Endocrinology L8

Introduction to thyroid disease and

hyperthyroidism

Hussein Ali Nwayyir - MD, FICMS, MSc. (Endo.)

Lecturer: University of Basrah, College of Medicine, Department of Medicine
Goiter

! A goiter or goiter (Latin gutteria, struma), is a swelling of the

thyroid gland.

! Goiter can be:

I. Diffuse
II. Nodular
III. Multinodular
Thyroid Hormone Synthesis

o Iodine in the gland is incorporated into thyroglobulin which leads to the

formation of thyroxin (T4) which will change to triiodothyronine (T3)
which is the active thyroid hormone.

o The synthesis is under the control of thyrotropin-releasing hormone

(TRH) and thyroid stimulating hormone (TSH) feedback mechanism.

o Iodine is absorbed from the small bowel.

o Deficiency of Iodine in the food causes hypothyroidism.
Thyroid Function Test (Biochemical Tests)

1. TSH (N 0.27–4.2 mU/L)

2. FreeT4 (N 0.93-1.7 ng/dL)

3. Total T4(N 5.1-14.1 µg/dL)

4. Total T3 (N 0.8-2.0 ng/mL)

Other Thyroid Tests

1. Thyroglobulin (Tg) level (N up to 78 ng/mL)

2. Calcitonin

3. Thyroid antibodies
I. Thyroid Peroxidase antibodies (Anti TPO Ab)
II. Thyroglobulin antibodies (Anti-TG Ab)
III.TSH receptor antibodies (TRAB)
•
 Prevalence of thyroid autoantibodies (%) in different thyroid
diseases
Anti TPO Ab Anti-TG Ab TRAB

Normal 8-27 5-20 0

Graves' disease 50-80 50-70 80-95

Autoimmune 90-100 80-90 10-20
hypothyroidism
Multinodular 30-40 30-40 0
goiter
Thyroiditis 30-40 30-40 0
Imaging:

• US neck with Doppler study

• Thyroid Scintigraphy (Isotope scan) and uptake measurements
• A thyroid scan is a type of nuclear medicine imaging.
• The radioactive iodine uptake test (RAIU) is also known as a thyroid uptake.
• It is a measurement of thyroid function, but does not involve imaging
Thyroid Isotope Imaging (123I or 131I)

• Given orally
• Radionuclide imaging of the thyroid gland provides structural as well as
functional information about the thyroid gland and can be very helpful
in the differential diagnosis of hyperthyroidism.

• Used in the evaluation of the size and location of thyroid Tissue and
evaluation of hyperthyroidism.
Radioactive iodine uptake (RAI) scans (123I or 131I)

• Given orally
• Radioactive iodine ( 123 I) administered orally (RAI Uptake) is often
used as the radioisotope, and a scan is obtained 4–24 h later.
• The radioactive form of iodine is actively accumulated (trapped) by the
thyroid follicular cell and covalently incorporated into thyroglobulin
(uptake).
• Is useful for differentiating hyperthyroidism from other forms of
thyrotoxicosis (e.g., thyroiditis and thyrotoxicosis factitia).
• Thyroid Uptake You will be given radioactive iodine ( 123 I or 131 I) in
liquid or capsule form to swallow.
" Whole-Body Imaging (123I or 131I):
# For thyroid carcinoma in determining the presence and location of
residual functioning thyroid tissue after surgery for thyroid cancer or
after ablative therapy with radioactive iodine.

" Technetium-99m Pertechnetate (99mTc) Scan:

# Technetium-99m pertechnetate (99mTc) can be administered
intravenously, and images are obtained 30–60 min later.

$ Note:
• Radioisotope scanning divides thyroid nodules into hyperfunctioning
(“cold”), is functioning (“warm”), and hyperfunctioning (“hot”) nodules.
• Functioning nodules are less likely to be malignant.
Fine-Needle Aspiration Biopsy (FNAC)

# Its main purpose is to differentiate benign nodules from malignant

ones.
 Non-Thyroidal Illness

• Old names (Euthyroid sick syndrome, euthyroid sick syndrome,

non-thyroidal illness syndrome)
• Seen in hospitalized patients in CCU and ICU with severe illness.
• Low serum total T3 (TT3), normal to low free T4 (FT4), and a high
reverse T3 (rT3).
• These typical changes may be observed in up to 75% of hospitalized
patients.
• TSH levels may be low, but only on rare occasions TSH levels are
undetectable due to nonthyroidal illness alone. TSH may be transiently
elevated even to greater than 20 mU/L during nonthyroidal illness
recovery.
• No treatment indicated for this condition.
 Hyperthyroidism/Thyrotoxicosis
# Thyrotoxicosis is a hypermetabolic state resulting from excess thyroid
hormone.
# Hyperthyroidism is a type of thyrotoxicosis due to thyroid disease.
# Thyrotoxicosis can also cause by exogenous L-thyroxin therapy and
hydatidiform mole.
" Epidemiology
• Hyperthyroidism affects 2% of women and 0.2% of men in their
lifetimes.
" Causes
o Graves’ disease 80-90%
o Toxic adenoma
o Toxic multinodular goiter
o TSH-secreting pituitary adenoma - TSHoma (Very rare)
Clinical Presentation: (Symptoms)
• Patients with hyperthyroidism generally present with sweating, itching
tachycardia, tremor, increased appetite, weight loss, hyperreflexia,
anxiety, irritability, emotional lability, panic attacks, heat intolerance,
sweating, increased appetite, hyperdefecation, wide pulse pressure
with systolic hypertension, onycholysis, hair fall and proximal muscle
weakness.

• Men: Gynecomastia, reduced libido, and erectile dysfunction.

• Women: Menstrual dysfunction (oligomenorrhea, amenorrhea),

Clinical Presentation: (Signs)
Lid retraction and lid lag
Goiter with thyroid bruit
# Goiter can be diffuse (Graves’ disease), nodular (Toxic nodular goiter),
and single nodule (toxic adenoma).
Splenomegaly
Lymphadenopathy
Vitiligo as a marker of autoimmune disease

# Note
• In patients older than 60, when you think hyperthyroidism, it’s usually
hypothyroidism, and when you think hypothyroidism, it’s usually
hyperthyroidism; the diseases become increasingly atypical with age.
Tips:
! Clinical signs of hyperthyroidism in the elderly may be masked by
manifestations of coexisting disease (e.g., new-onset atrial fibrillation,
exacerbation of congestive heart failure).

! Patients with Graves’ disease may present with exophthalmos (50% of

patients), clubbing of nails (Graves’ acropachy) and pretibial
myxedema may also be noted.
! Exophthalmos prevalence and severity increased in smokers.

! Pretibial myxedema is localized dermopathy (1% of patients) and most

frequent in the anterolateral aspects of the shin but can be found at
other sites (especially after trauma)

! Untreated hyperthyroidism will increase risk of atrial fibrillation and

osteoporosis.
" Features of hyperthyroidism specific for Graves’ disease:
a. Exophthalmos
b. Pretibial myxedema
c. Clubbing of nails
d. Splenomegaly
e. Lymph nodes enlargement

" Features of hyperthyroidism due to hyperadrenergic state

a. Tachycardia
b. Sweating
c. Termer
d. Lid lag
e. Lid retraction
Laboratory Tests:
$ TSH <0.1 mU/L

$ FT4 >1.7 ng/dL (in pregnancy, total T4(TT4) may be more reliable)

$ High TT3 (generally not necessary for diagnosis).

# Unless hyperthyroidism is a result of the rare toxic thyroid nodule where they
are liable for T3 toxicosis with normal FT4.

• TSH receptor antibodies (TRAB) are seen in 80-95 % of Graves disease.

• Thyroid autoantibodies are useful in selected cases to differentiate Graves’

disease from toxic multinodular goiter (absent thyroid antibodies).
Imaging Studies
o 24-hr radioactive iodine uptake (RAIU) is useful to distinguish
hyperthyroidism from iatrogenic thyroid hormone excess
(thyrotoxicosis factitia) and thyroiditis.

o An overactive thyroid shows increased uptake, whereas a normal

underactive thyroid (iatrogenic thyroid ingestion, painless or subacute
thyroiditis) shows normal or decreased uptake.
o The RAIU results also vary with the etiology of the hyperthyroidism .
# Graves’ disease: increased homogeneous uptake
# Multinodular goiter: increased heterogeneous uptake
# Hot nodule: single focus of increased uptake

o RAIU is also generally performed before the therapeutic administration

of radioactive iodine to determine the appropriate dose.
Thyroid US:

• US Thyroid will give a clue whether the goiter diffuse, nodular or single nodule.
 Treatment

1. Medical

2. Surgical

3. Radioiodine
Medical Treatment
• Thiourea - antithyroid drugs (Methimazole/Carbimazole/Propyl
thiouracil)
# Inhibit thyroid hormone synthesis by blocking the production of thyroid
peroxidase.
# Iraq, we use Carbimazole, which is converted to Methimazole in the
body.
# Three - four weeks are required for the drug to take effect as the
thyroid may have large stores of hormone which must be depleted.
# Carbimazole should be avoided in the first trimester of pregnancy
because of teratogenicity and Propylthiouracil should be used in this
period of pregnancy.
# Dosage: Carbimazole 15 to 60 mg/day given in divided doses and
after one-month single daily dose.
# Antithyroid drugs can be used as the primary form of treatment or as
adjunctive therapy before radioactive therapy or surgery or afterward if
the hyperthyroidism recurs after surgery or radioactive iodine.
# Side effects: skin rash (3% to 5% of patients), arthralgias, myalgias,
neutropenia (1/1000).
# Rare side effects are aplastic anemia, hepatitis from PTU, cholestatic
jaundice from methimazole.
# If the patient develops these side effects, the drug should be stopped
immediately, and treatment changed to surgery or radioiodine.
# When antithyroid drugs are used as primary therapy, they are usually
given for 12-18 months. Monitor FT4 each month until normal.
# 50% of patients with Graves’ disease will relapse once antithyroid
drug stopped.
# Beta-blockers are given for one month to control symptoms while
waiting for the antithyroid effect to take effect.
Radiation Therapy (radioactive iodine [RAI; 131I])

# RAI is the treatment of choice for patients who have not achieved
remission after one year of antithyroid drug therapy.
# RAI is also used in hyperthyroidism caused by a toxic adenoma or toxic
multinodular goiter.
# Contraindicated during pregnancy (can cause fetal hypothyroidism)
and lactation.
# Pregnancy should be excluded in women of childbearing age before RAI
is administered.
# A single dose of RAI is effective in inducing a euthyroid state in nearly
80% of patients.
# There is a high incidence of post-RAI hypothyroidism (>50% within the
first year and two%/year after that); these patients should frequently
be evaluated for the onset of hypothyroidism.
Surgical Therapy (subtotal or total thyroidectomy)

$ Indicated in obstructing goiters, in any patient who refuses RAI and

cannot be adequately managed with antithyroid medications (e.g.,
patients with toxic adenoma or toxic multinodular goiter), and in
pregnant patients who cannot be adequately managed with antithyroid
medication or develop side effects to them.

$ Patients should be rendered euthyroid with antithyroid drugs before

surgery.

$ Complications of surgery include hypothyroidism (28% to 43% after

ten years), hypoparathyroidism, and vocal cord paralysis (1%).
$ Hyperthyroidism recurs after surgery in 10% to 15% of patients.
Elderly Hyperthyroid:

• Patients may have only subtle signs (weight loss, tachycardia, fine skin,
brittle nails).
• This form is known as apathetic hyperthyroidism and manifests with
lethargy rather than hyperkinetic activity.
• An enlarged thyroid gland may be absent.
• Coexisting medical disorders (most common cardiac disease) may also
mask the symptoms.
• These patients often have unexplained congestive heart failure,
worsening of angina, or new-onset atrial fibrillation resistant to
treatment.
Subclinical Hyperthyroidism:

• Is defined as normal both FT4 and TT3 with a TSH level suppressed
below 0.1 mU/L.
• These patients usually do not present with signs or symptoms of overt
hyperthyroidism.
• An indication of treatment is optional.
Thyrotoxic Crisis (thyroid storm):

• A Severe complication of hyperthyroidism. Symptoms can include an

increase in body temperature to over 40 degrees Celsius, tachycardia,
arrhythmia, vomiting, diarrhea, dehydration, coma, and death.

Exophthalmos:
• May stay even after curing of thyrotoxicosis.
Flowchart for care of hyperthyroidism

TSH
<0.1mU/L

Free T4

High treat
TRAB US
thyroid

Normal FT4 each 4-

8 week
Treat
medical for
12-18
TT3

Normal
Subclinical High T3
hyperthyroi toxicosis
dism