CLINICAL CHEMISTRY II TERM02

LECTURE / BSMT MED202

ENDOCRINOLOGY
─ In endocrinology, we will tackle a lot of HORMONES
various endocrine organs that is essential in ─ A chemical substance produced by a
the body’s metabolism and daily function specific endocrine gland which has a
─ There are two major controlling systems in specific regulatory effect on the activity of
the body: Nervous System and Endocrine an organ or organs
System ─ They will give chemical signals produced by
• Nervous System specialized cells secreted into the blood
o regulates the activity of muscles and stream, carried into the target of action.
glands by means of Can be a free hormone or bound to
electrochemical responses transport protein.
delivered by neurons ─ The major function of regulation for
• Endocrine System hormones is to maintain the constancy of
o Influences the metabolic activities of chemical composition between ECF
cells by means of hormones which (Extracellular Fluid) and ICF (Intracellular
are chemical messengers Fluid)
─ Also known as “Chemical Messengers”
ENDOCRINOLOGY
─ Study of the function and pathology of the HORMONE REGULATION
endocrine system ─ Positive feedback mechanism
─ Endocrine System • ↓ product = ↑ activity, ↑ production rate
• Group of ductless glands that secrete • Enhances the original stimulus to
hormones necessary for normal growth accelerate the activity depending on the
and development, reproduction, and needs of the body
homeostasis of the body. • Ex: When a baby is about to be born,
─ Endocrine Glands the oxytocin is to be released more on
• Ductless glandular structures that more because the cervix need to have
release their hormonal secretions into more contractions. The process will
the extracellular space where they work to increase on product which will
access circulating plasma, in turn there then stimulate the production of another
will be an effect in our body’s functions. product.
• This positive feedback loop refers to the
ENDOCRINE GLANDS greater stimulation a gland receives, as
─ Pineal glands a result, more hormone is produced.
─ Parathyroid Glands ─ Negative feedback mechanism
─ Adrenal Glands • ↑ product = ↓ activity, ↓ production rate
─ Pancreas • More common in hormones
─ Hypothalamus • This is good when it comes to
─ Pituitary Gland homeostasis because it gives an
─ Thyroid Gland internal stability or equilibrium.
─ Thymus • Ex: An increase in body temperature,
─ Ovaries this will be detected by the control
─ Testes center of the brain which is the
Note: These are arranged in chronological Hypothalamus. This will then send
order based on the importance or function signals that will cause vasodilation to

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release heat to the skin surface. If the CLASSIFICATION OF HORMONES
normal temperature is not achieved, – According to Action
then sweating will occur through the – According to Composition
activation of various sweat glands then – According to Interaction
you will be sweating as an evaporation – According to Tissue Origin
of water from the skin and has a
powerful cooling effect. After the body ACCORDING TO ACTION
has returned to the normal body Type Site of Site of Action
temperature, the Hypothalamus will Secretion Release
receive a signal that the temperature is Endocrine One Blood Binds to
normal which will then trigger the location circulation specific
negative feedback mechanisms. receptor to
Hypothalamus will stop the heat loss elicit
because the body does not need to physiologic
al response
reduce heat anymore.
Paracrine Endocrine Interstitial Binds into
CHARACTERISTICS OF HORMONES cells space specific
─ Produced by a specific tissue receptor in
─ Released directly from the tissue into the adjacent
cell and
bloodstream and carried to the site of affects its
action. function
─ Act at a specific target site or sites to Autocrine Endocrine Interstitial Binds into
induce biochemical changes. cells space specific
─ There will always be a stimulus that will receptor on
trigger the release of specific hormones cell of origin
especially when there are unusual events resulting to
self-
on the body. regulation
of its
FUNCTIONS OF HORMONES function
─ Maintain homeostasis Juxtacrine Endocrine Remains Acts on
• Regulation of blood glucose (insulin, cells in relation immediate
glucagon, cortisol, epinephrine) to plasma adjacent
membrane cell by
o Depends if the glucose levels are direct cell-
increased or decreased to-cell
• Regulation of serum calcium (PTH) contact
• Water and electrolytes metabolism Exocrine Endocrine Lumen of Affects
(aldosterone, renin, ADH) cells gut function in
─ Regulate growth and development gut
Neurocrine Neurons Extracellul Binds to
• Gonadal steroid, grow hormone, ar space receptor in
cortisol, thyroxine nearby cell
─ Promote sexual maturation, sexual rhythms and affects
and facilitate reproduction its function
─ Regulate energy production Neuroendo Neurons Nerve Interacts
─ Adapt/adjust the body to crine endings with
stressful/emergency situations receptor of
cells at
─ Promote/inhibit production or release of distant site
other hormones

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 ENDOCRINOLOGY
─ Endocrine has the longest half-life ─ Interact with membrane-associated
because it has to enter the bloodstream receptors and use a 2nd messenger system
and travel to the target site. ─ Derived from amino acids and intermediary
─ Autocrine has the shortest half-life it is between steroid and protein hormones.
secreted into its cell of origin being ─ Examples:
targeted. • Epinephrine, Norepinephrine, T3, T4,
Serotonin
ACCORDING TO COMPOSITION
POLYPEPTIDES OR PROTEINS ACCORDING TO INTERACTION
─ Water soluble and circulate freely in SYNERGISTIC
plasma bound to carrier protein ─ 2 or more hormones are
─ Short half-life (<10 to 30 mins) additive/complementary in effect
─ Cannot cross the cell membrane ─ More than 1 hormone produces the same
• Produce their effects in the outer effect on the target cell and they
surface of the cell complement well.
─ The concentration of polypeptides or ─ Example: Thyroid hormone + Growth
proteins fluctuate depending on the hormones; Glucagon + Epinephrine
physiological circumstances. • Glucagon and epinephrine both cause
─ Initiates response by binding to cell the liver to release glucose. When
membrane receptor and triggering a combined, the liver release glucose
“second messenger” system. more than the usual.
─ Ex:
• Glycoprotein – FSH, hCG, TSH, ANTAGONISTIC
Erythropoietin ─ Effect of one hormone is against the
• Polypeptides – ACTH, ADH, GH, action of another
Angiotensin, Calcitonin, ─ Example: Insulin and glucagon; Insulin
Cholecystokinin, Gastrin, Glucagon, decreases glucose level while glucagon
insulin, MSH, Oxytocin, PTH, Prolactin, increases glucose level.
Somatostatin.
PERMISSIVE
STEROIDS ─ 1 hormone will enhance the
─ Lipid molecules that have cholesterol as a responsiveness of a target to another
common precursor hormone
─ Hydrophobic and insoluble in water ─ Example: ↑ Thyroid hormone → ↑ response
─ Half-life: 30 to 90 mins to catecholamine; Epinephrine +
─ Circulates in plasma, but not bound to Norepinephrine
carrier protein • Increase in thyroid hormone will
─ Enter the cell by passive diffusion and bind increase the response to catecholamine
with intracellular receptors in the cytoplasm • Thyroid hormone is necessary for
or in the nucleus. normal timely development of
─ Ex: Aldosterone, Cortisol, Estradiol, reproductive structure by reproductive
Estrone, Progesterone, Testosterone hormones. Without thyroid hormone,
reproductive system development is
AMINES being delayed.
─ Water soluble and circulates in plasma ─ Permissiveness, in which the presence of
─ Half-life: one hormone is required in order for
• Protein-bound: 7-10 days another hormone to exert its full effect on
• Free and unbound: <1 minutes target cell.

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ACCORDING TO TISSUE ORIGIN HYPOTHALAMUS: FUNCTIONS
─ Hypothalamus – TRH, GnRH, CRH 1. Direct control of autonomic nervous
─ Anterior Pituitary – TSH, ACTH, FSH, LH, system (visceromotor behaviors)
prolactin, GH • Parasympathetic and sympathetic
─ Posterior Pituitary – Vasopressin, effects
Oxytocin • Thermodetectors, chemoreceptors
─ Adrenal Medulla – Epinephrine, 2. Communication with limbic
Norepinephrine system/midbrain
─ Adrenal Cortex – Cortisol, Aldosterone • Hunger and satiety centers, drinking
─ Parathyroid – PTH center
─ Thyroid – T3, T4, calcitonin • Circadian rhythms (Sleep/wake
─ Pancreas – Insulin, Glucagon patterns, arousal, biological clock)
─ Ovaries – Estrogen • Emotions (Fear, rage, aversion,
─ Testes – Testosterone, Other androgens pleasure or reward)
3. Hormonal control of endocrine system
TYPES OF HORMONE INTERACTION • Release/release-inhibiting factors for
─ Potentiation Reaction homeostatic control of pituitary
• The presence of 1 hormone increases hormones (LH, FSH, ACTH, TSH)
the action of another. • Osmoreceptors – vasopressin and
─ Stimulatory Reaction oxytocin
• Presence of 1 hormone stimulates the • Gonadal hormones
secretion of another.
─ Inhibitory Reaction HYPOTHALAMUS: HORMONES
• Presence of 1 hormone inhibits the
secretion of another. Hormone Action
Thyrotopin Releases TSH and
HYPOTHALAMUS releasing hormone Prolactin
─ Hypothalamus is the link between the (TRH)
nervous system and the endocrine system. Gonadotropin Release LH and FSH
─ Integrative center for many homeostatic releasing hormone
circuits. (GnRH)
─ Portion of brain located in the walls and Corticotropin Releases ACTH
floor of the third ventricle. releasing hormone
─ Located above the pituitary gland (CRH)
connected to the posterior pituitary by the Growth Hormone Releases GH
infundibulum (pituitary stalk). Releasing
• Infundibulum contains a number of small hormone (GHRH)
nuclei with a variety of functions Somatostatin Inhibits GH and TSH
release
Dopamine Inhibits prolactin
release

PINEAL GLAND
─ Attached to the midbrain
─ Gland that releases melatonin (sleep
hormone)
─ Secretions of pineal gland are controlled by
nerve stimuli
• Pineal gland follows a cycle
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PITUITARY GLAND
─ “Master Gland”
─ Also known as “True Endocrine Gland”
─ Regulates the release and production of
various hormones
─ Also called Hypophysis
• -physis is used to denote growth or
nature
─ Main body of the pituitary is contained in a
small bony cavity called sella turcica
(“Turkish saddle”) surrounded by dura
mater
─ Pituitary Gland is responsible for some of
the body’s feedback loops, vasotile
secretions, diurnal rhythms, and
environmental or external modifications of
its performance
PITUITARY GLAND: ANATOMY
─ Anterior pituitary (adenohypophysis)
• Hormones which target other endocrine
glands
─ Intermediate lobe (pars intermedialis)
• Little functional capacity
─ Posterior pituitary (neurohypophysis)
• Stores and releases oxytocin and
vasopressin (ADH) when needed by the
body
PITUITARY GLAND: ANTERIOR PITUITARY
─ This classification depends on the color
reaction using H&E stain
─ Acidophil (red color rxn)
• Somatotrophs: Growth hormone
• Lactotrophs/mammotrophs: Prolactin
─ Basophil (blue color rxn)
• Thyrotrophs: Thyroid stimulating
hormones (TSH)
• Gonadotrophs: Follicle stimulating
hormones & Luteinizing hormone (FSH
&LH)
─ Chromophobe cells (no color rxn)
• Corticotrophs: adenocorticotrophic
hormone (ACTH)
HYPOTHALAMIC – HYPOPHYSEAL UNIT
─ Response pattern characteristics
• Open-look negative feedback
mechanism
o Influenced by higher neural input or
other hormones
• Pulsatility
o For all anterior pituitary hormones
o Example: GnRH -> LH and FSH
• Cyclicity
o Circadian/diurnal rhythm – internal
biologic clock
o Example:
▪ ↑ACTH 6am to 9 am; ↓ACTH
11pm to 3am
▪ ↑TSH at night; ↓TSH in the
morning
PITUITARY GLAND: HORMONES
─ The ff. are hormones produced by two
areas of Pituitary gland
─ Anterior Pituitary
• Growth hormone (GH)
• Follicle-stimulating hormone (FSH)
• Luteinizing Hormone (LH)
• Thyroid-stimulating hormone (TSH)
• Adrenocorticotropic hormone (ACTH)
• Prolactin (PRL)
─ Posterior Pituitary
• Oxytocin
• Anti-diuretic hormone (ADH)
ANTERIOR PITUITARY HORMONES
─ May be peptides or glycoproteins
─ Types of cells:
• Somatotropes – secrete GH
• Lactotropes or mammotropes – secrete
PRL (Prolactin)
• Thyrotropes – secrete TSH
• Gonadotropes – secrete FSH and LH
• Corticotropes – secrete ACTH
─ Classification:
• Tropic Hormones
o Acts specifically for another
endocrine gland
o Ex: FSH, LH, TSH, ACTH
o FSH – Stimulates ovaries to produce
eggs or ova in women and sperm
production in men
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o LH – helps in regulating testosterone hypoglycemia may occur if both Grown
in males and estrogen in females Hormone and ACTH are deficient
o ACTH – stimulates the suprarenal
gland that produce cortisol. ACTH is STIMULATORS
a hormone that has circadian/diurnal Growth hormone is the one with the highest
rhythm. Triggers the pulse amplitude concentration in all of the pituitary hormones.
not pulse alterations in the pulse It is also secreted in episodic burst which
frequency means during early sleep, few hours after
o Cortisol is a stress hormone which eating, and after exercise are the times when
means production of it is triggered by secretion of GH is high.
stressful situations. − Meals
• Direct effector hormones − Exercise
o Acts directly on peripheral tissue − Sleep
o Ex: GH for bones and muscle, PRL − Hypoglycemia
for mammary gland − Major stimulus: Deep sleep = Markedly
increased GH
GROWTH HORMONE
− Also called somatotropin INHIBITORS
• Structurally related to Prolactin and − Glucose loading
Human Placental Lactogen − Epinephrine
− Promotes growth of the body by affecting − Emotional/psychogenic stress
protein hormone formation, cell − Nutritional deficiencies
multiplication and differentiation − Insulin deficiency
− Release is stimulated by GHRH − Major inhibitor: Somatostatin or
• Secretion occurs in pulse every 2-3 Somatomedin C
hours
• Peaks at the onset of sleep GROWTH HORMONE DISORDERS
− Inhibited by somatostatin and sometimes
Somatomedin C ACROMEGALY

METABOLIC ACTIONS
− Influences both anabolic and catabolic
processes
• Amphibolic hormone
− Allows effective transition from a fed state
to a fasting state without shortage of
substrates
− Directly antagonizes effect of insulin on
glucose metabolism
− Provides hepatic gluconeogenesis
− Stimulates lipolysis
− Enhances protein synthesis in skeletal − Overproduction of GH (>50 ng/mL)
muscle & other tissues − Usually caused by pituitary tumors
− Stimulates production of insulin-like growth
factor (IGF-1) CLINICAL FEATURES
• IGF-1 inhibits lipolysis − Enlargement of the extremities
− Growth hormone deficiency in children is − Organomegaly (enlarged heart and/or
hypoglycemia. While in adults, liver)

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− Facial coarsening CLINICAL FEATURES IN CHILDREN
− Intestinal polyposis (PITUITARY DWARFISM)
− Premature cardiovascular disease − Short stature
• Most common cause of death − Low growth velocity
− Hyperhidrosis (increased sweating) − Immature facial
− Skin tags appearance
− Joint disease − Retarded bone age on
− Myopathy with weakness radiologic examination
− Insulin resistance − Increased adiposity
− Diabetes mellitus
CLINICAL FEATURES IN ADULTS
− Reduced muscle mass
− Increased adiposity
− Osteoporosis with decreased bone density
− Increase in fracture risk
− Decreased quality of life
− Dyslipidemia
TREATMENT − Increased risk for cardiovascular disease
Tumor ablation or GH suppression so there
will be decrease in GH production TREATMENT
− GH replacement therapy
GIGANTISM − Surgical removal of tumor because
− Has same clinical tumors found in the growth hormone can
features as alter the mechanism being done in the
acromegaly production of growth hormone
• Over
production of GROWTH HORMONE TESTS
Growth − Specimen: preferably fasting serum
Hormone − GH deficiency tests
− Extreme tall • Insulin tolerance test (gold standard)
stature o Insulin is administered to provoke
− GH excess occurs hypoglycemia because it induces
before epiphyseal the release of Growth Hormone
fusion is complete
• Arginine stimulation test (second
− Usually manifests in adults
confirmatory test)
− Childhood growth hormone excess
o The first test being done is the
screening test known as the exercise
GH DEFICIENCY
test. If GH fails to increase,
CAUSES
confirmation is done by doing
− Familial confirmatory testing.
− Tumors such as craniopharyngiomas o Arginine is directly proportional to
− Structural or functional abnormalities of glucose level and growth hormone
pituitary gland • Normal: >5 ng/mL in adults; >10
− Consequence of aging ng/mL in children
− Genetic mutations in the GHRH or GH gene • 24 hour or nighttime monitoring - If
− Not all individuals with growth there is a failure of GH to rise >5 in
retardation can equate to having GH adults and >10 in children, confirmatory
deficiency testing is needed to be performed.

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TEST FOR GH PRODUCTION
− Screening test for Acromegaly
• Insulin growth factor 1/somatomedin C
o IGF/IGF1 is produced in the liver and
if a patient has Acromegaly, there is
an increased value of IGF level. GH
deficiency, there is a decrease in
IGF1 level.
− Confirmatory test for Acromegaly
• Glucose Suppression test
o GH is stimulated by low glucose
in blood
o Check what will happen if glucose
level in the body is suppressed
− Interpretation of results
• Normal response is suppression of GH
(<1 ng/ml)
• If GH fails to decline = acromegaly
• Failure of GH to be suppressed (<0.3
microgram/l) + elevated IGF-1 =
Acromegaly
• Suppression of GH + normal IGF-1 =
excludes acromegaly from diagnosis
• Suppression of GH + increased IGF-1 =
follow-up and monitoring
GONADOTROPINS: FSH AND LH
− Both present in the blood of male and
female
− Low frequency Gonadotropin hormone-
releasing hormone (GnRH) pulses lead
to FSH release whereas, high frequency
GnRH pulses stimulates Luteinizing
Hormone.
− Control the growth of the ovary and testes
and the hormonal and reproductive
activities
− Diagnostic markers for fertility and
menstrual cycle disorders
• ↑ FSH = premature menopause
• ↑ FSH and ↑ LH after menopause = lack
of estrogen
FSH
− Men ♂: aids in spermatogenesis
− Women ♀: necessary for ovulation and
follicular growth
LH
− Men ♂: helps Leydig cells produce
testosterone
− Women ♀: necessary for ovulation and
follicular growth
THYROID-STIMULATING HORMONE (TSH)
− Also known as thyrotropin
− Main stimulus for the uptake of iodide by
thyroid gland
• Controls the rate of secretion of the
thyroxine and triiodothyronine
− Acts to increase the number and size of
follicular cells
− Stimulates thyroid hormone synthesis
ADRENOCORTICOTROPIC HORMONE
(ACTH)
− Also known as corticotropin
− Structure: Single-chain peptide without
disulfide bonds
− Stimulates the adrenal cortex to
secrete glucocorticoids
• ↓ cortisol in circulation → ↑ ACTH
production → ↑ cortisol production in
adrenal cortex
− Best time in collecting the sample is
8am - 10am
− Samples of Glucocorticoids: Cortisol,
aldosterone, and androgen
− ACTH deficiency
• Leads to atrophy of zona glomerulosa
and zona reticularis
− ↑ ACTH: Addison’s disease, ectopic tumors,
after protein-rich meals
− Diurnal rhythm: ↑ 6am to 8am; ↓ 6pm to
11pm
− Specimen should be collected in prechilled
plastic tubes
• ACTH adheres to glass surface
PROLACTIN
− Considered as a stress hormone
− Functions in relation to reproduction
• Breast growth during pregnancy
• Milk secretory activity/Production
− Stimulated by TRH and inhibited by
dopamine
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− Causes of Hyperprolactinemia
• Medications (phenothiazines, reserpine,
methyldopa)
• Disruption of the pituitary stalk which
interrupts flow of dopamine
• Physiologic stressors (exercise,
seizures)
− Prolactinoma
• Pituitary tumor which directly secretes
prolactin
• Menstrual irregularity / amenorrhea,
infertility, or galactorrhea
• Reduced libido or erectile dysfunction
− Idiopathic galactorrhea
• Lactation occurring in women with
normal prolactin levels
PITUITARY GLAND: HORMONES
POSTERIOR PITUITARY HORMONES
− Connected to the supraoptic and
paraventricular hypothalamic nuclei where
vasopressin and oxytocin are being
produced
− Releases ADH and oxytocin
− Hormones are synthesized in the
supraoptic nuclei (ADH) and paraventricular
nuclei (oxytocin) of the hypothalamus
− Hormones are controlled by the CNS
OXYTOCIN
− Functions
• Lactation/Release
o Milk let-down reflex
o Synthetic of oxytocin by husbands
during delivery
• Stimulator of uterine smooth muscle
o “Fergusson reflex”
o Pitocin – Synthetic oxytocin used to
enhance labor contractions
• Linked to maternal nurturing behavior
and mother-infant bonding
o Which is why it is called the “Love
hormone”.
− Inhibited by alcohol
ANTI-DIURETIC HORMONE
− Also known as vasopressin or arginine
vasopressin (AVP)
− Functions
• Regulates water excretion in the renal
tubules (DCT and collecting ducts)
• Assists in water balance
• Potent pressor agent and affects blood
clotting
o Increases blood pressure
• ↑ Factor VII and vWF
• Responsible for water reabsorption,
vasoconstriction, and blood clotting
− Stimuli for the release of ADH include
cholinergic drugs, barbiturates,
morphine, nicotine, and histamine
− Inhibitors include ethanol, cortisol,
lithium, and alcohol
− Secretion is regulated by hypothalamic
osmoreceptors and vascular baroreceptors
• Osmoreceptors - responsible for
plasma osmolality which is the principal
regulator of ADH secretion
• Baroreceptors - for blood volume and
pressure. When there is a decrease in
water intake, osmolality will increase.
− ↑ osmolality (>295 mOsm/kg) → ↑ ADH
− ↓ osmolality (<284 mOsm/kg) → ↓ ADH
− ↓ BP → ↑ ADH
− Ethanol inhibits ADH release
DIABETES INSIPIDUS
− ADH deficiency
− Clinical features
• Normoglycemia
• Polyuria with low sp. gravity
• Polydipsia
• Occasional polyphagia
TYPES OF DIABETES INSIPIDUS
− True diabetes insipidus
• Hypothalamic/neurogenic/cranial/central
diabetes insipidus
• Pituitary gland does not secrete ADH
• Urine excretion >3 L/day (Polyuria)
− Nephrogenic diabetes insipidus
• Normal ADH but abnormal ADH
receptor
o Renal resistance to ADH action
• Kidneys do not respond to ADH
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SYNDROME OF INAPPROPRIATE ANTI-
DIURETIC HORMONE (SIADH)
− Sustained ADH production without
known stimuli
− Clinical features
• ↓ urine volume
• ↓ plasma osmolality
• Normal or ↑ urine Na
• ↓ plasma electrolytes
− Reference values: 2.3 – 3.1 pg/mL
− Test:
• Water deprivation test
o After 8-12 hours of fluid deprivation,
urine osmolality does not rise >300
mOsm/kg

HYPOPITUITARISM
− Failure of pituitary or hypothalamus
• Loss of anterior pituitary function
− Panhypopituitarism
• Complete loss of function of anterior
pituitary hormones
• Absent or inadequate production of
anterior pituitary hormone caused by
pituitary destruction, tumor, Sheehan’s
syndrome, and hypothalamic problems.
o Sheehan’s syndrome - postpartum
pituitary necrosis
− Monotropic hormone deficiency
• Loss of only a single pituitary hormone,
primarily tropic hormones (ACTH, TSH,
LH, and FSH)
− GH and gonadotropins secretions are
affected before ACTH levels
− Laboratory diagnosis
• Differentiate between primary and
secondary deficiencies
o Measure both tropic and target
hormone levels
• Anorexia nervosa may clinically
resemble hypopituitarism
o Also has ↓ gonadotropins,
amenorrhea/oligomenorrhea
o Weight loss is more severe
o Frequent cachexia
o No loss of hair
o ↑ plasma cortisol and GH

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