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					  Functional Anatomy of the Thyroid and
           Parathyroid Glands
Thyroid        glands     are
located in the neck, in
close approximation to the
first part of the trachea.
Close examination of a
thyroid gland will reveal
one or more small, light-
colored nodules on or
protruding from its surface
- these are parathyroid
glands (meaning "beside
the thyroid").
            Thryroid Cellular Organization
 Thyroid epithelial cells - synthesis of thyroid hormones - are
arranged in spheres called thyroid follicles.
 Thyroid follicle is the functional unit of the TG and follicles are
filled with colloid, a proteinaceous depot of thyroid hormone
 The thyroid gland houses another important endocrine cell called
parafollicular / C cells and it secretes the hormone calcitonin.
 The structure of a parathyroid gland is distinctly different from a
thyroid gland. The cells that synthesize and secrete parathyroid
hormone are arranged in rather dense cords or nests around abundant
              Thyroid Physiology

•   Uptake of Iodine by thyroid
•   Coupling of Iodine to Thyroglobulin
•   Storage of MIT / DIT in follicular space
•   Re-absorption of MIT / DIT
•   Formation of T3, T4 from MIT / DIT
•   Release of T3, T4 into serum
•   Breakdown of T3, T4 with release of Iodine
                 Thyroid Glands
Secretes hormones:
     Thyroxine (T4) (98.5%   of the circulatory hormone)

     Triiodothyroxine (T3) (1.5% T3)
     Calcitonin (aids to decrease blood calcium
     level and facilitates the storage of calcium in
Total Hormone load is influenced by serum binding
     Thyroid Binding Globulin 70%
          Albumin 15%
          Transthyretin 10%
            Chemistry of Thyroid Hormones
 Thyroid hormones are derivatives of the amino acid
tyrosine bound covalently to iodine (at 3 pr 4 position).
The two principal thyroid hormones are:
thyroxine (also known as T4 / L-3,5,3',5'-tetraiodothyronine)
triiodothyronine (T3 or L-3,5,3'-triiodothyronine)

 Thyroid hormones are poorly soluble in water and more than
99% is in the bound form with carrier proteins such as Thyroxine
Binding Globulin.
Two principles for making thyroid hormones are:
1. Tyrosines are provided from a large glycoprotein
scaffold called thyroglobulin (synthesized by thyroid
epithelial cells & secreted into the lumen of the follicle -
colloid is essentially a pool of thyroglobulin). A molecule
of thyroglobulin contains 134 tyrosines, although only a
few of these are actually used to synthesize T4 and T3.

2. Iodine, or more accurately iodide (I-), is avidly taken up
from blood by thyroid epithelial cells, which have on
their outer plasma membrane a sodium-iodide
symporter or "iodine trap". Once inside the cell, iodide is
transported into the lumen of the follicle along with
• Enzyme thyroid peroxidase (TPO), an integral membrane protein
  present in the apical (colloid-facing) plasma membrane of
  thyroid epithelial cells. Thyroid peroxidase catalyzes two
  sequential reactions:
• Iodination of tyrosines on thyroglobulin (also known as
  "organification of iodide").
• Synthesis of thyroxine or triiodothyronine from two
  Through the action of thyroid peroxidase, thyroid hormones
  accumulate in colloid, on the surface of thyroid epithelial cells.
  Remember that hormone is still tied up in molecules of
  thyroglobulin - the task remaining is to liberate it from the
  scaffold and secrete free hormone into blood.
• Thyroid hormones are excised from their
  thyroglobulin scaffold by digestion in
  lysosomes of thyroid epithelial cells. This
  final act in thyroid hormone synthesis
  proceeds in the following steps:
• Thyroid epithelial cells ingest colloid by
  endocytosis from their apical borders -
  that colloid contains thyroglobulin
  decorated with thyroid hormone.
• Colloid-laden endosomes fuse with
  lysosomes, which contain hydrolytic
  enzymes that digest thyroglobluin,
  thereby liberating free thyroid hormones.
• Finally,    free     thyroid     hormones
  apparently diffuse out of lysosomes,
  through the basal plasma membrane of
  the cell, and into blood where they
  quickly bind to carrier proteins for
  transport to target cells.
                  T4        T3

  Potency          1        10

Protein Bound    10-20       1

  Half-Life       5-7d     < 24h

 Secreted by    100 ug/d   6 ug/d
Control of Thyroid Hormone Synthesis and
Regulation of the Thyroid Gland
Thyroid Hormone Actions
There is also evidence that thyroid hormones can
have rapid, non-genomic effects on membrane
receptors independent of protein synthesis. These
include stimulation of sugar transport, Ca2+ATPase
activity and increased Na+ transport in muscle. The
receptors for these effects have not been identified.

In most tissues (exceptions include brain, spleen
and testis), thyroid hormones stimulate the
metabolic rate by increasing the number and size of
mitochondria, stimulating the synthesis of enzymes
in the respiratory chain and increasing membrane
Na+-K+ ATPase concentration and membrane
Na+ and K+ permeability.
Thyroid Hormone and Metabolic Activity
Thyroid Hormones in Growth and
Symptoms                                      Signs


Anxiety and irritability (~ >90%)             Tachycardia (~ 100%)

Palpitations (~ 90%)                          Tremor (~ 95%)

Increased perspiration and heat intolerance
                                              Goiter (~ 100%)
(~ 90%)

                                              Warm moist skin (~
Fatigability (~ 80%)

Weakness (~ 70%)

Increased appetite and weight loss (~ 85%)

                             Less common

                                              Atrial fibrillation (~
Dyspnoea (~ 65%)

Increased bowel frequency (~ 30%)             Onycholysis (~ <5%)

Anorexia (~ 10%)                              ‘Liver palms’ (~ 5%)

Weight gain (~ <5%)                           Heart failure (~ 5%)

Oligomenorrhea (~ 25%)


Pruritus (~ <1%)

Periodic paralysis (~ <1%)
Tissue/organ                 Deficiency                         Excess
                 Pale, dry, puffy skin
                                                     Pink, warm, moist skin
Skin/hair        (myxedema) Dry, brittle hair,
                                                     Onycholysis of nails
                 brittle nails
                 Decreased blood volume and
                                                     Increased cardiac output,
                 cardiac output; dilated, pale,
                                                     decreased peripheral
Cardiovascular   poorly contractile myocardium;
                                                     resistance; supraventricular
                 pericardial effusion; sinus
                                                     tachycardia/atrial fibrillation
                 Pleural effusions (small),
                                                     Decreased vital capacity
                 alveolar hypoventilation in
Respiratory                                          (myopathy of respiratory
                 severe hypothyroidism,
                 obstructive sleep apnea
                                                     Increased appetite, weight
                 Modest weight gain, decreased       loss, increased motility (loose
                 motility (ileus or constipation),   motions), nausea and
Gut              small ascites, associated           vomiting (especially in
                 pernicious anemia and               pregnancy), associated
                 achlorhydria                        pernicious anemia and
                                                     achlorhydria or celiac disease
                 In childhood — poor neuronal
                                                     Nervousness, emotional
CNS              development and myelination
                                                     lability, hyperkinesia, tremor
                 In adulthood — slowed
                 intellectual functions, paranoid
                 or depressive psychiatric
                 disorder, perceptive deafness,
                 night blindness, cerebellar
                 ataxia, slow-relaxing reflexes,
Tissue/organ              Deficiency                              Excess
                                                     Weakness, fatigability, proximal
               Stiffness and aching (especially
                                                     myopathy with loss of type 2
               in cold), firm, tender muscles,
Muscle                                               myocytes; may be associated with
               myoclonus, loss of type 1 muscle
                                                     myasthenia gravis; hypokalemic
                                                     periodic paralysis
               Poor growth and maturation of         Demineralization of bone;
Skeleton       bone,    decreased urinary            increased urinary excretion of
               excretion of Ca2+                     Ca2+ and PO43-; hypercalcemia
                Renal blood flow, glomerular           Renal blood flow, glomerular
               filtration rate, tubular resorption   filtration rate and tubular
               & secretory functions, urinary        resorption and secretory function
               water excretion
                red cell mass; normochromic            red cell mass; associated
Bone marrow    normocytic anemia; associated         pernicious & macrocytic anemia
               pernicious & macrocytic anemia
               Low resting metabolic rate
               (RMR), decreased appetite,
               weight gain, cold intolerance,        Increased RMR, and appetite;
               reduced body temperature, flat        weight loss; decreased glucose
Metabolic      glucose tolerance curve with          tolerance; increased synthesis and
               delayed insulin response;             degradation of both lipids and
               increased insulin sensitivity;        proteins
               decreased synthesis and
               degradation of lipids
Abnormal Thyroid Functions
                 Thyroid Disease
• Hypothyroidism

• Hyperthyroidism

• Thyroid Nodules &
- Simple Cyst
- Multinodular goitre
- Follicular adenoma
- Follicular carcinoma
- Papillary carcinoma
- Modullary carcinoma
         Hashimoto’s (Chronic, Lymphocytic)
•   Most common cause of hypothyroidism
•   Autoimmune. Result of antibodies to TPO, TBG
•   Commonly presents in females 30-50 yrs.
•   Usually non-tender and asymptomatic.
    - Fatigue and sluggishness           - Increased sensitivity to cold
    - Constipation                       - Pale, dry skin
    - A puffy face                       - Hoarse voice
    - An elevated blood cholesterol level
    - Unexplained weight gain            - Muscle aches, tenderness and
    - Pain and stiffness in your joints and swelling in your knees or the small
    joints in your hands and feet
    - Muscle weakness especially in lower extremities
• Lab values
   – High TSH
   – Low T4
   – Anti-TPO Ab
   – Anti-TBG Ab
• Treat with Levothyroxine
• Runs in Family
• Endemic goiter
  – Caused by dietary deficiency
    of Iodide
  – Increased TSH stimulates
    gland growth
• Goiter in developed countries
  – Hashimoto’s thryoiditis
  – Subacute thyroiditis
• Other causes
  – Excess Iodide (Amiodarone,
    Kelp, Lithium)
  – Adenoma, Malignancy
  – Genetic / Familial hormone
    synthesis defects
     Subacute (de Quervain’s) Thyroiditis
• Preceding viral infection

• Infiltration of the gland with granulomas

• Painful goitre

• Hyperthyroid phase  Hypothyroid phase
               Graves' Disease

• is a thyroid disorder characterized by goiter,
  exophthalmos, "orange-peel" skin, and
        Hormone Binding Factors
• Increased TBG
   – High estrogen states (pregnancy, OCP, HRT,
   – Liver disease (early)
• Decreased TBG
   – Androgens or anabolic steroids
   – Liver disease (late)
• Binding Site Competition
   – NSAID’s
   – Furosemide IV
   – Anticonvulsants (Phenytoin, Carbamazepine)
                Parathyroid Glands
• Four small ovoid structures,
embedded in the thyroid gland
• Located on the cranial and
caudal poles of both thyroids,
having own connective tissue
• Its capsule carry in blood vessels,
lymphatics, and nerves
• Produce PTH (84 aa) to maintain
normal blood calcium level
• Parathyroid hormone-related
proteins (PTHrP, binds to same
receptor, regulate the development)
   Physiology of parathyroid hormone, PTH
• Mobilization of calcium from bone: a well-documented effect
  of parathyroid hormone is to stimulate osteoclasts to reabsorb
  bone mineral, liberating calcium into blood.
• Enhancing absorption of calcium from the small intestine:
  Facilitating calcium absorption from the small intestine would
  clearly serve to elevate blood levels of calcium. Parathyroid
  hormone stimulates this process, but indirectly by stimulating
  production of the active form of vitamin D in the kidney.
  Vitamin D induces synthesis of a calcium-binding protein in
  intestinal epithelial cells that facilitates efficient absorption of
  calcium into blood.
• Suppression of calcium loss in urine: In addition to
  stimulating fluxes of calcium into blood from bone and intestine,
  parathyroid hormone puts a brake on excretion of calcium in
  urine, thus conserving calcium in blood. This effect is mediated
  by stimulating tubular reabsorption of calcium. Another effect of
  parathyroid hormone on the kidney is to stimulate loss of
  phosphate ions in urine.
Parathyroid Hormone (PTH)
                     Disease States
• Primary hyperparathyroidism is the result of parathyroid gland
  disease, most commonly due to a parathyroid tumor
  (adenoma). Common manifestations are chronic elevations
  of blood Ca concentration (hypercalcemia), kidney stones
  and decalcification of bone.
• Secondary hyperparathyroidism is the situation where disease
  outside of the parathyroid gland leads to excessive secretion
  of parathyroid hormone. A common cause of this disorder is
  kidney disease - if the kidneys are unable to reabsorb
  calcium, blood calcium levels will fall, stimulating continual
  secretion of parathyroid hormone to maintain normal
  calcium levels in blood. Secondary hyperparathyroidism can
  also result from inadequate nutrition - for example, diets
  that are deficient in calcium or vitamin D, or which contain
  excessive phosphorus (e.g. all meat diets for carnivores). A
  prominent is decalcification of bone, leading to pathologic
• Inadequate production of parathyroid hormone -
  hypoparathyroidism - typically results in decreased
  concentrations of calcium and increased concentrations
  of phosphorus in blood. Common causes of this
  disorder include surgical removal of the parathyroid
  glands and disease processes that lead to destruction of
  parathyroid glands. The resulting hypocalcemia often
  leads to tetany and convulsions, and can be acutely life-
  threatening. Treatment focuses on restoring normal
  blood calcium concentrations by calcium infusions, oral
  calcium supplements and vitamin D therapy.

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