DFT-MEDICINE D2-09/10/2025-MAXEMO

A patient presents with lethargy and confusion. The examination reveals coarse, dry skin, periorbital puffiness, and a markedly delayed relaxation phase of the ankle jerk reflex. Laboratory investigations show a serum sodium of 124 mEq/L. Which hormonal profile is the most likely underlying cause?

• Elevated TSH, decreased free T4

• Decreased ACTH, decreased cortisol

• Elevated ADH, normal serum cortisol

• Elevated aldosterone, decreased renin

Answer explanation

The clinical signs (myxedema facies, pseudomyotonia) and hyponatremia are classic for severe primary hypothyroidism. The hyponatremia is due to an SIADH-like state with impaired free water clearance.

The extrathyroidal manifestations of Graves' disease, such as infiltrative ophthalmopathy and pretibial myxedema, are primarily caused by TSH receptor-stimulating autoantibodies targeting which specific cell type in these tissues?

• Fibroblasts

• Keratinocytes

• Endothelial cells

• Langerhans cells

Answer explanation

TSH receptor autoantibodies stimulate orbital and dermal fibroblasts, causing them to proliferate and secrete excessive amounts of hydrophilic glycosaminoglycans (like hyaluronic acid), leading to tissue edema and expansion.

The characteristic non-pitting edema of pretibial myxedema and the proptosis seen in Graves' orbitopathy are both initiated by the same underlying mechanism. Which molecular pathway is central to this shared pathophysiology?

• TSH receptor antibody stimulation of fibroblasts leading to glycosaminoglycan deposition

• Thyroid hormone-mediated increase in systemic beta-adrenergic receptor sensitivity

• Type IV hypersensitivity reaction targeting dermal and retro-orbital collagen

• Direct infiltration of orbital and dermal tissue by activated T-lymphocytes

Answer explanation

Both manifestations are caused by TSH receptor antibodies (TRAb) binding to and activating fibroblasts in the dermis and orbit. This triggers excessive production and deposition of hydrophilic glycosaminoglycans (like hyaluronic acid), causing edema and tissue expansion.

A patient presents with progressive dysphagia and a non-tender, diffusely enlarged thyroid gland. On palpation, the gland is 'stony-hard' and feels fixed to adjacent structures. Thyroid function tests are normal. This clinical picture is most characteristic of which condition?

• Riedel's thyroiditis

• Anaplastic carcinoma

• Hashimoto's thyroiditis

• Acute suppurative thyroiditis

Answer explanation

Riedel's thyroiditis. This rare, IgG4-related disease is defined by extensive fibrosis originating from the thyroid, leading to a fixed, "stony-hard" or "woody" gland with compressive symptoms. Patients are often euthyroid.

A non-obese patient diagnosed with diabetes shows an unusually sensitive glycemic response to low-dose sulfonylurea therapy. A detailed history reveals that multiple family members across three generations were diagnosed with non-obese diabetes. This clinical picture is most characteristic of a mutation in which gene?

• HNF1A

• GCK

• HLA-DQA1

• INS

Answer explanation

A heterozygous mutation in the Hepatocyte Nuclear Factor 1-alpha (HNF1A) gene causes MODY 3. This condition is classically defined by a high sensitivity to sulfonylureas and a strong autosomal dominant inheritance pattern.

A patient with type 2 diabetes and a history of symptomatic heart failure with reduced ejection fraction requires intensification of their glycemic therapy. Based on the predominant mechanism of adverse effects, which of the following drugs is contraindicated?

• Pioglitazone

• Empagliflozin

• Liraglutide

• Acarbose

Answer explanation

Pioglitazone, a thiazolidinedione, can cause significant fluid retention and plasma volume expansion, which can precipitate or exacerbate congestive heart failure. It carries a black box warning for this reason.

A patient in diabetic ketoacidosis (DKA) is started on an intravenous regular insulin infusion. His initial serum potassium was 5.6 mEq/L. A repeat lab draw 3 hours later shows a potassium of 3.4 mEq/L. This change is primarily due to insulin's direct stimulation of which of the following?

• Na+/K+-ATPase pump

• Renal Outer Medullary Potassium (ROMK) channels

• Na+/H+ antiporter

• H+/K+-ATPase pump

Answer explanation

Insulin directly stimulates the Na+/K+-ATPase pump on cell membranes, promoting the influx of potassium into cells and causing a rapid decrease in serum potassium levels.

A patient with type 2 diabetes and end-stage renal disease on hemodialysis has poorly controlled blood sugars on home monitoring. However, their HbA1c is consistently in the low-normal range. Which of the following markers would provide a more accurate assessment of glycemic control over the preceding 2-3 weeks in this patient?

• Serum fructosamine

• Repeat HbA1c measurement

• 1,5-Anhydroglucitol

• Serum C-peptide

Answer explanation

 Fructosamine measures glycated albumin and other serum proteins, reflecting glycemic control over 2-3 weeks. It is less affected by the reduced erythrocyte lifespan common in ESRD, which falsely lowers HbA1c.

The patient in the scenario presents with severe metabolic acidosis (HCO3- 10 mEq/L) and ketonemia. In the absence of insulin, which hormone's unopposed action on the liver is the primary driver for the conversion of free fatty acids into ketone bodies?

• Glucagon

• Cortisol

• Epinephrine

• Growth Hormone

Answer explanation

Glucagon is the key counter-regulatory hormone that, unopposed by insulin, activates hepatic ketogenesis by stimulating the CPT-I enzyme system, which facilitates the entry of fatty acids into mitochondria for beta-oxidation.

A 68-year-old male with a 20-year history of poorly controlled Type 2 Diabetes Mellitus presents with an HbA1c of 8.9%. His recent lab work reveals an estimated GFR (eGFR) of 25 mL/min/1.73m², and he is scheduled to begin hemodialysis next month. His current medications include metformin and glimepiride. Which of the following oral hypoglycemic agents can be initiated without the need for dose adjustment?

• Linagliptin

• Glipizide

• Sitagliptin

• Insulin Aspart

Answer explanation

Linagliptin is a DPP-4 inhibitor that is unique in its class as it is primarily excreted via the enterohepatic system, not the kidneys. Therefore, it requires no dose adjustment even in severe renal impairment or ESRD.