Physiology
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Endocrine
A 46 year old woman complains of feeling lethargic and dizzy on standing. On examination you note darkening of her lips and gums. Blood tests demonstrate hyperkalaemia, hyponatraemia and metabolic acidosis. Which of the following is the most likely diagnosis:
Answer:
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)
- 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
Physiology / Endocrine / Adrenal Function
Last Updated: 21st April 2019
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 |
