Endocrine Nurses Conference

1
Endocrine Nurses Conference

Cushings Disease
Veronica Kieffer MA BSc (Hons) RGN Endocrine
Nurse Specialist Leicester Royal Infirmary,
Leicester
2
History

• October 1997
• Miss A
• 16 year old girl
• Moon face
• Hirsutism
• Central obesity
• Purple striae
• Proximal myopathy
• Primary amenorrhoea

3
Investigations

• Urea and Electrolytes (UE)
• Liver Function Test (LFT)
• Thyroid function tests (TFTs)
• LH/FSH
• Oestrogen
• Prolactin
• Growth hormone
• Cortisol
• Adrenocorticotrophic hormone (ACTH)
• 24 hour Urinary Free Cortisol (UFC)

4
Results

• LFTs, UEs, TFTs all normal
• LH 0.9iu/L
• FSH 2.8iu/L
• Prolactin 120iu/L ( 50-400 iu/L)
• Oestradiol lt50pmol/L
• Cortisol 568nmol/L
• UFC 257 nmol/24hours
• 
  (28-221nmol/24hrs)
• ACTH 60ng/L (0-50ng/L)

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Further Investigations

• Circadian rhythm cortisol
• Midnight cortisol
• Low dose Dexamethasone suppression test
• CRH test
• MRI Pituitary gland
• CT Adrenal glands
• Petrosal Sinus Catheter

6
RESULTS

• Circadian rhythm
• 0930 --- 556nmol/L
• 1200 --- 663nmol/L
• 1700 --- 635nmol/L
• Mean --- 618nmol/L
• Midnight cortisol --- 490nmol/L
• Low Dose Dexamethasone Test
• Dex 20 --- 568nmol/L
• Dex 248--- 246nmol/L

7
Results

• CRH Test
• No change in cortisol levels so not useful in
  diagnosing cause
• MRI Pituitary
• ?Right Pituitary microadenoma
• CT Adrenals
• No lesion found

8
Petrosal Sinus Catheter
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Treatment

• 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

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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.

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Treatments for Cushings Disease.

• Trans-sphenoidal removal of tumour.
• Remission in 75-80 cases
• External pituitary radiation
• Slow acting. Effective in 50-60 cases.
• Medical Therapy to reduce ACTH (Bromocriptine)
• Rarely effective
• Bilateral Adrenalectomy
• Effective last resort

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Surgery

• Trans-sphenoidal hypophysectomy 10/03/1998
• 18/03 - 0900 cortisol --- 768nmol/l
• 19/03 - 0900 cortisol --- 992nmol/l
• Trans-sphenoidal hypophysectomy 17/04/1998
• 22/04 - 0900 cortisol --- 738nmol/l
• 23/04- 0900 cortisol --- 624nmol/l
• 25/04 -0900 cortisol --- 596nmol/l
• Pan hypopituitarism with diabetes insipidus
• Restart Block and Replace

13
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

• Tablets - such as Metyrapone
• Radiotherapy to the pituitary gland.
• An operation to remove both adrenal glands.

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Options

• Not easily controlled tablets
• Tablets would be necessary several years after
  radiotherapy
• Recommend bilateral adrenalectomy refer to
  surgeon
• Miss A and family agreed.

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Treatment

• 23/12/1998
• Bilateral adrenalectomy -
• 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

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February 1999

• Day curve levels cortisol good
• mean 392 nmol/l
• No features Cushings
• Suppressed Renin levels (Fludrocortisone)
• ACTH 602ng/l
• Oestrogen replacement (Mercilon)
• ?Nelsons syndrome

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Nelsons Syndrome

• 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.
• Muscle weakness
• Hyperpigmentation

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June 1999

• Progressive darkening skin
• Increase Hydrocortisone 10mg/10mg/5mg
• Repeat Hydrocortisone day curve
• Repeat ACTH levels

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September 1999

• Blood Cortisol levels and UFC at day curve top
  end acceptable level
• mean bloods 559nmol/L
• UFC 552nmol/24hrs
• ACTH lower 181ng/L (increased suppression
  corticotroph adenoma)
• Weight gain
• Stretch marks
• Balancing act
• MRI

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March 2000

• DNA MRI appointment October 1999
• February 2000
• MRI reported as
• Macroadenoma on left pituitary fossa extending
  into cavernous sinus.Not visible on previous MRIs
  or at surgery.
• Increasing pigmentation
• Pituitary radiotherapy June 2000

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September 2000

• Pigmentation less
• Continues Hydrocortisone 10mg/10mg/5mg
• ACTH still elevated
• 9000ng/L pre morning Hydrocortisone
• 640ng/L 2 hours after
• Weight gain but risk of enhancing growth adenoma
  if dose Hydrocortisone reduced.

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ACTH levels
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Follow Up 2003-2005

• 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.

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2006

• Well
• No changes in pigmentation
• ACTH before and after Hydrocortisone
• Higher than previously (post 808ng/l)
• Hydrocortisone increased
• Monitor

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2007

• Increased pigmentation
• ACTH pre and 2 hours post Hydrocortisone
• Post 4,760nmols/l
• MRI pituitary
• Significant Lt lateral extension passing through
  cavernous sinus Significant enlargement compared
  to previous films mostly laterally but now
  filling fossa.

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Treatment

• 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 HypophysectomyDecember 2007

• Post op MRI encouraging but many scars of
  battle
• Plan further MRI June
• ACTH 2 hour post hydrocortisone
• 133ng/L
• June MRI Good clearance but possible small
  amount residual tissue.
• Continue monitoring ACTH and MRI

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June 2008

• ACTH Pre and post Hydrocortisone levels
• Pre gt1250ng/L
• Post 423ng/L

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Conclusion

• Cushings syndrome
• 2 transsphenoidal hypophysectomies
• Bilateral adrenalectomy
• Nelsons syndrome
• Radiotherapy
• 3rd transsphenoidal hypophysectomy
• ? Nelsons recurring

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The Future?

• Watchful wait
• Gamma knife therapy
• No further radiotherapy after that
• Repeated de-bulking surgery
• Careful monitoring