Hypergastrinemia

Non-Ulcerogenic causes:
- Renal failure
- Atrophic gastritis
- Pernicious anemia
- Previous vagotomy
- Short-gut syndrome
- PPI

Ulcerogenic causes:
- ZES
- Retained or excluded antrum
- G-cell hyperplasia
- Gastric Outlet Obstruction

Gastrinoma

Most common site of gastrinoma:
- D2: 70%
- D1: 57%
- Pancreatic head: 27%, body: 23%, tail 50%

Hypercalcemic Crisis

Presentation:
- severe dehydration
- hypotension,
- altered mental status
- dysrhythmias

Management:
- hydrate: normal saline at a rate of 300 ml/hr; rehydration promotes calcium excretion in proximal tubule which is associated with Na flux
- Loop diuretics: reduce fluid overload and inhibit calcium resorption in the loop of Henle, thus promoting increased renal calcium excretion. 
- Dialysis: Patients with renal failure should be dialyzed with low-calcium dialysate

Pharmacologic agents to be used after rehydration:
- Steroids: Glucocorticoids lower calcium by inhibiting effects of vitamin D, increasing renal calcium excretion, and inhibiting osteoclast-activating factor. 
- hydrocortisone is 200 to 400 mg IV per day for 3 to 5 days
- Bisphosphonates inhibit osteoclast activity, thus preventing bone resorption induced by PTH. 
- Pamidronate (90 mg IV) or zoledronic acid (4 mg IV initial treatment, 8 mg on retreatment) normalizes calcium levels in most patients
- Calcitonin acts quickly (within 24 to 48 hours) to lower serum calcium levels and is more effective when used in combination with glucocorticoids. It should not be used in patients with salmon allergies. 

After patients with PHPT and hypercalcemic crisis are stabilized and serum calcium levels have been reduced to acceptable levels, preoperative localization studies should be obtained expeditiously in anticipation of an urgent parathyroidectomy.

Cameron 9th ed

Parathyroid Hormone

Single most important regulator of calcium and phosphate homeostasis in the body.

Effects:
Direct effects on bone and kidneys
Indirect effects on intestines (mediated viaVitD)

Effects on Bone:
- complex interaction activating osteoblasts and osteoclasts
- act indrectly on osteoclasts but have direct ligands on osteoblasts
- acts first to mobilize minerals from areas of rapid equilibrium
- prolonged PTH exposure results in further bone mineralization as lysozomal and hydrolytic enzymes are synthesized

Effects on Kidney:
- PTH has 3 effects on kidneys
- increases production of alpha-hydroxolase, resulting in increased hydroxylation of cholecalciferol to calciferol.
- increases reabsorption of calcium in distal nephron (loop of henle and proximal tubule Ca reabsorption is linked to Na and not influenced by PTH)
- prevents reabsorption of both phosphate and bicarbonate

Effects on Intestine:
- indirect and results in increased calcium absorption by increased VitD hydroxylation in kidney

Feedback inhibition is regulated by calcium levels.
- increased calcium normally results in inhibition of PTH secretion
- decreased calcium levels result in increased PTH secretion

Li-Fraumeni Syndrome

mutations of p53 gene
- breast cancer
- sarcoma
- brain tumors
- adrenocortical carcinomas
- leukemia

TMcM - adrenal talk

Aldosteronoma:
- usually very small tumors
- if larger tumor on one side --> is it a redherring and its actullay another type of adrenal tumor
NP25 scan available at CCI for localizing
Adrdrenal venous sampling
pheo 30% are thought to be genetic
- now all pts get screened MEN2a/b, vHL, NF-1, tuberous sclerosis, SDH mutations
- pheos alpha block 2-3 wks before OR
- fluid load 3L day of surgery
- can tank pressures from other causes

Zollinger-Ellison Syndrome

Triad:
- gastric acid hypersecretion
- severe PUD
- islet cell tumors

- Rare, 50% are malignant

Diagnosis:
- serum gastrin off PPIs
- secretin stimulation testing
- Basal acid output
- Somatostatin Receptor Scintigraphy (localizes gastrinoma in 85%)

Passaro's Triangle: (70-90% of gastrinomas will be found within these limits)
- cystic duct
- 2nd/3rd part of duodenum
- jxn of head and body of pancreas

Rule out MEN1 prior to OR:
- in MEN1 pts resection rarely normalizes gastrin levels and does not affect long-term survival
- manage hypergastrinemia with very high doses of PPI
- in comparison sporadic cases should be treated aggressively with surgery as 50% 5-yr disease free survival

Surgical Management:
- warranted in absence of metastatic disease
- sporadic gastrinomas
- resection will largely depend on site of tumor
- limited hepatic resection for mets may be considered
- if widespread disease may consider vagotomy and antrectomy to avoid need for long-term PPIs

Multiple Endocrine Neoplasia Syndromes

MEN1: (P followed by a vowel)

- Pituitary (anterior) tumors

- Parathyroid hyperplasia

- Pancreatic islet tumor

MEN2a: (2 MPH)

- Medullary Thyroid cancer

- Pheochromocytoma

- Hyperparathyroidism

MEN 2b: (3M Plastics)

- Marfanoid

- Mucosal neuromas

- Meduallary thyroid cancer

- Pheochromocytoma

Adrenal Metastases:

Most common cancer metastasizing to the adrenals:
- Lung ca
- RCC
- melanoma
- breast ca
- gastrointestinal ca
- HCC
- lymphoma

Work-up:
- patients with a solitary adrenal mass and symptoms suggestive of malignancy should have screening colonoscopy, mammography and CXR to try and identify the primary tumor
- PET scan may be helpful to identify the primary disease
- FNA can be performed: but only after a pheo has been ruled out

Presence of a solitary met - may benefit from adrenalectomy
- usually small and contained within capsule.
- lap adrenalectomy has been shown to have an equally effective outcome as open adrenalectomy
- 5 year survival 25%

Virilizing and Feminizing Adrenal Tumors

- Rare
- usually symptomatic

>80% are malignant
- almost all feminizing tumors malignant
- 50% of virilizing tumors are malignant

- because they are so rare, testing for sex hormone excess during work-up of incidentaloma should only be done if there are clinical signs of virilization or feminization

Diagnosis:
- Virilizing tumors: serum testosterone, serum dihydroepiandrostenedione, 24 hr urine 7-hydroxysteroid, 24 hr urine 7-ketosteroids (serum androgens and 24 hr urine keto-steroids suppressed if ovarian cause)
- dexamethasone suppression test can differentiate between adrenal and ovarian cause
- Feminizing tumor: serum estrogen and suppressed FSH, LH and gonadotropins confirm feminizing adrenal tumor (as opposed to testicular tumor)
- CT scan can generally localize a tumor

Consider that most are malignant when deciding if going to attempt laparoscopically

Adrenal Cushing's syndrome

Cushing's syndrome: caused by glucocorticoid excess
- central obesity, hypertension, moon facies, easy brusibility, weakness, depression, polyuria, glucose intolerance and diabetes

Gluccocorticoid secreting lesiosn:
- adrenal: adenomas, hyperplasia, adrenocortical carcinomas
- pituitary: adenomas, hyperplasia
- ectopic: SCLLC, bronchial carcinoid tumors, thymomas, pancreatic islet cell tumors

Diagnosis:

- elevated 24-hour urinary free cortisol most sensitive and specific test

- if 24 hour urine is negative formal low-dose dexamethasone suppression test can be performed

Important distinction during work-up:
- ACTH dependent or independent (adrenal adenoma and candidate for resection)
- measure plasma ACTH levels: should be low in ACTH independent tumors
Imaging:
- CT or MRI both can be used for localizing the tumor
- if pituitary or ectopic lesion suspected then imaging of head/chest may be warranted

Pre-op considerations:
- treat with stress-dose of steroids: taper slowly (the contralateral adrenal will be suppressed from pre-operative excess steroid secretion)
- pre-op antibiotics (due to immunosuppression from steroids)

TReatment:
- surgical resection of bilateral hyperplasia is indicated in this disease
- patient will requirer lifetime glucocorticoid and mineralocorticoid replacement (Florinef 0.1mg qD)

Aldosteronoma

Classic triad of Conn's syndrome:
- Hypertension
- Hypokalemia
- Polyuria

Diagnostic test is PAC:PRA >30
- PAC: plasma aldosterone concentration
- PRA: plasma renin activity
- second confirmatory test is an aldosterone stimulation test (positive if urinary aldosterone level elevated during a saline infusion)

Workup: adenoma vs. hyperplasia
- important step in working patient with suspected aldosteronoma is to determine if you are dealing with a unilateral adrenocortical adenoma (2/3 of patients) or bilateral hyperplasia
- other very rare causes include adrenocortical carcinoma, angiotensin II responsive adenomas, familial hyperaldosteronism type I and type II
- this can be done by imaging - CT scan may show a solitary lesion

Indications for selective adrenal vein catheterization:
- sampling of adrenal vein may be necessary to localize adenoma.  placement of catheter confirmed by increase in cortisol concentration as compared to IVC
- looking for ~5 fold increase in aldosterone compared to the other side
- indicated with there is adrenal hypertrophy, bilateral nodules, no lesions

Pre-operative considerations:
- patient begins spironolactone pre-operatively to control hypertension and normalize potassium levels.
- other antihypertensives are added as needed
- stop spironolactone immediately post-op

Calcium replacement post-op hypocalcemia

Elemental calcium 2-4g per day +\- rocalcitrol 0.25 ug qd
Calcium carbonate: (1g CaCarbonate has 400mg elemental calcium)

If symptomatic 1 amp calcium gluconate in 50ml d5w over 20 min
Replace magnesium

Primary Hyperparathyroidism

Presentation:
- most present asymptomatically and come to attention after screening bloodwork reveals hypercalcemia.
- otherwise look for signs of hypercalcemia - stones, bones, psychiatric overtones, abdominal moans

Investigations:
- PTH, calcium, phosphate
- 24h urine calcium to differentiate for FHH
- 99Tc sestamibi and high resolution ultrasound.
- together these imaging tests will usually localize the lesion and allow for unilateral neck exploration.
- if not localized by above studies consider CT, MRI or PET scan

Indications to operate hyperpara:
- symptomatic - some would argue this includes vague symtpoms such as dysphoria and failure to thrive in the elderly
- serum calcium > 3 mmol/l
- 24h urine calcium > 400 mg/l
- age <50
- bone density < 2 sd
- unable yo follow up with medical observation

Unilateral exploration:
- should be accompanied ideally with intraop PTH assay.
- if not available then ?frozen section
- if PTH assay not available ?warn pt about possible need to return to explore other side

Perioperative Complications:
- hungry bone syndrome: if preop calcium was very high > 3, then there may be rapid bone reabsorption of calcium postoperative. May need yo give patient supplemental calcium postoperatively.
- severe hypercalcemia: may need to give IV palmidrobate infusion over 4 hours to decrease calcium. Effects can last days to weeks. If not sufficient the give IV bisphosphonates (inhibits osteoclastic bone reabsorption)

Operative Management of Pheochromocytoma

"No-Touch" technique:
- ligate the central draining vein first to prevent secretion of catacholamines into the systemic circulation.
- "no-touch" also thought to prevent wide blood pressure swings.

Open technique:
- Advantages were to facilitate "no-touch" technique, permit bilateral and central exploration.
- however, with improvements in laparoscopic technique and pre-operative imaging, currently open technique reserved for large pheos and obviously malignant lesions.

Laparoscopic technique:
- Lateral Transperitoneal Lap Adrenalectomy is now the gold standard for most-benign appearing pheos <8cm in size.
- Right adrenal is easier to excise whereas left side requires more extensive visceral medialization or access to the lesser sac.
- describe laparoscopic right and left adrenalectomy...

Management of intraoperative complications:
- hypotension: phenylephrine or ephedrine and volume expansion
- hypertension: nitroprusside
- ventricular arrhythmia: lidocaine

Post-operative care:
- blood pressure will commonly be low (SBP<100) in 1st 12hrs post-op until the pre-op doses of alpha-blocker absorbed
- hold all anti-hypertensive medications post-op unless the pt was taking chronic B-blocker
- Specimen examined pathologically for DNA ploidy.  Diploid tumors behave in malignant fashion, however, even 30% of nondiploid tumors will also recur.

Pheochromocytoma

-Tumor arising from chromaffin cells and sustentacular cells of the adrenal medulla or extraadrenal paraganglia.
- Classically secrete epinephrine, norepinephrine or dopamine.  However, can also secrete a host of other hormones.
- Distinction between benign and malignant is the presence of local invasion or presence of distant mets.

Presentation:
- Classic triad: (PHEo) Paroxysmal HTN, Palpatations, Headache, Excess sweating
- Most (90%) will present with some clinical manifestation, whereas 10% will present initially as an adrenal incidentaloma.
- Number of familial conditions associated with pheo - notably MEN2a and 2b.

Diagnosis:
- Most specific test is combination of 24 hr urine metanephrines and catacholamines.
- Plasma testing, while very sensitive, is very expensive and not as specific.
- Any elevated 24hr urine metanephrine or 2x normal 24 hr urine catacholamine result is considered positive.
- Many drugs (notably, TCAs) can falsely elevate urine catacholamines.
- CT abdo/pelvis most cost-effective method to localize pheo once diagnosed.  However, other modlities such as MRI, MIBG scan, and PET scan  may be used as adjunctive imaging tests.
- With newer contrast agents - precipitation of hypertensive crisis is not as much of a concern and non-contrast CT not necessary

Perioperative Management:
- Important step in operative management in order to prevent hypertensive crisis intra-op.
- Unopposed alpha-stimulation once pheo removed will cause vasoconstriction and decreased intravascular volume
- alpha-blockade should begin immediately once diagnosis is made
- Phenoxybenzamine started at 20-30 mg qD in divided doses.  Increase dose until the pt is symptomatic with orthostatic hypotension and/or nasal stuffiness.
- in order to combat side-effects instruct pt to increase salt and fluid intake.
- Beta-blockade with propranolol can be added to manage tachycardia, arrythmias or ischemia