CLINICAL CHEMISTRY 2

ENDOCRINE SYSTEM ClassificaCon of Hormones According to

•network of ductless glands that secrets ComposiCon or Structure
hormones
• regulatory system of the body Amines
HORMONES - Derived from an amino acid
• chemical signals produced by - Intermediary between steroid and protein
specialized cells hormones
• For growth and development of an
individual Pep6des
• regulated by the metabolic ac:vity -chain of amino acid
-pep:de hormones are hydrophilic
MAJOR FUNCTION: -not bound to carrier protein
- maintain constancy of chemical
composi:on of extracellular and Protein
intracellular fluids -chain of amino acid
- control metabolism -Primary, secondary, terCary structure
- Growth -formed from a large number of amino acid
- Fer:lity residues (50 a.a)
- responses to stress
Glycoprotein
Types of Hormone AcCons -conjugated proteins bound to carbohydrate,
Endocrine which include galactose, mannose or fructose
- Cellular messages are sent via bloodstream
- secreted in one locaCon and release into Steroids
blood circula:on - cholesterol as a common precursor
Paracrine - Produced by adrenal glands, ovaries, testes,
- Is secreted in endocrine cells and released and placenta
into intersCCal space - water insoluble and circulate bound to a
Autocrine carrier protein
- Binds to specific receptor cell of origin - Can cross cellular membranes easily
resul:ng to self regula:on of its - Delayed effect
func:on.
Juxtacrine Fa<y acids
- Acts immediately to adjacent cell by -made up of small faOy acid deriva:ves of
direct sell-to-cell contact arachidonic acid
Intracrine -rapidly degraded
- Secreted in the endocrine cells and
remained as well as func:on inside the
synthesis of origin
Exocrine
- secreted in the endocrine cells and released
into lumen of gut / gastrointesCnal tract

Neurocrine
- Secreted in neurons and released into
extracellular space

Neuroendocrine
- Secreted in neurons and released from nerve
endings

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CLINICAL CHEMISTRY 2

CLASSIFICATION OF MAJOR HORMONES

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CLINICAL CHEMISTRY 2

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CLINICAL CHEMISTRY 2

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CLINICAL CHEMISTRY 2
Hormone Metabolism
• Includes both Catabolism and
Anabolism
• 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 eliciFng their
intended effect
ALCOHOL CONSUMPTION
• Alcohol appears to increase
degradaFon of testosterone
• Reduced hormone concentraFon
ADRENAL STEROID HORMONE SYNTHESIS
• Produced via cascade of enzymaFc
reacFon
• Deficiency in 11-Beta-hydroxylase:
Dec in aldosterone and
glucocorFcoids, Shunt all cholesterol
into the sex steroid pathway
Mechanism of EliminaCon
• Organs for eliminaCng hormones:
Kidney and Liver
• EliminaCon of STEROID hormones:
inacFvaFng metabolic pathways and
excreFon in urine or bile
• InacCvaCon of THYROID hormones:
intracellular deiodinase
• DegradaCon of CATHECOLAMINES
within the blood circulaFon
• InacCvaCon of FATTY ACID
derivaCves via metabolism and are
acFve for a short period of Fme
Hormone Transport
• Circulate in the bloodstream in one
of the two forms: FREE (UNBOUND)
or PROTEIN BOUND
• Free floaFng hormones: suscepFble
to degradaFon
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WAYS THAT HORMONES CAN TRAVEL TO
DISTANT SITES IN THE BODY:
A. Solubility
B. Carrier Proteins
C. Micelles
Feedback mechanism
• PosiCve Feedback system:
- Is a system in which an increased in the
product results to elevaCon of the acCvity
of the system and the producFon rate
• NegaCve Feedback system:
- Is a system in which an increased in the
product results to decreased acCvity of the
system and the producFon rate
Other factors that affect Hormone Levels
• EmoFonal stress
• Time of the day
• Menstrual cycle
• Menopause
• Food intake/ Diet
• Drugs
HYPOTHALAMIC AND
PITUITARY FUNCTION
Hypothalamus
• Link between nervous system and
endocrine system.
• GnRH, GHRH, TRH, CRH,
somatostaFn, dopamine
• ADH (vasopressin), oxytocin
Pineal gland
• Melatonin - sleep hormone
Pituitary
-“spit mucus”
-master gland
-hypophysis (undergrowth)
-resides in a pocket of the sphenoid (the
sella turcica, meaning “Turkish saddle”)
-Anterior pituitary receives 80% to 90% of
its blood supply
CLINICAL CHEMISTRY 2

EMBRYOLOGY AND ANATOMY

3 DisCnct parts
-Anterior pituitary (adenohypophysis)
-Largest porFon
-Intermediate lobe (pars intermedialis)
-poorly developed in humans
-li[le funcFonal capacity
-Posterior pituitary (neurohypophysis)
-arises from the diencephalon
-storage and release of oxytocin and
vasopressin (ADH)
ANTERIOR PITUITARY HORMONES
*Pituitary funcFon can be detected Direct effectors
between the seventh and ninth weeks of - GH: Fmulates the liver to produce
gestaCon growth factors
- ProlacCn
FUNCTIONAL ASPECTS OF THE
HYPOTHALAMIC–HYPOPHYSEAL UNIT Tropic hormones
-LH: directs testosterone producFon from
Leydig cells in men and ovulaFon in women
-FSH: ovarian recruitment and early
folliculogenesis in women and
spermatogenesis in men
-TSH: directs thyroid hormone producFon
from the thyroid
-ACTH: regulates adrenal steroidogenesis

PITUITARY TUMORS
• ProlacCn-secreCng pituitary tumors
(Most common)
• NonfuncFoning or null cell tumors
A. Anterior Pituitary (Adenohypophysis) • Tumors that secrete GH,
- True Endocrine gland gonadotropins, ACTH, or TSH
- Released and producFon of hormones • Atypical pituitary tumors
such as ProlacFn, GH, Gonadotropins • MIB-1 proliferaFve index
(FSH, LH), TSH, and ACTH greater than 3%
5 TYPES OF CELLS BY IMMUNOCHEMICAL • MIB-1 : monoclonal anFbody
TEST that is used to detect the Ki-
Somatotrophs: secrete GH 67 anFgen
Lactotrophs or mammotrophs: secrete • marker of cell proliferaFon
prolacFn • high “proliferaCon index” suggests
Thyrotrophs: secrete TSH higher degree of atypia
Gonadotrophs: secrete LH and FSH • excessive p53
CorCcotrophs: Secretes immunoreacFvity
prooplomelanocorFn • increased mitoFc acFvity
• macroadenomas (i.e., >1 cm
in diameter)
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CLINICAL CHEMISTRY 2
• Enlargement of the pituitary
• seen during puberty and
pregnancy (lactotroph
hyperplasia)
GROWTH HORMONE
• somatotropin
• structurally related to prolacFn and
human placental lactogen
• sFmulated by growth hormone–
releasing hormone (GHRH)
• inhibited by SomatostaFn
• GH is secreted in pulses (interpulse
interval of 2 to 3 hours)
• reproducible peak occurring at the
onset of sleep
• Ghrelin : nutrient sensing, appeFte
and in glucose regulaFon
• potent sFmulator of GH
secreFon.
AcCons of GH
• amphibolic hormone (directly
influences both anabolic and
catabolic processes)
• allows an individual to effecFvely
transiCon from a fed state to a
fasCng state without experiencing a
shortage of substrates required for
normal intracellular oxidaFon
• antagonizes the effect of insulin on
glucose metabolism, promotes
hepaFc gluconeogenesis, and
sFmulates lipolysis.
• Anabolic effects :enhanced protein
synthesis in skeletal muscle and
other Fssues
• indirect effects : somatomedins
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• shieed to insulin- like growth
factor (IGF) : somatomedin C
(IGF-1)
TesCng
• DefiniCve test: oral glucose loading
• Performed aeer an overnight
fast
• Px t is given a 100 g oral
glucose load
• GH is measured at Fme zero
and at 60 and 120 minutes
aeer glucose ingesFon.
• NORMAL: GH
UNDETECTABLE
• ACROMEGALY: GH levels fail
to suppress and may even
paradoxically rise.
• insulin-induced
hypoglycemia : Gold
standard
• Infusions of GHRH and the amino
acid L-arginine or an infusion of L-
arginine coupled with oral L-DOPA
• GH levels rise above 3 to 5
ng/mL, it is unlikely that the
paFent is GH deficient
Acromegaly
• autonomous GH excess
• OVER PRODUCTION OF GH
(>50 NG/ML OR 2210
PMOL/L)
• pituitary tumor
• result of the ectopic producFon of
GHRH
• GH-producing tumor: paFent
develops giganFsm
• overt diabetes can occur.
• lee untreated, acromegaly shortens
life expectancy
• paFents with acromegaly also have a
greater lifeFme risk of developing
cancer
• GH to glucose loading is the
definiFve test
• Transsphenoidal adenomectomy:
procedure of choice
CLINICAL CHEMISTRY 2
GH Deficiency
• occurs in both children and adults
• CHILDREN: may be geneFc or
it may be due to tumors
(craniopharyngiomas)
• recessive mutaCon in the GHRH
gene: Failure of GH secreFon
• structural lesions of the pituitary or
hypothalamus
• adult GH deficiency syndrome:
complete or even parFal failure of
the anterior pituitary
Idiopathic growth hormone deficiency
• Most common cause of GH
deficiency in children
• Pituitary dwarfism, normal
proporFons are retained
• No intellectual abnormaliFes
Pituitary Adenoma
-Most common eFology in adult-onset GH
deficiency
DiagnosCc Test:
-Px Prep: Complete rest 30 mins before
blood collecFon
-Spx req: preferably fasFng
TEST FOR GH DEFICIENCY
A. Screening Test: Physical AcFvity Test
(Exercise Test)
-Result: INC serum GH
-If GH fails to INC, CONFIRMATION must be
made
B. Confirmatory Test
-Insulin Tolerance Test: Gold standard
-Arginine sFmulaFon test: 2nd confirmatory
test
-Procedure: 24 hr or nighime monitoring
of GH
Test For Acromegaly
A. Screening Test : Somatomedin C or
insulin-like growth factor (IGF-1)
-IGF-1: INC in px with Acromegaly
B. Confirmatory Test: Glucose Suppression
Test –OGTT (75g glucose)
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-Blood is collected every aeer 30 mins for 2
hrs
-FasFng sample is required
PROLACTIN
• structurally related to GH and human
placental lactogen (lactogenic hormone)
• stress hormone
• direct effector hormone
• ProlacCn inhibitory factor (PIF) :
capable of inhibiFng prolacFn secreFon
• dopamine : only neuroendocrine signal
that inhibits prolacFn (elusive PIF)
• TRH directly sFmulates prolacFn
secreFon
• Estrogens also directly sFmulate
lactotrophs to synthesize prolacFn
• HyperprolacFnemia may also be seen in
renal failure and polycysFc ovary
syndrome.
• Physiologic stressors, such as exercise
and seizures, also elevate prolacFn
• HIGHEST SERUM LEVEL (DURING
SLEEP): 4 AM AND 8am; 8pm and 10 pm
• Method: immunometric assay
ProlacCnoma
• pituitary tumor that directly secretes
prolacFn
• most common type of funcFonal
pituitary tumor.
• depends on the age and gender of
the paFent and the size of the
tumor.
Other Causes of HyperprolacCnemia
-elevaFons in prolacFn (>150 ng/mL)
indicate prolacFnoma
-Modest elevaFons in prolacFn (25 to 100
ng/mL): pituitary stalk interrupFon
-Breast or genital sFmulaFon: elevate
prolacFn
-pregnancy
-macroprolacCnemia: 150-kD form
CLINICAL CHEMISTRY 2
Clinical EvaluaCon of HyperprolacCnemia
• TSH and free T4 to eliminate primary
hypothyroidism
• pituitary tumor : assessment of
other anterior pituitary funcFon
• basal corFsol
• LH
• FSH
• gender-specific gonadal
steroid [either estradiol or
testosterone]
• evaluaFon of sellar anatomy
with a high-resoluFon MRI
Management of ProlacCnoma
• observaFon, surgery, radiotherapy, or
medical management with dopamine
agonists.
• macroadenomas [tumor size >10 mm):
less likely to be “cured”
• microadenomas [tumor size < 10 mm]
• Dopamine agonists are the most
commonly used therapy for
microprolacFnomas
• bromocripFne mesylate (Parlodel) or
cabergoline (DosFnex)
Idiopathic Galactorrhea
• LactaFon occurring in women with
normal prolacFn levels
• manifestaFon of a localized increased
sensiFvity to prolacFn in breast Fssue.
HYPOPITUITARISM
-Panhypopituitarism : Complete loss of
funcFon
-Monotropic hormone deficiency: loss of
only a single pituitary hormone
-loss of a tropic hormone (ACTH, TSH, LH,
and FSH) : cessaFon of the affected
endocrine gland.
CAUSES OF HYPOPITUITARISM
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Treatment of Panhypopituitarism
• PaFents are treated with thyroxine,
glucocorFcoids, and gender-specific
sex steroids
• PulsaFle GnRH infusions have
induced puberty and restored
ferFlity in paFents with Kallmann's
syndrome
• Gonadotropin preparaFons have
restored ovulaFon/spermatogenesis
in people with gonadotropin
deficiency.
Gonadotropins-Follicle SCmulaCng
Hormone (FSH) and LeuCnizing Hormone
(LH)
• Important markers in diagnosing
ferFlity and menstrual cycle
• FSH aids in spermatogenesis
• LH helps Leydig cells to produce
testosterone (MALE)
• LH for ovulaCon and final follicular
growth (FEMALE)
• ElevaFon of FSH: diagnosis of
premature menopause
• Increased of FSH and LH aeer
menopause: Lack of estrogen
Thyroid SCmulaCng Hormone (TSH)
• Known as thyrotropin
• Main sFmulus for the uptake of
iodide by the thyroid gland
• Blood levels may contribute in the
evaluaFon of inferFlity
AdenocorCcotrophic Hormone (ACTH)
• Produced in response to low serum
corFsol
• Regulator of adrenal androgen
synthesis
• ACTH Deficiency : atrophy of zona
glomerulosa and zona reFcularis
• Highest level: 6 am to 8am; Lowest:
6pm to 11pm
• Increased: Addison’s disease, Ectopic
tumor, aeer protein rich meals
CLINICAL CHEMISTRY 2
Posterior Pituitary gland
(Neurohypophysis)
– capable of releasing but not producing
– SupraopFc nuclei - ADH
– Paraventricular nuclei - Oxytocin
– SFmuli: osmolality and suckling
Oxytocin
• cyclic nonapepFde
• criFcal role in lactaFon
• major role in labor and parturiFon
• uterine contracFons propagate oxytocin
release
• SFmulates contracFon of the
gravid uterus “FERGUSSON
REFLEX”
• SyntheCc preparaCon: To increase weak
uterine contracFons during labor and to
aid in lactaFon
Vasopressin
• major acFon is to regulate renal free
water excreFon (central role in
water balance)
• coupled to adenylate cyclase
• potent pressor agent and effects
blood cloing
• promoFng factor VII release
(hepatocytes)
• von Willebrand factor release
( endothelium )
• vasopressin receptors (V1a and V1b)
are coupled to phospholipase C.
• Hypothalamic osmoreceptors:
sensiFve plasma osmolality
• As plasma osmolality
increases, vasopressin
secreFon increases.
• Inhibitor: ethanol, corFsol lithium,
and demeclocycline
Clinical Disorder
• Diabetes Insipidus: deficiency of
ADH; result in severe polyuria (> 3 L
of urine/day)
CLINICAL PICTURE INCLUDES:
1. Normoglycemia
2. Polyuria with low SG
3. Polydipsia (secondary to polydipsia)
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4. Polyphagia (occasional)
Major Types of Diabetes Insipidus
A. True Diabetes Insipidus (Hypothalamic/
Neurogenic/ Cranial/Central Diabetes
Insipidus)
-deficiency of ADH with normal ADH
receptor
-failure of pituitary gland to secrete ADH
-large volume of urine excreted (3-20 L/day)
B. Nephrogenic Diabetes Insipidus
-normal ADH but abnormal ADH receptor
DiagnosCc Test for Diabetes Insipidus
• Overnight Water DeprivaCon Test
(ConcentraCon Test)
• FasFng: 10pm onwards (8-12 hrs)
• Aeer 8 to 12 hrs without fluid
intake, urine osmolality does not
rise above 300 mOsm/kg.
• Neurogenic DI: Dec ADH
• Nephrogenic DI: Normal or
Increase ADH
REFERENCE:
• Bishop, Michael et al. (2010). Clinical
Chemistry: Techniques, Principles,
Correla6ons 9th edi6on. USA: LippincoO
Williams & Wilkins. (textbook)
• McPherson, R. and Pincus, M. (2011).
Henry’s Clinical Diagnosis and
Management by Laboratory Methods
24nd edi6on. Philadelphia: Elsevier
• Rodriguez, Maria Teresa (2018). Clinical
Chemistry Review Handbook For
Medical Technologists.
PREPEARED BY:
CHARLENE PRINCESS TOLENADA, RMT,MSMT 😊