Clinical Endocrinology

0202401

Thyroid Gland
Medical Laboratory
Sciences Department

Textbook:
- Bishop, (2018). Clinical Chemistry, 8th edition
- William Marshall. (2020). Clinical Chemistry, 9th edition
 Objectives
• After attending a series of lectures on thyroid gland, the student will:
• Identify/Describe the hypothalamic-pituitary-thyroid axis and how it regulates
thyroid hormone production. (TL1)
• Identify/Describe the principles of each thyroid function test discussed. (TL1)
• Correlate laboratory information with regard to suspected thyroid disorders, given a
patient’s clinical data. (TL2)
• Evaluate laboratory data to recognize and report the appropriate laboratory thyroid
function testing protocol to use to effectively evaluate or monitor patients with
suspected thyroid disease. (TL3)
• Correlate laboratory information with regard to suspected thyroid disorders, given a
patient’s clinical data. (TL3)
• Select the laboratory thyroid function testing protocol used to effectively evaluate or
monitor patients with suspected thyroid disease. (TL3)
• After demonstrating short videos during lecture, the student will: (TLI)
• Detect/identify what causes thyroid disease?
• Detect/identify what is thyroglobulin protein?
• Detect/identify the mechanism of thyroxine action 2
Thyroid Anatomy and Development
• Largest Endocrine organ in the body
• Involved in production, storage, and release of thyroid
hormone
• Positioned in lower anterior neck & shaped like a butterfly
• Made up of 2 lobes that rest on each side of trachea; band of
thyroid tissue (isthmus) runs anterior to trachea & bridges
lobes
• Iodine is an essential component of thyroid hormone; iodine
deficiency leads to hypothyroidism, mental retardation,
cretinism.
• Parathyroid glands: posterior to thyroid; regulate serum
calcium levels & recurrent laryngeal nerves that innervate
vocal cords
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 The Thyroid

• Produces 3 hormones

• Thyroid hormone (T3 & T4):

• T4 and T3 are produced by the follicular cells
• critical in regulating body metabolism,
neurologic development, & other functions
• Calcitonin:
• secreted by para-follicular C cells
• involved in calcium homeostasis

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Thyroid Hormone Synthesis
–Iodine
• Trace element & key component of thyroid hormone
• Iodine is essential for normal thyroid function.
• Source: seafood, seaweed, kelp, dairy products, vegetables
and iodized salt, vitamins & breads.
• Intake of <50 μg daily leads to hypothyroidism.
• Recommended iodine intake for:
–Adults: 150 μg/day
–pregnant and lactating women: 250 μg/day
–Follicles
• Site of thyroid hormone synthesis
• Spheres of thyroid cells surrounding a colloid core
• Inside thyroid cell, iodine is oxidized & bound with tyrosyl
residues on thyroglobulin to form thyroid hormone.

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- T4 is converted to T3
(active) by 5’ deiodinase
- T4 can be converted to rT3
(inactive) by 5 deiodinase
- T3 is converted to rT2
(inactive)by 5 deiodinase
- rT3 is inactive but
measured by serum tests

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–Two active forms of thyroid hormone:
• Triiodothyronine (T3)
• Tetraiodothyronine (Thyroxine) (T4)
–Thyroid hormone circulates in bloodstream.
–In cytoplasm, T4 is deiodinated into T3 .
Protein Binding of Thyroid Hormone
–Three major binding proteins:
• 1. Thyroxine-binding globulin (TBG)
• (70%) of T4 & T3 is bound to TBG
• 2. Thyroxine-binding pre-albumin (TBPA)
• 3. Albumin
–Free active hormone is: fT4: 0.04%, fT3 : 0.4%
–Bound to plasma proteins: T 4: 99.97%, T3: 99.7%

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 (Hereditary TBG excess)

,opiates
Acute intermittent porphyria

Chronic liver disease

Acromegaly

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 Thyroxine and its precursors: Activity

• T4 mainly functions as a prohormone.

• T3 is the main active thyroid hormone and has the highest

binding affinity for thyroid hormone receptor (TR).

• Thyroid hormone activity can be increased in plasma without

new synthesis by converting T4 to T3.

• If too much thyroid activity is present T4 is converted to the

inactive metabolite rT3 to reduce activity.
http://www.youtube.com/watch?v=YUv9PFQper4

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Control of Thyroid Function
• Hypothalamic-pituitary-thyroid axis regulates thyroid
hormone production

• Function influenced by
• Central axis (TRH) (pulsatile, circadian)
• Pituitary function (TSH)
• Some diseases (Cirrhosis, Graves, etc.)
• Environmental factors (iodine intake)

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Actions of Thyroid Hormone
• Required for normal foetal neural growth & brain (CNS)
development, hence in:
• Hypothyroidism: mental retardation
• Hyperthyroidism: restlessness, tremors, irritability
• Energy expenditure, increased heat production
• thus. increase body temperature
• Increased oxygen consumption
• Increases ventilation rate
• Regulates the menstrual cycle, thickens endometrium in females,
erythropoiesis
• Organogenesis & tissue growth
• Decreases cholesterol (formation of LDL & liver uptake),
• Increases lypolysis

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Action of TH
• promote bone growth & bone turnover, skeletal development,
hence excess:
• Hypercaleamia
• increases risk of fracture
• Demineralization because of loss of Ca & P in urine & faeces
• Muscle contraction and relaxation
• Regulates basal metabolic rate BMR
• Protein, carbohydrate and fat metabolism
• Gut motility, increase carbohydrates absorption
• Increased number of beta-adrenergic receptors, potentiating the
effects of catecholamines (such as dopamine and adrenaline) , thus :
• increase heart rate &
• Improves cardiac contractility, and peripheral vascular
resistance ,
• Hence: high T3&T4: tachycardia and arrhythmia, heart failure
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Diseases of the Thyroid

• Non-thyroidal illness
• Hypothyroidism
• Subclinical disease
• Congenital
• Hyperthyroidism

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Nonthyroidal Illness

• Abnormalities in thyroid function tests of hospitalized

patients (especially critically ill patients)
• Characterized by low total T4, free T4, & TSH
• Less T4 is converted to active T3, leading to decreased
levels of T3 and higher levels of reverse T3 (inactive).
• Central hypothyroidism (Hypothalamic) & thyroid
hormone-binding changes are associated with severe
illness.
• Changes may be appropriate adaptations to illness.

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Hypothyroidism
• Under-activity (hypothyroidism, causing myxoedema)
• Low free T4 level with a normal or high TSH
• One of most common disorders of thyroid gland, occurring in
5–15% of women >65 years old
• Iodine deficiency is a major cause of hypothyroidism in
undeveloped countries
• Most common cause in developed countries is chronic
lymphocytic thyroiditis.
• Individuals should be tested beginning at age 35 & every 5
years thereafter; more frequently if risk factors are present.
• Can lead to hyponatremia, anemia, hyperlipidemia

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Hypothyroidism
 Can be divided into primary, secondary, or tertiary disease

1. 1ry Hypothyroidism
• TSH high
• TRH high
• fT4/fT3 low/suppressed
2. secondary hypothyroidism: TSH deficiency of the pituitary gland.
• TSH low
• fT4/ft3 low/suppressed
3.Tertiary hypothyroidism: hypothalamic failure,
• TRH low
• TSH low
• fT4/ft3 low

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Hypothyroidism
• Diagnosis
• Low FT4, High TSH (Primary, check for antibodies)
• Low FT4, Low TSH (Secondary or Tertiary, TRH stimulation test, MRI)
• Subclinical
• Increased cholesterol,
• decreased ACE and ALP,
• anaemia (macrocytic)
Treatment
 Levothyroxine (T4) due to longer half life
 Treatment will: prevents bone loss, cardiomyopathy, myxedema

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Causes of Hypothyroidism
• Common causes of hypothyroidism
• Thyroiditis
• Hashimoto’s Thyroiditis
• Drug induced thyroid dysfunction
• Sub-acute thyroiditis
• Congenital hypothyroidism (cretinism)
• Consequent conditions:
• Myxoedema
• goiter

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Causes and clinical features of hypothyroidism

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Subclinical hypothyroidism
• In the absence of clinical features of hypothyroidism, this
is termed subclinical or compensated hypothyroidism.

• It is not unusual to find patients whose plasma TSH

concentration is elevated though with free thyroxine
within the reference range.

• Associated with a history of treated hyperthyroidism but

can occur de novo, particularly in the elderly.

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Thyroiditis
• Inflammation of the thyroid gland
• Due to:
• infection (usually viral) or autoimmune disease.
• In viral thyroiditis,
• associated with Coxsackie, mumps and adenovirus,
• the inflammation lead to an increase thyroid hormones
• Patients may become transiently, and usually only
mildly, thyrotoxic (6 wks).
• After another 6 wks thyroid hormone decreased,
• Thereafter, normal function is regained.

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Hashimoto’s thyroiditis (Chronic, Lymphocytic)
• Most common cause of 1ry hypothyroidism
• Autoimmune destruction of thyroid gland
• Very occasionally, transient hyperthyroidism may occur early in
the course of the disease, then …. Hypothyroidism
• Result of antibodies against (to) TPO, TBG
• Commonly presents in females 30-50 yrs.
• Usually non-tender and asymptomatic
• Lab values
• High TSH
• Low T4
• +ve Anti-TPO Ab
• +ve Anti-TBG Ab
• +ve Anti-microsomal Ab
• Treated: with Levothyroxine T4
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Drug-Induced Thyroid Dysfunction
• Amiodarone-Induced Thyroid Disease
• Amiodarone
• Used to treat cardiac arrhythmias
• Fat-soluble with a long half-life (50 days)
• 37% of molecular weight is iodine.
• Effects
• Inhibits thyroid hormone production.
• Blocks T4 to T3 conversion
• Leads to hypothyroidism in 8–20% of patients &
hyperthyroidism in 3%

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Sub-acute Thyroiditis
• Characterized by transient changes in thyroid hormone
levels
• Associated with inflammation of thyroid gland, leakage
of stored thyroid hormone, repair of gland
• Three classifications
• Postpartum: occurs in 3–16% of women in
postpartum
• Painless: similar to postpartum type, except with no
associated pregnancy
• Painful: characterized by neck pain, low-grade fever,
myalgia, tender diffuse goiter, swings in thyroid
function test

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Congenital Hypothyroidism (cretinism)

• Thyroid hormone is critical to neurologic development of fetus.

• That’s why, every newborn baby is checked for TSH, free T4

• Causes
• Structural abnormalities (absent gland, ectopic)
• Enzyme defects (I transport, organification)
• Iodoprotein secretion
• T3 transporter mutation
• Maternal antibodies (transient)

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Congenital Hypothyroidism
• 1:4000 births
• If Untreated:
• growth failure, mental
retardation (cretinism),
immature sex
• If treatment is started 1st 1-2
w; good prognosis

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Congenital Hypothyroidism

• Heal prick 5-8d

• Measure TSH
• 6-10 mU/L repeat
• 10-20 mU/L urgent
repeat
• >20mU/L immediate
referral
• Measure TSH & T4
to prevent cretinism

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Hypothyroidism Consequent Conditions

•Myxoedema
•Goiter

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Myxoedema
• Myxoedema is a rare life threatening consequence of
hypothyroidism

• Usually in individuals with long-standing

hypothyroidism
• Most often seen in the winter months
• More common in elderly women with under-
diagnosed or undertreated hypothyroidism

• Atrophic myxoedema, the end result of autoimmune

destruction of the gland.

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Myxoedema
• Predisposing factors:
• Infection
• CHF
• Trauma
• Exposure to cold
• Drugs
• Sedatives
• Lithium
• Amiodarone

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Diagnosis of Myxoedema

• Shows clinical features of hypothyroidism and also patients

may present with
• Hypothermia
• Altered mental status
• Coma, delusions, and psychosis (myxedema maddness)
• Hyponatraemia
• Dilutional secondary to decreased free-water clearance
• Hypotension
• Hypoglycemia
• Secondary to impaired gluconeogenesis
• Bradycardia
• Respiratory Failure
• Secondary to decreased strength of respiratory muscle
• Hypercapnia and hypoxia is common

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Diagnosis of Myxoedema cont’d

• Laboratory evaluation:
• Anemia
• Hyponatremia
• Hypoglycemia
• ↑ Transaminases
• ↑ CK
• ↑ LDH
• ↓Po2 and ↑PCo2 on ABG’s

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Goitre
• Goitre, or enlargement of the thyroid
• Endemic goiter
• Caused by dietary deficiency of Iodide
• Increased TSH stimulates gland growth
• Also results in cretinism
• Goiter in developed countries
• Hashimoto’s thryoiditis
• Subacute thyroiditis
• Other causes
• Excess Iodide (Amiodarone, Lithium)
• Adenoma, Malignancy
• Genetic / Familial hormone synthesis defects
• May be related with: normal thyroid function (euthyroid),
hyperthyroidism or hypothyroidism

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Goitre 42