1. ENDOCRINE MANIFESTATION OF MALAGNANCY PARANEOPLASTIC SYNDROME
By Dr. Zahoor

2. Paraneoplastic Syndrome
Endocrine manifestation of cancer are usually paraneoplastic syndrome i.e. rare manifestations of malignancy, but are not due to direct effect of cancer cells

3. Paraneoplastic Syndrome
Why we get paraneoplastic syndrome?
The mechanism involves the production of hormones or other substances that act in endocrine or paracrine manner resulting in systemic manifestation

4. Paraneoplastic Syndrome
Paraneoplastic Syndrome arise due to tumor secretion of hormones, peptides or cytokines
Paraneoplastic Syndrome may affect other organ systems like Endocrine, Neurologic, Dermatologic, Rheumatologic and Hematologic systems

5. Paraneoplastic Syndrome
Most commonly associated malignancies include small cell lung cancer, breast cancer, gynecologic tumor

6. Paraneoplastic Syndrome
History
More than 100 years ago, it was recognized that certain cancers cause various symptoms not attributable to direct tumor invasion or compression
These symptoms were labeled as paraneoplastic syndrome in 1940, but were poorly understood

7. Paraneoplastic Syndrome (PNS)
History (cont)
Now we know these syndrome occur due to secretion of peptide or hormone (endocrine PNS) or cross activity between tumor and normal host tissue (neurologic paraneoplastic syndrome)
Note – PNS can manifest before a cancer diagnosis specially in neurologic paraneoplastic disorders

8. Paraneoplastic Endocrine Syndrome
These usually occur due to production of hormones or peptide
The commonest endocrine paraneoplastic syndrome include
1- Inappropriate anti-diuretic hormone
secretion (SIADH)
2- Hypercalcaemia
3- Cushing Syndrome
There may be presenting features of an underlying malignancy
We will study each one

9. Paraneoplastic Endocrine Syndrome
Syndrome of inappropriate ADH secretion (SIADH)
Increased ADH secretion causes hyponatremia, hypo-osmolality
Cause of SIADH- small cell lung cancer, which produces ADH
Patient may need hypertonic saline to correct serum sodium level

10. Paraneoplastic Endocrine Syndrome
Hypercalcemia
Hypercalcemia can occur in cancer patients due to secretion of parathyroid hormone related protein (PTHrP) by tumor cells
Tumors which cause hypercalcemia
- Squamous cell carcinoma lung, breast cancer, multiple myeloma, lymphoma

11. Paraneoplastic Endocrine Syndrome
Cushing Syndrome
Due to increased secretion of ACTH, which increases release of Cortisol from adrenal gland
Cancer which cause hypercalcemia
- Small cell lung cancer
Patient may present with Cushing syndrome (features of hypertension, hypokalemia, muscle weakness) before the diagnosis of cancer is made

13. Paraneoplastic Neurologic Syndrome

14. Paraneoplastic Neurologic Syndrome (PNS)
They occur due to immune cross reactivity between tumor cells and components of nervous system
Patient produces tumor related antibodies and they can attack the nervous system
Patient condition can be diagnosed by PNS before cancer is diagnosed in 80% of cases

15. Paraneoplastic Neurologic Syndrome (PNS)
PNS - CNS symptoms include
- Personality changes
- Cranial nerve deficits
- Weakness or numbness
- Lambert – Eaten myasthenic syndrome
- Myasthenia gravis

16. Paraneoplastic Neurologic Syndrome (PNS)
PNS - CNS symptoms include (cont)
- Cerebellar degeneration
- Sensory neuropathy
- Autonomic neuropathy
NOTE – These conditions can occur itself due to other causes and may not be paraneoplastic

17. Paraneoplastic Neurologic Syndrome (PNS)
Lambert – Eaten myasthenic syndrome
There is muscle weakness, which improves on exercise
It is associated with small cell lung cancer
Myasthenia gravis
Patient complains of muscle weakness which increases on exercise
Myasthenia gravis is associated with Thymoma

18. Paraneoplastic Dermatologic and Rheumatologic Syndrome
Paraneoplastic Dermatologic Syndrome
Acanthosis Nigricans
It is characterized by thickened, hyper- pigmented skin, predominantly in axilla and neck region
Most common cancer associated with Acanthosis nigricans is gastric adenocarcinoma

19. Acanthosis nigricans

20. Acanthosis nigricans

21. Paraneoplastic Dermatologic Syndrome
Dermatomyositis
It is inflammatory Myopathy, there is proximal Myopathy
Heliotrope rash (purple color) on upper eyelid
Erythromatous rash on face, neck, chest
Commonly associated malignancies – breast, ovary, lung, prostate
Creatine phosphokinase is raised

22. Heliotrope rash (purple color) on upper eyelid

23. Paraneoplastic Dermatologic Syndrome
Sweet Syndrome
Sudden onset of painful, Erythematosus plaques, papule, nodules on the face, trunk and extremities. There is fever and neutrophalia
Association - acute myeloid leukemia
and other tumors like breast, GIT

24. Sweet Syndrome

25. Paraneoplastic Rheumatologic Syndrome
Hypertrophic osteoarthropathy
It is characterized by periostosis and sub periosteal bone formation along the shaft of long bones and phalanges, joint swelling and pain
Associated with cancer lung (Bronchogenic carcinoma)

26. Hypertrophic osteoarthropathy - Periostitis, Knee and Ankle

27. Paraneoplastic Hematologic Syndrome
These conditions are usually detected after the cancer diagnosis
Paraneoplastic Eosinophilia
Associated with lymphoma and Leukemias but may be seen with carcinoma lung, GIT, gynecologic tumors

28. Paraneoplastic Hematologic Syndrome
Pure red cell aplasia
Associated with thymoma
Polycythemia
Associated with renal tumor
Paraneoplastic Thrombocytosis

29. Conclusion
The ability to recognize and treat paraneoplastic syndrome may have effect on clinical outcome ranging from early cancer diagnosis, to improved quality of life and increased delivery of tumor directed therapy

30. Thank you