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Thyroid Gland

Physiology and
Testing
Marion Mae Pernia MD
Level II IM Resident
QCGH
LEARNING OBJECTIVES
● Discuss the anatomy and development of the thyroid
gland
● Understand the TPO axis
● Identify the different steps on thyroid hormone
synthesis
● Understand thyroid hormone action and role of serum-
binding proteins
● Review the physical examination of the thyroid gland
● Identify the different laboratory evaluation of thyroid
hormones and thyroid gland
Table of Contents

01 Anatomy & 02 The TPO axis 03 Thyroid Hormone


Development Synthesis

04 Thyroid Hormone 05 Physical 06 Laboratory


Action Examination of evaluation
the Thyroid gland
ANATOMY &
Development
• The thyroid (Greek thyreos, shield, plus
eidos, form) consists of two lobes
connected by an isthmus
• located anterior to the trachea between the
cricoid cartilage and the suprasternal
notch.
• normal thyroid is 12–20 g in size, highly
vascular, and soft in consistency

Reference: Harrisons Principles of Internal Medicine 20th ed


ANATOMY &
Development
• right lobe is normally more vascular than
the left connected by an isthmus
• major arterial blood supply:
 superior thyroid artery
 inferior thyroid artery

• Estimates of thyroid blood flow range from


4 to 6 mL/minute per gram,

Reference: William’s Textbook of Endocrinology 12th ed


ANATOMY &
Development
• thyroid gland develops from the floor of the primitive pharynx
during the third week of gestation
• developing gland migrates along the thyroglossal duct to reach its
final location in the neck
• Thyroid hormone synthesis normally begins at about 11 weeks’
gestation.

Reference: Harrisons Principles of Internal Medicine 20th ed


ANATOMY &
Development
• Development is orchestrated by the coordinated expression of several
developmental transcription factors

• Thyroid transcription factor (TTF)-1, TTF-2, NKX2-1, and paired homeobox-8 (PAX-
8)
• They dictate thyroid cell development and the induction of thyroid-specific genes
such as thyroglobulin (Tg), thyroid peroxidase (TPO), the sodium iodide symporter
(Na+/I–, NIS), and the thyroid-stimulating hormone receptor (TSH-R).

Reference: Harrisons Principles of Internal Medicine 20th ed


ANATOMY

• consists of numerous spherical follicles


composed of thyroid follicular cells that
surround secreted colloid

Reference: Guyton & Hall: Textbook of Medical Physiology, 12th edition


gulation of thyroid axis
TSH, secreted by the
thyrotrope cells of the
anterior pituitary

Reference: Harrisons Principles of Internal Medicine 20th ed


Iodine
Metabolism and
Transport

Reference: Guyton & Hall: Textbook of Medical Physiology, 12th edition


Thyroglobulin
and chemistry
of Thyroxine

Reference: Guyton & Hall: Textbook of Medical Physiology, 12th edition


Organification
and coupling

Storage

Reference: Guyton & Hall: Textbook of Medical Physiology, 12th edition


Organification
and coupling

Storage

Reference: Guyton & Hall: Textbook of Medical Physiology, 12th edition


THYROID HORMONE ACTION
Type I deiodinase

Passive difussion TRs alpha and beta

Type II deiodinase
 MCT8
 TRB2
MCT10
isoform
 Organic anion- TRa2 isoform
transporting
polypeptide 1C1
THYROID HORMONE TRANSPORT AND
METABOLISM:
Serum-Binding Proteins
• Bound to plasma proteins
• Thyroxine-binding globulin (TBG)
• transthyretin (TTR, formerly known as thyroxine-binding prealbumin,
or TBPA)
• Albumin
• The plasma-binding proteins increase the pool of circulating hormone,
delay hormone clearance, and may modulate hormone delivery to selected
tissue sites.

Reference: Harrisons Principles of Internal Medicine 20th ed


THYROID HORMONE TRANSPORT AND
METABOLISM:
Serum-Binding Proteins

• the effects of the various binding proteins are combined, ~99.98% of


T4 and 99.7% of T3 are protein-bound.
• fraction of unbound T3 is greater than unbound T4, but there is less
unbound T3 in the circulation because it is produced in smaller
amounts and cleared more rapidly than T4.
• The unbound hormone is thought to be biologically available to
tissues.

Reference: Harrisons Principles of Internal Medicine 20th ed


Reference: Harrisons Principles of Internal Medicine 20th ed
Transient increase in hCG Estrogen-induced rise in TBG

● Weakly stimulates the


TSH-R

Increased urinary iodide


Thyroid gland excretion
in Pregnancy
Alterations in the immune
system
● Leading to the onset, exacerbation
or amelioration of underlying
autoimmune thyroid disease Increased thyroid hormone by
the placenta

Reference: Harrisons Principles of Internal Medicine 20th ed


PHYSICAL EXAMINATION

Reference: Harrisons Principles of Internal Medicine 20th ed


LABORATORY EVALUATION

Measurement of Radioiodine Uptake


thyroid hormones and Thyroid Scanning

Tests to Determine the


Etiology of Thyroid Thyroid Ultrasound
Dysfunction
MEASUREMENT OF THYROID HORMONES
TSH
• a logical approach to thyroid testing is to first determine whether TSH is
suppressed, normal, or elevated
• This strategy depends on the use of immunochemiluminometric assays
(ICMAs) for TSH that are sensitive enough to discriminate between the
lower limit of the reference interval and the suppressed values that occur
with thyrotoxicosis.
• Extremely sensitive assays can detect TSH levels ≤0.004 mIU/L, but, for
practical purposes, assays sensitive to ≤0.1 mIU/L are sufficient.

Reference: Harrisons Principles of Internal Medicine 20th ed


MEASUREMENT OF THYROID HORMONES
• Automated immunoassays are widely available for serum total T4 and total T3
• It is useful to measure the free, or unbound, hormone levels, which correspond to the
biologically available hormone pool.
• Two direct methods are used to measure unbound thyroid hormones:
• (1) unbound thyroid hormone competition with radiolabeled T4 (or an analogue) for binding to
a solid-phase antibody
• (2) physical separation of the unbound hormone fraction by ultracentrifugation or equilibrium
dialysis.
• Indirect methods:
(1) calculate the free T3 or free T4 index from the total T4 or T3 concentration and the thyroid
hormone binding ratio (THBR)

Reference: Harrisons Principles of Internal Medicine 20th ed


MEASUREMENT OF THYROID HORMONES

• the unbound T4 level is sufficient to confirm thyrotoxicosis, but 2–5% of patients have only an
elevated T3 level (T3 toxicosis).
• Subnormal TSH levels:
• the first trimester of pregnancy (due to hCG secretion), after treatment of hyperthyroidism
(because TSH can remain suppressed for several months), and in response to certain
medications (e.g., high doses of glucocorticoids or dopamine).

Reference: Harrisons Principles of Internal Medicine 20th ed


Etiology of Thyroid Dysfunction

• the unbound T4 level is sufficient to confirm thyrotoxicosis, but 2–5% of patients have only an
elevated T3 level (T3 toxicosis).
• Subnormal TSH levels:
• the first trimester of pregnancy (due to hCG secretion), after treatment of hyperthyroidism
(because TSH can remain suppressed for several months), and in response to certain
medications (e.g., high doses of glucocorticoids or dopamine).

Reference: Harrisons Principles of Internal Medicine 20th ed


Radioiodine Uptake

Reference: Harrisons Principles of Internal Medicine 20th ed


Thyroid scintigraphy

Reference: Harrisons Principles of Internal Medicine 20th ed


Reference: Harrisons Principles of Internal Medicine 20th ed
References:
Thank you for your kind
attention.
Have a pleasant evening
doctors

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