Cushing syndrome Flashcards
What is the definition of Cushing’s syndrome?
Cushing’s Syndrome is the clinical state produced by chronic glucocorticoid excess
What is the definition of Cushing’s Disease?
Cushing’s Disease is Cushing’s syndrome caused by bilateral adrenal hyperplasia from an ACTH secreting pituitary adenoma (usually a microadenoma)
What is Nelson’s syndrome?
Occurs post bilateral adrenalectomy resulting in unsuppressed ACTH production
This results in
1) Macroadenomas of the pituitary to inc ACTH production 🡪 mass effects
- visual disturbances (due to compression on optic chiasm)
- headaches (due to infiltration into bony structures / meninges)
2) Excessive ACTH =
- ↑ beta-MSH and ACTH
- hyper-pigmentation of the skin
What are the causes of ACTH independent Cushings?
Adrenal adenoma, carcinoma or Bilateral adrenal hyperplasia (i.e. Primary Hypercortisolism)
Iatrogenic (99%): Steroids, TCM, Jammu
What are the causes of ACTH dependent Cushings?
Pituitary disease (Cushing’s disease)
- Adenoma
- Hyperplasia
Ectopic ACTH
- Small cell lung carcinoma (can also produce PTHrP)
- Carcinoid tumour
Ectopic CRH
- Medullary Thyroid carcinoma
What are the signs suggesting suggesting adrenal carcinoma as underlying cause of Cushing?
- Palpable abdominal mass
- Signs of virilisation in females: acne & hirsutism (since carcinoma will not only increase cortisol production but also androgen production)
- Gynaecomastia in males
What are the signs suggesting suggesting ectopic ACTH production as underlying cause of Cushing?
Ectopic ACTH tumors tend to be more aggressive, releasing more cortisol with lesser time for physical changes to occur
- Absence of Cushingoid body habitus unless tumour has been slow growing and allowed time for Cushingoid features to develop
- More prominent oedema and hypertension
- More severe muscle weakness from hypokalaemia
- History usually of more rapid onset of symptoms and signs
- Pigmentation (only in ACTH dependent)
What are the presenting complications of someone with Cushing’s?
Increase appetite and weight
Skin changes
Change in appearance
Metabolic Syndrome: DM, HTN, HLD
Hypokalaemia due to mineralocorticoid effect: Arrhythmia, Weakness
Muscle weakness (Proximal myopathy)
Osteoporosis: Any recent #, bone pain / spine pain
Poor Immune system: recurrent illnesses
Mood changes (depression, lethargy, irritability, psychosis): Result of cortisol’s effect in the degradation of hippocampus
Sleep disturbances
Erectile dysfunction (men) or amenorrhea & hirsutism (women)
What are the skin changes in a patient with Cushing’s?
- Acanthosis nigricans from IR (areas of dark, velvety discoloration in body folds and creases)
- Easy bruising
- Acne, hirsutism
- Purple striae typically on abdomen
- Hyperpigmentation (only in ACTH dependent cushing’s)
What are the changes in appearance in a patient with Cushing’s?
- Rounded countenance, moon-like facies, lemon on sticks appearance
- Supraclavicular fat pad & dorsocervical fat pad (Buffalo Hump)
- Facial plethora
Why will a patient with Cushing’s have muscle weakness?
Due to catabolic effect of cortisol
Also due to hypoK which causes muscle weakness
What hx would you ask to elucidate aetiology of cushing syndrome?
Use of any exogenous steroids / TCM
Any S&S of
- Lung Ca
- GI Ca, Carcinoid Syndrome
Central
- Hyperpigmentation;
- Mass effect in pituitary – BOV, Headache. Rare B/c most ACTH-producing adenomas are MICROADENOMAS <1cm
Past Medical History/Drugs
- Previous history of endocrine condition
- History of hypertension, diabetes
- Any current treatment with long-term steroids?
- Any TCMs/Jammu?
Family History
- Family history of any pituitary tumours?
What signs to look out for in the upper limbs when examining a patient with Cushing’s?
Thin arms (Lemon on sticks)
Fingers for etiological clues
- Clubbing, tar staining (lung cancer)
- Joint deformities in RA, SLE (exogenous steroid use)
- Rashes: dermatomyositis, psoriasis, SLE
Skinfold thickness on the backs of hands (double pinch test – pinch pt’s skin & your own)
Bruising
Proximal myopathy
What signs to look out for in the face when examining a patient with Cushing’s?
- Conjunctival pallor (BGIT from steroid)
- Cataracts
- Acne & Hirsutism
- Telangiectasia (small dilated vessels near skin surface/mucous membranes)
- Plethora (red, florid condition: ensure absence of polycythemia)
- Moon-like facies (use “Rounded countenance” instead in the presence of patient)
- Oral thrush
What signs to look out for in the neck when examining a patient with Cushing’s?
- Acanthosis nigricans
- Supraclavicular fat pads
- Dorsocervical fat pad (Buffalo hump)
What signs to look out for in the trunk when examining a patient with Cushing’s?
- Central obesity
- Purple striae
- Palpate for bony tenderness of vertebral bodies (crush fractures from osteoporosis: steroid anti-Vitamin D effect and increased urinary Ca2+ loss)
- Hepatomegaly (fat deposition, adrenal carcinoma deposits)
What signs to look out for in the lower limbs when examining a patient with Cushing’s?
- Proximal myopathy
- Bruising
- Poor wound healing
- Palpate for oedema (salt and water retention)
What are examinations to perform in a patient with Cushing’s?
Blood pressure
Urine dipstick (glycosuria)
Respiratory examination (lung cancer, ILD, asthma)
Abdo Exam for adrenal masses (adrenal carcinoma palpable over renal area)
Visual field testing
- Bitemporal hemianopia in pituitary tumour
- Not likely in Cushing’s because it is usually a microadenoma)
Fundoscopy (optic atrophy, hypertensive, diabetic changes)
What is the workup for exogenous steroid use?
Paired ACTH / SST (Short Synacthen Test)
- Stop steroid / TCM for up to 2 weeks (if outpatient) before Synacthen
- IM/IV Synacthen (250mcg) given & Cortisol measured at 0th (8am), 30th, 60th min
- 0th min: 8am cortisol <250nmol/L due to chronic
- 30th/ 60th min: suboptimal rise in cortisol (normal- cortisol DOUBLES AND > 500nmol/L )
When doing short synacthen test, SST: 200 🡪 220 🡪 250; ACTH high (normal <10.1Umol/L). What are the differential diagnoses?
Acute Primary hypocortisolism: Due to acute dysfunction 🡪 there is loss of adrenal function = suboptimal rise
Eg: Acute adrenal hemorrhage
- APS (Antiphospholipid Syndrome) from SLE
- Waterhouse-Friderichsen Syndrome (from meningococcemia)
When doing short synacthen test, SST: 50 🡪 60 🡪 70; ACTH high (normal <10.1Umol/L). What are the differential diagnoses?
Due to chronic dysfunction 🡪 there is loss of adrenal function = suboptimal rise
Eg: Addison’s
When doing short synacthen test, 50 🡪 300 🡪 600; ACTH inappropriately normal or low (normal <10.1Umol/L). What are the differential diagnoses?
Adrenals are still very responsive due to acute nature = hence optimal rise
Eg: Post Pituitary Surgery, Pituitary Apoplexy (Sheehan’s syndrome from PPH)
OR Patient was given a few doses of dexamethasone by family physician few days before admission (dexamethasone would suppress the exogenous glucocorticoid function, explaining low 0 min level. However, as the adrenals are not atrophied yet, the adrenal would mount a robust response to Synacthen administered).
When doing short synacthen test, 50 🡪 60 🡪 70; ACTH inappropriately normal or low (normal <10.1Umol/L). What are the differential diagnoses?
Adrenals are no longer responsive due to chronic suppression = suboptimal rise
Eg: 6 weeks post Pituitary Surgery; chronic steroid use
What is the management of exogenous Cushing?
Stop all exogenous steroids (esp TCM, b/c steroid dose is uncontrolled)
Give controlled & small steroid dose @ physiological levels
- Hydrocortisone 10mg on waking, 5mg at 5pm
- Mild-moderate illness (eg: runny nose, sore throat) <39 degrees 🡪 2x dose for 2-3 days till mild illness is over
- Severely unwell >39 degrees / severely unwell, diarrhoea, vomiting 🡪 Please come to hospital for parenteral steroids – b/c you are at HIGH RISK of Addisonian crisis
Continue steroid provision until axis “wakes up”: However, if extremely chronic use of TCM 🡪 Axis may NEVER wake up, requiring life-long steroids
