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ENDOCRINE MANIFESTATION OF MALAGNANCYPARANEOPLASTIC SYNDROME

By Dr. Zahoor

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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

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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

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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

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Paraneoplastic Syndrome

Most commonly associated malignancies include small cell lung cancer, breast cancer, gynecologic tumor

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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

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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

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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

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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

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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

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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

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Paraneoplastic Neurologic Syndrome

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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

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Paraneoplastic Neurologic Syndrome (PNS)

PNS - CNS symptoms include - Personality changes - Cranial nerve deficits - Weakness or numbness - Lambert – Eaten myasthenic

syndrome - Myasthenia gravis

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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

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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

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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

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Acanthosis nigricans

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Acanthosis nigricans

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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

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Heliotrope rash (purple color) on upper eyelid

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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

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Sweet Syndrome

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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)

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Hypertrophic osteoarthropathy - Periostitis, Knee and Ankle

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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

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Paraneoplastic Hematologic Syndrome

Pure red cell aplasia Associated with thymoma

Polycythemia Associated with renal tumor

Paraneoplastic Thrombocytosis

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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

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Thank you