LESSON : 7

CLINICAL CHEMISTRY 2
Endocrinology (LECTURE)
Cristhoper James Dicang || FEB 2 2023

ENDOCRINOLOGY ▪ so this positive feedback is to greater

Endocrinology
stimulation a gland receive as a result
● Study of the function and pathology of the endocrine more hormone is being produced.
system

Endocrine System o Negative feedback mechanism

● Group of ductless glands that secrete hormones
necessary for normal growth and development, ▪ ↑ product = ↓ activity, ↓ production rate
reproduction and homeostasis
▪ More common in hormones
Endocrine glands ▪ Good thing when it comes to
● Ductless glandular structures that release their hormonal
HOMEOSTASIS. It gives an internal
secretions into the extracellular space where they
stability or equilibrium
access circulating plasma
▪ Example: There is s certain stimulus, an
Endocrine Glands increase in body temperature or having a
● Pineal gland hot environment
● Parathyroid glands
▪ so this will be detected by the control
● Adrenal glands
● Pancreas center of the brain which is our
● Hypothalamus hypothalamus this will then send signals
● Pituitary gland that will cause vasodilation or widening of
● Thyroid gland the blood vessels to produce heat in the
● Thymus skin surface
● Ovaries ▪ .Sweating will occur to the activation
● Testes
various sweat glands and you will be
sweating as an evaporation of water from
the skin and it has a powerful cooling
Hormones effect. So when the body return to normal
● A chemical substance produced by a specific endocrine temperature the brain’s hypothalamus
receives the signal okay na ang
gland which has a specific regulatory effect on the activity of
temperature.
an organ or organs
● They will give chemical signals to produced by specialized
● Characteristics of hormones
cells secreted into the bloodstream and carried to the active
site of action as a free hormone or bound to transport ▪ Produced by specific tissue
protein.
▪ Released directly from the tissue into the bloodstream
● The major function of the regulation for hormone is to
and carried to the site of action
maintain the constancy of chemical composition between
extracellular fluid (ECF) and the intracellular fluid for the ICF ▪ Acts at a specific target site or sites to induce
biochemical changes
● “Chemical messengers”

● Hormone regulation Functions of Hormones

o Positive feedback mechanism 1. Maintain homeostasis

▪ ↓ product = ↑ activity, ↑ production rate ▪ Regulation of blood glucose (insulin, glucagon,

cortisol, epinephrine)
▪ enhances the original stimulus to
▪ Regulation of serum calcium (PTH)
accelerate the activity
▪ EXAMPLE: ▪ Water and electrolyte metabolism (aldosterone,
renin, ADH)
▪ When to baby is about to be born or 2. Regulate growth and development
delivered. ▪ Gonadal steroids, growth hormone, cortisol,
▪ The OXYTOCIN is to be released more thyroxine
and more because the cervix need more 3. Promote sexual maturation, sexual rhythms and facilitate
contraction so the process will work to reproduction
increase on the product which will then 4. Regulate energy production
stimulate the production of another product 5. Adapt/adjust body to stressful/emergency situations
[CC2] ENDOCRINOLOGY
6. Promote/inhibit production or release of other hormones
● Initiates response by binding to cell membrane receptors
Classification of Hormones and triggering a “second messenger” system
1. According to action ● Examples:
2. According to composition o Glycoprotein – FSH, hCG, TSH, Erythropoetin
3. According to interaction o Polypeptides – ACTH, ADH, GH, Angiotensin,
4. According to tissue origin Calcitonin, Cholecystokinin, Gastrin, Glucagon,
Insulin, MSH, Oxytocin, PTH, Prolactin,
Classification of Hormones: Somatostatin
According To Action
2. Steroid
Type Site of Site of Action ● Lipid molecules that have cholesterol as a common precursor
Secretion Release
Endocrine one blood binds to specific ● Hydrophobic and insoluble in water
location circulation receptor to elicit ● Half-life: 30 to 90 mins
physiological
response ● Circulates in plasma, but not bound to carrier protein they
It has the longest
enter the cell by passive diffusion bind with intracellular
half -life because it
receptor in the cytoplasm or the nucleus
has to enter the
bloodstream and ● Examples:
travel to the target o Aldosterone, Cortisol, Estradiol, Estrone,
site Progesterone, Testosterone
Paracrine endocrine interstitial binds into specific
cells space receptor in 3. Amines
adjacent cell and
● Water soluble and circulates in plasma
affects its function
Autocrine endocrine interstitial binds into specific ● Half-life
cells space receptor on cell of o Protein-bound: 7-10 days
origin resulting to o Free and unbound: <1 minute
self-regulation of
its function ● Interact with membrane-associated receptors and use a 2nd
It has a shorted messenger system
half-life because it ● they are derived from the amino acids
secreted to the cell
of origin being ● they are intermediary between steroid and protein hormones
targeted
● Examples:
Juxtacrine endocrine remains in acts on immediate
cells relation to adjacent cell by o Epinephrine, Norepinephrine, T3, T4, Serotonin
plasma direct cell-to-cell
membrane contact
Exocrine endocrine lumen of Affects function in
cells gut gut
Neurocrine neurons extracellul binds to receptor
ar space in nearby cell and
affects its function
Neuroendocrine neurons nerve interacts with
endings receptor of cells at
distant site

Classification of Hormones:
According To Composition
1. Polypeptides or Proteins
● Water soluble and circulate freely in
plasma bound to carrier protein
● Short half-life (≤10 to 30 mins)

● Cannot cross the cell membrane

o produce their effects in the outer
surface of the cell

Transcriber: Geronimo, Claudine E.

[CC2] ENDOCRINOLOGY

Classification of Hormones:
According To Tissue Origin
● Hypothalamus – TRH, GnRH, CRH

● Anterior Pituitary – TSH, ACTH, FSH, LH, prolactin, GH

● Posterior Pituitary – Vasopressin, oxytocin

● Adrenal Medulla – Epinephrine, norepinephrine

● Adrenal Cortex – Cortisol, aldosterone

● Parathyroid – PTH

● Thyroid – T3, T4, calcitonin

● Pancreas – Insulin, glucagon

● Ovaries – Estrogen

● Testes – Testosterone, other androgens

Types of hormone interaction

● Potentiation reaction
- the presence of one hormone increases the action of
another
● Stimulatory reaction
Classification of Hormones: - the presence of one hormone stimulate the secretion
According To Interaction of another
1. Synergistic ● Inhibitory reaction
● 2 or more hormones are additive/complementary in effect - the presence of one hormone inhibits the secretion of
another
● Example: Thyroid Hormone + Growth Hormone
Hypothalamus and
● glucagon and epinephrine
Pituitary Gland
● They both cause the liver to release the glucose when they Hypothalamus
are together the amount of glucose being release is actually ● the link between the nervous system
more than the usual
and endocrine system this is
considered to be the Integrative
2. Antagonistic
center for many homeostatic circuits
● Effect of one hormone is against the action of another ● Portion of brain located in the walls
● Example: Insulin and glucagon and floor of the third ventricle
● Located above the pituitary gland
● One increases the glucose level and one decreases the
o Connected to the posterior pituitary by the
glucose level
infundibulum (pituitary stalk)
● The regulation for your plasma glucose involves glucagon so
for increae blood glucose and insulin for the decrease blood Hypothalamus: Functions
glucose hormones. 1. Direct control of autonomic nervous system
(visceromotor behaviors)
3. Permissive
● Parasympathetic and sympathetic effects
● 1 hormone will enhance the responsiveness of a target to
another hormone ● Thermodetectors, chemoreceptors

● Example: ↑ thyroid hormone → ↑ response to catecholamine

2. Communication with limbic system/midbrain
● The thyroid hormone is necessary for normal timely ● Hunger and satiety centers, drinking center
development of reproductive hormones. Withoud this thyroid
hormone the reproductive system development will is being ● Circadian rhythms
delayed . So the permissiveness in which the presence of
● Emotions
one hormone is required in order for another hormone to
exert for its target cell

Transcriber: Geronimo, Claudine E.

[CC2] ENDOCRINOLOGY
3. Hormonal control of endocrine system
● Release/release-inhibiting factors for homeostatic control
of pituitary hormones (LH, FSH, ACTH, TSH)
● Osmoreceptors – vasopressin and oxytocin
● Gonadal hormones
Pituitary Gland: Anterior pituitary(adenohypophysis)
● The classification depending on the color reaction using your
H & E stain or the Hematoxylin and eosin stain
Acidophil
● red color reaction in H & E stain

Hypothalamus: Hormones ● Somatotrophs: Growth Hormone

● Lactotrophs/ mammotrophs: Prolactin

Hormone Action
Basophil
Thyrotropin releasing hormone Releases TSH and prolactin
(TRH) ● blue color reaction in H & E stain
Gonadotropin releasing Releases LH and FSH ● Thyrotrophs: Thyroid stimulating hormone
hormone (GnRH)

Corticotropin releasing hormone Releases ACTH ● Gonadotrophs: Follicle stimulating hormone & Luteinizing
(CRH) hormone
Growth hormone releasing Releases GH
hormone (GHRH)
Chromophobe cells

Somatostatin Inhibits GH and TSH release ● no stain or no color reaction in H & E stain

Dopamine Inhibits prolactin release ● Corticotrophs: Adrenocorticotrophic Hormone

Pineal gland Hypothalamic-Hypophyseal Unit

● attached to the midbrain ● Response pattern characteristics

o Open-loop negative feedback mechanism
● the gland that releases melatonin (sleep hormone) the o Influenced by higher neural input or other hormones
secretion of the pineal gland is controlled by the nerve stimuli
● Pulsatility
o For all anterior pituitary hormones
o Examples: GnRH → LH and FSH

● Cyclicity
o Circadian/diurnal rhythm – internal biologic clocks
o Examples:
Pituitary Gland o ↑ ACTH 6am to 9am; ↓ ACTH 11pm to 3am
o ↑ TSH at night; ↓ TSH in the morning
● “Master gland”

● Also called Hypophysis Pituitary Gland: Hormones

Anterior pituitary
● Main body of the pituitary is contained in a small bony cavity 1. Growth hormone (GH)
called sella turcica (“Turkish saddle”) surrounded by dura 2. Follicle-stimulating hormone (FSH)
mater 3. Luteinizing hormone (LH)
4. Thyroid-stimulating hormone (TSH)
● responsible for the body feedback loops and versatile
5. Adrenocorticotropic hormone (ACTH)
secretion and diurnal rhythms and environmental or external 6. Prolactin (PRL)
modification of its performance
Posterior pituitary
Pituitary Gland: Anatomy 1. Oxytocin
2. Anti-diuretic hormone (ADH)
● Anterior pituitary (adenohypophysis)
o Hormones which target other endocrine glands
● Intermediate lobe (pars intermedialis) Pituitary Gland: Hormones
o Little functional capacity Anterior pituitary hormones

● Posterior pituitary (neurohypophysis) ● May be peptides or glycoproteins

o Stores and releases oxytocin and vasopressin ● Types of cells
(ADH) o Somatotropes – secrete GH
o Lactotropes or mammotropes – secrete PRL
o Thyrotropes – secrete TSH

Transcriber: Geronimo, Claudine E.

[CC2] ENDOCRINOLOGY
o Gonadotropes – secrete FSH and LH
▪ in adults, the hypoglycemia occurs in both GH and
o Corticotropes – secrete ACTH
ACTH are deficient
“true endocrine gland”
● Stimulators
● Classification o Meals
o Exercise
▪ Tropic hormones o Sleep
o Acts specifically for another endocrine gland o Hypoglycemia
o FSH, LH, TSH, ACTH o stimulate the production or secretion of our growth
o FSH- stimulates the ovaries to produce hormone in our body
eggs/ova in women and sperm production in o GHH is the most abundant; the one who has highest
men concentration in all of pituitary hormone
o LH- it helps regulating testosterone in male o secreted in an episodic burst.], during the early sleep,
and estrogen levels in female few hours after eating and after exercise the times
o ACTH- It stimulates the suprarenal gland to highest in secretion
produce your cortisol (stress hormone). The
production of this hormone is triggered by the
● Inhibitors
stressful situation. Example of circadian
rhythm or diurnal rhythm. It is the lowest o Glucose loading
secretion is between 11 pm up until 3 am and o Epinephrine
the peak occurring in the morning or in o Emotional/psychogenic stress
awakening at 6 am and 9 am. This will triffer o Nutritional deficiencies
the pulse altitude not alteration in the pulse o Insulin deficiency
frequency o Major stimulus for growth hormone secretion is deep
▪ Direct effector hormones sleep. It gives markley increase growth hormone
production
o Acts directly on peripheral tissue
o the major inhibitor of growth hormone secretion is
o GH (bone and muscles) , PRL (mammary
somatostatin or somatomedin
gland) o
Growth Hormone: Disorders
Growth Hormone
Acromegaly
● Also called somatotropin
● Overproduction of GH (>50 ng/mL)
● It is structurally related to prolactin and human placental
● Usually caused by pituitary tumors
lactogen
● Promotes growth of the body by affecting protein hormone
● Clinical features:
formation, cell multiplication and differentiation
o Enlargement of the extremities
● Release is stimulated by GHRH o Organomegaly (enlarged heart
o Secretion occurs in pulse every 2-3 hours and/or liver)
o Peaks at the onset of sleep o Facial coarsening
o Intestinal polyposis
● Inhibited by somatostatin and sometimes Somatomedin C
o Premature cardiovascular disease
o Hyperhidrosis (increased
● Metabolic Actions sweating)
o Influences both anabolic and catabolic processes o Skin tags
o Joint disease
▪ Amphibolic hormone o Myopathy with weakness
o Allows effective transition from a fed state to a fasting o Insulin resistance
state without shortage of substrates o Diabetes mellitus
o Directly antagonizes effect of insulin on glucose
metabolism ● Treatment: Tumor ablation or GH suppression
o Provides hepatic gluconeogenesis
o Stimulates lipolysis
o Enhances protein synthesis in skeletal muscle & other
tissues
o Stimulates production of insulin-like growth factor (IGF-
1)
▪ IGF-1 inhibits lipolysis

▪ The growth hormone deficiency in children may be

accompanied by hypoglycemia

Transcriber: Geronimo, Claudine E.

[CC2] ENDOCRINOLOGY
Gigantism
▪ Insulin growth factor 1/somatomedin C
● Has same clinical features as acromegaly
▪ Insulin growth hormone (IGH) Factor 1 this is
● Extreme tall stature produce in the liver
● GH excess occurs before epiphyseal fusion is complete ▪ there is an increased value of IGF level

● child growth hormone excess o Confirmatory test for Acromegaly

GH Deficiency ▪ Glucose Suppression test

o Interpretation of results
● Causes:
▪ Normal response is suppression of GH (<1 ng/ml)
o Familial
o Tumors such as craniopharyngiomas ▪ If GH fails to decline = acromegaly
o Structural or functional abnormalities of pituitary gland
o Consequence of aging ▪ Failure of GH to be suppressed (< 0.3 microgram/l) +
o Genetic mutations in the GHRH or GH gene elevated IGF-1 = Acromegaly
o Not all individual with growth retardation can equate
▪ Suppression of GH + normal IGF-1 = excludes
Growth hormone deficienc
acromegaly
● Clinical features in children (pituitary dwarfism) ▪ Suppression of GH + increased IGF-1 = follow-up and
o Short stature monitoring
o Low growth velocity
o Immature facial appearance Gonadotropins: FSH and LH
o Retarded bone age on radiologic examination ● Control the growth of the ovary and testes and the hormonal
o Increased adiposity
and reproductive activities
● Diagnostic markers for fertility and menstrual cycle disorders
● Clinical features in adults
o ↑ FSH = premature menopause
o Reduced muscle mass
o ↑ FSH and ↑ LH after menopause = lack of estrogen
o Increased adiposity
o Osteoporosis with decreased bone density
o Increase in fracture risk ● FSH
o Decreased quality of life o ♂: aids in spermatogenesis
o Dyslipidemia o ♀: necessary for ovulation and follicular growth
o Increased risk for cardiovascular disease
● LH
o ♂: helps Leydig cells produce testosterone
● Treatment: o ♀: necessary for ovulation and follicular growth
o GH replacement therapy
o Surgical removal of tumor (it can alter the mechanism Thyroid-Stimulating Hormone
being done in the production of GH
● Also known as thyrotropin
Growth Hormone: Tests ● Main stimulus for the uptake of iodide by thyroid gland
● Specimen: preferably fasting serum o controls the rate of secretion of the thyroxine and
triiodothyronine
● GH deficiency tests
● Acts to increase the number and size of follicular cells
o Insulin tolerance test (gold standard)
o first screening test : exercise test if GH fails to increase ● Stimulates thyroid hormone synthesis
the confirmation must be made administer insulin to
provoke hyperglycemia because it induce the release of
GH Adrenocorticotropic Hormone
● Also known as corticotropin
o Arginine stimulation test (2nd confirmatory test)
o arginine is directly proportional to glucose level and GH ● Structure: Single-chain peptide without disulfide bonds

o Normal: >5 ng/mL in adults; >10 ng/mL in children
o 24 hr or Night time monitoring of growth hormone
o if fail to increase or to have normal levels we need to
perform confirmatory testing
● Test for GH production
o Screening test for Acromegaly
● Stimulates the adrenal cortex to secrete glucocorticoids
o ↓ cortisol in circulation → ↑ ACTH production → ↑ cortisol
production in adrenal cortex
● ACTH deficiency
o Leads to atrophy of zona glomerulosa and zone
reticularis
Transcriber: Geronimo, Claudine E.
[CC2] ENDOCRINOLOGY

● ↑ ACTH: Addison’s dse, ectopic tumors, after protein-rich meals ▪ “Fergusson reflex”

● Diurnal rhythm: ↑ 6am to 8am; ↓ 6pm to 11pm ▪ Pitocin – Synthetic oxytocin used to enhance labor
contractions
● Spx should be collected in prechilled plastic tubes
o Linked to maternal nurturing behavior and mother-infant
o ACTH adheres to glass surface bonding

Prolactin
● Functions in relation to reproduction Anti-Diuretic Hormone
o Breast growth during pregnancy ● Also known as vasopressin or arginine vasopressin (AVP)
o Milk secretory activity
● Functions
● Stimulated by TRH and inhibited by dopamine o Regulates water excretion in the renal tubules (DCT and
collecting ducts)
● Causes of Hyperprolactinemia o Assists in water balance
o Potent pressor agent and affects blood clotting
o Medications (phenothiazines, reserpine,
o ↑ Factor VII and vWF
methyldopa)
o Disruption of the pituitary stalk which interrupts flow
of dopamine
o Physiologic stressors (exercise, seizures) ● Secretion is regulated by hypothalamic osmoreceptors and
vascular baroreceptors
● Prolactinoma
o Pituitary tumor which directly secretes prolactin ● ↑ osmolality (>295 mOsm/kg) → ↑ ADH
o Menstrual irregularity/amenorrhea, infertility, or
● ↓ osmolality (<284 mOsm/kg) → ↓ ADH
galactorrhea
o Reduced libido or erectile dysfunction ● ↓ BP → ↑ ADH

● Ethanol inhibits ADH release

● Idiopathic galactorrhea
o Lactation occurring in women with normal prolactin
levels ● Diabetes insipidus
o ADH deficiency
o Clinical features
Pituitary Gland: Hormones
▪ Normoglycemia
Anterior pituitary
1. Growth hormone (GH) ▪ Polyuria with low sp. gravity
2. Follicle-stimulating hormone (FSH)
3. Luteinizing hormone (LH) ▪ Polydipsia
4. Thyroid-stimulating hormone (TSH)
5. Adrenocorticotrophic hormone (ACTH) ▪ Occasional polyphagia
6. Prolactin (PRL)
● Types of Diabetes insipidus
Posterior pituitary
1. Oxytocin o True diabetes insipidus
2. Anti-diuretic hormone (ADH) ▪ Hypothalamic/neurogenic/cranial/central diabetes
insipidus
▪ Pituitary gland does not secrete ADH
Posterior pituitary
▪ Urine excretion >3 L/day
● Releases ADH and oxytocin o Nephrogenic diabetes insipidus
● Hormones are synthesized in the supraoptic nuclei (ADH) ▪ Normal ADH but abnormal ADH receptor
and paraventricular nuclei (oxytocin) of the hypothalamus
● Renal resistance to ADH action
● Hormones are controlled by the CNS
▪ Kidneys do not respond to ADH

Oxytocin ● Syndrome of inappropriate anti-diuretic hormone (SIADH)

● Functions o Sustained ADH production without known stimuli
o Lactation o Clinical features

▪ Milk let-down reflex ▪ ↓ urine volume

o Stimulator of uterine smooth muscle
Transcriber: Geronimo, Claudine E.
[CC2] ENDOCRINOLOGY

▪ ↓ plasma osmolality

▪ N or ↑ urine Na

▪ ↓ plasma electrolytes

● Reference values: 2.3 – 3.1 pg/mL

● Test:
o 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
o Loss of anterior pituitary function
● Panhypopituitarism
o Complete loss of function of anterior pituitary
hormones
● Monotropic hormone deficiency
o Loss of only a single pituitary hormone, primarily
tropic hormones

● GH and gonadotropins secretions are affected before ACTH

● Laboratory diagnosis
o Differentiate between primary and secondary
deficiencies
▪ 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

Endocrinology

Hypothalamus and
Pituitary Gland

Transcriber: Geronimo, Claudine E.