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By Dr. Zahoor 1 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 2 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 3 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 4 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 5 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 6 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 7 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 8 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 9 10 11 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 12 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 13 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 14 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 15 Acanthosis nigricans 16 Acanthosis nigricans 17 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 18 Heliotrope rash (purple color) on upper eyelid 19 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 20 Sweet Syndrome 21 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) 22 Hypertrophic osteoarthropathy - Periostitis, Knee and Ankle 23 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 24 Pure red cell aplasia Associated with thymoma Polycythemia Associated with renal tumor Paraneoplastic Thrombocytosis 25 MEN I – Pituitary, Parathyroid, Pancreas (3 Ps) (It is also called Wermer MEN1 as he noted in 1954, this syndrome is Autosomal dominant) MEN IIa – Medullary Thyroid Ca, Pheochromocytoma, Parathyroid (1M, 2Ps) (Also called Sipple Syndrome as he described in 1961) MEN IIb - Medullary Thyroid Ca, Pheochromocytoma, Mucosal Neuroma (2Ms, 1P) (Described by William in 1966) 26 27 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 28 29