Flashcards in Endocrine Deck (159):
Where is the drainage of the left adrenal vein?
Left renal vein
Where is the drainage of the right adrenal vein?
What is CRH?
Released from anterior hypothalamus and causes released of ACTH from anterior pituitary
What is ACTH?
Released from anterior pituitary, which in turn causes adrenal glands to release cortisol
What feeds back to inhibit ACTH secretion?
What is Cushing's syndrome?
Excessive cortisol production.
What is the most common cause of Cushing's syndrome?
Iatrogenic (e.g. prednisone)
What is the second most common cause of Cushing's syndrome?
What is Cushing's disease?
Cushing's syndrome caused by excess production of ACTH by anterior pituitary
What is an ectopic ACTH source?
Tumor not found in the pituitary that secretes ACTH, which in turn causes adrenal gland to release cortisol without the normal negative feedback loop
What are the signs and symptoms of Cushing's syndrome?
Truncal obesity, hirsutism, moon facies, acne, buffalo hump, purple striae, hypertension, diabetes, weakness, depression, easy bruising, myopathy
How can cortisol levels be indirectly measured over a short duration?
By measuring urine cortisol or 17-OHCS (breakdown product of cortisol)
What is a direct test of serum cortisol?
Serum cortisol level (highest in morning)
What initial tests should be performed in Cushing's syndrome?
Electrolytes, serum cortisol, urine-free cortisol, urine 17-OHCS, low-dose dexamethasone suppression test
What is the low-dose dexamethasone suppression test?
Dexamethasone is a synthetic cortisol that results in negative feedback on ACTH secretion and subsequent cortisol secretion in healthy patients
After the dexamethasone suppression test, what is done next?
Check ACTH levels
Can plasma ACTH levels be checked directly?
In ACTH-dependent Cushing's syndrome, how do you differentiate between a pituitary vs. an ectopic ACTH source?
High-dose dexamethasone test
What is the test for equivocal results for differentiating pituitary vs. ectopic ACTH tumor?
Bilateral petrosal vein sampling, especially with CRH infusion
What is the most common site of ectopic ACTH tumor?
66% are oat-cell tumors of the lung
How is adrenal adenoma treated?
Adrenalectomy (usually unilateral)
How is adrenal carcinoma treated?
Surgical excision (33% are operable)
How is an ectopic ACTH-producing tumor treated?
Surgical excision, if feasible
How is Cushing's disease treated?
What medication must be given to a patient who is undergoing surgical correction of Cushing's syndrome?
Cortisol (usually hydrocortisone until PO resumed)
What medications inhibit cortisol production?
Ketoconazole, metyrapone, aminoglutethimide, mitotane
What is the mechanism of action of ketoconazole?
Inhibits 11 beta-hydroxylase, c17-20 lyase, and cholesterol side-chain cleavage
What is the mechanism of action of aminoglutethimide?
Inhibits cleavage of cholesterol side chains
What is the mechanism of action of mitotane?
Inhibits 11 beta-hydroxylase and cholesterol side-chain cleavage
What is the mechanism of action of metyrapone?
Inhibits 11 beta-hydroxylase
What is a complication of bilateral adrenalectomy?
What is Nelson's syndrome?
Functional pituitary adenoma producing excessive ACTH and mass effect producing visual disturbances, hyperpigmentation, amenorrhea
What is an adrenal incidentaloma?
Tumor found in the adrenal gland incidentally on a CT scan
What is the incidence of adrenal incidentaloma?
4% of CT scans
What is the most common cause of adrenal incidentaloma?
What is the differential diagnosis of adrenal incidentaloma?
Non-functioning adenoma, pheochromocytoma, adrenocortical carcinoma, aldosteronoma, metastatic disease, nodular hyperplasia
What is the treatment for adrenal incidentaloma?
Small/medium-sized: surgery controversial
Large (> 6 cm): resection
What are the indications for removal of adrenal incidentaloma less than 6 cm?
MRI T2 signal > 2, hyper-functioning tumor, enlarging cystic lesion, doesn't look like adenoma
What tumor must be ruled out prior to biopsy or surgery for any adrenal mass?
Pheochromocytoma (24-hour urine for catecholamine, VMA, metanephrines)
What is pheochromocytoma?
Tumor of the adrenal medulla and sympathetic ganglion (from chromaffin cell lines) that produces catecholamines
Which age group is most likely to have pheochromocytoma?
What are the associated risk factors for pheochromocytoma?
MEN-II, family history, von Recklinghausen disease, von Hippel-Lindau disease
What are the signs and symptoms of pheochromocytoma?
3. Episodic diaphoresis
Also, hypertension, anxiety, weight loss, tachycardia, hyperglycemia, polycythemia
How can the pheochromocytoma symptoms triad be remembered?
Palpitations, Headache, Episodic diaphoresis
What is the most common sign of pheochromocytoma?
What is the differential diagnosis of pheochromocytoma?
Renovascular hypertension, menopause, migraine, carcinoid syndrome, preeclampsia, neuroblastoma, anxiety disorder with panic attacks, hyperthyroidism, insulinoma
What diagnostic tests should be performed for pheochromocytoma?
Urine screen: VMA, metanephrine, normetanephrine (breakdown products of catecholamines)
Urine/serum epinephrine, norepinephrine
What are the possible sites for pheochromocytoma?
Adrenal gland, organ of Zuckerkandl, thorax, bladder, scrotum
What are the pheochromocytoma localization tests?
CT, MRI, I-MIBG, PET scan, OctreoScan
What does I-MIBG stand for?
How does the I-MIBG scan work?
I-MIBG is a norepinephrine analog that collects in adrenergic vesicles and, thus, in pheochromocytomas
What is the role of PET scan in pheochromocytoma?
Helpful in localizing pheochromocytomas that do not accumulate MIBG
What is the scan for imaging adrenal cortical pheochromocytoma?
NP-59 (a cholesterol analog)
What is the localizing option if a pheochromocytoma is not seen on CT, MRI or I-MIBG?
IVC venous sampling for catecholamines (gradient will help localize tumor)
What is the pheochromocytoma tumor site if epinephrine is elevated?
Must be adrenal or near the adrenal gland, because non-adrenal tumors lack the capability to methylate norepinephrine to epinephrine
What percentage of patients with pheochromocytoma have malignant tumors?
Can histology be used to determine malignancy of a pheochromocytoma?
No; only distant metastasis or invasion
What is the classic pheochromocytoma "rule of 10"?
10% in children
10% multiple tumors
What is the preoperative/medical treatment for pheochromocytoma?
Increase intravascular volume with alpha-blockers (e.g. phenoxybenzamine, prazosin) to allow reduction in catecholamine-induced vasoconstriction and resulting volume depletion.
Treatment should start as soon as diagnosis is make.
What is the surgical treatment for pheochromocytoma?
Tumor resection with early ligation of venous drainage and minimal manipulation (lower possibility of catecholamine crisis)
What are the possible perioperative complications of pheochromocytoma surgery?
Hypertensive crisis with manipulation (treat with nitroprusside); hypotension with total removal of tumor; cardiac dysrhythmias
In the patient with pheochromocytoma, what must be ruled out?
What is the organ of Zuckerkandl?
Body of embryonic chromaffin cells around the abdominal aorta (near IMA).
Normally atrophies during childhood, but is the most common site of extra-adrenal pheochromocytoma
What is Conn's syndrome?
Primary hyperaldosteronism due to high aldosterone production
How do you remember what Conn's syndrome is?
CONn's disease = HYPERALdosteronism:
CON HYPER AL
What are the common sources of Conn's syndrome?
Adrenal adenoma or hyperplasia
What is the normal physiology for aldosterone secretion?
1. BP in the renal artery is low.
2. Low sodium and hyperkalemia cause renin secretion from juxtaglomerular cells.
3. Renin then converts to angiotensinogen to angiotensin I.
4. ACE in the lung then converts angiotensin I to angiotensin II.
5. Angiotensin II then causes the adrenal glomerulosa cells to secrete aldosterone.
What is the normal physiologic effect of aldosterone?
Sodium retention for exchange of potassium in the kidney, resulting in fluid retention and increased BP
What are the signs and symptoms of Conn's syndrome?
Hypertension, headache, polyuria, weakness
What are the 2 classic clues of Conn's syndrome?
Classically, what kind of hypertension is seen in Conn's syndrome?
What are the renin levels with Conn's syndrome?
Normal or decreased
What percentage of all patients with hypertension have Conn's syndrome?
What diagnostic tests should be ordered for Conn's syndrome?
1. Plasma aldosterone concentration
2. Plasma renin activity
What ratio of aldosterone to renin is associated with primary hyperaldosteronism?
What is secondary hyperaldosteronism?
Results from abnormally high renin levels
What diagnostic tests should be performed for secondary hyperaldosteronism?
CT, adrenal venous sampling for aldosterone levels, saline infusion test
What is the saline infusion test?
Saline infusion will decrease aldosterone levels in normal patients but not in Conn's syndrome
What is the preoperative treatment for Conn's syndrome?
Spironolactone, K supplementation
What is spironolactone?
Anti-aldosterone medication (works at kidney tubule)
What are the causes of Conn's syndrome?
Adrenal adenoma, bilateral idiopathic adrenal hyperplasia, adrenal carcinoma
What is the treatment for adrenal adenoma?
What is the treatment for unilateral adrenal hyperplasia?
What is the treatment for bilateral adrenal hyperplasia?
Spironolactone (no surgery)
What are the renin levels in patients with primary hyperaldosteronism?
Normal or decreased
What is Addison's disease?
Acute adrenal insufficiency
What are the electrolyte findings in Addison's disease?
What is an insulinoma?
Insulin-producing tumor arising from beta cells
What are the associated risk factors for insulinoma?
(PPP = Pituitary, Pancreas, Parathyroid tumors)
What are the signs and symptoms of insulinoma?
Sympathetic nervous system symptoms resulting from hypoglycemia: palpitations, diaphoresis, tremulousness, irritability, weakness
What are the neurologic symptoms of insulinoma?
Personality changes, confusion, obtundation, seizures, coma
What is Whipple's triad?
1. Hypoglycemic symptoms produced by fasting.
2. Blood glucose
What is the differential diagnosis for insulinoma?
Reactive hypoglycemia, functional hypoglycemia with gastrectomy, adrenal insufficiency, hypopituitarism, hepatic insufficiency, Munchausen syndrome (insulin self-injections), non-islet cell tumor causing hypoglycemia, surreptitious administration of insulin or OHAs
What lab tests should be performed for insulinoma?
Glucose and insulin levels during fast; C-peptide and proinsulin levels (if self-injection is a concern, as insulin injections have no proinsulin or C-peptides)
What diagnostic tests should be performed for insulinoma?
Fasting hypoglycemia with inappropriately high levels of insulin; 72-hour fast, then check glucose and insulin levels q6hr
What is the diagnostic fasting insulin:glucose ratio for insulinoma?
What localizing tests should be performed for insulinoma?
CT, A-gram, endoscopic U/S, venous catheterization (to sample blood along portal and splenic veins), intra-operative U/S
What is the medical treatment of insulinoma?
Diazoxide (suppress insulin release)
What is the surgical treatment of insulinoma?
What is the prognosis for insulinoma?
80% of patients have benign solitary adenoma that is cured by surgical resection
What is a glucagonoma?
Where is a glucagonoma located?
Pancreas, usually the tail
What are the symptoms of glucagonoma?
Necrotizing migratory erythema (usually below the waist), glossitis, stomatitis, diabetes
What are the skin findings with glucagonoma?
Necrotizing migratory erythema is a red, often psoriatic-appearing rash with serpiginous borders over the trunk and limbs
What are the associated lab findings with glucagonoma?
Hyperglycemia, low amino acid levels, high glucagon
What is the classic CBC finding with glucagonoma?
What is the classic nutritional finding with glucagonoma?
Low amino acid levels
What stimulation test is used for glucagonoma?
Tolbutamide stimulation test: IV tolbutamide results in elevated glucagon levels
What test is used for localization of glucagonoma?
What is the medical treatment of necrotizing migratory erythema?
Somatostatin, IV amino acids
What is the treatment of glucagonoma?
What is a somatostatinoma?
Pancreatic tumor that secretes somatostatin
What is the diagnostic triad of somatostatinoma?
2. Diarrhea (steatorrhea)
3. Dilation of the gallbladder with gallstones
What is used to make the diagnosis of somatostatinoma?
CT and somatostatin levels
What is the treatment of somatostatinoma?
Surgical resection (no not enucleate)
What is the medical treatment for unresectable somatostatinoma?
Streptozocin, decarbazine, or doxorubicin
What is Zollinger-Ellison syndrome?
Gastrinoma: non-beta islet cell tumor of the pancreas (or other locale) that produces gastrin, causing gastric hyper secretion of HCl acid, resulting in GI ulcers
What syndrome is associated to ZES?
What percentage of patients with ZES have MEN-I syndrome?
What percentage of patients with MEN-I will have ZES?
With ZES, what lab tests should be ordered to screen for MEN-I?
1. Calcium level
2. Parathyroid hormone level
What are the symptoms of ZES?
Peptic ulcers, diarrhea, weight loss, abdominal pain
What causes diarrhea in ZES?
Massive acid hypersecretion and destruction of digestive enzymes
What are the signs of ZES?
PUD (epigastric pain, hematemesis, melena, hematochezia), GERD, diarrhea, recurrent ulcers, ulcers in unusual locations
What are the possible complications of ZES?
GI hemorrhage, GI perforation, gastric outlet obstruction/stricture, metastatic disease
What is the differential diagnosis of ZES?
Post-vagotomy, gastric outlet obstruction, G-cell hyperplasia, pernicious anemia, atrophic gastritis, short gut syndrome, renal failure, H2 blocker, PPI
Which patients should have a gastrin level checked?
Recurrent ulcer; ulcer in unusual position; ulcer refractory to medical management; before any ulcer operation
What lab tests should be performed for ZES?
Fasting gastrin level; post-secretin challenge gastrin level; Ca (MEN-I); BMP
What are the associated gastrin levels in ZES?
Normal fasting = 100 pg/mL
ZES fasting = 200-1000 pg/mL
What is the secretin stimulation test?
IV secretin is administered and the gastrin level is determined.
Patients with ZES have a paradoxic increase.
What are the classic secretin stimulation results?
Normal = decreased gastrin
ZES = increased gastrin
What tests are used to evaluate ulcers?
EGD, UGI, or both
What tests are used to localize a ZES tumor?
Octreotide scan (somatostatin receptor scan); abdominal CT; MRI; endoscopic U/S
What is the most common site of a ZES tumor?
What is the most common non-pancreatic site of a ZES tumor?
What are possible sites for a ZES tumor?
Pancreas, duodenum, stomach, lymph nodes, liver, kidney, ovary
What is the next step if the ZES tumor cannot be localized?
Exploratory surgery (pancreas, duodenum); proximal gastric vagotomy if not found
What is the medical treatment for ZES?
H2 blockers, omeprazole, somatostatin
What is the surgical treatment for gastrinoma in the head of the pancreas?
Enucleation of tumor; Whipple procedure if main pancreatic duct is involved
What is the surgical treatment for gastrinoma in the body or tail of the pancreas?
What is the surgical treatment for gastrinoma in the duodenum?
What is the surgical treatment for unresectable gastrinoma?
High selective vagotomy
What percentage ZES tumors are malignant?
What is the most common site of metastasis in ZES?
What is the treatment for ZES patients with liver metastasis?
Excision, if feasible
What does MEN stand for?
Multiple Endocrine Neoplasia
What is MEN syndrome?
Inherited condition of propensity to develop multiple endocrine tumors
How is MEN inherited?
Autosomal dominant (but with varying penetrance)
Which patients should be screened for MEN?
All family members of patients diagnosed with MEN
What is Wermer's syndrome?
Where is the gene defect in MEN-I?
What are the most common tumors and incidences in MEN-I?
Parathyroid hyperplasia (90%)
Pancreatic tumors (ZES, insulinoma) (66%)
Pituitary tumors (50%)
Also, adrenal and thyroid adenomas
What is Sipple's syndrome?
What is the gene defect in MEN-IIa?
What are the most common tumors and incidences in MEN-IIa?
Medullary thyroid carcinoma (calcitonin) (100%)
What are the most common abnormalities, incidences and symptoms in MEN-IIb?
Mucosal neuromas (100%): nasopharynx, oropharynx, larynx, conjunctiva
Medullary thyroid carcinoma (85%)
Marfanoid body habitus
What is the anatomic distribution of medullary thyroid carcinoma in MEN-IIb?
Almost always bilateral
What is the most common GI complaint of patients with MEN-IIb?
Constipation resulting from ganglioneuromatosis of GI tract