Endocrine and metabolic complications of advanced cancer

Question 1

Cushing’s Syndrome

Answer 1

• paraneoplastic syndrome from ectopic ACTH secretion
• lung cancer most common
• thymoma, pancreatic islet ca
• Hypercortisolism
  
  • osteoporosis
  • hypertension
  • facial plethora
  • stria
  • muscle weakness
  • bruising
  • glucose intolerance
  • weight loss

Question 2

Diagnosis of Cushing’s syndrome

Answer 2

• 24 urinary cortisol (x3 ULN)
• overnight dex suppression test
  
  • am cortisol < 50

Question 3

treatment of Cushing’s syndrome secondary to ectopic ACTH

Answer 3

• tumour resection
• medications to inhibit synthesis of cortisol
  
  • ketoconazole
  • metyrapone
  • mitotane
  • octreotide
  • mifepristone
• monitor with 24 hour urinary cortisol
• will require homone replacement therapy
  
  • steroids for mineralocorticoid replacement

Question 4

SIAD (definition)

Answer 4

• concentrated urine and hypoosmolar and hyponatremic plasma
• abnormal free water excretion by kidneys
• inapppropriate antidiuresis

Question 5

Pathophysiology of SIAD

Answer 5

• ADH acts on kidneys
• absorbs water but loses sodium in urine

Etiology

• CNS causes (infection, bleeding, MS)
• Cancer (ectopic ADH)
  
  • (small cell, mesothelioma, GI, GU, sarcoma, lymphoma)
• Drugs
  
  • carbamazepine
  • valproic acid
  • SSRI
  • morphine
  • Amitriptyline
• Sarcoidosis
• Pulmonary causes
  
  • Pneumonia
  • abscess
  • asthma, CF

Question 6

Clinical presentation of SIAD

Answer 6

• hyponatremia
  
  • confusion, coma, seizure
• depends on rate of decline

Question 7

Diagnosis of SIAD

Answer 7

EUVOLEMIC hyponatremia from AHD from posterior pituitary

ADH secretion increases water absorption from kidneys –> dilution of sodium in body —> hypoosmolar hyponatremia

Diagnosis

• hypoosmolar hyponatremia
• plasma osm < 275, plasma Na < 135
• HIGH urinary sodium and osmo
• urine osmo > 100, urine Na > 20 mEq/L

PLASMA : LOW OSMO, LOW NA

URINE : HIGH osmo, HIGH Na

• may correct with fluid restriction
• will not correct with IV fluids
• water load test :
  
  • give 20 ml/kg water load
  • normal to excrete > 90 % in 4 hours
  • normal to dilute urine to osmo < 100
  • if those don’t occur: SIAD

Question 8

SIAD treatment

Answer 8

• Acute:
  
  • CNS sx
  • hypertonic saline
  • correction 0.5 mmol/L/ HOUR
  • Go slowly
• Chronic
  
  • fluid restriction 500 ml/day
  • target urine output < 500 ml/day
  • go slow to avoid demyelination
  • not practical for comfort in pall care
• Other
  
  • demeclocycline
  • tolvaptan (ADH receptor antagonist)
  • Urea (increases free water excretion)

Question 9

Hypoglycemia

Answer 9

• common with pancreatic islet cell tumours (secrete insulin)
• can occur in other tumours
  
  • retroperitoneal, intrathoracic large tumours
  • secrete abnormal IGF-2 that binds to insulin receptors, cause hypoglycemia

Question 10

Hypoglycemia symptoms/ presentation

Answer 10

• confusion
• agitation
• coma
• seizure
• tremours
• nausea
• malaise
• often following exercise or fasting

Question 11

Investigations for hypoglycemia

Answer 11

• insulin levels (low)
• C peptide (low)
• reviews meds for other causes
• liver failure (impaired gluconeogenesis)

Question 12

Hypoglycemia treatment

Answer 12

• IV d50W x 1 amp
• debulking surgery / chemo
• steroids
• glucagon
• frequent feeding

Question 13

Features and common sites of insulinomas

Answer 13

• neuroglycopenia
• beta islet cell tumours of pancreas
• MEN tumours

Question 14

Palliative therapy for insulinomas

Answer 14

• frequent feeding
• IV glucose
• Diazoxide + HCTZ
• Octreotide

Question 15

Gastrinoma : features and common sites

Zollinger-Ellison syndrome

Answer 15

• peptic ulceration
• diarrhea, weight loss, malabsorption
• gastric dumping
• pancreas
• duodenum

Question 16

Treatment of gastrinoma (Zollinger-Ellison)

Answer 16

• gastrectomy
• PPI
• H2 blocker
• octreotide
• debulking sx of liver

Question 17

VIPoma (vasoactive intestinal polypeptide) : features and common sites

Answer 17

• causes secretory diarrhea
• diarrhea
• hypoglycemia
• Achlorydia
• hypercalcemia
• hyperglycemia
• hypomagnesemia

Pancreas

Neurblastoma

SCLC

Pheo

Question 18

VIPoma treatment

Answer 18

• octreotide
• glucocorticoids
• potassium, bicarb

Question 19

Glucagonoma : features and sites

Answer 19

• migratory necrolytic erythema
• DM
• muscle wasting
• anemia
• diarrhea
• VTE
• stomatitis
• encephalitis
• PANCREAS

Treatment

• octreotide
• debulking sx of liver lets
• oral hypoglycemic agents
• DVT prophylaxis

Question 20

Octreotide for treatment of enteropancreatic hormone syndromes

Answer 20

• inhibits hormone secretion
  
  • gastrin
  • VIP
  • insulin
  • glucagon
  • secretin
• may cause abdo cramping, diarrhea, flatulence
• Valuable for palliation of symtoms

Question 21

Carcinoid syndrome:

pathophysiology

Answer 21

• Tumours that arise from SEROTONIN producing cells
• neuroendocrine tumours
• GI tract, pancreas, lungs
• often associated with hepatic mets

Question 22

Carcinoid Syndrome : clinical presentation

Answer 22

• Secretion of serotonin and vasoactive substances:
• diarrhea
• flushing
• asthma
• cardiac : TR, pulmonary valve stenosis, endomyocardial fibrosis
• pellagroid rash (redness, peeling in sun exposed areas)

Question 23

Diagnosis of carcinoid syndrome

Answer 23

• octreotide scan or PET most sensitive and localizing
• 24 hour urinary excretion of 5-HIAA (serotonin metabolism) : midgut tumours
  
  • not all tumours will secrete

Question 24

Carcinoid Syndrome: Treatment

Answer 24

• Octreotide
  
  • flushing, diarrhea
  • relief in 80%
• debulking surgery
• Diarrhea control
  
  • lomotil, loperamide, codeine
  • Telotrsitat
• SABA for asthma /wheeze
• avoid alcohol
• cyprohepatadine for flushing

Question 25

Pheochromocytoma

Answer 25

• tumours from adrenal medulla
• secrete catecholamines (NE, E, dopamine)
• Sx:
  
  • flushing, anxiety, tremour, hypertension, sweating, HA, diarrhea, polyuria
• Tx:
  
  • alpha and beta blockade
  • prazosin
  • then beta blockage for tachycardia
  • propanolol
  • Metirozine (inhibitor of catecholamine synthesis)

Question 26

Gonadotrophin secreting tumours

Answer 26

• Pituitary, trophoblastic, germ cell tumours
• FSH, LH, HCG, estrogen
• clinical presentation:
  
  • precocious puberty
  • secondary amennhorea
  • gynecomastia men
• treatment
  
  • counselling
  • gonadorelin to suppress pit GNRH receptors
  • antiandrogens (spironolactone, finasteride)
  • amenorrhea : HRT, topical estrogen

Question 27

Gynecosmastia (causes and treatment)

Answer 27

• increased estrogen : androgen
• causes:
  
  • chemo
  • antiemetics (metoclopramide)
  • anti androgens
  • GNRH analogues
  • tumour secretion of estrogen, hcg (testicular, breast, NSCLC, pancreatic)
• treatment
  
  • tamoxifen
  • clomiphene
  • surgery?
  • radiation
  • stop offending drugs

Question 28

Hyperthyroidism in malignancy : causes, treatment

Answer 28

• Tumours secreting large amounts of HCG
• hcg structurally similar to TSH
• rx: chemo, surgery
• methimazole medical treatment

Question 29

Hyperprolactinemia in malignacy (causes, treatment)

Answer 29

• Pituitary tumours
• Rare RCC, SCLC
• may cause galactorrhea
• Rx: Bromocriptine (dopamine agonist)

Question 30

Pyrexia in advanced cancer : causes, treatment

Answer 30

• infection, drugs, paraneoplastic
• Paraneoplastic pyrexia
  
  • dx of exclusion
  • pyrogenic cytokines secreted by tumour
  • leukemia, lymphoma, RCC, hepatoma, sarcoma
• infectious workout
• rx: ice, fan, antipyretics, steroids (?)

Question 31

Hyperglycemia in advanced cancer (causes, treatment)

Answer 31

• liver dysfunction
  
  • increased gluconeogenesis
  • low glucose tolerance, insulin resistence
• cancel cells can alter glucose metabolism and secrete insulin antagonists
• Medications : steroids!
• Treatment:
  
  • looser BG control in pall patients
  • BG < 15 for symptoms
  • avoid lows
  • OHA and insulin prn

Question 32

MEN

Multiple endocrine neoplasia

Answer 32

• MEN 1 (pituitary, parathyroid, pancreatic)
• MEN IIa (Pheo, thyroid, parathyroid)
• MEN IIb (pheo, thryoid, mucosal neuromas)

Question 33

Hyperglycemia / DM2 management overview

Answer 33

• metformin +/- insulin
• if CVD, add antihypergycemic with CV benefit (empaglifozin)
• If on metform and gliclazide:
  
  • add SGLT2, GLP1

Question 34

Renal failure in malignancy

Answer 34

• Pre-renal
• Renal
• Post renal (obstructive)
• Meds:
  
  • chemo
  • radiation
  • NSAIDS etc
• Malignancy
  
  • GN
  • thrombotic microangiopathy
  • minimal change disease
  • membranoproliferative GN
  • paraproteinemia
  • hypercalcemia
  • Uric acid
  • amyloid

Question 35

Management of Renal Failure in Malignancy

Answer 35

• dry mouth
• anorexia
• decrease / stop medications
• opioids and antispasmodics
• Percutaneous nephrostomy tubes
• Stenting

Question 36

Liver Failure in malignancy (causes and treatment)

Answer 36

• Biliary obstruction
  
  • US
  • Perc drain
  • biliary stent
  • Symptomatic reliefe
• Hepatic mets
  
  • jaundice, pruritis, anorexia, liver pain, ascites, coagulopathy
  • prognosis poor with extensive mets
  • Steroids for liver capsular pain
  • maxeran
  • nausea
  • treat hepatic encephalopahy if indicated.