan hypopituitarism with diabetes insipidus
Restart ‘Block and Replace’
Block and Replace
16/11/1998
Metyrapone 250mg t.d.s/ Hydrocortisone
10mg o.d.
0930 --- 555nmol/l
 1200 --- 273nmol/l
 1430 --- 103nmol/l
 1700 --- 101nmol/l
 Mean 258nmol/l
 24 hour UFC 63nmol/24hours
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Options
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Tablets - such as
Metyrapone
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Radiotherapy to the
pituitary gland.
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An operation to remove
both adrenal glands.
Options
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Not easily controlled tablets
Tablets would be necessary
several years after
radiotherapy
Recommend bilateral
adrenalectomy– refer to
surgeon
Miss A and family agreed.
Treatment
23/12/1998
Bilateral adrenalectomy 
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Hydrocortisone 10mg,5mg,5mg
Fludrocortisone 100mcg o.d.
Pigmentation knuckles and palmar
creases
Close watch on ACTH
TFTs normal on Thyroxine
Desmopressin still for Diabetes Insipidus
Gonadotrophin deficiency
February 1999
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Day curve – levels cortisol good
 mean 392 nmol/l
No features Cushing’s
Suppressed Renin levels
(Fludrocortisone)
ACTH 602ng/l
Oestrogen replacement (Mercilon)
?Nelson’s syndrome
Nelson’s Syndrome
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Rapid enlargement of a pituitary adenoma
following bilateral adrenalectomy
Lack of negative feedback from cortisol
Mass effects
 Increased production ACTH
 Increased production melanocyte stimulating
hormone.
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• Muscle weakness
• Hyperpigmentation
June 1999
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Progressive darkening skin
Increase Hydrocortisone
10mg/10mg/5mg
Repeat Hydrocortisone day curve
Repeat ACTH levels
September 1999
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Blood Cortisol levels and UFC at day
curve top end acceptable level
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mean bloods 559nmol/L
UFC 552nmol/24hrs
ACTH lower 181ng/L (increased suppression
corticotroph adenoma)
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Weight gain
Stretch marks
Balancing act
MRI
March 2000
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DNA MRI appointment October 1999
February 2000
MRI reported as:
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Macroadenoma on left pituitary fossa
extending into cavernous sinus.Not
visible on previous MRIs or at surgery.
Increasing pigmentation
Pituitary radiotherapy –June 2000
September 2000
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Pigmentation less
Continues Hydrocortisone
10mg/10mg/5mg
ACTH still elevated
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9000ng/L pre morning Hydrocortisone
640ng/L 2 hours after
Weight gain but risk of enhancing growth
adenoma if dose Hydrocortisone
reduced.
ACTH levels
6000
5000
4000
3000
2000
1000
0
0
lu -0
J
1
lu -0
J
2
lu -0
J
3
lu -0
J
4
lu -0
J
5
lu -0
J
6
lu -0
J
7
lu -0
J
Follow Up 2003-2005
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Continued to be stable and no
changes in pigmentation
MRI July 2003 – adenoma stable
ACTH level lower in 2003
Gynae problems
GH deficient but declined
treatment.
2006
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Well
No changes in pigmentation
ACTH before and after
Hydrocortisone
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Higher than previously (post
808ng/l)
 Hydrocortisone
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Monitor
increased
2007
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Increased pigmentation
ACTH pre and 2 hours post
Hydrocortisone
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Post 4,760nmols/l
MRI pituitary
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Significant Lt lateral extension
passing through cavernous sinus
Significant enlargement compared
to previous films mostly laterally
but now filling fossa.
Treatment
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MDT discussion
Further de-bulking surgery –but
unlikely to be completely
resectable as wrapped around
carotid and ocular motor nerves
 Possible gamma knife therapy
 Cabergoline –no effect
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Trans-sphenoidal Hypophysectomy
December 2007
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Post op MRI – encouraging but many
‘scars of battle’
Plan further MRI June
ACTH 2 hour post hydrocortisone
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133ng/L
June MRI – Good clearance but possible
small amount residual tissue.
Continue monitoring ACTH and MRI
June 2008
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ACTH Pre and post
Hydrocortisone levels
Pre >1250ng/L
 Post 423ng/L
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Conclusion
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Cushing’s syndrome
2 transsphenoidal hypophysectomies
Bilateral adrenalectomy
Nelson’s syndrome
Radiotherapy
3rd transsphenoidal hypophysectomy
? Nelson’s recurring
The Future?
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Watchful wait
Gamma knife therapy
No further radiotherapy after that
Repeated de-bulking surgery
Careful monitoring