This document discusses various paraneoplastic syndromes and their treatments according to Harrison's 18th Edition. It addresses endocrine syndromes like humoral hypercalcemia of malignancy, which can be treated by removing excess calcium from the diet and IV bisphosphonates. It also discusses ectopic vasopressin syndrome and its treatment through fluid restriction and vasopressin receptor antagonists. Cushing's syndrome caused by ectopic ACTH production is discussed alongside treatments like adrenalectomy, ketoconazole, and metyrapone. Hematologic syndromes like erythrocytosis, thrombocytosis, eosinophilia and thrombophlebitis are covered as well treatments such as phle

1. DR. JUAN CARLOS BECERRA MARTÍNEZ
CÁTEDRA DE MEDICINA INTERNA-MC3087
Tecnológico de Monterrey
Campus Guadalajara

2. Paraneoplastic syndromes
Harrison’s 18th Edition.
 Paraneoplastic syndromes is the term used
to refer to the disorders that accompany
benign or malignant tumors but are not
directly related to mass effects or invasion.

3. Endocrine Paraneoplastic
Syndromes
Harrison’s 18th Edition.

4. Treatment: Humoral Hypercalcemia
of Malignancy
Harrison’s 18th Edition.
 Removal of excess calcium in the diet, medications, or IV solutions.
 Oral phosphorus (e.g., 250 mg Neutra-Phos 3–4 times daily) should be given
until serum phosphorus is >1 mmol/L (>3 mg/dL).
 Saline rehydration is used to dilute serum calcium and promote calciuresis.
 Forced diuresis with furosemide or other loop diuretics
 Bisphosphonates such as pamidronate (60–90 mg IV), zoledronate (4–8 mg
IV), and etidronate (7.5 mg/kg per day PO for 3–7 consecutive days
 Dialysis should be considered in severe hypercalcemia.
 Calcitonin (2–8 U/kg SC every 6–12 h) should be considered when rapid
correction of severe hypercalcemia is needed.

5. Endocrine Paraneoplastic
Syndromes
Harrison’s 18th Edition.

6. Endocrine Paraneoplastic
Syndromes
Harrison’s 18th Edition.

7. Ectopic Vasopressin: Tumor-
Associated SIADH
Harrison’s 18th Edition.
 Most patients with ectopic vasopressin production develop hyponatremia
 The disorder should be corrected gradually unless mental status is altered or there is risk of
seizures.
 Fluid restriction to less than urine output,
 Salt tablets and saline are not helpful unless volume depletion is also present.
 Demeclocycline (150–300 mg orally three to four times daily) can be used to inhibit vasopressin
action on the renal distal tubule, but its onset of action is relatively slow (1–2 weeks).
 Conivaptan, a nonpeptide V2-receptor antagonist, can be administered either PO (20–120 mg bid)
or IV (10–40 mg) and is particularly effective when used in combination with fluid restriction in
euvolemic hyponatremia.
 Severe hyponatremia (Na <115 meq/L) or mental status changes may require treatment with
hypertonic (3%) or normal saline infusion together with furosemide to enhance free water clearance.
 The rate of sodium correction should be slow (0.5–1 meq/L per h) to prevent pontine myelinolysis.

8. Ectopic Vasopressin: Tumor-
Associated SIADH
Harrison’s 18th Edition.

9. Treatment: Cushing's Syndrome
Caused by Ectopic ACTH
Production
Harrison’s 18th Edition.
 Depression or personality changes because of extreme cortisol
excess.
 Metabolic derangements, including diabetes mellitus and
hypokalemia, can worsen fatigue.
 Adrenalectomy is not practical for most of these patients but
should be considered if the underlying tumor is not resectable and
the prognosis is otherwise favorable (e.g., carcinoid).
 Medical therapy with ketoconazole (300–600 mg PO bid),
metyrapone (250–500 mg PO every 6 h), mitotane (3–6 g PO in
four divided doses, tapered to maintain low cortisol production), or
other agents that block steroid synthesis or action.

10. Endocrine Paraneoplastic
Syndromes
Harrison’s 18th Edition.

11. Endocrine Paraneoplastic
Syndromes
Harrison’s 18th Edition.

12. Hematologic Syndromes
Harrison’s 18th Edition.

13. Hematologic Syndromes
Harrison’s 18th Edition.

14. Treatment: Erythrocytosis
 Successful resection of the cancer
 Phlebotomy may control any symptoms
related to erythrocytosis
Harrison’s 18th Edition.

15. Treatment: Thrombocytosis
 IL-6, a candidate molecule for the etiology of paraneoplastic
thrombocytosis, stimulates the production of platelets in vitro
and in vivo.
 Another candidate molecule is thrombopoietin, a peptide
hormone that stimulates megakaryocyte proliferation and
platelet production.
 Thrombocytosis is present in 40% of patients with lung and
gastrointestinal cancers; 20% of patients with breast,
endometrial, and ovarian cancers; and 10% of patients with
lymphoma.
 Paraneoplastic thrombocytosis does not require treatment.
Harrison’s 18th Edition.

16. Treatment: Eosinophilia
 Definitive treatment is directed at the
underlying malignancy:
 Symptoms resolve with the use of oral or inhaled
glucocorticoids.
Harrison’s 18th Edition.

17. Treatment:
Thrombophlebitis
 Deep venous thrombosis and pulmonary
embolism are the most common thrombotic
conditions in patients with cancer.
 The coexistence of peripheral venous
thrombosis with visceral carcinoma,
particularly pancreatic cancer, is called
Trousseau's syndrome.
Harrison’s 18th Edition.

18. Treatment:
Thrombophlebitis
 IV unfractionated heparin or low-molecular-weight heparin
for at least 5 days, and warfarin should be started within 1
or 2 days.
 The warfarin dose should be adjusted so that the
international normalized ratio (INR) is 2–3.
 Patients with proximal deep venous thrombosis and a
relative contraindication to heparin anticoagulation
(hemorrhagic brain metastases or pericardial effusion)
should be considered for placement of a filter in the
inferior vena cava (Greenfield filter) to prevent pulmonary
embolism.
Harrison’s 18th Edition.

19. Treatment:
Thrombophlebitis

20. Paraneoplastic Neurologic
Syndromes
Harrison’s 18th Edition.

21. Lambert-Eaton Sx

22. Guillain Barre Sx

23. SMNS vs SMNI

24. Antibodies
Harrison’s 18th Edition.

25. Antibodies
Harrison’s 18th Edition.