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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_1382_Библиотеки_им_академика_М_И_Перельмана.pdf
CONTRIBUTORS
xx
David Taı¨eb, MD, PhD
Department of Nuclear Medicine
Service Central de Biophysique et de Me´decine
Nucle´aire
Centre hospitalo-universitaire de la Timone
Marseille
France
Geoffrey B. Thompson, MD
Department of Surgery
Mayo Clinic College of Medicine
Rochester, MN
USA
Ling-Ming Tseng, MD
Department of Surgery
Taipei Veterans General Hospital
National Yang-Ming University
Taipei
Taiwan
R. Michael Tuttle, MD
Joan and Sanford I. Weill Medical College
of Cornell University
Memorial Sloan Kettering Cancer Center
New York
USA
Jon A. van Heerden, MD, FACS
Department of Surgery
Medical University of South Carolina
Charleston, SC
USA
Sam Van Slycke, MD
Department of Endocrine Surgery
Service de Chirurgie Endocrinienne
Centre hospitalo-universitaire de la Timone
Marseille
France
David Vela´zquez-Ferna´ndez, MD, MSc, PhD
Department of Surgery
Instituto Nacional de la Nutrici´on Salvador
Zubira´n
Mexico City
Mexico
Adrian Vella, MD, FRCP(Edin)
Division of Endocrinology and Metabolism
Mayo Clinic
Rochester, MN
USA
Johan Westerdahl, MD, PhD
Department of Surgery
Lund University Hospital
Lund
Sweden
Rasa Zarnegar, MD
Department of Surgery
Weill Cornell Medical College
New York
USA
Section 1
Thyroid
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1
Thyroid Embryology, Anatomy, and Physiology: A Review for the Surgeon
Todd P.W. McMullen and Leigh W. Delbridge
The thyroid gland, an obligate structure in all
vertebrates, is essential for normal development
and metabolism. As a response to the varying
maladies of the thyroid, surgeons have devised
various techniques to extirpate part or all of the
gland. Recent advances include new tools such
as the ultrasonic dissector (Harmonic scalpel)
and the electrothermal bipolar sealing system
(LigaSure) as well as the application of minimally invasive and endoscopic techniques. As
surgical approaches have evolved, so has our
understanding of the genetics of thyroid morphogenesis and the biochemistry of thyroid
function. This review integrates recent work
on thyroid physiology with our present knowledge of thyroid development and anatomical
variations.
Thyroid Organogenesis
and Anatomy
Thyroid Embryogenesis
The thyroid gland is a composite of two different cell types, the follicular cells responsible for
the production of thyroid hormones triiodiothyronine (T3) and thyroxine (T4), and
the parafollicular C cells that produce calcitonin. Thyroid follicular cells (TFC) are recruited
to the thyroid fate from the endodermal epithelium of the foregut. C-cell precursors migrate
from the neural crest to the fourth pharyngeal
pouch located symmetrically on both sides of
the neck. Specification of these two cell types
marks the beginning of the morphogenesis of
the thyroid gland. The development of the thyroid, through anatomic studies in humans and
genetic studies in mice, can be described generally in the following steps [1–6]. The first
visible manifestation of the thyroid, the thyroid
anlage, begins as a thickening of the endodermal epithelium in the midline of the primitive
pharynx at embryonic day 20 (see Fig. 1.1).
Cellular proliferation of the TFC results in a
thyroid bud that begins to migrate caudally
from the pharyngeal floor leaving a remnant of
descent known as the thyroglossal duct. The
developing thyroid will pass through, or adjacent to, the hyoid bone on its course to the
trachea (day 30–40) and the migration process
nears completion by day 45. Under normal circumstances the thyroglossal duct, which connects the thyroid to its pharyngeal origin
(known as the foramen cecum), will disappear.
Simultaneous to the thyroid migration process,
the C cells within the fourth pharyngeal pouch
have localized to a transient embryologic region
called the ultimobranchial body (Fig. 1.1). From
its lateral origin, the ultimobranchial bodies will
migrate medially from either side of the neck.
By day 70, the TFC and C cells that make up the
mature and differentiated thyroid gland have
now merged anterior to the cricoid cartilage
on the trachea. The thyroid gland then begins
J.G.H. Hubbard et al. (eds.), Endocrine Surgery, Springer Specialist Surgery Series,
DOI 10.1007/978-1-84628-881-4_1, Ó Springer-Verlag London Limited 2009
3
Fig. 1.1. Thyroid organogenesis. (top) A coronal section of the
pharyngeal arch demonstrating the thyroid anlage and diverticulum forming. Laterally, the parathyroids and thymus derive
from the third or fourth pharyngeal pouches. (bottom) As the
thyroid diverticulum migrates caudally to its final resting position, the thyroglossal duct may persist and there may be an
extensive pyramidal lobe along the line of descent. The parathyroids are localized generally as shown, with the superior
glands migrating a shorter distance than the inferior glands.
Thymic rests of thyroid tissue may also exist that may or may
not be in continuity with the gland.
4
ENDOCRINE SURGERY
to expand and the TFC, which vastly outnumber
the interspersed C cells, organize into follicles.
The final dispersion of C cells within the thyroid
is not uniform as they are concentrated within
the middle and upper thirds of the lateral lobes
of the gland [2, 7]. Functional differentiation of
the TFC, and ultimately hormone production, is
the final step in normal organogenesis. The
proteins and pathways required for hormone
synthesis are expressed once the thyroid
reaches its final location on the trachea. Mice
models demonstrate that T4 is present shortly
after folliculogenesis begins and human fetal
serum contains both thyroid-stimulating hormone (TSH) and T4 after 12 weeks.
Much of what drives thyroid morphogenesis,
as described above, has been determined from a
combination of studies on inherited disorders
of the thyroid and mice models which are considered an excellent homolog for human thyroid
development [1]. Summarized in Table 1.1 are
the functional changes undergone by TFC, and
the relevant controller genes, at the various
stages of morphological development. The
genes central to the morphogenesis of the thyroid gland and the functional differentiation of
TFC are Titf1/Nkx2-1, Foxe1, Pax8, and Hhex
[1, 8–12]. The simultaneous presence of these
four genes is the hallmark of a differentiated
thyroid cell. At the earliest stage of development, all four genes are required for the recruitment of TFC and organization of the thyroid
bud. These genes will continue to drive thyroid
development until the gland has completed
migration and begins to enlarge. At this stage
other genes are activated and pathways for hormone synthesis begin to develop (see Table 1.1).
In the 10th and 11th week it is the serial expression of genes such as Fgfr2 and Tshr that
prompts the production of thyroglobulin (Tg),
thyroid peroxidase (TPO), and the TSH
Table 1.1. Thyroid Embryogenesis
Functional differentiation Controller genes
Morphology Tg, TPO, Tshr NIS Thyroid hormones Titf1, Foxe1, Pax8, Hhex Fgfr2 Tshr NIS
Thyroid anlage – – – + – – –
Thyroid bud – – – + – – –
Expansion – – – + + – –
Folliculogenesis + – – + + + –
Hormone synthesis + + + + + + +
Source: Data from De felice M, di Lauro R. Thyroid development and its disorders: genetics and molecular mechanisms. Endocrine Rev 2004;25:722.
5
THYROID EMBRYOLOGY, ANATOMY, AND PHYSIOLOGY
receptor (Tshr) [1, 13]. By the 12th week the
sodium-iodide symporter (NIS) gene is activated and soon after the NIS is found in thyroid
cell membranes. This heralds the final step in
cellular differentiation as thyroid hormone is
detected in fetal circulation shortly after NIS
expression (week 12).
Developmental Abnormalities
of the Thyroid
Abnormalities in thyroid organogenesis, collectively termed thyroid dysgenesis (TD), may
result in thyroid ectopy, hypoplasia, hemiagenesis, or athyreosis [14–16]. In certain cases of
ectopy and hypoplasia, and in all cases of athyreosis (complete developmental failure), the
production of thyroid hormone is impaired,
resulting in congenital hypothyroidism (CH).
Clinically, CH is manifest as impaired cognitive
development and physical growth, and its phenotype is directly proportional to the duration
and severity of the hypothyroidism [16–18]. CH
is the most common endocrine disorder in newborns with an incidence of 1 in 3500 births in
iodine-sufficient regions. Ninety percent of CH
cases are due to some form of TD, while the
remaining 10% are secondary to isolated defects
in thyroid hormone synthesis [15, 16]. In cases
of hypoplastic or ectopic thyroid glands, the
function of the glands may or may not be disrupted significantly, depending on the overall
cell mass. In many cases both hypoplastic and
ectopic glands will demonstrate normal or nearnormal levels of TSH and thyroid hormone with
no clinical sign of impaired development [1].
Due to the complex relationship between thyroid function and morphology, studies of the
prevalence of the varying types of TD in CH
have documented discrepant results [1, 19, 20].
A recent review of studies using
phy or ultrasound indicates that athyreosis and
ectopy represent the vast majority of malformed
thyroid glands [1]. Most cases of TD, regardless
of phenotype, stem from isolated sporadic
mutations but there is an inheritable component as relatives of patients with TD are 15
times more likely to exhibit a thyroid anomaly
[1, 21, 22]. Interestingly, the type of thyroid
anomaly will also vary in many types of related
mutations. This suggests that mutations in a
single gene such as Foxe1 (see Table 1.1) may
99
Tc scintigra-
account for multiple different phenotypic
abnormalities including ectopy and athyreosis.
There is also evidence for postzygotic events
influencing pathogenesis as monozygotic twins
do not demonstrate the same rates or types of
TD [21]. Thus a single genotype may disrupt
thyroid development at different stages of
development causing varying phenotypes and
clinical sequelae. The genetic mechanisms
underpinning the major classes of thyroid
developmental abnormalities are outlined
below.
Athyreosis
Complete absence of TFC may stem from an
early error in the formation of the thyroid bud
or from a defect in the survival pathway of
thyroid cells. Patients lacking a developed and
functional thyroid gland may demonstrate only
cystic remnants of the thyroglossal duct without
any thyroid tissue [1, 16, 17]. However, other
patients may exhibit thyroid tissue by ultrasound. A mutation early in proliferation can
prevent the cells from completing differentiation to the mature thyroid cell capable of producing thyroid hormone. Gene knockout studies
in mice have shown definitively that mutations
to any one of the four key genes shown in
Table 1.1 will result in athyreosis. When exam-
ining for the genetic mutations in humans
responsible for these abnormalities, mutations
to the Foxe1 and Pax8 genes were found in
patients lacking a thyroid gland and Foxe1 has
Mendelian inheritance (Bamfort–Lazarus syndrome) [1].
Hypoplasia
A hypoplastic but orthotopic thyroid gland is
relatively uncommon. As in athyreosis, the
hypoplastic phenotype may stem from a significant reduction in cell mass or there may be a
metabolic defect in hormone synthesis limiting
hormone production within the cells. A broad
range of mutated genes including Titf1/Nkx2-1,
Pax8, Tshr, Hoxa-3, ET-1, Pax-3 are postulated
to attribute to hypoplastic phenotypes [1, 15].
The Tshr gene is considered a consistent cause
for the disrupting glandular growth in humans
and over 20 different mutations have been
found in familial cases of hypoplasia [1]. In
certain mutations of the Tshr gene, the cells
ENDOCRINE SURGERY
6
fail to respond to the TSH-mediated signal
for proliferation and gland expansion. Other
mutations will disrupt TSH-mediated signals
in thyroid hormone synthesis. Thus different mutations in the Tshr gene may demonstrate subclinical, mild, or severe degrees of hypoplasia with a
broad spectrum of variation of TSH and T4 levels
in affected individuals.
Hemiagenesis
In a unique subset of patients with reduced
thyroid mass, it is the left lobe that fails to
develop. Known as hemiagenesis, these patients
are uniquely different from those with hypoplasia because the function of the gland is not
significantly disturbed with both TSH and thyroid hormone levels remaining in the normal
range [1, 23]. In studies using ultrasound, hemiagenesis may occur in 0.05–0.2% of the population [23]. It is unclear in humans which genes
may be responsible, but in mouse models heterozygous for both Titf1
hemiagenesis of the thyroid has been documented [1].
+/–
and Pax 8
+/–
genes,
Ectopic Thyroid
Ectopic thyroid glands represent the largest single group of TD and perhaps are the most heterogenous in terms of morphology [1, 24–27].
Thyroid ectopia is subject to all pathology of a
normal gland and should be considered in surgical approaches to thyroid disease. Ectopic
thyroid may rest anywhere between the foramen
cecum superiorly and the mediastinum inferiorly. In most cases, the ectopic tissue is a midline position above the hyoid bone. Known as
the lingual thyroid, the gland usually functions
normally. Less frequently, the gland may descend and come to rest above or below the hyoid
bone and may even be present within the trachea. Moreover, isolated rests of thyroid or prolonged extensions of the thyroid lobe may also
be found in the thyrothymic tract. These thyrothymic rests were identified in more than half
of the surgical specimens analyzed by Sackett
et al. [28]. Lateral ectopic thyroid tissue, for
example, in the submandibular region, has also
been documented [1, 26]. This was postulated to
be a consequence of defective migration of a
lateral thyroid component from the ultimobranchial body [2, 26]. However, there is little evidence supporting follicular cell derivation in the
ultimobranchial body [1]. It is more likely that
the lateral derivation of thyroid does not exist
and the observed ‘‘lateral’’ ectopic tissue is actually a disordered remnant of the median thyroid
anlage [1]. Not limited to the neck or mediastinum, ectopic thyroid tissue has been reported in
locations including the heart, duodenum, and
ovaries [27, 29–31]. Outside the neck and mediastinum, it is unlikely for abnormal migrationto
account for thyroid ectopia. Thyroid tissue inthe
abdomen and other compartments is likely
resulted from aberrant differentiation of uncommitted cells [1]. The genetic mechanisms behind
ectopic tissue are unclear, and in humans no
single gene has been characterized as a causative
factor. In mouse models, selective disruption of
the Foxe-1 gene leads to abnormal migration and
subsequent ectopic thyroid [1].
Abnormalities of Thyroid Migration
Normally, after migration of the thyroid to the
cricothyroid, the thyroglossal tract obliterates
by day 30–40 of gestation. However, in a significant proportion of the population, the thyroglossal duct persists [1, 32, 33]. Due to varying
degrees of incomplete ablation, the midline
thyroglossal duct remnant will vary in size and
location from the foramen cecum to hyoid bone.
In the largest reported series of patients, 60% of
thyroglossal duct cysts were located adjacent to
the hyoid bone, 24% between the hyoid bone
and base of the tongue, 13% distal to the hyoid
bone, and the remaining 3% intralingual [32].
The pyramidal lobe is another anomaly of thyroid descent with TFC extending up to, and
sometimes beyond, the hyoid bone. This midline remnant may represent a small outcropping
of tissue barely distinguishable from the gland,
or it may extend up along the laryngeal cartilage
and represent a significant fraction of the overall mass of the thyroid.
Anatomy of the Thyroid Gland
and Related Structures
Driven by the perceived benefits of smaller incisions and less tissue trauma, significant effort
has been applied to developing minimally invasive approaches to thyroid and parathyroid surgery. Reduced exposure requires a thorough
understanding of the anatomical relationships
of the thyroid gland to the structures at risk
7
THYROID EMBRYOLOGY, ANATOMY, AND PHYSIOLOGY
during surgery, namely, the recurrent laryngeal
nerve (RLN), the external branch of the superior
laryngeal nerve (EBSLN) and the parathyroid
glands. This review emphasizes recent studies
on anatomical variations of these structures
and their relationship to the thyroid gland
[34–48].
Thyroid Gland
Under normal circumstances the thyroid gland
rests on the anterolateral aspect of the cricothyroid and trachea. The boundaries of the
thyroid gland are typically demarked posteriomedially by the trachea and esophagus, laterally
by the carotid sheath, and anterolaterally by the
overlying strap and sternocleidomastoid muscles. The gland itself has a bilobed shape and
typically weighs 15–25 g, depending on sex and
age. It also has an intervening bridge of tissue of
varying sizes, the isthmus, connecting each
lobe. The typical bilobed shape is preserved in
most people but the size and symmetry of the
thyroid can vary significantly and other anomalies can exist as follows. Superiorly, a pyramidal
extension of the gland may be found on the
anterior aspect of the cricothyroid. Laterally,
the tubercles of Zuckerkandl, a consequence of
median anlage and ultimobranchial body
fusion, may form significant protrusions of
thyroid tissue in the tracheoesophageal (TE)
groove. The tubercle, which ranges from inconsequential to as large as 3 cm, can be identified
in two thirds of patients undergoing thyroidectomy. Inferiorly, thyrothymic thyroid rests may
be found in over 50% of patients [28]. These are
classified by the nature of their connection to
the main body of the thyroid and may be connected to, or completely distinct from, the
gland. In pathological situation, the thyroid
can enlarge and, in some circumstances, reach
100 its normal size. Enlarging glands may
expand inferiorly into the thorax to become
retrosternal and reach as caudad as the
pericardium.
In terms of attachments and supporting
structures, the gland itself has a capsule that is
the extension of the pretracheal fascia. This
capsule has extensions within the gland that
form macroscopic lobules. The visceral fascia
of the thyroid gland is attached anteriorly to
the cricothyroid and thyroid cartilage. The
Ligament of Berry affixes the posteromedial
aspect of the gland to the underlying cricoids
and tracheal rings. The thyroid is a highly vascular gland that has a redundant arterial supply
from the superior thyroid artery (a branch of
the external carotid artery) and the inferior
thyroid artery (ITA) (a branch of the thyrocervial trunk) with abundant collaterals [38–41].
The arteria thyroidea ima is a relatively uncommon third arterial feed to the gland. Venous
drainage is via three paired vessels, the superior,
middle, and inferior thyroid veins that form a
network of collaterals that can be quite impressive in pathology such as Grave’s disease. Lymphatic drainage of the gland may extend superiorly to the delphian node or laryngeal nodes,
inferiorly to the pretracheal nodes or laterally to
the paratracheal nodes and cervical chain. Patterns of drainage based on sentinel lymph node
studies indicate that the first regional draining
bed is typically the central compartment followed by the lateral neck compartments [49].
Lastly, the gland is innervated with fibers from
sympathetic and parasympathetic autonomic
nerves that may alter aspects ofthyroid function
through changes in vascular supply.
Recurrent Laryngeal and Superior
Laryngeal Innervation of the
Cricothyroid
The RLN supplies the motor component to the
intrinsic muscles of the larynx as well as the
sensory innervation to the glottic larynx [38,
42–47]. Damage to this nerve can alter phonation and reduce volume as well as cause varying
degrees of dysphagia. Knowledge of the path of
the RLN in the neck is crucial tosafe thyroid and
parathyroid surgery. Originating from the
vagus, the left RLN arises at the level of the
aortic arch and courses through the TE groove
to the insertion point in the cricothyroid joint.
The right RLN follows the same description, but
arises at the level of the subclavian artery. Both
the right and the left RLN may run laterally or
anterior to the TE groove, and the angle of the
nerve relative to the trachea is usually more
oblique on the right side. The right RLN may
have a nonrecurring course (0.3%) and derive
directly from the vagus approaching the cricothyroid directly without traveling in the TE
groove. This is a consequence of a displaced
ENDOCRINE SURGERY
8
right subclavian arterial takeoff from the distal
aortic arch. As such, a nonrecurrent nerve is not
seen on the left except in cases of situs inversus.
It is also important to note that communicating
branches between the cervical sympathetic
chain and the RLN are common (sympathetic
inferior laryngeal nerve anastomotic branch or
SILAB). They may be mistaken at surgery for a
nonrecurrent RLN. Both left and right RLN may
give multiple smaller branches to the trachea
and esophagus as well as bifurcate or trifurcate
prior to its entry at the cricothyroid joint. As the
RLN ascends the TE groove, it crosses the ITA.
In both surgical and cadaveric dissections the
relations of the nerve and artery are complex
and variable [43–47]. The RLN may run posterior, anterior, or between the branches of the
ITA as illustrated in Fig. 1.2. Cadaveric dissections demonstrated 20 different configurations,
but the results of these studies did not agree
on the most common arrangement and there
does not appear to be a propensity for a single
Fig. 1.2. (with kind permission of Dr Levent Efe, CMI) The
path of the recurrent laryngeal nerve relative to the tubercle of
Zuckerkandl and inferior thyroid artery is complex and may be
completely posterior (A) or anterior (B) to these structures.
There are multiple variations to these two extremes depending
on the size of the tubercle and the branches of the nerve and
artery. Note that symmetry is not necessarily maintained for
right and left in a given patient.
configuration. The studies did agree that the
arrangements were not necessarily symmetrical
for the left and right sides in a given patient [42,
47]. Surgical series also demonstrated that variations in RLN and ITA anatomy should be considered normative with multiple branches of
each structure compounding the complexity of
this region [44–46, 50]. In devising methods to
complete a safe dissection of the RLN, the tubercle of Zuckerkandl has been documented as an
important landmark useful in its identification
and preservation (see Fig. 1.2). The tubercle is
situated on the posterolateral aspect of the
gland in the TE groove in proximity to the cricothyroid membrane and thus is a relatively
consistent landmark for the location of the RLN
[48, 50, 51].
The EBSLN serves as the primary innervation
to the cricothyroid muscle, and it is essential in
the production of high tones and modulating
voice frequency. This nerve arises as a branch of
the inferior vagal ganglion and descends along
the pharynx travelling medially to the carotid
then piercing the inferior constrictor muscle
before running with the superior thyroid artery
to innervate the cricothyroid muscle [52–58]. In
virtually all patients there are also communicating branches between the EBSLN and the dorsal
branch of the RLN (Galen’s anastomosis). The
significance of these are unclear and may represent sympathetic innervation although there is
evidence of motor function. The proximity of
the EBSLN to the thyroid gland has forced surgeons to devise techniques to minimize damage
to this structure while ligating the superior pole
vessels. Cernea and coworkers have completed
anatomical studies to classify the major configurations of the nerve relative to the superior
pole vessels [53–55]. Type 1 EBSLN are located
more that 1 cm from the upper pole vessels and
thus are not significantly at risk. However, Type
2a and 2b (see Fig. 1.3), comprising >1/3 of the
configurations found anatomically, are within
the range of dissection and may be disrupted
with ligation of the superior pole vessels. As
shown in Fig. 1.3b, Type 2b nerves are at considerable risk in that these nerves cross the
vessels along the thyroid parenchyma. It is
now understood that dissection utilizing the
avascular space between the cricothyroid and
the upper pole can reveal the EBSLN safely in
>90% of cases and thus preserve its function
[44, 50].
9
THYROID EMBRYOLOGY, ANATOMY, AND PHYSIOLOGY
Fig. 1.1). The majority of inferior parathyroid
glands may be found on the anterior or posterolateral aspect of the inferior thyroid lobe or
within the thyrothymic ligament. In a fraction
of cases the inferior glands may be in proximity
to the superior parathyroids or as deep as the
mediastinum.Arecentsurgicalseriesofover200
patients revealed that 16% had ectopic glands
overall, with inferior glands comprising >60%
of these cases [59]. Ectopic superior glands were
most commonly retroesophageal or in the TE
groove. Ectopic inferior glands were found primarily within the thymus, mediastinum, or
intrathyroidal. The common origin of the parathyroids and thymus with migration toward the
mediastinum is the cause for the more varied
distribution of inferior parathyroid glands.
Fig. 1.3. The external branch of the superior laryngeal nerve
as outlined by the Cernea et al. [53] For the Cernea classification 2a (A), the nerve is within the proximity of the superior
pole vessels as it travels superiorly. In configuration 2b (B) the
nerve is at significant risk during ligation of the superior pole
vessels due to its anterior tract over the thyroid gland. Type 1
nerves are more than 1 cm above the superior pole and at
decreased risk of injury (not shown).
Parathyroid Glands
The paired inferior and superior parathyroid
glands are derived from the third and fourth
pharyngeal pouches, respectively (see Fig. 1.1).
It is this embryologic derivation and the subsequent migration of these pouches that accounts
for the final location of these glands. These
glands have been studied extensively in cadaveric dissections as well as surgical case series
[59–62]. Approximately 85% of the population
has four glands, with the remaining 13% having
5 glands and a small fraction having 3
glands. The paired superior glands, migrating
a relatively short distance with the branchial
bodies, are typically found on the posterior
aspect of the middle third of each thyroid lobe,
or in a juxtacricothyroidal position. A broader
definition is that in 90% of people, the glands
are located within 1 cm of the intersection of the
ITA and the RLN [59]. The arrangement is typically symmetrical. The inferior parathyroid
glands and the thymus migrate together and
travel a longer path to their final position (see
Thyroid Physiology
The hormone products of the thyroid gland
comprise two different endocrine systems. Produced by the TFC, the thyroid hormones T3 and
T4 are essential for fetal development as well as
growth and metabolic regulation. Para-follicular C cells are responsible for the production of
calcitonin which acts in concert with parathyroid hormone (PTH) and vitamin D to regulate
serum calcium levels. The histologic organization of the gland is dominated by the TFC which
organize into follicles with a central space full of
colloid for storage of thyroid hormone.
Iodide Metabolism
One of the unique features of thyroid physiology is its requirement for iodine in the production of thyroid hormones. The importance of
iodide metabolism is perhaps best illustrated
by the work of Dobson [63], who postulated
that incremental improvements in iodine trapping, leading to more effective thyroid hormone
production, was an important evolutionary
development in Homo sapiens. Clinically, an
important relationship between iodine intake
and thyroid disease has been understood for
150 years [64–68]. Iodine is an essential dietary
requirement and deficient intake can lead to
hypothyroidism, goiter, cretinism and malignancy. Equally detrimental is iodine excess
which is associated with autoimmune thyroid