What 72-hour fasting test biochemical results diagnose an Insulinoma?

Symptomatic hypoglycemia (plasma glucose = 3 mcU/mL), elevated C-peptide (>= 0.6 ng/mL), elevated proinsulin (>= 5 pmol/L), and negative screening for oral sulfonylureas/meglitinides.

What nuclear receptor is activated by Thiazolidinediones (e.g. Pioglitazone), and what are their primary adverse effects?

Peroxisome Proliferator-Activated Receptor gamma (PPAR-gamma), upregulating adiponectin and GLUT4 to increase peripheral insulin sensitivity; adverse effects include fluid retention / peripheral edema (contraindicated in NYHA Class III/IV heart failure), weight gain, and increased bone fracture risk.

What clinical tetrad defines a VIPoma (Verner-Morrison Syndrome / WDHA Syndrome)?

Watery Diarrhea, Hypokalemia, and Achlorhydria (WDHA syndrome); autonomous secretion of Vasoactive Intestinal Peptide (VIP) from a pancreatic islet tumor causes copious, secretory 'tea-colored' diarrhea (> 1-3 L/day) that persists during fasting; treated with octreotide.

What tumor suppressor gene and clinical triad define Multiple Endocrine Neoplasia Type 1 (MEN 1 / Wermer Syndrome)?

Autosomal dominant mutation in MEN1 gene on chromosome 11 encoding MENIN; Triad of '3 Ps': 1) Parathyroid hyperplasia (primary hyperparathyroidism, ~95%); 2) Pancreatic neuroendocrine tumors (gastrinoma, insulinoma); 3) Pituitary adenomas (prolactinoma most common).

What is the classic rash and clinical constellation of a Glucagonoma ('4 Ds')?

Pancreatic alpha-cell neuroendocrine tumor producing excess glucagon; presents with '4 Ds': 1) Dermatitis (Necrolytic Migratory Erythema: pruritic, painful erythematous scaling plaques with central bullae and bronze hyperpigmentation); 2) Diabetes (mild hyperglycemia); 3) DVT (thrombosis); 4) Depression and weight loss.

What inhibitory clinical triad characterizes a Somatostatinoma?

Pancreatic delta-cell neuroendocrine tumor secreting excess somatostatin; inhibits multiple endocrine and exocrine pathways, producing: 1) Diabetes mellitus (inhibits insulin release); 2) Steatorrhea and Gallstones/cholelithiasis (inhibits CCK and gallbladder contraction); 3) Hypochlorhydria (inhibits gastrin).

What initial laboratory screening tests diagnose Pheochromocytoma, and what imaging localizes the lesion?

Measurement of plasma free metanephrines (normetanephrine and metanephrine) or 24-hour urinary fractionated metanephrines and catecholamines; localized using abdominal contrast CT or MRI, followed by 123I-MIBG (metaiodobenzylguanidine) scintigraphy if extra-adrenal or metastatic.

What is the earliest clinically detectable sign of diabetic nephropathy, and what medication classes slow its progression?

Moderately increased albuminuria (microalbuminuria: urine albumin-to-creatinine ratio 30-300 mg/g); progression is slowed by ACE inhibitors or Angiotensin Receptor Blockers (ARBs), which dilate efferent arterioles to reduce intraglomerular hypertension, and SGLT2 inhibitors.

What is the vascular pathogenesis and fundoscopic distinction between non-proliferative and proliferative diabetic retinopathy?

Pericyte loss and microaneurysms cause retinal ischemia; Non-proliferative: microaneurysms, dot-and-blot hemorrhages, hard lipid exudates, and cotton-wool spots (microinfarcts); Proliferative: VEGF secretion induces NEOVASCULARIZATION (fragile vessels on optic disc/retina prone to vitreous hemorrhage and traction retinal detachment).

What is the mechanism of action of Metformin, its clinical benefits, and its primary black box contraindication?

Activates AMP-activated protein kinase (AMPK), inhibiting hepatic gluconeogenesis and increasing peripheral insulin sensitivity; causes no hypoglycemia and promotes modest weight loss; contraindicated in severe renal impairment (eGFR < 30 mL/min) or severe tissue hypoxemia due to the risk of fatal LACTIC ACIDOSIS.

What are the classic components of the 'Rule of 10s' for Pheochromocytoma?

10% bilateral (adrenal), 10% extra-adrenal (paragangliomas, e.g. organ of Zuckerkandl), 10% malignant, 10% pediatric, 10% familial (MEN 2, VHL, NF1), and 10% calcified.

What three clinical criteria constitute Whipple Triad for evaluating hypoglycemia?

1) Symptoms consistent with hypoglycemia (autonomic: diaphoresis, tremor, palpitations; neuroglycopenic: confusion, visual changes, seizures); 2) Documented low plasma glucose (< 55 mg/dL); 3) Prompt relief of symptoms following administration of carbohydrate/glucose.

What dual defects drive Type 2 Diabetes Mellitus, and what histopathological deposit characterizes pancreatic islets in long-standing disease?

Progressive peripheral insulin resistance (skeletal muscle, liver, adipose) combined with beta-cell secretory failure; histopathologically characterized by dense extracellular deposition of AMYLOID polypeptide (amylin) within the islets of Langerhans.

What is the autoimmune pathogenesis, genetic HLA association, and primary circulating autoantibodies in Type 1 Diabetes Mellitus?

Autoimmune destruction of pancreatic beta cells mediated by CD8+ cytotoxic T cells; associated with HLA-DR3, HLA-DR4, and HLA-DQ2/DQ8; autoantibodies include Anti-Glutamic Acid Decarboxylase (anti-GAD65), Anti-Islet Cell Antigen-2 (anti-IA-2), and Anti-Zinc Transporter 8 (anti-ZnT8).

How does C-peptide measurement distinguish factitious insulin injection from an insulinoma or sulfonylurea overdose?

C-peptide is cleaved in equimolar amounts to endogenous insulin; Exogenous insulin administration causes hypoglycemia with ELEVATED insulin and UNDETECTABLE / low C-peptide; Insulinoma and sulfonylurea toxicity produce hypoglycemia with ELEVATED insulin and ELEVATED C-peptide.

When should 5% Dextrose be added to intravenous fluids during the management of DKA, and why?

When serum glucose reaches 200-250 mg/dL, add 5% dextrose (e.g. D5 1/2 NS) to the IV fluids while CONTINUING insulin infusion; this prevents hypoglycemia and cerebral edema while allowing insulin to remain running until the high anion gap closes and ketoacidosis resolves.

How do DPP-4 inhibitors (e.g. Sitagliptin, Linagliptin) differ mechanistically and in efficacy from GLP-1 receptor agonists?

DPP-4 inhibitors inhibit the degradation of endogenous GLP-1 and GIP; they are weight-neutral, orally administered, have low hypoglycemia risk, but have modest glycemic efficacy and do NOT confer the major weight-loss or cardiovascular mortality benefits of injectable GLP-1 receptor agonists.

What are the common clinical manifestations of diabetic autonomic neuropathy affecting the cardiovascular, GI, and GU systems?

Cardiovascular: resting tachycardia and orthostatic hypotension (denervation of sympathetic/parasympathetic tone); Gastrointestinal: diabetic gastroparesis (delayed gastric emptying, early satiety, nausea/vomiting); Genitourinary: neurogenic bladder (urinary retention and overflow incontinence) and erectile dysfunction.

What is the molecular target and mechanism of action of Sulfonylureas (e.g. Glipizide, Glimepiride)?

Bind to and close the ATP-sensitive potassium channel (SUR1 subunit) in pancreatic beta-cell membranes; this depolarizes the membrane, opening voltage-gated calcium channels, causing calcium influx and exocytosis of preformed endogenous insulin granules (risk of hypoglycemia and weight gain).

What is Zollinger-Ellison Syndrome (ZES), and how does the Secretin Stimulation Test confirm diagnosis?

A gastrin-secreting neuroendocrine tumor (gastrinoma, usually duodenal/pancreatic) driving massive gastric acid hypersecretion and refractory peptic ulcerations; IV secretin paradoxically STIMULATES gastrin release from gastrinoma cells (raising serum gastrin > 120-200 pg/mL), whereas it inhibits normal antral G cells.

What is the mandatory clinical rule regarding serum potassium prior to starting intravenous insulin in DKA?

Insulin drives potassium into cells via the Na+/K+-ATPase; if serum K+ is 3.3 mEq/L, to prevent lethal ventricular arrhythmias and respiratory muscle arrest.

What clinical features distinguish MEN 2B from MEN 2A?

Both feature Medullary Thyroid Carcinoma and Pheochromocytoma (due to RET proto-oncogene mutations); MEN 2B uniquely features Mucosal neuromas (lips, tongue, gastrointestinal ganglioneuromatosis) and a Marfanoid habitus, but LACKS parathyroid hyperplasia.

What is the mandatory sequence of pharmacological adrenergic blockade prior to surgical resection of a pheochromocytoma, and why?

Phenoxybenzamine (irreversible alpha-adrenergic blocker) MUST be administered for 10-14 days FIRST; beta-blockers (e.g. propranolol) are added only AFTER adequate alpha-blockade; administering beta-blockers first leaves alpha-1 receptors unopposed, precipitating catastrophic hypertensive crisis.

What is the biochemical cascade that generates ketone bodies in Diabetic Ketoacidosis (DKA)?

Absolute insulin deficiency and glucagon excess stimulate hormone-sensitive lipase in adipose tissue, releasing free fatty acids; in the liver, increased carnitine palmitoyltransferase-1 (CPT-1) activity shunts fatty acids into beta-oxidation, producing excess Acetyl-CoA converted into beta-hydroxybutyrate and acetoacetate.

How do serum glucose, arterial pH, serum bicarbonate, and effective osmolality differ between DKA and HHS?

DKA: Glucose typically 250-600 mg/dL, arterial pH 12), positive ketones; HHS: Glucose > 600 mg/dL, arterial pH > 7.30, serum HCO3- > 18 mEq/L, normal/near-normal anion gap, negative/trace ketones, effective serum osmolality > 320 mOsm/kg.

What is the pathophysiological reason that Hyperosmolar Hyperglycemic State (HHS) lacks significant ketosis compared to DKA?

In HHS, residual endogenous insulin secretion is sufficient to suppress lipolysis in adipose tissue and inhibit hepatic ketogenesis, but insufficient to prevent severe hepatic gluconeogenesis and peripheral hyperglycemia (> 600 mg/dL), leading to profound hyperosmolar diuresis.

What are the multi-organ actions of GLP-1 receptor agonists (e.g. Semaglutide, Liraglutide), and what thyroid warning exists?

Enhance glucose-dependent insulin secretion, suppress glucagon release, delay gastric emptying, and promote central satiety (significant weight loss and cardiovascular risk reduction); black box contraindication in patients with personal or family history of Medullary Thyroid Carcinoma or MEN 2.

What is the nephron site of action and cardiorenal benefits of SGLT2 inhibitors (e.g. Empagliflozin, Dapagliflozin)?

Inhibit the Sodium-Glucose Cotransporter 2 in the proximal convoluted tubule, blocking ~90% of glucose reabsorption to produce glucosuria and natriuresis; proven to reduce heart failure hospitalizations, slow progression of chronic kidney disease, and reduce cardiovascular mortality in T2D.

What sensory modalities are lost first in diabetic sensorimotor polyneuropathy, and what physical exam tool screens for foot ulcer risk?

Small unmyelinated fibers (burning pain and temperature loss) and large myelinated fibers (vibration sense via 128-Hz tuning fork and ankle reflexes) are lost in a symmetric 'stocking-glove' distribution; screened annually using the 10-gram Semmes-Weinstein monofilament to detect loss of protective sensation.

What is the classic clinical paroxysmal triad of Pheochromocytoma, and what tissue gives rise to this tumor?

Adrenal medullary chromaffin cells (derived from neural crest); presents with paroxysmal or sustained hypertension accompanied by the classic triad of: 1) Episodic pounding Headache; 2) Profuse diaphoresis (Sweating); 3) Palpitations / Tachycardia.

What are the four formal ADA diagnostic laboratory criteria for Diabetes Mellitus?

1) Fasting plasma glucose >= 126 mg/dL (after 8-hr fast); 2) 2-hour plasma glucose >= 200 mg/dL during a 75 g OGTT; 3) Hemoglobin A1c >= 6.5%; 4) In a patient with classic symptoms of hyperglycemia (polyuria, polydipsia, weight loss), a random plasma glucose >= 200 mg/dL.

What proto-oncogene mutation and clinical triad define Multiple Endocrine Neoplasia Type 2A (MEN 2A / Sipple Syndrome)?

Autosomal dominant gain-of-function mutation in the RET proto-oncogene on chromosome 10; Triad of '1 M, 2 Ps': 1) Medullary Thyroid Carcinoma (100%, calcitonin-secreting); 2) Pheochromocytoma (~50%, frequently bilateral); 3) Parathyroid hyperplasia (~20-30%).

Endocrinology II — Type 1 & Type 2 Diabetes, DKA vs HHS, Pheochromocytoma & Multiple Endocrine Neoplasia (MEN 1 & 2)

Diabetes mellitus pathogenesis and complications, diabetic emergencies, chromaffin cell neoplasms, and MEN syndromes

Level: intermediate
Languages: en → en
Cards: 32
Markdown: Endocrinology II — Type 1 & Type 2 Diabetes, DKA vs HHS, Pheochromocytoma & Multiple Endocrine Neoplasia (MEN 1 & 2) (.md)

Flashcards (32)

#	Front (Term / Question)	Back (Definition / Answer)
1	What 72-hour fasting test biochemical results diagnose an Insulinoma?	Symptomatic hypoglycemia (plasma glucose < 55 mg/dL) accompanied by inappropriately elevated serum insulin (>= 3 mcU/mL), elevated C-peptide (>= 0.6 ng/mL), elevated proinsulin (>= 5 pmol/L), and negative screening for oral sulfonylureas/meglitinides.
2	What nuclear receptor is activated by Thiazolidinediones (e.g. Pioglitazone), and what are their primary adverse effects?	Peroxisome Proliferator-Activated Receptor gamma (PPAR-gamma), upregulating adiponectin and GLUT4 to increase peripheral insulin sensitivity; adverse effects include fluid retention / peripheral edema (contraindicated in NYHA Class III/IV heart failure), weight gain, and increased bone fracture risk.
3	What clinical tetrad defines a VIPoma (Verner-Morrison Syndrome / WDHA Syndrome)?	Watery Diarrhea, Hypokalemia, and Achlorhydria (WDHA syndrome); autonomous secretion of Vasoactive Intestinal Peptide (VIP) from a pancreatic islet tumor causes copious, secretory 'tea-colored' diarrhea (> 1-3 L/day) that persists during fasting; treated with octreotide.
4	What tumor suppressor gene and clinical triad define Multiple Endocrine Neoplasia Type 1 (MEN 1 / Wermer Syndrome)?	Autosomal dominant mutation in MEN1 gene on chromosome 11 encoding MENIN; Triad of '3 Ps': 1) Parathyroid hyperplasia (primary hyperparathyroidism, ~95%); 2) Pancreatic neuroendocrine tumors (gastrinoma, insulinoma); 3) Pituitary adenomas (prolactinoma most common).
5	What is the classic rash and clinical constellation of a Glucagonoma ('4 Ds')?	Pancreatic alpha-cell neuroendocrine tumor producing excess glucagon; presents with '4 Ds': 1) Dermatitis (Necrolytic Migratory Erythema: pruritic, painful erythematous scaling plaques with central bullae and bronze hyperpigmentation); 2) Diabetes (mild hyperglycemia); 3) DVT (thrombosis); 4) Depression and weight loss.
6	What inhibitory clinical triad characterizes a Somatostatinoma?	Pancreatic delta-cell neuroendocrine tumor secreting excess somatostatin; inhibits multiple endocrine and exocrine pathways, producing: 1) Diabetes mellitus (inhibits insulin release); 2) Steatorrhea and Gallstones/cholelithiasis (inhibits CCK and gallbladder contraction); 3) Hypochlorhydria (inhibits gastrin).
7	What initial laboratory screening tests diagnose Pheochromocytoma, and what imaging localizes the lesion?	Measurement of plasma free metanephrines (normetanephrine and metanephrine) or 24-hour urinary fractionated metanephrines and catecholamines; localized using abdominal contrast CT or MRI, followed by 123I-MIBG (metaiodobenzylguanidine) scintigraphy if extra-adrenal or metastatic.
8	What is the earliest clinically detectable sign of diabetic nephropathy, and what medication classes slow its progression?	Moderately increased albuminuria (microalbuminuria: urine albumin-to-creatinine ratio 30-300 mg/g); progression is slowed by ACE inhibitors or Angiotensin Receptor Blockers (ARBs), which dilate efferent arterioles to reduce intraglomerular hypertension, and SGLT2 inhibitors.
9	What is the vascular pathogenesis and fundoscopic distinction between non-proliferative and proliferative diabetic retinopathy?	Pericyte loss and microaneurysms cause retinal ischemia; Non-proliferative: microaneurysms, dot-and-blot hemorrhages, hard lipid exudates, and cotton-wool spots (microinfarcts); Proliferative: VEGF secretion induces NEOVASCULARIZATION (fragile vessels on optic disc/retina prone to vitreous hemorrhage and traction retinal detachment).
10	What is the mechanism of action of Metformin, its clinical benefits, and its primary black box contraindication?	Activates AMP-activated protein kinase (AMPK), inhibiting hepatic gluconeogenesis and increasing peripheral insulin sensitivity; causes no hypoglycemia and promotes modest weight loss; contraindicated in severe renal impairment (eGFR < 30 mL/min) or severe tissue hypoxemia due to the risk of fatal LACTIC ACIDOSIS.
11	What are the classic components of the 'Rule of 10s' for Pheochromocytoma?	10% bilateral (adrenal), 10% extra-adrenal (paragangliomas, e.g. organ of Zuckerkandl), 10% malignant, 10% pediatric, 10% familial (MEN 2, VHL, NF1), and 10% calcified.
12	What three clinical criteria constitute Whipple Triad for evaluating hypoglycemia?	1) Symptoms consistent with hypoglycemia (autonomic: diaphoresis, tremor, palpitations; neuroglycopenic: confusion, visual changes, seizures); 2) Documented low plasma glucose (< 55 mg/dL); 3) Prompt relief of symptoms following administration of carbohydrate/glucose.
13	What dual defects drive Type 2 Diabetes Mellitus, and what histopathological deposit characterizes pancreatic islets in long-standing disease?	Progressive peripheral insulin resistance (skeletal muscle, liver, adipose) combined with beta-cell secretory failure; histopathologically characterized by dense extracellular deposition of AMYLOID polypeptide (amylin) within the islets of Langerhans.
14	What is the autoimmune pathogenesis, genetic HLA association, and primary circulating autoantibodies in Type 1 Diabetes Mellitus?	Autoimmune destruction of pancreatic beta cells mediated by CD8+ cytotoxic T cells; associated with HLA-DR3, HLA-DR4, and HLA-DQ2/DQ8; autoantibodies include Anti-Glutamic Acid Decarboxylase (anti-GAD65), Anti-Islet Cell Antigen-2 (anti-IA-2), and Anti-Zinc Transporter 8 (anti-ZnT8).
15	How does C-peptide measurement distinguish factitious insulin injection from an insulinoma or sulfonylurea overdose?	C-peptide is cleaved in equimolar amounts to endogenous insulin; Exogenous insulin administration causes hypoglycemia with ELEVATED insulin and UNDETECTABLE / low C-peptide; Insulinoma and sulfonylurea toxicity produce hypoglycemia with ELEVATED insulin and ELEVATED C-peptide.
16	When should 5% Dextrose be added to intravenous fluids during the management of DKA, and why?	When serum glucose reaches 200-250 mg/dL, add 5% dextrose (e.g. D5 1/2 NS) to the IV fluids while CONTINUING insulin infusion; this prevents hypoglycemia and cerebral edema while allowing insulin to remain running until the high anion gap closes and ketoacidosis resolves.
17	How do DPP-4 inhibitors (e.g. Sitagliptin, Linagliptin) differ mechanistically and in efficacy from GLP-1 receptor agonists?	DPP-4 inhibitors inhibit the degradation of endogenous GLP-1 and GIP; they are weight-neutral, orally administered, have low hypoglycemia risk, but have modest glycemic efficacy and do NOT confer the major weight-loss or cardiovascular mortality benefits of injectable GLP-1 receptor agonists.
18	What are the common clinical manifestations of diabetic autonomic neuropathy affecting the cardiovascular, GI, and GU systems?	Cardiovascular: resting tachycardia and orthostatic hypotension (denervation of sympathetic/parasympathetic tone); Gastrointestinal: diabetic gastroparesis (delayed gastric emptying, early satiety, nausea/vomiting); Genitourinary: neurogenic bladder (urinary retention and overflow incontinence) and erectile dysfunction.
19	What is the molecular target and mechanism of action of Sulfonylureas (e.g. Glipizide, Glimepiride)?	Bind to and close the ATP-sensitive potassium channel (SUR1 subunit) in pancreatic beta-cell membranes; this depolarizes the membrane, opening voltage-gated calcium channels, causing calcium influx and exocytosis of preformed endogenous insulin granules (risk of hypoglycemia and weight gain).
20	What is Zollinger-Ellison Syndrome (ZES), and how does the Secretin Stimulation Test confirm diagnosis?	A gastrin-secreting neuroendocrine tumor (gastrinoma, usually duodenal/pancreatic) driving massive gastric acid hypersecretion and refractory peptic ulcerations; IV secretin paradoxically STIMULATES gastrin release from gastrinoma cells (raising serum gastrin > 120-200 pg/mL), whereas it inhibits normal antral G cells.
21	What is the mandatory clinical rule regarding serum potassium prior to starting intravenous insulin in DKA?	Insulin drives potassium into cells via the Na+/K+-ATPase; if serum K+ is < 3.3 mEq/L, insulin MUST BE WITHHELD and intravenous potassium aggressively repleted until K+ > 3.3 mEq/L, to prevent lethal ventricular arrhythmias and respiratory muscle arrest.
22	What clinical features distinguish MEN 2B from MEN 2A?	Both feature Medullary Thyroid Carcinoma and Pheochromocytoma (due to RET proto-oncogene mutations); MEN 2B uniquely features Mucosal neuromas (lips, tongue, gastrointestinal ganglioneuromatosis) and a Marfanoid habitus, but LACKS parathyroid hyperplasia.
23	What is the mandatory sequence of pharmacological adrenergic blockade prior to surgical resection of a pheochromocytoma, and why?	Phenoxybenzamine (irreversible alpha-adrenergic blocker) MUST be administered for 10-14 days FIRST; beta-blockers (e.g. propranolol) are added only AFTER adequate alpha-blockade; administering beta-blockers first leaves alpha-1 receptors unopposed, precipitating catastrophic hypertensive crisis.
24	What is the biochemical cascade that generates ketone bodies in Diabetic Ketoacidosis (DKA)?	Absolute insulin deficiency and glucagon excess stimulate hormone-sensitive lipase in adipose tissue, releasing free fatty acids; in the liver, increased carnitine palmitoyltransferase-1 (CPT-1) activity shunts fatty acids into beta-oxidation, producing excess Acetyl-CoA converted into beta-hydroxybutyrate and acetoacetate.
25	How do serum glucose, arterial pH, serum bicarbonate, and effective osmolality differ between DKA and HHS?	DKA: Glucose typically 250-600 mg/dL, arterial pH < 7.30, serum HCO3- < 18 mEq/L, elevated anion gap (> 12), positive ketones; HHS: Glucose > 600 mg/dL, arterial pH > 7.30, serum HCO3- > 18 mEq/L, normal/near-normal anion gap, negative/trace ketones, effective serum osmolality > 320 mOsm/kg.
26	What is the pathophysiological reason that Hyperosmolar Hyperglycemic State (HHS) lacks significant ketosis compared to DKA?	In HHS, residual endogenous insulin secretion is sufficient to suppress lipolysis in adipose tissue and inhibit hepatic ketogenesis, but insufficient to prevent severe hepatic gluconeogenesis and peripheral hyperglycemia (> 600 mg/dL), leading to profound hyperosmolar diuresis.
27	What are the multi-organ actions of GLP-1 receptor agonists (e.g. Semaglutide, Liraglutide), and what thyroid warning exists?	Enhance glucose-dependent insulin secretion, suppress glucagon release, delay gastric emptying, and promote central satiety (significant weight loss and cardiovascular risk reduction); black box contraindication in patients with personal or family history of Medullary Thyroid Carcinoma or MEN 2.
28	What is the nephron site of action and cardiorenal benefits of SGLT2 inhibitors (e.g. Empagliflozin, Dapagliflozin)?	Inhibit the Sodium-Glucose Cotransporter 2 in the proximal convoluted tubule, blocking ~90% of glucose reabsorption to produce glucosuria and natriuresis; proven to reduce heart failure hospitalizations, slow progression of chronic kidney disease, and reduce cardiovascular mortality in T2D.
29	What sensory modalities are lost first in diabetic sensorimotor polyneuropathy, and what physical exam tool screens for foot ulcer risk?	Small unmyelinated fibers (burning pain and temperature loss) and large myelinated fibers (vibration sense via 128-Hz tuning fork and ankle reflexes) are lost in a symmetric 'stocking-glove' distribution; screened annually using the 10-gram Semmes-Weinstein monofilament to detect loss of protective sensation.
30	What is the classic clinical paroxysmal triad of Pheochromocytoma, and what tissue gives rise to this tumor?	Adrenal medullary chromaffin cells (derived from neural crest); presents with paroxysmal or sustained hypertension accompanied by the classic triad of: 1) Episodic pounding Headache; 2) Profuse diaphoresis (Sweating); 3) Palpitations / Tachycardia.
31	What are the four formal ADA diagnostic laboratory criteria for Diabetes Mellitus?	1) Fasting plasma glucose >= 126 mg/dL (after 8-hr fast); 2) 2-hour plasma glucose >= 200 mg/dL during a 75 g OGTT; 3) Hemoglobin A1c >= 6.5%; 4) In a patient with classic symptoms of hyperglycemia (polyuria, polydipsia, weight loss), a random plasma glucose >= 200 mg/dL.
32	What proto-oncogene mutation and clinical triad define Multiple Endocrine Neoplasia Type 2A (MEN 2A / Sipple Syndrome)?	Autosomal dominant gain-of-function mutation in the RET proto-oncogene on chromosome 10; Triad of '1 M, 2 Ps': 1) Medullary Thyroid Carcinoma (100%, calcitonin-secreting); 2) Pheochromocytoma (~50%, frequently bilateral); 3) Parathyroid hyperplasia (~20-30%).