Download endocrine manifestation of malagnancy

By Dr. Zahoor
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Endocrine manifestation of cancer are usually
paraneoplastic syndrome i.e. rare
manifestations of malignancy, but are not
due to direct effect of cancer cells
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 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
Most commonly associated malignancies
include small cell lung cancer, breast cancer,
gynecologic tumor
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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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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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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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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 3% saline (hypertonic) to
correct serum sodium level
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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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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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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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PNS - CNS symptoms include
- Personality changes
- Cranial nerve deficits
- Weakness or numbness
- Lambert – Eaten myasthenic syndrome
- Myasthenia gravis
- 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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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 Syndrome
Acanthosis Nigricans
 It is characterized by thickened, hyperpigmented 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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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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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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Hypertrophic osteoarthropathy
 It is characterized by peristosis 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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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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Pure red cell aplasia
 Associated with thymoma
Polycythemia
 Associated with renal tumor
Paraneoplastic Thrombocytosis
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MEN I – Pituitary, Parathyroid, Pancreas
(3 Ps)
(It is also called Wermer MEN1 as he noted in 1954, this
syndrome is Autosomal dominant)
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MEN IIa – Medullary Thyroid Ca, Pheochromocytoma,
Parathyroid
(1M, 2Ps)
(Also called Sipple Syndrome as he described in 1961)
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MEN IIb - Medullary Thyroid Ca, Pheochromocytoma,
Mucosal Neuroma
(2Ms, 1P) (Described by William in 1966)
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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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