MTY 1405: CLINICAL CHEMISTRY 2 | LABORATORY WEEK #

TITLE
Mx. Charlene Princess Tolenada TRANSCRIBED BY: SECTION 3
2nd Semester 2023 - 2024

HORMONES
• Chemical signals produce by specialized cells
• For growth and development of an individual
• Regulated by the metabolic activity CLASSIFICATION OF HORMONES ACCORDING TO
COMPOSITION OR STRUCTURE
MAJOR FUNCTION:
o Maintain constancy of chemical composition of
Derived from an amino acid
extracellular and intracellular fluids
Amines Intermediary between steroid and protein
o Control metabolism
hormones
o Growth
Chain of amino acid
o Fertility
Peptides Peptide hormones are hydrophilic
o Responses to stress
not bound to carrier protein
Chain of amino acid
Primary, secondary, tertiary structure
Protein
Formed from a larger number of amino acid
residues (50 a.a)
Conjugated protein bound to carbohydrate,
Glycoprotein
which include galactose, mannose, or fructose
Cholesterol as a common precursor
Produced by adrenal gland, ovaries, testes,
and placenta
Steroids Water insoluble and circulate bound to a
carrier protein
Can cross cellular membranes easily
Delayed effect
Made up of small fatty acid derivatives or
TYPES OF HORMONE ACTIONS Fatty acids arachidonic acid
Rapidly degrades
Cellular messages are sent via bloodstream
Endocrine secreted in one location and release into blood
circulation
Paracrine secreted in endocrine cells and released into
interstitial space
Autocrine binds to specific receptor cell of origin resulting to
self-regulation of its function
Juxtacrine acts immediately to adjacent cell by direct cell-to-
cell contact

1|Page
 Organ Source Classification Effects Regulation
• Body growth
Production tightly regulated through
Peptide • Basal metabolic functions
GH Anterior Pituitary several complex feedback
• Acute phase stress reactant
mechanisms and lifestyle factors

• Negative feedback regulation:

• Regulates cortisol o Serum glucocorticoid
ACTH Anterior Pituitary Protein
• Regulates Androgen production concentration
o Neural input

Thyrotropin releasing
Tropic hormone to regulate T4 hormone (TRH) release from the
TSH Anterior Pituitary Protein
production hypothalamus and negative feedback
by circulating serum T4 levels
• Pulsatile GnRH secretion from
hypothalamus
o Women: Initiate follicular
o Women: Negative feedback from
FSH Anterior Pituitary Glycoprotein maturation and estrogen production
estrogen levels
o Men: Spermatogenesis
o Men: Negative feedback from
inhibin B
• Pulsatile GnRH secretion from
hypothalamus
o Women: Initiation of ovulation
o Women: Negative feedback from
LH Anterior Pituitary Glycoprotein o Men: Activate testicular
estrogen levels
testosterone production
o Men: Negative feedback from
inhibin B
• Dopamine-mediated
hypothalamic regulation
• Nipple stimulation
PRL Anterior Pituitary Peptide Lactation
• Light
• Olfaction
• Stress
Activation of ADH-sensitive water pores
Osmotic receptors in the
ADH Posterior Pituitary Peptide in the collecting duct to regulate
hypothalamus
osmolarity
Calcitonin C-cells of Thyroid Protein Inhibits osteoclastic breakdown Negative feedback from elevated Ca2+
CALC-1 gene expression,
Parafollicular C-cells of
PCT Peptide Prohormone to calcitonin linked with calcitonin
Thyroid
regulation
• Increases circulating calcium ions, by
promoting Ca2+ absorption in the
intestines Negative feedback from elevated
PTH Parathyroid cell Peptide
• promotes Ca2+ reabsorption serum Ca2+ and PO2−
• blocks PO4− reabsorption

Drops plasma glucose Secreted primarily in

Levels: bind directly to insulin receptors response to glucose, but fats and
Insulin β cells of the pancreas Protein
on cell surfaces to allow glucose entry amino acids can create more robust
into cells through GLUT4 channels insulin secretion
α cells do not express a glucagon
Increases glycogenolysis and
receptor and are therefore considered
Glucagon α cells of the pancreas Protein gluconeogenesis by binding to G-coupled
to regulate their own secretion
protein receptors throughout the body
through insulin
G cells the pyloric Directly stimulated by vagal neurons
Induces HCl secretion from the parietal
Gastrin antrum of the Peptide and presence of amino acids in the
cells in the stomach
stomach stomach
Induces HCl secretion
S cells in the
Secretin Peptide from parietal cells and bicarbonate Stimulated by gastric acid
duodenum
release from the pancreas

2|Page

Syncytiotrophoblast
β-hCG
cells of the placenta
Zona fasciculata in the
Cortisol
adrenal cortex
Zona glomerulosa in
Aldosterone
the adrenal cortex
Regulated by several
Stimulates the corpus luteum in the
hormones, growth factors, cytokines,
Peptide ovary to produce progesterone to
PPARγ ligands, and the homeobox
maintain pregnancy
gene (DLX3)
• Immune response
Hypothalamic-pituitary-adrenal (HPA)
Steroid • Stress response
axis
• Glucose homeostasis
Increase sodium absorption in the distal
Renin–angiotensin–aldosterone
Steroid tubules and proximal collecting ducts of
system (RAAS)
the nephrons

Men: Regulate sex determination, male

Zona reticularis in the sex characteristics,
Testosterone Steroid HPA axis
adrenal cortex spermatogenesis,
fertility

• Relatively weak androgen

Zona reticularis in the
DHEA Steroid Serves as a precursor for testosterone HPA axis
adrenal cortex
and estrogen
• Zona reticularis in
the adrenal
Promote development of the
cortex
endometrial lining and allow for an Regulated by several factors that
Progesterone • Gonads Steroid
increase in FSH during the menstrual affect the duration of pregnancy
• Corpus luteum of
cycle
pregnancy in the
ovary
Regulation by:
• Breast development
• sex hormone binding globulin
• Endometrial proliferation
(SHBG)
Zona reticularis in the • Proliferation of vaginal mucosal cells
Estrogens Steroid • albumin binding
adrenal cortex • Bone development
Negative feedback:
• Increase HDL-C
• hypothalamus
• Decrease LDL-C
• anterior pituitary gland
• Dopamine
• Epinephrine • availability of tyrosine
• Norepinephrine • glucocorticoid upregulation
Amine • Create the "fight or flight" response: • degradation via catechol-o-
Catecholamines Adrenal Medulla
neurotransmitter o Vasoconstriction methyl transferase (COMT) or
o Tachycardia monoamine oxidase (MAO)
o Sweating activity
o Anxiety

Regulation by:
• albumin binding
• Activate metabolism
Thyroxine Thyroid follicular cells Steroid • thyroxine binding globulin (TBG)
• Increase the basal metabolic rate
• Negative feedback through TSH
by circulating serum T4 levels
• Mainly in the central nervous
• CNS: Perception, memory, mood system nuclei
Amine • Intestines: Intestinal motility • also found in the
Serotonin Neural cells
neurotransmitter • Platelets: Blood vessel tone and enterochromaffin cells located
functionality throughout the digestive tract
and platelets

3|Page
 HORMONE METABOLISM PINEAL GLAND
• Includes both Catabolism and Anabolism • Melatonin – sleep hormone
• The speed at which they are created (Anabolism) or broken
down (Catabolism) determines the extent to which they are
capable of binding to receptors and eliciting their intended
effect.

ALCOHOL CONSUMPTION
• Alcohol appears to increase degradation of testosterone
• Reduced hormone concentration

ADRENAL STEROID HORMONE SYNTHESIS

• Produced via cascade of enzymatic reaction PITUITARY
• Deficiency in 11-Beta-hydroxylase: Decrease in aldosterone • “Spit mucus”
and glucocorticoids, Shunt all cholesterol into the sex steroid • Master Gland
pathway • Hypophysis (undergrowth)
• Resides in a pocket of the sphenoid (the sella turcica, meaning
HORMONE TRANSPORT “Turkish saddle”)
• Circulate in the bloodstream in one of the two forms: • Anterior pituitary receives 80% to 90% of its blood supply
o FREE (UNBOUND)
o PROTEIN BOND
• Free floating hormones: susceptible to degradation

WAYS THAT HORMONES CAN TRAVEL TO DISTANT SITES IN THE BODY:

• Solubility
• Carrier Proteins
• Micelles
OTHER FACTORS THAT AFFECT HOMONE LEVELS:
• Emotional stress
• Time of the dat
• Menstrual Cycle
• Menopause
• Food intake/Diet EMBRYOLOGY AND ANATOMY
• Drugs
• Largest portion (Rathke
Anterior Pituitary
Pouch)
HYPOTHALAMIC AND PITUITARY FUNCTION
• Poorly developed in humans
HYPOTHALAMUS Intermediate Lobe
• Little functional capacity
• Link between nervous system and endocrine system
• Arises from the diencephalon
• GnRH, GHRH, TRH, somatostatin, dopamine, PIF
• Storage and release of
• ADH (vasopressin), ocytocin Posterior Pituitary
oxytocin and vasopressin
(ADH)

4|Page
 FUNCTIONAL ASPECTS OF THE HYPOTHALAMIC-HYPOPHYSEAL UNIT • Sleep • Glucose loading
• Exercise • Β-Agonists (e.g.,
• Physiologic stress epinephrine)
• Amino acids (e.g., • α-Blockers (e.g.,
arginine) phentolamine)
• Hypoglycemia • Emotional/psychogenic
• Sex steroids (e.g., stress
estradiol) • Nutritional deficiencies
• α-Agonists (e.g., • Insulin
norepinephrine) deficiency/hyperglycemia
• β-Blockers (e.g., • Thyroxine deficiency
propranolol)

ACTIONS OF GROWTH HORMONE

ANTERIOR PITUITARY (ADENOHYPOPHYSIS)
• Amphibolic hormone
• True Endocrine gland
• Allows an individual to effectively transition from a fed state to
• Released and production of hormones such as Prolactin, GH,
a fasting state without experiencing a shortage of substrates
Gonadotropins (FSH, LH), TSH, and ACTH
required for normal intracellular oxidation
• 5 TYPES OF CELLS BY IMMUNOCHEMICAL TEST
• Antagonist of insulin
o Somatotrophs: secrete GH
• Anabolic effects: enhanced protein synthesis in skeletal muscle
o Lactotrophs or mammotrophs: secrete prolactin
and other tissues
o Thyrotrophs: secrete TSH
• Indirect effects: somatomedins
o Gonadotrophs: secrete LH and FSH
o Shifted to insulin-like growth factor (IGF):
o Corticotrophs: secrete prooplimelanocortin
somatomedin C (IGF-1)
ANTERIOR PITUITARY HORMONES
TESTING
• Direct effectors:
• Definitive test: oral glucose loading
o GH: stimulates the liver to produce growth factors
o Performed after an overnight fast
o Prolactin
o Px is given a 100g oral glucose load
• Tropic hormone:
o GH is measured at time zero and at 60 and 120
o LH: directs testosterone production from Leydig cells in
minutes after glucose ingestion
men and ovulation in women
o NORMAL: GH undetectable
o FSH: ovarian recruitment and early folliculogenesis in
o ACROMEGALY: GH levels fail to suppress and may
women and spermatogenesis in men
even paradoxically rise
o TSH: directs thyroid hormone prodcution from the
• Gold standard: Insulin-induced hypoglycemia
thyroid
• Infusion of GHRH and the amino acid L-arginine or an infusion
o ACTH: regulates adrenal steroidogenesis
of L-arginine coupled with oral L-DOOA
o GH levels rise above 3 to 5 ng/mL, it is unlikely that
GROWTH HORMONE
the patient is GH deficient
• Somatotropin
• Structurally related to prolactin and human placental lactogen
ACROMEGALY
• Stimulated by growth hormone-realizing hormone (GHRH)
• >50 ng/mL or 2210 pmol/L
• Inhibited by Somatostatin
• Pituitary tumor
• GH is secreted in pulses (interpulse interval of 2 to 3 hours)
• Result of the ectopic production of GHRH
• Reproducible peak occurring at the onset of sleep
• GH-producing tumor: patient develops gigantism
• Ghrelin: nutrient sensing, appetite and in glucose regulation
• Overt diabetes can occur
o Potent stimulator of GH secretion
• Left untreated, acromegaly shortens life expectancy
OTHER MODIFIERS OF GROWTH HORMONE SECRETION • Patients with acromegaly also have a greater lifetime risk of
STIMULATES GROWTH INHIBIT GROWTH HORMONE developing cancer
HORMONE SECRETION SECRETION • Definitive test: GH to glucose loading

5|Page
• Procedure of choice: Transsphenoidal adenomectomy • Hyperprolactinemia may also be seen in renal failure and
TEST FOR ACROMEGALY polycystic ovary syndrome.
• Screening Test: Somatomedjn C or insulin-like growth factor • Idiopathic Galactorrhea:
(IGF-1) o Lactation occurring in women with normal prolactin
• Confirmatory Test: Glucose Suppression Test—OGTT levels
o Manifestation of localized increased sensitivity to
GH DEFICIENCY prolactin in breast tissue
• Occurs in both children and adults • Physiologic stressors, such as exercise and seizures, also
o CHILDREN: may be genetic or it may be due to tumors elevate prolactin
(craniopharryngiomas) • Highest Serum Level (DURING SLEEP): 4 AM-8am; 8pm - 10 pm
• Recessive mutation in the GHRH gene: failure of GH secretion • Method: Immunometric Assay
• Structural lesions of the pituitary or hypothalamus
PROLACTINOMA
• Adult GH deficiency syndrome: complete or even partial
• Pituitary tumor that directly secretes prolactin
failure of the anterior pituitary
• Most common type of functional pituitary tumor
• Most common cause of GH
• Depends on the age and gender of the patient and the size of
deficieny in children
Idiopathic Growth the tumor
• Pituitary dwarfism, normal
Hormone Deficiency • Other Causes of Hyperprolactinemia:
proportions are retained
o Elevations in prolactin (>150 ng/mL) indicate
• No intellectual abnormalities
Prolactinoma
• Most common etiology in o Modest elevations in prolactin (25 to 100 ng/mL):
adult-onset GH deficiency Pituitary Stalk Interruption
• Diagnostic test: o Breast or genital stimulation: elevate prolactin
o Px prep: complete o Pregnancy
Pituitary Adenoma
rest 30 mins before o Macroprolactinemia: 150-kD form
blood collection
o Spx req: preferably CLINICAL EVALUATION OF HYPERPROLACTINEMIA
fasting • TSH and free T4 to eliminate primary hypothyroidism
• Pituitary tumor: assessment of other anterior pituitary
TEST FOR GH DEFICIENCY function
• Screening Test: Physical Activity Test (Exercise Test) o Basal cortisol
o Result: INC serum GH o LH
o If GH fails to INC, confirmation must be made o FSH
• Confirmatory Test: o gender-specific gonadal steroid [either estradiol or
o Gold Standard: Insulin Tolerance Test testosterone]
o 2nd confirmatory test: Arginine stimulation test o evaluation of sellar anatomy with a high-resolution
o Procedure: 24hr or nighttime monitoring of GH MRI
• Interpretation: failure to rise >5 ng/mL (adult) and >10 ng
(child) in all the test is confirmed GH deficieny
MANAGEMENT OF PROLACTINOMA
PROLACTIN
• Observation, surgery, radiotherapy, or medical management
• structurally, related to GH and human placental lactogen with dopamine agonists
(lactogenic hormone)
• Macroadenomas [tumor size >10 mm): less likely to be "cured"
• Stress hormone; Direct effector hormone
• Microadenomas [tumor size < 10 mm]
• Prolactin inhibitory factor (PIF): capable of inhibiting prolactin
• Dopamine agonists are the most commonly used therapy for
secretion
microprolactinomas
• Dopamine: only neuroendocrine signal that inhibits prolactin o Bromocriptine mesylate (Parlodel)
(elusive PIF) o Cabergoline (Dostinex)
• TRH: directly stimulates prolactin secretion
• Estrogens: also directly stimulate lactotrophs to synthesize
prolactin

6|Page
 HYPOPITUITARISM
• Panhypopituitarism: Complete loss of function
o Treatment:
▪ Patients are treated with thyroxine,
glucocorticoids, and gender-specific sex
steroids.
▪ Pulsatile GnRH infusions have induced
puberty and restored fertility in patients
with Kallmann's syndrome.
▪ Gonadotropin preparations have restored
ovulation/spermatogenesis in people with
gonadotropin deficiency.
• Monatropic hormone deficiency: loss of only a single pituitary
hormone
• Loss of a tropic hormone (ACTH, TSH, LH, and FSH): cessation
of the affected endocrine gland.
• CAUSES OF HYPOPITUITARISM:
1. Pituitary tumors
2. Parapituitary/hypothalamic tumors
3. Trauma
4. Radiation therapy/surgery
5. Infarction
6. Infection
7. Infiltrative disease
8. Immunologic
9. Familial
10. Idiopathic
GONADOTROPINS-FOLLICLE STIMULATING HORMONE (FSH)
AND LEUTENIZING HORMONE (LH)
• Important markers in diagnosing fertility and menstrual cycle
• FSH: aids in spermatogenesis
• LH: helps Leydig cells to produce testosterone (MALE)
• LH: for ovulation and final follicular growth (FEMALE)
• Elevation of FSH: diagnosis of premature menopause
• Increased of FSH and LH after menopause: Lack of estrogen
THYROID STIMULATING HORMONE (TSH)
• Known as thyrotropin
• Main stimulus for the uptake of iodide by the thyroid gland
• Blood levels may contribute in the evaluation of infertility
ADENOCORTICOTROPHIC HORMONE (ACTH)
• Produced in response to low serum cortisol
• Regulator of adrenal androgen synthesis
• ACTH Deficiency: atrophy of zona glomerulosa and zona
reticularis
• Highest level: 6 am to 8am; Lowest: 6pm to 11pm
• Increased: Addison's disease, Ectopic tumor, after protein rich
meals
7|Page
POSTERIOR PITUITARY GLAND (NEUROHYPOPHYSIS)
• capable of releasing but not producing
• Supraoptic nuclei - ADH
• Paraventricular nuclei - Oxytocin
• Stimuli: osmolality and suckling
• Oxytocin - delivers milk
OXYTOCIN
• Cyclic nonapeptide
• Critical role in lactation
• Major role in labor and parturition
• Uterine contractions propagate oxytocin release
• Stimulates contraction of the gravid uterus "FERGUSSON
REFLEX”
• Synthetic preparation: To increase weak uterine contractions
during labor and to aid in lactation
VASOPRESSIN (ADH)
• Major action is to regulate renal free water excretion (central
role in water balance)
• Coupled to adenylate cyclase
• Potent pressor agent and effects blood clotting
o Promoting factor VII release (hepatocytes)
o von Willebrand factor release (endothelium)
• Vasopressin receptors (V1a and V1b) are coupled to
phospholipase C.
• Hypothalamic osmoreceptors: sensitive plasma osmolality
o As plasma osmolality increases, vasopressin
secretion increases.
• Inhibitor: ethanol, cortisol lithium, and demeclocycline
CLINICAL DISORDER
• Diabetes Insipidus: deficiency of ADH; result in severe
polyuria (23 L of urine/day)
• CLINICAL PICTURE INCLUDES:
1. Normoglycemia
2. Polyuria with low SG
3. Polydipsia (secondary to polydipsia)
4. Polyphagia (occasional)
 MAJOR TYPES OF DIABETES INSIPIDUS
A. True Diabetes Insipidus (Hypothalamic/ Neurogenic/
Cranial/Central Diabetes Insipidus)
o deficiency of ADH with normal ADH receptor
o failure of pituitary gland to secrete ADH
o large volume of urine excreted (3-20 L/day)
B. Nephrogenic Diabetes Insipidus
o normal ADH but abnormal ADH receptor

DIAGNOSTIC TEST FOR DIABETES INSIPIDUS

• Overnight Water Deprivation Test (Concentration Test)
o Fasting: 10pm onwards (8-12 hrs)
o After 8 to 12 hrs without fluid intake, urine
osmolality does not rise above 300 mOsm/kg.
o Neurogenic DI: Dec ADH
o Nephrogenic DI: Normal or Increase ADH

8|Page