Endocrine Flashcards
Complications of adrenalectomy
IVC injury
devascularized kidney -> HTN
Nerve injury can mimic a hernia
Clinical finding in ectopic ACTH secretion
Bronze skin
Top 5 ectopic ACTH secreting tumors
SSC of Lung PNET Thymic neuroendocrine tumor Pheo MTC
What is size cutoff to safely do a MIS adrenalectomy?
< 6cm
What are perioperative medications for a bilateral adrenalectomy?
preop steroids
post-op steroids with mineralicosteroids (hydrocortisone + Florinef)
4 benefits of Radioactive iodine
Destroy microscopic foci of disease (adjuvant therapy)
Minimize the risk of development of de-novo papillary thyroid cancers in at-risk patients
Improve the specificity of thyroglobulin (Tg) as a tumor marker
Increase the specificity of 131-I scanning for detection of recurrent or metastatic disease
Who should not get radioactive iodine?
No high risk features (LVI, histology)
●Unifocal cancer <1 cm even with less than five lymph nodes measuring less than 2 mm)
●Multifocal cancer when all foci are <1 cm
●Intrathyroidal cancer <4 cm
Who should definitely get radioactive iodine
any gross extrathyroidal extension (T4)
any distant metastatic disease.
Who is intermediate risk who should consider getting RAI?
Tumors > 4cm
microscopic extrathyroidal extension
central and lateral LN involvement
contraindication to RAI
pregnancy and breastfeeding
preparations for RAI
total thyroidectomy
stop synthroid 3-4 weeks before
Must wait 1-3 months from last contrasted CT scan
low iodine diet for 1 week
alternative to stopping sythroid before RAI?
give patient recombinant TSH during therapy
RAI dose for genetic risk
(remnant ablation), 30 mCi
RAI dose for adjuvant therapy
~100 mCi are used
RAI dose for metastatic disease
100 to 200 mCi
Can you do RAI on dialysis?
yes
standard radioiodine dose followed by more frequent dialysis
how to follow patient after RAI?
Tg levels
I131 scan at 6-12 months if not decreasing
toxicities of RAI?
sialoadenitis
secondary cancers
infertility
Advice for radioactive patient after RAI:
The treated patient should remain 6 feet away from other people for about 24 hours after treatment.
especially avoid pregnant women and children
How long to delay pregnancy after RAI?
6 months
Staging for advanced thyroid cancer?
Contrast CT will delay RAI, but RAI is never an emergency…
Adjuvant therapies for parathyroid cancer?
Radiation is effective
[Munson Cancer 2003]
what is the rate of an intrathyroid parathyroid gland?
1-3%
What is the rate of an intrathyroid parathyroid cancer?
<1%
Parathyroid looks white/gray and is invading the RLN? what do you do?
Do en-bloc resection of parathyroid and ipsilateral thyroid lobe with RLN.
Leave the nodes alone if clinically benign.
What syndromes are associated with parathyroid cancer?
MEN
Jaw tumor syndrome
Mechanism of cinacalcet
Calciummemetic, blocks calcium receptor
Is a frozen section helpful for parathyroid cancer?
No need architecture showing invasion or a distant met to make the diagnosis
5 year survival in parathyroid cancer?
40-80%; only retrospective series
Causes of death in parathyroid cancer?
pulmonary mets
renal failure from hypercalcemia.
Absent thyroid lobe
check for ectopic thyroid tissue (tongue)
False negative rate of thyroid nodule < 4 cm
1-4%
False negative rate of a thyroid nodule > 4 cm
10%
Superior margin of a sistrunk procedure?
circumvali papillae in base of tongue
major complication of a sistrunk procedure?
airway injury
Can pyramidal lobe bifurcate?
yes
Chemo for ACC
Mitotane
Pheo lab work-up
plasma metanephrines first, then 24 hour urine for specificity
Aldosteronoma work-up
Lytes, Renin:Angiotensin ratio
IVC sampling is confirmatory and lateralizing test.
Malignancy risk of a 6 cm adrenal mass?
25%
When do you FNA an adrenal mass?
When suspicious for metastatic disease
Path cannot tell an ACC on needle biopsy.
Genetic syndrome associated with ACC
Lynch syndrome
How long to give mitotane for an ACC?
Can give for 5 years; most patients stop sooner due to side effects
Confirmatory test to evaluate for ectopic ACTH?
Ask IR to perform inferior petrossal sampling
ACTH work-up
low dose dex
high dose dex
Bilateral adrenalectomy for an unresectable ACTH secreting tumor?
never for MTC, SCC as survival is too poor. Maybe for a well selected PNET or thymic tumor.
What is mortality from Cushings refractory to medical management?
50% at 2 years
Get a frozen section on a thyroid nodule?
No, not useful
Thyroid nodule with decrease TSH, next step?
start propranolol
technicium uptake scan
only do lobectomy for a functional adenoma
FNA result shows suspicion for Hurthle cell neoplasm,
chance of cancer?
Management?
30% chance this is a Hurthle Cell cancer
would do lobectomy
Pancreatic enucleation is appropriate for?
hormonally functional PNETs
MEN I gene and function
mennin - transcription factor
Best palliative treatment for liver PNETs
TACE
Resect primary tumor in metastatic midgut carcinoid?
yes!
Good retrospective data it improves symptoms in 80% of patients.
Is there a survival benefit to removing primary tumor in metastatic midgut carcinoid?
Debatable. Some retrospective series say yes, but cannot account for selection bias.
Shave nodes off the SMA in metastatic carcinoid?
no.
Still good survival when leaving nodal disease behind.
Median survival after carcinoid resection with bulky nodal disease left behind?
> 6 years in some retrospective series.
HIPEC for carcinoid?
Has been done and abandoned in Europe
No difference in OS
Small PFS improvement, but high morbidity
First citation for 90% debulking of NETs
Sarmiento 2003. Retrospective study with suggesting good OS for these patients with no comparison arm, thus this threshold can be debated
PMID 12735141
What percent of patients recur after Liver debulking for carcinoid?
95%
Who should not get liver debulking for carcinoid?
comorbids that preclude liver surgery
over 50% replacement of hepatic parenchyma
disseminated mets outside the liver.
What percent of thyroid nodules are malignant?
5-10% all comers
US findings suggesting malignant thyroid nodule (6)
hypoechogenicity calcifications vascularity taller than wide ill defined margins absent halo
FNA cutoff for thyroid nodules?
all > 1.5 cm
all > 1 cm with suspicious features
High risk patients for thyroid cancer
history of radiation
genetics
any PET avid node
MEN1 gene
mennin - autosomal dominant
MEN2 gene
RET - autosomal dominant
What percent of MTC are hereditary?
25%
What MTC patients get genetic testing?
all!
MTC with RLN involvement
take the RLN
Operation for MTC
always to total
do central LND if calcitonin >40
transplant all the paras into the forearm
MENIIB gene
RET mutation in codon M918T
MENIIA thyroid management
some data to tailor to specific mutation
follow calcitonin from birth
Perform total thyroidectomy when calcitonin level >150 or patient at age 5
MENIIB thyroid management
Remove thyroid before age 1
Start screening for pheo at age 11
What do you use to guide lymphadenectomy for MTC?
Some use calcitonin levels; (others rely on US)
<20: no nodal dissection
20-50: central and ipsilateral
>50: bilateral neck dissection
>500: add mediastinal lymph node dissection
Who should do thyroidectomies for MENIIB?
should send to quarternary center to manage the incredibly small parathyroids in infants.
Is ultrasound useful for neck nodes in MTC?
not sensitive enough, rely on calcitonin, but need to take ultrasound positive nodes.
Jaw Tumor Syndrome
High risk of parathyroid cancer
Best test to find a parathyroid gland in reoperative scenario?
4DCT
three tumors in VHL
Pheos
RCCs
PNETs
appearance of VHL pancreatic tumors?
Cystic with solid components
Workup for VHL pancreatic tumor?
get a pancreatic MRI look closely for the cystic component.
Most common MEN1 pancreatic tumor
non-hormonal PNET
Steps of a Thompson Procedure for MENI pancreas?
- Subtotal Distal Pancreatectomy
- Enucleate all Head tumors
- perform longitudinal duodenotomy and explore duodenum if gastrin is up.
Outcomes with the Michigan/Thompson Procedure
General Morbidity does not support and 30 of first 40 patients still required reoperation.
When to do a pancreas operation for MENI patient?
tumors >3cm
enlarging tumor
all insulinomas
Perioperative imaging for a MENI pancreas
octroscan preop
intraoperative ultrasound
When to do a duodenotomy for MENI pancreas?
for all elevated gastrin cases
Modern approach to MENI pancreas
Once in the OR do an enucleation for all detectable tumors
only do a whipple for gastrinoma of for recurrence.
rate of adrenal masses in autopsy studies?
7%
CT evaluation of adrenal masses
get a non-contrast CT benign if:
<10 Hounsfield units
well circumscribed
< 4cm
What else do you look for when looking at an adrenal mass?
check to make sure a contralateral adrenal is present!
ACC risk factors for peritoneal recurrence?
numerous risk factors suggesting laparoscopic technique is associated with peritoneal recurrence.
Node positivity rate of ACC?
10%
Any benefit to lymph node dissection for ACC?
no evidence to prove it.
FIRM ACT trial
ACC neoadjuvant trial for mitotane +/- EDT
Higher response rate with EDT but no OS benefit
EDT chemotherapy
Etoposide
Doxorubicin
Cisplatin
ACC with caval thrombus?
Give neoadjuvant EDT and mitotane
intraoperative ultrasound to evaluate extent of thrombus.
tumor thrombectomy
Try to get distal control on IVC. Could guide a balloon from IJ to below the hepatic veins.
RCC <2cm from renal vein can be “milked back”
thrombus below hepatic veins, a simple thrombectomy.
thrombus above hepatic veins, cardiopulmonary bypass
Advanced imaging for pheochromocytoma
PET/Dotatate - most sensitive test.
Would only do if you are still searching for a primary after a normal CT or MRI.
what drugs mess up 24hr urine for metanephrines?
amphetamines, cocaine, MAO and tricyclic antidepressants.
genetic testing for pheos?
test all positive patients and then all 1st degree relatives.
three genetic conditions associated with pheos
Von Hippel Lindau
MENII
Neurofibromatosis I
Observation of PNETs?
can observe low grade <1.5 cm
resect all >1.5 cm and all intermediate and high grade.
Observation of PNETs in MENI patients?
resect all > 1 cm
embryologic origin of PNET tumors
neural crest
resect the primary in small bowel stage IV PNET?
usually should do given that symptomatic relief is well established and some retrospective studies suggest survival benefit
pancreatic PNET management?
consider enucleation.
Ultrasound follow-up of non-FNA thyroid nodules?
●6 to 12 months for subcentimeter nodules with suspicious characteristics
●12 to 24 months for nodules with low to intermediate suspicion on ultrasound
●2 to 3 years for very-low-risk nodules
Suspicious findings for thyroid nodule?
Irregular margins
Microcalcifications
Taller than wide shape
Rim calcifications
check a calcitonin for thyroid nodule?
no, especially if you cannot do a pentagastrin confirmatory test.
FNA a PET avid thyroid nodule?
yes if >1cm
Bethesda Classification
I Nondiagnostic (unsatisfactory) 5 to 10%
II Benign 0 to 3%
III Atypia of undetermined significance (AUS) or follicular lesion of undetermined significance (FLUS) 10 to 30%
IV Follicular neoplasm (or suspicious for follicular neoplasm) 25 to 40%
V Suspicious for malignancy 50 to 75%
VI Malignant 97 to 99%
Thyroid FNA - no follicular tissue is obtained
Bethesda I nondiagnostic - need repeat FNA
Thyroid FNA - dense lymphocytic infiltration and lymphoid germinal centers.
Plasma cell
Hürthle cell changes
fibrosis
Hashimotos Thyroiditis - correlate clinically do not operate.
Thyroid FNA - mild nuclear atypia and lesions with extensive oncocytic (Hürthle cell) change but not enough to be classified as Hürthle cell neoplasm.
Atypia of undetermined significance - Bethesda III - repeat FNA v lobectomy
Thyroid FNA - mixed macrofollicular and microfollicular pattern
Folicular lesion of undetermined significance - Bethesda III - repeat FNA v lobectomy
Thyroid FNA - microfollicles, scant colloid, the absence of follicle formation, cells arranged in clusters and clumps, and varying nuclear atypia and cellular pleomorphism
Follicular neoplasm Bethesda IV - lobectomy
Thyroid FNA - large polyclonal cells with abundant oxyphilic cytoplasm.
Hurthle Cells- bethesda IV - need lobectomy, diagnosis of cancer can only be made after excision
Thyroid FNA - large cells, where cytoplasm has a “ground glass” appearance, nucleoli are prominent, and the nuclei demonstrate clefts and grooves and intranuclear cytoplasmic inclusions (“Orphan Annie eyes”)
Psammoma bodies
dense “sticky” colloid may also be seen
diagnostic for papillary thyroid cancer
Thyroid FNA - eccentrically placed nuclei and cytoplasmic tails. The cytoplasm may be slightly granular and is usually configured as a tear drop or cytoplasmic tail
Medullary Thyroid cancer - may not always be picked up.
immunostain positive for calcitonin
Medullary Thyroid cancer
Thyroid FNA - marked pleomorphism, bizarre giant cells, and spindle cells
AnaplasticThyroid cancer
Pathology of thyroid lymphoma
difficult to distinguish from hashimoto’s thyroiditis
rate of distant mets with anaplastic thyroid cancer?
15-50%
most common location for anapastic thyroid cancer to met?
extensive lung and mediastinum
labs for an anaplastic thyroid cancer
Thyroid function tests
CBC/CMP
Serum calcium and phosphorus
hypercalcemia of malignancy
hypocalcemia due to compromise of the parathyroids
Serum thyroglobulin
image based staging of anaplastic thyroid cancer
PET and brain MRI
Metastatic disease seen with anaplastic TC primary
~30 percent of patients with ATC have coexisting differentiated thyroid cancer,
metastases may not originate from anaplastic thyroid cancer.
thyroglobulin level and/or PET scan may help distinguish between the two
stage IV anaplastic TC management
There is no curative therapy for metastatic anaplastic thyroid cancer, and the disease is uniformly fatal.
median survival 4.2 months, compared with six months in those without metastases.
best case scenario with anaplastic thyroid cancer
with complete R0 resection and post-op radiation, median OS is 2 years.
chemo for anaplastic thyroid cancer
strongly consider clinical trials (basket trials)
doxorubicin
check for BRAF status for vemurafenib/trabetenib
PTC is found in contralateral lobe in what percent?
80%
PTC recurs clinically after what percent of thyroid lobectomies?
3-5%
Offer genetic testing for Bethesda II-IV thyroid nodules?
Probably not ready for primetime/board answer.
Safety is generally established at high experience centers but NPV depends on local incidence.
Multiple validation studies have questioned NPV at different institutions.
non-invasive follicular thyroid neoplasm with papillary like features. (NIFTP)
usually diagnosed at time of diagnostic lobectomy
No completion lobectomy
does need ultrasound surveilance of contralateral lobe.
Ideal candidate for PTC observation?
young patient
small tumor (~<2cm?)
tumor not near capsule, airway or RLN
Observe a Papillary TC?
Probably wouldn’t offer personally but offer referral to quarternary hospital that was following result prospectively.
Saftey seems established at MSKCC and Japanese studies.
Patients who will eventually need PTC resection after o
tumor grows >3mm or >50% from baseline
Evidence of stable persistent thyroid cancer after resection?
This is the norm, try to avoid overtreatment. Consider Tg doubling time.
previous Papillary TC. Tg> 10 and I131 scan is negative, what next?
PET scan
Local recurrence after resection of PTC?
make sure to read old op notes and path notes to gauge quality of previous operation
What disease is RAI most effective for?
very effective for pulmonary mets
minimally effective for bone mets. (consider palliative RT?)
TKIs for stage IV Papillary TC?
sorafenib
Lenvatinib (preferred)
(both dirty TKIs)
what med screws up aldosteronoma work-up?
need to take patient off spirinolactone
AUS/FLUS and benign molecular diagnostics
observation
Goal TSH for high risk PTC patient?
< 0.1 mU/L
Additional supplements when patient of TSH suppression Synthroid?
Calcium
Vitamin D
First measurement of TSH and Tg after PTC resection?
6 - 12 weeks
PTC CNS mets?
gamma knife RT
Hoarsness is a presenting symptom for?
supraglottic or glottic cancer
Treatment for glottic cancer?
T1-T2 definitive RT + laser surgery
Neck node with occult primary?
FNA the node -> SSC
fine cut CT/MRI of the H&N
PET Scan
Labs for occult SSC?
HPV/EBV
Thyroglobulin
Calcitonin
Pax 8
Procedural work-up for SSC occult primary level IV or V node?
tripple endoscopy
laryngoscopy, consider tonsillectomy
bronchoscopy
esophagoscopy
When to get ThyroSeq?
Bethesda 3-4 lesions
if low then <5% chance of cancer
When is it an emergency to give RAI?
never
Pre OR work-up for all thyroid cases?
TSH, T3/T4, thyroglobulin, calcium
laryngoscopy
Neck ultrasound
What is the mortality in the MSKCC PTC observation series?
zero
Risks of thyroidectomy?
3% RLN injury
3% permanent hypothyroid
1% risk of bleeding requiring reoperation
hypoparathyroidism refractory to Ca and other supplements
NATPARA
recombinant PTH injections
Black box warning on NATPARA
caused osteosarcomas in animal experiments
Non-operative options for chyle leak
TPN/no fat diet
if fails, can get IR to sclerose the thoracic duct.
Lambatinib
1st line in RAI non-responsive PTC
Anaplastic Thyroid Cancer
Start with chemoradiation while sending of tumor sequencing
targeted therapy based on sequencing
basket trials
What stage is Anaplastic Thyroid Cancer
Stage IV at presentation
RAI for anaplastic thyroid cancer?
NO!
When to trach anaplastic thyroid cancer?
only when symptomatic
tumor will often grow out of wound and cause bleeding issues.
Gastrinoma management?
are mostly managed with PPIs now.
what to do for a RLN injury?
call for backup
repair with 9-0 suture
Consult a laryngeal specialist after to help with tone.
Bilateral RLN injury?
Need to do an emergent tracheostomy
ACC tumor thrombus
usually small.
See if you can resect and reconstruct that segment
if you can’t go on veno-venous bypass, open vessel and tumor will usually “slide right out.”
ATA 2016 guidelines for RAI?
give for:
extrathyroid extension
R2
distant mets of LN >3cm
selective use: aggressive histologies microscopic extension LVI >5 lymph nodes
Post-op care for parathyroid cancer patient?
trend calcium levels q6hrs.
give standing calcitriol and tums
IV only if symptomatic
dosage for calcitriol
half a microgram daily PO
intense workup of functional adrenal tumors?
dexamethasone supression test
plasma metanephrines
renin/aldosterone levels
hormonal work-up for an ACC?
yes, and not unusual to secrete more than one hormone
Dosing of phenoxybenzamine for pheo?
stat at 10 mg daily
max 100 mg daily
Timing of phenoxybenzamine for a pheo?
at leas two weeks preop
Timing of b-blocker for a pheo?
3-5 days preop
dosing of b-blocker for a pheo?
propranolol 10mg q 6
can change to extended release
alternatives to a/b-blockade for a pheo?
calcium channel blocker
metyrosine (inhibits catacholamine synthesis)
Side effects of metyrosine?
sedation/depression/anxiety nightmares diarrhea urolithiasis galactorrhea extrapyramidal signs
Screening after pheo resection?
Don’t forget genetic testing
Imaging if malignant tumor
annual urine metanephrines
immaging options for an occult Pheo?
standard PET
Dotatate scan
Unresectable stage IV pheo?
XRT
Tace/RFA for liver
I-131 if MIGB scan positive
How do you protect the thyroid if giving I-131 for a pheo?
give patient potassium-iodide
Lutathera for Pheo?
not yet FDA approved, but promising;
could present at tumor board/look for trials
Chemical surveillance of carcinoids/NETs?
chromogrannin level
urinary 5HIAA levels
preparation before a procedure for carcinoids?
give preop octrotide 500 mcg IV
hypotension during carcinoid case?
“carcinoid crisis”
start an octreotide gtt
generally refractory to volume/pressors
can happen during TACE too!
medical therapy for aldosteronoma?
spirinolactone
post-op management after removal of aldosteronoma
check an aldosterone level
Q6 hr lytes to watch for hyperkalemia
Adrenal venous sampling pearls?
can give with cosyntropin infusion to increase sensitivity
need ratio of 1:5 in stimulated test
typically the unaffected side will be even less than the IVC since it is supressed.
patient presents with hypokalemia and hypertension?
aldosteronoma
young patient with unexplained weight change, facial plethora
cushings syndrome (exctopic corticosteroids)
how to rule out Munchausen’s with cushings?
check urinary cortisol, if low then likely patient is taking pills.
cushing’s work-up?
need at least 2 screening tests
low dose dexamethasone supression (1 mg)
urinary cortisol levels
late night salivary levels
high dose dexamethasone supression test
4-8 mg dexamethasone
if plasma cortisol/ACTH supressed then pituitary source.
if no supression, then ectopic tumor
patient presents with adrenal mass and virulazation?
think ACC
what percent of virulizing tumors are cancer?
~50%
What percent of ACC secrete hormones?
50% cortisol
25% androgens
Blood tests for virulizing tumor
adrenal androgens
- —-DHEAS
- —-androstenedione
- —-testosterone
- —-17-hydroxyprogesterone
- —-serum estradiol (men, old women)
control of cortisol secreting ACC?
Mitotane 1 g four times a day
if refractory
metyrapone 250 mg four times a day
control of androgen secreting ACC?
finasteride
tamoxifen
who gets adjuvant mitotane?
high-grade disease (Ki67 >10 percent or mitotic rate greater than 20 per 50 high-power fields [HPF]), incompletely resected disease
intraoperative tumor spillage or fracture
large tumors
vascular or capsular invasion
Any RCTs for ACC?
ADIUVO
RCT for mitotane for low grade resected ACCs
How do you dose Mitotane?
Needs pharmacy serum monitoring
levels between 14 and 20 mcg/mL
tumor markers for MTC?
calcitonin
CEA
5 year recurrence of MTC if biochemical cure?
<5%
follow-up MTC?
complete genetic testing if not done
follow calcitonin/CEA
Get a repeat neck ultrasound at year 1
workup for elevated post-op calcitonin?
<150 start with neck ultrasound
>150 Neck ultrasound and CT c/a/p
Mildly elevated post-op calcitonin and no radiologic evidence of disease?
suspect microscopic disease in the neck,
present at tumor board for consideration of neck irradiation
Symptoms of metastatic MTC?
Diarrhea - usually from large calcitonin producing liver mets
Cushings - ectopic ACTH
Palliation of MTC diarrhea?
imodium (check a c.diff)
octreotide
TACE
palliative debulking
Palliation of MTC cushings?
Vandatanib - dirty TKI hits RET
Mitotane - inhibits synthesis
Bilateral adrenalectomy - select patients carefully
Systemic therapies for stage IV MTC?
consider observation for Mets <1cm and asymptomatic
variety of TKIs (vandatanib 1st)
chemo has <10% response rate
LUTATHERA is emerging
Resect a primary MTC in the setting of stage IV disease?
only for palliation of airway or esophageal compression.
usefulness of postop PTH?
multiple studies show that PTH < 10 predicts symptomatic hypocalcemia and can be used to guide calcium replacement.
critical error to avoid on a parathyroid cancer?
rupture caries a high risk of neck carcinomatosis.
when to enucleate an insulinoma?
tumors < 2cm away from the main duct
Test for MEN I first so you don’t miss additional lesions
malignancy rate of insulinomas?
10%
most common non-adrenal location of a pheo?
organ of zuckerkandl at the aortic bifurcation.
jaw tumor syndrome
hyperparathyroidism
mandible fibromas
kidney lesions
patient presents with high PTH and calcium?
get genetic testing first before going into hyperparathyroid work-up!
Lymph node dissection for follicular carcinoma?
NO! spreads hematogenously
remainder of treatment is as per PTC
Initial work-up for an insulinoma?
fasting glucose and insulin level
c-peptide
get genetic testing or Brain MRI Ca++/PTH to rule our MEN I
What to do before OR for an insulinoma?
Admit night before for D10 infusion while NPO