Clinical Features
| Face: moonface, plethoric complexion, acne, hirsutism
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| Weight gain and distribution of obesity (central obesity, buffalo hump, supraclavicular fat pad)
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| Thin skin, easy bruising, wide purple striae on abdomen, breasts, thighs &/or axillae.
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| Proximal myopathy and muscle wasting (can patient rise from squat?)
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| Kyphosis/loss of height/back pain
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| Hypertension, nocturia, lower limb oedema
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| Menstrual disturbances in females. Low libido and erectile dysfunction in males
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| Psychiatric symptoms - labile mood, insomnia, depression, psychosis
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NB The presence of truncal obesity, round facies, thin skin with striae and proximal myopathy are specific signs which require further investigation
OUTPATIENT SCREENING
24 hour Urine Free Cortisol (UFC) x 2
Useful as a screening test in patients with normal renal function. Collect into plain 24h urine bottles.
Overnight Dexamethasone Suppression Test
1. Give 1mg dexamethasone orally at 2200 - 2400h.
2. 0900h the following morning take blood for cortisol estimation (gold top vial with gel).
Interpretation guide
Urine free cortisol may give 15% false positive results, especially in obese or sick patients or
those with pseudocushing's.
Suppression test: serum cortisol should suppress to <50nmol/L in normal subjects. False
positives may be found in obese patients, those with alcoholism or depression.
Patient's with Cushing's syndrome fail to suppress adequately.
Patients with psychiatric illness, severe physical or psychological stress and those on oral
oestrogen therapy often have false positive UFCs and suppression tests. Investigation
should be deferred for at least 6 weeks after recovery or cessation of oestrogen use.
If either test is abnormal please refer to the Endocrine Clinic
Instructions for Investigations on Admission
Measure baseline pituitary function tests LH, FSH, prolactin, TSH, fT4 & testosterone;
FBC, U &E and LFTs on the morning of day 1.
| DAY | DEXAMETHASONE | SERUM
0900hr | CORTISOL
MIDNIGHT | ACTH *
|
| 1 | | Yes | Yes | Yes at 0900hr
|
| 2 | | Yes | Yes | Yes at 0900hr
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| Low dose dexamethasone suppression
|
| 3 | 0.5mg 6 hourly | Yes | No |
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| 4 | 0.5mg 6 hourly | Yes | No |
|
| If serum cortisol suppresses to <50nmol/L the test may be stopped.
|
|
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| High dose dexamethasone suppression
|
| 5 | 2mg 6 hourly | Yes | No |
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| 6 | 2mg 6 hourly | Yes | No |
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| 7 | | Yes | No |
|
Dexamethasone must be GIVEN EXACTLY 6 hourly, i.e. 0900,1500, 2100 & 0300h.
·
PLEASE USE THE 24 HOUR CLOCK FOR ALL TIMINGS
*ACTH samples must be collected into 3 x 4.5ml EDTA vials cooled in iced water and taken to the laboratory immediately.
Please let the laboratory know when ACTH samples are being sent.
Cushing's Syndrome Interpretation Guidelines
Confirm diagnosis
Midnight Cortisol
Loss of circadian rhythm of cortisol secretion is seen in Cushing's syndrome and is documented by a serum cortisol of >50nmol/L at midnight, providing the patient is asleep.
Low dose dexamethasone suppression test
In patients with Cushing's syndrome there is failure to suppress serum cortisol measured after 48hr of 0.5mg Dexamethasone 6 hourly to <50nmol/L.
Differential diagnosis
ACTH
ACTH levels are undetectable in Cushing's syndrome secondary to an adrenal neoplasm and are an indication for imaging the adrenal glands.
There is considerable overlap between concentrations of ACTH seen in ectopic ACTH production and pituitary Cushing's syndrome.
Serum potassium
Hypokalaemia (S.K<3.2mmol/l) is found in almost all patients with ectopic ACTH production but is found only in 10% of patients with Cushing's disease.
High dose dexamethasone suppression test
Suppression of serum cortisol concentrations to >50% of baseline value following 48h of 2mg Dexamethasone 6 hourly is strongly indicative of Cushing's disease.
Imaging
(1) CT adrenals if ACTH levels are undetectable.
(2) MRI pituitary (with contrast): will detect an adenoma in only 60% of patients with Cushing's disease.
(3) MRI/CT chest and abdomen: if ectopic ACTH production is suspected
FOLLOW UP OF PATIENTS WITH CUSHING'S SYNDROME FOLLOWING TRANSPHENOIDAL ADENECTOMY
6 monthly follow up
Aims:
(i) to detect recurrent Cushing's
(ii) to recognise when recovery of the pituitary adrenal axis occurs.
Investigations:
Omit evening and morning hydrocortisone dose and perform 0900hr serum cortisol. If <70nmol/l then repeat 6 monthly.
If >70nmol/l then must exclude recurrence of Cushing's syndrome and confirm recovery of pituitary-adrenal axis.
- admit and stop steroids
- 24hr UFC x 2 (plain bottles)
- 0900h & midnight cortisol (buff top with gel, vial)
- low dose dexamethasone suppression test
- short synacthen test
