ENDOCRINE PART 2

ANTERIOR (PITUITARY)
1. Growth hormone
2. Prolactin
3. Thyrotropic
4. Adrenocorticotropic
5. Gonadotropic hormones PITUITARY DWARFISM

GROWTH HORMONE
 Effects is directed to the growth of
skeletal muscles and long bones of
the body
 Hyposecretion: pituitary dwarfism
(adult height of 4 feet)
 Hypersecretion: gigantism (8-9 feet)
 Acromegaly – occurs after long bone
GIGANTISM
growth has ended, particularly the
lower jaw and the bony ridges INCREASE SECRETION OF GROWTH
HORMONE
ABNORMALITIES ASSOCIATED WITH
GROWTH HORMONE  Short life span leading to suffer
hyperglycemia and ketosis due to
 Decrease secretion: before puberty metabolic effects of hormones
 Before puberty – giantism
 Pituitary dwarfism – no growth
 After puberty – Acromegaly – lateral
hormone receptor, abnormal growth growth, spade like hands & feet
of cartilage  Prognantism - enlargement of jaw or
 Cretinism – normal growth hormone mandible
levels but thyroid hormone is deficient  Macroglasia – enlargement of the
(ugly dwarf – cretin) tongue

Cretinism
 ACROMEGALY
PROLACTIN
 Known target in human is the breast
 After birth, it stimulates and maintains
milk production by the mother’s breast
MELANOCYTE STIMULATING HORMONE
 MSH may resemble ACTH and
responsible for the darkening and
pigmentation of the skin (Addison’s
disease & Nelson’s disease since
there is hypersecretion of ACTH)
 Target cells are the melanocyte

Wonders of Melanocyte Stimulating

Hormone

ADRENOCORTICOTROPHIC HORMONE
(ACTH)

 Regulates the endocrine activity of

the cortex portion of the adrenal gland
GONADOTROPIC HORMONES
LUTEINIZING HORMONE
 Luteinizing Hormone (LH, also
known as lutropin) is a hormone
produced by the anterior pituitary
gland.
 In the female, an acute rise of LH –
the LH surge – triggers ovulation
 In the male, where LH had also been
called Interstitial Cell Stimulating
Hormone (ICSH), it stimulates Leydig
cell production of testosterone
FSH
 Follicle – stimulating Hormone
(FSH) is a hormone synthesized and
secreted by gonadotropes in the
anterior pituitary gland
 FSH regulates the development,
growth, pubertal maturation and
reproductive processes of the human
body
 FSH and Luteinizing Hormone (LH)
act synergistically in reproduction.
 A lobe in the forebrain, secretes
melatonin hormone
 In mammals, the amount of light
influence the pineal’s secretion of
melatonin in an inverse relationship,
the more light the less melatonin
 Melatonin, in turn inhibits the release
of gonadotrophic hormones.
THYROID GLAND
 Located in front of and each side of
the thyroid cartilage of the larynx
 The hormone stimulates general
metabolism & growth
 Increase in sensitivity of various
organs especially the CNS
 Has pronounced effect on the change
from infertile to adult form
 Controlled by anterior lobe of the
pituitary

PINEAL GLAND

ANATOMY
 Consists of 2 lobes located in the
lower part of the neck
 Lobes are connected by a narrow
band called isthmus (right lobe
larger than left)
 Lobes weigh 20-30 g each
measuring 4.0 cm. In length and 2
cm to 2.5 cm in width
 2 types of cells are follicular
(cuboidal) & perifollicular cells
 Follicular cells are secretory &
produce thyroxine (T4) and
triiodothyronine (T3)
COLLOID MATRIX - THYROGLOBULIN
 The perifollicular cells or C cells
are situated in clusters along
interfollicular or C cells
 C cells produce Calcitonin - involve
in calcium regulation
THYROID HORMONE
– Majority of circulating hormone is T4
 98.5% of T4
 1.5% of T3
– Total Hormone load is influenced by
serum binding proteins (TBP,
Albumin??)
 Thyroid Binding
Globulin 70%
 Albumin 15%
 Transthyretin 10%
– Regulation is based on the free
component of thyroid hormone
FEEDBACK REGULATION THE
HYPOTHALMIC – PITUITARY – THYROID
AXIS
 Hormones derived from the pituitary
that regulate the synthesis and/or
secretion of other hormones are
known as trophic hormones.
 Key players for the thyroid include:
1. TRH – Thyrophin Releasing
Hormone
2. TSH – Thyroid Stimulating
Hormone
3. T4/T3 – Thyroid Hormones
Thyroid Hormone Control
THYROID (CONT.)
 Regulates basal metabolic rate
 Improves cardiac contractility
 Increases the gain of catecholamines
 Increases bowel motility
 Increases speed of muscle
contraction
 Decreases cholesterol (LDL)
 Required for proper fetal neural
growth
BIOSYNTHESIS, TRANSPORT, AND
ACTION
 Iodine is the most important element
in the biosynthesis of thyroid
hormones
 Thyroid gland traps iodide 70
mg/day for active transport.
 Iodide is then transported to the
follicular lumen
 Iodide molecule is oxidized by
perioxidase and transform into
reactive form I0 or I + and combine
with glycoprotein thyroglobulin
(thyroid follicle)
 Thyroglobulin acts as matrix
containing tyrosyl group to which
iodine attaches to form
 Monoidotyrosine (MIT) and
Diiodotyrosine (DIT)
 Next step is the enzymatic coupling
of the iodinated tyrosine molecules
catalyzed by peroxidase to form T4 or
T3.
 1 DIT + 1 MIT = T3 (3,5,3’
triiodothyronine or reverse T3 (rT3)
(3,3’,5’ triiodothyronine) which is
form from peripheral deiodination of
T4.
 T3 - contains 2 iodine atoms in the
tyrosyl ring and one iodine atom in
phenolic ring
 rT3 – contains 2 iodine atom in the
phenolic ring and one iodine atom
in the tyrosyl ring.
 2 DIT molecules = T4 (thyroxine”)
50% greater than T3 and bound to
serum proteins
 Most iodothyronine (T3 & T4) are
secreted directly in the blood stream
while iodothyrosines (MIT and DIT)
are deiodinated within the thyroid and
the iodide is used in producing
iodoamino acids.
TSH REGULATION OF THYROID
FUNCTION
 TSH binds to specific cell
surface receptors that
stimulate adenylate cyclase
to produce cAMP.
 TSH increases metabolic
activity that is required to
synthesize Thyroglobulin (Tg)
and generate peroxide.
 TSH stimulates both I- uptake
and iodination of tyrosine
resides on Tg.
ION TRANSPORT BY THE THYROID
FOLLICULAR CELL
THYROGLOBULIN SYNTHESIS IN THE
THYROID FOLLICULAR CELL
THYROID HORMONES IN THE BLOOD
 Approximately 99.98% of T4 is bound
to 3 serum proteins: Thyroid Binding
Globulin (TBG) ~ 75%; Thyroid
Binding Prealbumin (TBPA or
transthyretin) 15-20%; Albumin - 5-
10%
 Only ~ 0.02% of the total T4 in blood
is unbound or free.
 Only ~ 0.4% of total T3 in blood is free
THYROID HORMONE METABOLISM
THYROID PHYSIOLOGY
 Uptake of iodine by the 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
SPECIFIC ACTIONS OF THYROID
HORMONE: METABOLIC
 Regulates of Basal Metabolic
Rate (BMR)
 Increases oxygen consumption in
most target tissues.
 Permissive actions: TH increases
sensitivity of target tissues to
catecholamines, therevy elevating
lipolysis, glycogenolysis, and
gluconeogenesis.
SPECIFIC ACTIONS OF THYROID
HORMONE: DEVELOPMENT
 TH is critical for normal
development of the skeletal
system and musculature
 TH is also essential for normal
brain development and regulates
synaptogenesis, neuronal
integration, myelination and cell
migration
 Cretinism is the term for the
constellation of defects resulting
from untreated neonatal
hypothyroidism.
EXAMPLES OF THYROID DISEASES  Specimens are collected in clot tube
(red or yellow)
 Not fasting
 Serum separated after clotting but if
delayed refrigerate for 24 hours or
frozen for 30 days
 Specimen are free of lipemia and
hemolysis are preferred.

5 CATEGORIES OF TEST
1. Those that assess the state of the
hypothalamic – pituitary –thyroid axis
2. Estimates of T3 and T4
concentrations in the serum
3. Tests that reflect the impact of thyroid
hormone on tissues
4. Tests for the presence of autoimmune
thyroid disease
5. Tests that provide information about
thyroidal iodine metabolism

 TOTAL THYROXINE (TT4)

 When there is an increase
more T4 will bind resulting
increase TT4
 Decrease results in less
binding sites which decreases
TT4
 Factors: serum concentration
of T4, pregnancy, acute
illnesses or effects of drugs

 THYROID HORMONE RATIO OR T3

UPTAKE (T3U) TEST
 THBR is used to measure the
available binding sites of the
ASSAYS FOR THYROID FUNCTION thyroxine binding proteins
(TBG)
 Assays for thyroid hormones used to  I125, enzyme, fluorophore and
determine and confirm the nature and chemiluminescence labelling
extent of hyperthyroidism or techniques is used.
hypothyroidism
  Serum is mixed with labelled
T3 and a binding material
such as resin.
 CALCULATED FREE THYROXINE
INDEX (FT4I)
 TT4 and THBR are test used to
calculate the level of free
thyroxine (FT4)
 FT4I - is an indirect measure of
free hormone concentration and is
based on the equilibrium
relationship of bound T4 and FT4
 Useful in correcting euthyroid
individual
 Adequate indicator thyroid status.
 MEASURED FREE THYROXINE
(FT4)
 Most reliable in severe NTI or
susceptible thyroid disease
 Specific in differentiating euthyroid
 Differentiating hyperthyroid from
hypothyroid
 TSH TEST
 First and best laboratory test for
identification of thyroid
abnormalities
 Most important thyroid function
test & screening test
 Confirmation of suspected
primary hypothyroidism &
hyperthyroidism and also
borderline cases
 Subclinical hyperthyroidism –
abnormal TSH, normal TT4 or
FT4 no overt symptoms
 THYROID RELEASING HORMONE
(TRH) STIMULATION TEST –
THYROTROPIN RELEASING
HORMONE
 Detects residual TSH stores in the
pituitary gland
 Patients with primary hypothyroidism
would have an increase value
 Differentiating between NTI sick and
hyperthyroid patients
 Euthyroid patients will respond to
TRH whereas hyperthyroid will not
– Increased TSH
 Primary hypothyroidism
 Hashimoto’s thyroiditis
 Thyrotoxicosis due to pituitary
tumor
 TSH antibodies
 Thyroid Hormone resistance
– Decreased TSH
 Primary hyperthyroidism
 Secondary and Tertiary
hypothyroidism
 Treated Grave’s disease
 Euthyroid sick disease
 Over replacement of thyroid hormone
in hypothyroidism
 THYROGLOBULIN ASSAY (Tg)
 Used as post-operative marker of
thyroid cancer
 Used in monitoring the course of
metastatic or recurrence of thyroid
cancer
 Decreased levels: infants with
goitorous hypothyroidism,
thyrotoxicosis
  Increased: untreated and
metastatic differentiated thyroid
cancer and hyperthyroidism
 THYROID BINDING PROTEIN (TBG)
AND THYROGLOBULIN
 Used to measure to confirm
results of FT3 or FT4 or
abnormalities in the relationship of
the TT4 and THBR test
 Thyroglobulin – used as
postoperative marker of thyroid
cancer
 Low level may indicate the
presence of thyrotoxicosis
 TOTAL T3 (TT3) FREE T3 (FT3)
AND FREE T3 INDEX (FT3I)
 T3 levels clinically relates the states
of the patient
 TT3 level or FT3 used to confirm
hyperthyroidism especially in T3
thyrotoxicosis in which TSH is
decreased but the FT4I or FT4 is
within normal
 FT3I= T3 x THBR
 REVERSE T3 (RT3)
 Help in the resolution of borderline or
conflicting laboratory results
 Elevated in patients with NTI in which
TT3 levels is decreased.
 Amniotic diagnosis of rT3 is useful
in diagnosis of fetal hypothyroidism
and thyroiditis
 THYROID ANTIBODIES
 Thyrotropin receptor (TSHR)
 Thyroperoxidase (TPO) /
antimicrosomal antibodies
 Antithyroglobulin antibodies
 Thyroid disease produce
antibodies against thyroid follicles
 RADIOACTIVE IODINE UPTAKE
(RAIU) AND THYROID SCAN
 RAIU – used to measure the
ability of the thyroid gland to trap
iodine
 Radioactive iodine – is ingested
by mouth and radioactivity is
counted as various length of time
(2 – 4 – 6 – 24 hrs)
 Useful in helping to determine the
cause of hyperthyroidism
 THYROID SCAN
 Used to determine the size,
shape, activity of thyroid tissue or
nodules
 An isotope is administered to the
patient and is taken up by the
thyroid gland and distribution is
measured by a scan
 The scan is useful in determining
hyperthyroidism and extrathyroid
iodide concentrating tissue
 Important in Identification of areas
where decrease or increase
uptake within the gland
 Nodules as small as 1 cm can be
detected
1. Cold – non-functioning
2. Hot – hyperfunction
3. Warm – normal functioning
  FINE NEEDLE ASPIRATION
 Provide the malignant potential of
thyroid nodule
 RECOMBINANT HUMAN TSH
 Used to patients with thyroid cancers
for the presence of residual or
recurrent disease.
*Serum Calcitonin Test – tumor marker for
detecting residual thyroid metastasis in
medullary thyroid carcinoma (MTC)
 TANNED ERYTHROCYTE
HEMAGGLUTINATION MTD
 Test for antithyroglobulin antibodies.
REMEMBER:
 Free T4 and TSH are the best
indicator of thyroid status
 Free T3 and T4 are more specific
indicators of thyroid function than the
measurements of total hormone
because the values are not affected
by the TBG amount
 Patients with increased T4 binding
protein have an elevated T3 or T4
but not free T4 or TSH
THYROID DISORDERS AND CLINICAL
CORRELATIONS
 Hypothyroidism – insufficient levels
of thyroid hormones to provide
metabolic needs at cellular level
 Affects four times more than
female
 Slows down metabolic process
 Symptoms: enlargement of the
thyroid (goiter), impairment of
cognition, fatigue, slowing of
physical & mental performance,
change in personality, intolerance
to cold, exertional dyspnea,
hoarseness, constipation,
decreased sweating, easy
bruising, muscle cramps & dry
skin
 Associated with increased
cholesterol LDL, apoB &
increased risk of coronary disease
 Myxedema
 Worsen hypothyroidism
 Described as peculiar nonpitting
swelling of the skin, puffy
appearance of the face especially
around the eyes
 Skin is dry has a yellowish color,
body hair is lost, scalp hair often
becomes dry and coarse
 Progressive mental deterioration
 Atherosclerosis is accelerated
due to accumulation of TAG &
CHOLE
*Anemia – normocytic
normochromic
 Congenital Hypothyroidism /
Cretinism
 Caused by hormone dysgenesis
 Puffy face, open mouth with
enlarged protruding tongue,
hoarse cy, short thick neck,
narrow forehead, pug nose,
short legs, distended abdomen,
hirsutism & lethargy, mental
retardation if treatment is not
done
 TT4 is the primary screening
test, TSH is confirmatory &
detects TBG deficiency.
Ge
 ACQUIRED HYPOTHYROIDISM
 Inadequacy of hormone due to
damaged thyroid gland
 Due to: chronic thyroiditis,
surgical or radioactive iodine
treatment of hyperthyroidism,
goiter, or cancer, idiopathic
atrophy, and other proliferative
disorder.
 CHRONIC AUTOIMMUNE
THYROIDITIS (HASHIMOTO’S
DISEASE)
 Most common cause of primary
hypothyroidism (unidentified
abnormality in the immune
system)
 The patient is either euthyroid or
hypothyroid
 There is a massive infiltration of
thyroid by lymphocytes
 Plasma cells are abundant &
increased amount of connective
tissue
 Clinical Hypothyroidism (primary
or secondary) – decreased s-TSH,
TT4, FT4, TRH to differentiate
secondary to tertiary
 HYPERTHYROIDISM
 Thyrotoxicosis – is a group of
syndromes caused by high
levels of free thyroid hormones.
 Symptoms include nervousness,
irritability, insomnia, fine tremor,
excessive sweating, heat
intolerance, flushed face, pruritis,
tachycardia, palpations, frequent
bowel movements, hyperkinesis,
gynecomastia, oligomenorrhea to
amenorrhea, decreased libido,
loss of muscle mass, decreased
cholesterol, tendency towards
ketosis.

 SUBCLINICAL HYPOTHYROIDISM
 Mild elevation of TSH with normal
T4, T3 and FT4
 May result to adjustment from NTI
or pregnancy

LABORATORY EVALUATION

 TSH Concentration – primary

hypothyroidism
 Progression: decreased FT4I, FT4,
TT4, TT3, rT3
 Thyroid TPO and antithyroid
antibodies can rule out autoimmune
disease
  THYROID STORM
 Known as thyrotoxic crisis – a life
threatening complication with
fever & tachycardia & neurologic
changes

CAUSES OF THYROTOXICOSIS
1. Increased RAIU – grave’s disease,
toxic multinodular goiter, TSH
secreting tumor, trophoblastic tumor &
toxic adenoma
2. Decreased RAIU – subacute
thyroiditis, chronic thyroiditis,
metastatic thyroid carcinoma

 EUTHYROID SICK
 Results from inactivation of 5’-
Deiodinase resulting in
conversion of FT4 or rT3
 Generally occurs in critically ill
patients but may occur with DM,
malnutrition, iodine loads, or
medications (Amiodarone, PTU,
glucocorticoids)
 Treatment
- Avoid above medication
- Treat primary illness
- T2, T4 not helpful