Transcript Endocrinology

Endocrinology Review
A Smattering.
•
55F w/ FASTING blood glucose of 130 at her
state fair. She has no symptoms of polyuria or
polydipsia. Her mother and sister have
developed T2DM in their 50’s. On physical
Exam, Bp 130/75, P 72, BMI 28.
Which should be done next to establish the dx of
DM?
A.
B.
C.
D.
E.
Measure HgbA1c
Repeat fasting plasma glucose measurement
Perform 100g glucose tolerance test
Measure 2-hr postprandial blood glucose level
Measure fasting plasma insulin level
Textbook Answer - B. Repeat
Fasting Glucose
• ADA criteria for DM are:
1) Fasting plasma Glucose >126
2) 2hr plasma glucose >200 after 75g oral
load
3) Random gluose >200 plus symptoms of
DM.
*** Now HgbA1c >6.5% is accepted
• A 26F is seen in the ED for episodes of lower abdominal/pelvic
discomfort. BP is 160/90 during this episode, and was normal prior.
BMI 26, no hirsutism, striae, or central adiposity. CBC, Glucose,
Electrolytes normal. CT scan of the abdomen reveals 1.8cm
irregularity in the right adrenal gland. She feels better and is
released.
Which of the following is the most appropriate follow-up?
A. MRI of the abdomen
B. Observation only
C. Repeat CT scan in 1 to 3 months
D. Screen for pheochromocytoma, Cushing’s syndrome, and primary
aldostertonism.
D. Screen!!
• Incidentalomas discovered in up to 6.9% of
abdominal/pelvic imaging studies
• Most hormonally silent, recent study of 2000
masses revealed 82% were nonfunctional
• Most Endocrinologist recommend Screen!
– Cushing’s: Overnight dexamethasone
– Pheo: Fractionated plasma metanephrines
– Hypertensive pts: plasma aldo/renin activity
• Non-functioning Lesions <4 cm in diameter do
not require surgical intervention but should be
re-imaged in 3-6months
• Lesions >4 cm in diameter OR any size lesions
that are hormonally active should be referred for
resection.
• CT vs. MRI? Go with CT. MRI more costly and
of little extra benefit.
• 36M is seen in the ED for HA and palpitations. He is anxious,
tremulous, and diaphoretic. Bp 198/106 and pulse 110.
Hypertensive x2 years and suboptimally controlled on a 4 drug
regimen. He frequently experiences similar episodic HA and
diaphoresis, during which his BP is alarmingly high. He was
prescribed propranolol for migraine headaches which increased
their frequency and severity.
Which of the following tests is the most appropriate next step?
A. Serum Catecholamines
B. Serum potassium
C. Insulin-like growth factor 1
D. Fractionated plasma metanephrines
E. 24-hour urine collection for cortisol
D. Fractionated Plasma
Metanephrines
• The classic triad of HA, Palpitations, and Diaphoresis is
suggestive Pheochromocytoma.
• The sensitivity of fractionated plasma metanephrines for
catecholamine-producing tumors is nearly 97%,
Specificity (false positives) 85%.
• Acetaminophen is the only drug that interferes with the
test and should be withdrawn for 48hrs.
• Can confirm plasma metanephrines test with 24hr urine
metanephrines ~94% specificity.
•
38F w/ 3cm heterogeneous mass in the right adrenal gland is
found to have plasma fractionated metanephrines 2x the upper
limit of normal. 24hr urine collection of metanephrines contains
2.5x the normal daily excretion. Pheochromocytoma is suspected
and laparoscopic adrenalectomy is planned w/n 14-21 days. Her
blood pressure is 206/110 and her pulse is 104. She is taking no
other meds.
Which of the following is indicated prior to surgery?
A. Carvediolol therapy
B. Blood transfusions
C. Fine-needles aspiration of the mass
D. Phenoxybenzamine therapy
D. Phenoxybenzamine (alphaantagonist)
• Surgical resection is the only cure for a PHEO.
• Perioperative mortality ~4%, blood pressure control should be
started w/n 2wks prior to nonemergent surgery using alphaadrenergic antagonists. Goal is <140/90.
• Alpha-antagonists can minimize hypertensive crisis during
intubation, induction, and tumor manipulation, but its half life of
24hrs can contribute to post-op hypotension.
• Beta-blockers should never be administered prior to alpha blockade
as it permits unopposed alpha activity causing HTN crisis.
• Fine-needles aspiration may precipitate a hypertensive crisis, and
the procedure is never preformed if PHEO is suspected.
•
33M seen for a mass in the right side of his neck. He
has no neck pain, hoarseness, or dysphagia. No hx of
radiation exposure. No family hx of thyroid tumors or
disorders. On physical Exam he has a 2.5cm right
thyroid nodule that is moderately mobile and
nontender. No palpable cervical lymph nodes.
Which serum test is the most important to order?
A.
B.
C.
D.
E.
TSH
Thyroglobulin
Antithyroid Peroxidase and Antithyroglobulin
Antibodies
Total T3
Calcitonin
A. TSH
• The first step in the eval of a thyroid nodule is
measurement of serum TSH.
• If TSH is normal the nodule is most likely nonfunctioning
or “COLD.” In this case FNA would be indicated to r/o
malignancy.
• If TSH is low the nodule is more likely hyperfunctioning
or “HOT.” A HOT nodule has low likelihood of being
malignant so an FNA would not be necessary in most
patients. But a thyroid scan would be indicated to
confirm the presence of a HOT nodule and see if others
are present.
• Measurement of serum thyroglobulin is useful for
following thyroid cancers in response to treatment, but
not useful to distinguish benign from malignant nodules.
45F seen for a sensation of fullness in her neck and occasional
difficulty swallowing. She feels well otherwise. No hx of
head/neck radiation. Her mother developed a goiter at age 40.
On physical exam the thyroid gland is 2x normal size and there is a
dominant 2-cm nodule in the left lobe. No cervical lymph nodes
are palpable. TSH is 1.8. Thyroid U/S reveals multiple small
nodules in both lobes and a 2.2cm dominant nodule in the left
lobe.
Which of the following is the next best step?
A. Thyroid Scan
B. FNA of dominant nodule
C. Serum thyroglobulin test
D. Serum antithyroid peroxidase and antithyroglobulin antibodies
E. Serial ultrasound measurements
B. Fine Needle Aspiration
• A dominant nodule in multinodular goiter has the
same risk of malignancy as a solitary one.
• TSH should always be measured
• Ultrasound is recommended to define the
characteristics of the dominant nodule and other
nodules.
• The next step would be FNA, if it is benign then
serial monitoring to assess size stability would
be reasonable.
•
69M admitted to MICU w/ hypotension,
urosepsis, and CHF. No hx of thyroid
dysfunction. Pulse 64, no proptosis, no goiter.
DTR slightly diminished. T4 4.7(ug/dl), Free
T4 0.8 (ng/dl) (boderline low), Total T3
5.21(ng/dl) -- LOW, and TSH 6.1. Antithyroid
peroxidase and antithyroglobulin abs are
negative.
A.
B.
C.
D.
Levothyroxine 1.6ug/kg PO
Levothyroxine 0.05ug/kg IV
No thyroid hormone therapy
Liothyronine (T3) 12.5ug PO BID
C. No thyroid hormone
replacement
• Euthyroid Sick Syndrome  precipitous drop in serum
total free T3 levels and a concomitant increase in
reverse T3 (rT3).
• TSH may be low, normal, or high.
• Can occur in a host of non-thyroidal illness (sepsis,
major surgery).
• Change in thyroid hormone level during acute illness are
believed to be adaptive, protecting the body from
catabolic illness.
• Thyroid hormone replacement therapy in patients with
euthyroid sick syndrome has not been shown to be
beneficial.
•
38F w/ 6kg wgt gain over the last 2 years. She has
fasting blood glucose of 130 and 136 on 2 separate
visits. She is not taking any other medications. On
physical exam her BMI is 32 and Bp is 160/94. She
has scant terminal hairs over her chin, mild acne over
her face, and violaceous striae approximately 1cm wide
bilaterally over her lateral abdomen. Her face is full,
abdomen prominent, and her arms an legs seem
disproportionately thin.
Which of the following is the best next step?
A. Serum cortisol 1600
B. 24hr urine collection for cortisol
C. Serum cortisol 0800 following dex 8mg the prior
evening
D. Serum ACTH 0800
E. MRI of the HEAD.
B. 24hr Urine Cortisol
• Patients w/ Cushing’s produce 3-4x the amount
of urine free cortisol than normal
• The three screening tests for Cushing's
syndrome are measurement of urine free
cortisol, overnight dex suppression test, and the
late-evening salivary cortisol test.
• Initial testing for Cushing’s syndrome relies on
demonstartion of excess cortisol production.
• 24hr urine cortisol is often the first test in pts with strong
suspicion for Cushing’s. (CRI should be known prior)
• Overnight Dex w/ 1mg (8mg used to differentiate b/t ACTHdependent forms of Cushing’s) at 2300 is adequate to suppress
ACTH by the normal central axis, but not corticotropin-producing
pituitary adenomas or cortisol producing adrenal adenomas.
0800 cortisol will be suppressed in normal patients, but not
Cushing’s
• Saliva contains cortisol that is unbound, if collected at 2300
during the normal phsyciologic nadir of production, it may
indicate autonomous cortisol production. This screening is not
widely available, but gaining experience with this assay is
growing.
• 1600 cortisol levels are not sensitive or specific for diagnosis.
• 0800 ACTH is useful if ectopic source of ACTH is present
• MRI not performed unless excess hormonal excess performed
(high incidence of incidentalomas in pituitary will confound
diagnosis)
•
38F evaluated for ELEVATED salivary cortisol
concentration collected at 2300hrs on two
separate occasions. The patient has poorly
controlled diabetes mellitus and signs of
cortisol excess. Serum ACTH is 29 (normal).
Which is the next best test?
A. Dex 8mg suppression test
B. MRI of the head
C. Somatostatin receptor scintigraphy
D. Inferior petrosal sinus sampling
A. 8mg Dex suppresion test
•
Causes of ACTH dependent Cushing’s can be distinguished by the dex 8mg
(high dose) suppression test and Corticotropin-releasing hormone
stimulation test (CRH).
•
Patient has evidence of excess cortisol production based on 2300hrs
salivary cortisol test. Cortisol is cyclically produced w/ nadir of ACTH and
cortisol near midnight.
•
Her ACTH is in the normal range which may represent the source of ACH
may be a corticotrope adenoma or ectopic production by a tumor.
•
If the source of ACTH is a corticotrope then 8mg of dex will suppress ACTH
and cortisol production by at least 68%. If the source is ectopic then the
source is negliable.
•
CRH stimulation test increases ACTH by 35-50% over baseline in
corticotrope adenomas. Cortisol concentrations rise by 20-50%.
Nonpituitary tumors producing ectopic ACTH do not respond.
•
40F w/ new HTN and T2DM is noted to have central
adiposity and wide violaceous striae over her flanks.
Two 24h urine collections for free cortisol contain 4x the
normal amount. Serum ACTH is in the mid-normal
range. Dex 8mg suppression test is given and cortisol
is only supprsed by 30%. CRH stimulation causes a
rise in ACTH by 70% and a rise in cortisol by 60%.
MRI reveals no pituitary abnormalities.
Which test will differentiate the source of ACTH?
A. Inferior petrosal sinus sampling
B. Somatostatin receptor scintigraphy
C. Selective adrenal venous sampling
D. PET
A. Inferior Petrosal Sampling
• Inferior Petrosal Sampling is the confirmatory test for Cushing’s
syndrome in patients with ambiguous results in screening tests.
This is very sensitive and specific, but costly, difficult, and somewhat
hazardous.
• A pt w/ suspected Cushing’s dz, confirmed biochemically (dex
suppression, CRH), and who has pituitary adenoma on MRI, may be
taken directly for resection.
• When CRH and Dex 8mg suppression are equivocal or conflicting,
petrosal sampling is required.
• If both tests did indicate a pituitary source, but no abnormality noted
on MRI (up to 40% of cases) then inferior petrosal sinus sampling is
again suggested.
•
28F seen for serum calcium level of 11.0 obtained
during routine physical exam. All other labs are normal.
PTH level was 40pg/ml (normal). Pt is healthy, no
polyuria, constipation, or fatigue. Her mother and
grandfather have a history of hyperparathyroidism and
both underwent parathyroidectomy but remained mildly
hypercalcemic. The patient had a recent renal u/s that
showed no evidence of stones. Her diet is rich in dairy
products and no hx of GI illness.
Which of the following tests is likely to confirm dx?
A. 25-hydroxyvitamin D
B. 1,25-dihydroxyvitamin D
C. Urine Calcium/creatinine clearance ratio
D. Parathyroid hormone related peptide
E. Prolactin
C. Urine Calcium/Creatinine
• In an asymptomatic patient w/ mild hypercalcemia and
an inappropriately normal PTH (represents a
parathyroid-dependent cause), the differential includes
primary hyperparathyroidism vs. benign familial
hypocalciuric hypercalcemia.
• Familial hypocalciuric hypercalcemia is diagnosed by
urinary calcium/creatinine clearance ratio <0.01
measured in a fasting morning urine spot collection.
• BFH is characterized by lifelong mild asymptomatic
hypercalcemia. Autosomal Dominant mutation of the
calcium-sensing receptor. These people DO NOT
REQUIRE SURGERY, so it is important to differentiate.
A 51-year-old man is undergoing a routine physical examination. He has no
significant personal or family medical history. He still exercises regularly,
running 2 to 3 miles at least three times a week. He does not smoke,
drink alcohol, or use recreational drugs. Physical examination is normal.
Laboratory tests are normal other than a calcium level of 11.0 mg/dL
(2.74 mmol/L). A subsequent serum parathyroid level is 120 pg/mL (120
ng/L). A 24-hour urine calcium excretion is 250 mg (6.3 mmol). The
creatinine clearance is normal. A DEXA scan shows a T score of 0.99 at
the left femoral neck, 0.68 at the lumbar spine, and −2.5 at the distal third
of the forearm.
Which of the following is the most appropriate management for this patient?
A.
B.
C.
D.
E.
Calcium and vit D supplementation
Alendronate
Parathyroidectomy
Nasal calcitonin
Ibandronate
•
•
•
Primary hyperparathyroidism is the most common cause of hypercalcemia in the
outpatient setting
Single parathyroid adenoma is the cause in 85% of cases
Double adenoma or multi-gland hyperplasia in 15% of cases. Usually associated with
MEN type 1 or MEN type 2 syndromes
2002 National Institutes of Health consensus conference guidelines for the management
of asymptomatic primary hyperparathyroidism
Indications for surgery
–
–
–
–
–
Serum calcium level >1 mg/d above upper limit of normal
24-Hour urine calcium excretion > 400 mg
Creatinine clearance reduced by ≥ 30%
Bone mineral density: T-score <−2.5 at any site
Age younger than 50 years
Recommended follow-up measurements for patients not undergoing surgery
–
–
–
Biannual serum calcium
Annual serum creatinine
Annual bone mineral density (lumbar spine, proximal femur, distal forearm)
•
55F is concerned about osteoporosis. Her mother had
a hip fracture at 65. The patient is healthy and
exercises 3x/wk for 45 minutes at the gym. She eats a
balanced diet and attempts to consume two servings of
mild or yogurt a day. She attained menopause at 50.
She does not drink or smoke. She has a hx of HTN
which is treated with ramipril. PE reveals BMI of 26, Bp
120/70. All labs are normal.
Which of the following is the most appropriate evaluation
for the patient?
A. DEXA scan at 65
B. DEXA now
C. Radiographs of the hip and lumbosacral spine
D. Serum osteocalcin
E. Urine pyridinoline and deoxypyridinoline cross-links of
bone
B. DEXA now
• Risk factors – age >65, female, white, Asian, fx of osteoporosis,
small body size or weight, premature or surgical menopause,
inadequate calcium intake, smoking, excessive etoh consumption,
excessive physical activity causing amenorrhea, corticosteroids,
anticonvulsants, hormonal, lifestyle, nutrition, medications, and
medical conditions.
• Indications for measurement of bone mass include women >65
years of age who have at least one risk factor for osteoporosis other
than menopause, post menopausal women who present with
fractures, women receiving hormonal replacement, and women who
are on steroids for more than 3 months.
• Since this patient is post-menopausal and has a family hx of
osteoporosis, the DEXA scan should be done now.
•
34F seen for polyuria and polydipsia. Hx of
depression, BMI 28, no Fhx of DM. No meds. Fasting
PBG 100, no glucose in urine. Her urine spec gravity is
<1.005. Her measured 24hr urine output is 7-8L!
Serum Na is 140, and other lytes are normal. A water
deprivation test raises the sodium to 148 and the urine
osm remains < 300 and the plasma osm increases to
300. Despite no oral intake her UOP remains 275ml/hr.
At this time blood is collected to measure ADH and 1ug
of vasopressin is administered subcutaneously. One
hour later her urine osm increases to 600 and the UOP
is less than 100ml/hr.
What is the most likely dx?
A. Normal, no pathology
B. Nephrogenic DI
C. Central DI
D. Primary Polydipsia
C. Central DI
• In the H20 deprivation test, impaired ability to concentrate urine is
consistent with either nephrogenic or central DI.
• In the H20 deprivation test, a large increase in Uosm after the
administration of desmopressin is indicative of central DI, no such
increase occurs in nephrogenic DI (resistance to ADH).
• Primary Polydipsia patients can usually partially concentrate their
urine in response to H20 Deprivation, but can be difficult to
distinguish from partial-central DI…in these cases ADH level may be
helpful.
• After h20 deprivation, ADH lvls are undetectable in complete central
DI, very low in partial central DI, and variable in primary polydipsia,
and usually >5 in nephrogenic DI. ADH levels only help confirm the
dx, as it was made