Endocrine CPC
Download
Report
Transcript Endocrine CPC
Endocrine CPC
Tim Miller, MD
1/22/2008
Case
CC: I have been having headaches
HPI: Pt is a 33 year old Hispanic male
seen for routine yearly follow up
Reports headaches for 3 months
Seen at walk-in clinic and diagnosed with
migraines
Midrin and Maxalt were not effective
Case
Headaches start behind both eyes and
encompass his entire head
Recently (past 2 weeks) headaches
occur on a daily basis and are more
severe
Headaches mainly occur at night
Seem to be worse with exertion
Case
Associated Signs/Symptoms
Nausea
Photophobia
Phonophobia
Roommate says he “looks pale” with attacks
Sweats will accompany headaches, mainly
at night
Experiences “fluttering” in his chest and
notes that his pulse is around 120
Case
Pertinent Negatives
No lacrimation
No vision changes
Location does not change
Case
PMHx:
Seasonal allergies
Eczema
Positive PPD – currently on INH therapy
NAFLD with elevated LFT’s (discovered
prior to initiation of INH)
Hypertriglyceridemia
Case
PSHx:
None
FH:
Not given
Meds:
INH
All:
NKDA
SocHx:
Nonsmoker
Occasional EtOH
No drugs
Entomology graduate
student at Texas A&M
Born in Cuba and
moved to Texas to
study
Traveled to Peruvian
rainforest for research
within the last year
Case
Review of Systems:
General: no weight loss
HEENT: no vision/hearing changes, no
odynophagia/dysphagia
Pulmonary: no SOB, no cough
Cardiovascular: no chest pain, (+) palpitations
GI: no jaundice, no abd pain, no changes in bowel
habits
GU: no changes in bladder habits
Case
Physical Exam:
BP 144/84 P 110 T 98.4 BMI 26
General: well nourished, healthy appearing male
HEENT: NCAT, PERRLA, EOMI, no icterus, mm
moist, conjunctiva pink
Fundoscopic: no papilledema
Neck: supple, no LAD, no bruits, no supraclavicular
fat pad
CV: tachycardic (110) and regular, no murmurs,
gallops, or rubs
Case
Physical Exam cont:
Resp: clear bilaterally, good resp effort
Abd: mild TTP with deep palpation on the right,
lateral to umbilicus, (+) BS, no HSM, no
rebound/guarding
Ext: no C/C/E
Neuro: CN 2-12 intact, strength 5/5 x 4, no gait
abnormalities
Psych: normal mood and affect
Skin: eczematous changes to palms and bilateral
antecubital fossae
Case
Labs & Studies:
CBC normal
CMP normal other than ALT 131
Hepatitis Panel negative
Ferritin normal
Thyroid function tests normal
2-view CXR normal
CT head w/wo contrast negative
Problem List
ACUTE
Headache x 3 months
Progressively worsening
Looks pale with attacks
Sweats with headaches
Palpitations
Hypertension
Tachycardia
Travel to Peruvian
Rainforest
CHRONIC
Positive PPD
INH Therapy
Seasonal Allergies
Eczema
NAFLD Elevated LFT’s
Hypertriglyceridemia
Differential Diagnosis
Chronic Headache
Migraine
Cluster
Tension
TB Meningitis
CNS Neoplasm
Hypertensive
Headache
Endocrine Headache
Pheochromocytoma
Cushing’s Disease
Pituitary Adenoma
Headache - Epidemiology
Among the most common medical
complaints
Overall prevalence 12-16%; accounts for
1-2% of ER visits and up to 4% of outpatient
office visits
90% of headaches fall into categories of
migraine, cluster, and tension
Headache - Classification
Acute
New onset or clearly different than previous
headaches
Often are a sign of serious illness
Subarachnoid hemorrhage
Meningitis
Acute glaucoma
Hypertensive encephalopathy
Headache - Classification
Subacute
Occurs over a period of weeks to months
May or may not be related to underlying
systemic illness
Recent subdural hematoma
Subacute meningitis
Primary or metastatic tumor
Giant cell arteritis
Optic Neuritis
Headache - Classification
Chronic
Continues
intermittently for years
Usually has a benign
cause
Migraine
Cluster
Tension
Sinusitis
Dental Disease
Headache – Approach to
Diagnosis
Age of onset
Timing of pain
Precipitating factors
Characteristics of pain
Location of pain
Associated symptoms
History of prior
headaches and course
of this type of headache
Physical Exam
Migraine Headache
Unilateral and usually
pulsatile
Often associated with
nausea, photo- and
phonophobia
Moderate to severe intensity
55% occur initially prior to
age 20
Usually familial
Auras occur in 10% of
patients
Most often occur in women
Migraine Headache
Clinical Presentation
Classic Migraine (preceded by aura)
Visual, noxious, or sensory alterations followed
by intense unilateral throbbing headache Usually
do not occur more frequently than weekly
Last between 4 and 72 hours
Common Migraine (lacks aura)
Usually unilateral and throbbing
Cluster Headache
Clinical Presentation
Brief, severe, constant, nonthrobbing
headache
Lasts 15-180 minutes without treatment
Always unilateral
Much more common in men
Mean age of onset is 25
Episodes are separated by months or even
years
Cluster Headache
Begins with
sensation by the
nose or behind the
eye
Ipsilateral
lacrimation,
conjuntival injection,
or ptosis may occur
Key to diagnosis is
brevity of symptoms
Tension Headache
Clinical Presentation
Lacks features of migraine or cluster
Frequent (possibly daily), bilateral occipital,
nonthrobbing
Often a band distribution
Rarely nausea, vomiting, or visual prodrome,
although may occasionally have features of
migraine
Tension Headache?
Women more
common then men
Secondary gain?
Headache - Imaging
Danger signs that indicate need for imaging
Sudden onset of worst headache ever or headache
that reaches full intensity in minutes
Absence of similar terrible headaches in past
Worsening pattern
Focal neurologic signs or papilledema
Fever
Change in mental status or personality
Rapid onset with strenuous exercise
Presentation to any ER with headache
Differential Diagnosis
Chronic Headache
Migraine
Cluster
Tension
TB Meningitis
CNS Neoplasm
Hypertensive
Headache
Endocrine Headache
Pheochromocytoma
Cushing’s Disease
Pituitary Adenoma
CNS Tuberculosis
3 Categories
TB Meningitis
Intracranial Tuberculoma
Spinal tuberculous arachnoiditis
Account for 1% of all TB cases
Quite rare in United States
Fatal in 15-40% of cases, usually within 5-8 weeks
Active TB outside the CNS is not necessary to make
diagnosis
Send CSF for acid fast smear, TB culture, and TB PCR
Differential Diagnosis
Chronic Headache
Migraine
TB Meningitis
CNS Neoplasm
Hypertensive
Headache
Endocrine Headache
Pheochromocytoma
Cushing’s Disease
Pituitary Adenoma
CNS Neoplasm
Headache is a common symptom in
patients with brain malignancies
Worst symptom in half of patients
Usually described as dull and constant,
occasionally throbbing
Typically tension-type (77%); can be
migraine-type (9%), or other (14%)*
Severe headaches are infrequent
*Forsyth, PA, Posner, JB. Headaches in patients with brain tumors. Neurology 1993; 43:1678.
CNS Neoplasm
Other clues to malignant headaches
40% have nausea and vomiting
Change in prior headache pattern
Abnormal neurologic exam
May worsen with maneuvers that increase the ICP (bending
over, sneezing, coughing)
Tend to be worse at night (vasodilatation from transient
increase in PCO2)
Typical location is bifrontal but may be generalized if ICP is
increased
Headache, nausea, papilledema ( ICP)
Other signs of CNS malignancy include seizures, syncope,
cognitive dysfunction, focal neurologic deficits
Differential Diagnosis
Chronic Headache
Migraine
CNS Neoplasm
Hypertensive
Headache
Endocrine Headache
Pheochromocytoma
Cushing’s Disease
Pituitary Adenoma
Hypertensive Headache
Routine essential hypertension has not been
shown to directly cause headaches*
Can lead to conditions that cause headaches
Intracerebral or subarachnoid bleeding
Sudden onset of severe headaches
Hypertensive encephalopathy
Insidious onset of headache, N/V, followed by
restlessness and confusion, and eventually seizure
and coma if not treated
*Strovmer LJ, Vatten L, et al. Blood pressure and risk of headache. J Neurol Neurosurg Psychiatry 2002;72:463–6.
Hypertensive Headache
Law, et al studied whether blood pressure meds
lowered headaches in a meta-analysis
94 randomized placebo-controlled trials using 4 major types of
BP meds (thiazides, b-blockers, ACE-I, and ARB)
Separated into treatment and placebo groups
Average SBP fell by 9.4 and DBP fell by 5.5 in treatment
groups
8% reported headaches in treatment groups and 12.4%
reported headaches in placebo groups
RRR 33% (P<.001)
However, many observational studies do not support
hypertension as a cause of headaches
Law M, Morris JK, Jordan R, Wald N. Headaches and the treatment of blood pressure. Circulation. 2005; 112: 2301–
2306.
Differential Diagnosis
Chronic Headache
Migraine
Hypertensive
Headache
Endocrine Headache
Pheochromocytoma
Cushing’s Disease
Pituitary Adenoma
Cushing’s Disease
Chronic excess of glucocorticoid
Clinical features:
Progressive obesity including moon facies,
supraclavicular fat pad and buffalo hump
Skin changes of easy bruisability and striae
Osteoporosis
Proximal muscle weakness
Hypertension
Headache in up to 47% of patients
Pituitary Adenoma
Microadenoma < 1 cm
Macroadenoma > 1 cm
Arise from anterior pituitary
Secrete hormones depending on type of tumor
(Prolactin, ACTH, GH)
Clinical Presentation
Visual defects are most common presenting symptom of
nonfunctioning adenomas
Bitemporal hemianopsia
Headaches are common and nonspecific
Pituitary apoplexy causes severe headache and diplopia and
cranial nerve deficits
Differential Diagnosis
Chronic Headache
Migraine
Endocrine Headache
Pheochromocytoma
Cushing’s Disease
Pituitary Adenoma
Pheochromocytoma General
Catecholamine secreting tumors of chromaffin
cells arising from the adrenal medulla
Epinephrine and norepinephinre; rarely dopamine
Stimulate alpha and beta adrenergic receptors
Approximately 0.2% of patients diagnosed with
hypertension will have a pheochromocytoma
Equal incidence in men and women
Peak incidence between 3rd and 5th decade
Catecholamines
Epinephrine, Norepineprhine, and
Dopamine secreted from the adrenal
medulla
Act on α1 (peripheral vasoconstriction)
and α 2 receptors and β1 (heart rate and
inotropy), β2 (muscle and liver
vasodilatation)
Effects of Catecholamines
Increase force of cardiac
contractility
Increases heart rate (epi >
norepi)
Peripheral vasoconstriction
Dilates bronchioles
Glycogynolysis (mobilizing
glucose)
Increased metabolic rate
Dilates pupils
Inhibits non-essential
processes such as GI motility
Norepinephrine and epinephrine levels in human venous
blood in various physiologic and pathologic states
Cryer PE: Physiology and pathophysiology of the human sympathoadrenal neuroendocrine system. N Engl J Med 1980;303:436.
Pheochromocytoma Clinical Presentation
Clinical Triad
Episodic Headaches
Sweating
Tachycardia
(or palpitations)
Frequency ranges from multiple times per day to
monthly
Worsens with time and becomes more frequent
Half will have paroxysmal hypertension and a third
appear to have essential hypertension
5-15% present with normal blood pressure
Pheochromocytoma –
Clinical Presentation
Headaches occur in 90% of symptomatic
patients
May be mild or severe and are variable in duration
Sweating occurs in 60-70% of patients
Other signs and symptoms
Dyspnea
Generalized Weakness
Panic Attack
Pheochromocytoma –
Presentation
May often be unmasked during routine
procedure or drug administration
Anesthesia induction
Cold Medications
Opiates
Dopamine Antagonists
Cocaine or TCA’s which inhibit catecholamine
reuptake
Childbirth
Trauma
Pheochromocytoma –
Rule of 10’s
10% Bilateral
10% Malignant
10% Extra-adrenal
10% Calcify
10% Familial
10% Children
Pheochromocytoma –
Familial Conditions
MEN 2a
Pheochromocytoma
Medullary Thyroid
Cancers
Parathyroid Tumors
MEN 2b
Pheochromocytoma
Medullary Thyroid
Cancers
Neuromas
Von Hippel-Lindau
Cerebellar
Hemangioblastomas
Retinal Angiomas
Renal Cell Carcinoma
Pheochromocytoma
Neurofibromatosis
Café-au-lait spots
Neurofibromas
Pheochromocytoma
Pheochromocytoma –
Evaluation
Which patients should be evaluated for
pheochromocytoma?
Patients with difficult to control hypertension
Patients receiving more than 4 BP meds
Patients with onset of htn before age 35
Patients with onset of htn after age 60
Patients with signs or symptoms of
pheochromocytoma as mentioned before
Patients with familial history of predisposing
disorders
Severe pressor response during anesthesia
Pheochromocytoma –
Lab Diagnosis
Free plasma metanephrine level
Screening Test for at risk patients
96% sensitive but 85% specific (better if
drawn during an attack)
Standard venipuncture test
Pheochromocytoma –
Lab Diagnosis
Urinary catecholamines and metanephrines
Confirmatory test
87% sensitive and up to 99% specific
Must be collected in a 24-hour urine specimen
Order metanephrines (best test), catecholamines,
and vanillylmandelic acid (worst test)
Ensure creatinine is measured to ensure adequacy
Collect during or immediately after an attack if
possible
2-3x increase in levels is diagnostic
Pheochromocytoma –
Lab Diagnosis
Other diagnostic tests
Clonidine Suppression Test
Confirmatory test; 90% accurate
Clonidine normally suppresses release of catecholamines
centrally, but not from a pheo
Administer Clonidine and measure plasma metanephrines
before, and 3 hours after
Levels will decrease in essential hypertension
Levels remain increased in pheochromocytoma
Chromogranin A level
Increased in 80% of patients with pheochromocytoma
Not specific for pheochromocytoma
Pheochromocytoma –
Imaging
Imaging should only be
obtained after biochemical
diagnosis has been confirmed
MRI has reported sensitivity
of 100% for adrenal pheos
Better than CT for picking up
extra-adrenal tumors as well
MRI can distinguish between
incidentilomas on T2weighted images
CT may miss tumors smaller
than 1 cm
Pheochromocytoma –
Imaging
MIBG Nuclear Medicine
Scan is reserved for
biochemically proven
cases with negative MRI
or CT
MIBG structure
resembles norepi and
concentrates in adrenal
or extra-adrenal pheos
Used in familial
syndromes, recurrent
pheo, or malignant pheo
Malignant
Pheochromocytoma
10 % of pheochromocytomas are
malignant
Direct invasion into surrounding tissue
Distant metastasis
Clinical, biochemical, or histological features
cannot predict malignancy
Common metastatic sites include bone, liver,
and lymph nodes
Extra-adrenal
Pheochromocytoma
90% of pheochromocytomas
are located in the adrenal
glands
98% located in the abdomen
Extra-adrenal
pheochromocytomas arise in
paraganglion chromaffin
tissue of the sympathetic CNS
Anywhere from the base of
the brain to the bladder
Pheochromocytoma –
After Diagnosis
Rule out familial pheochromocytoma
syndromes
PTH level and Calcium level (MEN 2a)
Ophtho consult to rule out retinal angiomas
and MRI head to rule out cerebellar
hemangioblastomas (VHL)
CT pancreas and kidneys
Consider genetic testing for family
Pheochromocytoma –
Treatment
Block alpha receptors first with pure alpha
blocker Phenoxybenzamine
After alpha blockade is achieved, begin
nonselective beta-blockers
Administer last doses the morning of surgery
Hydrate well and expand volume with isotonic
saline
Surgically resect tumor; give stress-dose
steroids if bilateral adrenalectomy is planned
Pheochromocytoma –
Long term follow up
Test plasma free metanephrines 2 weeks
post-operatively, then every 5 years
thereafter
Ensure resolution of hypertension and
associated complications
Problem List
ACUTE
Headache x 3 months
Progressively worsening
Looks pale with attacks
Sweats with headaches
Palpitations
Hypertension
Tachycardia
Travel to Peruvian
Rainforest
CHRONIC
Positive PPD
INH Therapy
Seasonal Allergies
Eczema
NAFLD Elevated LFT’s
Hypertriglyceridemia
Differential Diagnosis
Chronic Headache
Migraine
Endocrine Headache
Pheochromocytoma
Final Diagnosis:
Pheochromocytoma
Test of Choice:
24-hour urine
catecholamines,
metanephrines, and VMA
References
1.
2.
3.
4.
5.
6.
7.
Forsyth, PA, Posner, JB. Headaches in patients with brain tumors: a study of
111 patients. Neurology 1993; 43:1678.
Cryer PE: Physiology and pathophysiology of the human sympathoadrenal
neuroendocrine system. N Engl J Med 1980;303:436.
Headache classification committee of international headache society.
Classification and diagnostic criteria for headache disorders, cranial neuralgias,
and facial pain. Cephalalgia 1988; 9 Suppl 7:1.
Headache Classification Committee of the International Headache Society. The
International Classification of Headache Disorders. Cephalalgia 2004; 24:1.
Strovmer LJ, Vatten L, et al. Blood pressure and risk of headache: a prospective
study of 22 685 adults in Norway. J Neurol Neurosurg Psychiatry 2002;72:463–
6.
Law M, Morris JK, Jordan R, Wald N. Headaches and the treatment of blood
pressure: results from a meta-analysis of 94 randomized placebo-controlled
trials with 24 000 participants. Circulation. 2005; 112: 2301–2306.
www.uptodate.com