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Paraneoplastic Syndromes

January 29, 2026 · 1 h 5 min

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Ninja Nerds!

In this episode of the Ninja Nerd Podcast, Zach and Rob deliver a high-yield, case-based discussion on paraneoplastic syndromes, exploring how certain cancers cause systemic effects that extend beyond the primary tumor.

We begin with SIADH in small-cell lung cancer, breaking down the classic lab pattern of hyponatremia with inappropriately concentrated urine and the dangers of seizures or osmotic demyelination from overcorrection. Next, we cover ectopic ACTH production from small-cell lung cancer, reviewing the clinical features of Cushing syndrome, stepwise testing, and complications like infections, thromboembolism, and severe metabolic derangements.

The discussion moves into Lambert-Eaton myasthenic syndrome (LEMS), highlighting proximal muscle weakness that improves with activity, autonomic symptoms, and the link to voltage-gated calcium channel antibodies. We then review hypercalcemia of malignancy, focusing on PTHrP secretion by squamous lung cancers and the potential for acute kidney injury and arrhythmias.

We shift to the neurologic realm with anti-NMDA receptor encephalitis associated with ovarian teratomas, a syndrome marked by psychiatric changes, seizures, and autonomic instability that improves with tumor removal and immunotherapy. This is followed by dermatomyositis as a paraneoplastic marker for ovarian carcinoma, with its characteristic rashes, muscle weakness, and high malignancy risk.

Next, we cover myasthenia gravis linked to thymoma, emphasizing fluctuating ocular and bulbar symptoms, diagnostic testing, and the need for thymectomy in appropriate cases. Finally, we discuss Trousseau syndrome and nonbacterial thrombotic endocarditis (NBTE) in pancreatic adenocarcinoma, where migratory thrombophlebitis and unexplained clots should raise suspicion for underlying malignancy.

We conclude with a rapid wrap-up of high-yield associations:

  • Small-cell lung cancer: SIADH, ectopic ACTH, LEMS
  • Squamous cancers: PTHrP hypercalcemia
  • Ovarian teratoma: Anti-NMDA encephalitis
  • Thymoma: Myasthenia gravis
  • Pancreatic adenocarcinoma: Trousseau syndrome and NBTE

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