Diseases of the

Thyroid Gland

DR L CHIN-HARTY
MBBS REVIEW 2015
Thyroid Gland
 Located in the
neck, anterior to
the trachea
 Produces T4 and T3
 Regulated by
negative feedback
axis
Thyroid Gland
 T4 made exclusively in
thyroid gland
 Ratio of T4 to T3 5:1
 Potency of T4 to T3 1:10
 T4 is the most important
source of T3 by peripheral
deiodination
 More that 90% of the
physiological effects are
due to binding of T3 to
thyroid receptors in
peripheral tissues
Effects of Thyroid Hormone
 Affects every cell in the body. Modulates
oxygen consumption, growth rate,
maturation and cell differentiation, turnover
of vitamins, hormones, proteins
 Acts by binding to nuclear receptors,
increasing protein synthesis
 At mitochondrial level, increases number
and activity to increase ATP production
 At cell membrane increases ions and
substrate transmembrane flux
Effects of Thyroid Hormone
 Calorigenesis- controls the basal metabolic
rate
 CHO metabolism
 Increasesglucose absorption of the git, glucose
consumption by peripheral tissues, glucose
uptake by the cells, glycolysis, gluconeogenesis
 Growth & maturation rate
Effects of Thyroid Hormone
 CNS development & function
 Necessary in newborns, modulation of brain and mood
modulation

 Fat & protein metabolism

 Increase lipolysis & lipid mobilisation with cholesterol, triglycerides,
free fatty acids

 Muscle metabolism
 Electrolyte balance
Effects of Thyroid Hormone
 Vitamin metabolism
 Hematopoietic system
 Cardiovascular system
 Heart rate, cardiac output, peripheral resistance, oxygen
consumption, arterial pressure

 Gastrointestinal- modulate bowel movements and

absorption

 Pregnancy- growth rate, lactation

Disorders
 Functional
 Hyperthyroidism

 Hypothyroidism

 Neoplasms
 Benign

 Malignant
Hyperthyroidism
 Thyrotoxicosis-
state of thyroid
hormone excess

 Hyperthyroidism-the result of
excessive thyroid gland
function
Hyperthyroidism Symptoms
 Hyperactivity/ irritability/ dysphoria
 Heat intolerance and sweating
 Palpitations
 Fatigue and weakness
 Weight loss with increase of appetite
 Hyperdefecation
 Polyuria
 Oligomenorrhoea, loss of libido
Hyperthyroidism Signs
 Tachycardia (AF)
 Tremor
 Goiter
 Warm moist skin
 Proximal muscle
weakness
 Lid retraction or lag
 Gynecomastia
Causes of Hyperthyroidism
Most common causes
 Graves disease
 Toxic multinodular goiter
 Autonomously functioning
nodule
Rarer causes
 Thyroiditis or other
causes of destruction
 Thyrotoxicosis factitia
 Iodine excess (Jod-
Basedow phenomenon)
 Struma ovarii
 Secondary causes (TSH
or ßHCG)
Other Causes of Thyrotoxicosis

 Drugs: Iodine excess

 Secondary hyperthyroidism
 TSH secreting pituitary
adenoma
 Thyroid hormone resistance
syndrome
Graves Disease
 Autoimmune disorder
 Abs directed against TSH receptor with intrinsic
activity. Thyroid and fibroblasts
 Responsible for 60-80% of Thyrotoxicosis
 More common in women
Graves Disease Eye Signs
N - no signs or symptoms
O – only signs (lid retraction or
lag) no symptoms
S – soft tissue involvement (peri-
orbital oedema)
P – proptosis (>22 mm)(Hertl’s
test)
E – extra ocular muscle
involvement (diplopia)
C – corneal involvement
(keratitis)
S – sight loss (compression of the
optic nerve)
Graves Disease Other
Manifestations
 Pretibial mixoedema
 Thyroid acropachy
 Onycholysis
 Thyroid enlargement
with a bruit frequently
audible over the
thyroid
Diagnosis of Graves Disease
 TSH , free T4
 Thyroid auto
antibodies
 Nuclear thyroid
scintigraphy (I123,
Te99)
Graves’ Disease

 Diagnosis:
 Low TSH, High FT4 and/or FT3
 If eye signs are present, the diagnosis of Graves’
disease can be made without further tests
 If eye signs are absent and the patient is hyperthyroid
with or without a goitre, a radioiodine uptake test
should be done.
 Radioiodine uptake and scan:
 Scan shows diffuse uptake
 Uptake is increased
 TSH-R Ab (stim) is specific for Graves’ disease. May be
a useful diagnostic test in the “apathetic” hyperthyroid
patient or in the pt who presents with unilateral
exopthalmos without obvious signs or laboratory
manifestations of Graves’ disease
Treatment of Graves
Disease
 Reduce thyroid hormone
production or reduce the amount
of thyroid tissue
 Antithyroid drugs: propyl-thiouracil,
carbimazole
 Radioiodine
 Subtotal thyroidectomy – relapse after
antithyroid therapy, pregnancy, severe
thyroid eye disease
 Symptomatic treatment
 Propranolol
Treatment of Grave’s Disease

 A. Medical therapy:
 Antithyroid drug therapy:
 Most useful in patients with small glands and mild
disease
 Treatment is usually continued for 12-18 months
 Relapse occurs in 50% of cases
 There are 2 drugs:
 Neomercazole (methimazole or carbimazole): start
30-40mg/D for 1-2m then reduce to 5-20mg/D.
 Propylthiouracil (PTU): start 100-150mg every 6hrs for
1-2m then reduce to 50-200 once or twice a day
 Monitor therapy with fT4 and TSH
 S.E.: 5% rash, 0.5% agranulocytosis (fever, sore
throat), rare: cholestatic jaundice, hepatocellular
toxicity, angioneurotic edema, acute arthralgia
Management of Grave’s
disease
 A. Medical therapy:
 Propranolol 10-40mg q6hrs to control
tachycardia, hypertension and atrial fibrillation
during acute phase of thyrotoxicosis. It is
withdrawn gradually as thyroxine levels return
to normal
 Other drugs:
 Ipodate sodium (1g OD): inhibits thyroid
hormone synthesis and release and prevents
conversion of T4 to T3
 Cholestyramine 4g TID lowers serum T4 by
binding it in the gut
Management of Grave’s
disease
 B. Surgical therapy:
 Subtotal thyroidectomy is the treatment of
choice for patients with very large glands
 The patient is prepared with antithyroid drugs
until euthyroid (about 6 weeks). In addition 2
weeks before the operation patient is given
SSKI 5 drops BID to diminish vascularity of
thyroid gland
 Complications (1%):
 Hypoparathyroidism
 Recurrent laryngeal nerve injury
Management of Grave’s
Disease
 C. Radioactive iodine therapy:
 Preferred treatment in most patients
 Can be administered immediately except in:
 Elderly patients
 Patients with IHD or other medical problems
 Severe thyrotoxicosis
 Large glands >100g
 In above cases it is desirable to achieve euthyroid
state first
 Hypothyroidism occurs in over 80% of cases.
 Female should not get pregnant for 6-12m after
RAI.
Management of Grave’s
Disease
 Management of opthalmopathy:
 Management involves cooperation between the
endocrinologist and the opthalmologist
 A course of prednisone immediately after RAI
therapy 100mg daily in divided doses for 7-14
days then on alternate days in gradually
diminishing dosage for 6-12 weeks.
 Keep head elevated at night to diminish
periorbital edema
 If steroid therapy is not effective external x-ray
therapy to the retrobulbar area may be helpful
 If vision is threatened orbital decompression can
be used
Management of Grave’s
Disease
 Management during pregnancy:
 RAI is contraindicated
 PTU is preferred over neomercazole
 FT4 is maintained in the upper limit of normal
 PTU can be taken throughout pregnancy or if
surgery is contemplated then subtotal
thyroidectomy can be performed safely in
second trimester
 Breastfeeding is allowed with PTU as it is not
concentrated in the milk
Treatment of Graves Disease-
Special consideration
 Thyroid Storm
 Life threatening exacerbation of thyrotoxicosis
accompanied by fever, delirium, seizures, coma,
vomiting, diarrhea, jaundice.
 Mortality rate is up to 30% even with treatment
 Usually precipitated by an acute illness such as
stroke, infection, trauma, dka, surgery
 IV PTU
 Radioiodine
 Propranolol
 Glucocorticoids
 benzodiazepines
Thyroid storm (Thyrotoxic crisis)

 Initiate prompt therapy after free T4, free T3, and TSH
drawn without waiting for laboratory confirmation.
 Therapy
 1. General measures:
 Fluids, electrolytes and vasopressor agents should
be used as indicated
 A cooling blanket and acetaminophen can be
used to treat the pyrexia
 Propranolol for beta–adrenergic blockade and in
addition causesdecreased peripheral conversion
of T4 T3 but watch for CHF.
 The IV dose is 1 mg/min until adequate beta-
blockade has been achieved. Concurrently,
propranolol is given orally or via NG tube at a dose
of 60 to 80 mg q4h
Thyroid storm (Thyrotoxic crisis)

 Therapy
 2. Specific Measures:
 PTU is the anti-thyroid drug of choice and is used in
high doses: 1000 mg of PTU should be given p.o. or be
crushed and given via nasogastric tube, followed by
PTU 250mg p.o. q 6h. If PTU unavailable can give
methimazole 30mg p.o. every 6 hours.
 One hour after the loading dose of PTU is given –give
iodide which acutely inhibits release of thyroid
hormone, i.e. Lugol’s solution 2-3 drops q 8h OR
potassium iodide (SSKI) 5 drops q 8h.
 Dexamethasone 2 mg IV q 6h for the first 24-48 hours
lowers body temperature and inhibits peripheral
conversion of T4-T3
 With these measures the patient should improve
dramatically in the first 24 hours.
 3. Identify and treat precipitating factor.
Hypothyroidism
Hypothyroidism Symptoms
 Tiredness and weakness  Weight gain with poor
 Dry skin appetite
 Feeling cold  Hoarse voice
 Hair loss  Menorrhagia, later oligo and
amenorrhoea
 Difficulty in concentrating and
poor memory  Paresthesias
 Constipation  Impaired hearing
Hypothyroidism Signs
 Dry skin, cool extremities
 Puffy face, hands and feet
 Delayed tendon reflex
relaxation
 Carpal tunnel syndrome
 Bradycardia
 Diffuse alopecia
 Serous cavity effusions
Causes of Hypothyroidism
 Autoimmune  Drugs: iodine excess,
hypothyroidism lithium, antithyroid
(Hashimoto’s, atrophic drugs, etc
thyroiditis)  Iodine deficiency
 Iatrogenic  Infiltrative disorders of
(I123treatment, the thyroid:
thyroidectomy, amyloidosis,
external irradiation of sarcoidosis,haemochro
the neck) matosis, scleroderma
Lab Investigations of
Hypothyroidism
 TSH , free T4
 Ultrasound of thyroid – little value
 Thyroid scintigraphy – little value
 Anti thyroid antibodies – anti-TPO
 S-CK , s-Chol , s-Triglyceride
 Normochromic or macrocytic anemia
 ECG: Bradycardia with small QRS
complexes
Hypothyroidism

 Diagnosis:
 A iFT4 and hTSH is diagnostic of primary hypothyroidism
 Serum T3 levels are variable (maybe in normal range)
 +ve test for thyroid autoantibodies (Tg Ab & TPO Ab)
PLUS an enlarged thyroid gland suggest Hashimoto’s
thyroiditis
 With pituitary myxedema FT4 will be i but serum TSH will
be inappropriately normal or low
 TRH test may be done to differentiate pituitary from
hypothalamic disease. Absence of TSH response to TRH
indicates pituitary deficiency
 MRI of brain is indicated if pituitary or hypothalamic
disease is suspected. Need to look for other pituitary
deficiencies.
 If TSH is h & FT4 & FT3 are normal we call this condition
subclinical hypothyroidism
Treatment of
Hypothyroidism
 Levothyroxine
 If
no residual thyroid function 1.5
μg/kg/day
 Patients under age 60, without cardiac
disease can be started on 50 – 100
μg/day. Dose adjusted according to
TSH levels
 Inelderly especially those with CAD
the starting dose should be much less
(12.5 – 25 μg/day)
Hypothyroidism- Special
considerations
 Myxedema coma
 Reduced level of consciousness, seizures, hypotension/shock,
hypothermia, hyponatremia
 Usually in elderly hypothyroid patients
 High mortality rate
 IV levothyroxine
 Adrenal insufficiency may be precipitated by administration
of thyroid hormone therefore hydrocortisone 100 mg IV q 8h
is usually given until the results of the initial plasma cortisol is
known.
 Thyroxine replacement in hypoadrenalism
 Pregnancy
 Elderly patients
 Coronary artery disease
Thyroiditis
Thyroiditis
 Acute: rare and due to suppurative infection of
the thyroid
 Sub acute: also termed de Quervains thyroiditis/
granulomatous thyroiditis – mostly viral origin
 Chronic thyroiditis: mostly autoimmune
(Hashimoto’s)
Acute Thyroiditis
 Bacterial – Staph, Strep
 Fungal – Aspergillus, Candida, Histoplasma,
Pneumocystis
 Radiation thyroiditis
 Amiodarone (acute/ sub acute)
Painful thyroid, ESR usually elevated, thyroid function
normal
Sub Acute Thyroiditis
Viral (granulomatous) – Mumps, coxsackie, influenza,
adeno and echoviruses
Mostly affects middle aged women, Three phases,
painful enlarged thyroid, usually complete
resolution
Rx: NSAIDS and glucocorticoids if necessary
Sub Acute Thyroiditis (cont)
Silent thyroiditis
No tenderness of thyroid
Occur mostly 3 – 6 months after pregnancy
3 phases: hyper hypo resolution, last 12 to 20 weeks
ESR normal, TPO Abs present
Usually no treatment necessary
Clinical Course of Sub
Acute Thyroiditis
Chronic Thyroiditis
Hashimoto’s
 Autoimmune
 Initially goiter later very
little thyroid tissue
 Rarely associated with
pain
 Insidious onset and
progression
 Most common cause of
hypothyroidism
 TPO abs present (90 –
95%)
Chronic Thyroiditis
Reidel’s
 Rare
 Middle aged women
 Insidious painless
 Symptoms due to compression
 Dense fibrosis develop
 Usually no thyroid function impairment
Thyroiditis
 The most common form of thyroiditis is Hashimoto
thyroiditis, this is also the most common cause of
long term hypothyroidism
 The outcome of all other types of thyroiditis is
good with eventual return to normal thyroid
function
Multinodular goitres
Cause: presence of areas of hyperplasia &
areas of hypoplasia in gland.

Appearance: Large, irregular, nodular goiter

Effect: euthyroid & pressure effect

Small risk of malignant transformation

Thyroxine suppression therapy to reduce size
Multinodular goitres
Table 17-1. Factors that may be involved in the
evolution of multinodular goiter.
PRIMARY FACTORS
•Functional heterogeneity of normal follicular
cells, most probably due to genetic and
acquisition of new inheritable qualities by
replicating epithelial cells. Gender (women) is
an important factor.
•Subsequent functional and structural
abnormalities in growing goiters.
SECONDARY FACTORS
•Elevated TSH (induced by iodine deficiency,
natural goitrogens, inborn errors of thyroid
hormone synthesis)
•Smoking, stress, certain drugs
•Other thyroid-stimulating factors (IGF-1 and
others)
•Endogenous factor (gender)
 Multinodular goitres
Table 17-2. Natural goitrogens associated with Multinodular Goiter
Goitrogens Agent Action
Millet, soy beans Flavonoids Impairs thyroperoxidase
Cassava, sweet potato, sorghum Cyanogenic glucosides Inhibits iodine thyroidal
metabolized to thiocyanates uptake
Babassu coconut Flavoniods Inhibits thyroperoxidase
Cruciferous vegetables: Cabbage, Glucosinolates Impairs iodine thyroidal
cauliflower, Broccoli, turnips uptake
Seaweed (kelp) Iodine excess Inhibits release of thyroidal
Hormones

Malnutrition, Iron deficiency Vitamin A deficiencyIron Increases TSH

deficiency stimulationReduces heme-
dependent thyroperoxidase
thyroidal activity

Selenium Selenium deficiency Accumulates peroxidase

and cause deiodinase
deficiency ; impairs thyroid
hormone synthesis
Modified and adapted from Medeiros-Neto & Knobel, ref. 33
Toxic Multinodular Goitre

 Usually occurs in older pts with long-standing MNG

 PE reveals a MNG that may be small or quite large and
may even extend substernally
 RAI scan reveals multiple functioning nodules in the gland
or patchy distribution of RAI
 Hyperthyroidism in pts with MNG can often be ppt by
iodide intake “jodbasedow phenomenon”.
 Amiodarone can also ppt hyperthyroidism in pts with MNG
 Treatment: Same as for Grave’s disease. Surgery is
preferred.
Thyroid
Neoplasms
Adenomas
 Discrete solitary masses
 Derived from follicular epithelium (ie follicular
adenomas)
 Not predecessors of malignancy
 Mostly nonfunctional
 Small percentage produce hormones
Adenomas
 Usually present as unilateral painless mass
 Take up less radioactive iodine compared to
normal cells- “cold” nodules ( 10% malignant)
 Biopsy is the gold standard for diagnosis
Other benign tumors
 Cysts
 Lipomas
 Hemangiomas
 Dermoid cysts
 Teratomas (mainly in infants)
Thyroid Carcinomas
 Most appear in adults (papillary Ca may present in
childhood)
 Female predominance in the early and middle adult age
groups
 Most are well differentiated
 Papillary Ca 80%
 Follicular Ca 15%
 Medullary Ca 5%
 Anaplastic Ca <5%
Prognosis of Thyroid
Carcinomas
Papillary Best prognosis

Follicular

Medullary

Anaplastic Worst prognosis

Papillary Carcinoma
 Most common of thyroid ca
 Any age
 Vast majority is associated with ionising radiation
exposure
 Solitary or multifocal nodules
 Metastasise via lymph nodes
Follicular Carcinoma
 Second most common form
 Increased incidence in areas of dietary iodine deficiency
 Do no arise from preexisting adenomas
 Present most often as “cold” solitary nodules
 Metastasize via blood to lungs, bone and liver
Medullary Carcinoma

 A disease of the C cells (parafollicular cells)

 More aggressive than papillary or follicular carcinoma but not as
aggressive as undifferentiated thyroid cancer
 It extends locally, and may invade lymphatics and blood vessels
 Calcitonin and CEA are clinically useful markers for DX and F/U
 80% of medullary ca are sporadic and the rest are familial. There are 4
familial patterns:
 FMTC without endocrine disease
 MEN 2A: medullary ca + pheochromocytoma + hyperparathyroidism
 MEN 2B: medullary ca + pheochromocytoma + multiple mucosal neuromas
 MEN 2 with cutaneous lichen amyloidosis
 The familial syndromes are associated with mutations in the ret proto-
oncogene (a receptor protein kinase gene on chrom. 10)
 Dx is by FNA bx. Pt needs to be screened for other endocrine
abnormalities found in MEN 2. Family members need to be screened for
medullary ca and MEN 2 as well.
Anaplastic Carcinoma
 Most aggressive
 Predominantly in elderly patients in areas with
endemic goiter
 Death in <1 year
 Distant metastases is common
Secondary Tumours

 Direct extensions from: larynx, pharynx,

oesophagus etc.
 Metastasis from: renal
cell carcinoma, large intestinal carcinoma,
malignant melanoma, lung carcinoma, breast
carcinoma etc.
Cases
 29 year old Female felt a nodule in
her neck incidentally while she was
getting ready for work one
morning.
 She went to her GP, who ordered a
thyroid ultrasound, which
demonstrated a 2cm nodule in the
right lobe of the thyroid.
Cases
 After thorough history and physical, what would
you order first for this patient?

 A. Thyroid function tests (TSH, T4)

 B. CT neck
 C. MRI neck
 D. Radioactive Iodine uptake scan
 E. All of the above
Cases
 What would you order first for this patient?
 A. Thyroid function tests (TSH, T4)

It is important to first establish the patient’s

thyroid function. This will help determine if the
known thyroid nodule is hyperfunctioning,
hypofunctioning, or nonfunctioning.

At this point, you should also obtain Fine Needle

Aspiration (FNA) with ultrasound guidance, if
necessary, to obtain cells for cytopathology.
This will help determine if nodule is benign or
malignant
Cases
 Important points in history:

 Family history of thyroid disease or thyroid

cancer?
 Familial syndromes (MEN)
 Personal history of radiation to head/neck
 Increased risk of thyroid cancer
 Hoarseness, SOB, difficulty swallowing
 Compressive symptoms of thyroid goiter
Cases
 Patient is sent for labs as well as FNA. Patient
returns to clinic the following week with FNA report
reading “follicular cells, cannot rule out follicular
neoplasm”. Is surgery indicated for your patient at
this time?

 Yes
 No
Cases
Surgery is indicated. Follicular cells on FNA can be a
benign finding or may indicate follicular carcinoma.
Follicular carcinoma cannot be diagnosed solely on
FNA (normal thyroid contains follicular cells.)
Perform at least hemithyroidectomy for tissue
diagnosis

Tissue taken at time of surgery must be sent for

pathology to evaluate for extracapsular extension,
lymphovascular invasion, or metastasis.

Therefore, in the case that follicular neoplasm is

suspected based on H&P and FNA results, patient
should be taken to surgery for pathologic diagnosis
and treatment.
Complications of
thyroidectomy
- Intraoperative
- Bleeding
- Damage to arteries/veins of neck
If patient develops expanding
- Postoperative presentation neck hematoma
postoperatively, treatment
- Injury to recurrent laryngeal nerve involves immediate opening of
sutures to evacuate clot and
- Unilateral: hoarseness return to OR to explore and
- Bilateral: respiratory distress stop bleed

- Bleeding
- Expanding hematoma – causes compression,
shortness of breath
- Hypocalcemia
- Removal or injury to parathyroid glands or their blood
supply
- Scar
Case 2

 A 50 year old housewife complains of progressive

weight gain of 20 pounds in 1 year, fatigue, postural
dizziness, loss of memory, slow speech, deepening of
her voice, dry skin, constipation, and cold
intolerance.
 Physical examination: Vital signs include a
temperature 96.8oF, pulse 58/minute and regular, BP
110/60. She is moderately obese and speaks slowly
and has a puffy face, with pale, cool, dry, and thick
skin. The thyroid gland is not palpable. The deep
tendon reflex time is delayed.
 Laboratory studies: CBC and differential WBC are
normal. The serum T4 concentration is 3.8 ug/dl
(N=4.5-12.5), the serum TSH is 1 uU/ml (N=0.2-3.5),
and the serum cholesterol is 255 mg/dl (N<200).
Case 2
 What is the likely diagnosis?
 Secondary hypothyroidism or tertiary
hypothyroidism (less likely).
 There are certain features that are very suggestive
for hypothyroidism such as:
 a deep voice
 delayed Achilles' tendon reflex time
 bradycardia
Case 3
 A 35 year old nurse complained of nervousness, weakness,
and palpitations with exertion for the past 6 months.
Recently, she noticed excessive sweating and wanted to
sleep with fewer blankets than her husband. She had
maintained a normal weight of 120 pounds but was eating
twice as much as she did 1 year ago. Menstrual periods
have been regular but there was less bleeding.
 Physical examination: Pulse was 92/minute and BP was
130/60. She appeared anxious, with a smooth, warm, and
moist skin, a fine tremor, a bounding cardiac apical
impulse, a pulmonic flow murmur, and she couldn't rise
from a deep knee bend without aid. Her thyroid contained
3 nodules, 2 on the right and one on the left with a total
gland size of 60 grams (3 times normal size), all nodules
being of firm consistency and there was no
lymphadenopathy. Her eyes were not prominent
(proptotic) and she had no focal skin thickening.
 Laboratory studies: Serum T4=15.6 ug/dl and serum T3=250
ng/dl (N=80-160