Paraneoplastic Syndromes: Endocrinologic/Hematologic Flashcards
rapid correction of severe hypercalcemia
Calcitonin (2–8 U/kg SC every 6–12 h)
treatment of symptomatic eosinophilia
steroids
Causes of ectopic ACTH secretion with percentage
SCLC(>50%)
thymic carcinoid(15%)
islet cell tumors(10%)
bronchial carcinoid(10%)
other carcinoids(5%)
pheochromocytoma(2%)
oncogenic osteomalacia is caused by benign tumors located at
extremities and head
Most common paraneoplastic endocrine syndromes
hypercalcemia from overproduction of PTHrP
hyponatremia from excess vasopressin
Cushing’s syndrome from ectopic ACTH
lab values in oncogenic osteomalacia
Low serum phosphate level
normal PTH
Normal serum calcium
low 1,25-dihydroxyvitamin D
The transcription factor expressed at abnormally high levels in SCLC associated with ectopic ACTH
hASH 1
human achaete-scute homologue 1
Growth hormone producing tumors
lung
pancreatic islet
Testing for PE in cancer pts
CXR
ECG
ABG
Ventilation perfusion scan
D dimer in diagnosis of paraneoplastic DVT
Not very predictive
elevations seen in pts older than 65 years without DVT
Causes of tumor induced hypoglycemia in HCC
Reduced gluconeogenesis due to large mass
IGF2
Tumors causing hyperthyroidism
Hydatidiform mole, embryonal tumors, struma ovarii
Clinical manifestations of ectopic ACTH production
Easy bruising,skin fragility
hyperpigmentation
steroid psychosis
prevalence of granulocytosis in different cancers
Lung 40%
GIT 40%
Breast cancer 20%
brain tumors 30%
ovarian tumors 30%
hodgkin 20%
RCC 10%
CRH producing tumors
Pancreatic islet, carcinoid, lung, prostate
Tumor induced SIADH is aggravated by
free water intake oral or iv
Tumors causing oncogenic osteomalacia
Hemangiopericytomas, osteoblastomas, fibromas, sarcomas, giant cell tumors, prostate, lung
Cause of tumor induced eosinophilia
IL-5
Prognosis in the presence of paraneoplastic thrombocytosis
poor
Dose of bisphosphonates used for treatment of hypercalcemia
Pamidronate 60-90mg iv
Zoledronate 4-8mg iv
etidronate 7.5 mg/kg per day PO for 3–7 consecutive days
Ectopic ACTH secretion accounts for _______ % of cushing syndrome
10-20%
hereditary X-linked hypophosphatemia is due to
inactivating mutations in the PHEX gene
When should you look for cancer in DVT pts?
Refractory clots
Unusal sites
Migratory or recurrent thrombophlebitis
granulocytosis
Granulocyte count> 8000/µL
Solid tumors producing thrombocytosis
Lung cancer
Gastrointestinal cancer
Breast cancer
Ovarian cancer
Lymphoma
Tumors producing PGE2
Renal
lung
Rx of ectopic cushing
Treatment of primary tumor(rarely sufficient)
Unresectable tumor with good prognosis(carcinoid): adrenalectomy
Medical therapy:
Ketoconazole(300–600 mg PO bid)
metyrapone(250–500 mg PO every 6 h)
Mitotane(3–6 g PO in four divided doses)
Jeopardy
IL-5
Cause of tumor induced eosinophilia
Percentage of pts with RCC,HCC and cerebellar hemangioblastoma having erythrocytosis
RCC 3%
HCC 10%
Cerebellar hemangioblastoma 15%
bisphosphonates can reduce calcium within
1-2 days
Tumors producing PTH
Lung
Ovary
protein causing thrombocytosis in solid malignancies
IL-6
Cancers associated with thrombophlebitis
Lung cancer
Pancreatic cancer
Gastrointestinal cancer
Breast cancer
Genitourinary cancer
Ovarian cancer
Prostate cancer
Lymphoma
Tumors producing Insulin like growth factor-2
Mesenchymal tumors, sarcomas, adrenal, hepatic, gastrointestinal, kidney, prostate
Tumors associated with excess PTHrP
Squamous cell (head and neck, lung, skin), breast, genitourinary, gastrointestinal
hCG alpha production is high in which cancers
Lung cancer
pancreatic islet cancer
Tumors producing eosinophilia
Lymphoma
Leukemia
Lung cancer
Dose of oral phosphorus
neutra phos 250mg tds
Cause for severe hypokalemia in ectopic ACTH secretion
excess minerelocorticoids due to ACTH stimulation of adrenal gland
high cortisol levels overwhelm 11ß -hydroxysteroid dehydrogenase type II enzyme
Phex gene codes for
protease that inactivates FGF23
Incidence of SIADH in SCLC
50% of SCLC patients
diagnosis of tumor induced hypoglycemia
Low serum glucose levels
low insulin
symptoms of hypoglycemia
Symptoms with severe eosinophilia(>5000/µL)
shortness of breath
wheezing
Difference btw ectopic ACTH secretion and pitutary ACTH
Ectopic ACTH doesnot respond to high dose dexamethasone suppression test
Trousseau’s syndrome
peripheral venous thrombosis with visceral carcinoma
TIO
Tumor induced osteomalacia
Diff btw HHM and Primary hyperparathyroidism
PTH level
HHM: Metabolic alkalosis
Hyperparathyroidism: Hyperchloremic acidosis
PTHrP leads to a drop in urinary bicarbonate excretion rather than the increase in urinary bicarbonate produced by PTH
Difference in clinical manifestation between ectopic ACTH and other causes of cushing syndrome
Ectopic ACTH:
Less weight gain and centripetal fat distribution
How long should warfarin be given for cancer pts with DVT
3-6 months
Humoral hypercalcemia of malignancy occurs in ________ % of cancer patients
Diagnosis of ectopic ACTH secretion
Urine free cortisol levels
plasma ACTH >100pg/ml
Jeopardy
IL-6
protein causing thrombocytosis in solid malignancies
Rx of proximal DVT in cancer pts with relative contraindication to anticoagulation
Placement of IVC filters(greenfield)
Tumors producing calcitonin
Lung, colon, breast, medullary thyroid carcinoma
Definitive test to differentiate pitutary ACTH excess with ectopic ACTH excess
Petrosal vein sampling after CRH stimulation
ratio >3:1 between Petrosal and peripheral ACTH is suggestive of pitutary source
Ectopic hormones causing diarrhea
calcitonin
VIP
Tumor producing excess 1,25 dihydroxy VitD
Lymphomas
Relative contraindication to heparin anticoagulation for DVT in cancer patients
hemorrhagic brain metastases
pericardial effusion
Defence of body to tumor induced SIADH
decreased thirst
Dose of steroids in HHM
40-100mg Po QID
Steroids are useful for treatment of hypercalcemia due to
Lymphoma
leukemia
multiple myeloma
Jeopardy
inactivating mutations in the PHEX gene
hereditary X-linked hypophosphatemia is due to
Why weight gain and fat redistribution is less in ectopic ACTH production?
exposed to steroids for short time
cancer induced cachexia and weight loss
Cancers causing granulocytosis as paraneoplastic syndrome
Lung cancer
Gastrointestinal cancer
Ovarian cancer
Genitourinary cancer
Hodgkin’s disease
Treatment of tumor induced hypoglycemia
Treatment of underlying malignancy
frequent meals
IV glucose during fasting and sleep
glucagon
glucocorticoids
Paraneoplastic syndrome
Disorders that accompany benign or malignant tumors but are not directly related to mass effects or invasion
Jeopardy
protease that inactivates FGF23
Phex gene codes for
Indication for heparin prophylaxis in cancer pts
Those who undergo major surgery
Proteins that sequester IGF2
ALS(acid labile subunit)
IGF binding protein 3
Ectopic hormones causing cushing syndrome
ACTH
CRH
GIP(gastric inhibitory peptide)
LH
hCG
Last three are associated with macronodular adrenal hyperplasia
Serum IGF2 levels in tumor induced hypoglycemia
May not be increased
As hypoglycemia is due to release of hormone from binding proteins
Women with hCG producing tumors
asymptomatic
Factors causing granulocytosis associated with solid tumors
G CSF
GM CSF
IL-6
ACTH producing tumors
Lung (small cell, bronchial carcinoid, adenocarcinoma, squamous), thymus, pancreatic islet, medullary thyroid carcinoma
Features that favor HHM, as opposed to primary hyperparathyroidism
Known malignancy, recent onset of hypercalcemia, and very high serum calcium levels
tumors producing VIP
Pancreas, pheochromocytoma, esophagus
action of FGF23
inhibits renal tubular reabsorption of phosphate
inhibits renal conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D
Vassopressin secretion due to adaptive circulatory mechanisms is seen in
HF
cirrhosis
hypotension
Ectopic sources of ACTH which respond to high dose dexamethasone test
bronchial and other carcinoids
Also show ACTH responsiveness to adrenal blockade with metyrapone
Dose of warfarin prophylaxis in cancer pts
1 mg/day
The prevalence of thrombocytosis in different cancers
Lung and GIT 40%
20% of patients with breast, endometrial, and ovarian cancers
Lymphoma 10%
Renin secreting tumors
Hypertension
Juxtaglomerular tumors, kidney, lung, pancreas, ovary
________ % of pts with thrombocytosis have an underlying diagnosis of cancer
35
Cause of gynacomastia in hCG secreting tumors
high hCG►increased steroidogenesis and aromatase activity in leydig cells of testis►increased estrogen
warfarin prophylaxis in cancer patients
Breast cancer patients undergoing chemotherapy
Pts with implanted catheters
thrombocytosis
Platelet count> 4,00,000/µL
Rx of DVT or PE in cancer pts
UFH/LMWH for 5 days
Warfarin started within 1 or 2 days
Maintain INR btw 2-3
GHRH producing tumors
Pancreatic islet, bronchial and other carcinoids
Tumors causing SIADH
Lung (squamous, small cell), gastrointestinal, genitourinary, ovary
Precocious puberty in boys or gynacomastia in men
measurement of hCG
consideration of a testicular tumor or another source of ectopic hCG production
Clinical features of oncogenic osteomalacia
Muscle weakness
bone pain
osteomalacia
Factor responsible for oncogenic osteomalacia
Phosphatonin [fibroblast growth factor 23 (FGF23)]
treatment of oncogenic osteomalacia
removal of tumor
supplementation with phosphate and vitamin D
Ectopic factors responsible for hypercalcemia of malignancy
Parathyroid hormone-related protein (PTHrP)
1,25 dihydroxyvitamin D
Parathyroid hormone (PTH)
Prostaglandin E2 (PGE2)
last two are rare causes
target Phosphorus levels in HHM
>3 mg/dl
Metabolic manifestations of ectopic ACTH production
fluid retention
hypertension
hypokalemia
metabolic alkalosis
glucose intolerance
Rx of SIADH
Water restriction
Vaptans: conivaptan
oral: 20-120mg bd
IV: 10-40mg
Demeclocycline :
150–300 mg orally three to four times daily
Granulocytosis is more likely to be seen in ________ stages of disease
Advanced
High dose dexamethasone suppression test
8mg of dexamethasone PO supresses 8am serum cortisol(
Tests to diagnose DVT
Impedence plethysmography
b/l compression USG of leg veins
Role of octreotide in oncogenic osteomalacia
Reduces phosphate wasting in some patients with tumors that express somatostatin receptor subtype 2
Tumor producing insulin
Cervix (small cell carcinoma)
What to do in equivocal V/P scans in suspected PE pts?
USG to screen for DVT
If present,start anticoagulation
If absent,do pulmonary angiogram
Jeopardy
measurement of hCG
consideration of a testicular tumor or another source of ectopic hCG production
Precocious puberty in boys or gynacomastia in men
Oncogenic osteomalacia is similar to
hereditary X-linked hypophosphatemia
_______ % of pts with APLAS have cancers
20%
Tumors causing male feminisation
tumors secreting hCG
Testis (embryonal, seminomas), germinomas, choriocarcinoma, lung, hepatic, pancreatic islet
Nonparaneoplastic causes of granulocytosis
Infection
tumor necrosis
Glucocorticoid administration
