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USMLE Step 1 High‐Yield Endocrine Topics
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Endocrine
High Yield USMLE Step 1 Notes
Welcome to the Endocrine High-Yield Notes for Step 1.
These are the most commonly tested topics on the exam—ideal for quick review in your last 2 weeks before the exam, when you’re short on time, or when you’re just starting out and want to focus on what is high yield. Created and peer-reviewed by physicians who scored 260+ on Step 1 in a Q&A style to reinforce active learning.
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Table of Contents
Adrenal gland
1. A 32-year-old man presents with fatigue, hypotension, and eosinophilia. Labs show hyponatremia and hyperkalemia. What best explains these findings?
➔ Primary adrenal insufficiency (Addison’s disease)
- Note: Due to destruction of the adrenal cortex (autoimmune, TB if immigrant, metastatic cancer, such as melanoma).
- Leads to low cortisol and aldosterone → hyperkalemia, hyponatremia, hypotension. ACTH is elevated, causing hyperpigmentation.
2. A patient has low cortisol, low androgens, but normal aldosterone. What is the most likely explanation for this presentation?
➔ Secondary adrenal insufficiency
- Note: Caused by low ACTH (e.g., pituitary dysfunction). Aldosterone is preserved because it’s controlled by the renin-angiotensin system.
- No hyperkalemia or hyperpigmentation.
3. The previous patient developed meningococcal sepsis. What is the next step in management?
➔ Emergency requiring IV steroids and antibiotics
- Note: Adrenal hemorrhage due to Neisseria meningitidis sepsis “Waterhouse-Friderichsen syndrome”.
- Leads to acute adrenal insufficiency and shock.
4. A patient has hypertension. The exam reveals an abdominal bruit. What is the most likely etiology?
➔ Renal artery stenosis
- Note: Decreased renal perfusion triggers renin release → secondary hyperaldosteronism.
- If the patient <40, think fibromuscular dysplasia. If >40, think atherosclerosis.
- Another key: creatinine rises after starting lisinopril due to a decrease in GFR. Suspect also in resistant hypertension.
5. A hypertensive man has low potassium and low renin. What is the treatment?
➔ Eplerenone or spironolactone
- Note: Primary hyperaldosteronism (Conn syndrome); Adrenal adenoma or bilateral hyperplasia. Aldosterone ↑ → sodium retention, potassium loss, suppressed renin.
- Confirm with the aldosterone-to-renin ratio.
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6. A neonate has ambiguous genitalia, hypoglycemia, and hyperkalemia. What condition best explains these findings?
➔ 21-hydroxylase deficiency
- Note: Most common congenital adrenal hyperplasia. Impaired cortisol and aldosterone synthesis, with shunting to androgens.
- Labs show ↑ 17-hydroxyprogesterone.
7. A hypertensive female has hypokalemia, hypoglycemia, and ambiguous genitalia. Which enzyme is deficient in this patient?
➔ 11-beta hydroxylase deficiency
- Note: Excess 11-deoxycorticosterone acts like aldosterone.
- Labs: low renin, high 11-deoxycorticosterone, high androgens.
| Enzyme Deficiency | Aldosteron | Cortisol “hypoglycemia” | Sex Hormones | BP | K | Labs | Presentation |
|---|---|---|---|---|---|---|---|
| 17α-hydroxylase | ↑ | ↓ | ↓ | ↑ | ↓ | – | XY: ambiguous genitalia. |
| 21-hydroxylase “Most common” | ↓ | ↓ | ↑ | ↓ | ↑ | ↑ 17-hydroxyprogesterone | XX: ambiguous genitalia. |
| 11β-hydroxylase | ↓ aldosterone | ↓ | ↑ | ↑ | ↓ | ↑ 11-deoxycorticosterone | XX: virilization |
8. An older smoker has a cough, hemoptysis, and Cushingoid features. What is the most likely etiology?
➔ Ectopic ACTH production (e.g., small cell lung cancer)
- Note: ACTH stimulates cortisol → Cushing syndrome, hyperpigmentation, and metabolic alkalosis.
- Labs show ↑ cortisol and ↑ ACTH that do not suppress with high-dose dexamethasone.
9. A woman with chronic RA on steroids has moon facies and abdominal striae. What condition best explains these findings?
➔ Exogenous Cushing syndrome
- Note: ↓ ACTH and CRH due to negative feedback, and no hyperpigmentation. Aldosterone is normal.
10. A patient has episodic headaches, palpitations, and high blood pressure. What is the most likely explanation for this presentation?
➔ Pheochromocytoma
- Note: Diagnose with 24-hour urine metanephrines or plasma metanephrines.
- Start alpha-blocker (phenoxybenzamine), then beta-blocker. Giving BB before alpha blockers can lead to a hypertensive crisis during surgery.
11. A child has an abdominal mass crossing midline, opsoclonus-myoclonus, and elevated VMA and HVA. What condition best explains these findings?
➔ Neuroblastoma
- Note: Adrenal medulla tumor in children. Originates from neural crest cells.
- Associated with N-myc amplification. Elevated catecholamine metabolites in urine. “That is asked much with both Pheochromocytoma and Neuroblastoma.”
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PTH & Vitamin D & Ca
12. A young man has high calcium, low phosphate, and subperiosteal bone resorption. What is the most likely etiology?
➔ Primary hyperparathyroidism
- Note: Caused by parathyroid adenoma or hyperplasia. PTH increases calcium, decreases phosphate, and leads to bone breakdown.
- Subperiosteal bone resorption and bone cysts may be seen on X-ray
- The resulting hypercalcemia causes kidney stones and abdominal pain due to constipation.
13. An elderly smoker has hypercalcemia with suppressed PTH. What is the most likely etiology?
➔ PTHrP secretion from squamous cell carcinoma
- Note: PTH-related peptide mimics PTH actions but suppresses endogenous PTH. also seen in renal cell carcinoma.
14. A patient with chronic kidney disease has bone pain and elevated alkaline phosphatase. What condition best explains these findings?
➔ Secondary hyperparathyroidism
- Note: CKD leads to phosphate retention and low calcium → triggering high PTH. Labs: low calcium, high phosphate, high PTH.
15. An African American patient presents with a dry cough, hypercalcemia, and suppressed PTH. What is the most likely explanation for this presentation?
➔ Sarcoidosis (hypervitaminosis D)
- Note: Granulomas activate vitamin D → increases calcium absorption. Labs: high calcium, low PTH, elevated 1,25(OH)₂ vitamin D.
- Noncaseating granulomas on biopsy. Treated with steroids.
16. A woman with metastatic breast cancer presents with elevated calcium. What condition best explains these findings?
➔ Osteolytic bone metastases
- Note: Common cause of hypercalcemia in malignancy. Local bone destruction releases calcium. Seen in breast, lung, and multiple myeloma.
- Labs: high calcium, low PTH, normal or low PTHrP.
17. A man develops muscle cramps and facial twitching after thyroid surgery. What condition best explains these findings?
➔ Hypoparathyroidism
- Note: Accidental removal of parathyroid glands during thyroidectomy. Leads to low PTH, hypocalcemia. Signs include Chvostek and Trousseau signs.
- Requires calcium and vitamin D supplementation.
18. An alcoholic has persistent low calcium and potassium despite replacement. What is the most likely etiology?
➔ Hypomagnesemia
- Note: Low magnesium impairs PTH release and action → secondary hypocalcemia. Also causes renal potassium wasting.
- Must correct magnesium to normalize calcium and potassium.
19. A child has bowed legs, craniotabes, and costochondral thickening. What condition best explains these findings?
➔ Rickets (vitamin D deficiency)
- Note: Defective mineralization of osteoid in growing bones. Common in malnutrition, lack of sun exposure.
- Other signs include rachitic rosary, frontal bossing, and widened growth plates.
GH & Prolactin
20. A postpartum woman fails to lactate and has fatigue. Labs show low ACTH and TSH. What best explains these findings?
➔ Pituitary infarction due to postpartum hemorrhage, Sheehan syndrome
- Note: It causes failure of lactation (low prolactin), amenorrhea, hypothyroidism, constipation and fatigue, and adrenal insufficiency.
21. A woman presents with amenorrhea, galactorrhea, and headache. What is the most likely explanation for this presentation?
➔ Prolactinoma
- Note: Most common pituitary adenoma. Elevated prolactin inhibits GnRH → ↓ LH/FSH → amenorrhea, and infertility. Headache from mass effect.
- Treat with dopamine agonists (cabergoline or bromocriptine).
- Note: High TRH in primary hypothyroidism stimulates prolactin release.
22. A woman with schizophrenia on risperidone develops amenorrhea. What condition best explains these findings?
➔ Antipsychotic-induced hyperprolactinemia
- Note: Risperidone blocks dopamine → increases prolactin. Common side effects include galactorrhea, amenorrhea, and sexual dysfunction.
23. A man presents with coarse facial features, diabetes, and large hands. IGF-1 is elevated. What is the most likely explanation for this presentation?
➔ Acromegaly
- Note: GH-secreting pituitary adenoma. IGF-1 promotes the growth effects of GH. Produced mainly in the liver. Responsible for bone and tissue growth.
- Measure IGF-1 as a screening. Confirm with an oral glucose suppression test. GH does not suppress in acromegaly.
- Cardiomyopathy is the leading cause of mortality.
24. A woman presents with episodic flushing, diarrhea, and a right-sided heart murmur. What condition best explains these findings?
➔ Carcinoid syndrome
- Note: Caused by serotonin-secreting neuroendocrine tumor, often from small intestine. Symptoms appear only after liver metastasis. Right-sided heart lesions occur due to serotonin in systemic circulation.
- Urine shows elevated 5-HIAA.
Thyroid Gland
25. A woman presents with bradycardia, depression, and menorrhagia. The patient has dry skin, delayed reflexes, constipation, and high CK. What is the diagnosis?
➔ Hypothyroidism
- Note: Common symptoms include fatigue, cold intolerance, weight gain, and menstrual irregularities. Elevated CK indicates myopathy. Reflexes show a delayed relaxation phase
26. A hypothyroid woman on levothyroxine becomes pregnant. What should be done?
➔ Increase the levothyroxine dose
- Note: Estrogen increases TBG, requiring more T4 to maintain free levels.
27. A woman presents with amenorrhea, high TSH, low T4, and lymphocytic infiltrate on thyroid biopsy. What is the most likely etiology?
➔ Hashimoto thyroiditis
- Note: The most common cause of hypothyroidism. Associated with anti-TPO and anti-thyroglobulin antibodies. Decreased radioactive iodine uptake.
- Untreated Hashimoto leads to thyroid lymphoma, an enlarging neck mass with dysphagia and hoarseness of voice.
28. A postpartum woman has fatigue and high TSH with low T4. She has painless thyroid enlargement and suppressed TSH. What is the most likely etiology?
➔ Postpartum thyroiditis
- Note: Autoimmune inflammation. May present with hyperthyroidism that ends with hypothyroidism.
- Reduced radioactive iodine uptake. Usually resolves spontaneously.
29. A woman presents with a painful thyroid, elevated ESR, and low radioactive iodine uptake following a recent viral illness. What condition best explains these findings?
➔ Subacute thyroiditis (de Quervain
- Note: Granulomatous inflammation on biopsy. Hyperthyroid phase followed by hypothyroid and recovery. Pain and tenderness are keywords.
30. A woman on lithium develops fatigue, constipation, and weight gain. What condition best explains these findings?
➔ Lithium-induced hypothyroidism
- Note: Amiodarone can cause the same presentation in an arrhythmia patient.
31. A patient with atrial fibrillation, hand tremors, and weight loss. What is the most likely explanation for this presentation?
➔ Hyperthyroidism
- Note: Increased beta-adrenergic tone. May present with palpitations, heat intolerance, and anxiety. CVS symptoms treated with BB
32. A patient has weight loss, tremor, exophthalmos, and a thyroid scan with diffusely increased RAIU. What is the most likely etiology?
➔ Graves’ disease
- Note: Autoimmune stimulation of TSH receptors by thyroid-stimulating immunoglobulins. Labs show low TSH, high T3/T4. Associated with pretibial myxedema and orbitopathy.
- ➔ Exogenous thyroxine use Note suppresses TSH. The thyroid gland is small due to a lack of stimulation. Low thyroglobulin level helps differentiate from endogenous causes.
33. A woman treated with methimazole or PTU develops fever and sore throat. What is the diagnosis?
➔ Agranulocytosis
- Note: Stop the drug immediately and start broad-spectrum antibiotics.
34. A thyroid nodule biopsy shows Orphan Annie nuclei or psammoma bodies. What is the most likely etiology?
➔ Papillary thyroid carcinoma
- Note: Histology: nuclear grooves
- Follicular thyroid carcinoma shows capsular and vascular invasion.
35. A woman with a thyroid mass has calcitonin-positive staining or Congo red positivity. What condition best explains these findings?
➔ Medullary thyroid carcinoma
- Note: Arises from parafollicular C cells. Produces calcitonin.
- May show amyloid deposits. Associated with MEN 2A/2B. Screen RET mutations.
36. A post-thyroidectomy patient presents with hoarseness and hypocalcemia. What condition best explains these findings?
➔ Recurrent laryngeal nerve injury and hypoparathyroidism
- Note: Hoarseness due to nerve damage; hypocalcemia due to removal or damage to parathyroid glands.
37. A child has a midline neck mass that moves with swallowing. What is the diagnosis?
➔ Thyroglossal duct cyst
- Note: Result of failure to involute thyroglossal tract.
38. A neonate presents with macroglossia, hypotonia, and umbilical hernia. What is the most likely explanation for this presentation?
➔ Cretinism (congenital hypothyroidism)
- Note: Most commonly due to thyroid dysgenesis. Also causes constipation, delayed milestones, and enlarged fontanelles.
- Neonatal screen with TSH and T4. Early treatment prevents intellectual disability.
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MEN
39. A man presents with recurrent peptic ulcers and kidney stones. What is the most likely etiology?
➔ MEN 1 (Multiple Endocrine Neoplasia type 1)
- Note: Involves the 3 Ps — Parathyroid adenomas, Pancreatic tumors (e.g., gastrinomas causing Zollinger-Ellison syndrome), and Pituitary adenomas (e.g., prolactinomas). Caused by a mutation in the MEN1 (menin) gene.
40. A woman has episodic hypertension and a thyroid mass. What is the diagnosis?
➔ MEN 2A
- Note: Characterized by medullary thyroid carcinoma, pheochromocytoma, and parathyroid hyperplasia. Associated with the RET proto-oncogene mutation. Prophylactic thyroidectomy is recommended.
- MEN 2B Includes medullary thyroid carcinoma, pheochromocytoma, and mucosal neuromas (on lips, tongue). No parathyroid involvement. Also caused by a RET mutation. Features include long limbs, joint laxity, and a high-arched palate.
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ADH
41. What is the mechanism of action of ADH in the kidney?
➔ ADH binds V2 receptors → inserts aquaporin-2 channels in the collecting duct
- Note: Promotes water reabsorption in the medullary collecting duct, concentrating the urine and reducing serum osmolality.
42. An elderly patient presents with cough, hemoptysis, and hyponatremia. What is the most likely etiology?
➔ Small cell lung carcinoma
- Note: Produces ectopic ADH ➞ SIADH. Leads to dilutional hyponatremia with low serum osmolality and inappropriately concentrated urine. Labs: low serum Na, low serum osmolality, high urine Na, and osmolality.
- Common after CNS or lung pathology. Leads to water retention and euvolemic hyponatremia.
- Treat with fluid restriction or vasopressin antagonists as conivaptan.
43. A man develops hyponatremia following subarachnoid hemorrhage. What condition best explains these findings?
➔ SIADH (syndrome of inappropriate ADH secretion)
- Note: Common after CNS or lung pathology. Leads to water retention and euvolemic hyponatremia.
- Labs: low serum Na, low serum osmolality, high urine Na, and osmolality.
44. A man with head trauma develops polyuria and hypernatremia. What is the diagnosis?
➔ Central diabetes insipidus
- Note: Deficiency of ADH due to hypothalamic or pituitary injury. Labs show high serum osmolality, low urine osmolality. Treat with desmopressin (DDAVP).
45. A bipolar patient on lithium presents with polyuria and dilute urine. What is the most likely etiology?
➔ Nephrogenic diabetes insipidus
- Note: Kidneys are resistant to ADH. Labs show high serum osmolality, low urine osmolality.
- Does not respond to desmopressin. Treat with thiazide.
Insulin & Glucagon & DM
46. A patient on IV glucose has an insulin rise than with oral glucose. What is the explanation?
➔ Incretin effect (GLP-1, GIP)
- Note: Oral glucose stimulates more insulin due to incretins—GLP-1 and GIP—which enhance insulin release and inhibit glucagon.
- GLP-1 agonists enhance insulin release, delay gastric emptying, and suppress appetite. Examples: liraglutide, semaglutide.
47. Through which receptor does insulin mediate glucose uptake in muscle and fat?
➔ GLUT-4
- Note: Insulin-dependent. In contrast, glucose uptake in pancreatic β-cells and the liver uses GLUT-2, which is insulin-independent.
48. A child presents with polyuria, polydipsia, and weight loss. What is the diagnosis?
➔ Type 1 diabetes mellitus
- Note: Lymphocytic infiltrate and anti-islet cell antibodies.
- Usually presents acutely in childhood. May first appear with DKA.
- Type 2 tends to occur in obese adults, associated with amyloid deposition in the pancreas.
49. A pregnant woman delivers a large baby with neonatal hypoglycemia. What condition best explains these findings?
➔ Gestational diabetes mellitus
- Note: Due to insulin resistance from human placental lactogen (HPL).
- Maternal hyperglycemia stimulates fetal islet cell hyperplasia and insulin production. After delivery, insulin remains high while glucose supply drops ➞ hypoglycemia.
50. What triggers insulin release from pancreatic β-cells?
➔ Glucose metabolism → ↑ ATP → Ca²⁺ influx → insulin exocytosis
- Note: ATP-sensitive K⁺ channels close, depolarizing the membrane and allowing Ca²⁺ entry.
- Same as the sulfonylurea mechanism of action!
- Note: The Kidney is a major site of insulin degradation. Dose reduction is necessary to prevent hypoglycemia.
51. A diabetic patient was brought to the emergency department with hypoglycemia. He has high insulin, high C-peptide, and a negative sulfonylurea screen. What is the most likely explanation for this presentation?
➔ Insulinoma
- Note: Endogenous insulin-producing tumor. Presents with hypoglycemia, neuroglycopenic symptoms, and fasting episodes. High C-peptide is the key!
- Low C-peptide and a negative sulfonylurea screen confirm exogenous insulin use.
- If the patient abuses sulfonylurea, then the sulfonylurea screen would be positive and C-peptide will be high
52. A DM patient has HbA1C of 7, fasting glucose of 100 mg/dL, and postprandial glucose of 310 mg/dL. What is the next step?
➔ Add rapid-acting insulin
- Note: Controls post-meal spikes. Options include Lispro, Aspart, and Glulisine.
53. A woman on metformin develops rising creatinine. What is the next step?
➔ Discontinue metformin
- Note: Risk of lactic acidosis increases with impaired renal function. Check eGFR before continuing.
- When you see metformin in the question, look at BUN and Creatinine.
- TZDs cause fluid retention and can worsen heart failure. Contraindicated in CHF.
54. A man with T2DM and recurrent UTIs is on a new glucose-lowering drug. What is the likely medication?
➔ SGLT2 inhibitor
- Note: Increases renal glucose excretion. Side effects: UTIs, vagina candida infections, volume depletion. Examples: empagliflozin, dapagliflozin.
55. An elderly T2DM patient is confused, severely dehydrated, and glucose >600 mg/dL. What is the diagnosis?
➔ Hyperosmolar hyperglycemic state (HHS)
- Note: No ketosis, “HCO3 will be normal” due to some insulin activity. Treat with fluids, insulin, and electrolyte correction.
56. A child presents with abdominal pain, fruity breath, and Kussmaul breathing. What is your next step?
➔ IV fluids, insulin, and potassium
- Note: Diabetic ketoacidosis (DKA); Glucose usually <600 mg/dL. Labs show low bicarb, high anion gap, and hyperkalemia despite low total body K⁺.
- Monitor for hypokalemia during therapy. Resolution is indicated by ↓ ketones and anion gap.
57. A man with T2DM reports early satiety, weight loss, and heartburn. What is the diagnosis?
➔ Gastroparesis
- Note: Autonomic neuropathy affecting GI motility. Diagnose with a gastric emptying study. Treat with metoclopramide or erythromycin.
- Chronic DM can also cause diabetic nephropathy, “KW nodules”.
58. Fundoscopic findings in a noncompliant diabetic patient?
➔ Microaneurysms, hemorrhages, hard exudates
- Note: Signs of nonproliferative diabetic retinopathy. Control glucose and blood pressure. Screen annually.
- Note: Coronary artery disease is the most common cause of death in diabetics
59. Which hormone is elevated during prolonged fasting?
➔ Glucagon
- Note: Maintains blood glucose via hepatic gluconeogenesis and glycogenolysis. Stimulated by low glucose.
- Stimulated by: low glucose, catecholamines.
- Inhibited by: insulin, somatostatin, amylin, and high glucose.
60. A diabetic presents with a necrolytic rash and depression. What is the diagnosis?
➔ Glucagonoma
- Note: pancreatic α-cell tumor. Causes hyperglycemia, weight loss, and necrolytic migratory erythema. Diagnose with elevated glucagon levels.
- New DM in a thin old man is classic!
61. A hypoglycemic diabetic is unconscious. What is the next step?
➔ Give intramuscular glucagon
- Note: Glucagon raises blood glucose by promoting hepatic glucose release. If conscious, give oral glucose.
62. A fasting patient has increased appetite and gastric motility. Which hormone is high?
➔ Ghrelin
- Note: Secreted by the stomach. Stimulates hunger and gastric motility. Acts on the hypothalamus.
- Ghrelin is abnormally elevated in Prader-Willi. It contributes to excessive hunger and early-onset obesity. It decreases with gastrectomy.
- Leptin acts on the hypothalamus to suppress appetite. Levels correlate with fat mass. Leptin resistance is a common feature of obesity.
63. What are the hormonal levels during dieting or starvation?
➔ High ghrelin, low leptin, and low insulin
- Note: Ghrelin rises to stimulate appetite. Leptin and insulin fall due to reduced fat and glucose availability.
64. What type of receptor does insulin use?
➔ Tyrosine kinase receptor
- Note: Leads to autophosphorylation and downstream effects like glucose uptake (via GLUT-4), glycogen synthesis, and lipogenesis.
65. What signaling pathway does glucagon use?
➔ Gs protein → ↑ cAMP
- Note: Activates protein kinase A. Promotes glycogenolysis, gluconeogenesis, and lipolysis in the liver.
- ADH also ⇑ cAMP Increases aquaporin-2 insertion in the collecting duct ➞ water reabsorption and urine concentration.
66. What receptor do oxytocin and vasopressin (V1) use for vasoconstriction?
➔ Gq protein → IP3/DAG pathway
- Note: V1 receptor mediates vasoconstriction via smooth muscle contraction. Oxytocin uses similar Gq signaling for uterine contraction and milk letdown.
67. Which hormones use intracellular steroid receptors?
➔ Cortisol, aldosterone, testosterone, estrogen, progesterone, vitamin D, T3/T4
- Note: These hormones are lipophilic and cross the cell membrane to bind nuclear receptors, altering gene transcription.
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🏁 Final Thoughts
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Disclaimer
Version 1.0 May 2025. No part of this document may be reproduced or distributed without written permission. For personal study only. Medical information herein is for educational purposes and does not constitute clinical advice. Always confirm with current guidelines and your institution’s policies.
Prefer a narrative review instead of Q&A style? Scroll down to the section below for high-yield concepts in paragraph format (they cover the same concepts).
Narrative Format
High-Yield Endocrine Topics
High-yield Endocrine review for USMLE Step 1. Master key hormones, their regulation, associated diseases (Diabetes, Thyroid, Adrenal, Parathyroid), and common testing points.
Table of Contents
- Insulin
○ Diabetes Mellitus
○ Diabetes Mellitus Complications
○ Oral Hypoglycemics for Type 2 DM - Parathyroid Hormone (PTH)
○ Hyperparathyroidism
○ Hypoparathyroidism - Antidiuretic Hormone (ADH)
- Prolactin
- Growth Hormone
- Adrenal Gland
○ Adrenal Cortex
○ Congenital adrenal hyperplasia (CAH)
○ Adrenal Medulla - Thyroid Gland
○ Hypothyroidism
○ Hyperthyroidism
○ Thyroid Cancer - Pancreatic Tumors
- Multiple Endocrine Neoplasia (MEN)
- Signaling Pathways of Endocrine Hormones
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Insulin
Synthesized as preproinsulin, then proinsulin, then cleaved into insulin + C-peptide. Released in response to ↑ Blood glucose (most potent stimulus), ↑ Amino acids, and Incretins (GLP-1, GIP, released after meals, enhance insulin secretion). Inhibited by ↓ Blood glucose, Somatostatin. Cleared by kidneys.
How is it tested: 1. DM patient with CKD having recurrent hypoglycemic episodes: decrease insulin dose. 2. Oral glucose increases blood insulin more than IV glucose? due to GLP release
3. C-peptide level comes in arrows questions; low with exogenous insulin and high with insulinoma, and Sulfonylureas use.
Insulin acts via a receptor tyrosine kinase:
- ↑ GLUT-4 insertion in skeletal muscle & adipose tissue (insulin-dependent uptake). ↑ Glycogenesis (stimulates glycogen synthase) and ↓ Gluconeogenesis and inhibits glucagon.
- ↑ Lipogenesis, ↓ Lipolysis and Ketogenesis increasing BMI.↑ Protein synthesis(anabolic effect). Increased cellular uptake of K.
Insulin release:
Glucose enters β cells via GLUT-2 and undergoes glycolysis, releasing ATP that closes K channels leading to activating Voltage-gated Ca2+ channels and Ca2+ influx and stimulation of insulin exocytosis.
How is it tested: very common biochemistry questions comparing between effect of fasting state” ↑ insulin” vs fed state “↑ glucagon” on different metabolic pathways and their enzymes, ex: insulin increases glycolysis.
Diabetes Mellitus
Type 1 DM:
- Autoimmune destruction of β-cells (HLA-DR3/DR4), leukocyte infiltrate and autoantibodies (islet cell Abs)→ insulin deficiency and “C-peptides” → Polyuria, polydipsia, weight loss, DKA risk.
Treatment: Lifelong insulin therapy “Long-acting (Glargine, Detemir) + Rapid-acting (Lispro, Aspart, Glulisine) for postprandial control
How is it tested: a child with weight loss, polyuria, and polydipsia. His situation is associated with? leukocyte infiltrate and autoantibodies
Type 2 DM (T2DM):
Visceral obesity and genetic predisposition leading to Insulin resistance, amyloid deposits in the pancreas. “↑ Insulin (early),↑ C-peptide”.
Gestational DM leads to fetal hyperinsulinemia due to B islet cell hyperplasia and macrosomia and neonatal transient hypoglycemia.
How is it tested: A neonate presents with irritability, crying, and jitteriness. Blood glu is low/ his mother had GDM. What is the pathology; islet cell hyperplasia.
Diabetes Mellitus Complications
Nonenzymatic Glycation:
- Microangiopathy → Hyaline arteriolosclerosis causes:
○ Diabetic retinopathy (nonproliferative: hemorrhages, hard exudates; proliferative: neovascularization).
○ Diabetic nephropathy (nodular glomerulosclerosis → Kimmelstiel-Wilson nodules, proteinuria, ESRD).
○ Diabetic neuropathy. - Macroangiopathy → atherosclerosis leads to:
○ Coronary artery disease (CAD) → Myocardial infarction (most common cause of death in diabetics).
○ Cerebrovascular disease → Stroke.
○ Peripheral vascular disease (PVD) → Claudication, ulcers “ at the sole of the foot”.
How is it tested: a patient with uncontrolled DM with multiple complications. Adequate glucose control would prevent which symptoms? Prevents microangiopathy not macroangiopathy.
Osmotic Damage (Sorbitol Accumulation)
- Neuropathy:
○ Sensory & motor neuropathy (distal symmetric polyneuropathy in “glove-and-stocking” pattern).
○ Autonomic dysfunction (gastroparesis, GERD, diabetic diarrhea, orthostatic hypotension, erectile dysfunction). - Cataracts
Oral Hypoglycemics for Type 2 DM
Metformin, First Line for T2DM
- Mechanism: ↓ Hepatic gluconeogenesis, ↑ glycolysis and glu uptake by cells. No hypoglycemia or weight loss.
- Side Effects: Lactic acidosis (avoid in renal failure, stop if GFR <30), B12 deficiency.
How it is tested: they will give you a DM patient on metformin who has CKD or high creatinine. Stop metformin to avoid lactic acidosis.
Sulfonylureas (Glipizide, Glyburide, Glimepiride)
Close K⁺ channels in β-cells → Depolarization → Ca²⁺ influx → Insulin release “v c-peptide”. Side Effects similar to insulin: Hypoglycemia (esp. in renal failure), and weight gain.
How is it tested: a female with multiple emergency department visits has hypoglycemia, with a low c-peptide level. A common scenario for factitious disorder (Exogenous Insulin).
GLP-1 Agonists “Liraglutide, Exenatide, Dulaglutide, Semaglutide”
Mechanism: ↑ Insulin, ↓ Glucagon, slows gastric emptying, promotes satiety and ↓Weight.
How is it tested: 1. A T2DM patient desiring weight loss. describe a GLP-1 agonist. 2. Oral glucose increases insulin release more than iv glucose.
SGLT2 Inhibitors “Empagliflozin, Canagliflozin, Dapagliflozin” Block SGLT2 in the proximal tubule → ↑ Glucose excretion in urine. Weight loss, BP reduction, renal & CV protection (esp. in CKD, CHF).
Side Effects: Recurrent UTIs and fungal infections.
How is it tested: A patient with T2DM and HF, which drugs should be prescribed?
6. Thiazolidinediones “Pioglitazone, Rosiglitazone”
↑ Insulin sensitivity via PPAR-γ activation → ↑ GLUT-4 expression.
Side Effects: Weight gain, edema, heart failure exacerbation.
How is it tested: A T2DM patient with CHF should avoid TZDs due to fluid retention.
Diabetic Ketoacidosis (DKA)
- Pathophysiology: insulin deficiency in DM 1→ ↑ Lipolysis → ↑ Free fatty acids → Ketogenesis → Anion gap metabolic acidosis. Triggered by Infection and stress.
- Symptoms: Polyuria, polydipsia, abdominal pain, Kussmaul breathing, fruity breath (acetone), and altered mental status.
- Labs: ↑ Ketones, metabolic acidosis (low pH, low HCO₃⁻), hyperkalemia (but total body K⁺ depleted).
- Treatment: IV fluids, Insulin “IV regular”, and K⁺ replacement.
How is it tested: A child with polyuria, deep rapid breathing, hyperglycemia, and fruity breath. In addition to treating with insulin and fluids, we should give K.
Hyperosmolar Hyperglycemic State (HHS)
- Pathophysiology: Severe hyperglycemia → Osmotic diuresis → Dehydration (no ketones, no acidosis). Polyuria, polydipsia, confusion, severe dehydration.
- Labs: Glucose >600 mg/dL, high serum osmolality (>320 mOsm/kg), no ketones.
- Treatment: IV fluids, Insulin, and K⁺ replacement.
How is it tested: An elderly diabetic patient with confusion, dehydration, and hyperglycemia → HHS, treated as DKA.
Hypoglycemia: Sweating, tremors, palpitations, confusion, seizures. Treat by Oral glucose if awake, IV dextrose or glucagon if unconscious. Be careful, BB mask symptoms of hypoglycemia.
How is it tested: A diabetic patient with confusion and tremors improves after drinking juice: hypoglycemia.
Parathyroid Hormone (PTH)
Released in response to low serum calcium, high phosphorus, or low vit D and acts to increase serum calcium and decrease phosphate levels:
- Bone resorption: Stimulates RANK-L activating osteoclasts “at high levels”.
- Kidney:
○ ↑ Ca²⁺ reabsorption in the distal tubule, ↓ Phosphate reabsorption in the proximal tubule.
○ ↑ 1α-hydroxylase activity → ↑ Calcitriol (1,25-(OH)₂ D₃) production, increasing gut Ca²⁺ and phosphate absorption.
Hyperparathyroidism
Primary Hyperparathyroidism: “Parathyroid adenoma (most common) or hyperplasia”
- Bones: Osteitis fibrosa cystica (subperiosteal bone resorption, brown tumors).
- Stones: calcium oxalate stones. Groans: Abdominal pain and constipation.
- Psychiatric Overtones: Depression, confusion, fatigue.
- ↑ PTH, ↑ Ca²⁺, ↓ Phosphate, ↑ ALP (bone turnover marker), ↑ cAMP in urine.
Treatment: parathyroidectomy.
How it is tested: 1. In a patient with high Ca, low P, next step is to check PTH to rule out primary hyperparathyroidism. 2. MEN 1, 2A scenarios; a patient with a history of resistant peptic ulcer disease presents with kidney stones symptoms, labs show ↑ Ca. Dx? MEN1
Secondary Hyperparathyroidism:
- Chronic kidney disease (CKD): ↓ 1α-hydroxylase activity → ↓ Calcitriol → ↓ Ca²⁺ absorption → ↑ PTH. Also, low Ca and high P.
Treatment: Vitamin D supplementation.
How is it tested: A patient with chronic kidney disease, what is the level of those labs; Ca, P, PTH, Vit D? ↑P, ↑ PTH, ↓ Ca, ↓ Vit D.
Hypoparathyroidism
Causes:
- Surgical removal (thyroid surgery, most common), Autoimmune, and DiGeorge syndrome (22q11.2 deletion, absent 3rd/4th pharyngeal pouches).
○ Tetany, perioral tingling, seizures.
○ Chvostek’s sign (facial twitch with tapping CN VII).
○ Trousseau’s sign (carpal spasm with BP cuff inflation). - ↓ PTH, ↓ Ca²⁺, ↑ Phosphate.
Treatment:
- Calcium and calcitriol (1,25-(OH)₂ D₃) supplementation.
How is it tested: A post-thyroidectomy patient with facial twitching and muscle spasms: hypoparathyroidism. Also, hoarsness of voice due to RLN injury.
PTH-Related Peptide (PTHrP)
PTHrP mimics PTH and causes hypercalcemia in malignancies (e.g., squamous cell lung cancer, renal cell carcinoma); ↑ Ca²⁺, ↓ PTH (suppressed by hypercalcemia), ↑ PTHrP.
How is it tested: A smoker with cough and weight loss with hypercalcemia and low PTH: squamous cell carcinoma producing PTHrP.
Antidiuretic Hormone (ADH)
Synthesized in the hypothalamus (SO and PVN ) and stored IN the posterior pituitary. Its primary function is to increase water reabsorption in the kidney’s collecting ducts via the V2 receptor in response to low blood volume or high osmolality (kidney, CAMP → aquaporin-2 insertion in collecting ducts).
Diabetes Insipidus (ADH Deficiency or Resistance)
Diabetes insipidus (DI) is characterized by polyuria, polydipsia, dilute urine (low urine osmolality), and hypernatremia.
- Central DI: ↓ ADH secretion due to hypothalamic (permanent DI) or pituitary (Transient DI) damage (e.g., trauma, Sheehan’s).
- Nephrogenic DI: Kidney resistance to ADH, often due to lithium toxicity.
Diagnosis:
- Water deprivation test:
○ In normal individuals or primary polydipsia, urine osmolarity increases.
○ In DI, urine remains dilute. - Desmopressin (DDAVP) test:
○ Central DI → Urine osmolality increases (responds to ADH).
○ Nephrogenic DI → No response (kidneys resistant to ADH).
Treatment:
- Central DI: Desmopressin (DDAVP, ADH analog). Nephrogenic DI: Thiazide diuretics.
How is it tested: A patient with polyuria, polydipsia, and dilute urine. Urine concentration increase after adding desmopressin: Central DI. if did not improve then Nephrogenic DI, a bipolar patient on Lithium complaining of polyurea.
SIADH (excess ADH)
- Small cell lung cancer (paraneoplastic ADH secretion, most common), also pneumonia.
- CNS disorders (stroke, trauma, infection, hemorrhage)
- Drugs (SSRIs, carbamazepine, cyclophosphamide, vincristine)
Euvolemic hyponatremia (dilutional) → Causes confusion, seizures, and coma. ↓ Serum osmolality, ↑ Urine osmolality
Treated by ADH antagonists (Conivaptan, Tolvaptan)
How is it tested: 1. An old smoker with a recent cough and weight loss has confusion, seizures, low sodium: SIADH from small cell lung cancer. 2. Another scinario for a patient with subarachnoid hemmorage, he was stabilized but labs show low sodium….. etc
Prolactin
Regulation of secretion:
- Dopamine (D2 receptors) from the hypothalamus inhibits the prolactin “tuberoinfundibular pathway”.
- TRH and estrogen (pregnancy, OCPs) stimulate prolactin.
- Breastfeeding stimulates prolactin via a neural reflex that inhibits dopamine release.
Prolactin inhibits GnRH, leading to low FSH/LH, causing amenorrhea, anovulation, and infertility in women and hypogonadism in men.
How is it tested: 1. A postpartum women who are breastfeeding experience natural contraception due to prolactin-induced suppression of GnRH. 2. Cutting pituitary stalk decreases all pitutary hormones except prolactin “low dopamin increases prolactin”.
2. Hyperprolactinemia
- Prolactinoma (most common pituitary adenoma)
- Dopamine antagonists (antipsychotics, metoclopramide)
- Hypothyroidism (↑ TRH stimulates prolactin release)
Symptoms:
- Women: Amenorrhea, galactorrhea (milky nipple discharge), infertility, ↓ libido.
- Men: Hypogonadism, gynecomastia, ↓ libido, erectile dysfunction.
- Compression effects: Bitemporal hemianopsia if large enough to press on the optic chiasm.
Diagnosed by Serum prolactin level (>200 ng/mL highly suggestive of prolactinoma), MRI of the brain to check for pituitary adenoma
Treated by Dopamine agonists (Cabergoline, Bromocriptine, first-line treatment), Surgery only if unresponsive to medical therapy
How is it tested: 1. For a woman with amenorrhea, galactorrhea, low FSH/LH, and headache, the next step is to check prolactin and MRI for prolactinoma. 2. a woman with schizophrenia who is stable on drugs complaining of amenorrhea and galactorrhea, high prolactin.
Growth Hormone
GH acts via the JAK-STAT signaling pathway, stimulating the liver to produce insulin-like growth factor-1 (IGF-1). IGF-1 mediates bone growth, protein synthesis, and muscle hypertrophy. GH also has anti-insulin effects, leading to increased gluconeogenesis, lipolysis, and decreased glucose uptake. It is stimulated by GHRH from the hypothalamus and is inhibited by somatostatin.
Acromegaly: “Excess GH, mostly due to pituitary adenoma”
Enlarged jaw, hands, feet, and frontal bossing, Macroglossia, deep voice. Insulin resistance (diabetes), hyperlipidemia, hypertension, HCM. Carpal tunnel syndrome, arthritis. Increased risk of colon polyps/cancer
IGF-1 levels are persistently high and used for screening. Diagnosis is confirmed by an oral glucose tolerance test (OGTT): GH remains elevated instead of suppressed.
Treated by Transsphenoidal resection of the pituitary adenoma, If surgery fails: Octreotide.
How is it tested: is a middle-aged man with joint stiffness, coarse facial features, and diabetes. 1. The next best step is? IGF-1 measurement, 2. Cause of death is? HCM.
Adrenal Gland
Adrenal Cortex
- Zona Glomerulosa → Produces Aldosterone, regulated by RAAS.
- Zona Fasciculata → Produces Cortisol, regulated by ACTH from the pituitary.
- Zona Reticularis → Produces Androgens (DHEA, androstenedione), regulated by ACTH.
How is it tested: arrows questions about hormonal regulations, for example a patient taking exogenous cortisol for an autoimmune disease, what is the level of ACTH, CRH, Aldosteron? ↓ ACTH,↓ CRH, normal Aldosteron.
Congenital adrenal hyperplasia (CAH)
- 21-hydroxylase deficiency (most common):
○ ↓ Aldosterone & Cortisol → Hypotension and hyperkalemia
○ ↑ Androgens → ambiguous genitalia and virilization in females - Diagnosis with: high 17 hydroxyprogesterone.
11β-hydroxylase deficiency:
↓ Aldosterone but ↑ 11-deoxycorticosterone (weak mineralocorticoid), ↑ Androgens → Hypertension, hypokalemia, virilization in females. - 17α-hydroxylase deficiency:
↓ Cortisol & Androgens, ↑ Aldosterone → Hypertension, hypokalemia, ambiguous genitalia in males, primary amenorrhea in females.
How is it tested: 1. a patient with hypotension, hyperkalemia, and elevated 17 hydroxyprogesterone/hirsutism; 21-hydroxylase deficiency
2. A female neonate with ambiguous genitalia and hypoglycemia/ hyperkalemia; 21-hydroxylase deficiency.
Cushing Syndrome
Hypertension, central obesity, moon facies, buffalo hump, osteoporosis, hyperglycemia, muscle weakness, striae, and neuropsychiatric as depression or irritability.
- Exogenous steroids (most common) → low ACTH.
- ACTH-secreting pituitary adenoma or small cell lung cancer → high ACTH.
How is it tested: arrows questions about hormonal regulations, for example a patient taking exogenous cortisol for an autoimmune disease, what is the level of ACTH, CRH.
Primary Adrenal Insufficiency (Addison’s Disease)
Caused by adrenal gland failure → ↓ Cortisol; Fatigue, hypoglycemia, and high esinophils. ↓Aldosterone; hypotension, hyperkalemia, and salt craving, weight loss, hyperpigmentation (due to high MSH due to high ACTH), hyperkalemia, and acidosis.
- Autoimmune, TB (most common worldwide), and Metastatic tumors.
- Waterhouse-Friderichsen syndrome (meningococcal sepsis, adrenal hemorrhage, shock).
Diagnosis: 8 am cortisol (↓), ACTH (↑), ACTH stimulation test (no cortisol rise).
Treatment: Glucocorticoid (hydrocortisone) + Mineralocorticoid (fludrocortisone) replacement.
How is it tested: A patient with hypothyroidism comes with low BP, hyperpigmentation, and hyperkalemia. → Primary adrenal insufficiency. Remember, autoimmune diseases go together.
Secondary & Tertiary Adrenal Insufficiency
- Secondary adrenal insufficiency: Pituitary dysfunction (low ACTH, low cortisol, normal aldosterone) → No hyperpigmentation, no hyperkalemia.
- Tertiary adrenal insufficiency: Chronic steroid use with abrupt withdrawal → Only affects cortisol. Do not stop cortisol suddenly → adrenal crisis.
How is it tested: A postpartum woman who had bleeding during delivery complains of fatigue, low BP, and hyperkalemia. “Sheehan’s”
Hyperaldosteronism
- Adrenal adenoma or bilateral adrenal hyperplasia leading to hypertension, hypokalemia, metabolic alkalosis, and low renin. Aldosterone ↑, Renin ↓.
Treatment: Aldosteron receptor blockers; Spironolactone or eplerenone. - Secondary hyperaldosteronism is due to renin excess due to RAAS activation (e.g., renal artery stenosis, CHF, cirrhosis). Aldosterone ↑, Renin ↑.
How is it tested: 1. In a hypertensive patient with low K⁺ and metabolic alkalosis, the next step is checking the aldosterone-renin ratio. 2. A patient with HF and edema, he is most likely to have? Low K due to RAAS activation
Adrenal Medulla
– Arises from neural crest cells and acts as a sympathetic ganglion releasing catecholamines in response to stress.
– Norepinephrine → Epinephrine (via phenylethanolamine N-methyltransferase [PNMT], upregulated by cortisol).
How is it tested: They ask why adrenal insufficiency leads to decreased epinephrine production and high NE.
Pheochromocytoma:
– Could be associated with (MEN2A, MEN2B, NF1, VHL)
– Patients present with episodic hypertension, headache, diaphoresis, and palpitations. These episodes are often triggered by exercise, stress, and surgery. Diagnosed by measuring plasma and urine metanephrines (vanillylmandelic and homovanillic acid).
– Before surgery, we treat it by α-blockers first (phenoxybenzamine) then β-blockers as giving a β-blocker before an α-blocker leads to unopposed α-mediated vasoconstriction → severe hypertensive crisis.
How is it tested: A patient with episodic HTN, headaches, sweating, and tachycardia → Suspect pheochromocytoma. Confirm with plasma metanephrines and treat with α-blockers before surgery.
Neuroblastoma
It arises from neural crest cells and is associated with N-MYC oncogene amplification and neuron-specific enolase. Patients present with abdominal mass and opsoclonus-myoclonus (“dancing eyes, dancing feet”). Homer-Wright rosettes on histology. Urine VMA/HVA levels are elevated.
How it is tested: A child with an abdominal mass crossing the midline, abnormal feet movements, and nystagmus→ Think neuroblastoma.
Thyroid Gland
Develops at the foramen cecum and descends via the thyroglossal duct (remnant may form a thyroglossal duct cyst).
How is it tested: a patient with midline tender neck mass that moves with tongue protrusion, what is the embryologic origin of the mass? thyroglossal duct
Thyroid Anatomy:
It has laryngeal nerves “recurrent and external” running near it making it liable to injury during thyroidectomy leading to hoarseness of voice.
Thyroid Hormone Physiology
- Regulation: TRH increases TSH, increasing T3,4. Too many arrow questions for “ primary and secondary hyper and hypothyroidism, and effect of exogenous levothyroxine on TSH and TRH”.
- Thyroid peroxidase enzyme is a key enzyme for thyroid synthesis, it helps oxidation, organification, and coupling of iodine. Inhibited by antithyroid drugs.
- Thyroid-binding globulin (TBG) binds T4 in blood.
○ ↑ TBG = Pregnancy, OCPs (↑E). ↓ TBG = Liver failure, nephrotic syndrome.
○ How it is tested: A patient taking levothyroxine for hypothyroidism planning to get pregnant; what is the next step? Increase levothyroxine dose.
Hypothyroidism
- Symptoms: Fatigue, weight gain, cold intolerance, bradycardia, HTN, constipation, myxedema (generalized nonpitting edema), muscle weakness, delayed reflexes, hyponatremia, carpal tunnel syndrome, high cholesterol, dementia, and depression.
How is it tested: a patient presents with dementia/ muscle weakness plus bradycardia/ hyporeflexia and weight gain.
○ Hashimoto thyroiditis
◼️ Anti-TPO, anti-thyroglobulin antibodies.
◼️ Histology: Lymphoid aggregates with germinal centers, Hurthle cells. Increased risk of non-Hodgkin lymphoma.
◼️ Decreased RAIU.
How is it tested: a patient with hypothyroidism and a neck mass, biopsy would show: lymphocytic infiltrate.
○ Subacute granulomatous thyroiditis (de Quervain’s):
◼️ Painful, tender thyroid following viral infection.
◼️ ↑ ESR, granuloma with multinucleated giant cells.
How is it tested: a patient with hypothyroidism and a tender painful neck mass, biopsy would show: granuloma with multinucleated giant cells.
○ Riedel thyroiditis:
◼️ Rock-hard, fibrotic thyroid; can compress trachea/esophagus.
◼️ Fibrosis can extend to local structures (IgG4-related disease).
○ Congenital hypothyroidism (Cretinism): mostly due to thyroid agenesis, normal at birth due to passage of maternal thyroid hormone through the placenta, if not treated it presents with mental retardation, short stature, coarse facial features, macroglossia, umbilical hernia.
○ Drugs such as amiodarone and lithium “both hypo and hyperthyroidism”. But most questions will ask about hypothyroidism.
How is it tested: A bipolar patient complains of constipation and fatigue: hypothyroidism due to Lithium
Hyperthyroidism
- Symptoms: Weight loss, heat intolerance, tachycardia “atrial fibrillation”, HTN, tremors, hyperreflexia, diarrhea, muscle weakness, osteoporosis ”d.t osteoclast activation”, high-output heart failure.
○ Graves’ Disease (most common):
◼️ Anti-TSH receptor antibodies (stimulating) → ↑ T3/T4 and goiter.
◼️ Exophthalmos, pretibial myxedema (fibroblasts express TSH receptors secreting glycosaminoglycans).
Thyroid Cancer
- Malignant (PAP-MF):
○ Papillary carcinoma (most common):
◼️ Orphan Annie eyes nuclei, psammoma bodies, nuclear grooves.
◼️ RET, BRAF mutations, associated with radiation exposure.
○ Follicular carcinoma:
○ Medullary carcinoma:
◼️ Parafollicular C cells → calcitonin. MEN 2A/2B (RET mutation).
◼️ Histology: Congo red stain → amyloid deposits.
How it is tested: You have a patient with a thyroid mass. biopsy shows nuclear grooving. Dx? Papillary thyroid cancer. Mutation? BRAF mutation
- Treatment:
○ Hypothyroidism: Levothyroxine (T4). Increase the dose if the patient is pregnant or taking OCPs.
○ Hyperthyroidism:
1. Beta Blockers “Propranolol”: decreases the conversion of T4 to T3 and controls sympathetic hyperactivity symptoms.
2. Thionamides “Propylthiouracil, methimazole”; Block thyroid peroxidase + decrease Peripheral conversion of T4 to T3. PTU in the first Trimester while Methimazole used in the second and third Trimester d.t teratogenicity. AE: agranulocytosis and hepatotoxicity.
How is it asked; a patient treated for hyperthyroidism now has a fever and sore throat. The next step is stopping all thyroid drugs and initiating broad-spectrum antibiotics.” neutropenia”
3. potassium iodide decreases the uptake of iodine.
Pancreatic Tumors
1. Zollinger-Ellison Syndrome (ZES) – Gastrinoma
- Multiple, recurrent, or refractory peptic ulcers to treatment (often in unusual locations like the jejunum).
- Diarrhea due to excess acid inactivating pancreatic enzymes.
- ↑ Serum gastrin (>1000 pg/mL) despite high gastric acid.
- Octreotide and Surgical resection.
How is it asked: A patient with recurrent ulcers in the jejunum, diarrhea, and high gastrin despite PPI therapy: Zollinger-Ellison syndrome.
2. Insulinoma
- Hypoglycemia symptoms (confusion, palpitations, sweating, tremors).improve with glucose administration.
- ↑ Insulin, ↑ C-peptide, ↑ Proinsulin (endogenous source).
- ↓ Blood glucose (<50 mg/dL) during fasting. Negative sulfonylurea screen
How is it asked: A patient with recurrent episodes of confusion, sweating, and low blood sugar, relieved by eating → Check insulin, C-peptide, and proinsulin for insulinoma.
3. Glucagonoma
- Necrolytic Migratory Erythema (NME) → Painful, pruritic, red-brown plaques with central clearing, New-onset diabetes mellitus, depression. Ttt by octreotide and surgical resection
How is it asked: A patient with diabetes, weight loss, and a rash with central clearing on the groin: glucagonoma.
4. Carcinoid Syndrome
Carcinoid tumors secrete serotonin (5-HT), most commonly arising in the small intestine, appendix, or lung. Symptoms occur only if the tumor metastasizes to the liver, as serotonin is usually metabolized in the liver.
- Flushing, diarrhea, and wheezing due to bronchospasm.
- right-sided valvular disease → tricuspid, pulmonic stenosis; left heart spared due to lung MAO-A breakdown of 5-HT.
- ↑ 24-hour urinary 5-HIAA (serotonin metabolite), Chromogranin A and synaptophysin (+) neuroendocrine markers.
Treated by Octreotide and Surgical resection if localized.
How is it asked: A patient with flushing, diarrhea, and right-sided heart murmur → Check 5-HIAA levels for carcinoid syndrome.
Multiple Endocrine Neoplasia (MEN)
MEN 1 (“3 P’s”), Mutation in MEN1 (Tumor suppressor)
- Pituitary adenoma (Prolactinoma or GH-secreting).
- Parathyroid hyperplasia (Primary hyperparathyroidism → hypercalcemia).
- Pancreatic tumors (Zollinger-Ellison, Insulinoma, Glucagonoma).
How is it asked: A patient with kidney stones, recurrent ulcers, and hypercalcemia: MEN1.
MEN 2A (“2 P’s, 1 M”), Mutation in RET proto-oncogene
- Medullary thyroid carcinoma. 2. Pheochromocytoma 3. Parathyroid hyperplasia
How is it asked: A patient with episodic HTN and headache, thyroid mass: MEN 2A.
MEN 2B (“1 P, 2 M’s”), Mutation in RET proto-oncogene
- Medullary thyroid carcinoma 2. Pheochromocytoma
- Mucosal neuromas + Marfanoid habitus (Thick lips, intestinal ganglioneuromas).
How it is asked: A tall patient with tongue nodules, thyroid cancer, and episodic HTN: MEN 2B.
Signaling Pathways of Endocrine Hormones
Created with BioRender.com
cAMP Pathway (G-protein coupled receptor → Adenylate cyclase → ↑ cAMP → PKA activation)
- Hormones: FSH, LH, ACTH, TSH, CRH, hCG, ADH (V₂ receptor), MSH, PTH, Calcitonin, Histamine (H₂ receptor), Glucagon, GHRH (FLAT ChAMPs CHuGG).
- Key: Used for rapid, short responses like metabolism, water balance, and stress.
cGMP Pathway (Guanylate cyclase → ↑ cGMP → Vasodilation)
- Hormones: BNP, ANP, NO.
- Key: Think about vasodilation and diuresis. (BAD GraMPa)
IP₃ Pathway (G-protein coupled receptor → Phospholipase C → IP₃ → Ca²⁺ release)
- Hormones: GnRH, Oxytocin, ADH (V₁ receptor), TRH, Histamine (H₁ receptor), Angiotensin II, Gastrin (GOAT HAG)
- Key: Used for muscle contraction, exocrine gland secretion, and hormone release.
Intracellular Receptors (Steroid & Thyroid Hormones)
- Hormones: (Progesterone, Estrogen, Testosterone), Cortisol, Aldosterone, T₃/T₄, Vitamin D and A (PET CAT in TV)
- Key: Lipophilic hormones regulate gene expression by binding nuclear receptors.
Receptor Tyrosine Kinase (MAP kinase pathway)
- Hormones: IGF-1, FGF, PDGF, EGF, Insulin
- Key: Growth factors and cell proliferation. (Get Found In the MAP)
Non-Receptor Tyrosine Kinase (JAK/STAT Pathway)
- Hormones: G-CSF, Erythropoietin, Thrombopoietin, Prolactin, Immunomodulators (IL-2, IL-6, IFN), GH (GET a JAKed PIG)
- Key: Think acidophils (GH, Prolactin) and cytokines (IL, IFN, EPO).
The most common in questions are ADH, Glucagon, NO, BNP, Oxytocin, lipophilic hormones, insulin, IGF-1
How it is asked: A woman presents with thirst and frequent urination with high plasma osmolality and low urine osmolality, which does not correct with water deprivation but improves with desmopressin administration. Which of the following signaling pathways is most likely involved in the action of the administered medication? cAMP
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