Endocrine effects of non-endocrine tumors

Endocrine effects of non-endocrine tumors

Endocrine effects of non-endocrine tumors

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Paraneoplastic Syndromes - Hormones Rogue

Tumors producing hormones not native to their tissue of origin, causing systemic effects.

  • Ectopic ACTH (Cushing Syndrome):
    • Source: Small Cell Lung Cancer (SCLC), pancreatic cancer.
    • Effect: ↑Cortisol → Cushingoid features, hypertension, hypokalemia.
  • Ectopic ADH (SIADH):
    • Source: SCLC, CNS tumors.
    • Effect: ↑ADH → Hyponatremia, ↓serum osmolality.
  • PTH-related peptide (PTHrP):
    • Source: Squamous Cell Lung Cancer, Renal/Bladder/Breast Ca.
    • Effect: Hypercalcemia (mimics hyperparathyroidism).
  • Ectopic Erythropoietin (EPO):
    • Source: Renal Cell Carcinoma, Hepatocellular Carcinoma.
    • Effect: Polycythemia.

Small Cell Lung Cancer (SCLC) is the most common cause of both ectopic ACTH and ADH production, making it a classic culprit for multiple paraneoplastic syndromes.

Ectopic Cushing & SIADH - Small Cell's Double Trouble

  • Small Cell Lung Cancer (SCLC) is notorious for paraneoplastic syndromes via ectopic hormone production.

  • Ectopic Cushing Syndrome:

    • Cause: Ectopic ACTH secretion.
    • Features: Rapid onset hypertension, hypokalemic metabolic alkalosis, and hyperglycemia. Classic cushingoid signs (e.g., moon facies) are often absent.
    • Diagnosis: ↑ ACTH & cortisol levels that are not suppressed by a high-dose dexamethasone test.
  • SIADH (Syndrome of Inappropriate ADH):

    • Cause: Ectopic ADH secretion.
    • Features: Euvolemic hyponatremia with ↓ serum osmolality (<275 mOsm/kg) but ↑ urine osmolality (>100 mOsm/kg).

High-Yield: The most common paraneoplastic syndrome associated with SCLC is SIADH, while ectopic Cushing syndrome is the second most common endocrine manifestation.

Algorithm for diagnosing Cushing's syndrome

Hypercalcemia of Malignancy - Bone Breakers

  • Most common paraneoplastic syndrome. Presents with "stones, bones, groans, thrones, psychiatric overtones."
  • Primary Mechanisms:
    • Humoral (HHM): Accounts for ~80% of cases. Mediated by parathyroid hormone-related protein (PTHrP).
      • Mimics PTH: ↑ bone resorption, ↑ renal Ca²⁺ reabsorption.
      • Associated Tumors: Squamous cell (lung), renal, bladder, breast, ovarian.
    • Local Osteolysis: Direct bone destruction from metastases (e.g., breast cancer, multiple myeloma) releasing osteoclast-activating cytokines.
    • Ectopic Vitamin D: Rare. Tumor production of $1,25-( ext{OH})_2 ext{D}_3$ (calcitriol), seen in lymphomas.

⭐ In Humoral Hypercalcemia of Malignancy, labs show ↑ serum Ca²⁺ and ↑ PTHrP, but endogenous PTH is suppressed (↓ PTH).

Hypercalcemia of Malignancy: Mechanisms, Symptoms, Treatment

Other Notable Syndromes - The Rare Rebels

  • Stauffer Syndrome: Paraneoplastic hepatic dysfunction (non-metastatic) seen in Renal Cell Carcinoma (RCC).

    • Features: Fever, hepatosplenomegaly, ↑ ALP, ↑ ESR, ↑ prothrombin time.
    • Mechanism: Likely cytokine-mediated (e.g., IL-6); resolves after nephrectomy.
  • Hypertrophic Osteoarthropathy: Triad of digital clubbing, arthritis, and periostitis of long bones.

    • Strongly associated with non-small cell lung cancer (especially adenocarcinoma).
  • Polycythemia: Ectopic erythropoietin (EPO) production leading to ↑ RBC mass.

    • Associated tumors: Renal Cell Carcinoma, Hepatocellular Carcinoma, Cerebellar Hemangioblastoma.

Trousseau Syndrome (Migratory Thrombophlebitis): Superficial venous thromboses appearing in different locations over time. It is a classic sign of visceral malignancy, particularly mucin-producing adenocarcinomas of the pancreas or lung.

High‑Yield Points - ⚡ Biggest Takeaways

  • Ectopic Cushing syndrome is most often from small cell lung cancer (SCLC) secreting ACTH.
  • SIADH, causing hyponatremia, is also commonly associated with SCLC.
  • Hypercalcemia, the most frequent syndrome, is often due to PTHrP from squamous cell lung cancer.
  • Hypoglycemia can be caused by tumors overproducing IGF-2, like hepatocellular carcinoma.
  • Polycythemia can result from ectopic EPO production by renal cell or hepatocellular carcinomas.
  • Carcinoid syndrome (flushing, diarrhea) is due to serotonin from metastatic carcinoid tumors.

Practice Questions: Endocrine effects of non-endocrine tumors

Test your understanding with these related questions

A 54-year-old man comes to the emergency department because of abdominal distension for the past 3 weeks. He also complains of generalized abdominal discomfort associated with nausea and decreased appetite. He was discharged from the hospital 3 months ago after an inguinal hernia repair with no reported complications. He has a history of type 2 diabetes mellitus, congestive heart failure, and untreated hepatitis C. His current medications include aspirin, atorvastatin, metoprolol, lisinopril, and metformin. His father has a history of alcoholic liver disease. He has smoked one pack of cigarettes daily for 30 years but quit 5 years ago. He drinks 3–4 beers daily. He appears cachectic. His vital signs are within normal limits. Examination shows a distended abdomen and shifting dullness. There is no abdominal tenderness or palpable masses. There is a well-healed surgical scar in the right lower quadrant. Examination of the heart and lung shows no abnormalities. He has 1+ bilateral lower extremity nonpitting edema. Diagnostic paracentesis is performed. Laboratory studies show: Hemoglobin 10 g/dL Leukocyte count 14,000/mm3 Platelet count 152,000/mm3 Serum Total protein 5.8 g/dL Albumin 3.5 g/dL AST 18 U/L ALT 19 U/L Total bilirubin 0.8 mg/dL HbA1c 8.1% Peritoneal fluid analysis Color Cloudy Cell count 550/mm3 with lymphocytic predominance Total protein 3.5 g/dL Albumin 2.6 g/dL Glucose 60 mg/dL Triglycerides 360 mg/dL Peritoneal fluid Gram stain is negative. Culture and cytology results are pending. Which of the following is the most likely cause of this patient's symptoms?

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Flashcards: Endocrine effects of non-endocrine tumors

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Which type of calcification (dystrophic or metastatic) occurs secondary to hypercalcemia or hyperphosphatemia? _____

TAP TO REVEAL ANSWER

Which type of calcification (dystrophic or metastatic) occurs secondary to hypercalcemia or hyperphosphatemia? _____

Metastatic

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