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Time Completed: 02:26:35

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Endocrinology

Question 100 of 180

A 70 year old woman presents to the Emergency Department with fatigue and loss of muscle strength. She has a past medical history of rheumatoid arthritis. On examination you note multiple abdominal striae. Her observations are recorded as:

  • Heart rate: 73 beats/minute
  • Blood pressure: 176/45 mmHg
  • Respiratory rate: 16 breaths/minute
  • Oxygen saturations: 98% on air
  • Temperature: 37.2°C

Which of the following is the most likely diagnosis?

Answer:

The most likely diagnosis is Cushing's syndrome secondary to exogenous steroid use. Clinical features of Cushing's syndrome:
  • Plethoric moon face
  • Weight gain and central obesity
  • Impaired glucose tolerance or diabetes
  • Hypertension
  • Menstrual irregularity
  • Decreased libido
  • Osteoporosis and fragility fractures
  • Purple striae and tendency to bruise easily
  • Proximal myopathy
  • Hirsutism and frontal alopecia
  • Ankle oedema
  • Interscapular fat pad
  • Acne
  • Musculoskeletal aches and pains
  • Unexplained psychiatric symptoms (including depression)
  • Poor wound healing
  • Polycythaemia

Cushing's Syndrome

Cushing's syndrome is the name given to the clinical symptoms and signs induced by pathological hypercortisolism from any cause.

Cushing's disease refers to the specific condition of excess cortisol as a result of an adrenocorticotrophic hormone (ACTH)-secreting pituitary adenoma.

Causes

This may occur due to:

  1. Excess secretion of ACTH
    • ACTH secreting pituitary adenoma (most common endogenous cause)
    • Ectopic ACTH secreting tumours  e.g. bronchogenic or neuroendocrine tumours
  2. Excess adrenal secretion of cortisol
    • Adrenal adenoma
    • Bilateral adrenal hyperplasia
    • Adrenal carcinoma
  3. Exogenous corticosteroid use (most common cause overall)

Clinical features

  • Plethoric moon face
  • Weight gain and central obesity
  • Impaired glucose tolerance or diabetes
  • Hypertension
  • Menstrual irregularity
  • Decreased libido
  • Osteoporosis and fragility fractures
  • Purple striae and tendency to bruise easily
  • Proximal myopathy
  • Hirsutism and frontal alopecia
  • Ankle oedema
  • Interscapular fat pad
  • Acne
  • Musculoskeletal aches and pains
  • Unexplained psychiatric symptoms (including depression)
  • Poor wound healing
  • Polycythaemia

By Mikael Häggström (Own work) [CC0], via Wikimedia Commons

Clinical Features of Cushing's Syndrome. (Image by Mikael Häggström (Own work) [CC0], via Wikimedia Commons)

Diagnosis

  • One of four high-sensitivity tests should be used as a first-line diagnostic test in patients with suspected Cushing syndrome. To increase the diagnostic performance, repeat performance of the initial diagnostic test should be undertaken:
    • Late-night salivary cortisol
    • Overnight 1 mg dexamethasone suppression testing
    • 24-hour urinary free cortisol
    • 48-hour 2 mg dexamethasone suppression testing.
  • Once hypercortisolism has been established, the aetiology should be sought. Morning plasma adrenocorticotrophic hormone (ACTH) is the test of choice in differentiating ACTH-dependent from ACTH-independent Cushing syndrome.
    • Suppressed ACTH levels indicate ACTH-independent Cushing syndrome. Further investigation should include imaging of the adrenal glands to identify adrenal pathology causing hypercortisolism, such as adenoma.
    • Unsuppressed ACTH levels indicate ACTH-dependent Cushing syndrome. Further investigation in such patients should begin with pituitary/sellar magnetic resonance imaging (MRI) to identify an ACTH-secreting pituitary adenoma. Those without definitive lesions on MRI should undergo inferior petrosal sinus sampling (IPSS). Patients with an IPSS central/peripheral gradient >2:1 or 3:1 after corticotrophin-releasing hormone (CRH) stimulation have Cushing's disease. Those without a gradient should have investigation for ectopic ACTH secretion. This evaluation generally includes computed tomography (CT) scanning of the chest, abdomen, and pelvis to look for a tumour secreting ACTH.

Management

  • Treatment should not be undertaken until the diagnosis is firmly established and the source of hypercortisolism is recognised. All patients with moderate to severe hypercortisolism should undergo therapy directed at its underlying cause.
  • Cushing's disease (pituitary adenoma)
    • First-line therapy is transsphenoidal (TSS) resection of the causative pituitary adenoma.
    • A somatostatin analogue (pasireotide), steroidogenesis inhibitors (osilodrostat, ketoconazole, metyrapone, mitotane, etomidate), or glucocorticoid receptor antagonist (mifepristone) is occasionally used for mild hypercortisolism, or short term for severe hypercortisolism, before other therapies are undertaken.
  • Adrenal adenoma
    • First-line therapy is almost always unilateral adrenalectomy of the affected adrenal gland.
  • Adrenal carcinoma
    • First-line therapy in many patients is surgical resection; however, at the time of diagnosis the disease has often progressed beyond the point where surgical therapy is effective. The effectiveness of chemotherapy and adjunctive therapies in both early- and late-stage disease has shown mixed results.
  • Bilateral adrenal disease
    • In these cases first-line therapy generally requires bilateral adrenalectomy. Steroidogenesis inhibitor therapy or glucocorticoid receptor antagonists can be used for patients who wish to avoid bilateral adrenalectomy.
  • Ectopic ACTH
    • The optimal first-line therapy involves locating and surgically resecting the ACTH-producing tumour. Not infrequently, complete resection of these tumours is not possible. Where surgical resection is not possible, second-line therapies include a glucocorticoid receptor antagonist, steroidogenesis inhibitor therapy, or bilateral adrenalectomy.

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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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