Physiology
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Endocrine
A patient presents to ED with a headache and is found to be severely hypertensive. She is currently under investigation for suspected Cushing's syndrome. What is the most likely cause of her Cushing's syndrome:
Answer:
The most common cause of Cushing's syndrome is the use of exogenous glucocorticoids. Endogenous Cushing's syndrome is divided into corticotropin-dependent and corticotropin-independent causes. Corticotropin-dependent causes account for about 80-85% of cases and 80% are due to pituitary adenomas (Cushing's disease). The remaining 20% are due to ectopic corticotropin syndrome, which is usually due to small-cell carcinoma of the lung and bronchial carcinoid tumours but may occur with almost any endocrine tumour. Corticotropin-independent Cushing's syndrome is most often due to a unilateral tumour: adrenal adenoma in 60% and adrenal carcinoma in 40% of cases. Very rare adrenal causes of Cushing's syndrome are corticotropin-dependent macronodular adrenal hyperplasia, primary pigmented nodular adrenal disease and McCune-Albright syndrome.Cushing's Syndrome
Physiology / Endocrine / Adrenal Function
Last Updated: 21st April 2019
Cushing's syndrome is the name given to the clinical symptoms and signs induced by chronic glucocorticoid excess.
Cushing's disease refers to the specific condition of excess corticosteroids as a result of an ACTH-secreting pituitary adenoma, leading to bilateral adrenal hyperplasia and excess cortisol secretion. Cushing's disease is also associated with hyperpigmentation due to the melanocyte-stimulating action of ACTH.
Causes
This may occur due to:
- Excess secretion of ACTH
- ACTH secreting pituitary adenoma (Cushing's disease)
- Ectopic ACTH e.g. lung cancer
- Excess secretion of cortisol
- Adrenal adenoma or carcinoma
- Exogenous steroids
Clinical Features
- Plethoric moon face
- Central obesity
- Impaired glucose tolerance or diabetes
- Hypertension
- Menstrual irregularity, erectile dysfunction
- Osteoporosis and kyphosis
- Purple striae and tendency to bruise easily
- Proximal myopathy
- Hirsutism and frontal alopecia
- Ankle oedema
- Interscapular fat pad
- Acne
- Musculoskeletal aches and pains
- Depression
- Poor wound healing
- Polycythaemia
![By Mikael Häggström (Own work) [CC0], via Wikimedia Commons](https://mrcemsuccess.com/wp-content/uploads/2017/10/Cushings_syndrome_vector_image.svg_.png)
Clinical Features of Cushing's Syndrome. (Image by Mikael Häggström (Own work) [CC0], via Wikimedia Commons)
Management
If an adrenal tumour is found, adrenalectomy is the treatment of choice. In ectopic ACTH, appropriate treatment of the underlying malignancy and medical control of cortisol levels are needed. In Cushing's disease, trans-sphenoidal removal of the pituitary adenoma is indicated. Medical treatment (e.g. metyrapone which blocks cortisol production) can be used pre-operatively if symptoms are severe, or there is uncontrolled hypokalaemia, diabetes and hypertension.
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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 |
