FMGE 2025 - Internal Medicine Practice Questions

Q: A young female presents with ptosis showing diurnal variation. CT chest shows an anterior mediastinal mass identified as thymus gland cancer. Which receptor is affected in this patient?

Post-synaptic ACh Receptor. ***Post-synaptic ACh Receptor*** - The clinical presentation of **ptosis** with **diurnal variation** (worsening weakness throughout the day) and an associated **thymoma** are hallmark features of **Myasthenia Gravis** [1]. - Myasthenia Gravis is an autoimmune disorder characterized by antibodies that bind to and block or destroy **post-synaptic nicotinic acetylcholine (ACh) receptors** at the neuromuscular junction, leading to impaired muscle contraction [2]. *Presynaptic ACh Receptor* - Autoantibodies in common neuromuscular junction disorders do not target presynaptic ACh receptors. These receptors are typically involved in modulating neurotransmitter release via feedback mechanisms. - The primary presynaptic autoimmune disorder, **Lambert-Eaton Myasthenic Syndrome**, involves antibodies against voltage-gated calcium channels, not ACh receptors [3]. *Voltage-gated calcium channels at the NMJ* - This is the pathological target in **Lambert-Eaton Myasthenic Syndrome (LEMS)**, where antibodies inhibit presynaptic calcium influx, reducing acetylcholine release [3]. - LEMS is clinically distinct, often presenting with weakness that **improves with activity** (incremental response) and is strongly associated with **small cell lung cancer** [3]. *Acetylcholinesterase* - **Acetylcholinesterase (AChE)** is the enzyme responsible for degrading acetylcholine in the synaptic cleft; it is not the target of autoimmunity in Myasthenia Gravis. - In fact, **AChE inhibitors** (e.g., pyridostigmine) are a primary treatment for Myasthenia Gravis, as they increase the concentration and duration of ACh in the synapse to better activate the reduced number of receptors [2].

Q: A 35-year-old female with progressive limb weakness for the past 1 year. On examination, muscle fasciculations and hypertonia are noted, and the sensory system is intact. What is the diagnosis?

ALS. ***Correct: ALS (Amyotrophic Lateral Sclerosis)*** - This patient presents with the classic triad of ALS: **progressive limb weakness, fasciculations (LMN sign), and hypertonia/spasticity (UMN sign)** [1] - The combination of **both upper and lower motor neuron signs** is pathognomonic for ALS [1] - **Sensory sparing** is characteristic - ALS affects motor neurons only [1] - Age and progressive course over 1 year fits the typical presentation - El Escorial criteria require UMN + LMN signs in multiple regions *Incorrect: Multifocal motor neuropathy* - This is a **pure lower motor neuron disorder** with conduction block - Would present with fasciculations and weakness but **NO hypertonia** (no UMN involvement) [1] - Treatable with immunotherapy, making it an important differential to exclude [1] *Incorrect: Becker muscular dystrophy* - This is a **primary muscle disease**, not a motor neuron disorder - **No fasciculations** would be present (fasciculations indicate motor neuron pathology) [2] - Predominantly affects males (X-linked), presents with proximal weakness and calf pseudohypertrophy - Elevated CK levels would be expected *Incorrect: Spinal muscular atrophy* - This is a **pure lower motor neuron disorder** due to anterior horn cell degeneration - Would NOT present with **hypertonia or UMN signs** - Typically presents in childhood/early life with symmetric proximal weakness - Associated with SMN1 gene mutations

Q: A patient presents with symmetrical leg weakness and areflexia. He had developed diarrhoea 2 weeks ago. He was diagnosed as having GBS. What is the cause?

Demyelination of A, B-fibers. ***Demyelination of A, B-fibers***- GBS is an acute **demyelinating polyneuropathy** primarily affecting the myelin sheath of peripheral nerves and nerve roots (PNS involvement) [1].- Demyelination of large myelinated **A-fibers** (motor and sensory) explains the severe **symmetrical weakness** and **areflexia** [1]; demyelination of **B-fibers** contributes to common **autonomic dysfunction**.*Demyelination of B-fibers*- B-fibers are primarily **preganglionic autonomic fibers**; their demyelination causes autonomic instability (e.g., blood pressure fluctuation) but does not account for the profound motor weakness and areflexia that define GBS [2].- The cardinal features of GBS (weakness and areflexia) result from damage to the larger **A-fibers** (motor nerves) [1]. *Demyelination of the spinal cord*- GBS is a disease of the **Peripheral Nervous System (PNS)**, affecting nerve roots and peripheral nerves [2].- Demyelination confined to the spinal cord is characteristic of **Central Nervous System (CNS)** demyelinating diseases, such as **Transverse Myelitis** or **Multiple Sclerosis** [3]. *Cord inflammation*- **Spinal cord inflammation** or myelitis is a CNS process and typically results in upper motor neuron signs (spasticity, brisk reflexes) or distinct sensory levels, which are not seen in GBS.- GBS involves inflammation and attack on the **peripheral nerve myelin** or axons, specifically in the nerve roots and distal peripheral nerves [1].

Q: A patient has developed a cough and weight loss for the last 3 months. Biopsy of lung mass shows expression of chromogranin and synaptophysin. Which paraneoplastic syndrome will most likely occur in this patient?

SIADH. ***SIADH*** - The biopsy findings of positive **chromogranin** and **synaptophysin** are characteristic of a **neuroendocrine tumor**, with **Small Cell Lung Cancer (SCLC)** being the most likely diagnosis given the clinical presentation. - **SCLC** is well-known for causing paraneoplastic syndromes, the most common of which is the **Syndrome of Inappropriate Antidiuretic Hormone (SIADH)**, resulting from ectopic **ADH** production [1]. *Hypercalcemia* - Paraneoplastic hypercalcemia is most frequently associated with **Squamous Cell Carcinoma** of the lung [2]. - This occurs due to the tumor's production of **Parathyroid Hormone-related Peptide (PTHrP)**, which is not a typical feature of SCLC [2]. *Cushing syndrome* - Paraneoplastic Cushing syndrome results from the ectopic production of **Adrenocorticotropic Hormone (ACTH)**, which can also be seen in **SCLC** [1]. - However, **SIADH** is a more common paraneoplastic endocrine syndrome associated with SCLC compared to Cushing syndrome. *Gynaecomastia* - Gynaecomastia as a paraneoplastic syndrome is classically associated with **Large Cell Carcinoma** of the lung. - This is due to the ectopic secretion of **human chorionic gonadotropin (hCG)** by the tumor cells.

Q: A patient presents with palpitations, headache, and sweating. His BP is $180/100 \mathrm{mmHg}$ . 24-hour urinary metanephrine values are elevated. What is the diagnosis?

Pheochromocytoma. Pheochromocytoma - The constellation of symptoms—palpitations, episodic sweating, severe headache, and hypertension (the classic triad)—is highly suggestive of excessive catecholamine release. - The diagnosis is confirmed by the elevated 24-hour urinary metanephrines (metabolites of epinephrine and norepinephrine), which is the definitive biochemical hallmark of this adrenal medullary tumor. Carcinoid tumor - This tumor primarily secretes serotonin and other vasoactive substances, leading to symptoms like flushing, diarrhea, and bronchospasm (carcinoid syndrome) [1]. - The biochemical marker for this condition is elevated urinary 5-hydroxyindoleacetic acid (5-HIAA), not metanephrines. Carcinoid crisis - This represents a severe, life-threatening exacerbation of carcinoid syndrome involving severe flushing, profound hypotension, and cardiac arrhythmias. - It is typically an acute event triggered by stressors such as surgery or chemotherapy, unlike the chronic presentation described. Neuroblastoma - This malignant tumor of the neural crest primarily affects infants and young children (usually under 5 years old), making it unlikely in an adult patient. - Although it can secrete catecholamines, its primary presenting features usually include an abdominal mass, fever, and metastasis, and the key diagnostic marker is often high urinary VMA (Vanillylmandelic acid) and HVA (Homovanillic acid).

Q: A 30-year-old male presents with deep-seated retro-orbital pain from cluster headache. What is the best management?

Oxygen. ***Oxygen*** - **High-flow oxygen** (100% at 7-15 L/min) is the safest and most effective **first-line abortive treatment** for an acute cluster headache attack [1] - It works rapidly to cause **vasoconstriction** and often terminates the severe retro-orbital pain within **15 to 20 minutes** - This is the preferred treatment for acute attacks due to its rapid onset and excellent safety profile *Verapamil* - Verapamil is a calcium channel blocker and is considered the **first-line prophylactic agent** for both episodic and chronic cluster headache, not acute treatment [1] - Its mechanism of action requires time, rendering it ineffective for terminating an ongoing acute pain episode - Used to prevent future attacks, not to abort current ones *Lithium* - Lithium is a prophylactic treatment reserved mainly for patients with **chronic cluster headache** or those who do not respond to Verapamil [1] - It has a slow onset of action and is not used to manage the acute pain of a cluster attack - Requires therapeutic monitoring due to narrow therapeutic window [1] *Topiramate* - Topiramate is an established prophylactic treatment primarily for **migraine**, and occasionally used as a second-line prophylactic agent for cluster headache - As a prophylactic medication, it plays **no role** in the acute termination or abortive management of a cluster headache episode

Q: Patient presents with hypertension and hypokalemic metabolic alkalosis. CT scan shows a unilateral adrenal mass with elevated ARR. What is the next best step for the management of this patient?

Adrenalectomy. ***Adrenalectomy*** - The combination of **hypertension**, **hypokalemic metabolic alkalosis**, elevated **Aldosterone-to-Renin Ratio (ARR)**, and a unilateral **adrenal mass** is diagnostic for Primary Aldosteronism, likely due to an Aldosterone-Producing Adenoma (**APA**) [1]. - **Unilateral adrenalectomy** is the definitive, potentially curative treatment for a confirmed APA, addressing the root cause of the hyperaldosteronism and hypertension [1]. *Spironolactone on a lifelong basis* - This treatment involves a **Mineralocorticoid Receptor Antagonist** and is the preferred therapy for patients with **Bilateral Adrenal Hyperplasia (BAH)** or for patients with an APA who are not surgical candidates [1]. - Since a likely unilateral adenoma is identified and surgery offers a cure, medical therapy is not the *next best step*. *ACTH stimulation test* - This test is used primarily to evaluate the reserve capacity of the adrenal cortex and diagnose **Adrenal Insufficiency** (e.g., Addison's disease or secondary adrenal insufficiency) [2]. - It is not indicated for the diagnosis or management of hyperaldosteronism. *Dexamethasone suppression test* - This test is the standard screening tool used to diagnose **Cushing's syndrome** (hypercortisolism) by assessing the feedback loop involving the hypothalamic-pituitary-adrenal axis [3]. - It is irrelevant in the workup for primary hyperaldosteronism.

Q: A 35-year-old male has had chronic hypercalcemia for the last 1.5 years, but PTH levels are normal. Which of the following is most likely the cause?

Sarcoidosis. ***Sarcoidosis*** - Causes hypercalcemia via ectopic synthesis of **1,25-dihydroxyvitamin D** (calcitriol) by activated macrophages in the granulomas, leading to increased intestinal calcium absorption [1]. - Although the resulting hypercalcemia usually suppresses PTH (making it low), in chronic, mild cases, the PTH level may appear in the lower end of the **normal reference range**, consistent with the clinical picture of a non-PTH-mediated cause [1]. *Malignancy* - Hypercalcemia related to solid tumors (Humoral Hypercalcemia of Malignancy) is typically mediated by **PTH-related peptide (PTHrP)**, resulting in high calcium. - This non-PTH mediated hypercalcemia leads to appropriate **suppression of the parathyroid glands**, meaning PTH levels would be significantly **low or undetectable**, not normal [1]. *Parathyroid hyperplasia* - This condition represents **primary hyperparathyroidism**, characterized by autonomous secretion of PTH [1]. - In primary hyperparathyroidism, PTH levels are typically inappropriately **elevated** (or grossly high-normal) despite the presence of hypercalcemia, which contradicts a normal PTH value [1]. *C.K.D* - Chronic kidney disease usually results in **hypocalcemia** due to impaired 1-alpha-hydroxylase function and resultant low 1,25(OH)₂D levels [2]. - If hypercalcemia were present (e.g., due to tertiary hyperparathyroidism), PTH levels would be markedly **elevated**, not normal, due to persistent glandular stimulation [2].

Q: A female presents with amenorrhea and galactorrhea. Serum prolactin is elevated. MRI shows pituitary adenoma. Best management for this patient?

Bromocriptine. ***Bromocriptine***- It is a **dopamine agonist** and represents the initial and standard treatment for **prolactinomas**, effectively reducing tumor size and lowering prolactin levels [1].- Dopamine agonists resolve symptoms such as **amenorrhea** and **galactorrhea** by inhibiting prolactin secretion from the pituitary [1]. *Letrozole*- This is an **aromatase inhibitor** primarily used in the management of hormone-sensitive breast cancer or for ovulation induction in conditions like PCOS. - Its mechanism is unrelated to suppressing prolactin secretion from the pituitary or shrinking a prolactinoma. *Tamoxifen*- This is a **Selective Estrogen Receptor Modulator (SERM)** most commonly used in the treatment and prevention of estrogen receptor-positive breast cancer. - It does not act on dopamine receptors and is ineffective in reversing elevated prolactin levels or associated symptoms. *Goserelin*- This agent is a **Gonadotropin-Releasing Hormone (GnRH) agonist** used primarily for conditions like endometriosis, uterine fibroids, or prostate cancer by initially stimulating then desensitizing the GnRH receptor. - While it suppresses LH and FSH [2], it is not the primary treatment for hyperprolactinemia caused by a pituitary adenoma.

Q: A 60-year-old female presents with weakness, back pain and repeated infections. Work up shows M spike on serum electrophoresis. Prognosis is determined by which of the following factors?

Albumin and $\beta_{2}$-microglobulin. ***Albumin and $\beta_{2}$-microglobulin*** - These two serum markers are the cornerstones of the **International Staging System (ISS)**, the most widely used system for determining prognosis in Multiple Myeloma. - High **$\beta_{2}$-microglobulin** levels reflect a high tumor burden and/or renal dysfunction, while low **serum albumin** indicates a more advanced disease state and poorer prognosis [1]. *IgG and albumin* - While **albumin** is a key prognostic factor, the specific type of immunoglobulin, such as **IgG**, is not a primary component of the main prognostic staging systems like the ISS. - The *quantity* of the monoclonal protein is used to monitor disease response, but the *type* is less critical for staging than **$\beta_{2}$-microglobulin**. *IgM and albumin* - A monoclonal gammopathy involving **IgM** is the hallmark of **Waldenström macroglobulinemia**, not Multiple Myeloma [1]. - Multiple Myeloma is characterized by the monoclonal proliferation of plasma cells that typically produce **IgG** or **IgA**, not **IgM** [1]. *Albumin and LDH* - While elevated **Lactate Dehydrogenase (LDH)** is an adverse prognostic factor, it is used in the **Revised-ISS (R-ISS)**, which builds upon the original ISS. - The foundational ISS, which is universally applied, is based on the combination of **serum albumin** and **$\beta_{2}$-microglobulin** levels.

Question 1

A young female presents with ptosis showing diurnal variation. CT chest shows an anterior mediastinal mass identified as thymus gland cancer. Which receptor is affected in this patient?

Accepted Answer

Post-synaptic ACh Receptor

Answer

Acetylcholinesterase

Answer

Voltage-gated calcium channels at the NMJ

Answer

Presynaptic ACh Receptor

Question 2

A 35-year-old female with progressive limb weakness for the past 1 year. On examination, muscle fasciculations and hypertonia are noted, and the sensory system is intact. What is the diagnosis?

Accepted Answer

ALS

Answer

Multifocal motor neuropathy

Answer

Becker muscular dystrophy

Answer

Spinal muscular atrophy

Question 3

A patient presents with symmetrical leg weakness and areflexia. He had developed diarrhoea 2 weeks ago. He was diagnosed as having GBS. What is the cause?

Accepted Answer

Demyelination of A, B-fibers

Answer

Cord inflammation

Answer

Demyelination of the spinal cord

Answer

Demyelination of B-fibers

Question 4

A patient has developed a cough and weight loss for the last 3 months. Biopsy of lung mass shows expression of chromogranin and synaptophysin. Which paraneoplastic syndrome will most likely occur in this patient?

Accepted Answer

SIADH

Answer

Gynaecomastia

Answer

Cushing syndrome

Answer

Hypercalcemia

Question 5

A patient presents with palpitations, headache, and sweating. His BP is $180/100 \mathrm{mmHg}$ . 24-hour urinary metanephrine values are elevated. What is the diagnosis?

Accepted Answer

Pheochromocytoma

Answer

Carcinoid crisis

Answer

Neuroblastoma

Answer

Carcinoid tumor

Question 6

A 30-year-old male presents with deep-seated retro-orbital pain from cluster headache. What is the best management?

Accepted Answer

Oxygen

Answer

Verapamil

Answer

Lithium

Answer

Topiramate

Question 7

Patient presents with hypertension and hypokalemic metabolic alkalosis. CT scan shows a unilateral adrenal mass with elevated ARR. What is the next best step for the management of this patient?

Accepted Answer

Adrenalectomy

Answer

Spironolactone on a lifelong basis

Answer

Dexamethasone suppression test

Answer

ACTH stimulation test

Question 8

A 35-year-old male has had chronic hypercalcemia for the last 1.5 years, but PTH levels are normal. Which of the following is most likely the cause?

Accepted Answer

Sarcoidosis

Answer

Malignancy

Answer

C.K.D

Answer

Parathyroid hyperplasia

Question 9

A female presents with amenorrhea and galactorrhea. Serum prolactin is elevated. MRI shows pituitary adenoma. Best management for this patient?

Accepted Answer

Bromocriptine

Answer

Tamoxifen

Answer

Goserelin

Answer

Letrozole

Question 10

A 60-year-old female presents with weakness, back pain and repeated infections. Work up shows M spike on serum electrophoresis. Prognosis is determined by which of the following factors?

Accepted Answer

Albumin and $\beta_{2}$-microglobulin

Answer

Albumin and LDH

Answer

IgM and albumin

Answer

IgG and albumin

FMGE 2025 — Internal Medicine