A 67-year-old woman presents with a 6-week history of generalized pain affecting her shoulders, hips, and neck, associated with marked morning stiffness lasting 3 hours. She reports fatigue and difficulty rising from a chair. She denies headache or visual symptoms. Examination reveals restricted range of movement in shoulders and hips due to pain, but normal muscle strength. Blood tests show: Hb 112 g/L, CRP 68 mg/L, ESR 76 mm/hr, normal creatine kinase, normal thyroid function. What is the most appropriate initial management?
Q142
A 26-year-old man presents with a 3-week history of daily fever up to 38.8°C, sore throat, and severe fatigue. He reports a faint rash that appears when febrile. Examination reveals temperature 38.5°C, pharyngeal erythema without exudate, small tender cervical lymph nodes, and mild splenomegaly. Blood tests show: Hb 135 g/L, WCC 14.2 × 10⁹/L (lymphocytes 62%, atypical lymphocytes present), ALT 156 U/L, AST 134 U/L. Monospot test is negative. What is the most appropriate next investigation?
Q143
A 52-year-old woman presents with a 5-month history of fatigue and persistent lower back pain radiating to her right thigh. The pain is worse at rest and wakes her at night. She has lost 7kg unintentionally. She smoked 20 cigarettes daily for 30 years but quit 2 years ago. Examination reveals tenderness over L3-L4 vertebrae. Blood tests show: Hb 98 g/L, MCV 88 fL, calcium 2.82 mmol/L (normal 2.20-2.60), ALP 156 U/L, ESR 78 mm/hr. What is the most likely diagnosis?
Q144
A 58-year-old man with no significant past medical history presents with a 7-week history of severe fatigue, 6kg weight loss, and drenching night sweats. He denies fever, cough, or travel history. Examination reveals multiple non-tender, rubbery lymph nodes in cervical and axillary regions, the largest 3cm in diameter. He has no hepatosplenomegaly. Blood tests show: Hb 108 g/L, WCC 8.2 × 10⁹/L, lymphocytes 4.5 × 10⁹/L, LDH 580 U/L, ESR 68 mm/hr. What is the most appropriate initial investigation?
Q145
A 34-year-old woman presents with a 4-week history of fever up to 39°C, arthralgia affecting her hands and knees, and a rash on her trunk. She returned from hiking in the Scottish Highlands 6 weeks ago. Examination reveals temperature 38.6°C, multiple erythema migrans-like lesions, and swollen metacarpophalangeal joints. Blood tests show: WCC 9.8 × 10⁹/L, CRP 45 mg/L, negative blood cultures. Chest X-ray is normal. What is the most appropriate next step?
Q146
According to NICE guidelines, which of the following time frames defines a fever as 'fever of unknown origin' (FUO) requiring systematic investigation?
Q147
A 70-year-old woman presents with a 3-month history of progressive fatigue, loss of appetite, and 9kg unintentional weight loss. She reports vague abdominal discomfort and early satiety. She has a history of hypertension. Examination reveals a palpable epigastric mass and shifting dullness suggestive of ascites. Blood tests show: Hb 108 g/L, albumin 28 g/L, CA-125 485 U/mL. What is the most likely diagnosis?
Q148
A 48-year-old woman presents with a 10-week history of fatigue and generalized aches. She reports difficulty climbing stairs and brushing her hair. She denies rash or Raynaud's phenomenon. Examination reveals proximal muscle weakness in both upper and lower limbs with normal distal strength. Blood tests show: CK 2,850 U/L (normal 25-200), ALT 78 U/L, ESR 42 mm/hr. What is the most likely diagnosis?
Q149
A 62-year-old man presents with a 5-week history of fever ranging from 37.8°C to 38.5°C, night sweats, and 4kg weight loss. He recently returned from visiting family in India 3 months ago. He has type 2 diabetes controlled on metformin. Examination reveals temperature 38.2°C, no rashes, clear chest, and no lymphadenopathy. Initial blood tests show: Hb 118 g/L, WCC 11.2 × 10⁹/L, CRP 85 mg/L, normal renal and liver function. Chest X-ray and urine culture are normal. What is the most important next investigation?
Q150
A 40-year-old office worker presents with a 4-month history of fatigue and difficulty concentrating. She reports sleeping 8-9 hours nightly but waking unrefreshed. She has gained 5kg despite no change in diet. Her periods are regular. She denies low mood but admits to feeling 'stressed' at work. Examination is unremarkable except for BMI 29 kg/m². Blood tests show: Hb 138 g/L, TSH 6.8 mU/L (normal 0.5-4.5), free T4 11 pmol/L (normal 10-22). What is the most appropriate management?
Undifferentiated Symptoms UK Medical PG Practice Questions and MCQs
Question 141: A 67-year-old woman presents with a 6-week history of generalized pain affecting her shoulders, hips, and neck, associated with marked morning stiffness lasting 3 hours. She reports fatigue and difficulty rising from a chair. She denies headache or visual symptoms. Examination reveals restricted range of movement in shoulders and hips due to pain, but normal muscle strength. Blood tests show: Hb 112 g/L, CRP 68 mg/L, ESR 76 mm/hr, normal creatine kinase, normal thyroid function. What is the most appropriate initial management?
A. Start prednisolone 15mg daily and monitor response (Correct Answer)
B. Refer urgently to rheumatology before starting treatment
C. Arrange temporal artery ultrasound before starting treatment
D. Start NSAIDs and review in 2 weeks
E. Check anti-CCP and rheumatoid factor
Explanation: ***Start prednisolone 15mg daily and monitor response***- The patient's age (>50), **bilateral girdle pain** (shoulders, hips, neck), and **prolonged morning stiffness** (>45 minutes, here 3 hours) with markedly **elevated inflammatory markers (ESR, CRP)** are highly characteristic of **Polymyalgia Rheumatica (PMR)**.- **Low-dose oral corticosteroids**, typically **prednisolone 15mg daily**, are the cornerstone of PMR treatment, leading to a rapid and dramatic symptomatic improvement within days, which also serves a diagnostic purpose.*Refer urgently to rheumatology before starting treatment*- For typical presentations of **PMR** without features of **Giant Cell Arteritis (GCA)**, initial management with corticosteroids can be started in **primary care**, especially given the rapid symptomatic relief it provides.- Delaying treatment while awaiting a specialist appointment is not appropriate for a condition that responds so well to readily available medication and causes significant patient discomfort.*Arrange temporal artery ultrasound before starting treatment*- This investigation is primarily used to diagnose **Giant Cell Arteritis (GCA)**, a vasculitis that can co-exist with PMR or present independently.- The patient explicitly **denies headache or visual symptoms**, which are the cardinal "red flag" symptoms suggesting GCA; therefore, immediate imaging for GCA is not warranted at this stage.*Start NSAIDs and review in 2 weeks*- **NSAIDs** are generally ineffective for the systemic inflammatory process of **PMR** and do not provide the rapid, significant symptomatic relief seen with corticosteroids.- Delaying effective treatment with **corticosteroids** by trying NSAIDs first would prolong the patient's severe symptoms and is not considered appropriate initial management for PMR.*Check anti-CCP and rheumatoid factor*- These tests are used to diagnose **Rheumatoid Arthritis (RA)**, which typically affects small joints symmetrically and is less likely to present with isolated **girdle pain** and **prolonged morning stiffness** as the primary symptoms, especially with normal muscle strength.- While RA can have elevated inflammatory markers, the clinical picture strongly favors **PMR**, making specific RA markers a less immediate diagnostic priority compared to initiating effective PMR treatment.
Question 142: A 26-year-old man presents with a 3-week history of daily fever up to 38.8°C, sore throat, and severe fatigue. He reports a faint rash that appears when febrile. Examination reveals temperature 38.5°C, pharyngeal erythema without exudate, small tender cervical lymph nodes, and mild splenomegaly. Blood tests show: Hb 135 g/L, WCC 14.2 × 10⁹/L (lymphocytes 62%, atypical lymphocytes present), ALT 156 U/L, AST 134 U/L. Monospot test is negative. What is the most appropriate next investigation?
A. EBV serology (IgM and IgG VCA, EBNA) (Correct Answer)
B. CMV serology (IgM and IgG)
C. Throat swab for bacterial culture
D. Abdominal ultrasound to assess splenomegaly
E. HIV serology
Explanation: ***EBV serology (IgM and IgG VCA, EBNA)***- The patient's presentation (fever, sore throat, lymphadenopathy, splenomegaly, **atypical lymphocytosis**, and transaminitis) is classic for **infectious mononucleosis**.- A **negative Monospot test** can occur, especially in young adults or early in the infection; **EBV-specific serology** (IgM and IgG to VCA, and EBNA) is the most sensitive and specific test to confirm or rule out acute EBV infection.*CMV serology (IgM and IgG)*- **Cytomegalovirus (CMV)** can cause a mononucleosis-like syndrome with fever, fatigue, splenomegaly, and atypical lymphocytosis, but typically presents with less prominent **pharyngitis** and lymphadenopathy compared to EBV.- While CMV is a differential, **EBV** is statistically more common and its serology is the primary investigation when Monospot is negative in a typical mononucleosis presentation.*Throat swab for bacterial culture*- The clinical picture, including **splenomegaly**, **atypical lymphocytosis**, and **transaminitis**, is not consistent with a primary bacterial pharyngitis.- The absence of **pharyngeal exudate** further decreases the likelihood of bacterial causes like Group A Streptococcus, which would not explain the systemic findings.*Abdominal ultrasound to assess splenomegaly*- **Splenomegaly** has already been identified on physical examination, indicating it is present.- An ultrasound would confirm the presence and size of the spleen but would not provide the **etiological diagnosis** for the underlying fever and other symptoms.*HIV serology*- **Acute HIV infection** (Acute Retroviral Syndrome) can present with fever, rash, sore throat, lymphadenopathy, and sometimes splenomegaly, mimicking mononucleosis.- However, the prominent **atypical lymphocytosis (62%)** and the classic triad of symptoms are more highly suggestive of **EBV infection** as the immediate next step, although HIV serology could be considered if other causes are ruled out or risk factors are present.
Question 143: A 52-year-old woman presents with a 5-month history of fatigue and persistent lower back pain radiating to her right thigh. The pain is worse at rest and wakes her at night. She has lost 7kg unintentionally. She smoked 20 cigarettes daily for 30 years but quit 2 years ago. Examination reveals tenderness over L3-L4 vertebrae. Blood tests show: Hb 98 g/L, MCV 88 fL, calcium 2.82 mmol/L (normal 2.20-2.60), ALP 156 U/L, ESR 78 mm/hr. What is the most likely diagnosis?
A. Mechanical low back pain with osteoporotic fracture
B. Multiple myeloma (Correct Answer)
C. Spinal tuberculosis
D. Metastatic lung carcinoma to spine
E. Primary hyperparathyroidism with osteoporosis
Explanation: ***Multiple myeloma***
- The constellation of **anaemia (Hb 98 g/L)**, **hypercalcaemia (2.82 mmol/L)**, significant **unintentional weight loss**, and **persistent back pain worse at rest** and at night, along with a markedly **elevated ESR (78 mm/hr)**, strongly points to multiple myeloma. These findings are classic components of the **CRAB** criteria (Calcium elevation, Renal dysfunction, Anaemia, Bone lesions).
- Multiple myeloma is a **plasma cell dyscrasia** leading to bone destruction through osteoclast activation, causing lytic lesions, bone pain, and hypercalcaemia, as well as bone marrow infiltration leading to anaemia.
*Mechanical low back pain with osteoporotic fracture*
- **Mechanical back pain** typically **improves with rest** and is exacerbated by activity, which contrasts with the patient's pain being **worse at rest** and waking her at night, suggesting an inflammatory or neoplastic cause.
- While osteoporosis can cause fractures and pain, it does not explain the **hypercalcaemia**, **anaemia**, **unintentional weight loss**, or significantly **elevated ESR** observed in this patient.
*Spinal tuberculosis*
- **Spinal tuberculosis (Pott's disease)** can cause chronic back pain, weight loss, and elevated ESR, but it is less commonly associated with **hypercalcaemia** and the specific pattern of **normocytic anaemia** seen here.
- Although it involves bone destruction, the constellation of symptoms and lab findings, particularly the severe hypercalcaemia, is more characteristic of multiple myeloma.
*Metastatic lung carcinoma to spine*
- The patient's **smoking history** is a risk factor for lung cancer, and metastases can cause back pain, weight loss, and elevated ESR. However, **hypercalcaemia** from lung cancer metastases is often associated with **PTHrP** production, and alkaline phosphatase may be more significantly elevated in osteoblastic or mixed lesions.
- While lytic metastases can occur, the combination of **hypercalcaemia**, **anaemia**, and a highly elevated ESR with this specific presentation makes **multiple myeloma** a more precise fit than general metastatic lung carcinoma without further evidence of a primary lung tumor.
*Primary hyperparathyroidism with osteoporosis*
- **Primary hyperparathyroidism** causes **hypercalcaemia** and can lead to bone loss (osteoporosis) and bone pain. However, it would not typically cause **anaemia**, **significant unintentional weight loss**, or such a markedly **elevated ESR**.
- The severity of systemic symptoms and the specific pattern of laboratory abnormalities strongly favor a malignancy like multiple myeloma over primary hyperparathyroidism as the sole diagnosis.
Question 144: A 58-year-old man with no significant past medical history presents with a 7-week history of severe fatigue, 6kg weight loss, and drenching night sweats. He denies fever, cough, or travel history. Examination reveals multiple non-tender, rubbery lymph nodes in cervical and axillary regions, the largest 3cm in diameter. He has no hepatosplenomegaly. Blood tests show: Hb 108 g/L, WCC 8.2 × 10⁹/L, lymphocytes 4.5 × 10⁹/L, LDH 580 U/L, ESR 68 mm/hr. What is the most appropriate initial investigation?
A. CT chest, abdomen and pelvis with contrast
B. Excision biopsy of the largest lymph node (Correct Answer)
C. Fine needle aspiration cytology of a lymph node
D. Bone marrow biopsy
E. Flow cytometry on peripheral blood
Explanation: ***Excision biopsy of the largest lymph node***
- An **excision biopsy** is the **gold standard** for diagnosing lymphoma as it preserves the **tissue architecture**, which is critical for accurate classification of Hodgkin and Non-Hodgkin lymphoma subtypes.
- The patient's presentation with **B symptoms** (weight loss, night sweats, fatigue), anemia, elevated LDH, and generalized lymphadenopathy necessitates a definitive tissue diagnosis, and a full node provides ample material for **histopathology**, **immunohistochemistry**, and molecular studies.
*CT chest, abdomen and pelvis with contrast*
- This imaging is primarily used for **staging** the extent of disease once a lymphoma diagnosis has been histologically confirmed, rather than for establishing the initial diagnosis itself.
- While it helps delineate the size and distribution of lymphadenopathy and potential organ involvement, it cannot provide the **tissue confirmation** required to identify the specific type of lymphoma.
*Fine needle aspiration cytology of a lymph node*
- **Fine needle aspiration (FNA)** only provides a cytologic sample and **loses the crucial nodal architecture**, which is frequently essential for accurately diagnosing and subtyping lymphoma, leading to high rates of inconclusive results.
- While it can sometimes differentiate between benign and malignant processes, it often lacks the specificity to classify lymphoma subtypes, which is vital for guiding appropriate treatment decisions.
*Bone marrow biopsy*
- A **bone marrow biopsy** is primarily indicated for **staging** lymphoma to assess for bone marrow involvement or to investigate unexplained cytopenias, rather than as the initial diagnostic procedure when accessible peripheral lymph nodes are present.
- It is an important part of the complete workup but is not the most appropriate first step to establish the primary diagnosis of lymphoma from readily available abnormal lymph nodes.
*Flow cytometry on peripheral blood*
- **Flow cytometry on peripheral blood** is most valuable for diagnosing **leukemias** or conditions with significant circulating malignant cells, which is not the typical primary presentation for most nodal lymphomas.
- While the patient exhibits mild lymphocytosis, the most direct and definitive diagnostic approach for suspected lymphoma originating in lymph nodes is to obtain tissue from the affected node.
Question 145: A 34-year-old woman presents with a 4-week history of fever up to 39°C, arthralgia affecting her hands and knees, and a rash on her trunk. She returned from hiking in the Scottish Highlands 6 weeks ago. Examination reveals temperature 38.6°C, multiple erythema migrans-like lesions, and swollen metacarpophalangeal joints. Blood tests show: WCC 9.8 × 10⁹/L, CRP 45 mg/L, negative blood cultures. Chest X-ray is normal. What is the most appropriate next step?
A. Start oral doxycycline and arrange Lyme serology (Correct Answer)
B. Start broad-spectrum antibiotics and arrange echocardiography
C. Arrange skin biopsy of the rash
D. Refer to rheumatology for suspected reactive arthritis
E. Arrange autoimmune screen including ANA and rheumatoid factor
Explanation: ***Start oral doxycycline and arrange Lyme serology***- The clinical presentation with **fever**, **arthralgia**, and crucially, **multiple erythema migrans-like lesions** after hiking in the **Scottish Highlands** (an endemic area for ticks) is highly suggestive of **disseminated early Lyme disease**.- **Oral doxycycline** is the first-line treatment for early Lyme disease, including disseminated forms, and should be initiated promptly to prevent further progression; **Lyme serology** (e.g., ELISA confirmed by Western blot) is appropriate for diagnosis confirmation.*Start broad-spectrum antibiotics and arrange echocardiography*- While a systemic infection is suspected, the presence of **erythema migrans-like lesions** strongly points away from **infective endocarditis** as the primary diagnosis.- **Echocardiography** would only be indicated if there were specific signs of cardiac involvement, such as new murmurs, chest pain, or conduction abnormalities, which are not described.*Arrange skin biopsy of the rash*- **Erythema migrans** is primarily a **clinical diagnosis**, and a skin biopsy is generally not required and can delay appropriate treatment.- Delaying the initiation of **antibiotic therapy** to perform an invasive procedure like a biopsy is not recommended, as prompt treatment is crucial to prevent chronic complications of Lyme disease.*Refer to rheumatology for suspected reactive arthritis*- **Reactive arthritis** typically presents with an **asymmetric oligoarthritis**, often involving lower extremities, and usually follows **gastrointestinal** or **genitourinary infections**, not typically associated with **erythema migrans** or tick exposure.- While arthralgia is present, the widespread rash and epidemiological link to tick exposure are not characteristic of reactive arthritis.*Arrange autoimmune screen including ANA and rheumatoid factor*- Although **fever** and **arthralgia** can be features of **autoimmune conditions** like rheumatoid arthritis or systemic lupus erythematosus, the presence of **erythema migrans-like lesions** makes an autoimmune process less likely as the primary cause.- Investigating for an infectious etiology like **Lyme disease** based on the distinctive rash and exposure history should precede or accompany an autoimmune workup, as treating the infection is paramount.
Question 146: According to NICE guidelines, which of the following time frames defines a fever as 'fever of unknown origin' (FUO) requiring systematic investigation?
A. Fever >38.0°C for more than 1 week without diagnosis despite initial investigation
B. Fever >37.8°C for more than 2 weeks with negative blood cultures
C. Fever >38.5°C for more than 10 days without identified source on clinical examination
D. Fever >38.3°C for more than 3 weeks without diagnosis despite appropriate investigation (Correct Answer)
E. Fever >38.0°C for more than 4 weeks despite hospital investigation
Explanation: ***Fever >38.3°C for more than 3 weeks without diagnosis despite appropriate investigation***
- This definition aligns with the **classic Petersdorf and Beeson criteria** for **fever of unknown origin (FUO)**.
- It specifies a temperature of **>38.3°C (101°F)** on several occasions, a duration of more than **3 weeks**, and no diagnosis despite **appropriate investigations**.
*Fever >38.0°C for more than 1 week without diagnosis despite initial investigation*
- A duration of **1 week** is generally too short to classify as FUO, as many common viral infections can cause fever for this period.
- The temperature threshold of **>38.0°C** is lower than the **>38.3°C** typically required for a formal FUO diagnosis.
*Fever >37.8°C for more than 2 weeks with negative blood cultures*
- The temperature of **>37.8°C** is below the standard **>38.3°C** threshold for defining FUO.
- While **negative blood cultures** are important, the duration of **2 weeks** is shorter than the **3 weeks** required by most FUO definitions.
*Fever >38.5°C for more than 10 days without identified source on clinical examination*
- A duration of **10 days** is insufficient for an FUO diagnosis; the standard requires at least **3 weeks**.
- The definition of FUO requires failed diagnosis despite **appropriate investigations**, not just clinical examination.
*Fever >38.0°C for more than 4 weeks despite hospital investigation*
- While a duration of **4 weeks** exceeds the 3-week threshold, the temperature criterion of **>38.0°C** is less specific than the **>38.3°C** generally accepted for FUO.
- The **3-week** duration is the established minimum for triggering a systematic FUO workup, making longer durations simply inclusive of the criteria.
Question 147: A 70-year-old woman presents with a 3-month history of progressive fatigue, loss of appetite, and 9kg unintentional weight loss. She reports vague abdominal discomfort and early satiety. She has a history of hypertension. Examination reveals a palpable epigastric mass and shifting dullness suggestive of ascites. Blood tests show: Hb 108 g/L, albumin 28 g/L, CA-125 485 U/mL. What is the most likely diagnosis?
A. Gastric carcinoma
B. Peritoneal tuberculosis
C. Ovarian carcinoma (Correct Answer)
D. Pancreatic carcinoma
E. Hepatocellular carcinoma
Explanation: ***Ovarian carcinoma***- The patient's presentation of **progressive fatigue**, **weight loss**, **abdominal discomfort**, **early satiety**, **ascites**, and a **palpable epigastric mass** in a 70-year-old woman is highly suggestive of advanced malignancy. - A significantly elevated **CA-125 (485 U/mL)** in this clinical context, especially with signs of peritoneal involvement like ascites and a mass, is a strong indicator of **epithelial ovarian carcinoma**.*Gastric carcinoma*- While **weight loss**, **early satiety**, and an **epigastric mass** can be features of gastric carcinoma, the markedly high **CA-125** is not its primary tumor marker, making it less specific.- The presence of **ascites** with such a high CA-125 in a postmenopausal woman points more strongly to **peritoneal carcinomatosis** of ovarian origin rather than a primary gastric tumor.*Peritoneal tuberculosis*- This condition can mimic malignancy with **ascites**, **weight loss**, and elevated **CA-125**, but it usually presents with systemic symptoms like **fever**, **night sweats**, and often a history of exposure.- The presence of a distinct **palpable epigastric mass** is less typical for peritoneal tuberculosis, which more commonly causes diffuse peritoneal involvement or lymphadenopathy.*Pancreatic carcinoma*- While it can cause **weight loss**, **abdominal discomfort**, and a mass, it frequently presents with **obstructive jaundice**, back pain, or new-onset diabetes, which are not mentioned here.- The primary tumor marker for pancreatic cancer is **CA 19-9**, and while CA-125 can be elevated, it is not typically the prominent marker in such a high range without other specific pancreatic symptoms.*Hepatocellular carcinoma*- This cancer typically develops in the setting of **chronic liver disease** or cirrhosis and is primarily associated with elevated **Alpha-Fetoprotein (AFP)**.- Although it can cause **ascites** and an abdominal mass, the absence of liver disease risk factors and the highly elevated **CA-125** make it less likely than ovarian carcinoma.
Question 148: A 48-year-old woman presents with a 10-week history of fatigue and generalized aches. She reports difficulty climbing stairs and brushing her hair. She denies rash or Raynaud's phenomenon. Examination reveals proximal muscle weakness in both upper and lower limbs with normal distal strength. Blood tests show: CK 2,850 U/L (normal 25-200), ALT 78 U/L, ESR 42 mm/hr. What is the most likely diagnosis?
A. Polymyalgia rheumatica
B. Polymyositis (Correct Answer)
C. Drug-induced myopathy
D. Hypothyroid myopathy
E. Inclusion body myositis
Explanation: ***Polymyositis***- Characterized by subacute onset of symmetrical **proximal muscle weakness** (e.g., difficulty climbing stairs or brushing hair) and is associated with a significantly **elevated Creatine Kinase (CK)**.- The absence of skin findings like a heliotrope rash or Gottron papules distinguishes it from **dermatomyositis**, while the presence of true muscle weakness and high enzymes points specifically to an inflammatory myopathy.*Polymyalgia rheumatica*- Presents primarily with **pain and stiffness** in the shoulder and pelvic girdles rather than objective **muscle weakness** on examination.- While the **ESR** is typically elevated, the **Creatine Kinase (CK)** levels remain within the normal range in this condition.*Drug-induced myopathy*- Commonly associated with medications such as **statins**, but usually correlates with recent drug initiation or dosage increases.- While it causes **elevated CK**, the clinical presentation here is highly characteristic of an autoimmune **inflammatory myositis**.*Hypothyroid myopathy*- Can cause proximal weakness and **elevated CK**, but often presents with other systemic features like **bradycardia**, weight gain, or delayed reflexes.- The markedly elevated **ESR** (42 mm/hr) seen here is much more suggestive of an **inflammatory process** like polymyositis.*Inclusion body myositis*- Typically develops in older patients (usually >50 years) and presents with a more **insidious progression** over years rather than weeks.- Frequently involves **asymmetric weakness** and early involvement of **distal muscles**, specifically the finger flexors and quadriceps.
Question 149: A 62-year-old man presents with a 5-week history of fever ranging from 37.8°C to 38.5°C, night sweats, and 4kg weight loss. He recently returned from visiting family in India 3 months ago. He has type 2 diabetes controlled on metformin. Examination reveals temperature 38.2°C, no rashes, clear chest, and no lymphadenopathy. Initial blood tests show: Hb 118 g/L, WCC 11.2 × 10⁹/L, CRP 85 mg/L, normal renal and liver function. Chest X-ray and urine culture are normal. What is the most important next investigation?
A. Blood cultures and echocardiography
B. CT chest, abdomen and pelvis
C. Interferon-gamma release assay (IGRA) for tuberculosis (Correct Answer)
D. HIV serology
E. Bone marrow biopsy
Explanation: ***Interferon-gamma release assay (IGRA) for tuberculosis***
- The patient's presentation with **fever of unknown origin**, constitutional symptoms (weight loss, night sweats), and a recent travel history to **India**, a region highly endemic for **Tuberculosis (TB)**, makes TB a strong diagnostic possibility.
- An **IGRA** is a highly sensitive and specific blood test for latent or active TB infection, crucial when **extrapulmonary TB** or **miliary TB** is suspected, especially since his **chest X-ray** is normal.
*Blood cultures and echocardiography*
- These investigations are primarily used to diagnose **infective endocarditis (IE)**, which is less likely given the absence of a heart murmur, new valvular disease, or peripheral stigmata of IE.
- While blood cultures are part of a general **fever of unknown origin (FUO)** workup, the strong epidemiological link to India points more specifically towards TB as the leading differential.
*CT chest, abdomen and pelvis*
- This imaging study is useful for localizing occult infections, inflammation, or malignancies, which could cause **FUO**, but it is typically performed after targeted infectious disease testing.
- While it might reveal **lymphadenopathy** or granulomas, an **IGRA** directly tests for TB infection, which is highly suspected based on the patient's history.
*HIV serology*
- **HIV infection** can cause chronic fever and constitutional symptoms and predispose individuals to various opportunistic infections, including TB.
- However, given the strong epidemiological link to **India** and the typical clinical presentation, **TB** is a more immediately probable and treatable cause of the current symptoms, making IGRA a more targeted initial step.
*Bone marrow biopsy*
- This is an invasive procedure generally reserved for diagnosing hematological malignancies, **miliary TB**, or other disseminated infections (e.g., fungal, leishmaniasis) when less invasive tests are inconclusive.
- It is not a first-line investigation in the initial workup for **fever of unknown origin**, especially when a strong infectious suspicion like TB can be screened for with a simpler blood test like IGRA.
Question 150: A 40-year-old office worker presents with a 4-month history of fatigue and difficulty concentrating. She reports sleeping 8-9 hours nightly but waking unrefreshed. She has gained 5kg despite no change in diet. Her periods are regular. She denies low mood but admits to feeling 'stressed' at work. Examination is unremarkable except for BMI 29 kg/m². Blood tests show: Hb 138 g/L, TSH 6.8 mU/L (normal 0.5-4.5), free T4 11 pmol/L (normal 10-22). What is the most appropriate management?
A. Refer to endocrinology
B. Repeat thyroid function tests in 3 months
C. Start levothyroxine 50 micrograms daily
D. Check thyroid peroxidase antibodies (Correct Answer)
E. Advise lifestyle modification and reassess in 6 weeks
Explanation: ***Check thyroid peroxidase antibodies*** - The patient presents with **subclinical hypothyroidism**, indicated by an **elevated TSH** (6.8 mU/L) and **normal free T4**, accompanied by symptoms like fatigue and weight gain. - Checking **thyroid peroxidase (TPO) antibodies** is crucial to ascertain if the condition is autoimmune (Hashimoto's thyroiditis), which strongly predicts progression to **overt hypothyroidism** and influences the decision to initiate **levothyroxine** therapy.*Refer to endocrinology* - Most cases of **subclinical hypothyroidism** with TSH <10 mU/L are managed in **primary care**, especially without severe symptoms or a **goiter**. - Referral to endocrinology is typically reserved for **TSH levels >10 mU/L** (or >20 mU/L depending on local guidelines), pregnancy, or complex presentations, which are not present here.*Repeat thyroid function tests in 3 months* - While repeat testing is appropriate for monitoring, it is not the immediate first step in a symptomatic patient with newly diagnosed **subclinical hypothyroidism**. - Identifying the **etiology** (e.g., autoimmune thyroiditis via **TPO antibodies**) is often recommended before merely retesting, as it guides long-term management and prognosis.*Start levothyroxine 50 micrograms daily* - Starting **levothyroxine** for **subclinical hypothyroidism** (TSH <10 mU/L) is generally considered after assessing **TPO antibody status** and persistent symptoms, as evidence for benefit is stronger with positive antibodies. - Without knowing the **autoimmune status**, empirical treatment might be premature, and a more conservative approach often involves confirming the etiology first.*Advise lifestyle modification and reassess in 6 weeks* - While beneficial for overall health and weight, **lifestyle modification** alone will not correct the **thyroid dysfunction** (elevated TSH) and is not the primary treatment for hypothyroidism. - Reassessing thyroid function typically occurs after **3 months** to allow for stabilization and to confirm persistence, not as early as 6 weeks.
