DFT-MEDICINE D3- 10-10-2025-MAXEMO

A patient is brought to the emergency department with altered sensorium. Point-of-care glucose is 38 mg/dL. Laboratory evaluation during the hypoglycemic episode reveals a high plasma insulin level, a suppressed C-peptide level, and low beta-hydroxybutyrate. What is the most likely cause?

• Exogenous insulin administration

• Insulinoma

• Sulfonylurea overdose

• Adrenal insufficiency

Answer explanation

The combination of high insulin with suppressed C-peptide is pathognomonic for the administration of exogenous insulin, as C-peptide is cleaved from proinsulin only during endogenous secretion.

A patient with a large retroperitoneal solitary fibrous tumor presents with recurrent severe hypoglycemia. Laboratory studies during an episode show suppressed insulin and C-peptide levels. Which mediator is most likely responsible for this paraneoplastic syndrome?

• Insulin-like growth factor 2 (IGF-2)

• Insulin-like growth factor 1 (IGF-1)

• Glucagon

• Proinsulin

Answer explanation

Non-islet cell tumors, particularly large mesenchymal tumors, can secrete high-molecular-weight IGF-2, which activates the insulin receptor, causing hypoglycemia while suppressing endogenous insulin and C-peptide secretion.

An infant presents in shock with vomiting, hyponatremia, and hyperkalemia. Physical examination reveals ambiguous genitalia and diffuse hyperpigmentation. Following fluid resuscitation, which intervention is the most critical next step in management?

• Intravenous hydrocortisone administration

• Commencement of oral fludrocortisone

• ACTH stimulation test for diagnosis

• Karyotyping for sex determination

Answer explanation

 In an adrenal crisis from salt-wasting CAH (likely 21-hydroxylase deficiency), immediate glucocorticoid replacement with stress-dose hydrocortisone is life-saving, stabilizing the patient hemodynamically and reducing adrenal androgen production.

A pregnant patient with a known gain-of-function mutation in the NR3C2 gene (coding for the mineralocorticoid receptor) experiences a significant and dangerous worsening of her hypertension during the third trimester. This exacerbation is primarily mediated by which endogenous substance?

• Progesterone

• Aldosterone

• Deoxycorticosterone (DOC)

• Estradiol

Answer explanation

This scenario describes Geller's syndrome. The specific mutation in the mineralocorticoid receptor causes progesterone, which rises to high levels during pregnancy, to act as a potent agonist, leading to severe volume expansion and hypertension.

A patient presents with treatment-resistant hypertension, hypokalemia, and metabolic alkalosis. Endocrine evaluation surprisingly reveals suppressed plasma renin activity and a very low plasma aldosterone concentration. Which of the following agents would be the most specific and effective long-term treatment?

• Amiloride

• Spironolactone

• Lisinopril

• Furosemide

Answer explanation

This presentation is classic for Liddle syndrome, a state of apparent mineralocorticoid excess due to a gain-of-function mutation in the ENaC. Amiloride directly blocks this channel, correcting the underlying pathophysiology.

A patient with chronic fatigue and postural dizziness is being evaluated. Which of the following clinical findings would most specifically suggest primary adrenal insufficiency over a pituitary etiology?

• Hyperpigmentation of palmar creases

• Hyponatremia

• Anorexia and weight loss

• Normal skin color with pallor

Answer explanation

Hyperpigmentation is the hallmark of primary adrenal insufficiency. It results from elevated levels of ACTH and other pro-opiomelanocortin (POMC) derived peptides, which stimulate melanocytes. This feature is absent in secondary adrenal insufficiency.

A patient with Addison's disease on maintenance hydrocortisone presents with persistent postural hypotension despite adequate glucocorticoid replacement. Laboratory results show persistent hyponatremia. What is the most appropriate medication to add?

• Fludrocortisone

• Dexamethasone

• Midodrine

• Spironolactone

Answer explanation

Fludrocortisone is a synthetic mineralocorticoid used to replace the deficient aldosterone in primary adrenal insufficiency. It corrects salt wasting, volume depletion, and postural hypotension.

A 29-year-old patient is diagnosed with an extra-adrenal, norepinephrine-secreting paraganglioma located in the organ of Zuckerkandl. Genetic testing is performed as part of the workup to assess syndromic association and long-term prognosis. The presence of a germline mutation in which of the following genes would confer the highest risk for future metastatic disease?

• SDHB

• VHL

• RET

• NF1

Answer explanation

Mutations in the succinate dehydrogenase subunit B (SDHB) gene are strongly associated with the highest risk of malignancy and metastasis (up to 40-50%) in patients with pheochromocytoma/paraganglioma, particularly for extra-adrenal tumors.

A biopsy of the thyroid nodule from the patient is performed. Histopathological examination reveals nests of polygonal cells separated by a fibrovascular stroma. Special staining is positive for calcitonin and carcinoembryonic antigen (CEA). What is the characteristic microscopic finding associated with this tumor?

• Amyloid deposition in the stroma

• Psammoma bodies

• Orphan Annie eye nuclei

• Hurthle cell change

Answer explanation

Medullary thyroid carcinoma is a neuroendocrine tumor derived from parafollicular C-cells. It characteristically features extracellular deposition of amyloid, which is derived from altered calcitonin molecules secreted by the tumor cells.

A patient is diagnosed with bilateral pheochromocytomas. Further evaluation reveals medullary thyroid carcinoma. A germline mutation in which of the following genes is most likely responsible for this patient's clinical presentation?

• RET proto-oncogene

• VHL gene

• NF1 gene

• SDHD gene

Answer explanation

The combination of bilateral pheochromocytomas and medullary thyroid carcinoma is the classic presentation of Multiple Endocrine Neoplasia type 2 (MEN 2A or 2B), which is caused by activating mutations in the RET proto-oncogene.