Differentials
| System |
What might it be? |
What might I find? |
|
| Endocrine |
Hyperthyroidism |
Caused by: Graves’ disease, toxic multinodular goitre, thyroiditis, etc.
Sweating, heat intolerance, tachycardia, weight loss, fatigue, tremor, loose stools, anxiety. Graves: above, + eye disease, goitre, thyroid acropachy. |
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|
Hypothyroidism |
Hashimoto’s, iodine deficiency’s, over treated thyrotoxicosis, amiodarone.
Fatigue, constipation, weight gain, dry skin, coarse hair, menorrhagia. |
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Type 1 Diabetes |
Cause unknown, possible genetic or viral trigger. Peak onset in childhood.
Weight loss, fatigue, polyuria, polydipsia. May present in DKA. |
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Type 2 Diabetes |
RF:↑age, family history, obesity, poor diet (↑sugar/carbohydrate).
Tiredness, polydipsia, polyuria, opportunistic infections, acanthosis nigricans. |
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Adrenal Insufficiency |
Primary (Addison’s disease), secondary (pituitary ↓ACTH), tertiary (hypothalamic suppression e.g., by long term exogenous steroid use).
Fatigue, muscle cramps, dizziness, thirst/salt craving, weight loss, depression. Hyperkalaemia, hypoglycaemia. ↑ACTH in primary AI, ↓ACTH in secondary AI. |
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Hyper-aldosteronism |
Primary ↑aldosteronism – excess aldosterone produced by adrenal glands.
Secondary ↑aldosteronism – excess renin causing ↑aldosterone secretion. Hypertension, headache, muscle weakness, fatigue, hypokalaemia. |
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Hypercalcaemia |
Causes: iatrogenic, hyperparathyroidism, malignancy, kidney failure.
Kidney stones, painful bones, abdominal groans (abdominal pain, vomiting, constipation), psychiatric moans (confusion, tiredness, depression). |
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Hyper-parathyroidism |
Common cause of hypercalcaemia (see above). ↑Parathyroid hormone (PTH).
Primary – parathyroid gland tumour. Secondary – secondary to low Vitamin D or CKD causing ↓calcium and thus ↑PTH via feedback mechanisms. Tertiary – parathyroid hyperplasia due to secondary hyperparathyroidism. |
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| Haematological |
Iron Deficiency Anaemia |
RF: ↓dietary intake, blood loss, ↓absorption, ↑requirement e.g, pregnancy.
Fatigue, light-headedness, pallor, breathlessness, palpitations, headache. |
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|
B12/Folate Deficiency |
Dietary insufficiency, pernicious anaemia (B12), iatrogenic (e.g., PPI). Megaloblastic, macrocytic anaemia, symptoms as above plus neuropathy. | ||
| Sleep |
Obstructive Sleep Apnoea |
RF: middle age, male, obesity, alcohol, smoker.
Fatigue, snoring, disturbed sleep due to apnoeas, morning headache, daytime somnolence, poor concentration, hypoxia during sleep. |
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Insomnia |
Short-term <3/12, long-term >3/12. Persistent difficulty getting to sleep, maintaining sleep or achieving restorative sleep causing daytime dysfunction.
Multiple underlying causes including psychogenic, medical co-morbiditiy. |
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Poor Sleep Hygiene |
Contributing factors: lack of routine, exposure to screens or blue light, overstimulation, caffeine intake, noisy/warm sleep environment, alcohol intake. | ||
| Miscellaneous |
Malignancy |
Tiredness may be causes by disease, treatment, complications e.g., anaemia or poor nutritional intake as well as psychological burden of cancer. | |
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Chronic Disease |
Chronic liver disease, chronic heart failure, CKD, COPD, autoimmune diseases, inflammatory conditions, post-viral syndromes, MS, etc. | ||
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Perimenopause |
↓oestrogen causes perimenopausal symptoms in the run-up to the cessation of menstruation and often beyond. Disturbed sleep common, as well as waking due to flushing. Fatigue and poor concentration common. | ||
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Psychogenic |
Depression, anxiety, and stress can all affect sleep and cause fatigue. Post-traumatic stress disorder may cause night-time flashbacks disturbing sleep. | ||
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Chronic Fatigue Syndrome |
RF: female, ↑BMI, associated physical or psychological co-morbidities.
>6 weeks of persisting fatigue, worse on exertion with delayed onset, not relieved by rest and disproportionate to activity undertaken. |
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Carbon Monoxide Toxicity |
RF: faulty/poorly maintained appliances, poor ventilation, blocked chimney.
Symptoms improved when not in the home and shared by all household. Fatigue, headache, nausea, dizziness, flushing, flu-like sx, cognitive change. |
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Iatrogenic |
Many culprit medications including: sedating antihistamine, mirtazapine, tricyclic antidepressants, benzodiazepines, opioids, gabapentinoids, etc. | ||
Checklist
| Preparation | Wash – Name – Explain | |
| Presenting Complaint | Open question to establish reason for presentation | |
| Allow patient time to talk uninterrupted | ||
| History of Presenting Complaint | Onset | |
| Timing | ||
| Sleep | ||
| Daytime function | ||
| Triggers | ||
| Associated symptoms | ||
| Exacerbating & relieving factors | ||
| Impact | ||
| System-specific | Weight change | |
| Urinary symptoms | ||
| Thirst | ||
| Tremor | ||
| Goitre | ||
| Temperature tolerance | ||
| Bowel changes | ||
| Lightheadedness or syncope | ||
| Red Flags | Rule in/out serious disease | |
| Relevant Systems Review | Haematological | |
| Psychological | ||
| ICE | What do you think is going on? | |
| Is there anything that is worrying you? | ||
| What were you hoping we would do today? | ||
| Past Medical History | Past medical history | |
| Past surgical history | ||
| Drug History | Prescribed medication | |
| Over-the-counter medication | ||
| Drug allergies | ||
| Social History | Smoking | |
| Alcohol | ||
| Diet | ||
| Exercise | ||
| Recreational drugs | ||
| Work | ||
| Driving | ||
| Who is at home? | ||
| Housing | ||
| Sick contacts | ||
| Forgeign travel | ||
| Family History | Do any family members have any endocrine problems? | |
| Do any health conditions run in the family? | ||
| Comm. Skills | Establish rapport | |
| Use open and closed questions appropriately | ||
| Structured history taking | ||
| Pick up on cues | ||
| Rule in/out differential diagnoses | ||
| Summarise succinctly |
Explanation
“I have been asked to speak to you today about the tiredness you have been experiencing. I will ask you some questions to try to determine what might be causing the problem. Does that sound all right?”
History of Presenting Complaint
Key points in a tiredness history include:
- Onset – when did it start?
- Timing
- Sleep
- Daytime function
- Triggers – can they think of anything that may have caused the problem?
- Associated symptoms
- Exacerbating and relieving factors (e.g., caffeine, altering sleep patterns)
- Impact – on the patient, their work, driving, etc.
Ask about timing. Do they feel tired all day, or is the tiredness worse as the day goes on? Waking from sleep in the morning feeling extremely tired and unrefreshed can be a symptom of obstructive sleep apnoea (OSA).
How is the patient sleeping? How many hours of sleep per night are they getting? Are they waking up during the night? Do they have good sleep hygiene (e.g., good routine, lack of screens, cool and dark bedroom, etc.)?
Ask about daytime functioning. Excessive daytime somnolence is seen in OSA.
System-specific History
Endocrine symptoms to enquire about include, but are not limited to:
- Weight change
- Urinary symptoms (e.g., urinary frequency or polyuria)
- Thirst (indicating possible diabetes or adrenal insufficiency)
- Tremor
- Goitre (e.g., Graves’ disease or Hashimoto’s thyroiditis)
- Temperature tolerance (e.g., heat or cold intolerance)
- Bowel changes
- Lightheadedness or syncope (associated with adrenal insufficiency)
Weight loss may be associated with type 1 diabetes, adrenal insufficiency, thyrotoxicosis or malignancy, whereas weight gain can be a symptom of hypothyroidism and a cause of OSA.
Type 1 diabetes typically presents with polyuria, polydipsia, weight loss and fatigue.
Thyroid dysfunction causes fatigue due to either over- or under-activity. Fatigue secondary to thyrotoxicosis (e.g., Graves’ disease) may be associated with goitre, heat intolerance, tremor, diarrhoea and weight loss. Hypothyroidism is associated with weight gain, constipation, cold intolerance and goitre.
Red Flags
Red flag symptoms in a tiredness history include:
- Unintentional weight loss
- Night sweats
- Lymphadenopathy
Malignancy may present with fatigue associated with other non-specific but concerning symptoms such as night sweats or significant unintentional weight loss, or symptoms concerning for specific malignancy such as dysphagia (oesophageal cancer), haemoptysis (lung cancer) or post-menopausal bleeding (endometrial cancer).
Relevant Systems Review
Relevant systems to review when taking a history of tiredness include the following:
- Haematological
- Psychological
Anaemia is a common cause of fatigue. Iron deficiency is the most common cause of anaemia, which in turn is most commonly caused by blood loss.
Ask about heavy menstrual bleeding (menorrhagia) and bleeding from the gastrointestinal tract (melaena, rectal bleeding, dyspepsia).
Psychological causes of tiredness include depression, anxiety, and post-traumatic stress disorder; either due to the condition itself or due to a secondary effect on sleep quality.
Psychological comorbidity is a risk factor for developing chronic fatigue syndrome.
Ideas, Concerns & Expectations (ICE)
Does the patient or their partner have any thoughts as to what might be causing their tiredness?
Is the patient worried about their symptoms (e.g., the possibility of a sinister underlying cause such as cancer)?
What does the patient want out of the consultation (e.g., a blood test, medication)?
Past Medical History
Pre-existing medical conditions that may be associated with tiredness include:
- Chronic disease (e.g., chronic liver disease, chronic heart failure, CKD, COPD, etc.)
- Cancer
- Depression
Fatigue associated with cancer is likely multifactorial, caused by disease burden, cancer treatments (e.g., chemotherapy), psychological distress, or complications (e.g., anaemia or hypercalcaemia).
Drug History
Common pharmacological causes of tiredness include:
- Antidepressants (e.g., tricyclic antidepressants or mirtazapine)
- Opiates
- Benzodiazepines
- Sedating antihistamine
- Gabapentinoids (e.g., gabapentin or pregabalin)
- Steroids
Long-term corticosteroid use is associated with adrenal insufficiency and steroid-induced diabetes.
Social History
Alcohol can have a long-term negative impact on sleep quality and mood, but is commonly used as a short-term coping mechanism for psychological distress and poor sleep.
Recreational drugs (e.g., cannabis) may be used for similar purposes.
Eating a diet of poor nutritional value can cause fatigue, as well as iron deficiency and obesity. Obesity can in turn cause type 2 diabetes or OSA.
Does the patient drive? OSA with significant daytime somnolence must be declared to the DVLA. There is specific driving guidance for patients taking diabetic medications causing hypoglycaemia (e.g., insulin or gliclazide).
What is the condition of the patient’s accommodation? Poor ventilation or faulty appliances are risks for carbon monoxide toxicity.
Family History
Several conditions associated with tiredness have a genetic predisposition:
- Diabetes
- Malignancy
- Thyroid disorders
Finishing
Thank the patient and wash your hands.
Consider your differential diagnosis and how you might narrow this down further through examination, bedside tests, or further investigation and imaging.
Last updated July 2025
Head to members.zerotofinals.com for practice OSCE stations, including an interactive checklist, specific cases and clinical findings.
