Disorders of the Thyroid

gland

Laxmikant Chavan
M.B.B.S, M.D(INT Med)
Anatomy

• Over Trachea
• Two Lobes connected
together by an
isthmus
• 15 to 20 g
 Thyroid gland

 Thyroid gland derives from the floor of embryonic

pharynx
 Begins to develop around 3 weeks of gestation
 Moves down the neck while forming its characteristic
bilobular structure
 Thyroid hormone synthesis normally begins at about
11 weeks’ gestation
 Thyroid gland size increase gradually by 1g/year until
age of 15 years were it achieves adult size (15-25 g)
Sites of normal & ectopic thyroid tissue
Thyroid Regulation
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 Thyroid gland
• Thyroid gland is composed over a million cluster of follicles
• Follicles are spherical & consists of epithelial cells surrounding a
central mass (colloid)
• Thyroglobulin is storage room
• Two main hormones:
•Tetraiodothyronine (Thyroxin)
•Triiodothyronine
FUNCTIONAL
UNIT IS THE
FOLLICLE
 Thyroid gland

• Thyroid gland mainly secretes mainly T4

• 70 % of T3 derived from T4 in peripheral tissues
• T4 is converted to T3 by 5-deiodinase enzyme
• Both T4 and T3 are in bound form (TBG, pre albumin
and albumin)
• Only 0.025% of T4 and 0.35% of T3 are free
• Free hormone concentration best correlates with
thyroid status
• T4 production is 5-6 g/kg/day in infancy with
gradual decrement to 1.5 g/kg/day in adult
 Thyroid hormone synthesis
1) Iodide pump
• Rate –limiting step in thyroid hormone synthesis which needs energy
• Follicles have in their basement membrane an iodide trapping
mechanism which pumps dietary I - into the cell
• Normal thyroid: serum iodine is 30-40:1
•Iodide uptake enhancers:
•TSH
•Iodine deficiency
•TSH receptors antibody
•Iodide uptake inhibitors
•Iodide ion
•Drugs
•Digoxin
•Thiocynate
•perchlorate
 Thyroid hormone synthesis
2) Iodide oxidation to iodine and Organification
• Inside the cells, iodide is oxidized by peroxidase system to more reactive
iodine
• Iodine immediately reacts with tyrosine residue on a thyroid glycoprotein
called “thyroglobulin” to form :
•T1= mono-iodotyrosyl thyroglobulin
•T2= di-iodotyrosyl thyroglobulin

• Both processes are catalyzed by thyroid peroxidase enzyme

Thyroid hormone synthesis

3) Coupling
• T1& T2 couple together to form T3 & T4
• MIT +DIT = T3 (Tri-iodothyronine)
• DIT + DIT = T4 (Thyroxin)
• All attached to thyroglobulin and stored in the
colloid Thyroglobulin molecule
• This process is stimulated by TSH
 Production of Thyroid Hormones
NIS (Na+/I- Sympoter)

TPO
 Effects of thyroid hormones
• Fetal brain & skeletal maturation
• Increase in basal metabolic rate
• Inotropic & chronotropic effects on heart
• Increases sensitivity to catecholamines
• Stimulates gut motility
• Increase bone turnover
• Increase in serum glucose, decrease in serum
cholesterol
• Conversion of carotene to vitamin A
• Play role in thermal regulation
Increase BMR ( Basal Metabolic Rate )
• ↑cellular metabolic activity by :
• ↑ size, total membrane surface & number of

mitochondria
• ↑ ATP formation
• ↑ active transport of ions ( Na+, K+ )

Promote growth & development of the brain

during fetal life and for the first few years of
postnatal life
 Cardiovascular system
 vasodilatation
 ↑ blood flow
 ↑ cardiac output
 ↑ heart rate

 Respiratory
 ↑ the rate and depth respiration

 CNS
 extreme nervous & psychoneurotic tendency

 Muscle
 make the muscles react with vigor ----->
 muscle tremor ( 10-15 times/sec )

 Sleep: extreme fatigue but is difficult to sleep

 Carbohydrate metabolism
 Enhanced glycolysis, gluconeogenesis,

 GI absorption & insulin secretion

 Fat metabolism
 Enhanced fat metabolism

 Accelerates the oxidation of free fatty acids by the cells

 plasma cholesterol, phospholipids & triglycerides

 Body weight
 ↑ the appetite, food intake, GI motility
---------------- but ↓ the body weight
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•TSH (0.4 – 4 mU/L)
•Free T4 (9 – 25 pmol/L)
•Free T3 (3.5 – 7.8 nmol/L)
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FT3

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Hypothyroidism
&
Myxedema Coma
 Hypothyroidism & Myxedema
Coma

• Hypothyroidism: Diminished production of thyroid hormone, leading to

clinical manifestations of thyroid insufficiency, including low metabolic
rate, tendency to weight gain, somnolence and sometimes myxedema.

•Steadman’s Dictionary
 Hypothyroidism &
Myxedema Coma
• Etiologies of Hypothyroidism
•Primary
•Chronic Throiditis (Hoshimoto’s)Autoimmune
•Idiopathic
•Post Surgical or Radioiodine Ablation,External Radiation
•Iodine Deficiency,
•Drugs: Lithium, Amiodarone
•Congenital,Heritable Biosynthetic Defects
•Infiltrative disorder:-Lymphoma, Sarcoid, Amyloidosis, Tb
 Hypothyroidism & Myxedema
Coma
• Etiologies of Hypothyroidism
•Secondary
•Panhypopituitarism {Pituitary}
•Tertiary
•Neoplasms
•Infiltrative
 Hashimoto’s Disease

• It is an Autoimmune Disease in which Thyroid gland is attacked

by Variety of cell- and Antibody-Mediated immune processes.
• Most common cause of hypothyroidism in North America (Rest
of the world- iodine defeciency!)
• Females(85%) > Males, Runs in Families
• Goitre Rubbery goitre, not always Symmetrical
• Other Autimmune Disease- Type1DM, Vitilogo, Pernicious
Anemia
• Antithyroid antibodies:
•TG Ab(Anti -Thyroglobulin Ab )
•Anti-Microsomal Ab
•TPO ab(anti-thyroid peroxidase) 
•TSH-R Ab (block)
 Hypothyroidism & Myxedema Coma

• Signs & Symptoms of Hypothyroidism

•Fatigue, Weight Gain, Cold Intolerance, Depression, Menstrual

Irregularities, Joint Pains, Muscle Cramps, Infertility.

•Hoarseness, Hypothermia, Periorbital Puffiness, Delayed Relaxation of

Ankle Jerk, Cool/Rough/ Dry Skin, Non-pitting Edema, Bradycardia,
Peripheral Neuropathy.
 Hypothyroidism & Myxedema Coma

• Lab Tests:
•TSH –Thyroid Stimulating Hormone
•T4 – Free T4 is used to assess Thyroid Fctn
•Thyroglobulin Levels
•Anti Thyroid Antibodies
•Thyroid Perioxidase Antibodies (TPOAb)
•Anti TSH Receptor Antibodies

• **Because of the prevelance of Hypothyroidism in females >

60y/o, a serum TSH routinely (per year) should be obtained.
 Hashimoto’s Disease

•Treatment:
•Thyroid Hormone Replacement
•Levothyroxine (T4)
•T3?, T4/T3 combo?, dessicated thyroid?
• No benefit to giving iodine!
•In fact, iodine may decrease hormone production
•Wolff-Chaikoff effect (lack of escape)
 Hypothyroidism

• Hypothyroidism Treatment:
•Thyroxine 50 – 100micrograms/ day initially
•Thyroxine 75 – 150 micrograms/ day average
 Hypothyroidism & Myxedema
Coma
• Myxedema Coma
•A rare clinical state of insidious onset, in an individual with pre-
existing hypothyroidism.
•This represents a life threatening decompensation of the patients
condition.

•Precipitants:
•Infection
•Cold Exposure
 Hypothyroidism & Myxedema Coma

• Myxedema Coma Findings:

•Stupor-Decrease mental status – from baseline
•Hypothermia/ Hypoglycemia/ Hyponatremia
•Bradycardia
•Hypoventillation
•Peri-orbital edema
•Non-pitting Edema
•Delayed Tendon Reflexes
 Hypothyroidism & Myxedema Coma

• Myxedema Coma Treatment:

•#1 Recognition!
•ABC’s
•Thyroid replacement w/ Levothyroxine 300 – 500 micrograms slow
IV then maintenance.
•Glucocorticoid – Hydrocortisone100mgIVq8*
•For Prevention of Adrenal Crisis
•Temp/ Electrolyte/ Glucose – Management
Hyperthyroidism &
Thyroid Storm
 Causes of Thyrotoxicosis

• Primary
• Central
hyperthyroidism
hyperthyroidism
•Graves dz
•Pituitary adenoma
•Toxic multinodular
goiter
•Toxic nodular goiter
•Iodine intake
 Causes of Thyrotoxicosis
• Thyroiditis
•Subacute painful (de Quervain) • Non-thyroidal dz
•Silent subacute •Ectopic thyroid tissue
•Postpartum(After Pregnancy) •Metastatic thyroid CA
•Radiation thyroiditis • Drug-induced
•Lithium
•Iodine
•Amiodarone
•Excessive TH ingestion
Sx of hyperthyroidism

• Weakness • ↑ appetite
• Fatigue • Weight loss
• Heat intolerance • Hyperdefecation
• Nervousness • Dyspnea
• Sweating • Menstrual abnormalities
• Tremor
• Palpitation
Signs of Hyperthyroidism
• Warm, moist skin
• Goiter
• Muscle weakness
• Thyroid bruit
• Hyperreflxia
• Hyperkinesis
• Tachycardia/
• Ophthalmopathy
• Arrhythmia
• Lid retraction/stare
• Lid lag • ↑ SBP
• Tremor • Widened pulse
pressure
 Grave’s Disease
• Triad of: Hyperthyroidism/Throtoxicosis + Exophthalmos+
Dermopathy/Pretibial Myxedema
• Diffuse Goiter
• Women 20-40 yrs ( 4th Decade)
• Autoantibodies (TSI),TBII, TRab
• Autoantibodies : Extraoccular muscles
• Autoimmune disorders
•Pernicious anemia
•Myasthenia
•Diabetes
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 Toxic Multinodular goitre

• Non – Autoimmune
•Consequence of simple goiter, 10 Years latter becomes toxic,It
start to Secretes Thyroid harmone
• Nodular goitre on exam
• Disease of the elderly- Cardiac Arythmia -AF
• Presentation :1.Arrythmia 2.CHF
• No Opthalmopathy
• Rx : Radioactive Iodine
•Antithyroid drugs, with beta blockers, can normalize thyroid
function and improve clinical features .

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 Thyroid Storm: signs/symptomsx

• Very High Fever >104 • CNS

• Tachycardia •Agitation
• Arrhythmia •Confusion
• CHF •Delirium
•Stupor
•Coma
•Seizure
Thyroid Storm: Precipitants
• Infection • w/d thyroid meds
• Trauma • Iodine
• DKA • Palpation of thyroid gland
• AMI • Ingestion of TH
• CVA • Unknown in 20-25% of cases
• PE
• General surgery
 DDX thyroid storm

• Sepsis • Malignant hyperthermia/

• Sympathomimetic • Neuroleptic syndrome
ingestion
•cocaine, amphetamine
• Hypothalamic stroke
• Heat stroke
• DTs
 Investigations
• TSH
• Free T4
•Free T3
• USG Thyroid
• RAUI
• If Nodule- FNAC

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Thyroid nodules
• U/S more sensitive than P.E., particularly for nodules that
are < 1 cm or located posteriorly in the gland.
• U/S also more SEN than thyroid scan
• U/S too Sensitive?
•Thyroid Incidentaloma (Carotid duplex, etc.)
Thyroid U/S

Benign Malignant
Characteristics Characteristics
Regular border Irregular border
Halo (sonolucent rim) No Halo
Hyperechoic Hypoechoic
(more vascular)
Egg shell calcification Microcalcification

N/A Intranodular vascular spots

(color doppler)
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 RAIU

• Normal 24h RAIU = 5-15 %

• 24h RAIU:
>25% Hyperthyroid
20-25% Equivocal (check TSH)
9-20% Normal
5-9% Equivocal (check TSH)
<5% Hypothyroid

• Dependent on dietary iodine intake!

• Must be: not pregnant! (ß-hCG), no ATD x 7d, no LT4 x 4d,
no large doses of iodine or radiocontrast for 2 wk (prefer
4-6 wk)
Thyroid Scan

Thyroid nodule: risk of malignancy 6.5%

only 5-10% of nodules

Cold nodule “Warm” Nodule Hot Nodule

16-20% malignant (indeterminant) Tc-99m < 5% malignan
5% malignant I123 < 1% malignant
Thyrotoxicosis Treatment

• Beta-blockers (hyperadrenergic symptoms)

• Hyperthyroidism:
•Anti-thyroid Drugs
•Propylthiouracil (PTU), Methimazole
•Radioiodine Ablation
•Surgical Thyroidectomy
• Thyroiditis:
•ASA, NSAIDS, +/- corticosteroids
• Iodine (high doses Wolff Chaikoff effect)
 TX thyroid storm

• #1 Decrease synthesis
•PTU: 600-1000mg PO, followed by 200-250mg Q4h

•Methimazole: 40mg PO, then

25mg PO Q6h
TX thyroid storm

• #2 Prevent release
•Iodine:
•Iapanoic acid (Telepaque): 1g IV Q8h x 24h, then 500mg IV bid, or
•Potassium Iodide (SSKI): 5gtts PO Q6h, or
•Lugol solution: 8-10gtts PO Q6h
•Lithium carbonate: 800-1200mg PO QD
TX thyroid storm

•Corticosteroids:
•Hydrocortisone 100mg IV Q8h, or
•Dexamethasone 2mg IV Q6h
•Antipyretics: cooling blanket, Tylenol 650mg PO q4h
•Avoid salicylates!
TX thyroid storm

• Prevent peripheral effects

•ß- blockade:
•Propanolol: titrate 1-2mg IV Q5min prn (may need 240-480mg PO QD), or
•Esmolol: 500µg/kg IV bolus, then 50-200 µg/kg/min
•Guanethidine: 30-40mg PO Q6h
•Reserpine: 2.5-5mg IM Q4-6h
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 Hypothyroidism & Myxedema Coma

• QUIZ:
•1. Most effecatious lab test for Hypothyoid?
•A. CBC
•B. TSH
•C. T-4
•D. T-3 Free
•2. T/F Myxedema Coma is life-threatening?
•3. T/F Initial Dose of Thyroxine is 50 – 100mg?
•4. The Dose of Thyroxine for Myxedema is______?
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