Download Outpatient workup and management of thyroid disorders

Where there is no
endocrinologist—
Outpatient workup and management of
common thyroid disorders—
selected case studies
9/19/13
Introductions
 Who are you?
 Who am I?
Amy Robinson, M.D.
Lobo Care Clinic
1101-A 4 Medical Arts Ave, NE
[email protected]
Asst. Professor, Division of
General Internal Medicine
Disclosures
 I have no known conflicts of interest
OBJECTIVES
1) to help you perform better on standardized
exams
2) to help you feel more comfortable managing
some common thyroid problems in an outpatient
setting. Some of the information presented here
will be very basic—no offense intended
Case #1:
A healthy 28 year old female c/o one year history of painless
swelling in her neck.
She denies weight loss, fatigue, and anxiety.
Family history is positive for thyroid disease in her mom and
maternal grandmother who both take levothyroxine.
She is thinking about trying to get pregnant.
Case #1 continued:
PE: BP 130/80, HR 94, RR 16, BMI 27.
Heart, Lungs, Abdomen, Ext: normal
Neck: thyroid gland palpable, minimally enlarged bilaterally,
and firm; no nodules palpated; no cervical lymphadenopathy
Labs: TSH =
(normal = 0.358-3.740)
Free T4 = 1.2
(normal = 0.7-1.6)
Free T3 = 4.0
(normal = 0.5-30.0)
Thyroid peroxidase antibodies =
(normal <20)
Q: What is the next most appropriate action?
A.
B.
C.
D.
Fine-needle aspiration of the thyroid gland
Start levothyroxine
Observe; repeat TSH in 6 weeks
Thyroid scan
B: Start levothyroxine
Important points:
1) What is her diagnosis?
2) Why is this her diagnosis?
What: Subclinical hypothyroidism.
Why: She has an elevated TSH with
normal T4 and T3
These people often have minimal to no
symptoms—you have probably already
seen this in clinic.
Treatment issue:
 At what TSH should treatment be initiated
for subclinical hypothyroidism?
 TSH> 10—consensus for non-pregnant
adult
 She is at risk of progression to overt
hypothyroidism due to +anti-TPO
antibodies, +family history and likely
pregnancy
What other problems might she encounter
with untreated subclinical hypothyroidism?
 Mild elevation of Total Cholesterol, LDL,
and CRP
 Increased risk for atherosclerosis and
cardiac events
 (BTW—data does not yet show that RX
with levothyroxine reverses these or
improves outcomes )
What would most practitioners actually do in
this situation?
Given her possibility of pregnancy, +antiTPO antibodies, goiter and strong FHX,
most practitioners would start
levothyroxine despite her mildly elevated
TSH (above normal but less than 10).
Why not biopsy her thyroid?
She did not have a palpable nodule.
What are the risks of untreated or inadequately
treated hypothyroidism in pregnancy?
 Low birth weight
 Increased risk of miscarriage
 Premature birth
 Fetal loss
Why?
The fetus requires transplacental
transfer of maternal thyroid
hormones during the first 12 weeks
of gestation.
What is the optimal TSH in a woman
considering pregnancy?
0.5-2.5
Wow!
Reference
Lazarus, JH. The continuing saga of postpartum
thyroiditis. J Clin Endocrinol Metab. 2011;
96(3):614-616. PMID: 21378224.
Case #2:
A 27 year old female has a positive HCG and is
estimated to be at 4 weeks gestation.
She has been well aside from a history of
hypothyroidism.
PMHX: Hashimoto’s thyroiditis
Meds: levothyroxine 125 mcg daily, PNV, FeSo4
Case #2 continued:
PE: T 37.1 C, BP 128/80, HR 95, RR 18, BMI 25.
Neuro: fine hand tremor
Normal heart, lungs, skin
Neck: thyroid slightly enlarged but smooth texture; no
nodules or bruits
Labs: TSH = 4.2
(normal= 0.358-3.740)
free T4 = 1.6
(normal= 0.7-1.6)
Q: What do you recommend?
A. increase the levothyroxine by 10% today
B. increase the levothyroxine by 30%
C. continue the same dose, repeat thyroid tests
in 5 weeks
D. repeat thyroid tests in the second trimester
Answer:
B. Increase the thyroid dose by 30% now!
(and repeat the thyroid tests in 4 weeks)
Why?
Pregnancy will likely increase the
levothyroxine requirements for most
women already on thyroid replacement
therapy, especially during the first and
possibly the second trimester.
Why?
 During the first half of pregnancy, there is increased serum
thyroxine-binding globulin (TBG) and TSH
 Increased thyroid hormone requirement is due to both
increased TBG production and decreased clearance
 The thyroid gland responds by increasing production of T3
and T4
 This change will plateau at 20 weeks such that the overall
production rate of thyroid hormones returns to prepregnancy rates
Ross, Douglas S. “Overview of Thyroid disease in pregnancy,”
UpToDateOnline, 10/3/2012.
What are the goal TSH levels by trimester?
--0.1-2.5 -- first trimester
--0.2-3.2 – second trimester
--0.3-3.0 – third trimester
Why worry?
Maternal subclinical or overt hypothyroidism may be
associated with
 Fetal neurocognitive impairment
 Increased risk of premature birth
 Low birth weight
 Increased miscarriage
 Increased risk of fetal death
Case Reference
 Yassa L, Marqusee E, Fawcett R, Alexander EK.
Thyroid hormone early adjustment in pregnancy (the
THERAPY) trial. J Clin Endocrinol Metab. 2010; 95 (7):
3234-3241. PMID: 20463094
A few other fun questions:
1) what is the prevalence of subclinical
hypothyroidism?
2) what is the prevalence of overt
hypothyroidism?
3) what should the normal range of TSH
actually be?
Fun question --answers
1) 4-15% = prevalence of subclinical hypothyroidism in
community surveys.
2) 0.1-2% = prevalence of overt hypothyroidism (note that the
prevalence of subclinical hypothyroidism is greater);
hypothyroidism is 8x more common in women than in men.
3) the normal reference range of TSH is much debated. Some
labs use 4-5 and others use values more in the 2-3 range.
Many believe that the normal TSH distribution will drift up w/
age, so 6-8 might represent a normal value in an
octagenarian.
Fun questions (!) continued:
4) what is the most appropriate starting dose for the
treatment of hypothyroidism?
5) After starting or changing levothyroxine, when do
you recheck the TSH?
6) If the patient has a normal TSH, when do you next
reassess the level?
7) What medications interfere with absorption of
thyroid medication?
More fun answers!
 4) Supplementation is recommended at
about 1.6 mcg/kg body weight which
amounts to 112 mcg/ day for a 70 kg
person. The actual requirement varies
considerably ranging from 50 to over
200 mcg per day. It correlates better
with lean body mass.
 5) the plasma half life of levothyroxine is one week (7
days). It takes six half-lives for a steady-state level to
be achieved, so it is advised to recheck the level in 6
weeks.
 6) when stable, recheck the TSH annually or sooner if
other important changes occur (e.g. pregnancy,
significant weight change, initiation of medications
which may affect absorption).
7) numerous drugs affect thyroid hormone levels by
affecting binding in serum (e.g. oral contraceptives,
tamoxifen, raloxifene, methadone, androgens,
glucocorticoids, salicylates, furosemide and heparin). GI
absorption is affected by cholestyramine, colestipol,
omeprazole, lansoprazole (note—normal gastric acid
levels are required for absorption), ferrous sulfate,
calcium carbonate, and ciprofloxacin).
7) continued- T3 production is reduced by amiodarone.
Thyroid hormone metabolism is affected by
phenobarbitol, carbamazepine, and rifampin, among
others.
Reference:
Surks, Martin I. “Drug Interactions with Thyroid
Hormones,” UpToDateOnline.
And more…
8) Should pregnant women be routinely
screened for hypothyroidism?
9) How is hypothyroidism diagnosed?
10) How is hypothyroidism categorized?
8) there is some debate about this, but routine
screening of all pregnant women is not currently
recommended.
It is advisable to check the TSH in at risk women which
would include
--symptoms of or family history of thyroid disease
--risk factors including goiter, type 1 diabetes, history of
head/neck radiation, iodine deficiency, or recent use of
lithium or amiodarone.
9) diagnosis relies upon lab tests because there is a lack
of specificity of clinical symptoms.
10) Primary hypothyroidism accounts for about 95% of
cases and is characterized by elevated TSH with low
free T4; subclinical hypothyroidism is characterized by
elevated TSH with normal free T4; secondary (central)
hypothyroidism is characterized by normal TSH and low
T4.
Case #3:
A 40-year old male presents to you for
evaluation of a small nodule in the right lobe of
the thyroid gland on a CT scan obtained
because of chest pain. He feels well now and
denies palpitations, feeling nervous, neck
discomfort, or dysphagia. His mom had papillary
thyroid cancer that was diagnosed in her 30s.
Case #3 continued:
On exam, he appears healthy and alert.
Vitals are normal; BMI is 28.
Lungs, Heart, Abd—normal
Neck—barely palpable thyroid; no nodules; no cervical
lymphadenopathy
Labs notable for normal TSH at 1.5 mU/L.
Neck US demonstrates right lobe 6 mm hypoechoic nodule
w/ microcalcifications, blurred margins and increased
vascularity. No enlarged cervical lymph nodes seen.
Which of the following is the most appropriate step?
A. Fine-needle aspiration biopsy
B. Repeat thyroid ultrasound in 3
months
C. Right thyroid lobectomy
D. Thyroid MRI
FNA of the nodule—right!
Key points:
-Most thyroid nodules are benign
-only about 5-15% are malignant
-Biopsy results are usually categorized as one of the
following: benign, suspicious for malignancy, follicular
neoplasm or papillary thyroid cancer
-FNA is the most sensitive and specific method to
characterize the nodule
How common are thyroid
nodules?
30-50% of healthy people are likely to
have a thyroid nodule on ultrasound
How do you decide which nodules to
biopsy?
 The American Thyroid Association recommends
biopsy of a nodule of at least 5 mm diameter in a
patient at high risk who also has worrisome
sonographic findings.
 Our patient here has a first-degree relative with
papillary thyroid cancer. Ultrasound showed
concerning qualities of hypoechoic shadowing with
blurred margins, microcalcifications and increased
central vascularity.
Why would it be inappropriate to
observe and follow with repeat
thyroid ultrasound in 3-6 months?
His nodule demonstrated
suspicious features and he had
significant risk factors
Why not perform thyroid lobectomy?
Thyroid lobectomy would be appropriate
for a cancerous thyroid nodule less than 1
cm diameter but is premature, because he
does not yet have a diagnosis of
malignancy.
Why didn’t you order an MRI?
It might be helpful in detecting local
extension of thyroid malignancies or
spread into the mediastinum or retrothyroid regions but is generally less clear
than Doppler ultrasonography for
imaging nodules within the thyroid gland.
(Not to mention the copay….)
Case reference
American Thyroid Association (ATA) Guidelines
Taskforce on Thyroid Nodules and Differentiated
Thyroid Cancer; Cooper DS, Doherty GM, Haugen
BR, et al. Revised American Thyroid Association
management guidelines for patients with thyroid
nodules and differentiated thyroid cancer (errata in
Thyroid. 2010; 20(6):674-675; and Thyroid.
2010:20(8):942). Thyroid. 2009; 19(11): 1167-1214.
PMID: 19860588
Objectives covered so far:
 Case 1: management of subclinical hypothyroidism in
a woman of childbearing age with multiple risk
factors
 Case 2: management of hypothyroidism in a woman
during early pregnancy
 Case 3: management of thyroid nodule with fineneedle aspiration
Case #4:
 An 88 year old man comes in for a routine
physical. He c/o moderate fatigue. He denies
weight change, nervousness, constipation,
dyspnea, and palpitations.
 PMHX: hypertension
 Meds: lisinopril, low dose aspirin
 P.E.: alert/oriented older gentleman
 Vitals: BP 140/85, others normal
 Heart: RRR with gr. 1/6 crescendo-decrescendo sys.
murmur
 Lungs: normal exam
 Neck: thyroid gland not palpable; no cervical
lymphadenopathy
 Ext/pulses--normal
Case #4 continued:
Labs:
CBC normal
CMP normal
Thyroid function tests (repeated and confirmed):
--TSH = 6.8
(normal = 0.358-3.740)
--Free T4 = 1.1
(normal = 0.7-1.6)
Thyroid peroxidase antibody titer = normal
Which of the following is the most
appropriate management?
A. Prescribe levothyroxine
B. Prescribe liothyronine
C. Radioactive iodine test
D. Observe
D. Observe
Why?
 “Several studies have shown that an elevated serum TSH
level in older patients is not associated with detrimental
medical outcomes (such as depressive symptoms and
impaired cognitive function) but, in fact, is associated with
a lower mortality rate. Although the precise numbers are
somewhat controversial, the normal reference range most
likely is approximately 1 to 7 microunits/mL (1-7
milliunits/L). It is now recognized that older patients
generally should not be given levothyroxine solely for an
elevated TSH level. A full consideration of the patient and
clinical context is necessary.”
Why not give levothyroxine?
He is asymptomatic aside from some
fatigue and is generally in good health.
Given his unremarkable physical exam
and normal TPO level, he does not need
exogenous levothyroxine.
Why not give liothyronine?
 There is no evidence to show clinical benefit of using
liothyronine over levothyroxine in patients who
require thyroid hormone supplementation.
 Liothyronine and other T3 preparations have a short
half-life and have been associated with acute spikes in
serum T3 levels. This is especially worrisome in older
patients and those with cardiac abnormalities.
Why not do a radioactive iodine test?
This test is not used for the diagnosis of
hypothyroidism and would therefore be
inappropriate.
Aside—when would you perform a
radioactive iodine test?
Choices:
A. Never—I let the endocrinologist do this
if needed.
B. I order this if my patient has a thyroid
nodule.
C. I order this if my patient has a low TSH.
D. I order this in a patient with a low TSH
and a thyroid nodule.
It depends…
If you still work at UNM, consider calling the
endocrinologist through the PALS line.
If you work somewhere else, call the endocrinologist
who you will send your patient to when you reach the
limit of your expertise.
Case 4 reference:
 Gussekloo, J, van Exel, de Craen AJ, Meinders AE,
Frolich M, Westendorp RG. Thyroid status, disability
and cognitive function, and survival in old age. JAMA.
2004; 292 (21): 2591-2599. PMID: 1557217.
Acknowlegements
 The cases presented here were forwarded to me by
Dr. Colombo and come from the MKSAP review.
 Additional information was from assorted articles in
UpToDateOnline.
 Cases on secondary amenorrhea, Graves’ disease,
medullary thyroid cancer, myxedema coma and TSHsecreting pituitary tumor were not included due to
their less common presentation in outpatient primary
care settings and time constraints.
Good luck
And thank you for your
attention!