Institute of Endocrinology and Diabetes, National Center of Childhood Diabetes

Schneider Childrens Medical Center of Israel

The Thyroid Gland

Dr. Liora Lazar

Thyroid gland
Physical examination of the thyroid gland

Inspection
Glass of water for swallowing

Palpation
Anteriorly
From behind

Each lobe measures : vertical dimension 2 cm

horizontal dimension 1 cm
Thyroid palpation

Texture soft / firm / hard

Surface smooth / seedy / lumpy

Shape diffuse / nodular

Presence of regional adenopathy

Disorders of the thyroid gland

Abnormal thyroid function

Hypothyroidism
Hyperthyroidism

Thyroid enlargement
Goiter
Thyroid nodules
Thyroid tumors
Hypothyroidism
Symptoms
Insidious course

Subtle but become more obvious as the condition worsens

Not specific (can mimic symptoms of other conditions)

Attributed to aging

The patient may become aware of symptoms only when

euthyroidism is restored
 Hypothyroidism-
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Hypothyroidism
Clinical presentation
Weakness and easy fatigability
Cold intolerance
Weight gain
Constipation
Hair loss and dry skin
Menstrual irregularities especially menorrhagia
Infertility
Muscle cramps
Difficulty concentrating and poor memory
Depression

The symptoms are related to a metabolic slowing of the body


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Hypothyroidism
Physical findings
Skin cool, rough, dry,
yellowish color
Face puffy
Voice hoarse ; slow speech
Goiter +/-
Bradycardia
Peripheral non-pitting edema
Reflexes slow
Hypothyroidism
CVS
Impaired muscular contraction

EKG - bradycardia, low voltage

of QRS complexes and
P and T waves

Echo - cardiac enlargement,

pericardial effusion (30%)

CBC : Hb-11.1gr% (13-16.5), MCV-88 (80-96)

ESR : 5/16

Renal and liver function tests : normal

Elevated CPK

Blood lipids :Cholesterol 232mg% (140-200)

Triglycerides 170mg% (10-190)
Cholesterol HDL 36mg% (40-120)
Cholesterol LDL 162mg% (50-130)

PT, Fibrinogen, INR : normal


Thyroid function tests
TSH 46 mU/L (0.4-4.0)
fT4 5.8 pmol/L (10.5-25.7)
TT3 0.7 nmol/L (1.1-2.7)

Antithyroid antibodies
Anti microsomal (TPO) 764 iu/ml (0-75)
Anti thyroglobulin (Tg) 247 iu/ml (0-150)
TBII not determined
Anti-thyroid antibodies

Women Men

Anti microsomal 103 per 1000 27 per 1000

Anti thyroglobulin 30 per 1000 9 per 1000

Hypothyroidism
Causes of hypothyroidism
Primary (fT4 ; TSH )

Autoimmune (Hashimotos) thyroiditis

Iatrogenic: 131I treatment, ionizing external irradiation, subtotal or total
thyroidectomy
Congenital: absent or ectopic thyroid gland, dyshormonogenesis,
TSH-R mutation
Iodine deficiency or iodine excess
Infiltrative disorders: amyloidosis, sarcoidosis, hemochromatosis,
scleroderma, cystinosis
Drugs: Amiodarone, Lithium, Interferon-, Interleukin-2
Hypothyroidism
Causes of hypothyroidism
Central - hypothalamic-pituitary dysfunction (fT4 ; TSH N/)

Tumors in the hypothalamic-pituitary region (pituitary adenoma, craniophryngioma,

meningioma, glioma, metastases)

Pituitary surgery or irradiation

Infiltrative disorders (sarcoidosis, hystiocytosis, hemochromatosis)

Trauma

Infections (tuberculosis, syphilis, toxoplasmosis)

Genetic forms of CPHD or isolated TSH deficiency

Drugs: dopamine, glucocorticoids

Autoimmune (Hashimotos) thyroiditis
Prevalence
5% - 15% of women
1% - 5% of men

Incidence
Women 4 per 1000 per year
Men 0.6 per 1000 per year

Sex ratio (F:M) 8 - 9:1

Genetic predisposition
Dr. Hakaru Hashimoto 1912
Autoimmune (Hashimotos) thyroiditis

Diagnostic criteria

Positive test for thyroid auto-antibodies

Lymphocytic infiltration of thyroid

Moderate goiter (atrophic thyroiditis)

Thyroid functions:
euthyroid
subclinucal hypothyroidism
overt hypothyroidism
hyperthyroidism
Sub-clinical hypothyroidism
Elevated TSH and normal fT4 and T3

Prevalence approximately 6% of the general

population

Eldery > young

Natural history
Normalization in approximately 5%

Progression to overt in approximately 5% per year

Presentation of Hashimotos thyroiditis

Euthyroidism and goiter

Subclinical hypothyroidism and goiter

Overt hypothyroidism

Alternating hypo and hyperthyroisim

Painless or silent thyroiditis

Postpartum thyroiditis
Autoimmune (Hashimiotos) thyroiditis
Associations with other diseases

Turner syndrome (50%)

Down syndrome (20%)
Klienfelter syndrome

Vitiligo
Pernicious anemia
Addisons disease
Alopecia areata
Myasthenia gravis
IDDM (Insulin dependent diabetes mellitus)
Celiac disease
Indications for screening for hypothyroidism
Established
Congenital hypothyroidism
Neck irradiation
Pituitary surgery or irradiation
Patients treated with
amiodarone or lithium
Hyperlipidemia
Probably worthwhile
T1DM
Women over 40 with non-
specific complaints
Refractory depression
Syndromes: Turner, Down
Autoimmune Addison disease
Obesity ?
Hypothyroidism - treatment
Levo-Thyroxine (LT4)
Overt hypothyroidism
1.6 mcg/kg/day (100-150 mcg/day)
Elderly patients lower dose
Adjustment: on the basis of TSH levels

Sub-clinical / mild hypothyroidism

Symptoms attributable to hypothyroidism
TSH > 8 10 mU/L
Strongly positive thyroid autoantibodies
Goiter

Surveillance TSH measurements q 6mo

Euthyroid goiter and positive thyroid autoantibodies

Hypothyroidism - treatment
Thyroid hormone administration
A single dose
In the morning to avoid insomnia.

Thyroid hormone absorption (small bowel) can be affected by

Malabsorptive states
Small bowel disease
Patient's age.
Food: soy beans
Drugs: iron, calcium carbonate, aluminum hydroxide, cholestyramine (LT4 administration should be
spaced at least 4 hours apart)

Anticonvulsants phenytoin and carbamazepine and the antituberculous agent rifampin, may
accelerate levothyroxine metabolism, necessitating higher levothyroxine doses.

Thyroid hormone replacement can precipitate adrenal crisis

In patients with adrenal insufficiency adrenal steroids treatment should be initiated prior to treatment
of hypothyroidism.

Thyroid hormone replacement in patients with existing cardiac disease

LT4 should be initially administered in smaller doses with small incremental increases.
Hypothyroidism - treatment
Toxic effects of LT4 therapy
Cardiac symptoms
(Paroxysmal atrial tachycardia or fibrillation)

Restlessness and insomnia

Tremor

Excessive warmth

Osteopenia
Hypothyroidism

Course and prognosis

Lifelong follow-up
Clinical
Laboratory
US / FNA

LT4 treatment
Myxedema coma
Coma with multisystem organ failure

An altered mental status: hallucinations, disorientation, seizures

Hypothermia
Edema all over the body
Pleural effusion, pericardial effusion and ascites
Cardiomegaly, cardiogenic shock
Bradycardia
Hypercarbia
Hyponatremia

Most commonly occurs in eldery patients with undiagnosed or untreated

hypothyroidism that are subjected to an external stress
Cold exposure
MI, CHF, CVA
Surgery
Infection
Hypnotic drugs: sedatives, narcotics, anesthesia
Hypothyroidism
Take home message
Hypothyroidism is a very common condition.

The symptoms of hypothyroidism are often subtle.

The diagnosis of hypothyroidism is based on clinical suspicion and
confirmed by laboratory testing.
The increase in TSH can precede the fall in thyroid hormones by
months or years (subclinical hypothyroidism).

Most patients can be treated in an ambulatory care setting.

With the exception of certain conditions, the treatment of
hypothyroidism requires life-long medication.
Thyrotoxicosis
The clinical presentation depends on

Severity of thyrotoxicosis
Duration of disease
Patients age
Individual susceptibility
Thyrotoxicosis -

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 Thyrotoxicosis
Typical Symptoms Atypical Symptoms

Nervousness, hyperactivity Hypokalemic periodic paralysis

Insomnia Pruritus
Easy fatigability
Palpitations
Excessive sweating In elderly population
Intolerance to heat
Diarrhea Atrial fibrillation
Weight loss / gain (5%) Apathetic hyperthyroidism (fatigue
Oligomenorrhea and weight loss)
Osteopenia
Photophobia, eye irritation, diplopia,
or a change in visual acuity

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Thyrotoxicosis
Signs
Tachycardia; wide pulse pressure
Tremor
Hyperreflexia
Warm, moist skin

Proximal muscle weakness / loss of muscle mass

Onycholysis
Clubbing
Gynecomastia

Neck - diffuse goiter / thyroid nodule / WNL


CBC : Hb -14.1gr% (13-16.5); MCV-83 (80-96)
WBC 11,000 (differential OK)
ESR : 5/16

Fasting blood glucose : 98 mg%

Liver function tests : increased SGOT, SGPT X2
Renal function tests : normal
Calcium (mild hypercalcemia) : 11 mg% (8.5-10.5)

TT3 - 8.4 nmol/l (1.1-2.7)

fT4 - 47 pmol/l (10.5-25.7)
TSH - <0.01 mU/l (0.4-4.0)
Thyrotoxicosis
Differential diagnosis
Primary hyperthyroidism
Graves disease (85%) ; Hashitoxicosis [TSI, antithyroid antibodies]
Toxic multinodular goiter - functionally autonomous nodules (> age 50 yrs)
Toxic adenoma - commonly among patients in their 30s and 40s
Struma ovarii - Ovarian teratoma with ectopic thyroid tissue
Drug-induced - Iodine , Amiodarone

Thyrotoxicosis without hyperthyroidism

Subacute thyroiditis (de Quervain thyroiditis)
Thyroid destruction radiation, infarction of adenoma
Iatrogenic - Thyrotoxicosis factitia

Secondary hyperthyroidism
Thyrotropin-producing pituitary tumors
hCG secreting tumors
Gestational thyrotoxicosis
Thyrotoxicosis
In individuals in whom Graves' disease is not obvious:

Recent iodine exposure

Prior or current thyroid hormone use

Medications: Amiodarone, iodine

Anterior neck pain

Pregnancy

A family history of thyroid disease should be sought.

Thyrotoxicosis thyroid scan

123I , 125I, 131I, 99mTc pertechnetate

Thyrotoxicosis: differential diagnosis

Thyroid scan
Increased Uptake Decreased Uptake

Graves disease Subacute thyroiditis

Toxic adenoma Iodine induced
Toxic multinodular goiter hyperthyroidism
Hashitoxicosis Thyroid hormone therapy
TSH producing pituitary
tumor
Subacute thyroiditis (de Quervains)
Etiology: Postviral inflammation of the thyroid

Symptoms: Fever, malaise, soreness in the neck,

symptoms of hyperthyroidism

Signs: Tender gland, signs of hyperthyroidism,

no exophthalmos

Laboratory: Increased ESR, elevated T3 & T4, suppressed TSH

Thyroid scan: No uptake
Treatment: Symptomatic salicylates; prednisone; - blockers

Course: Usually resolves completely; 5% remain hypothyroid

Graves disease
Thyrotoxicosis

Goiter

Ophthalmopathy
exophthalmos (50%)

Dermathopathy
pretibial myxedema (1%-2%)
Graves disease
Pathogenesis
HLA-DR polymorphism

T-cell mediated autoimmune response

TSI

Ophthalmopathy
Smoking
Muscles swelling
Infiltration of the extraocular muscles by T-cells
Release of cytokines => fibroblasts activation
Synthesis of glycosaminoglycans in fibroblasts
Graves ophthalmopathy
Classification of eye changes
0 No signs or symptoms
1 Lid lag, upper lid retraction, stare
2 Soft tissue involvement
(periorbital edema)
3 Proptosis (exophthlmos) 30%
4 Extraocular muscle involvement
with diplopia (inferior rectus) 5%-10%
5 Corneal involvement (keratitis)
6 Sight loss (optic nerve involvement)
Graves disease
Associations with other autoimmune diseases
IDDM (Insulin dependent diabetes mellitus)

Addisons disease

Vitiligo

Pernicious anemia

Myasthenia gravis

Celiac disease
Graves disease
Treatment
Specific treatment should generally be withheld until the biochemical diagnosis
and cause of hyperthyroidism are confirmed.

Symptomatic treatment
(-adrenergic blocking agents Deralin 20-40 mg q 6-8 h)
Antithyroid drug therapy
Radioiodine therapy
Surgical therapy

The patient should have a clear understanding of the indications and

implications of all forms of therapy, including risks, benefits, and side effects,
and should be an active participant in the decision-making process regarding
type of therapy.
Graves disease
Anti-thyroid drug therapy - Thionamides
(Carbimazole, Mercaptizole, Propylthiouracil*)

Inhibit the synthesis of thyroid hormones:

Suppression of TPO

Interference with T4 T3

Reduce thyroid antibody levels (?)

* T1/2 : MTZ- 6 h; PTU- 1.5 h

Graves disease
Anti-thyroid drug therapy

A primary form of therapy

Lower thyroid hormone levels before (and in some cases after)
radioactive iodine therapy or surgery

There is no clear-cut standard for duration of therapy with ATDs

When used as primary therapy 6 months to 2 years
A longer period of administration is acceptable

A regimen of combined ATD and thyroid hormone to avoid

frequent adjustments of ATD doses.
Graves disease
Anti-thyroid drug therapy side effects

Minor (5%)
Rash, urticaria

Arthralgia

Abnormalities of smell and taste

Increased liver enzymes

Fever

Lymphadenopathy
Graves disease
Anti-thyroid drug therapy side effects

Major (<1%)
Agranulocytosis

Thrombocytopenia, DIC

Hepatitis

Nephrotic syndrome

SLE-like syndrome
Graves disease
Course and prognosis
45%-55% - Remission and exacerbation over a
protracted period of time

30%-40% - Euthyroidism

15% - Hypothyroidism

Graves ophthalmopathy is independent on

thyroid status
Graves disease
Surgical treatment
Preoperative preparation
Lugol

-blockers

Near-total thyroidectomy

Side-effects
Hypothyroidism

Hypoparathyroidism

Recurrent laryngeal nerve damage

Hemorrhage
Graves disease
Radioactive Iodine treatment
I131 5-15 mci

Side-effects
Worsening of ophthalmopathy
Hypothyroidism
Radiation thyroiditis
Toxic Nodular Goiter (Plummer's disease)
Common in elderly patients.
Caused by multiple hyperfunctioning nodules or, less frequently, a
single hyperfunctioning nodule.
Ophthalmopathy - not present.
Thyroid autoantibodies - absent
Diagnosis - thyroid scan

Treatment
131I

Surgery - in large goiters, presence of symptoms of tracheal or

esophageal compression or if there is concern about thyroid
malignancy.
Patients with solitary hyperfunctioning thyroid nodules are usually
treated with radioiodine
Subclinical thyrotoxicosis

A laboratory diagnosis:
Suppressed TSH
With or without elevation of the fT4, and the T3 level

Absence of clear-cut clinical symptoms and

signs

A sufficient indication for therapy

In elderly patients with coincident cardiac disease
In patients with osteopenia
Thyrotoxic storm
A rare and potentially fatal complication of hyperthyroidism
Triggered by different events in patients with underlying thyrotoxicosis
Infection
Surgery
Cardiovascular events
Toxemia of pregnancy
Diabetic ketoacidosis, hyperosmolar coma, and insulin-induced hypoglycemia
Thyroidectomy
Discontinuation of antithyroid medication
Radioactive iodine

Patients typically appear markedly hypermetabolic with

Extremely high temperature
Nausea and vomiting
Severe diarrhea leading to dehydration
Tachycardia
Exaggerated emotional swings: tremulousness, agitation, and psychosis
Stupor => Coma

Thyroid storm must be recognized and treated on clinical grounds alone, as

laboratory confirmation often cannot be obtained in a timely manner.
Thyrotoxicosis

Take home message

Various underlying etiologies

Most cases are sub-clinical (osteopenia)

Atypical clinical presentation in older patients (atrial fibrillation)

Antithyroid drugs - serious adverse events

Remission rate - low