Oncology: Paraneoplastic Syndromes: Endocrinological – Flashcards
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What is a paraneoplastic syndrome?
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- a disorder within the body's structure or function that occurs DISTANT to the 1º tumor, not as a local extention
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Describe how a paraneoplastic syndrome might occur?
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- substances released from the tumor → enter bloodstream and have an effect at a distant site
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Why is it important to understand and recognize these syndromes?
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- can result in greater morbidity then primary tumor itself
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What are advantages of recognizing PNS?
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1. generally associated with 1º tumor → remove the tumor and syndrome goes away 2. can signal if a patient is coming out of remission prior to gross evidence of tumor recurrence or development of metastasis
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What are categories of PNS? 6
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1. Endocrinological PNS 2. gastrointestinal PNS 3. cutaneous PNS 4. hematological PNS 5. neurological PNS 6. miscellaneous
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What is the most common cause of hypercalcemia?
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- Cancer
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What other conditions can hypercalcemia occur secondary to?
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HOGS IN YARD Hyperparathyroidism Osteolytic lesions Granulomatous disease Spurious/Lab Error Idiopathic Neoplasia Youth Addisons Renal Vitamin D
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What are the three most common neoplasms that result in HM?
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1. Lymphoma → 10-35% 2. anal sac apocrine gland adenocarcinoma → > 25% of cases 3. multiple myeloma → approx 20%
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What are some other causes of HM?
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1. Ectopic production of parathyroid hormone or PTH related peptide 2. lytic bone lesions 3. tumor associated prostaglandins 4. interleukin-1 Beta
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What Is the primary clinical manifestation of hypercalcemia?
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renal impairment
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Where does the elevated calcium levels act on in the kidney? what does this result in?
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- distal renal tubules - decreased responsiveness to antidiuretic hormone → kidneys unable to concentrate urine
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What clinical sign to the inability for the kidneys to concentrate urine result in?
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Primary polyurea was secondary polydipsia
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What are some other effects of hypercalcemia on the kidneys?
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1. Severe vasoconstriction → decreased renal blood flow and GFR 2. calcium salt deposition within the renal parenchyma 3. renal necrosis
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What are other clinical signs associated with hypercalcemia?
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1. Bradycardia 2. hypertension 3. weakness 4. depression
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what are your steps taken when you have a hypercalcemia patient?
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1. Confirm calcium is truly elevated 2. perform a thorough PE 3. staging tests 4. PTH/PTH-rp assay
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How you confirm that your calcium is truly elevated?
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- Ionized calcium level
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Describe your physical exam?
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- Check all peripheral lymph nodes - rectal exam → careful palpation of anal glands - check some lumbar lymph nodes *** looking for enlargement
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What staging tests could you perform?
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1. Bloodwork/UA 2. radiographs, chest, abdomen 3. FNA, even if they are normal 4. abdominal ultrasound
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If you run a PTH/PTH-rP assay, what results would you expect if the hypercalcemia is due to cancer?
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- PTH low - PTH-rp high ***If secondary to a primary parathyroid tumor, would expect hi PTH and low calcium???
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when is emergency therapy for hypercalcemia indicated?
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- if Ca is > 4.5 mmol/L
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Describe the treatment for hypercalcemic patient?
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1. 0.9% saline diuresis 2. Furosemide 3. corticosteroids 4. bisphosphonates 5. calcitonin
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Why do we do a saline diuresis? 3
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1. ↑ GFR 2. ↑ calcuiresis and natriuresis 3. ↓ calcium resorption by the kidneys
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When should you only give furosemide? how does furosemide help?
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- Only once the patient is rehydrated - is a loop diuretics that inhibits calcium resorption in the ascending loop Henle
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When should you ONLY give corticosteroids?
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- Only give once a diagnosis of the cause has been made - corticosteroids will affect your ability to diagnose otherwise → kill a lot of round cell tumors making it hard to make the diagnosis later
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What are bisphosphonates?
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- anti osteoclastic activity - inhibit bone resorption → therefore Ca release
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What does calcitonin do?
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- opposes parathyroid hormone → Inhibits osteoclast activity
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What is the most important factor when trying to control hypercalcemia due to malignancy?
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Treat the underlying cause, adequate long-term control cannot be achieved without removing the tumor
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What are two types of tumors that may result in hypoglycemia? which is the most common?
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1. Pancreatic beta islet cell tumor → insulinoma (MOST COMMON) 2. Non Islet cell Tumors = tumors using up glucose
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What is the mechanism by which a pancreatic beta islet cell tumor causes hypoglycemia?
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- Increased insulin production
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What are the most common non-islet cell tumors?
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- hepatocellular carcinoma - may be seen with others: • lymphoma • HSA • Leiomyosarcoma • multiple myeloma
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What is the mechanism by which a non-islet cell tumor causes hypoglycemia? 5
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1. Ectopic insulin production 2. secretion of insulin like growth factors I and II 3. ↑ tumor consumption of glucose 4. ↓ hepatic glycogenolysis or gluconeogenesis 5. ↑ insulin binding M proteins in myeloma
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What are other differentials to consider if you have hypoglycemia
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1. Hypoadrenocorticism 2. starvation 3. sepsis 4. sample or lab error
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What are clinical signs of hypoglycemia?
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• Trembling • week • seizures • disorientation • comma
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How do you diagnose an insulinoma?
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- Concurrent glucose and insulin levels should be run - there will be hypoglycemia with the concurrent, inappropriately elevated insulin levels
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What is the most effective treatment for an insulinoma?
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Surgical excision: - partial pancreatectomy
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Describe medical management for an insulinoma? 4 describe how each medication may help
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1. Prednisone → promote glucogenolysis and GNG 2. small frequent meals 3. Diazoxide → enhances epinephrine induced glycogenolysis, inhibits insulin release and cellular uptake 4. Streptozotocin → chemo therapeutic, some activity against the islet cells of the pancreas
