3rd Joint JSED-AACE Congress

Thyroid Disease Update

Dr. Mohammad ALshorman

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 Causes, Course & Consequences of
• Subclinical hypothyroidism
• Overt hypothyroidism
• Subclinical hyperthyroidism
• Overt hyperthyroidism

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 What is Normal Serum TSH?
• Changing target & a matter of debate
• Lab reference range (0.5-5.0 mIU/L); adopted
from guidelines (0.3-3.0)
• Factors influencing TSH levels include age,
ethnicity, I-intake and autoimmune disease
• Individual range is very narrow, 0.5 mIU/L
over time

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 Serum TSH and Age
Age 20-29
Age 50-59
Age ≥80
%

Upper TSH concentration

TSH group (%)

TSH concentration groups (mIU/L)

JCEM 92:4575, 2007

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 Subclinical Hypothyroidism
(SCHypo)
• Prevalence 1-9% in 12 studies 1977-2002
• Elevated TSH with normal free T4
• TSH 5-10 mIU/L in 80% of cases
• TPOAb positive in 60-80%, depending on
serum TSH
• Also referred to as “Mild hypothyroidism”

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 Subclinical Hypothyroidism
Causes
• Autoimmune thyroiditis – most common
• Subacute thyroiditis
• Post 131I or thyroidectomy
• Medications (ATD, Lithium, I)
• Postpartum thyroiditis

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 SCHypo
38-year-old woman complains of fatigue,
excess weight and depressed mood; exam
shows an obese (BMI 33), euthyroid
woman with normal thyroid palpation
Serum TSH is 5.9, FT4 1.0, TPOAb 220,
cholesterol 258 and LDL 144; repeat
TSH is 6.2
Q: Should you treat with LT4?

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 Consequences of SCHypo
• Progression to overt hypothyroidism
• Symptoms (fatigue, mood, weight, etc)
• High cholesterol
• CV morbidity/mortality

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 Risk of Overt Hypothyroidism
1,184 Subjects with 13-Year Follow-Up

TSH Hypothyroid
TPO (mIU/L) (%)
+ ≤2.5 12
+ 2.5-4.0 55
+ >4.0 86

Walsh et al: JCEM 95:1095, 2010

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 Approach to SCHypo

TSH 5-10 mIU/L High risk

• Symptoms
Repeat TSH, FT4,
TPO in 3 mo • Goiter
• TPO +
Low-risk pt High-risk pt • Hyperlipidemia
• Infertility
Follow T4 Rx • Pregnancy

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 Serum TSH in Pregnancy
28-year-old woman is 2 weeks pregnant;
she feels well; thyroid exam is normal;
there is no family history of thyroid disease
Q: Should serum TSH be checked?

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 Recommendations for
TSH Screening in Pregnancy
Recommendation 72
•There is insufficient evidence to recommend
for or against universal TSH screening at
the 1st trimester visit
Recommendation 76
•Serum TSH should be obtained in high-risk
women (age >30; TPO+; TIDM; BMI >40; FH+)

Thyroid 21:1081, 2011

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61-Year-Old Woman
Reports fatigue, weight gain, cold
intolerance and puffy face
Exam shows a hypothyroid
woman with a deep voice, pallor,
puffy face, and a firm goiter
TFTs
• FT4 0.2 ng/dL (0.8-1.8)
• TT4 0.1 ug/dL (0.5-5.0)
• TPOAb positive
• TSH 88 mIU/L (0.5-5.0)

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 Hypothyroidism
• What is the most likely cause of
hypothyroidism?
• When is TPOAb measurement useful?
• How do you select T4 dose?

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 Hypothyroidism
• Hashimoto thyroiditis is the most common cause
• 95% of patients are women
• Goiter is nontender, diffuse, firm (rubbery) and
bosselated
• Diagnosis is confirmed by positive TPOAb and
FNA result

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 Thyroperoxidase Antibody (TPOAb)
• The most sensitive test for detecting
autoimmune thyroid disease (AITD)
• Should be measured in subclinical
hypothyroidism
• The use of TPOAb for monitoring Rx of AITD
is not recommended
• The presence of TPOAb does not require
Rx – except perhaps in pregnancy

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 T4 Dose
• Average dose ~100 mcg daily
• Women require more than men
• Age does not affect dose
•  BMI =  dose
• In presence of CAD starting dose should be
small (25 mcg) and gradual increase to
normal TSH
• Caution: watch for concomitant meds that
may alter T4 absorption or metabolism

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 Subclinical Hyperthyroidism
Common Causes
• LT4 Rx – most common
• Graves’ disease
• Nodular goiter (MNG or AFTA)
• Thyroiditis
• Medications

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 Causes of Low TSH
• SCHyper
• Central hypothyroidism
• Nonthyroidal illness (ESS)
• Drugs (steroids, Dopamine, Octreotide)
• Pregnancy

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 Consequences of SCHyper
• Overt hyperthyroidism (OH): progression to
clinically symptomatic disease
• CV effects: AF,  LV mass,  mortality
• Bone effects: reduced bone mineral density
(BMD) and  fractures
• Altered QOL; dementia

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 595,111 people

272,746 with TSH

2,024 low TSH

0.1-0.4 or <0.1

TSH at 2, 5, 7 years

Follow-up 0.1-0.4 <0.1 Normal

2 years 72% 51% 17%
7 years 50% 37.5% 35.6%

• Prevalence of SCH was 0.63%

• Change to OH was 0.5% at 7 years
• Most SCH cases remained SCH at 2 years (81.8%) and 7 years (63%)
• 35.6% reverted to normal; mostly TSH 0.1-0.4
JCEM 96:E1-E8, 2011

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 Natural Course of SCHyper
Follow-up data suggest that the natural
course of SCHyper is variable. The majority
of patients have sustained low TSH, while
many revert to normal TSH, and only a few
progress to overt hyperthyroidism.
Remission is more likely with GD than MNG
and when TSH is low but detectable.

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• 2007 persons >60 years; follow-up 10 years
• Incidence of AF was 28% with TSH 0.1 nU/L
• Incidence of AF was 11% with normal TSH
• Relative risk of AF was 3.1 (95% CI, 1.7-5.5; P<0.01)

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Does SCHyper Increase CV Mortality

No!

Yes!

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 SCHyper and CV Mortality
The association of endogenous SCHyper with
CV mortality is controversial, reflecting the
heterogeneity of the different population with
SCHyper in terms of causes, sex, age, race,
degrees of TSH suppression and duration of
the follow-up.

B Biondi: Expert Rev Endocrinol Metab 6:785-792, 2011

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 SCHyper and Bone
• SCHyper may cause increased bone
turnover,  BMD, and  fracture risk
• Some studies show increased risk of
hip fracture
• Current data suggest small  BMD,  risk of
fracture in postmenopausal women and in
men, but not in premenopausal women

J Endocrinol 213:209, 2012

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SCHyper: Risks and Age

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 SCH Cases
A 74-year-old woman with CAD, hypertension,
hyperlipidemia is referred because a recent TSH is
0.01. Thyroid gland is mildly enlarged and nodular.
Repeat TSH 0.01, FT4 1.6, T3 155. Thyroid isotope
scan shows heterogeneous uptake suggestive of
MNG; RAIU is 18%.
Do you Rx? Yes  No 

A 32-year-old woman with normal thyroid palpation,

serum TSH 0.01, FT4 1.5, T3 120, and small
homogenous gland on US.
Do you Rx? Yes  No 

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 Who Should Be Treated?
• Age ≥60 years
• TSH <0.1 mIU/L
• Documented persistent low TSH
• Cardiac disease (AF)
• Bone loss ( BMD)

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Hyperthyroidism
A 30-year-old man presents
with typical symptoms and
signs of Graves’ disease
He is a nonsmoker without
eye signs or symptoms
Thyroid is 2.0-fold enlarged
Initial TFTs
• FT4 2.3 ng/dL (0.8-1.8)
• T3 250 ng/dL (80-180)
• TSH <0.01 mIU/L
• 24-hr RAIU 70%

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 What is the Best Rx for this Patient?
Hypo-
Advantage thyroidism Disadvantage Cost

Recurrence
ATD Nonablative Low +
side-effects

RAI Definitive 100% Fear ++

Surgery Definitive 100% Complications +++

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Current Trends in the Management of
Graves’ Disease
Index Case
Surgery – 1%

MMI – 7%
RAI – 69%

PTU – 22%

Solomon B et al: J Clin Endocrinol Metab 70:1518, 1990

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 Differences and
Similarities in Diagnosis
Current Trends in and Treatment of Graves’
Management of Graves’ Disease in Europe, Japan
Disease: ATA Survey and the United States
RAI ATA
ATD ETA
Surgery JPN

43-y/o Man Older 19-y/o Anti- Radioiodide Surgery

woman woman woman thyroid
drugs
Solomon B et al: 1990 Thyroid 1:129, 1991

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 Rx Options for Graves’ Disease
Patients with overt Graves’ hyperthyroidism
may be treated with any of the following
modalities
•Radioactive iodine
•Antithyroid drug
•Thyroidectomy

Thyroid, 2011

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 Treatment of Graves’ Disease
• Discuss with patient logistics, benefits,
speed of recovery, drawbacks, potential
side effects and cost
• Final decision on choice of treatment
depends on patient preference and
physician experience

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Graves’ Disease
A 32-year-old woman has
typical GD; she has mild eye
findings and a thyroid that is
3-fold enlarged
Initial TFTs
• FT4 2.8 ng/dL (0.8-1.8)
• T3 250 ng/dL (80-180)
• TSH <0.005 mIU/L
• 24-hr RAIU 48%

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 32-Year-Old Woman
After discussing various treatment options,
she decides on a course of antithyroid
drug therapy
Q: Which ATD should be used?
A: Methimazole should be used in virtually
every patient who chooses antithyroid drug
therapy for Graves’ disease, except during 1 st
trimester of pregnancy when PTU is preferred

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 PTU-Associated Acute Hepatic Failure
• Occurs in approximately 1 in 10,000 adults
on PTU
• Prevalence in children is higher; 1 in 2,000
• Can occur at any time over the course of
treatment
• Onset is sudden and course is rapidly
progressive
• Routine monitoring of LFTs is not useful

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 32-Year-Old Woman
Q: Does she need a WBC before Rx?
A: Yes. Prior to initiating ADT Rx for GD patient should have a
baseline WBC and a liver profile.
Q: Does she need WBC monitoring?
A: No. A differential white blood cell count should be obtained
during febrile illness and at the onset of pharyngitis in all
patients taking antithyroid medication. Routine monitoring
of WBC is not recommended.
Q: Does she need follow-up LFTs?
A: Liver enzymes should be assessed in patients taking PTU
who experience pruritic rash, jaundice, light colored stool or
dark urine, joint pain, abdominal pain, anorexia, nausea, or
fatigue.

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 32-Year-Old Woman
Q: For how long should she be treated?
A: MMI should be continued for approximately 12-18 months,
then tapered or stopped if TSH is normal at that time.

6
24
Relapse (%)

* 12
18 6 18
12
42

Allannic Garcia Weetman Maugendre

1990 1995 1994 1998

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 32-Year-Old Woman
Q: If she relapses after 18 months, then what?
A: If a patient with GD becomes hyperthyroid after
completing a course of MMI, consideration should
be given to Rx with RAI or thyroidectomy; low
dose MMI Rx for longer than 12-18 months may be
considered in patients not in remission who prefer
this approach.

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 Conclusions
• A review of new concepts in hyper- and
hypothyroidism
• Most patients with SCHypo should be treated
• Trimester-specific TSH ranges in pregnancy should
be used
• SCHyper in the elderly is associated with high risk
of AF and bone loss and should be treated
• Patients with Graves’ disease may be treated with
drugs, RAI or surgery
• T4 monotherapy is preferred for hypothyroidism

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Thank You!

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Questions & Discussion

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