Type 1 diabetes — MCQs

10 questions

A 46-year-old man presents with recurrent episodes of severe flushing and diarrhea. CT shows liver metastases and a pancreatic mass. Chromogranin A is markedly elevated. What is the most likely primary tumor?

A 59-year-old woman presents with bone pain and fatigue. Blood tests show calcium 3.3 mmol/L, low albumin, and normal PTH. She has a history of breast cancer 5 years ago. What is the most likely mechanism?

A 43-year-old man presents with recurrent episodes of severe sweating, palpitations, and headache. His BP during episodes is 240/130 mmHg. What is the most appropriate preoperative management?

A 44-year-old woman presents with fatigue, muscle weakness, and weight loss. She has hyperpigmentation of palmar creases. Blood tests show Na+ 128 mmol/L, K+ 5.6 mmol/L. What is the most appropriate diagnostic test?

A 64-year-old woman presents with bone pain and fatigue. Blood tests show calcium 3.1 mmol/L, phosphate 0.7 mmol/L, and suppressed PTH. She has a history of sarcoidosis. What is the most likely cause of hypercalcemia?

A 47-year-old woman presents with fatigue, muscle weakness, and depression. She has purple striae and central obesity. 24-hour urine cortisol is elevated. What is the next most appropriate test?

A 45-year-old man presents with recurrent episodes of severe sweating, headache, and palpitations. His BP during attacks reaches 220/120 mmHg. 24-hour urine catecholamines are elevated. What is the most likely diagnosis?

A 29-year-old woman presents with episodes of severe anxiety, tremor, and palpitations. These occur mainly when fasting. Blood glucose during episodes is 2.1 mmol/L. Insulin and C-peptide are elevated. What is the most likely diagnosis?

A 67-year-old woman presents with bone pain and confusion. Serum calcium is 3.4 mmol/L, phosphate is low, and PTH is elevated. Parathyroid scan shows increased uptake. What is the most appropriate treatment?

Q10

A 49-year-old woman presents with recurrent episodes of severe flushing and diarrhea. CT shows multiple liver lesions and a pancreatic mass. Chromogranin A is elevated. What is the most likely diagnosis?

Type 1 diabetes UK Medical PG Practice Questions and MCQs

Question 1: A 46-year-old man presents with recurrent episodes of severe flushing and diarrhea. CT shows liver metastases and a pancreatic mass. Chromogranin A is markedly elevated. What is the most likely primary tumor?

A. Pancreatic adenocarcinoma
B. Pancreatic neuroendocrine tumor (Correct Answer)
C. Hepatocellular carcinoma
D. Cholangiocarcinoma
E. Gastrinoma

Explanation: ***Pancreatic neuroendocrine tumor*** - The classic presentation of recurrent **flushing** and **diarrhea**, combined with a **pancreatic mass** and **liver metastases**, is highly characteristic of a functional **neuroendocrine tumor (NET)**, specifically a **carcinoid syndrome**. - Markedly elevated **Chromogranin A** is a widely used and sensitive biochemical marker for **neuroendocrine tumors**, confirming this diagnosis. *Pancreatic adenocarcinoma* - This tumor typically presents with symptoms such as **jaundice**, **weight loss**, and **abdominal pain**, not **flushing** and **diarrhea**. - **Chromogranin A** is not elevated in pancreatic adenocarcinoma; **CA 19-9** is a more common tumor marker. *Hepatocellular carcinoma* - While **liver metastases** are mentioned, the primary tumor is a **pancreatic mass**, not a primary liver tumor. - It does not typically cause **flushing** and **diarrhea**, nor is **Chromogranin A** a marker for hepatocellular carcinoma. *Cholangiocarcinoma* - This is a cancer of the **bile ducts** and usually presents with **jaundice**, **pruritus**, and **dark urine**, not **flushing** and **diarrhea**. - The primary mass is in the **pancreas**, not the bile ducts, and **Chromogranin A** is not elevated in cholangiocarcinoma. *Gastrinoma* - A **gastrinoma** is a type of pancreatic neuroendocrine tumor that primarily causes **Zollinger-Ellison syndrome**, characterized by severe **peptic ulcer disease** and **diarrhea** due to excessive gastrin. - While it's a NET, the prominent **flushing** is not a typical feature of gastrinoma; this symptom strongly points towards a tumor producing other vasoactive substances (e.g., serotonin, VIP) consistent with a broader **carcinoid syndrome** presentation.

Question 2: A 59-year-old woman presents with bone pain and fatigue. Blood tests show calcium 3.3 mmol/L, low albumin, and normal PTH. She has a history of breast cancer 5 years ago. What is the most likely mechanism?

A. Parathyroid hormone excess
B. PTH-related protein (Correct Answer)
C. Vitamin D excess
D. Bone metastases
E. Sarcoidosis

Explanation: ***PTH-related protein***- This is the most common cause of **Humoral Hypercalcemia of Malignancy (HHM)**, especially in solid tumors like breast cancer, where **PTHrP** acts as a systemic hormone, mimicking the effects of **parathyroid hormone** on bone and kidney.- The presentation of **severe hypercalcemia** (3.3 mmol/L) with normal or **suppressed PTH** strongly indicates a PTH-independent mechanism, making HHM due to PTHrP the primary diagnosis over primary hyperparathyroidism.*Parathyroid hormone excess*- **Primary Hyperparathyroidism** causes hypercalcemia due to an adenoma or hyperplasia resulting in *high* or *inappropriately normal* circulating levels of **PTH**.- In this patient, the PTH level is normal (implying suppression by the high calcium), which effectively rules out PTH excess as the direct cause of the hypercalcemia.*Vitamin D excess*- Causes hypercalcemia by increasing **intestinal calcium absorption** and promoting bone resorption, identifiable by significantly elevated levels of **25(OH)D** or active **1,25(OH)₂D**.- While possible, this mechanism is far less likely than malignancy-associated hypercalcemia in a patient with a known history of breast cancer.*Bone metastases*- Breast cancer commonly metastasizes to bone, causing **osteolytic lesions** that release calcium via local cytokine-mediated osteoclast activation.- Although common, hypercalcemia caused solely by local osteolysis tends to be less severe than the level seen here; pronounced hypercalcemia with suppressed PTH is the hallmark presentation of **humoral hypercalcemia (PTHrP)**.*Sarcoidosis*- This granulomatous disease causes hypercalcemia via ectopic production of **1-alpha-hydroxylase** by activated macrophages, leading to unregulated synthesis of active **1,25-dihydroxyvitamin D**.- This mechanism is not typically associated with breast cancer and is usually accompanied by other features of sarcoidosis, such as pulmonary symptoms or cutaneous lesions.

Question 3: A 43-year-old man presents with recurrent episodes of severe sweating, palpitations, and headache. His BP during episodes is 240/130 mmHg. What is the most appropriate preoperative management?

A. Beta-blockers only
B. Alpha-blockers only
C. Alpha-blockers then beta-blockers (Correct Answer)
D. ACE inhibitors
E. Calcium channel blockers

Explanation: ***Alpha-blockers then beta-blockers***- The clinical presentation (paroxysmal **hypertension**, headache, palpitations, and sweating) is highly suggestive of a **pheochromocytoma**.- Preoperative stabilization requires adequate **alpha-adrenergic blockade** first (e.g., phenoxybenzamine or doxazosin) to control blood pressure and allow for volume expansion, followed by **beta-blockade** to manage tachycardia or arrhythmias.*Beta-blockers only*- Using beta-blockers alone is contraindicated as it causes **unopposed alpha-adrenergic stimulation**, leading to severe **vasoconstriction** and potentially a fatal hypertensive crisis or pulmonary edema.- Beta-blockers are only instituted *after* achieving complete alpha-blockade and adequate blood pressure control, typically to manage persistent tachycardia.*Alpha-blockers only*- While alpha-blockade is the essential first step, it is usually insufficient for full preoperative management, as patients often require subsequent **beta-blockade** to control catecholamine-induced tachycardia and arrhythmias.- Complete preparation requires both classes of medication to fully mitigate cardiovascular risk before surgery.*ACE inhibitors*- These medications target the **renin-angiotensin-aldosterone system** and are ineffective at blocking the direct severe vasoconstrictive effects of excessive circulating catecholamines.- They may also increase the risk of severe **hypotension** after tumor removal if the patient is relatively volume-depleted from prolonged vasoconstriction.*Calcium channel blockers*- While some CCBs (like nicardipine) can be used as **adjuncts** for blood pressure control, they cannot replace the mandatory initial step of **alpha-adrenergic blockade** and volume repletion.- They do not address the need for full adrenergic receptor blockade necessary to prevent cardiovascular catastrophe during surgical manipulation of the tumor.

Question 4: A 44-year-old woman presents with fatigue, muscle weakness, and weight loss. She has hyperpigmentation of palmar creases. Blood tests show Na+ 128 mmol/L, K+ 5.6 mmol/L. What is the most appropriate diagnostic test?

A. Dexamethasone suppression test
B. Synacthen stimulation test (Correct Answer)
C. 24-hour urine cortisol
D. Adrenal antibodies
E. ACTH levels

Explanation: ***Synacthen stimulation test*** - Also known as the **ACTH stimulation test**, this is the **gold standard** for diagnosing adrenal insufficiency, as the clinical signs (hyperpigmentation, hyponatremia, hyperkalemia) strongly suggest **Primary Adrenal Insufficiency** (Addison's disease). - The test assesses the adrenal gland's reserve capacity to produce cortisol; an insufficient rise in cortisol following the injection of synthetic **ACTH (Synacthen)** confirms the diagnosis. *Dexamethasone suppression test* - This test is primarily used to confirm or exclude **Cushing syndrome** (hypercortisolism) by checking if cortisol production can be suppressed by exogenous steroids. - It is inappropriate for suspected adrenal insufficiency, as it does not evaluate the maximum functional capacity of the adrenal glands. *24-hour urine cortisol* - This test measures the total amount of free cortisol excreted over a day and is typically used as a screening tool for **Cushing syndrome**. - While very low values might suggest adrenal failure, it is less sensitive and specific for diagnosing adrenal insufficiency compared to the **Synacthen test**. *Adrenal antibodies* - Detecting adrenal antibodies (e.g., against **21-hydroxylase**) is crucial for determining the **autoimmune etiology** of primary adrenal insufficiency. - However, measuring antibodies is a step in determining the *cause* of the disease, not the definitive *diagnostic test* for glandular failure. *ACTH levels* - Plasma **ACTH** measurement is essential for distinguishing between primary (high ACTH) and secondary (low ACTH) insufficiency *after* the diagnosis is confirmed by the Synacthen test. - It serves as a differentiation tool, but cannot confirm the initial diagnosis of adrenal insufficiency, which requires assessing the cortisol response to stimulation.

Question 5: A 64-year-old woman presents with bone pain and fatigue. Blood tests show calcium 3.1 mmol/L, phosphate 0.7 mmol/L, and suppressed PTH. She has a history of sarcoidosis. What is the most likely cause of hypercalcemia?

A. Primary hyperparathyroidism
B. Malignancy
C. Granulomatous disease (Correct Answer)
D. Vitamin D intoxication
E. Milk-alkali syndrome

Explanation: ***Granulomatous disease*** - Sarcoidosis, a common granulomatous disease, causes non-PTH mediated hypercalcemia due to the autonomous expression of **1-alpha-hydroxylase** by activated macrophages within the granulomas. - This enzyme overproduces **1,25-dihydroxyvitamin D (calcitriol)**, leading to increased intestinal calcium absorption and subsequent **suppression of PTH**. *Primary hyperparathyroidism* - This condition is characterized by an elevated or inappropriately normal **parathyroid hormone (PTH)** level in the setting of hypercalcemia, typically due to a parathyroid adenoma. - The patient's lab results show **suppressed PTH**, which effectively rules out primary hyperparathyroidism. *Malignancy* - Malignancy frequently causes hypercalcemia, often through osteolytic bone destruction or the secretion of **Parathyroid Hormone-related Protein (PTHrP)**, which also suppresses PTH. - Although PTH is suppressed, the strong history of **sarcoidosis** (a known non-malignant cause of calcitriol-mediated hypercalcemia) makes granulomatous disease the most probable specific diagnosis. *Vitamin D intoxication* - This typically results from massive exogenous intake of vitamin D, leading to extremely high levels of serum **25-hydroxyvitamin D** and subsequent elevation of serum calcium. - While it causes suppressed PTH and hypercalcemia, the known diagnosis of sarcoidosis provides a strong, intrinsic explanation that must be prioritized over exogenous intake. *Milk-alkali syndrome* - This syndrome is caused by the substantial intake of **calcium** and absorbable **alkali**, resulting in hypercalcemia, suppressed PTH, and often metabolic alkalosis. - The history provided emphasizes sarcoidosis rather than excessive antacid or calcium supplementation, making this diagnosis less likely.

Question 6: A 47-year-old woman presents with fatigue, muscle weakness, and depression. She has purple striae and central obesity. 24-hour urine cortisol is elevated. What is the next most appropriate test?

A. MRI pituitary
B. Dexamethasone suppression test (Correct Answer)
C. ACTH levels
D. Adrenal CT
E. CRH stimulation test

Explanation: ***Dexamethasone suppression test*** - An elevated 24-hour urine cortisol confirms hypercortisolism; the next step is to determine the underlying cause, which the **dexamethasone suppression test** helps to differentiate. - This test assesses the feedback control of the **hypothalamic-pituitary-adrenal axis** to differentiate among pituitary Cushing's disease, ectopic ACTH production, and adrenal tumors. *MRI pituitary* - **MRI pituitary** is primarily used for **localization** of a pituitary adenoma after ACTH-dependent Cushing's syndrome has been established. - It is not the initial test to *determine the cause* of hypercortisolism after it has been confirmed. *ACTH levels* - **ACTH levels** are crucial to differentiate between **ACTH-dependent** (pituitary or ectopic) and **ACTH-independent** (adrenal) causes of Cushing's syndrome. - While important, a **dexamethasone suppression test** is often performed first or concurrently to provide functional insight into cortisol suppressibility. *Adrenal CT* - **Adrenal CT** is performed to **localize an adrenal adenoma** or hyperplasia once ACTH-independent Cushing's syndrome (low ACTH) has been identified. - It is a localization step, not the primary diagnostic test to determine the *type* of Cushing's syndrome after initial confirmation of hypercortisolism. *CRH stimulation test* - The **CRH stimulation test** is typically used to help differentiate between **pituitary Cushing's disease** and **ectopic ACTH production** in cases of ACTH-dependent Cushing's syndrome. - It is a more specialized test performed after initial confirmation and differentiation steps like the dexamethasone suppression test and ACTH levels.

Question 7: A 45-year-old man presents with recurrent episodes of severe sweating, headache, and palpitations. His BP during attacks reaches 220/120 mmHg. 24-hour urine catecholamines are elevated. What is the most likely diagnosis?

A. Essential hypertension
B. Pheochromocytoma (Correct Answer)
C. Panic disorder
D. Hyperthyroidism
E. Cocaine use

Explanation: ***Pheochromocytoma*** - The highly suggestive clinical presentation includes the classic paroxysmal triad of severe **headache**, generalized **sweating**, and **palpitations** (tachycardia), often coinciding with **hypertensive crises** (220/120 mmHg).- The diagnosis is biochemically confirmed by finding significant evidence of excessive catecholamine production, such as **elevated 24-hour urine catecholamines** or metanephrines.*Essential hypertension*- Essential hypertension is a diagnosis of exclusion that typically does not present with severe, intermittent, and paroxysmal symptomatic crises.- It is not characterized by pathologically high levels of **catecholamines** or their metabolites in the urine or plasma.*Panic disorder*- Panic disorder can cause symptoms mimicking sympathetic overdrive (palpitations, sweating), but it rarely causes the severe, transient **hypertensive crises** seen in this patient (e.g., 220/120 mmHg).- Panic attacks are excluded as the primary cause by the finding of high levels of circulating and **urinary catecholamines**.*Hyperthyroidism*- While hyperthyroidism causes palpitations and sweating, the hypertension is usually predominantly **systolic** (leading to a wide pulse pressure), not spiking to 220/120 mmHg.- Diagnosis relies on elevated **thyroid hormone levels** (T3/T4) and a suppressed TSH, not elevated catecholamines.*Cocaine use*- Acute cocaine intoxication causes severe sympathetic hyperactivity and hypertension, but this is usually transient and related to recent drug ingestion.- If intoxication were the cause, laboratory findings would typically show evidence of drug use or metabolites, rather than chronic baseline elevation of **catecholamines** suggestive of a secreting tumor.

Question 8: A 29-year-old woman presents with episodes of severe anxiety, tremor, and palpitations. These occur mainly when fasting. Blood glucose during episodes is 2.1 mmol/L. Insulin and C-peptide are elevated. What is the most likely diagnosis?

A. Panic disorder
B. Insulinoma (Correct Answer)
C. Factitious hypoglycemia
D. Reactive hypoglycemia
E. Adrenal insufficiency

Explanation: ***Insulinoma*** - The presentation fulfills **Whipple's triad** (symptoms of hypoglycemia, low blood glucose, relief upon glucose administration) occurring specifically with **fasting**. - The key diagnostic findings are **fasting hypoglycemia** (2.1 mmol/L) combined with inappropriately **elevated insulin and C-peptide**, confirming excessive *endogenous* insulin secretion from a pancreatic **β-cell tumor**. *Panic disorder* - Although the symptoms (anxiety, tremor, and palpitations) mimic adrenergic symptoms of hypoglycemia, the coexisting **severe hypoglycemia** rules out pure panic disorder. - Panic disorder is a psychiatric diagnosis and does not cause underlying metabolic derangements like low blood glucose or hyperinsulinemia. *Factitious hypoglycemia* - If the patient were using **exogenous insulin**, the C-peptide level would be **suppressed or low**, as commercial insulin preparations do not typically contain C-peptide. - While sulfonylurea abuse (a form of factitious hypoglycemia) can raise both insulin and C-peptide, **insulinoma** remains the primary organic diagnosis when these findings occur spontaneously, especially with severe fasting symptoms. *Reactive hypoglycemia* - This condition is characterized by hypoglycemia occurring **postprandially** (2–4 hours after a meal) due to rapid glucose absorption and delayed insulin response, not during **fasting**. - It is often seen after gastric surgeries or in the initial stages of diabetes, and typically presents with milder symptoms. *Adrenal insufficiency* - Adrenal insufficiency causes hypoglycemia primarily through lack of **cortisol**, which is a counter-regulatory hormone to insulin. - Hypoglycemia secondary to this condition would present with **suppressed** or low insulin and C-peptide levels, as the pancreas is not producing excess insulin.

Question 9: A 67-year-old woman presents with bone pain and confusion. Serum calcium is 3.4 mmol/L, phosphate is low, and PTH is elevated. Parathyroid scan shows increased uptake. What is the most appropriate treatment?

A. IV fluids and bisphosphonates
B. Parathyroidectomy (Correct Answer)
C. Cinacalcet
D. High-dose vitamin D
E. Corticosteroids

Explanation: ***Parathyroidectomy*** - The presence of severe hypercalcemia (3.4 mmol/L), elevated PTH, and end-organ damage (bone pain, confusion) are clear indications for definitive surgical management of **Primary Hyperparathyroidism** (PHPT). - Parathyroidectomy is the curative treatment for PHPT, effectively removing the source of excess PTH production (likely an **adenoma**, localized by the scan) and normalizing calcium levels long-term. *IV fluids and bisphosphonates* - These agents are used for the initial, acute management of **hypercalcemic crisis** to rapidly reduce serum calcium, but they are not the definitive curative treatment for the underlying PHPT. - Bisphosphonates inhibit osteoclast activity, but the failure to address the sustained excess PTH means high calcium levels will recur shortly without definitive surgical intervention. *Cinacalcet* - Cinacalcet is a **calcimimetic** that increases the sensitivity of the calcium-sensing receptor, reducing PTH secretion and serum calcium. - It is typically reserved for PHPT patients who are poor surgical candidates or have intractable secondary hyperparathyroidism, not the **first-line curative treatment**. *High-dose vitamin D* - Vitamin D should be avoided as it would exacerbate the patient's hypercalcemia by increasing **intestinal calcium absorption** and mobilizing calcium from bone. - It is used to treat conditions causing **hypocalcemia** (like hypoparathyroidism or vitamin D deficiency), which is the opposite of this clinical scenario. *Corticosteroids* - Corticosteroids are primarily used to treat hypercalcemia associated with **malignancy** or **granulomatous diseases** (e.g., sarcoidosis) by reducing calcitriol production. - They are generally ineffective in managing the high calcium levels driven by increased PTH secretion caused by a **parathyroid adenoma**.

Question 10: A 49-year-old woman presents with recurrent episodes of severe flushing and diarrhea. CT shows multiple liver lesions and a pancreatic mass. Chromogranin A is elevated. What is the most likely diagnosis?

A. Pancreatic adenocarcinoma
B. Neuroendocrine tumor (Correct Answer)
C. Hepatocellular carcinoma
D. Cholangiocarcinoma
E. Lymphoma

Explanation: ***Neuroendocrine tumor***- The combination of **severe flushing** and secretory **diarrhea** (suggestive of **carcinoid syndrome**), coupled with a pancreatic mass and liver metastases, is highly specific for a functional Neuroendocrine Tumor (NET).- The elevated **Chromogranin A** confirms the neuroendocrine origin of the tumor, as this protein is stored and released by neurosecretory granules in NET cells.*Pancreatic adenocarcinoma*- This common pancreatic malignancy typically presents with **painless jaundice**, severe back pain, or weight loss, but **lacks the specific hormonal symptoms** of flushing and diarrhea.- The primary tumor marker for adenocarcinoma is usually **CA 19-9**, not Chromogranin A.*Hepatocellular carcinoma*- This primary liver cancer arises most often in the setting of chronic liver disease/cirrhosis and presents with mass effects or systemic decline, but **flushing and diarrhea are absent**.- The liver lesions in this case are likely **metastases** arising from the primary pancreatic neuroendocrine tumor, not primary HCC.*Cholangiocarcinoma*- This cancer of the bile ducts manifests primarily as **obstructive jaundice** and right upper quadrant pain.- It is not associated with the syndrome of flushing and diarrhea or the release of hormones that lead to elevated **Chromogranin A**.*Lymphoma*- Lymphoma typically presents with systemic **B symptoms** (**fever, night sweats, weight loss**) and significant lymphadenopathy.- It does not produce the hormones that cause flushing and diarrhea, nor is it associated with elevated serum **Chromogranin A**.

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