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Endocrinology > Cushing's syndrome > Flashcards

Cushing's syndrome Flashcards

1
Q

Glucocorticoid action (6)

A
  • catabolic hormones - proteolysis, lipolysis, gluconeogenesis
  • inhibit immune reactions
  • induce neutrophilia, lymphocytopenia and eosinophilopenia
  • induce euphoria, psychosis
  • potentiate vasoconstrictive catecholamines action
  • increase gastric acidity and the development of peptic ulcers
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2
Q

Regulation of glucocorticoid secretion (3)

A
  • ACTH –> stimulates cortisol secretion and adrenal cortex hyperplasia
  • secretion of ACTH is enhanced by corticotropin-releasing hormone (CRH) and vasopressin (AVP) produced in the hypothalamus
  • cortisol suppresses ACTH and CRH secretion
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3
Q

Cushing’s syndrome

  • definition
  • classification
A

-chronic exposure to excess glucocorticoids

  • exogenous - due to administration of exogenous glucocorticoids
  • endogenous:
    1. ACTH dependent (ACTH producing pituitary adenoma and Ectopic ACTH or CRH secretion)
    2. ACTH Independent (Adrenocortical adenoma, adrenocortical carcinoma, micro and macronodular adrenal hyperplasia)
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4
Q

Cushing’s syndrome

-epidemiology (3)

A
  • most often cause –> iatrogenic administration of glucocorticoids for immunosuppression or treatment of inflammatory disease
  • most often cause of endogenous –> ACTH producing pituitary adenoma (90-95% microadenoma)
  • women are 3-8 times more likely than men
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5
Q

Iatrogenic Cushing’s syndrome (3)

A
  • caused by administration of excessive amounts of synthetic glucocorticoid and only rarely by ACTH administration
  • iatrogenic administration of glucocorticoids –> inhibition of ACTH and CRH secretion –> atrophy of adrenal cortex
  • lab test –> reduced ACTH concentration and reduced cortisol concentration in serum, saliva and urine
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6
Q

Adrenal insufficiency after glucocorticoid intake (3)

A
  • <3 weeks of any dose of glucocorticoids intake does not cause dysfunction of hypothalamus-pituitary (HPA) axis
  • exogeneous glucocorticoids –> inhibition of CRH and ACTH secretion –> adrenal cortex atrophy
  • abrupt discontinuation of glucocorticoid intake may cause the development of acute adrenal insufficiency
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7
Q

Cushing’s syndrome

-pathogenesis (2)

A
  • autonomous ACTH secretion –> bilateral adrenal cortex hyperplasia –> glucocorticoid + adrenal androgen hypersecretion
  • normal ACTH and cortisol circadian rhythm is usually lost but pre-bedtime concentrations are high
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8
Q

Ectopic ACTH secretion

-pathogenesis (3)

A
  • ectopic tumors may secrete CRH and/or ACTH
  • most non-pituitary tumors are completely resistant to feedback inhibition
  • high dose (8mg) dexamethasone suppression test is used to differentiate pituitary adenoma and ectopic ACTH secretion
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9
Q

Cortisol-secreting adrenal tumors

-pathogenesis (4)

A
  • increased cortisol secretion –> suppresses CRH and ACTH secretion –> pituitary corticotropes and adrenal glands atrophy
  • adrenal adenomas produce cortisol very efficiently
  • adrenal carcinomas are inefficient in terms of steroid production
  • most are monoclonal –> result from accumulated genetic abnormalities
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10
Q

Bilateral adrenal hyperplasia

-pathogenesis (4)

A

-Bilateral adrenal micronodular hyperplasia –> both sporadic and familial

  • Bilateral adrenal macronodular hyperplasia –> adrenal glands contain multiple non-pigmented nodules greater than 5mm in diameter.
  • Increases in cortisol secretion –> mediated by overexpression of receptors or have activating protein G alpha subunit mutations
  • most are sporadic
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11
Q

Cushing’s syndrome

-signs and symptoms (7)

A
  • weight gain, central obesity, rounded fact, fat pad on back of neck
  • osteopenia, osteoporosis
  • weakness, proximal myopathy
  • hypertension, hypokalemia, edema, atherosclerosis, increase in plasma concentration of clotting factors
  • decreased libido, amenorrhea
  • irritability, depression
  • hypokalemia –> due to decreased renal conversion of cortisol
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12
Q

Cushing’s syndrome

-dermatologic changes (5)

A
  • easy bruisability - loss of subcutaneous connective tissue due to the catabolic effects of glucocorticoids
  • Purple + wide striae
  • Skin atrophy - loss of subcutaneous fat
  • Fungal infections - especially tinea versicolor
  • Hyperpigmentation - often in patients with Ectopic ACTH syndrome - ACTH binds to melanocyte stimulating hormone receptors
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13
Q

Cushing’s syndrome

-metabolic alterations (5)

A
  • glucocorticoids stimulate gluconeogenesis
  • obesity causes increased insulin resistance
  • glucose intolerance
  • dyslipidemia
  • hyperglycemia becomes much easier to control and may completely remit if hypercortisolism is reversed
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14
Q

Cushing’s syndrome

-bone changes (3)

A
  • osteoporosis (even in young patients) due to: decrease intestinal calcium absorption, decreased renal calcium reabsorption, decreased bone formation and increase bone resorption
  • pathologic fractures may occur
  • osteopenia
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15
Q

Cushing’s syndrome

-psychologic symptoms (5)

A
  • emotional lability
  • depression
  • irritability
  • anxiety
  • panic attacks
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16
Q

Cushing’s syndrome

-infections and immune function impairments (4)

A
  • increases susceptibility to infections,
  • increase WBC, eosinopenia,
  • hypercoagulation
  • glucocorticoids inhibit immune functions
17
Q

Cushing’s syndrome

-impairments of reproductive system (6)

A
  • menstrual irregularities –> due to suppression of secretion of gonadotropin-releasing hormone
  • low FSH, LH and estradiol
  • abnormal menstrual cycle, oligomenorrhea, amenorrhea
  • hirsutism, oily facial skin, acne
  • increase libido
  • virilization
18
Q

Cushing’s syndrome

-diagnosis steps

A
  1. Clinical suspicion
  2. Screening/ confirmation - dexamethasone suppression test, 24h urinary free cortisol, midnight salivary or plasma cortisol
  3. Differential diagnosis: plasma ACTH
  • it is essential to exclude exogeneous glucocorticoid intake
  • testing is recommended in all patients with adrenal incidentalomas
19
Q

Pseudo-Cushing’s syndrome (2)

A
  • mild hypercortisolism
  • can occur in disorders other than CS like: pregnancy, severe obesity, prolonged psychological stress, poorly controlled diabetes mellitus, chronic alcoholism
20
Q

Cushing’s syndrome

-screening tests

A

diagnosis is made when at least two different first line tests are abnormal:
1. Overnight 1mg dexamethasone suppression test –> plasma cortisol >50 nmol/L at 8-9am after 1mg at 11pm

  1. 24h urinary free cortisol (UFC) excretion (two measurements) –> increased above normal (3x)
  2. Late night salivary or plasma cortisol –> >130 nmol/or midnight salivary cortisol >5nmol/L
  3. Low dose DEX test if further confirmation is needed –> plasma cortisol >50 nmol/L
21
Q

Cushing’s syndrome

-differential diagnosis

A
  • plasma ACTH
    1. ACTH normal or high –>ACTH- dependent Cushing’s syndrome
    2. ACTH suppressed to <5 pg/ml –> ACTH independent Cushing’s syndrome
22
Q

Cushing’s syndrome

  • bilateral sinus petrosus sampling - complications
  • bilateral sinus petrosus sampling - results
A
  • cranial nerve palsy, hemiparesis, petrosal and/or cavernous sinus venous thrombosis, pulmonary embolism, inguinal or jugular hematomas
  • increased central/peripheral plasma ACTH ratio >2 at baseline and >3 at 2-5min after CRH injection –> Cushing’s disease
23
Q

Cushing’s syndrome

-treatment (5)

A
  • depends on the type!
  • glucocorticoid replacement needs to be initiated at the time of surgery and slowly tapered following recovery
  • it may require 6-18 months, years or it may not even recover
  • if surgery contraindicated –> medical therapy
  • pituitary irradiation or bilateral adrenalectomy –> when operation is contraindicated
24
Q

Ectopic ACTH syndrome

-treatment (3)

A
  • surgical excision of the tumor
  • if surgery not possible –> adrenal enzyme inhibitors or bilateral adrenalectomy
  • glucocorticoid receptor antagonist and somatostatin analogs are also useful
25
Q

ACTH- independent Cushing’s syndrome

-treatment (4)

A
  • removal of affected adrenal gland
  • glucocorticoid replacement needs to be initiated at the time of surgery and slowly tapered following recovery
  • it may require 6-18 months, years or it may not even recover
  • surgical bilateral adrenalectomy is used in patients with micronodular or macronodular adrenal hyperplasia –> life long glucocorticoid and mineralocorticoid replacement is required
26
Q

ACTH- independent Cushing’s syndrome vs. dependent

A

primary - ACTH- independent Cushing’s syndrome –> high levels of cortisol, decrease CRH and decrease ACTH

secondary ACTH- dependent Cushing’s syndrome

27
Q

ACTH-dependent Cushing’s syndrome

-differential diagnosis

A
  1. MRI - pituitary
  2. CRH test
  3. High dose DEX test
  • if CRH test and high dose DEX positive –> Cushing’s disease –> Transsphenoidal surgery
  • if CRH test and high dose DEX negative –> Ectopic ACTH production –> inferior petrosal sinus sampling –> locate and remove ectopic source –> bilateral adrenalectomy (if neg.)
28
Q

ACTH-independent Cushing’s syndrome

-differential diagnosis

A
  1. Unenhanced CT of adrenal gland
  • if unilateral mass –> adrenal tumor workup –> unilateral adrenalectomy
  • if bilateral micronodular or macronodular adrenal hyperplasia –> bilateral adrenalectomy
29
Q

If surgery is contraindicated, what are the possible medications?

A
  1. Adrenal enzyme inhibitors - metyrapone, ketoconazole, mitotane, etomidate
  2. Medical therapy targeting corticotroph tumor (carbergoline - dopamine agonist, pasireotide - somatostatin analogues)

Endocrinology (11 decks)

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