Endocrine, C57 P418-437 Flashcards
ADRENAL GLAND ANATOMY Where is the drainage of the left adrenal vein? P418
Left renal vein
ADRENAL GLAND ANATOMY Where is the drainage of the right adrenal vein? P418
Inferior vena cava (IVC)
ADRENAL GLAND
NORMAL ADRENAL PHYSIOLOGY
What is CRH?
P419
Corticotropin-Releasing Hormone:
released from anterior hypothalamus and
causes release of ACTH from anterior
pituitary
ADRENAL GLAND
NORMAL ADRENAL PHYSIOLOGY
What is ACTH?
P419
AdrenoCorticoTropic Hormone: released
normally by anterior pituitary, which in
turn causes adrenal gland to release
cortisol
ADRENAL GLAND NORMAL ADRENAL PHYSIOLOGY What feeds back to inhibit ACTH secretion? P419
Cortisol
ADRENAL GLAND CUSHING’S SYNDROME CUSHING’S SYNDROME What is Cushing’s syndrome? P419
Excessive cortisol production (Think:
Cushing’s = Cortisol
ADRENAL GLAND CUSHING’S SYNDROME What is the most common cause? P419
Iatrogenic (i.e., prescribed prednisone)
ADRENAL GLAND CUSHING’S SYNDROME What is the second most common cause? P419
Cushing’s disease (most common
noniatrogenic cause)
ADRENAL GLAND
CUSHING’S SYNDROME
What is Cushing’s disease?
P419
Cushing’s syndrome caused by excess
production of ACTH by anterior pituitary
ADRENAL GLAND CUSHING’S SYNDROME What is an ectopic ACTH source? P419
Tumor not found in the pituitary that
secretes ACTH, which in turn causes
adrenal gland to release cortisol without
the normal negative feedback loop
ADRENAL GLAND CUSHING’S SYNDROME What are the signs/ symptoms of Cushing’s syndrome? P419
Truncal obesity, hirsutism, “moon”
facies, acne, “buffalo hump,” purple
striae, hypertension, diabetes, weakness,
depression, easy bruising, myopathy
ADRENAL GLAND CUSHING’S SYNDROME How can cortisol levels be indirectly measured over a short duration? P419
By measuring urine cortisol or the
breakdown product of cortisol,
17 hydroxycorticosteroid (17-OHCS),
in the urine
ADRENAL GLAND CUSHING’S SYNDROME What is a direct test of serum cortisol? P419
Serum cortisol level (highest in the morning
and lowest at night in healthy patients)
ADRENAL GLAND CUSHING’S SYNDROME What initial tests should be performed in Cushing’s syndrome? P420
Electrolytes
Serum cortisol
Urine-free cortisol, urine 17-OHCS
Low-dose dexamethasone suppression test
ADRENAL GLAND CUSHING’S SYNDROME What is the low-dose dexamethasone suppression test? P420
Dexamethasone is a synthetic cortisol that results in negative feedback on ACTH secretion and subsequent cortisol secretion in healthy patients; patients with Cushing’s syndrome do not suppress their cortisol secretion
ADRENAL GLAND CUSHING’S SYNDROME After the dexamethasone test, what is next? P420
Check ACTH levels
ADRENAL GLAND CUSHING’S SYNDROME Can plasma ACTH levels be checked directly? P420
Yes
ADRENAL GLAND CUSHING’S SYNDROME What is the workup in a patient suspected of having Cushing’s syndrome? P420 (picture)
(see picture)
ADRENAL GLAND CUSHING’S SYNDROME In ACTH-dependent Cushing’s syndrome, how do you differentiate between a pituitary vs. an ectopic ACTH source? P421
High-dose dexamethasone test: Pituitary source—cortisol is suppressed Ectopic ACTH source—no cortisol suppression
ADRENAL GLAND CUSHING’S SYNDROME Summarize the “Cushing’s syndrome” lab values found in the majority of patients with the following conditions: Healthy patients P421
Normal cortisol and ACTH,
suppression with low-dose or
high-dose dexamethasone (<1/2)
ADRENAL GLAND CUSHING’S SYNDROME Summarize the “Cushing’s syndrome” lab values found in the majority of patients with the following conditions: Cushing’s disease (pituitary ACTH hypersecretion) P421
High cortisol and ACTH, no suppression
with low-dose dexamethasone, suppression
with high-dose dexamethasone
ADRENAL GLAND CUSHING’S SYNDROME Summarize the “Cushing’s syndrome” lab values found in the majority of patients with the following conditions: Adrenal tumor P421
High cortisol, low ACTH, no
suppression with low-dose or high-dose
dexamethasone
ADRENAL GLAND CUSHING’S SYNDROME Summarize the “Cushing’s syndrome” lab values found in the majority of patients with the following conditions: Ectopic ACTH-producing tumor P421
High cortisol and ACTH, no suppression
with low-dose or high-dose dexamethasone
ADRENAL GLAND
CUSHING’S SYNDROME
What is the test for equivocal results for
differentiating pituitary vs. ectopic ACTH tumor?
P421
Bilateral petrosal vein sampling,
especially with CRH infusion
ADRENAL GLAND CUSHING’S SYNDROME What is the most common site of ectopic ACTH-producing tumor? P421
>66% are oat cell tumors of the lung
#2 is carcinoid
ADRENAL GLAND CUSHING’S SYNDROME How are the following tumors treated: Adrenal adenoma? P421
Adrenalectomy (almost always unilateral)
ADRENAL GLAND CUSHING’S SYNDROME How are the following tumors treated: Adrenal carcinoma? P421
Surgical excision (only 33% of cases are operable)
ADRENAL GLAND CUSHING’S SYNDROME How are the following tumors treated: Ectopic ACTH-producing tumor? P421
Surgical excision, if feasible
ADRENAL GLAND CUSHING’S SYNDROME How are the following tumors treated: Cushing’s disease? P421
Transphenoidal adenomectomy
ADRENAL GLAND
CUSHING’S SYNDROME
What medication must be given to a patient who is undergoing surgical correction of Cushing’s syndrome?
P422
Cortisol (usually hydrocortisone until PO
is resumed)
ADRENAL GLAND CUSHING’S SYNDROME What medications inhibit cortisol production? P422
- Ketoconazole
- Metyrapone
- Aminoglutethimide
- Mitotane
ADRENAL GLAND CUSHING’S SYNDROME Give the mechanism of action: Ketoconazole (an antifungal) P422
Inhibits 11 ℬ–hydroxylase, c17-20 lyase,
and cholesterol side-chain cleavage
ADRENAL GLAND CUSHING’S SYNDROME Give the mechanism of action: Aminoglutethimide (an anticonvulsant) P422
Inhibits cleavage of cholesterol side
chains
ADRENAL GLAND CUSHING’S SYNDROME Give the mechanism of action: Mitotane P422
Inhibits 11 ℬ-hydroxylase and cholesterol
side-chain cleavage; causes irreversible
adrenocortical cells (and thus can be
used for “medical adrenalectomy”)
ADRENAL GLAND CUSHING’S SYNDROME Give the mechanism of action: Metyrapone P422
Inhibits 11 ℬ-hydroxylase
ADRENAL GLAND CUSHING’S SYNDROME What is a complication of BILATERAL adrenalectomy? P422
Nelson’s syndrome—occurs in 10% of
patients after bilateral adrenalectomy
ADRENAL GLAND
CUSHING’S SYNDROME
What is Nelson’s syndrome?
P422
Functional pituitary adenoma producing excessive ACTH and mass effect producing visual disturbances, hyperpigmentation, amenorrhea, with elevated ACTH levels Think: Nelson = Nuclear reaction in the pituitary
ADRENAL GLAND
ADRENAL INCIDENTALOMA
What is an incidentaloma?
P422
Tumor found in the adrenal gland
incidentally on a CT scan performed for
an unrelated reason
ADRENAL GLAND ADRENAL INCIDENTALOMA What is the incidence of incidentalomas? P422
4% of all CT scans (9% of autopsies)
ADRENAL GLAND ADRENAL INCIDENTALOMA What is the most common cause of incidentaloma? P423
Nonfunctioning adenoma ( >75% of cases)
ADRENAL GLAND ADRENAL INCIDENTALOMA What is the differential diagnosis of incidentaloma? P423
Nonfunctioning adenoma Pheochromocytoma Adrenocortical carcinoma Aldosteronoma Metastatic disease Nodular hyperplasia
ADRENAL GLAND ADRENAL INCIDENTALOMA What is the risk factor for carcinoma? P423
Solid tumor >6 cm in diameter
ADRENAL GLAND
ADRENAL INCIDENTALOMA
What is the treatment?
P423
Controversial for smaller/medium-sized tumors, but almost all surgeons would agree that resection is indicated for solid incidentalomas >6 cm in diameter because of risk of cancer
ADRENAL GLAND ADRENAL INCIDENTALOMA What are the indications for removal of adrenal incidentaloma less than 6 cm? P423
MRI T2 signal >2 Hormonally active = hyperfunctioning tumor Enlarging cystic lesion Does not look like an adenoma
ADRENAL GLAND ADRENAL INCIDENTALOMA What tumor must be ruled out prior to biopsy or surgery for any adrenal mass? P423
Pheochromocytoma (24-hour urine for
catecholamine, VMA, metanephrines)
ADRENAL GLAND
PHEOCHROMOCYTOMA
What is it?
P423
Tumor of the adrenal MEDULLA and
sympathetic ganglion (from chromaffin
cell lines) that produces catecholamines
(norepinephrine > epinephrine)
ADRENAL GLAND
PHEOCHROMOCYTOMA
What is the incidence?
P423
Cause of hypertension in ≈1/500
hypertensive patients (≈10% of U.S.
population has hypertension)
ADRENAL GLAND PHEOCHROMOCYTOMA Which age group is most likely to be affected? P423
Any age (children and adults); average age is 40 to 60 years
ADRENAL GLAND PHEOCHROMOCYTOMA What are the associated risk factors? P423
MEN-II, family history, von Recklinghausen
disease, von Hippel-Lindau disease
ADRENAL GLAND PHEOCHROMOCYTOMA What are the signs/ symptoms? P424
“Classic” triad: 1. Palpitations 2. Headache 3. Episodic diaphoresis Also, hypertension (50%), pallor → flushing, anxiety, weight loss, tachycardia, hyperglycemia
ADRENAL GLAND PHEOCHROMOCYTOMA How can the pheochromocytoma SYMPTOMS triad be remembered? P424
Think of the first three letters in the word PHEochromocytoma: Palpitations Headache Episodic diaphoresis
ADRENAL GLAND PHEOCHROMOCYTOMA What is the most common sign of pheochromocytoma? P424
Hypertension
ADRENAL GLAND PHEOCHROMOCYTOMA What is the differential diagnosis? P424
Renovascular hypertension, menopause, migraine headache, carcinoid syndrome, preeclampsia, neuroblastoma, anxiety disorder with panic attacks, hyperthyroidism, insulinoma
ADRENAL GLAND PHEOCHROMOCYTOMA What diagnostic tests should be performed? P424
Urine screen: VanillylMandelic Acid (VMA), metanephrine, and normetanephrine (all breakdown products of the catechols) Urine/serum epinephrine/ norepinephrine levels
ADRENAL GLAND PHEOCHROMOCYTOMA What are the other common lab findings? P424
Hyperglycemia (epinephrine increases glucose, norepinephrine decreases insulin) Polycythemia (resulting from intravascular volume depletion)
ADRENAL GLAND PHEOCHROMOCYTOMA What is the most common site of a pheochromocytoma? P424
Adrenal >90%
ADRENAL GLAND PHEOCHROMOCYTOMA What are the other sites for pheochromocytoma? P424
Organ of Zuckerkandl, thorax
(mediastinum), bladder, scrotum
ADRENAL GLAND PHEOCHROMOCYTOMA What are the tumor localization tests? P424
CT scan, MRI, I-MIBG, PET scan,
OctreoScan (In-pentetreotide scan)
ADRENAL GLAND PHEOCHROMOCYTOMA What does I-MIBG stand for? P425
IodineMetaIodoBenzylGuanidine
ADRENAL GLAND PHEOCHROMOCYTOMA How to remember MIBG and pheochromocytoma? P425
Think: MIBG = My Big = and thus
“My Big Pheo” = MIBG Pheo
ADRENAL GLAND PHEOCHROMOCYTOMA How does the I-MIBG scan work? P425
I-MIBG is a norepinephrine analog
that collects in adrenergic vesicles and,
thus, in pheochromocytomas
ADRENAL GLAND
PHEOCHROMOCYTOMA
What is the role of PET scan?
P425
Positron Emission Tomography is helpful
in localizing pheochromocytomas that do
not accumulate MIBG
ADRENAL GLAND PHEOCHROMOCYTOMA What is the scan for imaging adrenal cortical pheochromocytoma? P425
NP-59 (a cholesterol analog)
ADRENAL GLAND PHEOCHROMOCYTOMA What is the localizing option if a tumor is not seen on CT, MRI, or I-MIBG? P425
IVC venous sampling for catecholamines
gradient will help localize the tumor
ADRENAL GLAND PHEOCHROMOCYTOMA What is the tumor site if epinephrine is elevated? P425
Must be adrenal or near the adrenal gland
(e.g., organ of Zuckerkandl), because
nonadrenal tumors lack the capability to
methylate norepinephrine to epinephrine
ADRENAL GLAND PHEOCHROMOCYTOMA What percentage of patients have malignant tumors? P425
≈10%
ADRENAL GLAND PHEOCHROMOCYTOMA Can histology be used to determine malignancy? P425
No; only distant metastasis or invasion
can determine malignancy
ADRENAL GLAND PHEOCHROMOCYTOMA What is the classic pheochromocytoma “rule of 10’s”? P425
10% malignant 10% bilateral 10% in children 10% multiple tumors 10% extra-adrenal
ADRENAL GLAND PHEOCHROMOCYTOMA What is the preoperative/ medical treatment? P425
Increase intravascular volume with
a-blockade (e.g., phenoxybenzamine
or prazosin) to allow reduction in
catecholamine-induced vasoconstriction
and resulting volume depletion; treatment
should start as soon as diagnosis is made
+/– ℬ-blockers
ADRENAL GLAND PHEOCHROMOCYTOMA How can you remember phenoxybenzamine as a medical treatment of pheochromocytoma? P426
PHEochromocytoma =
PHEnoxybenzamine
ADRENAL GLAND PHEOCHROMOCYTOMA What is the surgical treatment? P426
Tumor resection with early ligation of
venous drainage (lower possibility of
catecholamine release/crisis by tying off
drainage) and minimal manipulation
ADRENAL GLAND PHEOCHROMOCYTOMA What are the possible perioperative complications? P426
Anesthetic challenge: hypertensive crisis
with manipulation (treat with nitroprusside),
hypotension with total removal of
the tumor, cardiac dysrhythmias
ADRENAL GLAND PHEOCHROMOCYTOMA In the patient with pheochromocytoma, what must be ruled out? P426
MEN type II (almost all cases are
bilateral)
ADRENAL GLAND PHEOCHROMOCYTOMA What is the organ of Zuckerkandl? P426
Body of embryonic chromaffin cells around the abdominal aorta (near the inferior mesenteric artery); normally atrophies during childhood, but is the most common site of extra-adrenal pheochromocytoma
ADRENAL GLAND
CONN’S SYNDROME
What is it?
P426
Primary hyperaldosteronism due to
high aldosterone production
ADRENAL GLAND CONN’S SYNDROME How do you remember what Conn’s syndrome is? P426 (picture)
CONn’s disease = HYPERALdosterone
= “CON HYPER AL”
ADRENAL GLAND CONN’S SYNDROME What are the common sources? P427
Adrenal adenoma or adrenal
hyperplasia; aldosterone is abnormally
secreted by an adrenal adenoma (66%)
> hyperplasia > carcinoma
ADRENAL GLAND CONN’S SYNDROME What is the normal physiology for aldosterone secretion? P427
BP in the renal afferent arteriole is low Low sodium and hyperkalemia cause renin secretion from juxtaglomerular cells Renin then converts angiotensinogen to angiotensin I Angiotensin converting enzyme in the lung then converts angiotensin I to angiotensin II Angiotensin II then causes the adrenal glomerulosa cells to secrete aldosterone
ADRENAL GLAND CONN’S SYNDROME What is the normal physiologic effect of aldosterone? P427
Aldosterone causes sodium retention for
exchange of potassium in the kidney, resulting
in fluid retention and increased BP
ADRENAL GLAND
CONN’S SYNDROME
What are the signs/symptoms?
P427
Hypertension, headache, polyuria,
weakness
ADRENAL GLAND CONN’S SYNDROME What are the two classic clues of Conn’s syndrome? P427
- Hypertension
2. Hypokalemia
ADRENAL GLAND CONN’S SYNDROME Classically, what kind of hypertension? P427
Diastolic hypertension
ADRENAL GLAND CONN’S SYNDROME What are the renin levels with Conn’s syndrome? P427
Normal or decreased!
ADRENAL GLAND CONN’S SYNDROME What percentage of all patients with hypertension have Conn’s syndrome? P427
1%
ADRENAL GLAND CONN’S SYNDROME What diagnostic tests should be ordered? P427
- Plasma aldosterone concentration
2. Plasma renin activity
ADRENAL GLAND CONN’S SYNDROME What ratio of these diagnostic tests is associated with primary hyperaldosteronism? P427
Aldosterone to renin ratio of >30
ADRENAL GLAND CONN’S SYNDROME What is secondary hyperaldosteronism? P428
Hyperaldosteronism resulting from
abnormally high renin levels (renin
increases angiotensin/aldosterone)
ADRENAL GLAND CONN’S SYNDROME What diagnostic tests should be performed? P428
CT scan, adrenal venous sampling for
aldosterone levels, saline infusion
ADRENAL GLAND CONN’S SYNDROME What is the saline infusion test? P428
Saline infusion will decrease aldosterone
levels in normal patients but not in
Conn’s syndrome
ADRENAL GLAND CONN’S SYNDROME What is the preoperative treatment? P428
Spironolactone, K⁺ supplementation
ADRENAL GLAND
CONN’S SYNDROME
What is spironolactone?
P428
Antialdosterone medication (works at the kidney tubule)
ADRENAL GLAND CONN’S SYNDROME What are the causes of Conn’s syndrome? P428
Adrenal adenoma (66%)
Bilateral idiopathic adrenal hyperplasia
(30%)
Adrenal cancer ( < 1%)
ADRENAL GLAND CONN’S SYNDROME What is the treatment of the following conditions: Adenoma? P428
Unilateral adrenalectomy (laparoscopic)
ADRENAL GLAND CONN’S SYNDROME What is the treatment of the following conditions: Unilateral hyperplasia? P428
Unilateral adrenalectomy (laparoscopic)
ADRENAL GLAND CONN’S SYNDROME What is the treatment of the following conditions: Bilateral hyperplasia? P428
Spironolactone (usually no surgery)
ADRENAL GLAND CONN’S SYNDROME What are the renin levels in patients with PRIMARY hyperaldosteronism? P428
Normal or low (key point!)
ADRENAL GLAND
ADDISON’S DISEASE
What is it?
P428
Acute adrenal insufficiency
ADRENAL GLAND ADDISON’S DISEASE What are the electrolyte findings? P428
HYPERkalemia, hyponatremia
ADRENAL GLAND ADDISON’S DISEASE How do you remember what ADDISON’s disease is? P428
Think: ADDison’s disease = ADrenal
Down
ADRENAL GLAND
INSULINOMA
What is it?
P428
Insulin-producing tumor arising from ℬ cells
ADRENAL GLAND
INSULINOMA
What is the incidence?
P429
#1 Islet cell neoplasm; half of ℬ cell tumors of the pancreas produce insulin
ADRENAL GLAND INSULINOMA What are the associated risks? P429
Associated with MEN-I syndrome
(PPP = Pituitary, Pancreas, Parathyroid
tumors)
ADRENAL GLAND INSULINOMA What are the signs/ symptoms? P429
Sympathetic nervous system symptoms
resulting from hypoglycemia:
palpitations, diaphoresis, tremulousness,
irritability, weakness
ADRENAL GLAND INSULINOMA What are the neurologic symptoms? P429
Personality changes, confusion,
obtundation, seizures, coma
ADRENAL GLAND
INSULINOMA
What is Whipple’s triad?
P429
1. Hypoglycemic symptoms produced by fasting 2. Blood glucose 50 mg/dL during symptomatic attack 3. Relief of symptoms by administration of glucose
ADRENAL GLAND INSULINOMA What is the differential diagnosis? P429
Reactive hypoglycemia Functional hypoglycemia with gastrectomy Adrenal insufficiency Hypopituitarism Hepatic insufficiency Munchausen syndrome (insulin self-injections) Nonislet cell tumor causing hypoglycemia Surreptitious administration of insulin or OHAs
ADRENAL GLAND INSULINOMA What lab tests should be performed? P429
Glucose and insulin levels during fast;
C-peptide and proinsulin levels (if selfinjection
of insulin is a concern, as insulin
injections have no proinsulin or C-peptides)
ADRENAL GLAND INSULINOMA What diagnostic tests should be performed? P429
Fasting hypoglycemia with
inappropriately high levels of insulin
72-hour fast, then check glucose and
insulin levels every 6 hours (monitor
very closely because patient can
develop hypoglycemic crisis)
ADRENAL GLAND INSULINOMA What is the diagnostic fasting insulin to glucose ratio? P430
> 0.4
ADRENAL GLAND INSULINOMA What localizing tests should be performed? P430
CT scan, A-gram, endoscopic U/S, venous
catheterization (to sample blood along
portal and splenic veins to measure insulin
and localize tumor), intraoperative U/S
ADRENAL GLAND INSULINOMA What is the medical treatment? P430
Diazoxide, to suppress insulin release
ADRENAL GLAND INSULINOMA What is the surgical treatment? P430
Surgical resection
ADRENAL GLAND
INSULINOMA
What is the prognosis?
P430
≈80% of patients have a benign solitary
adenoma that is cured by surgical resection
GLUCAGONOMA
What is it?
P430
Glucagon-producing tumor
GLUCAGONOMA
Where is it located?
P430
Pancreas (usually in the tail)
GLUCAGONOMA
What are the symptoms?
P430
Necrotizing migratory erythema
(usually below the waist), glossitis,
stomatitis, diabetes
GLUCAGONOMA
What are the skin findings?
P430
Necrotizing migratory erythema is a red,
often psoriatic-appearing rash with serpiginous
borders over the trunk and limbs
GLUCAGONOMA
What are the associated lab
findings?
P430
Hyperglycemia, low amino acid levels,
high glucagon levels
GLUCAGONOMA
What is the classic finding
on CBC?
P430
Anemia
GLUCAGONOMA
What is the classic nutritional
finding?
P430
Low amino acid levels
GLUCAGONOMA
What stimulation test is used
for glucagonoma?
P430
Tolbutamide stimulation test:
IV tolbutamide results in elevated
glucagon levels
GLUCAGONOMA
What test is used for
localization?
P430
CT scan
GLUCAGONOMA What is the medical treatment of necrotizing migratory erythema? P431
Somatostatin, IV amino acids
GLUCAGONOMA
What is the treatment?
P431
Surgical resection
SOMATOSTATINOMA
What is it?
P431
Pancreatic tumor that secretes somatostatin
SOMATOSTATINOMA
What is the diagnostic triad?
P431
DDD: 1. Diabetes 2. Diarrhea (steatorrhea) 3. Dilation of the gallbladder with gallstones
SOMATOSTATINOMA
What is used to make the
diagnosis?
P431
CT scan and somatostatin level
SOMATOSTATINOMA
What is the treatment?
P431
Resection (do not enucleate)
SOMATOSTATINOMA What is the medical treatment if the tumor is unresectable? P431
Streptozocin, dacarbazine, or doxorubicin
ZOLLINGER-ELLISON SYNDROME (ZES)
What is it?
P431
Gastrinoma: non- islet cell tumor of the pancreas (or other locale) that produces gastrin, causing gastric hypersecretion of HCl acid, resulting in GI ulcers
ZOLLINGER-ELLISON SYNDROME (ZES)
What is the incidence?
P431
1/1000 in patients with peptic ulcer
disease, but nearly 2% in patients with
recurrent ulcers
ZOLLINGER-ELLISON SYNDROME (ZES)
What is the associated
syndrome?
P431
MEN-I syndrome
ZOLLINGER-ELLISON SYNDROME (ZES)
What percentage of patients
with ZES have MEN-I syndrome?
P431
≈25% (75% of cases of Z-E syndrome
are “sporadic”)
ZOLLINGER-ELLISON SYNDROME (ZES)
What percentage of patients
with MEN-I will have ZES?
P431
≈50%
ZOLLINGER-ELLISON SYNDROME (ZES) With gastrinoma, what lab tests should be ordered to screen for MEN-I? P432
- Calcium level
2. Parathyroid hormone level
ZOLLINGER-ELLISON SYNDROME (ZES)
What are the signs/
symptoms?
P432
Peptic ulcers, diarrhea, weight loss,
abdominal pain
ZOLLINGER-ELLISON SYNDROME (ZES)
What causes the diarrhea?
P432
Massive acid hypersecretion and
destruction of digestive enzymes
ZOLLINGER-ELLISON SYNDROME (ZES)
What are the signs?
P432
PUD (epigastric pain, hematemesis,
melena, hematochezia), GERD, diarrhea,
recurrent ulcers, ulcers in unusual
locations (e.g., proximal jejunum)
ZOLLINGER-ELLISON SYNDROME (ZES)
What are the possible
complications?
P432
GI hemorrhage/perforation, gastric outlet
obstruction/stricture, metastatic disease
ZOLLINGER-ELLISON SYNDROME (ZES) What is the differential diagnosis of increased gastrin? P432
Postvagotomy Gastric outlet obstruction G-cell hyperplasia Pernicious anemia Atrophic gastritis Short gut syndrome Renal failure H(2)
ZOLLINGER-ELLISON SYNDROME (ZES)
Which patients should have
a gastrin level checked? blocker, PPI
P432
Those with recurrent ulcer; ulcer in
unusual position (e.g., jejunum) or
refractory to medical management;
before any operation for ulcer
ZOLLINGER-ELLISON SYNDROME (ZES)
What lab tests should be
performed?
P432
Fasting gastrin level
Postsecretin challenge gastrin level
Calcium (screen for MEN-I)
Chem 7
ZOLLINGER-ELLISON SYNDROME (ZES)
What are the associated
gastrin levels?
P432
NL fasting = 100 pg/ml
ZES fasting = 200–1000 pg/ml
Basal acid secretion; (ZES >15 mEq/hr,
nl <10mEq/hr)
ZOLLINGER-ELLISON SYNDROME (ZES)
What is the secretin
stimulation test?
P432
IV secretin is administered and the
gastrin level is determined; patients with
ZES have a paradoxic increase in gastrin
ZOLLINGER-ELLISON SYNDROME (ZES)
What are the classic secretin
stimulation results?
P433
Lab results with secretin challenge:
NL—Decreased gastrin
ZES—Increased gastrin (increased by
>200 pg/ml)
ZOLLINGER-ELLISON SYNDROME (ZES) How can you remember the diagnostic stimulation test for Z-E syndrome? P433
Think: “Secret Z-E GAS”: SECRETin
= Z-E GAStrin
ZOLLINGER-ELLISON SYNDROME (ZES)
What tests are used to
evaluate ulcers?
P433
EGD, UGI, or both
ZOLLINGER-ELLISON SYNDROME (ZES)
What tests are used to
localize the tumor?
P433
Octreotide scan (somatostatin receptor scan), abdominal CT, MRI, endoscopic ultrasonography (EUS)
ZOLLINGER-ELLISON SYNDROME (ZES)
What is the most common
site?
P433
Pancreas
ZOLLINGER-ELLISON SYNDROME (ZES)
What is the most common
NONpancreatic site?
P433
Duodenum
ZOLLINGER-ELLISON SYNDROME (ZES)
What are some other sites?
P433
Stomach, lymph nodes, liver, kidney, ovary
ZOLLINGER-ELLISON SYNDROME (ZES)
Define “Passaro’s triangle.”
P433 (picture)
A.k.a. “gastrinoma triangle,” a triangle drawn from the following points: 1. Cystic duct/CBD junction 2. Junction of the second and third portions of the duodenum 3. Neck of the pancreas
ZOLLINGER-ELLISON SYNDROME (ZES) What percentage of gastrinomas are in Passaro’s triangle? P434
≈80%
ZOLLINGER-ELLISON SYNDROME (ZES)
What is the next step if the
tumor cannot be localized?
P434
Exploratory surgery (if tumor is not in pancreas, open duodenum and look), proximal gastric vagotomy if not found
ZOLLINGER-ELLISON SYNDROME (ZES)
What is the medical
treatment?
P434
H(2) blockers, omeprazole, somatostatin
ZOLLINGER-ELLISON SYNDROME (ZES) What is the surgical treatment needed for each of the following: Tumor in head of pancreas? P434
- Enucleation of tumor
- Whipple procedure if main pancreatic
duct is involved
ZOLLINGER-ELLISON SYNDROME (ZES) What is the surgical treatment needed for each of the following: Tumor in body or tail of pancreas? P434
Distal pancreatectomy
ZOLLINGER-ELLISON SYNDROME (ZES) What is the surgical treatment needed for each of the following: Tumor in duodenum? P434
Local resection
ZOLLINGER-ELLISON SYNDROME (ZES) What is the surgical treatment needed for each of the following: Unresectable tumor? P434
High selective vagotomy
ZOLLINGER-ELLISON SYNDROME (ZES)
What percentage have
malignant tumors?
P434
66%
ZOLLINGER-ELLISON SYNDROME (ZES)
What is the most common
site of metastasis?
P434
Liver
ZOLLINGER-ELLISON SYNDROME (ZES) What is the treatment of patients with liver metastasis? P434
Excision, if technically feasible
ZOLLINGER-ELLISON SYNDROME (ZES) What is the surgical option if gastrinoma is in duodenum/head of pancreas and is too large for local resection? P434
Whipple procedure
ZOLLINGER-ELLISON SYNDROME (ZES) What is the prognosis with the following procedures: Complete excision? P435
90% 10-year survival
ZOLLINGER-ELLISON SYNDROME (ZES) What is the prognosis with the following procedures: Incomplete excision? P435
25% 10-year survival
MULTIPLE ENDOCRINE NEOPLASIA
What is it also known as?
P435
MEN syndrome
MULTIPLE ENDOCRINE NEOPLASIA
What is it?
P435
Inherited condition of propensity to
develop multiple endocrine tumors
MULTIPLE ENDOCRINE NEOPLASIA
How is it inherited?
P435
Autosomal dominant (but with a significant degree of variation in penetrance)
MULTIPLE ENDOCRINE NEOPLASIA
Which patients should be
screened for MEN?
P435
All family members of patients diagnosed
with MEN
MULTIPLE ENDOCRINE NEOPLASIA MEN TYPE I What is the common eponym? P435
Wermer’s syndrome
Think: Wermer = Winner = #1 = type 1
MULTIPLE ENDOCRINE NEOPLASIA MEN TYPE I What is the gene defect in MEN type I? P435
Chromosome 11 (Think: 11 = 1)
MULTIPLE ENDOCRINE NEOPLASIA MEN TYPE I What are the most common tumors and their incidences? P435
“PPP”: Parathyroid hyperplasia ( ≈90%) Pancreatic islet cell tumors (≈66%) Gastrinoma: ZES (50%) Insulinoma (20%) Pituitary tumors (≈50%)
MULTIPLE ENDOCRINE NEOPLASIA MEN TYPE I How can tumors for MEN-I be remembered? P435
Think: type 1 = Primary, Primary,
Primary = PPP = Parathyroid, Pancreas,
Pituitary
MULTIPLE ENDOCRINE NEOPLASIA MEN TYPE I How can the P’s associated with MEN-I be remembered? P435
All the P’s are followed by a vowel: PA,
PA, PI
MULTIPLE ENDOCRINE NEOPLASIA MEN TYPE I What percentage of patients with MEN-I have parathyroid hyperplasia? P435
≈90%
MULTIPLE ENDOCRINE NEOPLASIA MEN TYPE I What percentage of patients with MEN-I have a gastrinoma? P436
≈50%
MULTIPLE ENDOCRINE NEOPLASIA MEN TYPE I What other tumors (in addition to PPP) are associated with MEN-I? P436
Adrenal (30%) and thyroid (15%)
adenomas
MULTIPLE ENDOCRINE NEOPLASIA MEN TYPE IIa What is the common eponym? P436
Sipple’s syndrome (Think: Sipple =
Second = #2 = type 2)
MULTIPLE ENDOCRINE NEOPLASIA MEN TYPE IIa What is the gene defect in MEN type IIa? P436
RET (Think: reT = Two)
MULTIPLE ENDOCRINE NEOPLASIA MEN TYPE IIa What are the most common tumors and their incidences? P436
“MPH”: Medullary thyroid carcinoma (100%); Calcitonin secreted Pheochromocytoma (>33%); Catecholamine excess Hyperparathyroidism (≈50%); Hypercalcemia
MULTIPLE ENDOCRINE NEOPLASIA MEN TYPE IIa How can the tumors involved with MEN-IIa be remembered? P436
Think: type 2 = 2 MPH or 2 Miles
Per Hour = MPH = Medullary,
Pheochromocytoma, Hyperparathyroid
MULTIPLE ENDOCRINE NEOPLASIA MEN TYPE IIa How can the P of MPH be remembered? P436
Followed by the consonant “H”—
PHEOCHROMOCYTOMA (remember,
the P’s of MEN-I are followed by vowels)
MULTIPLE ENDOCRINE NEOPLASIA MEN TYPE IIa What percentage of patients with MEN-IIa have medullary carcinoma of the thyroid? P436
100%
MULTIPLE ENDOCRINE NEOPLASIA MEN TYPE IIb What are the most common abnormalities, their incidences, and symptoms? P436
“MMMP”: Mucosal neuromas (100%)—in the nasopharynx, oropharynx, larynx, and conjunctiva Medullary thyroid carcinoma (85%)— more aggressive than in MEN-IIa Marfanoid body habitus (long/lanky) Pheochromocytoma (50%) and found bilaterally
MULTIPLE ENDOCRINE NEOPLASIA MEN TYPE IIb How can the features of MEN-IIb be remembered? P437
MMMP (Think: 3M Plastics)
MULTIPLE ENDOCRINE NEOPLASIA MEN TYPE IIb How can you remember that MEN-IIb is marfanoid habitus? P437
Think: “TO BE marfanoid” = II B
marfanoid
MULTIPLE ENDOCRINE NEOPLASIA MEN TYPE IIb What is the anatomic distribution of medullary thyroid carcinoma in MEN-II? P437
Almost always bilateral (non–MEN-II
cases are almost always unilateral!)
MULTIPLE ENDOCRINE NEOPLASIA MEN TYPE IIb What are the physical findings/signs of MEN-IIb? P437
Mucosal neuromas (e.g., mouth, eyes) Marfanoid body habitus Pes cavus/planum (large arch of foot/ flatfooted) Constipation
MULTIPLE ENDOCRINE NEOPLASIA MEN TYPE IIb What is the most common GI complaint of patients with MEN-IIb? P437
Constipation resulting from
ganglioneuromatosis of GI tract
MULTIPLE ENDOCRINE NEOPLASIA MEN TYPE IIb What percentage of pheochromocytomas in MEN-IIa/b are bilateral? P437
≈70% (but found bilaterally in only 10%
of all patients diagnosed with
pheochromocytoma)
MULTIPLE ENDOCRINE NEOPLASIA MEN TYPE IIb What is the major difference between MEN-IIa and MEN-IIb? P437
MEN-IIa = parathyroid hyperplasia MEN-IIb = no parathyroid hyperplasia (and neuromas, marfanoid habitus, pes cavus [extensive arch of foot], etc.)
MULTIPLE ENDOCRINE NEOPLASIA MEN TYPE IIb What type of parathyroid disease is associated with MEN-I and MEN-IIa? P437
Hyperplasia (treat with removal of all
parathyroid tissue with autotransplant of
some of the parathyroid tissue to the
forearm)
MULTIPLE ENDOCRINE NEOPLASIA MEN TYPE IIb What percentage of patients with Z-E syndrome have MEN-I? P437
≈25%