A 66-year-old woman presents with a 16-week history of fatigue, poor appetite, and 7kg weight loss. She reports feeling generally unwell with muscle aches and low mood. Blood tests show: Hb 118 g/L, WCC 6.8×10⁹/L, platelets 245×10⁹/L, Na+ 128 mmol/L, K+ 5.2 mmol/L, urea 7.8 mmol/L, creatinine 88 μmol/L, glucose 3.8 mmol/L. What is the most appropriate next step?
Q22
A 45-year-old man presents with an 8-week history of recurrent fever, typically occurring every 3 days, associated with severe rigors, headache, and myalgia. He immigrated from Nigeria 15 years ago and recently visited his family in Lagos for 2 months, returning 10 weeks ago. He did not take malaria prophylaxis. Examination during a febrile episode shows temperature 39.8°C, mild splenomegaly, and jaundice. What is the most appropriate immediate investigation?
Q23
According to NICE guidance on the assessment of chronic pain in primary care, which statement best describes the recommended initial approach to evaluating a patient presenting with persistent widespread pain and fatigue lasting 6 months?
Q24
A 28-year-old woman presents with a 7-week history of fatigue, night sweats, and intermittent fever. She returned from a 6-month backpacking trip through Southeast Asia 3 months ago. Examination reveals temperature 38.3°C, cervical lymphadenopathy (2cm mobile nodes), and mild splenomegaly. Blood tests show: Hb 108 g/L, WCC 3.2×10⁹/L, platelets 142×10⁹/L, ESR 68 mm/hr. What is the most appropriate next investigation?
Q25
A 57-year-old man presents with a 4-month history of progressive fatigue and 9kg unintentional weight loss. He reports increased thirst and nocturia (4-5 times per night). His brother has type 2 diabetes. Examination reveals BMI 26 kg/m², mild muscle wasting, and dry mucous membranes. Random glucose is 18.2 mmol/L. Which additional investigation is most important to perform urgently?
Q26
A 32-year-old woman presents with a 5-month history of profound fatigue and cold intolerance. She reports gaining 8kg despite reduced appetite, constipation, and dry skin. Her periods have become heavier and irregular. On examination, her pulse is 54 bpm, BP 130/85 mmHg, and she has delayed relaxation of ankle reflexes. What is the most appropriate first-line investigation?
Q27
A 63-year-old man with metastatic prostate cancer presents for pain review. He reports constant deep aching pain in his lumbar spine and pelvis (7/10 severity) partially controlled with morphine sulfate modified-release 60mg BD. He experiences 4-5 episodes daily of sudden-onset severe shooting pain (9/10) in his right leg lasting 1-2 minutes, triggered by movement. Background pain is adequately controlled but breakthrough pain significantly impacts function. Current medications: morphine sulfate MR 60mg BD, paracetamol 1g QDS, and ibuprofen 400mg TDS. What is the most appropriate modification to his pain management?
Q28
A 49-year-old woman presents with a 22-week history of severe, unrelenting fatigue that is not relieved by rest. She describes post-exertional malaise lasting >24 hours after minimal activity, unrefreshing sleep, difficulty concentrating ('brain fog'), and orthostatic intolerance. Previously very active, she now struggles with basic daily tasks. Examination and extensive blood tests (FBC, U&Es, LFTs, TFTs, glucose, CRP, ferritin, B12, folate, coeliac serology) are all normal. What is the most appropriate diagnosis?
Q29
A 56-year-old man presents with a 17-week history of fatigue and 8kg weight loss. He reports vague abdominal discomfort and change in bowel habit with looser stools. He is a smoker (25 pack-years). Examination reveals BMI 23 kg/m², pulse 92 bpm, BP 134/82 mmHg, and vague epigastric tenderness. Blood tests show: Hb 118 g/L, MCV 88 fL, platelets 542 × 10⁹/L, albumin 34 g/L, bilirubin 42 µmol/L, ALT 68 U/L, ALP 324 U/L, GGT 186 U/L, CA19-9 680 U/mL (normal <37). What is the most likely diagnosis?
Q30
A 37-year-old woman presents with a 13-week history of fatigue, intermittent low-grade fever up to 37.9°C, and arthralgia affecting her hands and knees. She has noticed a rash on her shins. Examination reveals temperature 37.6°C, pulse 88 bpm, BP 124/78 mmHg, bilateral hilar lymphadenopathy on chest auscultation, and tender, erythematous nodules on both shins. Blood tests show: Hb 132 g/L, WCC 8.4 × 10⁹/L, platelets 312 × 10⁹/L, ESR 42 mm/hr, CRP 28 mg/L, corrected calcium 2.68 mmol/L, ACE 82 U/L (normal 20-70). Chest X-ray confirms bilateral hilar lymphadenopathy. What is the most likely diagnosis?
Undifferentiated Symptoms UK Medical PG Practice Questions and MCQs
Question 21: A 66-year-old woman presents with a 16-week history of fatigue, poor appetite, and 7kg weight loss. She reports feeling generally unwell with muscle aches and low mood. Blood tests show: Hb 118 g/L, WCC 6.8×10⁹/L, platelets 245×10⁹/L, Na+ 128 mmol/L, K+ 5.2 mmol/L, urea 7.8 mmol/L, creatinine 88 μmol/L, glucose 3.8 mmol/L. What is the most appropriate next step?
A. Measure 9 am serum cortisol (Correct Answer)
B. Check thyroid function tests
C. Measure serum ACTH
D. Arrange urgent endocrinology referral for suspected adrenal insufficiency
E. Perform short synacthen test
Explanation: ***Measure 9 am serum cortisol***- The patient presents with clinical signs of **adrenal insufficiency** (fatigue, weight loss, muscle aches, low mood) and classic biochemistry including **hyponatraemia**, **hyperkalaemia**, and **hypoglycaemia**.- A **9 am serum cortisol** is the recommended initial screening test in primary care; levels **<100 nmol/L** strongly suggest insufficiency, while **>500 nmol/L** generally exclude it.*Check thyroid function tests*- While **hypothyroidism** can cause fatigue and weight loss (though weight gain is more common), it does not typically cause **hyperkalaemia** or significant **hyponatraemia**.- Thyroid dysfunction should be part of a broader workup, but the electrolyte pattern makes **adrenal insufficiency** the clinical priority.*Measure serum ACTH*- **Serum ACTH** is used to differentiate between **primary** (Addison's) and **secondary** adrenal insufficiency once cortisol deficiency is confirmed.- It is not the initial step in the diagnostic pathway and is often interpreted alongside the results of a stimulation test.*Arrange urgent endocrinology referral for suspected adrenal insufficiency*- Referrals are typically indicated after an initial screening cortisol level is obtained, unless the patient is in an **addisonian crisis** (hemodynamically unstable).- This patient is currently stable, so the biochemical diagnosis should be initiated in the primary care setting first.*Perform short synacthen test*- The **short synacthen test** is the definitive gold standard for diagnosis but is usually performed in a **specialist setting** or after an abnormal 9 am cortisol.- In primary care, the **9 am cortisol** serves as the mandated first-line screen before proceeding to stimulation testing.
Question 22: A 45-year-old man presents with an 8-week history of recurrent fever, typically occurring every 3 days, associated with severe rigors, headache, and myalgia. He immigrated from Nigeria 15 years ago and recently visited his family in Lagos for 2 months, returning 10 weeks ago. He did not take malaria prophylaxis. Examination during a febrile episode shows temperature 39.8°C, mild splenomegaly, and jaundice. What is the most appropriate immediate investigation?
A. Thick and thin blood films for malaria parasites (Correct Answer)
B. Rapid malaria antigen detection test
C. Full blood count and liver function tests
D. Serology for dengue fever
E. Blood cultures
Explanation: ***Thick and thin blood films for malaria parasites***
- These are the **gold standard** for diagnosis; thick films offer high sensitivity to detect low parasite levels, while thin films allow for **species identification** and **quantification of parasitaemia**.
- Given the patient's travel to **Lagos**, cyclical fever symptoms (every 3 days suggests *Plasmodium vivax* or *ovale* or more commonly *P. malariae* for tertian, or *P. falciparum* for irregular), mild splenomegaly, jaundice, and lack of **prophylaxis**, this immediate test is essential to confirm malaria and assess clinical severity.
*Rapid malaria antigen detection test*
- While useful in settings with limited microscopy expertise, **RDTs** are generally less sensitive than microscopy and may provide **false negatives** in low parasitaemia cases or with certain species.
- They cannot determine the exact **percentage of infected red cells**, which is a critical metric for managing potential **Plasmodium falciparum** infections and assessing disease severity.
*Full blood count and liver function tests*
- These tests provide supportive evidence, such as **thrombocytopenia** (low platelets) and **hyperbilirubinemia** due to hemolysis, but they are not diagnostic of malaria itself.
- They should be performed alongside malaria-specific tests to monitor for complications like **anemia** or organ dysfunction, but they do not identify the causative pathogen directly.
*Serology for dengue fever*
- Dengue typically presents with high fever, **retro-orbital pain**, and a distinct rash, often with a shorter incubation period than the 10 weeks seen here, and is less likely to cause recurrent, cyclical fever.
- **Serology** is a retrospective diagnostic tool, primarily detecting antibodies, and does not provide the immediate diagnosis of acute infection required for a patient with severe symptoms and high malaria suspicion.
*Blood cultures*
- Blood cultures are necessary to rule out **enteric fever** (typhoid) or **bacterial sepsis**, which can present with fever in a returned traveler.
- Although important for investigating a fever in a returned traveler, the specific cyclical nature of the fever, travel history, and other findings (splenomegaly, jaundice) make **malaria** the most urgent and likely diagnosis, requiring a different immediate investigation.
Question 23: According to NICE guidance on the assessment of chronic pain in primary care, which statement best describes the recommended initial approach to evaluating a patient presenting with persistent widespread pain and fatigue lasting 6 months?
A. Comprehensive investigations including inflammatory markers, autoimmune screen, vitamin D, and thyroid function should be performed before making a diagnosis
B. A biopsychosocial assessment exploring physical symptoms, psychological factors, and social context should be the primary framework for evaluation (Correct Answer)
C. Pain should be quantified using a numerical rating scale, and analgesia optimised before further assessment
D. Referral to rheumatology for specialist evaluation should be arranged if examination is normal
E. MRI imaging of affected areas should be performed to exclude structural pathology
Explanation: ***A biopsychosocial assessment exploring physical symptoms, psychological factors, and social context should be the primary framework for evaluation*** - NICE guidance for chronic primary pain emphasizes a **biopsychosocial model** as the initial approach, considering the interplay of **biological**, **psychological**, and **social factors**.- This assessment prioritizes understanding the functional impact of pain on the patient's life, rather than solely focusing on a biomedical search for pathology. *Comprehensive investigations including inflammatory markers, autoimmune screen, vitamin D, and thyroid function should be performed before making a diagnosis* - NICE recommends a **targeted approach to investigations**, only performing tests indicated by the clinical history and examination, not a comprehensive screening battery.- Routine, exhaustive screening without specific red flags can lead to **unnecessary anxiety**, over-medicalization, and does not align with the initial **biopsychosocial assessment** for chronic pain. *Pain should be quantified using a numerical rating scale, and analgesia optimised before further assessment* - While pain quantification is useful, NICE guidance for chronic pain prioritizes a **holistic assessment** over immediate optimization of analgesia alone.- Focusing solely on medication without addressing the broader biopsychosocial context may not be effective for **chronic primary pain** and can lead to over-reliance on drugs. *Referral to rheumatology for specialist evaluation should be arranged if examination is normal* - A normal physical examination in the context of persistent widespread pain and fatigue, without **red flags**, typically points away from a primary rheumatological condition requiring immediate specialist referral.- NICE emphasizes **primary care-led management** using the biopsychosocial model, reserving specialist referrals for diagnostic uncertainty or complex management needs after initial assessment. *MRI imaging of affected areas should be performed to exclude structural pathology* - Routine **advanced imaging** like MRI is not recommended for chronic widespread pain without specific neurological signs or **red flags** as it rarely alters management.- Imaging often reveals incidental findings that can cause **unnecessary patient anxiety** and may not correlate with the patient's pain experience in chronic primary pain.
Question 24: A 28-year-old woman presents with a 7-week history of fatigue, night sweats, and intermittent fever. She returned from a 6-month backpacking trip through Southeast Asia 3 months ago. Examination reveals temperature 38.3°C, cervical lymphadenopathy (2cm mobile nodes), and mild splenomegaly. Blood tests show: Hb 108 g/L, WCC 3.2×10⁹/L, platelets 142×10⁹/L, ESR 68 mm/hr. What is the most appropriate next investigation?
A. Chest X-ray (Correct Answer)
B. Malaria blood film
C. HIV serology with hepatitis B and C screening
D. Abdominal ultrasound
E. Monospot test
Explanation: ***Chest X-ray***
- A **Chest X-ray** is the essential initial investigation for suspected **Tuberculosis (TB)**, which is strongly suggested by the patient's travel to Southeast Asia, night sweats, and persistent fever.
- Even in the absence of respiratory symptoms, it can reveal **hilar lymphadenopathy**, upper lobe infiltrates, or a **miliary pattern** consistent with systemic dissemination.
*Malaria blood film*
- While travel history is present, the **7-week duration** of symptoms and the 3-month gap since return make acute malaria less likely than more chronic infections.
- Malaria typically presents with a more acute, paroxysmal fever rather than the **pancytopenia** and significantly **elevated ESR** seen here.
*HIV serology with hepatitis B and C screening*
- Although constitutional symptoms can occur in **HIV**, the priority is to rule out transmissible and treatable chronic infections like TB first in a febrile traveler.
- These tests are important components of a **fever of unknown origin** workup but are generally performed alongside or after initial imaging.
*Abdominal ultrasound*
- While it could evaluate the **splenomegaly**, it is less likely to provide a definitive primary diagnosis compared to a chest X-ray in this clinical context.
- It would be more appropriate if the patient had localized abdominal pain or significant **deranged liver function tests**.
*Monospot test*
- The **Monospot test** for Infectious Mononucleosis is generally less useful here given the **7-week duration** of symptoms; most acute EBV infections resolve sooner.
- The travel history and the presence of **pancytopenia** point toward a more chronic, systemic infectious or granulomatous process.
Question 25: A 57-year-old man presents with a 4-month history of progressive fatigue and 9kg unintentional weight loss. He reports increased thirst and nocturia (4-5 times per night). His brother has type 2 diabetes. Examination reveals BMI 26 kg/m², mild muscle wasting, and dry mucous membranes. Random glucose is 18.2 mmol/L. Which additional investigation is most important to perform urgently?
A. Serum beta-hydroxybutyrate or urine ketones (Correct Answer)
B. HbA1c
C. C-peptide level
D. Fasting glucose
E. Glutamic acid decarboxylase (GAD) antibodies
Explanation: ***Serum beta-hydroxybutyrate or urine ketones***- This patient exhibits signs of **insulin deficiency** (weight loss, muscle wasting) and severe hyperglycemia; urgent screening for **ketosis** is the priority to rule out **Diabetic Ketoacidosis (DKA)**.- Detection of **ketones** is critical for immediate triage, as their presence indicates a medical emergency requiring urgent fluid resuscitation and insulin therapy.*HbA1c*- While useful for measuring **glycemic control** over the past 3 months and confirming a diagnosis of diabetes, it does not provide information on **acute metabolic stability**.- This test is not urgent and cannot identify life-threatening complications like **DKA** in the acute setting.*C-peptide level*- This is used to assess **endogenous insulin production** to differentiate between Type 1 and Type 2 diabetes but is not an emergency investigation.- Results are often unreliable during acute **glucose toxicity**, making it inappropriate for the initial urgent assessment.*Fasting glucose*- The random glucose of 18.2 mmol/L is already diagnostic of **diabetes mellitus** in a symptomatic patient, making a fasting sample redundant.- Delaying assessment to obtain a fasting state would be dangerous given the risk of **metabolic decompensation**.*Glutamic acid decarboxylase (GAD) antibodies*- These antibodies help identify **Latent Autoimmune Diabetes in Adults (LADA)** or Type 1 Diabetes but do not influence acute management.- **Serology** results take days to return and are secondary to the immediate need for excluding **ketoacidosis**.
Question 26: A 32-year-old woman presents with a 5-month history of profound fatigue and cold intolerance. She reports gaining 8kg despite reduced appetite, constipation, and dry skin. Her periods have become heavier and irregular. On examination, her pulse is 54 bpm, BP 130/85 mmHg, and she has delayed relaxation of ankle reflexes. What is the most appropriate first-line investigation?
A. Serum thyroid-stimulating hormone (TSH) (Correct Answer)
B. Full blood count and ferritin
C. Serum cortisol and ACTH
D. Serum free T4 only
E. Anti-thyroid peroxidase antibodies
Explanation: ***Serum thyroid-stimulating hormone (TSH)***
- This patient's symptoms, including profound **fatigue**, **cold intolerance**, **weight gain**, **constipation**, **dry skin**, **menorrhagia**, **bradycardia** (pulse 54 bpm), and crucially, **delayed relaxation of ankle reflexes**, are classic for **hypothyroidism**.
- **Serum TSH** is the most sensitive first-line screening test for primary hypothyroidism because it becomes elevated early as the pituitary gland compensates for falling thyroid hormone levels, often before free T4 levels drop significantly.
*Full blood count and ferritin*
- While **fatigue** and **menorrhagia** could suggest **iron deficiency anemia**, these tests do not explain the comprehensive constellation of symptoms like **cold intolerance**, **bradycardia**, or **delayed ankle reflexes**.
- Anemia might be a secondary finding, but it is not the primary diagnostic test for the metabolic disorder indicated by the patient's presentation.
*Serum cortisol and ACTH*
- These investigations are performed to assess **adrenal function** (e.g., Addison's disease or Cushing's syndrome), which can present with fatigue or weight changes.
- However, the specific combination of **cold intolerance**, **constipation**, **bradycardia**, and especially **delayed ankle reflexes** points strongly away from an adrenal pathology and towards thyroid dysfunction.
*Serum free T4 only*
- Measuring only **serum free T4** as a first-line test is less sensitive for detecting early or subclinical hypothyroidism compared to TSH.
- In early stages of primary hypothyroidism, TSH can be elevated while free T4 may still be within the normal or low-normal range, potentially leading to a missed diagnosis if TSH is not also checked.
*Anti-thyroid peroxidase antibodies*
- These antibodies are used to identify an **autoimmune etiology**, such as **Hashimoto's thyroiditis**, as the cause of established thyroid dysfunction.
- They are not a primary screening tool to initially diagnose the presence of hypothyroidism; rather, they provide information about the underlying cause once thyroid dysfunction has been confirmed biochemically.
Question 27: A 63-year-old man with metastatic prostate cancer presents for pain review. He reports constant deep aching pain in his lumbar spine and pelvis (7/10 severity) partially controlled with morphine sulfate modified-release 60mg BD. He experiences 4-5 episodes daily of sudden-onset severe shooting pain (9/10) in his right leg lasting 1-2 minutes, triggered by movement. Background pain is adequately controlled but breakthrough pain significantly impacts function. Current medications: morphine sulfate MR 60mg BD, paracetamol 1g QDS, and ibuprofen 400mg TDS. What is the most appropriate modification to his pain management?
A. Increase morphine sulfate MR to 90mg BD and add morphine immediate-release 20mg for breakthrough pain
B. Add gabapentin 300mg at night, titrating up gradually, and provide morphine immediate-release 10-20mg for breakthrough pain (Correct Answer)
C. Switch to transdermal fentanyl patch and discontinue oral morphine
D. Add amitriptyline 10mg at night and continue current opioid dose
E. Refer for urgent radiotherapy to painful bony metastases
Explanation: ***Add gabapentin 300mg at night, titrating up gradually, and provide morphine immediate-release 10-20mg for breakthrough pain***- The patient presents with **neuropathic breakthrough pain** (shooting, short-lived episodes, triggered by movement), which requires an adjuvant like **gabapentin** as opioids alone are often insufficient for this pain type.- He also requires a PRN (pro re nata) **immediate-release opioid** for breakthrough episodes, ideally calculated as **1/6th to 1/10th** of the total daily morphine dose (120mg/day, so 12-20mg).
*Increase morphine sulfate MR to 90mg BD and add morphine immediate-release 20mg for breakthrough pain*
- Increasing the **modified-release (MR)** background dose is inappropriate because his constant background pain is already **adequately controlled**.
- This modification primarily focuses on **nociceptive** pathways and fails to specifically target the **neuropathic component** described by the shooting pain.
*Switch to transdermal fentanyl patch and discontinue oral morphine*
- A **fentanyl patch** is indicated when pain is stable or if the patient cannot tolerate oral medication, but it is not the first-line choice for managing **uncontrolled breakthrough pain**.
- Switching opioids (opioid rotation) is not indicated here as the patient's **background pain** is already well-managed on his current morphine dose.
*Add amitriptyline 10mg at night and continue current opioid dose*
- While **amitriptyline** is a valid adjuvant for neuropathic pain, this option fails to address the critical need for **immediate-release morphine** for breakthrough episodes.
- Morphine MR alone does not provide the flexibility needed to manage sudden-onset, severe **movement-triggered pain** sessions.
*Refer for urgent radiotherapy to painful bony metastases*
- While **palliative radiotherapy** is effective for localized bone pain, it does not provide the **immediate pharmacological relief** required for breakthrough neuropathic symptoms.
- The priority in this clinical review is to optimize the medical management of both **neuropathic and breakthrough pain** components.
Question 28: A 49-year-old woman presents with a 22-week history of severe, unrelenting fatigue that is not relieved by rest. She describes post-exertional malaise lasting >24 hours after minimal activity, unrefreshing sleep, difficulty concentrating ('brain fog'), and orthostatic intolerance. Previously very active, she now struggles with basic daily tasks. Examination and extensive blood tests (FBC, U&Es, LFTs, TFTs, glucose, CRP, ferritin, B12, folate, coeliac serology) are all normal. What is the most appropriate diagnosis?
A. Chronic fatigue syndrome/Myalgic encephalomyelitis (CFS/ME) (Correct Answer)
B. Depression with somatic symptoms
C. Fibromyalgia
D. Hypothyroidism with normal thyroid function tests
E. Adrenal insufficiency
Explanation: ***Chronic fatigue syndrome/Myalgic encephalomyelitis (CFS/ME)***
- The patient meets the **NICE criteria** for CFS/ME, requiring severe fatigue for at least 3 months, **post-exertional malaise (PEM)** lasting >24 hours, unrefreshing sleep, cognitive impairment, and **orthostatic intolerance**.
- A diagnosis of CFS/ME is made clinically after a thorough workup has **excluded other potential causes** for the symptoms, which is consistent with the extensive normal blood tests.
*Depression with somatic symptoms*
- While fatigue, unrefreshing sleep, and **'brain fog'** can be symptoms of depression, the defining feature of severe **post-exertional malaise (PEM)** is not a primary diagnostic criterion for mood disorders.
- Depression typically features prominent **anhedonia** or persistent low mood, which are not the central complaints presented, despite the functional impact.
*Fibromyalgia*
- **Fibromyalgia** is primarily characterized by widespread **musculoskeletal pain** and tenderness at specific points, which is not described as the patient's main symptom.
- Although fatigue is common, the specific cluster of symptoms including severe **PEM** and orthostatic intolerance are more indicative of CFS/ME than fibromyalgia.
*Hypothyroidism with normal thyroid function tests*
- The patient's **normal thyroid function tests (TFTs)**, specifically normal TSH and T4 levels, effectively rule out hypothyroidism as the cause of her fatigue.
- A diagnosis of hypothyroidism requires **abnormal biochemical markers**, which are absent in this case.
*Adrenal insufficiency*
- Primary **adrenal insufficiency (Addison's disease)** typically presents with fatigue, but would also commonly show **electrolyte abnormalities** like hyponatremia and hyperkalemia, or hypoglycemia.
- The patient's **normal U&Es and glucose** levels, along with the absence of typical hyperpigmentation, make adrenal insufficiency an unlikely diagnosis.
Question 29: A 56-year-old man presents with a 17-week history of fatigue and 8kg weight loss. He reports vague abdominal discomfort and change in bowel habit with looser stools. He is a smoker (25 pack-years). Examination reveals BMI 23 kg/m², pulse 92 bpm, BP 134/82 mmHg, and vague epigastric tenderness. Blood tests show: Hb 118 g/L, MCV 88 fL, platelets 542 × 10⁹/L, albumin 34 g/L, bilirubin 42 µmol/L, ALT 68 U/L, ALP 324 U/L, GGT 186 U/L, CA19-9 680 U/mL (normal <37). What is the most likely diagnosis?
A. Chronic pancreatitis
B. Hepatocellular carcinoma
C. Pancreatic adenocarcinoma (Correct Answer)
D. Cholangiocarcinoma
E. Alcoholic liver disease with cirrhosis
Explanation: ***Pancreatic adenocarcinoma***- The patient's presentation with **significant weight loss**, **vague abdominal pain**, **change in bowel habit** (suggesting **steatorrhea**), and a **markedly elevated CA19-9** (680 U/mL) is highly suggestive of pancreatic adenocarcinoma.- The laboratory findings, including a **cholestatic liver pattern** (elevated ALP, GGT, and bilirubin) and **thrombocytosis**, are classic features often due to biliary obstruction and paraneoplastic effects, respectively.*Chronic pancreatitis*- While it can cause weight loss and abdominal pain, chronic pancreatitis pain is typically severe and episodic, often associated with a history of recurrent acute pancreatitis or **heavy alcohol use**.- It is less likely to present with such an acute elevation of **CA19-9** and **obstructive jaundice** without a clear acute flare, and imaging often shows **pancreatic calcifications**.*Hepatocellular carcinoma*- This malignancy is typically associated with **Alpha-fetoprotein (AFP)** elevation rather than CA19-9 as its primary tumor marker.- It usually arises in the setting of **chronic liver disease** or cirrhosis, which is not clearly established by the patient's history or liver enzyme pattern, which points to obstruction rather than hepatocellular injury.*Cholangiocarcinoma*- Although it presents with **obstructive jaundice** and elevated CA19-9, cholangiocarcinoma is less common than pancreatic cancer.- The **vague epigastric tenderness** and prominent **change in bowel habit** (steatorrhea) are often more characteristic of pancreatic head tumors, which can obstruct both bile and pancreatic ducts.*Alcoholic liver disease with cirrhosis*- This typically presents with an **AST:ALT ratio > 2:1** and signs of portal hypertension, which are not the primary features in this patient's laboratory results.- While it can cause low albumin and weight loss, it does not explain the **highly elevated CA19-9** or the significant **thrombocytosis**.
Question 30: A 37-year-old woman presents with a 13-week history of fatigue, intermittent low-grade fever up to 37.9°C, and arthralgia affecting her hands and knees. She has noticed a rash on her shins. Examination reveals temperature 37.6°C, pulse 88 bpm, BP 124/78 mmHg, bilateral hilar lymphadenopathy on chest auscultation, and tender, erythematous nodules on both shins. Blood tests show: Hb 132 g/L, WCC 8.4 × 10⁹/L, platelets 312 × 10⁹/L, ESR 42 mm/hr, CRP 28 mg/L, corrected calcium 2.68 mmol/L, ACE 82 U/L (normal 20-70). Chest X-ray confirms bilateral hilar lymphadenopathy. What is the most likely diagnosis?
A. Tuberculosis
B. Lymphoma
C. Sarcoidosis (Correct Answer)
D. Systemic lupus erythematosus
E. Rheumatoid arthritis with pulmonary involvement
Explanation: ***Sarcoidosis***
- This patient presents with the classic triad of **Löfgren syndrome**: **bilateral hilar lymphadenopathy (BHL)**, **erythema nodosum** (tender nodules on shins), and **arthralgia**.
- Laboratory findings of **elevated ACE levels** and **hypercalcemia** (corrected calcium 2.68 mmol/L) strongly support this diagnosis due to granuloma-mediated 1-alpha hydroxylase activity.
*Tuberculosis*
- While TB can cause hilar lymphadenopathy and fever, it usually presents with more prominent constitutional symptoms like **weight loss** and **night sweats**, and often unilateral adenopathy.
- The specific combination of **BHL**, **erythema nodosum**, and **arthralgia** (Löfgren syndrome) is highly characteristic of acute sarcoidosis, making TB less likely.
*Lymphoma*
- Lymphoma typically presents with **painless, firm lymphadenopathy** and can cause constitutional "B symptoms" such as significant weight loss and drenching night sweats.
- Although lymphoma can cause BHL, it does not typically associate with **erythema nodosum** or **elevated ACE** levels.
*Systemic lupus erythematosus*
- SLE commonly causes **arthralgia** and low-grade fever, but it classically presents with distinct dermatological features such as a **malar rash** or photosensitivity, not erythema nodosum.
- **Bilateral hilar lymphadenopathy** is highly atypical for SLE, which more commonly involves other serosal surfaces or interstitial lung disease.
*Rheumatoid arthritis with pulmonary involvement*
- RA pulmonary involvement usually manifests as **interstitial lung disease**, pleural effusions, or rheumatoid nodules, rather than primarily **bilateral hilar lymphadenopathy**.
- While RA causes **arthralgia**, the presence of **erythema nodosum** and **BHL** on chest X-ray points away from RA and directly toward a multisystem granulomatous disease like sarcoidosis.
