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Time Completed: 01:08:33

Final Score 46%

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97

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Physiology

Endocrine

Question 175 of 180

Which of the following clinical features is typical of Addison's disease:

Answer:

Typical Biochemistry in Addison's disease (primary insufficiency of the adrenal cortex):
  • Hyponatraemia (due to mineralocorticoid deficiency)
  • Hyperkalaemia (due to mineralocorticoid deficiency)
  • Hypoglycaemia (due to glucocorticoid deficiency)
  • Low morning cortisol
  • Elevated ACTH
  • Elevated plasma renin
  • Synacthen test (cortisol post Synacthen < 500 nmol/L)
  • Positive adrenal autoantibodies

Adrenal Insufficiency

Primary Adrenal Insufficiency

Primary insufficiency of the adrenal cortex, called Addison's disease, arises as a result of a destructive process in the adrenal gland or genetic defects in steroid synthesis. All three zones of the adrenal cortex are typically affected.

Causes

Causes of primary adrenal insufficiency include:

  • Autoimmune adrenalitis (over 70% of cases in the developed world)
  • Genetic e.g. congenital adrenal hyperplasia/hypoplasia
  • Iatrogenic e.g. bilateral adrenalectomy, drugs
  • Infarction/haemorrhage e.g. antiphospholipid syndrome, anticoagulants
  • Infection e.g. TB, fungal, AIDS
  • Infiltration e.g. amyloidosis, haemochromatosis
  • Malignancy e.g. lung, breast or kidney (symptomatic adrenal insufficiency uncommon)

Clinical Features

Symptoms/Signs:

  • Onset is usually gradual and symptoms may be non-specific
  • Fatigue, weakness, anorexia, weight loss, nausea and abdominal pain
  • Dizziness and postural hypotension (due to mineralocorticoid deficiency)
  • Increased pigmentation (due to ACTH excess from reduced cortisol negative feedback leading to melanocyte stimulation)
  • Reduced libido and loss of axillary/pubic hair in women (due to androgen deficiency)

Typical Biochemistry:

  • Hyponatraemia (due to mineralocorticoid deficiency)
  • Hyperkalaemia (due to mineralocorticoid deficiency)
  • Hypoglycaemia (due to glucocorticoid deficiency)
  • Low morning cortisol
  • Elevated ACTH
  • Elevated plasma renin
  • Synacthen test (cortisol post Synacthen < 500 nmol/L)
  • Positive adrenal autoantibodies

Management

Patients with primary adrenal failure need lifelong glucocorticoid and mineralocorticoid replacement therapy, typically given as hydrocortisone and fludrocortisone. Patients should be advised to increase the dose of their glucocorticoid at times of illness and glucocorticoids need to be administered IV/IM during surgery or in cases of prolonged vomiting/diarrhoea. Patients should be provided with a steroid emergency card, encouraged to wear medical alert jewellery, and be provided with emergency contact details for their endocrine team.

An acute exacerbation of Addison's disease is called an adrenal crisis. It is a life-threatening emergency characterised by hypotensive hypovolaemic shock and hypoglycaemia.  The mainstay of treatment is rehydration and urgent systemic glucocorticoid therapy.

Acute adrenal failure may also occur if long-term high-dose steroid treatment is stopped abruptly (as the prolonged steroid treatment has suppressed the HPA axis and natural ACTH release). Patients taking long-term steroids should thus be instructed not to stop their steroids abruptly, at least until an adequate adrenal reserve has been demonstrated.

Secondary Adrenal Insufficiency

Secondary adrenal insufficiency can arise as the result of any cause of hypopituitarism. Patients display similar features as above with the exception that pigmentation is absent as ACTH is not raised, and mineralocorticoid deficiency is not a feature, because aldosterone secretion is not significantly influenced by ACTH.

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  • Biochemistry
  • Blood Gases
  • Haematology
Biochemistry Normal Value
Sodium 135 – 145 mmol/l
Potassium 3.0 – 4.5 mmol/l
Urea 2.5 – 7.5 mmol/l
Glucose 3.5 – 5.0 mmol/l
Creatinine 35 – 135 μmol/l
Alanine Aminotransferase (ALT) 5 – 35 U/l
Gamma-glutamyl Transferase (GGT) < 65 U/l
Alkaline Phosphatase (ALP) 30 – 135 U/l
Aspartate Aminotransferase (AST) < 40 U/l
Total Protein 60 – 80 g/l
Albumin 35 – 50 g/l
Globulin 2.4 – 3.5 g/dl
Amylase < 70 U/l
Total Bilirubin 3 – 17 μmol/l
Calcium 2.1 – 2.5 mmol/l
Chloride 95 – 105 mmol/l
Phosphate 0.8 – 1.4 mmol/l
Haematology Normal Value
Haemoglobin 11.5 – 16.6 g/dl
White Blood Cells 4.0 – 11.0 x 109/l
Platelets 150 – 450 x 109/l
MCV 80 – 96 fl
MCHC 32 – 36 g/dl
Neutrophils 2.0 – 7.5 x 109/l
Lymphocytes 1.5 – 4.0 x 109/l
Monocytes 0.3 – 1.0 x 109/l
Eosinophils 0.1 – 0.5 x 109/l
Basophils < 0.2 x 109/l
Reticulocytes < 2%
Haematocrit 0.35 – 0.49
Red Cell Distribution Width 11 – 15%
Blood Gases Normal Value
pH 7.35 – 7.45
pO2 11 – 14 kPa
pCO2 4.5 – 6.0 kPa
Base Excess -2 – +2 mmol/l
Bicarbonate 24 – 30 mmol/l
Lactate < 2 mmol/l

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