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Endocrinology > Cushing's Syndrome (& disease) > Flashcards

Cushing's Syndrome (& disease) Flashcards

1
Q

Define Cushing’s syndrome

A

The clinical state produced by;

  1. Chronic glucocorticoid excess
  2. Loss of normal feedback of HPA axis
  3. Loss of circadian rhythm of cortisol secretion (normally highest on waking)
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2
Q

What are the symptoms & signs of Cushing’s syndrome?

A

CUSHINGOID

  • Central obestity
  • UUN FACE (plethoric)
  • Skin - striae (purple abdoo), thin, bruising, acne
  • Hyperglycaemia, Hypertension
  • Insufficient muscles
  • Neck (buffalo)/ supraclavicular hump
  • Gonadal dysfunction
  • Osteoporosis
  • Infections (immunosuppression)
  • Depression

Symptoms;

  • ↑Weight
  • Mood: depression, lethargy, irritability, psychosis
  • Proximal weakness
  • Gonadal dysfunction: irregular menses, hirsutism, erectile dysfunction
  • Acne
  • Recurrent achilles tendon rupture
  • Virilization (adopting mail characteristics)

Signs;

  • Central obesity
  • Plethoric moon face
  • Buffalo neck hump
  • Supraclavicular hump distribution
  • Skin & muscle atrophy
  • Bruises
  • Purple abdominal striae
  • Osteoporosis
  • ↑BP
  • ↑glucose
  • Infection prone
  • Poor healing
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3
Q

Outline the causes of Cushing’s syndrome

A

ACTH-dependent causes (↑ACTH)

  • Cushing’s disease
    • Bilateral adrenal hyperplasia from ACTH-secreting pituitary adenoma (usually microadenoma)
    • 1m:1female, 30-50yrs
  • Ectopic ACTH production
    • Esp. small cell lung cancer & carcinoid tumours
    • Specific features;
      • ↑↑ACTH causes pigmentation
      • Hypokalaemic metabolic alkalosis (↑↑cortisol leads to mineralocorticoid activity aldosterone])
    • Classical features often absent
  • Rarely ectopic CRF production (thyroid (medullary) and prostate cancers)

ACTH-independent causes (↓ACTH due to -ve feedback)

  • Adrenal adenoma/ cancer
  • Adrenal nodular hyperplasia
  • Iatrogenic (Steroids. VERY common)
  • Rarely Carney Complex or McCune-Albright syndrome
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4
Q

Which causes of Cushing’s syndrome would produce a high ACTH level?

A

ACTH-dependent causes (↑ACTH)

Cushing’s disease

  • Bilateral adrenal hyperplasia from ACTH-secreting pituitary adenoma (usually microadenoma)
  • 1m:1female, 30-50yrs

Ectopic ACTH production

  • Esp. small cell lung cancer & carcinoid tumours
  • Specific features;
    • ↑↑ACTH causes pigmentation
    • Hypokalaemic metabolic alkalosis (↑↑cortisol leads to mineralocorticoid activity aldosterone])
  • Classical features often absent

Rarely ectopic CRF production (thyroid (medullary) and prostate cancers)

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5
Q

Which causes of Cushing’s syndrome would produce a low level of ACTH & why?

A

ACTH-independent causes (↓ACTH due to -ve feedback)

  • Adrenal adenoma/ cancer
  • Adrenal nodular hyperplasia
  • Iatrogenic (Steroids. VERY common)
  • Rarely Carney Complex or McCune-Albright syndrome
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6
Q

What is Dexamethasone?

A
  • Synthetic glucocorticoid
  • 25 x more potent than cortisol!
  • Therefor -ve feedback will be more pronounced
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7
Q

How would you confirm the diagnosis of Cushing’s syndrome?

A

1st line - Overnight dexamethasone suppression test

  • Give 1mg PO at midnight → check serum cortisol at 8am
  • Normal: Causes -ve feedback
    • ↓ACTH
    • ↓Cortisol (<50nmol/L)
  • Cushing’s syndrome
    • NO SUPPRESSION!

2nd line - 48h (aka Low Dose) DXM suppression test

  • Give 0.5mg/6h PO for 2days → check serum cortisol at 0 and 48h
  • Normal: Causes –ve feedback
    • ↓ACTH
    • ↓Cortisol (<50nmol/L)
  • Cushing’s syndrome
    • NO SUPPRESSION!!

2nd line - Midnight cortisol

  • Cortisol is normally lowest at midnight and highest in morning
  • Circadian rhythm is lost in Cushing’s!
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8
Q

How would you localise the source of the problem?

(Locate the lesion)

A

1st – PLASMA ACTH. Is ACTH detectable?

NO (ACTH independent - adrenal tumour likely)

  • CT adrenal glands

YES (ACTH dependent - distinguish pituiary OR ectopic cause of ↑ACTH)

  • H DMX test (2mg/6h PO for 2days)
    • Measure plasma & urinary cortisol at 0 & 48hr
    • Complete/ partial suppression indicates Cushing’s disease (-ve feedback causes ↓ACTH and ↓Cortisol)
    • No change indicates ectopic (ectopic is not under feedback control)
  • CRH test (100ug ovine/ human IV)
    • Cortisol at 120min
    • Rises with pituitary, not with ectopic

Then imaging;

  • MRI pituitary if cortisol responds to manipulation
    • If no mass seen, bilateral inferior petrosal sinus blood sampling (for pituitary adenoma) where sinuses are sampled for ACTH release from pituitary
  • If cortisol doesn’t respond, hunt for ectopic
    • IV contrast CT of chest, abdo & pelvis
    • MRI of neck, thorax, abdo (eg for small ACTH secreting carcinoid tumours)
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9
Q

A patient’s undergoes an overnight DXM suppression test. They are found to have cortisol at 41nmol/L at 8am. What do you think?

A

They are normal. DXM causes -ve feedback and low cortisol levels (<50nmol/L)

If you still suspected Cushing’s syndrome do a low dose DXM suppression test and midnight cortisol.

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10
Q

A patient has a low dose DXM suppression test and at 48hrs their cortisoll levels are 52nmol/L. What do you think?

A

They have Cushing’s syndrome, the next stage is locating the lesion.

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11
Q

A patient undergoes a low dose DXM test and their cortisol levels at 48hrs are 67nmol/L. ACTH is undetectable. What do you think?

A

ACTH independent cause of Cushing’s syndrome.

Adrenal tumour likely - CT adrenal glands.

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12
Q

A patients midnight cortisol is high. ACTH is detectable. What do you think?

A

They have an ACTH dependent cause of Cushing’s syndrome.

Distinguish pituitary OR extopic cause.

  • H DMX test (2mg/6h PO for 2days)
    • Measure plasma & urinary cortisol at 0 & 48hr
    • Complete/ partial suppression indicates Cushing’s disease (-ve feedback causes ↓ACTH and ↓Cortisol)
    • No change indicates ectopic (ectopic is not under feedback control)
  • CRH test (100ug ovine/ human IV)
    • Cortisol at 120min
    • Rises with pituitary, not with ectopic
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13
Q

A patient has a cortisol level of 78nmol/L after a low dose DXM test. ACTH is detectable. They have low cortisol levels after a high dose DXM test. What do you think?

A

Cushing’s disease!

  • -ve feedback causes ↓ACTH and ↓Cortisol by managing to inhibit the pituitary
  • Bilateral adrenal hyperplasia from ACTH-secreting pituitary adenoma (usually microadenoma)
  • 1m:1female, 30-50yrs

MRI pituitary if cortisol responds to manipulation

  • If no mass seen, bilateral inferior petrosal sinus blood sampling (for pituitary adenoma) where sinuses are sampled for ACTH release from pituitary
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14
Q

A patient has a high midnight cortisol. ACTH is detectable. They have high cortisol levels after a high dose DXM test. What do you think?

A

Ectopic ACTH production!

  • Ectopic is not under feedback control of DXM.
  • Esp. small cell lung cancer & carcinoid tumours
  • Specific features;
    • ↑↑ACTH causes pigmentation
    • Hypokalaemic metabolic alkalosis (↑↑cortisol leads to mineralocorticoid activity aldosterone])
  • Classical features often absent
  • HUNT FOR ECTOPIC
    • IV contrast CT of chest, abdo & pelvis
    • MRI of neck, thorax, abdo (eg for small ACTH secreting carcinoid tumours)
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15
Q

Outline the treatment for Cushing’s syndrome with the following causes;

  • Iatrogenic
  • Cushing’s disease
  • Adrenal adenoma or carcinoma
  • Ectopic ACTH production
A

Iatrogenic

  • Stop medications if possible

Cushing’s disease

  • Selective removal of pituitary adenoma (trans-sphenoidally [through nose])
  • OR bilateral adrenalectomy is source unlocatable or post-op recurrence
  • Nelson’s syndrome: ↑‎skin pigmentation due to ↑‎↑‎ACTH from enlarging pituitary tumour, as after adrenalectomy theres no -ve feedback. Treatment = pituitary radiation.

Adrenal adenoma or carcinoma

  • Adrenalectomy ‘cures’ adenoma but rarely the cancer
  • Radiotherapy & adrenolytic drugs (mitotane) follow if carcinoma

Ectopic ACTH production

  • Surgery if tumour is located and hasnt spread
  • Metyrapone, ketoconazole & fluconazole ↓cortisol levels pre-op
  • Intubation
  • Mifepristone (competes with cortisol at receptors) + etomidate (blocks cortisol synthesis) if needed
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Endocrinology (11 decks)

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