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- Y6 Endocrinology > Adrenal insufficiency/ Addison's > Flashcards

Adrenal insufficiency/ Addison's Flashcards

1
Q

Describe the layers of the adrenal gland. What is produced by each layer?

A
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2
Q

Which axis if cortisol and androgen production under?

A

hypothalamic-pituitary-adrenal

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3
Q

What does the medulla of the adrenals synthesise?

A

catecholamines

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4
Q

What are the 3 types of steroids produced by the adrenal cortex? How are they classed?

A

Steroids:

  1. glucocorticoids e.g. (cortisol- equally good at mineralocorticoid effect), prednisolone, dexamethasone
  2. mineralocorticoids e.g. aldosterone
  3. androgens e.g. dihydrotestosterone

Classed based on predominant physiological effect

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5
Q

Describe the HPA axis.

A
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6
Q

How are types of adrenal insufficiency classified?

A

Primary: destruction or dysfunction of the adrenal gland

Secondary: inadequate pituitary adrenocorticotrophic hormone (ACTH) release and subsequent cortisol production

Tertiary: inadequate hypothalamic corticotropin-releasing hormone and subsequent ACTH release.

Primary cause = Addison’s disease - destruction of entire adrenal cortex (buy autoantibodies/TB etc) so gluco, mineralo and sex steroid production all cease.

Secondary causes = from inadequate ACTH production (HP disease) or long term steroid therapy leading to HPA suppression

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7
Q

What are the causes of Addison’s disease?

A
  • 80% in UK are autoimmune - antibodies against the adrenal cortex
  • TB most common cause in developing countries
  • 7-20% is post infectious including TB, disseminated fungal infection, HIV

Other:

  • infectious disease destroying adrenals e.g. Pseudomonas aeruginosa and meningococcal infection, systemic fungal infections (histoplasmosis and paracoccidioidomycosis), and opportunistic infections secondary to HIV infection
  • bilateral adrenal destruction by metastatic malignancy (lung, breast, stomach, colon, melanoma, and lymphoma)
  • adrenal haemorrhagic infarction (warfarin, heparin use and antiphospholipid syndrome)
  • drugs (etomidate, ketoconazole, suramin, metyrapone, aminoglutethimide, mitotane)
  • other conditions eg. congenital adrenal hyperplasia, mitochondrial disorders
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8
Q

What % of adrenal cortex must be destroyed to produce insufficiency?

A

90% approx

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9
Q

Describe a typical case history of Addison’s disease.

A

A 48-year-old man/woman has a 4-month history of increasing fatigue and anorexia. He has lost 5.5 kg and noticed increased skin pigmentation. He has been otherwise healthy. His mother has Hashimoto’s thyroiditis and one of his sisters has type 1 diabetes. His blood pressure is 110/85 mmHg (supine) and 92/60 mmHg (sitting). His face shows signs of wasting and his skin has diffuse hyperpigmentation, which is more pronounced in the oral mucosa, palmar creases, and knuckles.

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10
Q

How might patients with adrenal insufficiency present acutely?

A
  • Adrenal crisis
  • In adrenal crisis, patients are acutely unwell with vomiting, dizziness, fatigue, hypotension, syncopal episodes, and loss of consciousness. Adrenal crisis is life-threatening and requires immediate treatment. Patients occasionally present exclusively with fatigue or unexplained fever. Addison’s disease may present in association with other autoimmune disorders.
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11
Q

What are the risk factors for Addison’s disease?

A
  • Female sex
  • Adrenocortical autoantibodies
  • Adrenal haemorrhage

Other:

  • AI disease
  • TB or other bacterial infection
  • Fungal infection
  • HIV
  • Drugs that inhibit cortisol production
  • Malignancy
  • Coeliac disease
  • Sarcoidosis
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12
Q

What are the symptoms of Addison’s disease?

A
  • Fatigue
  • Anorexia
  • Weight loss
  • Nausea, vomiting

Other: salt craving (16%), arthralgia, myalgia

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13
Q

What are the signs of Addison’s on physical examination?

A

Hyperpigmentation - more in mucosa and sun exposed areas. palmar creases, areas of friction and scars.

Hypotension - systolic <110mmHg, and postural hypotension+dizziness(12%)

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14
Q

What is responsible for hyperpigmentation in Addison’s disease?

A

Reduced cortisol levels lead through -ve feedback to increased CRH and ACTH production

High ACTH production leads to hyperpigmentation. This is because MSH and ACTH share the same precursor (POMC) which gets cleaved into gamma-MSH, ACTH and beta-lipotropin. ACTH gets further cleaved to alpha-MSH which is important for skin pigmentation.

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15
Q

Why is hyperpigmentation not present in secondary adrenal insufficiency?

A

Secondary - no CRH (hypothalamus) or ACTH (anterior pituitary)

There is no pverproduction of ACTH so no hyperpigmentation

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16
Q

What bloods would you do for Addison’s disease?

A

Bloods:

  • Serum electrolytes - low sodium; elevated potassium(due to low mineralocorticoid); rarely, elevated calcium
  • Low glucose - fue to low cortisol
  • Blood urea - elevated
  • FBC - anaemia, eosinophilia
  • Serum cortisol - <83nm/L (<3microg/dL)
17
Q

What other diagnostic tests would you do for Addison’s disease?

A
  • Short ACTH stimulation test (DIAGNOSTIC)- Synacthen test - plasma cortisol done before and half an hour after tetracosactide (Synacthen) 250mcg IM. Any time of day.
    • Addison’s excluded if 30min cortisol is >550nmol/L.
    • Steroid drugs may interfere with assays: ask lab.
    • NB: in pregnancy and contraceptive pill, cortisol levels may be reassuring but falsely ↑, due to ↑cortisol-binding globulin.
  • 9AM ACTH
    • Elevated in Addison’s - >300ng/L = inappropriately high
    • Low in secondary causes
  • 21-Hydroxylase adrenal autoantibodies: +ve in autoimmune disease in >80%
  • Plasma renin & aldosterone: to assess mineralocortocoid status. Plasma renin elevated (to compensate) and aldosterone suppressed (because synthesis compromised)
  • Plasma DHEA - suppressed
18
Q

What imaging/other investigations could you do for Addison’s disease?

A

Adrenal CT/MRI - normal or atrophic (autoimmune adrenalitis), may be enlarged with or without calcification (suggesting infectious, haemorrhagic disease)

AXR/CXR - past TB could show upper zone fibrosis or adrenal calcification

Other: Test for TB, histoplasma, metastatic disease.

19
Q

Name 2 steroids (natural/synthetic) with a glucocorticoid and mineralocorticoid effect.

A
20
Q

How do you manage Addison’s disease/crisis?

A

Adrenal crisis - glucocorticoid and supportive therapy

  • hydrocortisone sodium succinate: 50-100 mg intravenously every 6-8 hours for 1-3 day
  • Saline to correct hypotension and dehydration - 1L rapidly and further 2-4L in 24hrs
  • Glucose to correct hypoglycaemia (or normal saline with 5% dextrose)

Stable (or after treatment of acute episode) - Glucocorticoid and mineralocorticoid

  • cortisone and fludrocortisone - for life; different doses given at different times of day
  • stress dosing - in people without adrenal insufficiency, cortisol levels increase physiologically in times of trauma, surgery infection. In Addison’s patients, glucocorticoid doses should be increased in these instances then weaned.
21
Q

What can be given to female Addison’s patients with decreased libido?

A

Androgen replacement - dehydroepiandrosterone (ovaries and adrenals are normal sources). DHEA is then converted to adrostenedione and testosterone

22
Q

What proportions of gluco/mineralocorticoi are given when in stable Addison’s patients?

A

Cortisone - two thrids given in the morning, one third in afternoon

Fludrocortisone - once daily

23
Q

What are the adverse effects of corticosteroid therapy?

A

Physiological

  • Adrenal and/or pituitary suppression

Pathological

Cardiovascular

  • Increased blood pressure

Gastrointestinal

  • Pancreatitis

Renal

  • Polyuria
  • Nocturia

Central nervous

  • Depression
  • Euphoria
  • Psychosis
  • Insomnia

Endocrine

  • Weight gain
  • Glycosuria/hyperglycaemia/diabetes
  • Impaired growth
  • Amenorrhoea

Bone and muscle

  • Osteoporosis
  • Proximal myopathy and wasting
  • Aseptic necrosis of the hip
  • Pathological fractures

Skin

  • Thinning
  • Easy bruising

Eyes

  • Cataracts (including inhaled drug)

Increased susceptibility to infection

  • (Signs and fever are frequently masked)
  • Septicaemia
  • Fungal infections
  • Reactivation of tuberculosis
  • Skin (e.g. fungi)
24
Q

What are the complications of Addisons? What is the prognosis with Addison’s?

A
  • Secondary Cushing’s syndrome - from over replacement of glucocorticiod
  • Osteopenia/osteoporosis - long-term excessive glucocorticoid replacement.
  • Hypertension and hypokalaemia (treatment related) - excessive mineralocorticoid replacement

Prognosis

Replacement therapy for life - adherence is high since non-complicance results in uncomfortable symptoms. Sometimes persistent fatigue despite treatment.

25
Q

Define secondary adrenal insufficiency/adrenal suppression?

A

Decreased cortisol production as a result of -ve feedback on the HPA axis, caused by excess glucocorticoids. The consequence is decreased production of both CRH from the hypothalamus and ACTH from the pituitary gland, leading to a decrease in serum cortisol levels.

26
Q

What is the aetiology of secondary adrenal insufficiency?

A
  • Exogenous glucocorticoids e.g. treatment of asthma, COPD, arthritis
  • Adrenal adenoma/carcinoma releasing ACTH causing Cushing’s syndrome can suppress the contalateral adrenal gland and adrenal insufficiency can result with the removal of the tumour without glucocorticoid supplementation
  • In contrast to Addison’s disease, secondary adrenal insufficiency occurs in patients with pituitary or hypothalamic involvement.
27
Q

What are the risk factors for secondary adrenal insufficiency?

A
  • Systemic glucocorticoid administration
  • High potency or dose of exogenous glucocorticoids
  • Local glucocorticoid administration
  • Glucocorticoid treatment >3 weeks
  • Megestrol use (appetite stimulant)
  • Medroxyprogesterone use (part of cancer therapy)
28
Q

What is the typical history/presenting symptoms of adrenal suppression?

A

(mostly Cushingoid symptoms)

  • Sudden cessation/tapering of glucocorticoids (AIS)
  • Gain weight and increased appetite (CS) OR fatigue, anorexia, weight loss (AIS)
  • Nausea and vomiting - AIS
  • Dizziness/orthostatic symptoms - AIS
  • Hx of depression, agitation, sleep disorder (CS)
  • Hx of easy bruising (CS)
  • Myalgia, arthrialgia (AIS)
  • Abdominal pain
29
Q

What are the signs of adrenal suppression? What is absent?

A

Adrenal insufficiency often presents with Cushingoid signs so a high index of suspicion is necessary.

  • Cushingoid features: moon facies, facial plethora, dorsocervical fat pad, bruising, violaceous abdominal striae, thin skin, proximal muscle weakness, and centripetal obesity.
  • Hx of difficult to control hypertension/diabetes
  • Interim hypertension
  • NO hyperpigmentation or autoimmune stigmata (e.g. vitiligo)
30
Q

How do you diagnose adrenal suppression?

A
  • Serum electrolytes - hypo/hyperglycaemia, hypokalaemia, hypomagnesaemia; NB: no hyperkalaemia because RAA is intact
  • ABG - contraction alkalosis
  • Urinalysis - for synthetic corticosteroids if patient does not remember taking them

Short ACTH stimulation test - plasma cortisol done before and half an hour after Synacthen 250mcg IM given. if 30min cortisol is >550nmol/L then not suppressed - but not reliable if adrenals have not had enough time to atrophy

Insulin tolerance test (ITT) and the overnight metyrapone test - address partial adrenal suppression. ITT relies on production of symptomatic hypoglycaemia to stimulate cortisol release so must be monitored closely for hypoglycaemic seizures. Metyrapone can theoretically cause acute adrenal suppression which is risky.

Morning cortisol salivary/serum - low if ACTH suppressed by exogenous corticosteroid (ACTH serum level not reliable) = adrenal suppression

31
Q

How do you manage secondary adrenal insufficiency? (adrenal crisis/ stress/ stable tapering)

A

In adrenal crisis (hypotension, circulatory failure)

  • IV hydrocortisone (stress dose)
  • Supportive measures - IV 5% dextrose in normal saline
  • Treat underlying condition e.g. infection
  • Taper oral corticosteroid when stable

Minor intercurrent stress/illness - double dose of existing corticosteroid for 2-3 days. Increase dose for minor procedures, surgery etc.

Stable patient taking corticosteroid but suitable for taper -

  • >3 weeks duration - taper hydrocortisone by 10mg every 3-4days to physiological dose then gradually by 2.5mg every 2-4 weeks.
  • 1-3 weeks - controversial whether there is need to taper unless hydrocortisone dose was >30mg/day
  • <1 week - can stop regardless of dose but disease may become reactivated
32
Q

What are the complications of adrenal insufficiency? What is the prognosis?

A
  • Corticosteroid dependance - depressed HPA axis BUT most patients are able to recover adrenal function and permenently discontinue corticosteroid therapy
  • Permanent sequelae of adrenal crisis e.g. end organ damage

Prognosis -

Adrenal crises and infections cause excess deaths: mean age at death for men is ~65yrs (11yrs

33
Q

Why might Addison’s be mistaken for anorexia? What distinguishes the two?

A

Addison’s is difficult to diagnose in general

You may diagnose a viral infection or anorexia nervosa in error (K+ is ↓ in anorexia nervosa but ↑ in Addison’s).

34
Q

Blood results: Hb 150 WBC 7 normal differential with no atypical lymphocytes Plat 245 Na+ 127 ↓ K+ 5.8 ↑ Urea 9.8 ↑ Creatinine 81 Glucose 5.6 . In combination with the blood results and image below, which diagnosis below is most likely?

A

Addison’s

Signs:

  • Oral pigmentation
  • Normal glucose so not diabetes
  • Hypokalaemia could also occur in with ectopic ACTH
  • Mineralocorticoid deficiency evident from low Na, high K and high Ur (occurs alongside glucocorticoid deficiency)
35
Q
  1. Random Cortisol is 36 nM (140-690 nM). Which diagnosis does this support?
  2. After administration of synthetic ACTH (Synacthan) the following cortisol levels are obtained: 30 mins = 76 nM; 4 hours = 80 nM; 24 hours = 76 nM. Also plasma ACTH measured at 0mins was high. Diagnosis does this support?
A
  1. Primary OR secondary hypoadrenalism
  2. High ACTH in the presence of a low cortisol = primary hypoadrenalism. In a normal individual a rise above 550 would be expected after ACTH.
    • In secondary hypoadrenalism - SynACTHen test may be normal if the onset of secondary adrenal failure (i.e. pituitary disease) was within 4 weeks.
    • But if lack of ACTH is longstanding then adrenals are likely atrophic and unable to be stimulated quickly.
    • So baseline ACTH should always be noted to differentiate 1o and 2o in SynACTHen test.
36
Q

Which of these are abnormal?

  • Hb 150
  • WBC 7 normal differential with no atypical lymphocytes
  • Plat 245
  • Na+ 127
  • K+ 5.8
  • Urea 9.8
  • Creatinine 81
  • Glucose 5.6
A
  • Na
  • K
  • Urea

Low sodium, raised potassium and raised urea indicate mineralocorticoid deficiency.

37
Q

Why are fludrocortisone AND hydrocortisone given in Addison’s?

A

Hydrocortisone to correct the MINERALOCORTICOID deficiency

Fludrocortisone to correct the GLUCOCORTICOID deficiency

38
Q

What are the electrolyte abnormalities associated with Addison’s?

A
  • hyperkalaemia
  • hyponatraemia
  • hypoglycaemia
  • metabolic acidosis

- Y6 Endocrinology (33 decks)

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