2. Any enlargement of the thyroid gland is referred
to as a goiter.
Most nontoxic goiters are thought to result from
TSH stimulation secondary to inadequate thyroid
hormone synthesis and other paracrine growth
factors.
The thyroid gland enlarges in order to maintain
the patient in a euthyroid state.
Goiters may be diffuse, uninodular, or
multinodular.
Familial goiters resulting from inherited
deficiencies in enzymes necessary for thyroid
hormone synthesis may be complete or partial.
The former leads to cretinism, whereas the latter
leads to mild hypothyroidism, elevated TSH, and
a goiter, although patients may be euthyroid.
3. Etiology of Non Toxic Goiter
Endemic: iodine deficiency, dietary
goitrogens
Medications: iodide, amiodarone,
lithium
Thyroiditis: subacute, cronic
Familial: Hormonal dysgenesis from
enzyme defects
Resistance to thyroid hormone
Neoplasm
4. Elevated TSH levels induce diffuse
thyroid hyperplasia
followed by focal hyperplasia resulting in
nodules that may or may not concentrate
iodine, colloid nodules, or microfollicular
nodules.
The TSH-dependent nodules progress to
become autonomous,
◦ possibly related to activation of the TSH
receptor gene, and,
◦ less commonly to the gsp proto-oncogene.
5. Clinical Features
Most patients with nontoxic goiters are asymptomatic,
although patients often complain of a pressure
sensation in the neck, particularly with motion.
As the goiters become very large, compressive
symptoms, such as dyspnea and dysphagia, ensue.
Patients also describe having to clear their throats
frequently (catarrh).
Dysphonia from recurrent laryngeal nerve injury is
rare, except when malignancy is present.
Obstruction of venous return at the thoracic inlet from a
substernal goiter results in a positive Pemberton's
sign—
◦ facial flushing and dilatation of cervical veins upon raising
the arms above the head
6. Sudden enlargement of nodules or
cysts because of hemorrhage may
cause acute pain.
Physical examination may reveal
◦ a soft, diffusely enlarged gland (simple
goiter) or
◦ nodules of various size and consistency in
case of a multinodular goiter.
Deviation of the trachea may be
apparent.
7. Diagnostic Tests
Patients are usually euthyroid with normal
TSH and low-normal or normal free T4 levels.
If some nodules develop autonomy, patients
have suppressed TSH levels or become
hyperthyroid.
RAI uptake often shows patchy uptake with
areas of hot and cold nodules.
FNA biopsy is recommended in patients who
have a dominant nodule or one that is painful
or enlarging,
◦ as carcinomas have been reported in 5 to 10% of
multinodular goiters.
CT scans are helpful to evaluate the extent of
retrosternal extension and airway
compression.
8. Treatment
Most euthyroid patients with small,
diffuse goiters do not require
treatment.
Some physicians give patients with
large goiters exogenous thyroid
hormone to reduce the TSH
stimulation of gland growth;
◦ this treatment may result in a decrease
and/or stabilization of goiter size.
Endemic goiters are treated by iodine
administration.
9. Surgical resection is reserved for goiters
that
◦ (1) continue to increase despite T4
suppression,
◦ (2) cause obstructive symptoms,
◦ (3) have substernal extension,
◦ (4) are suspected to be malignant or are
proven malignant by FNA biopsy, and
◦ (5) are cosmetically unacceptable.
Subtotal thyroidectomy is the treatment
of choice and patients require lifelong T4
10. Hyperthyroidism
The clinical manifestations of hyperthyroidism
result from an excess of circulating thyroid
hormone.
It is important to distinguish disorders
that result from increased production of thyroid
hormone
◦ such as Graves' disease and toxic nodular goiter
◦ lead to an increase RAIU
from those disorders that
◦ lead to release of stored hormone from injury to the
thyroid gland (thyroiditis)
characterized by low RAIU
◦ or other non-thyroid gland–related conditions.
12. Graves' Disease
Although originally described by the
Welsh physician Caleb Parry in 1825
The disease is known as Graves'
disease after Robert Graves, an Irish
physician who described three
patients in 1835.
Graves' disease is by far the most
common cause of hyperthyroidism in
North America, accounting for 60 to
80% of cases.
13. Graves disease
It is an autoimmune disease of unknown
cause with a strong familial
predisposition,
F:M = 5:1
peak incidence between the ages of 40
and 60 yrs
characterized by
◦ thyrotoxicosis,
◦ diffuse goiter, and
◦ extrathyroidal conditions, including
ophthalmopathy, dermopathy (pretibial
myxedema), thyroid
acropachy, gynecomastia, and other
manifestations.
14. Etiology, Pathogenesis, and
Pathology
The exact etiology of the initiation of the
autoimmune process in Graves' disease
is unknown.
Some conditions have been suggested
as possible trigger such as
◦ the postpartum state, iodine excess, lithium
therapy, and bacterial and viral infections
Genetic factors also play a role
Sensitized T-helper lymphocytes
stimulate B lymphocytes, which produce
antibodies directed against the thyroid
stimulating hormone receptor (TRAbs).
15. Clinical Features
Can be divided into those occurring in
any patient with hyperthyroidism and
those specific to Graves' disease.
Symptoms common to most patients with
hyperthyroidism include
◦ heat intolerance, increased sweating and
thirst, and weight loss despite adequate
caloric intake.
Symptoms of increased adrenergic
stimulation include
◦ palpitations, nervousness, fatigue, emotional
lability, hyperkinesis, and tremors.
16. The most common gastrointestinal
symptoms include increased frequency
of bowel movements and diarrhea.
Female patients -
amenorrhea, decreased fertility, and an
increased incidence of miscarriages.
Children - rapid growth with early bone
maturation
Older patients present with
cardiovascular complications
◦ such as atrial fibrillation and congestive heart
failure.
17. On P/E, weight loss and facial flushing
may be evident.
The skin may be warm and moist and
some darkening
Tachycardia or atrial fibrillation is present
◦ with cutaneous vasodilation leading to a
widening of the pulse pressure and
◦ a rapid falloff in the transmitted pulse wave
(collapsing pulse).
A fine tremor, muscle wasting, and
proximal muscle group weakness with
hyperactive tendon reflexes are often
present.
18. Clinically evident ophthalmopathy-50%.
Exophthalmos, proptosis, periorbital
swelling, congestion, and edema of the
conjunctiva
Eye symptoms include
◦ lid lag (von Graefe's sign),
◦ spasm of the upper eyelid revealing the sclera
above the corneoscleral limbus (Dalrymple's
sign)
◦ a prominent stare as a consequence of
catecholamine excess.
19.
20. True infiltrative eye disease results in
◦ periorbital edema
◦ conjunctival swelling and congestion
(chemosis)
◦ proptosis
◦ limitation of upward and lateral gaze (from
involvement of the inferior and medial
recti muscles, respectively)
◦ keratitis, and even blindness as a result of
optic nerve involvement.
21. The etiology of Graves' ophthalmopathy is
not completely known;
◦ however, orbital fibroblasts and muscles are
thought to share a common antigen with
thyrocytes, the TSH receptor.
Ophthalmopathy results from inflammation
caused by cytokines released from sensitized
killer T lymphocytes and cytotoxic antibodies.
Dermopathy occurs in 1 to 2% of patients
◦ characterized by deposition of
glycosaminoglycans leading to thickened skin in
the pretibial region and dorsum of the foot.
22. Pretibial myxedema may be found in 3
to 5% of patients with Graves' disease
Gynecomastia is common in young
men.
Thyroid acropachy-Rare bony
involvement
◦ subperiosteal bone formation and swelling
in the metacarpals
Onycholysis or separation of
fingernails from their beds, is a more
23. On physical exam, the thyroid is
usually diffusely and symmetrically
enlarged, as evidenced by an
enlarged pyramidal lobe.
There may be an overlying bruit or
thrill and loud venous hum in the
supraclavicular space.
24. Diagnostic Tests
Hyperthyroidism - a suppressed TSH with or
without an elevated free T4 or T3 level.
If eye signs are present, other tests are
generally not needed.
However, in the absence of eye findings, an
123I uptake and scan should be performed.
◦ An elevated uptake, with a diffusely enlarged
gland confirms the diagnosis of Graves' disease
and helps to differentiate it from other causes of
hyperthyroidism.
If free T4 levels are normal, free T3 levels
should be determined as they are often
elevated in early Graves' or Plummer's
disease (T3 toxicosis).
25. Anti-Tg and anti-TPO antibodies are
elevated in up to 75% of patients, but
are not specific.
Elevated thyroid-stimulating hormone
receptor (TSH-R) or TSAb are
diagnostic of Graves' disease
◦ are increased in approximately 90% of
patients.
MRI scans of the orbits are useful in
evaluating Graves' ophthalmopathy.
26. Treatment
Graves' disease may be treated by
any of three treatment modalities:
1. antithyroid drugs
propylthiouracil (PTU, 100 to 300 mg three
times daily) and methimazole (10 to 30 mg
three times daily).
The catecholamine response of thyrotoxicosis
can be alleviated by administering beta-
blocking agents-propranolol.
2. thyroid ablation with radioactive 131I
3. thyroidectomy
27. The choice of treatment depends upon
several factors, including
◦ the age of the patient,
◦ the severity of the disease,
◦ the size of the gland,
◦ any coexistent pathology,
◦ associated ophthalmopathy
◦ patient's preferences, and desire for
pregnancy
28. Thyroid Storm
Thyroid storm is a condition of
hyperthyroidism accompanied by fever, CNS
agitation or depression, cardiovascular
dysfunction that may be precipitated by
infection, surgery, or trauma.
Occasionally, thyroid storm may result from
amiodarone administration.
This condition was previously associated with
high mortality rates, but can be appropriately
managed in an ICU setting.
Beta blockers are given to reduce peripheral
T4-to-T3 conversion and to decrease the
hyperthyroid symptoms.
29. Oxygen supplementation and hemodynamic
support should be instituted.
Non-aspirin compounds can be used to treat
pyrexia,
Lugol's iodine or sodium ipodate
(intravenously) should be administered to
decrease iodine uptake and thyroid hormone
secretion.
PTU therapy blocks the formation of new
thyroid hormone and reduces peripheral
conversion of T4 to T3,
corticosteroids
◦ help to prevent adrenal exhaustion.
◦ also block hepatic thyroid hormone conversion.
