THYROID GLAND

DISORDERS
Aspects That Will Be Addressed

Hyperthyroidism
Hypothyroidism
Thyroiditis
Thyroid benign
tumor and carcinoma
 GENERAL ASPECTS OF THYROID GLAND

Anatomy: weight range from 12 to 30g

Located in the neck, anterior to the

traquea

Produces: T4 & T3 (active hormone)

Regulation: negative Feed-back axis

 THYROID GLAND REGULATION
negative Feed-back axis

Hypothalamus
(negative
effect)
(TRH positive effect)

Pituitary gland

(TSH, positive effect)

Thyroid gland

T3 & T4
 Thyroid hormones:

T4: (Thyroxine) is 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 tissue deiodination T4 to T3
 Thyroid hormones:

T3 (Triiodothyronine) main source is

peripheral deiodination

Ratio of T3 to T4 ; 1:5

Potency of T3 to T4; 10 :1

T3 is the most important because more than

90% of the thyroid hormones physiological
effects are due to the binding of T3 to
Thyroid receptors in peripheral tissues.
 THYROID HORMONE EFFECTS:
-not essential but very helpful
Affects every single cell in the body

Modulates:

Oxygen consumption

Growth rate

Maturation and cell differentiation

Turnover of vitamins, hormones, proteins, fat,

carbohydrate
 MECHANISMS OF THYROID
HORMONE ACTION

Act by binding to Nuclear receptors,

termed Thyroid Hormone Receptors
(TRs), Increasing synthesis of proteins

In mitochondrial level increases

number and activity to increasing ATP
production

In cell membrane increases ions and

substrates transmembrane flux
 THYROID HORMONE EFFECTS

CALORIGENESIS
Controls the Basal Metabolic Rate (BMR)

CARBOHYDRAT METABOLISM

Increases:
Glucose absorption of the GI tract
Glucose consumption by peripheral tissues
Glucose uptake by the cells
Glycolysis
Gluconeogenesis
Insulin secretion
 THYROID HORMONE EFFECTS

GROWTH & MATURATION RATE

CNS. DEVELOPMENT & FUNTION

ESSENTIAL in the newborn to prevent

development of CRETINISMS & to a
normal IQ

Modulation of brain cerebration

Mood modulation
 THYROID HORMONE EFFECTS

- FAT & PROTEIN METABOLISM

Increase lipolysis and lipid

mobilization with:
Cholesterol
Triglicerides
Free fatty acids

MUSCLE METABOLISM
Modulates
Strength & velocity of contraction
 THYROID HORMONE EFFECTS

ELECTROLYTE BALANCE

Low Thyroid hormones could induce

hyponatremia

VITAMIN METABOLISM

Modulates vitamin consumption

HEMATOPOIETIC SYSTEM

Could induce anemia

 THYROID HORMONE EFFECTS

CARDIOVASCULAR SYSTEM
Hyperthyroidism, increases:
Heart rate & myocardial strenght
Cardiac output
Peripheral resistances (Vasodilatation)
Oxygen consumption
Arterial pressure

Hypothyroidism, reduces:
Heart rate & myocardial strenght
Cardiac output
Peripheral resistances (Vasodilatation)
Oxygen consumption
Arterial pressure
 THYROID GLAND DISORDERS
THYROID HORMONE EFFECTS
GASTROINTESTINAL SYSTEM

Modulate bowel movements and absorption

ENDOCRINE SYSTEM

Modulates pituitary axis, affecting GH,

ACTH, FSH, LH, so-on

PREGNANCY

Modulates growth rate and affects lactation

 THYROID GLAND DISORDERS
DIVIDED INTO:

THYROTOXICOSIS (Hyperthyroidism)
Overproduction of thyroid hormones

HYPOTHYROIDISM (Gland destruction)

Underproduction of thyroid hormones

NEOPLASTIC PROCESSES
Benign
Malignant
 LABORATORY EVALUATION
TSH normal, practically excludes abnormality

If TSH is abnormal, next step: Total & Free T4 & T3

- TPO (Thyroid Peroxidase ) antibody

- Serum Tg (Thyroglobulin)

- Antimitochondrial Ab, TSI (Thyroid Stimulating Ig)

(rare)

- Radioiodine uptake & Thyroid scaning

- FNA, Fine-needle aspiration

- Thyroid ultrasound
 THYROID GLAND DISORDERS
TSH high usually means Hypothyroidism

Rare causes:
TSH-secreting pituitary tumor
Thyroid hormone resistance
Assay artifact

TSH low usually indicates Thyrotoxicosis

Other causes
First trimester of pregnancy
After treatment of hyperthyroidism
Some medications (Esteroids-dopamine)
 THYROTOXICOSIS:
is defined as the state of
thyroid hormone excess

HYPERTHYROIDISM:
is the result of excessive
thyroid gland function
 THYROID GLAND DISORDERS
Abnormalities of Thyroid Hormones

Thyrotoxicosis
Primary
Without Hyperthyroidism
Secondary
Exogenous or factitious

Hypothyroidism
Primary
Secondary
Peripheral
 THYROID GLAND DISORDERS
Causes of Thyrotoxicosis:
Primary Hyperthyroidism
Graves disease
Toxic Multinodular Goiter
Toxic adenoma
Functioning thyroid carcinoma
metastases
Activating mutation of TSH receptor
Struma ovary
Drugs: Iodine excess
 THYROID GLAND DISORDERS
Causes of Thyrotoxicosis:
Thyrotoxicosis without hyperthyroidism
Subacute thyroiditis
Silent thyroiditis
Other causes of thyroid destruction:
Amiodarone, radiation, infarction of an
adenoma
Exogenous/Factitia

Secondary Hyperthyroidism
TSH-secreting pituitary adenoma
Thyroid hormone resistance syndrome
Chorionic Gonadotropin-secreting tumor
Gestational thyrotoxicosis
 THYROTOXICOSIS
Symptoms:
Hyperactivity
Irritability
Dysphoria
Heat intolerance &
sweating
Palpitations
Fatigue & weakness
Weight loss with
increased appetite
Diarrhea
Polyuria
Sexual dysfunction
Thyrotoxicosis Signs
Tachycardia (AF)
Tremor
Goiter
Warm moist skin
Proximal muscle
weakness
Lid retraction or lag
Gynecomastia
Exophtalmus
Pretibial myxedema
 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)(Hertls
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)
 THYROID GLAND DISORDERS
Treatment Graves Disease

Reducing thyroid hormone synthesis:

Antithyroid drugs (Methimazole, Propylthyouracil)
Radioiodine (131I)
Subtotal thyroidectomy

Reducing Thyroid hormone effects:

Propranolol
Glucocorticoids
Benzodiazepines

Reducing peripheral conversion of T4 to T3

Propylthyouracil
Glucocorticoids
 Management of Graves 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 Graves 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
Thyrotoxic Crisis or Thyroid storm:

Life-threatening thyrotoxicosis :
fever,
Confusion, delirium, seizures,coma,
vomiting, diarrhea, jaundice,
cardiac failure ,pulmonary edema
Shock/hypotension

Mortality rate reachs 30% even with

treatment

Precipitating factor:
Stroke, infection,trauma, diabetic
ketoacidosis, surgery, radioiodine
treatment
Thyroid storm or Thyrotoxic crisis

Fluids, electrolytes and vasopressor agents

should be used as indicated
A cooling blanket and acetaminophen can
be used to treat the pyrexia
Propylthyouracil IV or Nasogastric tube
Propranolol for betaadrenergic blockade
and in addition causesdecreased peripheral
conversion of T4T3 but watch for CHF.
Radioiodine (131I)
Glucocorticoids, Benzodiazepines
 Toxic Adenoma
(Plummers Disease)
This is a functioning thyroid adenoma
Typical pt is usually > 40 yrs old who has noted
recent growth of a long-standing thyroid nodule
Thyrotoxic symptoms are present but no infiltrative
opthalmopathy.
PE reveals a nodule on one side
Lab: low TSH, high T3, slightly high T4
Thyroid scan reveals hot nodule with suppressed
uptake in contralateral lobe
Toxic adenomas are almost always follicular
adenomas and almost never malignant
Treatment: same as for Graves disease
 Toxic Multinodular Goiter
Usually occurs in older pts with long-standing
Multinodular goiter (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 Graves disease. Surgery is
preferred.
 Nontoxic Goitre
Enlargement of the thyroid gland from TSH
stimulation which in turn results from inadequate
thyroid hormone synthesis
Etiology:
Iodine deficiency
Goitrogen in the diet
Hashimotos thyroiditis
Subacute thyroiditis
Inadequate hormone synthesis due to inherited
defect in thyroidal enzymes necessary for T4 and
T3 biosynthesis
Generalized resistance to thyroid hormone (rare)
Neoplasm, benign or malignant
 Nontoxic Goitre
Symptoms and Signs:
Thyroid enlargement, diffuse or multinodular
Huge goitres may produce a positive Pemberton sign
(facial flushing and dilation of cervical veins on lifting the
arms over the head) especially when they extend inferiorly
retrosternally
Pressure symptoms in the neck with upward or downward
movement of the head
Difficulty swallowing, rarely vocal cord paralysis
Most euthyroid but some are mildly hypothyroid

RAI uptake and scan:

Uptake may be normal, low, or high depending on the iodide
pool
Scan reveals patchy uptake with focal areas of increased
and decreased uptake corresponding to hot and cold
nodules respectively
 Management of Nontoxic Goitre
L-thyroxine suppressive therapy:
Doses of 0.1 to 0.2mg daily is required
Aim is to suppress TSH to 0.1-0.4 microU/L (N 0.5-5)
Suppression therapy works in 50% of cases if
continued for 1 year
If suppression does not work or if there are
obstructive symptoms from the start then surgery is
necessary
 Subacute Thyroiditis
Acute inflammatory disorder of the thyroid gland most likely due to viral
infection. Usually resolves over weeks or months.
Viral : Mumps, coxsackie, influenza, adeno and echoviruses
Symptoms & Signs:
Fever, malaise, and soreness in the neck
Initially, the patient may have symptoms of hyperthyroidism with
palpitations, agitation, and sweat
PE: No opthalmopathy, Thyroid gland is exquisitely tender with no
signs of local redness or heat suggestive of abscess formation
Signs of thyrotoxicosis like tachycardia and tremor may be present
Lab:
Initially, T4 & T3 are elevated and TSH is low, but as the disease
progresses T4 & T3 will drop and TSH will rise
RAI uptake initially is low but as the pt recovers the uptake
increases
ESR may be as high as 100. Thyroid Ab are usually not detectable
in serum
 Sub Acute Thyroiditis
Mostly affects middle aged women, Three phases, painful
enlarged thyroid, usually complete resolution
Management:
In most cases only symptomatic e.g.
acetaminophen 0.5g four times daily
If pain, fever, and malaise are NSAID or a
glucocorticoid such as prednisone 20 mg three
times daily for 7-10 days may be necessary to
reduce the inflammation
L-thyroxine is indicated during the hypothyroid
phase of the illness. 10% of the patients will
require L-thyroxine
 Sub Acute Thyroiditis
Silent thyroiditis
No tenderness of thyroid
Occur mostly 3 6 months after pregnancy
3 phases: hyperhyporesolution, last 12 to
20 weeks
ESR normal, TPO Abs present
Usually no treatment necessary
 Causes of Primary
Hypothyroidism
Autoimmune Drugs: iodine excess,
hypothyroidism lithium, antithyroid
(Hashimotos, atrophic drugs, etc
thyroiditis) Iodine deficiency
Iatrogenic Infiltrative disorders of
(I123treatment, the thyroid:
thyroidectomy, external amyloidosis,
irradiation of the neck) sarcoidosis,haemochro
Kongenital matosis, scleroderma
 THYROID GLAND DISORDERS
HYPOTHYROIDISM

Secondary
Pituitary gland destruction
Isolated TSH deficiency
Bexarotene treatment
Hypothalamic disorders

Peripheral:
Rare, familial tendency
 HYPOTHYROIDISM

Symptoms: Signs:
Bradycardia
Tiredness Weight gain
Weakness Dry coarse skin
Sexual Puffy face, hands
and feet
dysfunction
Diffuse alopecia
Dry skin Peripheral edema
Hair loss Delayed tendon
reflex relaxation
Difficulty Carpal tunel
concentrating syndrome
poor memmory Serous cavity
effusions.
- Constipation
Menoragia,oligo or
amenorea
Hypothyroidism Signs
Dry skin, cool extremities
Puffy face, hands and feet
Delayed tendon reflex
relaxation
Carpal tunnel syndrome
Bradycardia
Diffuse alopecia
Serous cavity effusions
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-Trigliseride
Normochromic or macrocytic anemia
ECG: Bradycardia with small QRS complexes
 Management of Hypothyroidism
Start patient on L-thyroxine 0.05-0.1mg ( 50-100 ug/day PO OD.
L-thyroxine treats the hypothyroidism and leads to regression of
goitre.
If patient is elderly start 0.025mg (12.5 -25 ug/day PO OD.
Check TSH level after 4-6 weeks to adjust the dose of L-
thyroxine.
In case of secondary hypothyroidism monitor FT4 instead of TSH.
Hypothyroidism during pregnancy:
Check TFT every month. L-thyroxine dose requirement tends to go
up as the pregnancy progresses.

If patient has concommitant hyperprolactinemia and

hypercholesterolemia, treat if not normalized after adequate
thyroid replacement.
If no residual thyroid function 1.5 g/kg/day, if patient
euthyroid treatment contraindicated
 Myxedema Coma
Medical emergency, end stage of untreated hypothyroidism
Characterized by progressive weakness, stupor,
hypothermia, hypoventilation, hypoglycemia, hyponatremia,
shock, and death
The patient have previous thyroid disease, radioiodine
therapy or thyroidectomy
Gradual onset of lethargy progressing stupor or coma
amenorrhea or impotence with pituitary myxedema
iHR and marked hypothermia (as low as 24C
Obese elderly woman with yellowish skin, a hoarse voice, a
large tongue, thin hair, puffy eyes, ileus, and slow reflexes.
An anterior neck scar may be present. Scanty pubic or
axillary hair with pituitary myxedema
Lab: low FT4, TSH high, normal, or low, cholesterol high or
N, serum Na low
ECG: bradycardia and low voltage
Precipitating factor : HF, pneumonia, excessive fluid
administration, narcotics
 Management of Myxedema Coma
Initiate therapy if presumptive clinical diagnosis after TSH,
FT3 FT4 drawn. Also draw serum cortisol, ACTH, glucose.
General measures:
Patient should be in ICU setting
Support ventilation as respiratory failure is the major cause of
death in myxedema coma
monitors ABG`s
support blood pressure; hypotension may respond poorly to
pressor agents until thyroid hormone is replaced
hypothermia will respond to thyroxin therapy ; in interim use
passive warming only
hyponatremia will also be corrected by thyroxine therapy in
majority of cases
hypoglycemia requires IV glucose
avoid fluid overload
 Management of Myxedema Coma
Specific measure:
L-thyroxine 0.2-0.5 mg IV bolus, followed by 0.1
mg IV OD until oral therapy is tolerated
Results in clinical response in hours

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.

Identify and treat the underlying precipitant cause

 Thyroiditis
Acute: rare and due to suppurative infection
of the thyroid
Sub acute : de Quervains thyroiditis/
granulomatous thyroiditis mostly viral
origin
Chronic thyroiditis: mostly autoimmune
(Hashimotos) , 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
 Acute Thyroiditis
Bacterial Staph, Strep
Fungal Aspergillus, Candida,
Histoplasma, Pneumocystis
Radiation thyroiditis
Amiodarone (acute/ sub acute)
Painful thyroid, ESR usually elevated,
thyroid function normal
Hashimotos Thyroiditis
or Goitrous thyroiditis
Women 4:1000 Men 1:1000
Japanese, previous history,
high iodium intake
Average age: 60
Frequently associated to other
autoimmune disorders such as:
AR, SLE, Sjogrens so-on
Rarely associated with pain
Insidious onset and
progression
TPO abs present (90 95%)
Treatment: Levothyroxine
 Chronic Thyroiditis
Reidels
Rare
Middle aged women
Insidious painless
Symptoms due to compression
Dense fibrosis develop
Usually no thyroid function impairment
 THYROID GLAND DISORDERS
CONGENITAL HYPOTHYROIDISM

Prevalence: 1 in 3000 to 4000 newborns

Cause: Dysgenesis 85%
Dx: Blood screning (TSH &/or T4)

Treatment:
Supplemental Tx. With Levothyroxine is
essential for a normal C.N.S.
Development and prevention of mental
retardation
 Benign Thyroid Nodules
Thyroid nodules are common especially among older
women
Etiology:
Focal thyroiditis
Dominant portion of multinodular goitre
Thyroid, parathyroid, or thyroglossal cysts
Agenesis of a thyroid lobe
Postsurgical remnant hyperplasia or scarring
Postradioiodine remnant hyperplasia
Benign adenomas:
Follicular
Colloid or macrofollicular
Hurthle cell
Embryonal
Rare: Teratoma, lipoma, hemangioma
 Thyroid Cancer
Approximate frequency of malignant thyroid tumours

Papillary carcinoma (including mixed papillary and follicular 75%

Follicular carcinoma 16%

Medullary Carcinoma 5%

Undifferentiated carcinomas 3%

Miscellaneous (e.g. lymphoma, fibrosarcoma, squamous 1%

cell ca, teratoma, & metastatic ca)
 Papillary Carcinoma
Usually presents as a nodule that is firm, solitary,
cold on isotope scan, and usually solid on thyroid
US
In MNG, the cancer is usually a dominant nodule.
larger, firmer and different from the rest of the gland

Very slowly and remains confined to the thyroid gland

and local lymph nodes many years.
Later stages spread to the lung
Death usually from local disease or lung metastases
May convert to undifferentiated carcinoma
Many of these tumours secrete thyroglobulin which
can be used as a marker for recurrence or metastasis
of the cancer
 Follicular Carcinoma
Presence of capsular or vascular invasion

More aggressive than papillary ca, spread either by

local invasion of lymph nodes or by blood vessel
invasion with distant metastases to bone or lung

Death is due to local extension or to distant

bloodstream metastasis with extensive involvement
of bone, lungs & viscera

These tumours often retain the ability to concentrate

RAI
Thyroglobulin secretion by follicular carcinoma can
be used to follow the course of the disease
 Management of Papillary and Follicular
Carcinoma
Classified into low risk and high risk groups
The low risk group includes patients under age 45
with primary lesions under 1cm and no evidence of
intra- or extraglandular spread Lobectomy
All other patients are considered high risk total
thyroidectomy. Modified neck dissection if lymphatic
spread.
Surgery is usually followed by RAI ablation therapy

Patient is placed on L-thyroxine suppressive therapy

Follow up with thyroglobulin level, thyroid US, whole
body scan etc.
 Medullary Carcinoma
C cells (parafollicular cells)
More aggressive than papillary or follicular carcinoma
but not as aggressive as undifferentiated thyroid
cancer
It extends locally, invade lymphatics and blood
vessels
Calcitonin and CEA are clinically useful markers
80% of medullary ca are sporadic and the rest are
familial.
The familial syndromes are associated with mutations
in the ret proto-oncogene (a receptor protein kinase
gene on chrom. 10)
Diagnosis FNAB. Screened for other endocrine
abnormalities
Undifferentiated (Anaplastic) Carcinoma

This tumour usually occurs in older patients

history of goitre the gland suddenlyover
weeks or monthsbegins to enlarge and
produce pressure symptoms, dysphagia, or
vocal cord paralysis.

Death from massive local extension usually

occurs within 6-36 months

These tumours are very resistant to therapy