FMGE 2026 - Internal Medicine Practice Questions

Q: A patient with parathyroid hyperplasia, pancreatic neuroendocrine tumor, and recurrent peptic ulcer disease most commonly has mutation of which gene?

MEN1 (menin gene). ***MEN1 (menin gene)*** - This patient presents with the classic triad of **Multiple Endocrine Neoplasia type 1 (MEN1)** syndrome: **primary hyperparathyroidism** (due to hyperplasia), **pancreatic neuroendocrine tumors** (such as gastrinomas causing ZES), and **pituitary adenomas**. - The MEN1 condition is caused by a germline mutation in the **MEN1 tumor suppressor gene**, which encodes the protein **menin**. *RET* - Mutations in the **RET proto-oncogene** are characteristically associated with **Multiple Endocrine Neoplasia type 2 (MEN2A and MEN2B)**. - MEN2 conditions typically involve **medullary thyroid carcinoma**, **pheochromocytoma**, and **parathyroid hyperplasia** (in MEN2A), rather than the pancreatic/gastrinoma presentation described. *TP53* - Mutations in the **TP53 tumor suppressor gene** are pathognomonic for **Li-Fraumeni syndrome**. - This syndrome is characterized by a high predisposition to a wide variety of early-onset malignancies, such as **sarcomas**, breast cancer, and adrenal cortical carcinomas, not the endocrine triad described. *VHL* - Mutations in the **von Hippel-Lindau (VHL) gene** are responsible for **VHL syndrome**. - This disorder is marked by **hemangioblastomas**, **renal cell carcinoma**, and **pheochromocytomas**, which do not correlate with the patient's presentation of hyperparathyroidism and peptic ulcer disease.

Q: A 22-year-old male presents with anemia. Peripheral smear is given, and reticulocyte count is 6%. What is the most likely diagnosis?

Sickle cell disease. ***Sickle cell disease*** - In **Sickle cell disease**, the chronic hemolysis leads to a compensatory **reticulocytosis** (reticulocyte count > 2-3%), as the bone marrow attempts to replace destroyed red blood cells. - The peripheral smear typically reveals **sickled cells (drepanocytes)**, Howell-Jolly bodies (due to autosplenectomy), and target cells, confirming a diagnosis of hemolytic anemia. *Iron deficiency anemia* - Presents with **microcytic, hypochromic** anemia, and typically shows an **inappropriately low reticulocyte count** due to insufficient iron for erythropoiesis. - The peripheral smear classically demonstrates **pencil cells** and cigar-shaped cells, not the findings associated with hemolytic anemias. *Thalassemia trait* - Characterized by **microcytic, hypochromic** anemia with a very high red blood cell count out of proportion to the degree of anemia. - Reticulocyte counts in thalassemia trait are usually **normal or only slightly elevated**, reflecting the production of defective but not massively hemolyzed cells. *Aplastic anemia* - Defined by **pancytopenia** (affecting RBCs, WBCs, and platelets), meaning the bone marrow is failing. - The reticulocyte count is characteristically **very low (reticulocytopenia)** because the bone marrow is unable to produce new red blood cells.

Q: A patient is diagnosed with paroxysmal nocturnal hemoglobinuria (PNH). Which of the following drugs is used to reduce complement -mediated hemolysis in PNH?

Eculizumab. ***Eculizumab*** - Eculizumab is a **monoclonal antibody** that binds to **complement protein C5**, preventing the formation of the **membrane attack complex (MAC)**. - By inhibiting terminal complement activation, it effectively reduces **intravascular hemolysis**, stabilizes hemoglobin levels, and decreases the need for blood transfusions in patients with PNH. *Rituximab* - Rituximab is an **anti-CD20 monoclonal antibody** primarily used for **B-cell lymphoproliferative disorders** and certain autoimmune diseases like rheumatoid arthritis. - It has no role in the direct inhibition of the **complement cascade** required to manage the pathophysiology of PNH. *Prednisolone* - Prednisolone is a **corticosteroid** used to suppress the immune system in conditions like autoimmune hemolytic anemia (AIHA). - It is generally ineffective for the **complement-mediated lysis** seen in PNH, as the disease is driven by a defect in **CD55/CD59 expression** rather than lymphocyte-mediated mechanisms. *Hydroxyurea* - Hydroxyurea is an **antimetabolite** used to treat myeloproliferative neoplasms like **polycythemia vera** or essential thrombocythemia by reducing cell production. - It does not target the **complement pathway** and offers no therapeutic benefit in preventing the hemolysis associated with PNH.

Q: A 45-year-old man presents with splenomegaly and weight loss. Peripheral smear shows leukocytosis with a left shift. Bone marrow is hypercellular. Cytogenetic analysis reveals t(9;22). What is the treatment of choice?

Imatinib. ***Imatinib*** - This drug acts as a **tyrosine kinase inhibitor** that specifically targets the **BCR-ABL fusion protein** created by the **t(9;22)** chromosomal translocation. - It is the **first-line therapy** for chronic phase Chronic Myeloid Leukemia (CML) due to its high efficacy and minimal side-effect profile compared to older treatments. *Rituximab* - A monoclonal antibody directed against **CD20**, used primarily in the treatment of **B-cell non-Hodgkin lymphomas** and certain autoimmune conditions. - It is not indicated for CML treatment because the malignant cells in CML do not typically express the CD20 surface antigen. *IFN alpha* - Historically used as the treatment of choice for CML before the development of targeted therapies like tyrosine kinase inhibitors. - It is now mostly relegated to a second-line role or used when target-specific therapy is contraindicated, as it is associated with significant **flu-like side effects**. *Hydroxyurea* - A non-specific **myelosuppressive agent** used to provide temporary control of leukocyte counts in CML. - While it helps in reducing cytoreduction, it does not induce **molecular remission** or address the underlying BCR-ABL molecular driver, so it is not the curative treatment of choice.

Q: A middle-aged woman presents with weight gain, cold intolerance, and painless enlargement of th e thyroid gland. Which of the following antibodies is most commonly associated with this condition?

Anti TPO. ***Anti TPO*** - This patient presents with classic signs of **hypothyroidism** (weight gain, cold intolerance, thyroid enlargement), highly suggestive of **Hashimoto's thyroiditis**, which is an **autoimmune disorder**. - **Anti-thyroid peroxidase (anti-TPO)** antibodies are the most sensitive and specific markers found in the vast majority of patients with Hashimoto's thyroiditis. *Anti mitochondrial ab* - These antibodies are the hallmark diagnostic marker for **Primary Biliary Cholangitis (PBC)**, an autoimmune liver disease. - Clinical features of PBC include **pruritus** and elevated **alkaline phosphatase**, which are distinct from the thyroid dysfunction described here. *Anti ds DNA ab* - These are highly specific antibodies associated with **Systemic Lupus Erythematosus (SLE)**. - SLE typically presents with multisystem involvement, such as a **malar rash**, **arthritis**, and **serositis**, rather than isolated thyroid autoimmunity. *Anti TSH Rc* - These antibodies (Thyroid-stimulating immunoglobulin) are characteristic of **Graves' disease**, which causes **hyperthyroidism** rather than hypothyroidism. - They act to stimulate the **TSH receptor**, resulting in an overactive thyroid, tachycardia, and weight loss, opposite to this patient's presentation.

Q: A resident of North-East India, presents with fever and chills. Peripheral blood smear shows P. falciparum malaria. Which of the following treatment regimens should be given?

Artemether –Lumefantrine + Primaquine. ***Artemether–Lumefantrine + Primaquine*** - This regimen represents the **Artemisinin-based Combination Therapy (ACT)**, which is the **first-line recommended treatment** for uncomplicated *Plasmodium falciparum* malaria in India, including North-East regions where chloroquine resistance is high. - **Primaquine** is added as a **gametocytocide** to prevent the transmission of the parasite to mosquitoes, though it should be used cautiously after screening for **G6PD deficiency**. *Chloroquine + Primaquine* - While historically useful, **Chloroquine** is no longer effective for *P. falciparum* in most parts of India, particularly in **North-East India**, due to high levels of **antimalarial drug resistance**. - This combination is currently reserved specifically for **P. vivax malaria** treatment in regions where chloroquine sensitivity is maintained. *Oral quinine* - **Oral quinine** is not the first-line treatment for uncomplicated malaria and is associated with significant side effects like **cinchonism** (tinnitus, headache, dizziness). - It is generally reserved for **second-line therapy** or in specific cases of **severe malaria** when parenteral therapy is transitioned to oral, or where ACTs are unavailable. *Artesunate + Sulfadoxine-Pyrimethamine + Primaquine* - This combination was previously used in specific areas, but its efficacy has declined significantly due to the widespread emergence of **Sulfadoxine-Pyrimethamine resistance**. - Modern treatment guidelines prioritize **Artemether-Lumefantrine** or **Artesunate-Pyronaridine** over older ACT combinations for more reliable patient outcomes.

Question 1

A patient with parathyroid hyperplasia, pancreatic neuroendocrine tumor, and recurrent peptic ulcer disease most commonly has mutation of which gene?

Accepted Answer

MEN1 (menin gene)

Answer

RET

Answer

TP53

Answer

VHL

Question 2

A 22-year-old male presents with anemia. Peripheral smear is given, and reticulocyte count is 6%. What is the most likely diagnosis?

Accepted Answer

Sickle cell disease

Answer

Iron deficiency anemia

Answer

Thalassemia trait

Answer

Aplastic anemia

Question 3

A patient is diagnosed with paroxysmal nocturnal hemoglobinuria (PNH). Which of the following drugs is used to reduce complement -mediated hemolysis in PNH?

Accepted Answer

Eculizumab

Answer

Rituximab

Answer

Prednisolone

Answer

Hydroxyurea

Question 4

A 45-year-old man presents with splenomegaly and weight loss. Peripheral smear shows leukocytosis with a left shift. Bone marrow is hypercellular. Cytogenetic analysis reveals t(9;22). What is the treatment of choice?

Accepted Answer

Imatinib

Answer

Rituximab

Answer

IFN alpha

Answer

Hydroxyurea

Question 5

A middle-aged woman presents with weight gain, cold intolerance, and painless enlargement of th e thyroid gland. Which of the following antibodies is most commonly associated with this condition?

Accepted Answer

Anti TPO

Answer

Anti mitochondrial ab

Answer

Anti ds DNA ab

Answer

Anti TSH Rc

Question 6

A resident of North-East India, presents with fever and chills. Peripheral blood smear shows P. falciparum malaria. Which of the following treatment regimens should be given?

Accepted Answer

Artemether –Lumefantrine + Primaquine

Answer

Chloroquine + Primaquine

Answer

Oral quinine

Answer

Artesunate + Sulfadoxine -Pyrimethamine + Primaquine

FMGE 2026 — Internal Medicine