Hypothyroidism,

Hyperthyroidism;
Thyroid Nodular Disease
and Cancer
MCC San Antonio, Danniel
PGI – in – charge: Dr. Igcasan
Resident – in – charge: Dr. Penuela, Dr. Salinas,
Dr. Ventura
 Table of contents

01 Introduction 03 Hyperthyroidism

02 Hypothyroidism 04 Thyroid Nodular Disease

Benign and Malignant

05 Lesions
 01

Introduction
 Thyroid is a gland

The thyroid is a gland that produces two related hormones, thyroxine

(T4) and triiodothyronine (T3).

These hormones play a critical role in cell differentiation and

organogenesis during development and help maintain thermogenic and metabolic
homeostasis in the adult.
Anatomy
 Thyroid is a gland

Thyroid Gland

- Consist of 2 lobes

- Anterior to the trachea

- Normal size is 12 – 20g, highly vascular, and soft in consistency.

- 4 parathyroid glands are located posteriorly.

- Recurrent laryngeal nerves traverse the lateral borders.

Anatomy
 Thyroid is a gland

Thyroid Gland Development

- Floor of the primitive pharynx during the 3rd week of gestation.

- Migrates with the thyroglossal duct to reach its final location in the neck.

- Thyroid hormone synthesis begins at about 11 weeks’ gestation.

Thyroid Hormone Synthesis
 Thyroid is a gland

Thyroid Hormone Synthesis Steps

1. TRH release from Hypothalamus 6. Iodination of Tyrosine A.A.

2. Anterior Pituitary releases TSH
3. TSH stimulates follicular cells to
synthesize TGB
4. Iodide Trapping
5. Oxidation of Iodide (TPO)
7. Couple DITs and MITs
8. Endocytosis of TGB with T3 and T4
9. Lysosomal Enzymes cleave T3 and
T4 out of TGB
10. Exocytosis of T3 and T4 into
blood plasma
 02

Hypothyroidism
 Hypothyroidism

Iodine Deficiency à Most common cause

In areas where iodine is insufficient, autoimmune disease and

iatrogenic causes are most common.
 Hypothyroidism
Autoimmune Hypothyroidism

- Associated with a goiter (Hashimoto’s or goitrous thyroiditis) or, at later

stages, atrophic thyroiditis.
- Autoimmune process gradually reduces thyroid function, a compensation
phase happens when normal thyroid hormone levels are maintained by a rise
in TSH.
- Some patients may have minor symptoms (subclinical hypothyroidism) but
later T4 levels fall and TSH rise wherein symptoms become readily apparent
à usual TSH >10 mIU/L à clinical hypothyroidism or overt hypothyroidism.
 Hypothyroidism
Prevalence

- Mean annual incidence rate is up to 4 per 1000 women and 1 per 1000 men.
- More common in Japanese people because of genetic factors and exposure to
a high – iodine diet.
- Mean age at diagnosis is 60 years old. Prevalence of overt hypothyroidism
increases with age.
- Subclinical hypothyroidism à 6 – 8 % of women (10% over the age of 60), 3%
in men.
- Clinical Hypothyroidism à 4% when hypothyroidism is associated with + TPO
antibodies.
 Hypothyroidism
Pathogenesis

- HLA DR polymorphisms à HLA

- Tumor Necrosis Factor (TNF), IL-1,
DR3, DR4, and DR5 in Caucasians
and interferon γ (IFN γ)
- CTLA 4
- TPO and thyroglobulin (Tg) à
- High iodine, low selenium intake,
markers of thyroid autoimmunity
decreased exposure to
- TSH R blocking antibodies –
microorganisms in childhood =
hypothyroidism and thyroid
increased risk
atrophy à thyroid neonatal
- Smoking cessation transient
increase hypothyroidism.
- Alcohol Protective
 Hypothyroidism
Clinical Manifestations

Myxedema
- increased dermal glycosaminoglycan
content traps water which gives rise
to skin thickening without pitting.
- Puffy face with edematous eyelids
and nonpitting pretibial edema.

Weight Gain
- despite a poor appetite, it is mainly
due to fluid retention in the
myxedematous tissue.
 Hypothyroidism
FEATURES INCREASED DECREASED
Weight
Libido
Fertility
Myocardial Contractility
and Pulse Rate
Peripheral Resistance
Memory and
Concentration
Respiratory Muscle
Function
Relaxation of Tendon
Reflex
Prolactin
Hypothyroidism
 Hypothyroidism

Other causes of Hypothyroidism

à Iatrogenic Hypothyroidism – After radioiodine treatment and subtotal

thyroidectomy
à Iodine Deficiency
à Chronic Iodine Excess - Amiodarone
à Secondary Hypothyroidism – Low unbound T4 level
 Hypothyroidism
TREATMENT

Clinical Hypothyroidism
- Levothyroxine 1.6 ug/kg bodyweight (typically 100 – 150 ug), at least 30
min before breakfast.
- <60 years old without heart disease à 50 – 100 ug of Levothyroxine daily
- With hypothyroidism after the treatment of Graves’ disease à 75 – 125
ug/d
- Dose adjusted based on TSH level

Goal of Treatment à Normal TSH

 Hypothyroidism

TREATMENT

Subclinical Hypothyroidism
- Levothyroxine 12.5 or 25 ug
- TSH measured after 2 months

Goal of Treatment à Normal TSH

 03

Hyperthyroidism
 Hyperthyroidism

THYROTOXICOSIS HYPERTHYROIDISM

Refers to the biochemical and vsTermhormones

used for excessive production of
by the thyroid gland.
physiological manifestations of
excessive thyroid hormones.
Pathology is in the thyroid gland itself.
 Hyperthyroidism

THYROTOXICOSIS
- State of thyroid hormone excess and is not synonymous with
hyperthyroidism (which is the result of excessive thyroid function).

- Graves’ Disease, toxic multinodular goiter (MNG), and toxic adenomas.

Hyperthyroidism
 Hyperthyroidism
Graves’ Disease
Epidemiology
- 60 – 80% of thyrotoxicosis
- Genetic factors and iodine
intake
- 2% of women but is one – tenth
as frequent in men.
- Rarely begins before
adolescence and typically
occurs between 20 and 50 years
of age, also occurs in the
elderly.
Hyperthyroidism
 Hyperthyroidism

Clinical Manifestation

- Include features common to any

cause of thyrotoxicosis and
specific for Graves’ disease.
 Hyperthyroidism

Ophthalmopathy Thyroid Thyroid

Dermopathy Acropathy
 Hyperthyroidism

Ophthalmopath Thyroid Thyroid

y Dermopathy Acropathy
 Hyperthyroidism

- thyroid is diffusely enlarged (2- - Decreased GI transit time

3x) - Increased stool frequency
- Firm but not nodular (diarrhea and occasional mild
- Thrill or bruit steatorrhea)

- Sinus tachycardia most common

cardiovascular finding
- Atrial fibrillation
Hyperthyroidism
 Hyperthyroidism
TREATMENT
Reducing Thyroid Hormone Synthesis
- Antithyroid drugs à Thionamides,
Block oxidation/organification of
iodide by inhibiting TPO
- Reduce thyroid levels
(immunomodulation)
Reducing the amount of Thyroid Tissue
- Radioiodine (1311) treatment
- Thyroidectomy
Anti-thyroid Hormones (Thionamides)
- Carbimazole / methimazole: 10-20
mg every 8 hours or 12 hrs
- Propylthiouracil 100 – 200 mg every
6 – 8 hrs
- Daily Maintenance dose
- à2.5 – 10 mg of carbimazole or
methimazole
- 50 – 100 mg of PTU
 Hyperthyroidism
TREATMENT

Radioiodine à progressive destruction

of thyroid cells
Absolute Contraindication
Carbimazole or Methimazole
- Stopped 2-3 days before radioiodine à Pregnancy
adm. à Breastfeeding

Propylthiouracil (Radioprotective
effect)
- Stopped for a longer period before
adm.
 Hyperthyroidism

TREATMENT

Propylthiouracil
à 500 – 100 mg: 250 mg every 4 h PO or NGT or PR
Methimazole
à 20 Mg q6h stable iodide 5 drops SSKI every 6 h
Propranolol
à 60 – 80 mg PO q4h; or 2 mg IV q4h
Glucocorticoid Hydrocortisone
à 300 mg IV bolus, then 100 mg q8h
 Hyperthyroidism

Thyroid Storm

- Thyrotoxic Crisis
- Life threatening exacerbation of hyperthyroidism
- Fever, delirium, seizures, vomiting, diarrhea, jaundice and coma.
 Hyperthyroidism
Thyroiditis

Acute Thyroiditis
- Rare and due to suppurative
infection
- Piriform sinus – most common
cause in children and young adults
- Thyroid pain
- Small, tender goiter that may be
asymmetric
- Fever, dysphagia, erythema,
lymphadenopathy
- Increased ESR and WBC
- Normal Thyroid Function
- Fine needle aspiration (FNA)
biopsy
- Culture identify organism
- Antibiotics
- Surgery
 Hyperthyroidism

Thyroiditis

Sub-acute Thyroiditis
- de Quervain’s thyroiditis, granulomatous thyroiditis, or viral thyroiditis
- 30 – 50 years old
- 3x women > men
 Hyperthyroidism

Pathophysiology

- Characteristic patchy inflammatory infiltrate with disruption of the

thyroid follicles and multinucleated giant cells within some follicle.
- Follicular changes progress to granulomas
- Fibrosis
- Thyroid returns to normal several months after onset
 Hyperthyroidism

Clinical Manifestations

- Painful and enlarged thyroid

- Fever
- Malaise, URTI symptoms
- Sore throat, small goiter
- Pain referred to the jaw or ear.
 Hyperthyroidism

Clinical Manifestations

- Painful and enlarged thyroid

- Fever
- Malaise, URTI symptoms
- Sore throat, small goiter
- Pain referred to the jaw or ear.
 Hyperthyroidism

TREATMENT
- Aspirin à 600 mg every 4 – 6 h
- NSAIDs
- Glucocorticoids à 15 – 40 mg of prednisone, tapered over 6 – 8 weeks
- Monitor thyroid function every 2 – 4 weeks using TSH and unbound T4
levels
- Levothyroxine à 50 – 100 ug daily
 Hyperthyroidism

Thyroiditis

Silent Thyroiditis
- Painless thyroiditis or “silent” thyroiditis
- 5 % of women 3 – 6 months after pregnancy (postpartum thyroiditis)
- Brief phase of thyrotoxicosis
- Normal ESR and the presence of TPO antibodies
- Propranolol 20 - 40 mg TID/QID
- Thyroxine Replacement
 Hyperthyroidism

Thyroiditis

Drug Induced Thyroiditis

- IFN alpha or IL 2 or tyrosine kinase
- Painless thyroiditis, hypothyroidism, and Graves’ disease
- Most common in women with TPO antibodies
 Hyperthyroidism

Thyroiditis

Chronic Thyroiditis
à Hashimoto’s Thyroiditis – most common; autoimmune, firm or hard goiter
à Riedel’s Thyroiditis – Insidious, painless goiter; dense fibrosis; extends
outside the thyroid capsule; Open biopsy for diagnosis, Treatment is
surgery.
 Hyperthyroidism
Thyroiditis

Sick Euthyroid Syndrome

- Nonthyroidal Illness
- Caused by release of cytokines such as IL – 6
- Decrease in total and unbound T3 levels (low T3 syndrome)
- Normal levels of T4 and TSH
- Diagnosis is challenging, useful features to consider include previous
history of thyroid disease and thyroid function tests, severity and time
course of patient’s acute illness, documentation of medications,
measurements of rT3, together with unbound thyroid hormones and TSH.
 Hyperthyroidism

Amiodarone Effects on Thyroid

function
- Amiodarone is used as a type III
antiarrhythmic agents.
- Typical dose of 200 mg/d are
associated with very high iodine
intake, leading to greater than
fortyfold increase in plasma and
urinary iodine levels.
- Stored in adipose tissue
- Inhibits deiodinase activity.
Effects:
1. Acute, transient suppression of
thyroid function
2. Hypothyroidism in patients
susceptible to the inhibitory effects
of a high iodine load
3. Thyrotoxicosis
 Hyperthyroidism

2 Major Forms of AIT

Initiation of Amiodarone Treatment
- Transient decrease of T4 levels
Type 1 AIT
- Escape from iodide dependent
- Underlying thyroid abnormality
suppression (Wolf Chaikoff effect)
- Excessive thyroid hormone
- Predominant inhibitory effects on
synthesis
deiodinase activity and thyroid
- Jod – Basedow phenomenon
hormone receptor
- Increased T4, decreased T3,
Type 2 AIT
increased rT3, and a transient TSH
- No intrinsic thyroid abnormalities
increase (up to 20 mIU/L)
- Drug induced lysosomal activation
Hyperthyroidism
 Hyperthyroidism

Treatment
- Discontinuing of drug
- Potassium perchlorate – 200 mg q6h
- Glucocorticoids
- Lithium
- Near Total thyroidectomy
 Hyperthyroidism vs Hypothyroidism

TSH T4 DIFFERENTIAL TSH T4 DIFFERENTIAL

Decreased Increased Primary

Increased Normal Subclinical
Thyrotoxicosis
Hypothyroidism
Decreased Normal Subclinical
Hyperthyroidism Increased Decreased Primary (Overt)
(Inc. T3 Hypothyroidism
toxicosis)
Decreased Decreased Secondary
Increased Increased Secondary Hypothyroidism
Thyrotoxicosis
 Hyperthyroidism vs Hypothyroidism

TSH T4 DIFFERENTIAL TSH T4 DIFFERENTIAL

Decreased Increased Primary

Increased Normal Subclinical
Thyrotoxicosis
Hypothyroidism
Decreased Normal Subclinical
Hyperthyroidism Increased Decreased Primary (Overt)
(Inc. T3 Hypothyroidism
toxicosis)
Decreased Decreased Secondary
Increased Increased Secondary Hypothyroidism
Thyrotoxicosis
 04
Thyroid Nodular
Disease and
Cancer
 Thyroid Nodular Disease and Cancer

Goiter à Enlarged Thyroid Gland

Biosynthesis defects and iodine deficiency à reduced efficiency of thyroid

hormone synthesis à increased TSH à stimulates thyroid growth
(compensatory mechanism)

Hyperplastic or Neoplastic

Multinodular Goiter (MNG)

Common; 3 – 7 of adults by PE, 50% by imaging (UTZ)

 Thyroid Nodular Disease and Cancer
Diffuse Nontoxic (Simple) Goiter
• Diffuse enlargement of the thyroid
w/o nodules and hyperthyroidism
• More common in women
• Most commonly caused by iodine
deficiency (worldwide)
• Types:
• Simple goiter
• Colloid goiter
• Endemic goiter
• Sporadic goiter
• Juvenile goiter
• Iodine deficient areas-
compensatory effort to trap iodide
and produce sufficient hormone
• TSH levels are usually normal or
only slightly increased
• Goitrogens: cassava root ,
cruciferous vegetables (cabbage,
cauliflower) , milk goitrogens (+) (in
grass)
 Thyroid Nodular Disease and Cancer

Clinical Manifestations

• Asymptomatic
• symmetrically enlarged, nontender , generally soft gland without palpable
nodules
• total thyroid volume exceeding 30 mL is considered abnormal
• Substernal goiter
• Pemberton’s sign
 Thyroid Nodular Disease and Cancer

Diagnosis Treatment

• Thyroid Function Test

• Iodine Replacement
• Low total T4 with normal T3 and
• Subtotal or near total
TSH
thyroidectomy à cosmetic
• TPO antibodies
reasons; replacement of
• Low urinary iodine levels (<50
levothyroxine
ug/L)
 Thyroid Nodular Disease and Cancer
Nontoxic Multinodular Goiter

• 12% of adults
• Women > men
• Increases in prevalence with age
• More common in iodine deficient
Clinical Manifestations:
regions
• Most are asymptomatic and
euthyroid
• Large symptomatic
• Pain and compression
• Hoarseness - malignancy
 Thyroid Nodular Disease and Cancer

Diagnosis Treatment

• Distorted, multiple nodules of

varying size
• Pemberton’s sign
• Tracheal deviation
• Pulmonary function testing
• CT, MRI, or ultrasound
• Conservative management
• Radioiodine 1311 3.7 MBq (0.1
mCi) per gram of tissue
• Surgery
 Thyroid Nodular Disease and Cancer
Toxic Multinodular Goiter
• Functional Anatomy
• Subclinical or mild overt
hyperthyroidism
• Elderly
• Atrial fibrillation or palpitations,
tachycardia, nervousness, tremor,
or weight loss
• Decreased TSH, normal or
increased T4, increased T3
• Ultrasound presence of discrete
nodules corresponding to areas of
decreased uptake (“cold” nodules),
FNA
Treatment
• Antithyroid drugs
• Radioiodine TOC
• Surgery – definitive treatment
 Thyroid Nodular Disease and Cancer
Hyperfunctioning Solitary Nodule

• Toxic Adenoma
• Solitary, autonomously functioning
thyroid nodule
• Acquired somatic, activating
mutations in the TSH-R
• Thyrotoxicosis
• Thyroid scan
Treatment
• Radioiodine ablation treatment
of choice
• Surgical Resection
• Antithyroid drugs and beta
blockers
 05

Benign and
Malignant Lesions
 Benign and Malignant Lesions

Hyperplastic Neoplastic Hürthle Cell

Adenoma
• Both macro and • Encapsulated
• Oncocytic follicular
microfollicular adenomas
cells arranged in
• Mixed cystic/solid or • More monotonous
follicular pattern
• Spongiform lesions • Microfollicular pattern
 Benign and Malignant Lesions

Adenomas Diagnosis and Treatment

- Typically discrete, solitary - Ultrasound guided FNA
masses, derived from biopsy
follicular epithelium - Ethanol ablation
- Follicular adenomas, in - Levothyroxine Therapy
general, are not forerunners
to becoming carcinomas;
nevertheless there is still a
possibility
 Benign and Malignant Lesions

Thyroid Cancer

- Most common malignancy of the endocrine system

- Papillary thyroid cancer (PTC) or follicular thyroid cancer (FTC)
- Anaplastic thyroid cancer (ATC poor prognosis)
- 4.9 – 14.3 cases per 100,000
- Mortality Rate: 1%
- 2x women > Men
- Men and elderly > 65 years have the worse prognosis
Benign and Malignant Lesions
 Benign and Malignant Lesions

Hyperplastic
 Benign and Malignant Lesions
Pathogenesis and Genetic Basis

- Radiation
- TSH and Growth Factors
- Oncogenes and Tumor Suppressor Genes
• RET/PTC and PAX8 PPARy1
• RET-RAS-BRAF signaling pathway
 Benign and Malignant Lesions
Well Differentiated Thyroid Cancer

Papillary Follicular

• Most Common Type • Iodine Deficient

• Psammoma Bodies Regions
• Orphan Annie Nuclei • Hematogenous
• Lymphatic Spread • Hurthle Cell Histology
 Benign and Malignant Lesions
Treatment
• Surgery
• Lobectomy (unilateral)
• Near Total Thyroidectomy (Bilateral)
• Near Total Thyroidectomy
 Benign and Malignant Lesions
Anaplastic and Other forms of
Thyroid Cancer

Anaplastic Thyroid Lymphoma

• Poorly differentiated • Rapidly expanding
and aggressive thyroid mass
• Poor prognosis • Diffuse large cell
• Chemotherapy lymphoma à most
• External Beam common
radiation • Biopsy
• External Radiation
• Surgical Resection
Benign and Malignant Lesions

Medullary Thyroid Carcinoma

• Sporadic or Familial
• Familial MEN 2A, MEN 2B, and familial MTC without other
features of MEN
• MEN 2B > MEN 2A
• Familial MTC > Sporadic MTC
• Increased serum calcitonin
• RET gene mutations
• Surgery
Benign and Malignant Lesions
Consummatum Est!