Download Presentación de PowerPoint - American Association of Clinical

Pituitary and Adrenal “Perioperative” Endocrinology
Maria Fleseriu, MD, FACE
Professor , Director Northwest Pituitary Center
Oregon Health Science University
[email protected]
Disclosure
• Chiasma,Cortendo,Novartis,Pfizer
– Principal investigator: Research
funding to OHSU
– Scientific consulting fee
Do endocrinologists need to be consulted preoperatively
for pituitary and adrenal tumors?
Pituitary
 Does the patient need surgery from an endocrine
standpoint?
 How long should patients be monitored/ kept
inpatient?
 How and when do we re-evaluate the patient post
operatively?
 Do we have any data (randomized trials) for how to
best manage patients?
Adrenal
• Is this a secretory tumor?
• When do we need to find out if it is-inpatient or
outpatient?
• Will need removal from an endocrine point of view?
Case
CC: 54 y old with headache + altered mental status
HPI:
• Missed work which was unusual for him.
• He was called into work where he became increasingly
confused and disoriented while also complaining of a
headache.
• As part of his work up in ED, a CT revealed a large sellar
and suprasellar mass and he was transferred to our
hospital for further workup and management.
ROS: Headache, confusion, somnolence, vision loss?
4
Case continued
BP 118/65 | Pulse 64 | Temp 36.8 °C (98.2 °F) | RR 12 | Ht 1.803 m
(5' 11") | Wt 94.5 kg (208 lb 5.4 oz) | SpO2 96% | BMI 29.07 kg/(m^2)
General Appearance: Obese male, lying in bed, awakens to
voice briefly holding bridge of nose with eyes closed.
HEENT: MMM, mild conjunctival injection, no moon facies,
no facial plethora.
Neck: +dorso-cervical fat pad enlargement, no
supraclavicular fat pad enlargement.
Abdominal: soft, NT, +BS, no violaceous striae.
Skin: no acne, skin not oily, did not have multiple skin tags.
Neurologic: bilateral eyelid apraxia, upgaze deficit, no facial
droop, able to move all 4 extremities spontaneously against
gravity, somnolent, oriented to self and year.
5
Imaging
MRI with contrast homogenously 5.8 x 3.4 x 2.5 cm sellar, supra sellar mass
extending into the third ventricle and interpeduncular cistern causing
secondary obstructive hydrocephalus. The right cavernous carotid is
encased.
6
Hormonal work-up
•
•
•
•
•
•
•
•
TSH 0.64 mLU/l
Free T4: 0.7 (0.6-1.2)
Prolactin: 99*
ACTH: 22
Cortisol: 9.4 ug/dL
FSH<1, LH<1
Testosterone: 22
IGF-1 152 ng/ML (68-245ng/ML)
7
What is next?
• Patient underwent transphenoidal pituitary surgery
• Pathology
– Sections show fragments of anterior pituitary tissue with disrupted acinar
architecture (highlighted by reticulin stain) and involvement by sheets of
relatively monomorphic adenoma cells which strongly express prolactin.
– Adrenocorticotropic Hormone Negative
Human Growth Hormone Negative
Prolactin Positive
Cyto-Keratin CAM 5.2 Positive focal
Somatostatin Receptor 2A Positive
KI67 % Positive 5%
p53 Negative
Negative control slide for IHC stain Negative
SF-1 Positive focal
8
What Now?
What is the diagnosis?
Reminder:
PRL 99 with dilution
SF-1 positive
9
Cell Lineage
specific
transcription
factors
Pit-1
T-pit
SF-1
ER
TPit
10
Initial evaluation for large tumors
• Imaging- ideally pituitary dedicated MRI
• Visual field testing (if mass abuts/compresses optic nerve)
• Evaluate HPA axis
• Check for clinical and biochemical signs of hormone
excess
11
Evaluate for hormonal secretion
• Prolactin
• ACTH/ Cortisol
• IGF-1
• TSH/FT4
• LH/FSHestrogen/testoster
one*
• If prolactinomamedical therapy >
surgical therapy.
• Acromegaly and
Cushing's disease at
increased risk for
cardiovascular
complications.
12
Evaluate for hormonal deficiencies
Adrenal insufficiency
• Check AM cortisol +/- ACTH
• If results equivocal or clinical suspicion, cosyntropin
stimulation test
• Goal: treatment to prevent adrenal crisis, particularly if
patient is going for surgery
13
TSH
Evaluate for central hypothyroidism & central
hyperthyroidism
• Check Free T4 + TSH
• Central hyperthyroidism very rare
• TSH not reliable even if normal or elevated
• Exact cut- off for repletion varies
– Replacement can prevent hyponatremia, cardiac
complications and postoperative ileus
14
ADH
DI inadequate AVP response to serum osmolality
• More common in suprasellar lesions
– Craniopharyngyomas (81%-96% post op)
Adipsic DI- rare entity
• Craniopharyngiomas accounts for 13-30% of cases
– Particularly in tumors greater than 3.5 cm or causing hydrocephalus
• Other causes include other suprasellar lesions, congenital, infection, aneurism clipping,
toluene exposure
• Occurs when patients have inadequate thirst response for rising serum osom
• High morbidity and mortality
– Central sleep apnea
– Excess somnolence
– DVT
– AKI
15
GH /LH-FSH axes
• IGF-1 should be checked in all tumors in my opionion
• LH, FSH- can wait if patient will undergo surgery as they
will need re-evaluation post operatively
• No current role for alpha subunit
• Most “silent adenomas” are gonadotroph adenomas
16
Prolactin
• Typically degree of prolactin elevation correlates with
size of tumor
Uptodate
17
Other giant tumor
Fleseriu et a, J Neuroonc, 2006
18
Hook effect
• Prolactin levels in giant prolactinomas can be misleading
• Essentially antigen-(prolactin)interferes with assay by preventing
complex formation with capture antibody and signal antibody
• Dilution is required to lower
prolactin levels enough to enable
antibody complex formation
• Mild prolactin elevation in range of stalk effect can be misleading in
giant adenomas
–
verifying serial dilutions is key
Smith TP et al. 2007,Nat Clin Pract Endocrinol Metab 3: 279–289, Fleseriu et al, 2006, Neurooncology
19
MRI after surgery and Cabergoline
Fleseriu et a, J Neuroonc, 2006
20
Early postoperative complications
Surgical
• Sellar hematoma
visual loss
• Diplopia
• Headache
• CSF leak
• ICA injury
• Hydrocephalus
• Epistaxis
• Infection
– Meningitis
– Sinusitis
– Abscess
Endocrine
DI
SIADH
Adrenal insufficiency
21
Early Postoperative Management
•
•
•
•
•
•
•
•
•
Serial visual field assessments
Serial neurologic exams
Imaging if new neurologic deficit or suspected CSF leak
Strict ins and outs
Monitor serum sodium, urine SPG (less than 1.005) or
osm
UOP > 250 ml/h x 2-3 hours
DDAVP if indicated?
AM Cortisol*
Serum sodium in 5-7 days post op
22
Evaluation of remission in functional adenomas
• Moderately predictive of • CD
early and long term
– Multiple protocols to
remission.
evaluate “cure” Cushing's
POD 1
• Fasting AM GH less
than 1 or 2 ng/ml
• Prolactin level less than
10 ng/mL
• Cortisol *
– Steroids held and serial
measurements of post op
cortisol
– Particularly important as
they may either need
further treatment or are
adrenally insufficient
23
Electrolyte abnormalities following transphenoidal
pituitary surgery
Prospective study- N=57
• Day 0-14
• 75% of patients had some sodium abnormality
• 38.5% Isolated DI
• 21% isolated Hyponatremia
• 15.7% had combined DI + Hyponatremia
• 8.7% of patients required DDAVP for more than 3 months
• Pituitary manipulation most strongly correlated with risk of
DI
Kristof et al, J Neurosurg. 2009 Sep;111(3):555-62.
24
How long to keep the patient in the hospital?
For DI and SIADH
monitoring ?
Peak incidence DI: 24-48
hours.
Typically do not keep in
hospital to see if they
develop SIADH
To evaluate for remission
Cushing's
- We hold steroids and then
check cortisol q6 hours x 4
Acromegaly
-check am GH POD 1 & 2
25
Inpatient multidisciplinary pituitary team
• Retrospective study comparing outcomes before an after
implementation of a multidisciplinary team and protocol
• N:214, 113 before and 101 after protocol
• Median length of stay decreased from 3 to 2 days (P<0.01)
• No difference in rate of DI or SIADH or other complications
Carminucci AS, Ausiello JC, Page-Wilson G, Lee M, Good L, Bruce JN, Freda PU., Endocr Pract. 2016
26
Glucocorticoids for “non Cushing's” patients
• AM cortisol may be helpful in determining central adrenal
insufficiency post op.
• CST unreliable for at least two weeks
• Multiple different approaches including
– Empiric stress dose steroids before surgery + discharge on
physiologic replacement, evaluate in 6 weeks
– Steroids if post op am cortisol less than 10-15 mcg/dl
– Steroid sparing: no perioperative steroids and careful post
operative monitoring for AI
27
6 + 12 weeks postoperatively
• Evaluate HPA axis at week 6 + 12
– Cosyntropin stimulation test
• Reevaluation for other pituitary axes
• Initiate repletion for new hormonal deficits if any
• Post operative MRI at week 12 “new baseline”
28
Long term follow up
• Depends on the tumor type
• Periodic MRI (annually for 3-5 years)
• Monitoring for hormone excess
• Periodic HPA axis evaluation (at least annually)
– Recovery is higher than previously thought, especially in
acromegaly patients
29
Preoperative
Hormonal Evaluation:
Adrenal
Prolactin
Thyroid
GH
Gonadotroph
Early Inpatient
Monitoring
Neurologic status
Diabetes insipidus
SIADH
Replace thyroid and adrenal hormones if
insufficiency detected preoperatively
Transsphenoidal Surgery
Perioperative stress dose steroids if indicated
Outpatient Follow up
Early outpatient Assessment
1 week:
General status, sodium, cortisol
6 week:
General status, Adrenal, thyroid, GH,
Prolactin
Adapted from; AACE
Neuroendocrine and Pituitary Scientific
Committee. Endocr Pract. 2015
12 week:
General status, Adrenal, thyroid, gonad, GH,
Prolactin as clinically indicated
MRI – Baseline post op image
Long Term Follow up
Hormonal status evaluation
annually
or as dictated by clinical
state
Assessment for tumor
recurrence
Assessment for biochemical
remission
MOC question
• A 29‐year‐old woman is known to have partial
hypopituitarism (on replacement with Hydrocortisone 15
mg daily and Levothyroxine 100 mcg daily) after surgery
for a 2.4 cm pituitary adenoma several years ago.
Residual tumor significantly increased in the last 2 years
and a second pituitary surgery is planned. You see her in
the endocrinology clinic the week of her surgery and give
recommendations to the patient and the on-call
endocrinologist who will manage the patient in the
hospital.
31
Which of the following statements is TRUE?
1. Change her glucocorticoid regimen now from Hydrocortisone to
Prednisone to better prepare her for surgery
2. Increase her daily hydrocortisone from 15 mg to 20 mg daily a
week before surgery to avoid use of stress dose perioperatively
3. Stop levothyroxine in the hospital, it won't get absorbed anyway
and recheck TSH in the first 3-4 weeks after surgery
4. Fixed doses of DDAVP should be prescheduled in the immediate
postoperative period as this is her second pituitary surgery
5. She will need retesting of all pituitary axes starting at 6 weeks after
pituitary surgery and then periodically to monitor the development
or resolution of pituitary deficiencies.
Fleseriu M et al, Hormonal replacement in hypopituitarism in adults: an Endocrine
Society Clinical Practice Guideline. J Clin Endocrinol Metab 2016; 101: 3888–3921.
32
Adrenal mass-inpatient
• Is the mass functional?
• Physical signs or symptoms of hyperfunction?
• Biochemical work-up:
– Screen for pheocromocytoma
– Potassium/aldosterone/renin
– Cushing’s
• Is the mass malignant?
• Bilaterality of disease?
• Monitoring for hormone excess after surgery
Imaging
34
Imaging
35
Biochemical Workup
• Adrenal Incidentaloma
– Pheochromocytoma: 24 hour urine metanephrines
– Primary Hyperaldosteronism: If hypertensive (with or
without hypokalemia) do PAC/PRA ratio
– Cushing’s Syndrome: Screen for excess cortisol production
If not urgent, preferred work-up as outpatient
Plasma
METANEPHRINES (0.00 - 0.49 nmol/L)
NORMETANEPHRINES (0.00 - 0.89 nmol/L)
EPINEPHRINE CONCENTRATION
(10 - 200 pg/mL)
NOREPINEPHRINE(80 - 520 pg/mL)
DOPAMINE
(0 - 20 pg/mL)
Urine
METANE/CREA RATIO
ULN
NORMETANEPHRINE UR
NORMETAN/CRE RATIO
0 - 300 ug/g CRT
109 - 393 ug/d
0 - 400 ug/g CRT
19.10 38x ULN
>50
56x ULN
7,180
36xULN
39,520 76x ULN
1,480 74x ULN
13,488
16,415
45x
41xULN
36
37
Preoperative treatment in pheocromocytoma
38
Pheochromocytoma
Goals for inpatient treatment: Roizen criteria
39
Pheocromocytoma
• ~25-40% of otherwise sporadic PHEO-PGL now
attributed to a known genetic cause.
• Most patients don’t have clinical features to inform
genetic testing, therefore, inclusive (unbiased) gene panels
are reccomended ( for ex whole exome sequencing).
• If VHL, NF1, MEN2 diagnosed on basis of history or
clinical manifestations, direct testing of the suspected gene
is recommended.
Strong consideration for an individualized
surveillance plan- genetic counseling and testing
40
Cushing’s syndrome
• Low Dose DST is best test to assess adrenal autonomy
• 1mg Dexamethasone @ 2300, check cortisol @ 0800
AM Cortisol
Cutoff values
– Endocrine Society: >1.8ug/dL
• Sensitivity >95%
• Specificity 80%
Young, WF. The Incidentally Discovered Adrenal Mass. NEJM 356(6); 2007, 601-610.
41
Low dose Dex
• Consider cortisol-binding globulin
– Estrogen ↑s CBG → false + results if patient is on OCP
– Low albumin (ill patient, nephrotic syndrome) ↓s CBG →
Falsely low cortisol levels
• Consider altered clearance of dexamethasone
– Antiseizure medications, alcohol & rifampicin induce hepatic
clearance of dex
– Renal/liver failure decrease clearance of dex
– Check dexamethasone level at same time as cortisol level
• >5.6nmol/liter (0.22ug/dL) considered appropriate for
suppression
Nieman et al, Endocrine Society Guidelines on Cushing’s Syndrome. 2008.
42
Medical Therapy
Preoperative medical treatment in severe CS
Fleseriu. Endo Clinics of North America, 2015
Fleseriu. Neurosurg Clinics. 2012, Oct;23(4):653-68
43
Adrenal steroidogenesis inhibitors
Drug
Pros
Additional comments
Cons
Side effects: GI, male
hypogonadism
Ketoconazole
Rapid
action
Twice/thrice-daily dosing
May be preferred in women
New FDA warning LFTs
(rare, serious)
Gastric acidity required for
absorbtion
Many drug–drug interactions
Metyrapone
Mitotane
Etomidate
Rapid
action
Beneficial
in adrenal
cancer
Four-times-daily dosing
Side effects: GI, hirsutism,
hypertension, hypokalemia
Pregnancy? (not approved)
‘Escape’ ?
Avoid in women desiring
pregnancy within 5 years
Intravenous
Nieman L et al, JCEM, 2015, Biller BMK et al. JCEM 2008, Tritos & Biller, Discovery Medicine, 2012,
Fleseriu& Petersenn, Pituitary. 2012
Side effects: GI, neurologic,
teratogenic, adrenolytic
Delayed efficacy
Intensive ICU monitoring
44
Medical therapy before adrenalectomy in CS
•11 patients
• Mitotane
3.0–5.0 g
+ Metyrapone 3.0–4.5 g
+ Ketoconazole 400–1200
mg daily dose
•Side effects: GI, rise in
cholesterol , γGT
Kamenicky et al. J Clin Endocrinol Metab. 2011 Sep;96(9):2796-804
45
Time to recovery adrenal function after curative
surgery for CS
•
•
•
•
Retrospective analysis
91 patients with CS, 54 with CD
Mean follow up time 8 years
Time to recovery
– 0.6 years in ectopic Cushing's syndrome
– 1.4 years in Cushing's disease
– 2.5 years in adrenal Cushing's syndrome
• Patients with CD recover adrenal function after surgical “cure”
quicker than adrenal CS
• Average recovery of adrenal function in CS in recent study was
11.5 months
Berr, J Clin Endocinol Metab, April 2015
46
Primary hyperaldosteronism and subclinical
Cushing’s syndrome
• Cortisol co-secretion may appear in PA
• First studies: prevalence of subclinical Cushing’s 12-21%
• More studies are needed to evaluate prevalence
• Concern for potential misinterpreting of the adrenal vein
sampling
• Cosecretion of cortisol  can raise cortisol levels in the adrenal
vein draining the APA loss of lateralization (and a lost
opportunity to offer potentially curative surgery) or give the
impression that cannulation had failed on the contralateral side
• Risk of adrenal insufficiency after surgery if a diagnosis
of CS is not entertained preop
47
Conclusion
Multidisciplinary teams comprising many specialties are
instrumental in improving outcomes for patients with
pituitary and adrenal tumors.
Future work is needed to create multicenter
databases, especially in US to accumulate long- term data in
rare disorders.
48
Thank you!
References attached
49
References
•
•
•
•
•
•
•
•
Ausiello JC, Bruce JN, Feda PU. Postoperative assessment of the patient after transphenoidal pituitary
surgery. Pituitary. 2008;11:391-401.
Berr CM, Di Dalmazi G, Osswald A, Ritzel K, Bidlingmaier M, Geyer LL, Treitl M, Hallfeldt K, Rachinger W,
Reisch N, Blaser R. Time to recovery of adrenal function after curative surgery for Cushing's syndrome
depends on etiology. The Journal of Clinical Endocrinology & Metabolism. 2014 Dec 29;100(4):1300-8.
Carminucci AS, Ausiello JC, Page-Wilson G, Lee M, Good L, Bruce JN, Freda PU. OUTCOME OF
IMPLEMENTATION OF A MULTIDISCIPLINARY TEAM APPROACH TO THE CARE OF PATIENTS
AFTER TRANSSPHENOIDAL SURGERY. Endocrine Practice. 2015 Oct 5;22(1):36-44.
Dallapiazza RF, Grober Y, Starke RM, Laws Jr ER, Jane Jr JA. Long-term results of endonasal endoscopic
transsphenoidal resection of nonfunctioning pituitary macroadenomas. Neurosurgery. 2015 Jan 1;76(1):4253.
Fleseriu M, Lee M, Pineyro MM, Skugor M, Reddy SK, Siraj ES, Hamrahian AH. Giant invasive pituitary
prolactinoma with falsely low serum prolactin: the significance of ‘hook effect’. Journal of neuro-oncology.
2006 Aug 1;79(1):41-3.
Fleseriu M, Hashim I, Karavitaki N, Melmed S, Murad MH, Salvatori R, Samuels MH, Hormonal
replacement in hypopituitarism in adults: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol
Metab 2016; 101: 3888–3921.
Gondim JA, Almeida JP, de Albuquerque LA, Gomes E, Schops M, Mota JI. Endoscopic endonasal
transsphenoidal surgery in elderly patients with pituitary adenomas. Journal of neurosurgery. 2015
Jul;123(1):31-8.
Kristof RA, Rother M, Neuloh G, Klingmüller D. Incidence, clinical manifestations, and course of water and
electrolyte metabolism disturbances following transsphenoidal pituitary adenoma surgery: a prospective
observational study: clinical article. Journal of neurosurgery. 2009 Sep;111(3):555-62.
•
50
References
•
•
•
•
•
•
•
•
•
•
•
•
Winzeler B, Zweifel C, Nigro N, Arici B, Bally M, Schuetz P, Blum CA, Kelly C, Berkmann S, Huber A,
Gentili F. Postoperative copeptin concentration predicts diabetes insipidus after pituitary surgery. The
Journal of Clinical Endocrinology & Metabolism. 2015 Apr 29;100(6):2275-82.
Woodmansee WW, Carmichael J, Kelly D, Katznelson L. AMERICAN ASSOCIATION OF CLINICAL
ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY DISEASE STATE CLINICAL
REVIEW: POSTOPERATIVE MANAGEMENT FOLLOWING PITUITARY SURGERY. Endocrine Practice.
2015 Jul;21(7):832-8.
Glowniak JVLoriaux DL A double-blind study of perioperative steroid requirements in secondary adrenal
insufficiency. Surgery 1997;121123- 129
Salem MTainsh RE JrBromberg JLoriaux DLChernow B Perioperative glucocorticoid coverage: a
reassessment 42 years after emergence of a problem. Ann Surg 1994;219416- 425
Levy A Perioperative steroidcover. Lancet 1996;347846- 847
Yedinak C, Hameed N, Gassner M, Brzana J, McCartney S, Fleseriu M.Recovery rate of adrenal function
after surgery in patients with acromegaly is higher than in those with non-functioning pituitary tumors: a
large single center study. Pituitary. 2015 Oct;18(5):701-9.
Primary Aldosteronism – Endocrine society guidelines 2008
Huiras CMPehling GBCaplan RH Adrenal insufficiency after removal of apparently nonfunctioning adrenal
adenomas. JAMA 1989;261894- 898 Qi XP et al
Funder JW. Mineralocorticoid receptors: distribution and activation. Heart Fail Rev. 2005 Jan;10(1):15-22.
Remde H et al. Glucose Metabolism in Primary Aldosteronism. Horm Metab Res. 2015 Dec;47(13):987-93.
Muth A et al. Systematic review of surgery and outcomes in patients with primary aldosteronism. Br J Surg.
2015 Mar;102(4):307-17.
Stowasser M. Update in primary aldosteronism. J Clin Endocrinol Metab. 2015 Jan;100(1):1-10.
51
References
•
•
•
•
•
•
•
•
Stowasser M. Update in primary aldosteronism. J Clin Endocrinol Metab. 2015 Jan;100(1):1-10.
Lim V et al. Accuracy of adrenal imaging and adrenal venous sampling in predicting surgical cure
of primary aldosteronism. J Clin Endocrinol Metab. 2014 Aug;99(8):2712-9.
Lenders JWPacak KWalther MM et al. Biochemical diagnosis of pheochromocytoma: which
test is best? JAMA 2002;287 (11) 1427- 1434
JAMA Surg. 2015 Oct;150(10):974-8. doi: 10.1001/jamasurg.2015.1683. Differences Between
Bilateral Adrenal Incidentalomas and Unilateral Lesions. Pasternak et al
Lancet Oncol. 2014 May;15(6):648-55. Outcomes of adrenal-sparing surgery or total
adrenalectomy in phaeochromocytoma associated with multiple endocrine neoplasia type 2: an
international retrospective population-based study. Castinetti F et al
Adrenal Imaging Features Predict Malignancy Better than Tumor Size, Yoo et al , Ann Surg
Oncol. 2015 Dec;22 Suppl 3:721-7. doi: 10.1245/s10434-015-4684-z. Epub 2015 Jun 19.
Invited Commentary | October 2015 Nonoperative Management of Bilateral Adrenal
IncidentalomasThe Value of Restraint, Linwah Yip et al
Kudva YCSawka AMYoung WF Jr Clinical review 164: the laboratory diagnosis of adrenal
pheochromocytoma: the Mayo Clinic experience. J Clin Endocrinol Metab 2003;88 (10) 45334539
Endocr Pract. 2009 Jul-Aug;15(5):450-3, American Association of Clinical Endocrinologists and
American Association of Endocrine Surgeons Medical Guidelines for the Management
of Adrenal Incidentalomas. Zeiger MA, Thompson GB, Duh QY, Hamrahian AH, Angelos P, Elaraj
D, Fishman E, Kharlip J; American Association of Clinical Endocrinologists; American Association
of Endocrine Surgeons.
52
References
•
•
•
•
•
•
•
•
•
Riester A, Weismann D, Quinkler M, Lichtenauer UD, Halbritter R, Penning R, Spitzweg C,
Schopohl J, Beuschlein F, Reincke M, Life-threatening events in patients with
pheochromocytoma. Eur J Endocrinol. 2015 Sep 7. pii: EJE-15-0483.
Zelinka T, Petrak O, Turkova H, Holaj R, Strauch B, Kresk M, Vrankova AB, Musil Z, High
incidence of Cardiovascular Complications in Pheochromocytoma. Horm Metab Res 2012;44:379384.
Cardiovascular Manifestations of phaechromocytoma
Whitelaw B, Prague K., Mustafa, O. G., Schulte, K.-M., Hopkins, P. A., Gilbert, J. A., McGregor, A.
M. and Aylwin, S. J. B. Phaeochromocytoma crisis. Clin Endocrinol 2014; 80: 13–22.
Scholten, A.,Cisco, R., Vriens, M.R, Cohen J, Mitmaker J, Liu C, Tyrrell B, Shen T, Duh Y,
Pheochromocytoma is not a surgical emergency. J Clin Endocrinol Metab. 2013;98(2):581-91.
Sutton M, Sheps SG, Lie JL. Prevalence of clinically unsuspected pheochromocytoma;review of a
50-year autopsy series. Mayo Clin Proc. 1981;56:354–360.
McLeod MKThompson NWGross MDBondeson AGBondeson L Sub-clinical Cushing's
syndrome in patients with adrenal gland incidentalomas: pitfalls in diagnosis and
management. Am Surg 1990;56398- 403
Sippel RSChen H Subclinical Cushing's syndrome in adrenal incidentalomas. Surg Clin North
Am 2004;84875- 8
Terzolo MReimondo GBovio SAngeli A Subclinical Cushing's syndrome. Pituitary2004;7217223
53