hrmone

1. Endocrinology
1

2. Objectives
• Upon completion of this chapter the student
will be able to:
– Describe hormonal actions
– Classify hormones(structurally and functionally)
– Discuss the mechanisms of action (organ/system
level), control and regulation
– Discuss hormone secretion and regulation
– Describe the causes of hormone disorder
– Identify the endocrine glands
2

3. Objectives
• Describe the source, classification, chemical
nature and clinical significance and lad diagnosis
of:
– Anterior pituitary hormones
– Posterior pituitary hormones
– Adrenocortical hormones
– Adrenomedullary Hormones
– Thyroid hormones
– Gonadal hormones
– Parathyroid Hormones
3

4. Outline
• Definition
• hormonal actions
• Structural classes of
hormone
• Functional types of
hormones
• Mechanisms of action
• hormone secretion
• Regulation of hormones
• Hormone disorder
• Endocrine glands
• Anterior pituitary
hormones(GH, prolactin, TSH,
ACTH, FSH, LH)
• Posterior pituitary
hormones(ADH, oxytocin)
• Adrenocortical hormones
• Adrenomedullary Hormones
• Thyroid hormones
• Gonadal hormones
4

5. Introduction
• Endocrinology
– Science that deals with a group of ductless glands and the
action of their secretions which are transported via
bloodstream.
– The study of hormones and disorders associated with
abnormalities of these hormones.
• Hormones
– Any substance normally produced by specialized cells in some part of the
body, carried by the bloodstream to another from which it affects the
body as a whole.
– Substances that serve as vehicles for intracellular and extra cellular
communication
• Endocrine system: collection of endocrine glands, hormones,
carrier protein and other components of functional processes. 5

6. Hormonal actions
• Endocrine: hormones are synthesized in one location and
released into the bloodstream.
• Paracrine: hormones are synthesized in endocrine cells and
released into the interstitial space and act on neighboring cells.
• Autocrine: hormones are synthesized in endocrine cells and
typically act on a receptor in the cell of origin.
• Juxtacrine: hormones are synthesized in endocrine cells and act
on adjacent receptor cells by direct cell-to-cell contact.
• Neuroendocrine: hormones are synthesized in cells of the
nervous system and released into the blood circulation.
6

7. Hormonal actions
7

8. Permissive
Exposure to one hormone enhances action of second
hormone
Synergistic
Two or more hormones are required for one effect
Antagonistic
Two hormones have opposing actions
Hormonal Interactions
8

9. • Homeostasis: maintaining constant internal environment in
the body fluids
• Regulate growth/development of the body
• Promote sexual maturation, sexual rhythms, and facilitate
reproduction
• Regulate energy production and stabilize the metabolic rate
• Adapt/adjust body to stressful/emergency situations
– Stress, dehydration, starvation, hemorrhage, temperature extremes
• Promote/inhibit the production or release of other
hormones
• Helps to regulate the immune system.
Functions of Hormones
9

10. Forms of Hormones in the Blood
• Free
– It is not carried on a plasma protein
– It can bind directly to the receptors : active
– It is small in size , so can be filtered in urine
• Protein bound
– Carried on plasma protein
– It acts as a reservoir.
– It increases the half life of the hormone.
– It is more soluble in plasma
– It is large in size , and so is not filtered in urine .
10

11. • Structural classes of hormones: Steroids, proteins,
and amines.
– Result in differences in transport, mechanism of
action, and metabolic characteristics.
• Steroid hormones
– Lipid in nature, immediately diffuse through the cell
membrane
– water insoluble: the greatest concentration of hormone is
bound to a carrier molecule(protein)
– Has long plasma half-life: ranges from 4 to 120 minutes.
– Produced by adrenal gland (cortisol, aldosterone, sex
steroids), gonads and placenta(testesterone, estrogen,
progesterone)
– All synthesized from cholesterol in different sites
Structural classes
11
not T

12. • Protein hormones
– Either peptides or glycoproteins in nature.
– Most are synthesized as larger molecules or prohormones,
which are then cleaved to produce a smaller, active molecule.
– Water soluble and not bound to carrier molecules for
transportation in blood.
– Has shorter half-life than the steroid hormones.
• Typical plasma half-life is 4 to 40 minutes
• Example: Releasing hormones, Oxytoxin, Antidiuretic
hormone, Insulin, Glucagon, Parathyroid hormone, GH,
ACTH, TSH, FSH, HcG, LH
Structural classes cont’d
12

13. • Amine hormones
– Amino acid derivatives
– Poorly soluble in plasma
– Have properties between those of protein and
steroid hormones
– Includes:
• T3/T4-circulate bound to carrier protein
• Epinephrine and nonepinephrine: circulate
unbound to protein
Structural classes cont’d
13

14. a. Releasing factors: From the hypothalamus that
promote secretion of some pituitary hormones.
b. Inhibitory hormones
• Come from the hypothalamus or GI tract
• suppress the secretion of particular hormones.
c. Tropic hormones
• Come from the anterior pituitary gland
• Stimulate growth and activity of other hormones
d. Effector hormones
Functional types of hormones
14
W
R
I
T
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15. d. Non-tropic or effector hormones
– Secreted by all endocrine gland.
– Their target cells are: particular non-endocrine cells/tissue
cells (where they exert their metabolic effects)
– Exert a feedback effect upon either the hypothalamus or
anterior pituitary glands
• Negative feedback: an increase in the product causes a
decrease in the system
• Positive feedback: an increase in the product causes an
increase in the activity of the system
– Eg: T4 and T3: affect metabolic rate of all tissues
• GH: stimulate skeletal growth and affect many metabolic
process
Functional types of hormones
15

16. Hormonal action up on target cells
(mechanism of action)
Protein hormones and catecholamine
• On cell membrane of target cell hormone combines with its
specific receptor.
• This combination activates adenyl cyclase
• The activated adenyl cyclase convert ATP into Cyclic AMP.
• Cyclic AMP activates protein Kinases.
• The activated protein kinases catalyses phosphorylation of
proteins and alter their functions.
• Hormonal action on the cell membrane is usually
short-lived because of rapid conversion to inactivate
metabolites by enzymes. 16

17. mechanism of action cont’d
Steroid and thyroid hormones
• Hormones of these class enter the target organ
cells(cytoplasm) and bind with intracellular receptors.
• The combined hormone receptor diffuse into the nucleus.
• Then it activates the transcription process of specific
genes to form a messenger RNA.
• The messenger RNA diffuse to ‘ cytoplasm to promote
synthesis of specific protein & enzymes within ribosomes
• These hormones have relatively long term effects and
indirectly affect many metabolic systems
17

18. Comparison of Steroidal and Non-
steroidal Transport
18

19. • Signals that initiate production and secretion of
hormone by endocrine glands include:
– The nervous system: Stimulation of cerebral
cortex(neural centers) by thoughts, emotions, stress,
periodic rhythm, chemical transmitters at nerve
junction (dopamine, norepinephrine).
• These stimulates release of hypothalamic
hormones or adreno medullary hormones
– Change in plasma concentration of ions:
• Example: secretion of PTH(in low ca2+) and
insulin(when glucose level is high)
Hormone Secretion
19

20. Hormone Secretion cont’d
• Signals that initiate production and secretion of
hormone by endocrine glands include:
– Secretion of tropic hormones.
• Example: ACTH cause adrenal gland to secrete cortisol,
TSH cause thyroid gland to secrete T4 and T3
– Variation of blood osmolality
• Example: ADH secreated in increased plasma osmolality
– Foods:
• Example: food in stomach stimulates gastrin secretion
20

21. Regulation of Hormones
• Regulation by central nervous system
– secretion is regulated by interaction between
nervous and endocrine system
– It trigger the release or suppression of hormones by
action potential or neurotransmitter released within
the gland
• Eg: feeling of fear transmit a message from brain by
sympathetic nervous system to adrenal medulla→result
epinephrine secretion
– Hormone interact with brain by affecting mood and
emotion
21

22. Regulation by hypothalamus
• Located at base of brain and connected to pitutary stalk
• Role: it release hormones that selectively stimulate or inhibit the
secretion of specific anterior pitutary hormones
• Suffix “liberin”: for stimulating hormone, eg
somatoliberin(somatotropin releasing hormones)
• Suffix “statin”: for inhibitor, eg somatostatin
• The hormones include: GHRH, CRH, TRH, GnRH, PRH, PIF
• It is activated by CNS, emotion or stress to secrete releasing
factors → stimulate the anterior pitutary to secrete the
appropriate tropic hormones
• Has factors such as somatostatin (inhibit output of GH and
prolactin) and dopamine 22

23. Regulation by anterior pituitary
• Releasing hormones from hypothalamus
trigger secretion of:
– Tropic hormones: ACTH. TSH, FSH and LH:
• Act on adrenal cortex, thyroid, and gonads and
stimulate secretion of their particular hormones
– Effector hormone: GH and Prolactin,
• Exert feedback inhibition on hypothalamus(to
retard/block further secretion of releasing factors(RF)
and on anterior pitutary (to inhibit secretion of tropins)
23

24. Feedback Control mechanisms
• They are systems in which the function of one hormone
affects the function of another hormone.
• Has major role in the regulation of hormone levels
• Feedback control mechanisms can be either positive or
negative in nature.
• Negative feedback control mechanisms occur when the
concentration of one hormone causes a decrease in
another hormone
• Positive feedback control mechanisms occur when the
function of one hormone results in an increase in
another hormone
24

25. Neural and Sensory input
Hypothalamus
(Releasing and inhibiting factors)
Pituitary
(Tropic hormone)
Thyroid gland
(Secretory hormones)
Target tissue
+
+
_
_
Thyroxine
Thyroxine
SFL
LFL
25

26. Endocrine disorders
• Overproduction or underproduction of various
hormones leads to abnormalities.
• The endocrine dysfunction is complex problem and
caused by:
– Malfunction of the endocrine gland in question
– Deficiency of a tropic hormone (pituitary dysfunction)
– Deficiency of releasing factors (hypothalamus or feed
back control dysfunction)
– A defect in the target cells
– Other factors involving transport proteins or
autoimmune disease. 26

27. Endocrine disorders cont’d
• Pinpointing the pathologic process responsible for an
endocrine abnormality is further complicated by the
problem of ectopic hormones.
• Ectopic hormones are hormones produced else where
in the body than in the customary endocrine gland.
• Many types of malignancies produce ectopic hormones
that do not respond to the normal regulatory
processes of the body.
27

28. Endocrine Glands
• Pituitary gland (anterior & posterior)
• Thyroid gland
• Parathyroid gland
• Adrenal gland (cortex & medulla)
• Islets of langerhans ( in the pancreas)
• Male gonads ( testes) & Female gonads
• Placenta
28

29. 29

30. Other Endocrine Organs
• Stomach (gastrin)
• Small intestine (duodenumintesetinal gastrin,
secretin, cholecystokinin)
• Heart (atrial natriuretic peptide)
• Kidneys (erythropoietin, active vitamin D3, renin)
• Adipose tissue (leptid, resistin)
30

31. Pituitary hormones
• Pituitary gland situated at the base of the skull
• It is connected to ‘brain by’ pituitary stalk.
• It is referred to as the Master Gland
• Pituitary gland is composed of two distinct parts
• The anterior lobe(adenohypophysis)
• The posterior lobe(neurohypophysis)
31

32. 32

33. • Hormones of anterior pituitary :
– Tropic hormones
• Thyroid stimulating Hormone(TSH) : acts on thyroid gland.
• Adreno-cortico trophic Hormone(ACTH): acts on adrenal
cortex.
• Gonado trophic Hormone( FSH &LH): act on ovaries &
testes.
– Effector hormones
• Prolactin(PRL): act on mammary gland.
• Growth Hormone(GH) : generalized effects.
• Hormones of the Posterior Pituitary:
– Anti diuretic hormone.
– Oxytocin. 33

34. Anterior pituitary cells and hormones
Cell type Pituitary
populatio
n
Product Target
Corticotroph 15-20% ACTH Adrenal gland
Thyrotroph 3-5% TSH Thyroid gland
Gonadotroph 10-15% LH, FSH Gonads
Somatotroph 40-50% GH All tissues,
liver
Lactotroph 10-15% PRL Breasts
gonads
34

35. Growth hormone/Somatotropin
• A single peptide made up of 191 amino acids
• Produced in the largest quantity by the anterior pituitary
• Produced by somatotrophs under the control GH releasing
hormones from the hypothalamus.
• Plays an important role both at birth and at puberty
– Coordinates normal growth and development.
• Receptors that respond to GH exist on cells and tissues
throughout the body.
• The most pronounced effect of GH is on linear skeletal
development, but GH also greatly increases lean muscle
mass.
35

36. Actions of Growth Hormone
• GH has many diverse effects on metabolism
• it is considered an amphibolic hormone because it directly
influences both anabolic and catabolic processes
• enhanced protein synthesis in skeletal muscle and other
tissues, decreases protein catabolism
• GH directly antagonizes the effect of insulin on glucose
metabolism, promotes hepatic gluconeogenesis, and
stimulates lipolysis
– Effect on fats: it has a lipolytic effect: to give energy.
– Effect on CHO: It has diabetogenic effect
• Decrease glucose utilization, Increase glycogen deposition,
• Decrease number of insulin receptors, Decrease glucose
uptake by the cells
36

37. Actions of Growth Hormone cont’d
• GH also has indirect effects that are mediated by factors
that were initially called somatomedins
• Causes the liver to form somatomedins that strongly
increase all aspects of bone growth
– stimulation of osteoblasts, increased protein deposition by
chondrocytic & osteogenic cells
• Effects of somatomedins on growth are similar to that of
insulin so it is called Insulin like growth factors( IGFs).
• It cause increase glucose & amino acids uptake by the cells.
• Growth hormone exerts its effects on bones through
somatomedins
37

38. Actions and Control of GH
38

39. Other Effects of GH
• Stimulates Erythropoiesis.
• Increase Ca+ + absorption at GIT & produce
phosphate balance.
• Decrease urinary excretion of Na+, K+: both
needed for growth of tissues.
39
Wc is odd based on its action

40. Regulation Of GH Secretion
1. Hypothalamic control :1- G H R H & Somatostatin H. (G H IH)
• Mainly by negative Feed - Back Control
• Somatostatin produced by : hypothalamus and delta cell of
islets of langerhans of pancreas
• Somatostatin inhibits secretion of : Growth Hormone,insulin
glucagon.
2. IGFs: it is produced by the liver, it decrease G H secretion by
direct inhibition of pituitary& ↑somatostatin.
3. Ghrelin H, secreted by stomach→ ↑G H + ↑appetite.
40

41. Stimuli that increase GH secretion
• Hypoglycemia
• Decrease level of cell protein.
• Increase concentration of fatty acids in blood.
• Exercise, emotions, stress, deep sleep
• Growth Hormone level has diurnal variation.
41

42. Clinical correlation
• Dwarfism (very small stature)
– caused by underproduction of GH or IGF-I
– Slow bone & organ growth, reduced adult height & abnormal
body proportions
• Gigantism or acromegaly
– Overproduction of hGH or IGF-I
– Characterized by a very large stature.
– Gigantism is the result of hGH overproduction in early
childhood, leading to a skeletal height up to 8 feet (2.4 m)
• the epiphyseal plates of the long bones do not close, and
they remain responsive to hGH.
– Acromegaly results when hGH is overproduced after the onset
of puberty.
• Characterized by an enlarged skull, hands and feet, nose,
neck, and tongue owing to proliferation of connective
tissue.
42
T/F

43. Laboratory diagnosis
• Specimens heparin or EDTA plasma from a fasting
patient.
• The various tests are highly influenced by the fasting or
non-fasting state, presence or absence of recent
exercise
• Growth hormone in plasma or urine is usually measured
by radioimmunoassay (RIA).
• Fluorescent, Chemiluminescent and enzyme
immunoassays are also available
43

44. Lab diagnosis cont’d
• Diagnosis is made either by a provocative test or
measurement of IGF-I.
• Provocative testing for hGH deficiency involves:
– Administration of a drug known to stimulate release
of growth hormone
• Drugs used include arginine, insulin and
propranolol.
– Vigorous exercise: stimulate release of growth
hormone
44

45. Lab diagnosis cont’d
• In the exercise test, a blood sample is measured for
GH immediately following exercise performed
vigorously for 20 minutes.
– A level around 6 ng/ml rules out growth hormone
deficiency.
– A lower response is suggestive and is followed by
a drug stimulation test.
– Growth hormone is increased in approximately
90% of persons with acromegaly (caused by an
adenoma in the pituitary that produces GH)
45

46. Lab diagnosis cont’d
• A glucose suppression test
– Performed by giving 100 grams of glucose orally,
and collecting a blood sample one hour later.
– The glucose should suppress GH to below 1
ng/mL.
– Failure to do so is evidence of acromegaly
• A deficiency of IGF-I occurs in both GH deficiency and
protein malnutrition.
46

47. Normal value
• GH ranges from undetectable to 5ng/mL for adult
men, up to 10 ng/mL for adult women, and as high as
16 ng/mL in children over six years.
• Decreased levels are seen in GH deficiency,
dwarfism, hyperglycemia, and delayed sexual
maturity.
• Excess GH is responsible for the syndromes of
gigantism and acromegaly.
• Excess secretion is stimulated by anorexia nervosa,
stress, hypoglycemia, and exercise.
47

48. Prolactin(PRL)
• Effector hormone secreted by anterior Pituitary.
• Function :
– Stimulate milk secretion by mammary gland.
– Stimulate synthesis of fat & lactose by mammary gland.
– Inhibit the action of gonadoropin  inhibition of ovulation
amenorrhea & lactation.
• In males : unknown functions:
– If excess Prolactin  impotence.
48

49. Prolactin regulation
49

50. Prolactin cont’d
• Hyperprolactinemia is the most common hypothalamic-
pituitary disorder encountered.
• PRL concentration may be elevated
• In women who have alterations of fertility such as
anovulation with or without menstrual irregularity,
amenorrhea, and galactorrhea
• In men is frequently manifested as impotence
• Pituitary tumors
50

51. Lab diagnosis
• Prolactin levels should be drawn in the morning at
least two hours after the patient wakes
– samples drawn earlier may show sleep-induced peak levels
• No specific preparation is necessary for drawing, but
illness and stress can affect results significantly.
• Prolactin deficiency is rare, and like GH it cannot be
diagnosed without a provocative test because low
and normal levels overlap.
• As with GH, a normal or elevated level will rule out a
deficiency.
• Different immunoassay methods(RIA, EIA, CLIA, FPIA)
51

52. Reference range
• Generally between 3-15 ng/mL for adult males and 3.8-
23 ng/mL for non pregnant adult females.
• Prolactin levels in pregnancy vary greatly with the time
of gestation.
– Normal values in the third trimester are 95-475 ng/mL.
• Increased prolactin levels are found in:
– Galactorrhea, amenorrhea, hypothyroidism, prolactin
secreting pituitary tumors, infiltrative diseases of the
hypothalamus, and metastatic cancer of the pituitary gland.
– stress, which may be produced by anorexia nervosa, surgery,
strenuous exercise, trauma
• Decreased prolactin levels are seen in pituitary failure.
52

53. Thyroid stimulating hormones (TSH, thyrotropin)
• A glycoprotein composed of two chains (α and β
subunits.
– The α subunit is common to TSH, LH, FSH, and hCG,
but β-chain is unique.
• Major regulator of thyroid secretion and function
• Released by the anterior pituitary in response to thyroid
releasing hormone (TRH) from the hypothalamus.
• Results in synthesis, storage, and release of T3 and T4,
the thyroid hormones.
• Elevated levels of free T3 and T4 exert negative
feedback on the hypothalamus inhibiting the release of
TRH which reduces TSH. 53

54. TSH cont’d
• Serum TSH measurement is of value in the differential
diagnosis of thyroid disease
• Commonly measured by immunoassay
• The best screening test for diagnosis of both
hypothyroidism and hyperthyroidism.
• In primary hypothyroidism, the plasma level of free T4
will be low and TSH will be elevated.
• In primary hyperthyroidism, the plasma level of free T3
will be high and TSH will be low.
• In thyroid disease caused by pituitary failure, the TSH
and thyroid hormones will move in the same direction.
• For example, in secondary hypothyroidism, both free T4 and
TSH will be low 54

55. Adrenocorticotropin (ACTH)
• A long chain polypeptide that binds to cells of the
adrenal cortex and influence their activities
• Its initial action is to stimulate the formation of adrenal
steroids by increasing the synthesis of pregnenolone
from cholesterol.
– The net effect is an increase in the secretion of cortisol and
adrenal androgens
• ACTH production is controlled by the production of
corticotropin-releasing hormone (CRH) by the hypothalamus.
• The release of this neuropeptide is inhibited by plasma
cortisol via negative feedback
55

56. ACTH cont’d
• ACTH is measured by RIA or fluorescent and
chemiluminescent enzyme immunoassay.
• ACTH in plasma is measured in order to help
differentiate the cause of Cushing's disease.
• High levels of ACTH are found in:
– Primary adrenal cortical deficiency
– Cushing’s disease(hyperactivity of the adrenal cortex
by excessive pituitary ACTH secretion)
– Ectopic tumors that produce ACTH
56

57. Gonadotropins (FSH, LH)
• Glycoproteins necessary for proper maturation and
function of the gonads both in men and women
• Induce growth of the gonads and secretion of gonadal
hormones
• necessary for the reproductive process (development of
mature ova in females and spermatozoa in males)
• Regulated by the hypothalamic release of
gonadotropin-releasing hormone.
• In males, both hormones are inhibited via negative
feedback by testosterone.
• In females, both hormones are inhibited via negative
feedback by estrogen and progesterone. 57

58. FSH, LH cont’d
• FSH and LH are performed when a person exhibits
abnormal reproductive function.
– In women such conditions as precocious puberty,
polycystic ovaries, failure to ovulate,
dysmenorrhea, and the onset of menopause are
the primary reasons for measuring these
hormones.
– In males, these hormones are measured along
with testosterone to diagnose and differentiate
the cause of gonadal failure.
58

59. The Posterior Pituitary Lobe
• No hormones are made here.
• Hormones are initially synthesized in the cell bodies of
the supraoptic & paraventricular nuclei of the
hypothalamus, & then transported in combination with
“carrier” proteins called neurophysins down to the
nerve ending in the posterior pituitary.
• Two peptide hormones are released from the posterior
pituitary lobe (the neurohypophysis):
– ADH (antidiuretic hormone or vasopressin)
– OT (oxytocin)
59

60. 60

61. Function of Antidiuretic hormone(ADH)
• On the kidneys :
– ADH acts on the distal portions of nephrons (in the
collecting duct and collecting tubules), increasing
their permeability to water.
• ADH increases the reabsorption of water by the kidney.
• On blood vessels
– ADH is potent vasoconstrictor. It acts on vascular
smooth muscle.
– In moderate concentration has a very potent effect of
constricting the arterioles so, increasing the arterial
pressure. 61

62. Control Of ADH
• Osmotic stimuli
– Controlled by a feed back mechanism that act to
maintain the plasma osmolality close to 290
mosm/L.
– The change in osmolality is sensed by osmoreceptor
cells present in the hypothalamus which transmit
signals to cells secreting ADH.
• Volume depletion
– Decrease in circulatory volume and mean arterial
pressure will increase ADH.
62

63. Control Of ADH cont’d
• Angiotensin II
– Acting on the brain to increase vasopressin
secretion.
• Drugs
– Some drugs such as nicotine, morphine,
tranquilizer and some anesthetics lead to increase
ADH secretion.
– Alcohol decreases secretion of ADH.
• Stress
– Lead to increase ADH as severe pain, trauma,
exercise and surgical operation.
63

64. Clinical Significance of ADH
• Syndrome of inappropriate ADH Secretion (SIADH):
– Hypersecretion of ADH, excessive water retention
• Diabetes Insipidus
– Hyposecretion of ADH, inability to conserve water
appropriately
64

65. OXYTOCIN
• Function:
• Milk Ejection
– It causes contraction of special smooth muscle like
cells known as myoepithelial cells that line the
alveoli and ducts of the mammary gland thus
squeezing milk outwards through the nipple.
• Contraction of smooth muscle of uterus :
– It causes contraction of the smooth muscle fibers
of both pregnant or non-pregnant uterus. It is used
clinically for the induction of labor.
65

66. Control Of Oxytocin Secretion
1. The sucking of the breast stimulates touch receptors
in the nipple, sensory nerves transmit impulse upward
to the hypothalamus to cause release of oxytocin.
2. The secretion of oxytocin is increased by genital
stimulation.
3. Fear, Pain, anxiety and alcohol cause inhibition of
oxytocin release.
66

67. Adrenal gland hormones
67

68. Adrenal glands
• Adrenal glands: two small, triangular-shaped glands
located at the upper portion of each kidney
• It is composed of an outer cortex and an inner medulla
• Outer cortex
– Outermost zona glomerulosa: Synthesis site of
mineralocorticoids
– Central zona fasciculata: Synthesis site of glucocorticoids
– Inner zona reticularis: Synthesis site of adrenal sex steroid
hormones
• Inner medulla: Synthesis site of catecholamines
68

69. 69

70. 70

71. Adrenal cortical steroid synthesis
• The adrenal cortical steroid hormones are derived from the
cholesterol via a branched metabolic pathway
71

72. Glucocorticoid (Cortisol)
• Cortisol is the principal glucocrticoids
• Target organ - every cell of the body
• Effects
– Regulation of carbohydrate, protein and lipid
metabolism; maintenance of blood pressure and
suppression of the immune response
• General characteristics
– Steroids, lipid-soluble, protein bound, slow effects
72

73. Regulation of cortisol secretion
• Hypothalamic regulation: it produces cortico-tropin
releasing factor(CRF).
• Pituitary regulation: it produces ACTH in response to
CRF
• Negative feed-back: cortisol has direct –ve feed back
effect on hypothalamus to decrease CRF & on pituitary
to decrease secretion of ACTH.
• Effect of physiological stress on ACTH secretion: Physical
& mental stress can lead to increase cortisol secretion
within minutes via increase ACTH.
73

74. 74

75. CNS stimuli

Hypothalamic hormone CRH

Anterior pituitary hormone ACTH

Target gland Adrenals

Target hormones Glucocorticoids
Sex steroids
75

76. Glucocorticoid transport
• The lipid-soluble glucocorticoids are transported in
circulation bound to carrier proteins
– Cortisol is 90-97% protein-bound
• Cortisol-binding globulin (CBG) – major transport protein
• Albumin
• Sex-hormone binding globulin (SHBG)
– Conditions that change the level of binding protein affect the
level of total hormone, but not of the biologically active free
hormone
• Causes of increased CBG
– Estrogen, hyperthyroidism, etc.
• Causes of decreased CBG
– Malnutrition, chronic liver disease, etc.
76

77. Glucocorticoid variation
• ACTH and cortisol both exhibit a diurnal variation
pattern with the highest levels occurring in the
early morning – 8 am and lowest levels in the late
evening
– Diurnal variation pattern is related to sleep-wake cycles
– Stress is a powerful regulator of cortisol, able to
override the diurnal variation pattern and negative
feedback regulation
77

78. Pattern of cortisol level during the day
78

79. Hypersecretion of cortisol
• Cushing’s syndrome
– Clinical disorder that result from supraphysiological level of
cortisol in the circulation (hypercorticortisolism)
– The cause can be primary to the adrenal cortex (adrenal
adenoma in carcinoma) secondary to overproduction of ACTH
(pituitary adenoma) or an ectopic carcinoma that produce
ACTH, eg carcinoma of the lung.
– The diagnosis is confirmed by dexamethasone suppression
test.
– Plasma ACTH levels are low in primary adrenal disease and
high when there is uncontrolled production of ACTH by a
neoplams 79

80. Hyposecretion of cortisol
• Adreno cortical insufficiency, evident by a low plasma
cortisol concentration
• The causes may be:
– Primary to the adrenal cortex because of destruction of
cortical tissue by autoimmundisease or infection (addison’s
disease) or
– Secondary to ACTH deficiency
• The diagnosis is confirmed by finding a subnormal
cortisol response to the administration of exogenous
ACTH (rapid ACTH stimulation test)
80

81. Evaluation of adrenocortical function
• The three most important tests in the investigation of
Cushing's syndrome and Addison's disease:
– Measurement of blood cortisol, urine cortisol and
ACTH levels
• Simulation and suppression tests used to distinguish
between the causes.
• Cortisol levels in blood are subject to diurnal variation.
• Test results must be evaluated with regard to the time
of day the blood was collected.
81

82. Serum cortisol measurement
• Serum cortisol and ACTH is most frequently measured
by Immunoassay: RIA or FPIA
• Adrenocortical hormone tests are typically performed
on blood plasma or 24-hour urine samples.
82

83. Urine free cortisol
• Very little of the plasma cortisol is free, but when
cortisol is produced in excess, the binding proteins
become saturated, and excess free cortisol is excreted in
the urine.
• Measurement of 24-hour urinary free cortisol is not
influenced by serum binding protein levels and is not
subject to the diurnal variation (pulse variation)
• It is more sensitive than measurement of total serum
cortisol in detecting persons with Cushing's syndrome.
83

84. Stimulation and suppression tests
• Measurement of cortisol may not be definitive for the
diagnosis of Cushing's syndrome or Addison's disease,
several stimulation and suppression tests are available
• They are used to establish a diagnosis or to help
distinguish the cause of the disease.
• The most commonly used suppression test for
Cushing's syndrome is the dexamethasone suppression
test.
• Dexamethasone: powerful synthetic analog of cortisol
and will normally inhibit the pituitary release of ACTH,
and thus suppress cortisol secretion.
84

85. • Low dose overnight dexamethasone suppression test.
– 1 mg of dexamethasone is given orally at midnight and
the 8 AM cortisol is measured.
– The cortisol level is suppressed in normals and will be
less than 5 micrograms/dL.
– Persons with Cushing's syndrome will usually show no
suppression and the plasma cortisol will be 10
micrograms/dL or higher.
• High dose overnight dexamethasone suppression test.
– Patient is given 8 mg of dexamethasone at midnight.
– A blood sample is collected at 8 AM and cortisol is
measured.
– Persons with Cushing's disease show a suppression in
cortisol production of at least 50% of their baseline
– Persons with adenoma or ectopic ACTH tumors remain
unsuppressed. 85

86. ACTH stimulation test
• To distinguish between adrenal(primary) and
pituitary(secondary) causes of insufficient cortisol
production.
• Administration of synthetic ACTH over 2 to 3 days and daily
measurement of plasma cortisol levels
• In pituitary (secondary) causes, a step wise increase in
cortisol production will occur during the period of the test
as the atrophic adrenals again become responsible to
ACTH.
• In adrenal causes of insufficient cortisol production
(primary), no increase in cortisol production will occur.
86

87. Reference range
Reference ranges for blood serum cortisol levels:
• Adults (8 A.M.): 6-28 μg/dL;
• adults (4 P.M.): 2-12 μg/dL.
• Child 1-6 years (8 A.M.): 3-21 μg/dL;
• child 1-6 years (4 P.M.): 3-10 μg/dL.
Reference ranges for urine (free cortisol):
• Adult: 10-100 micrograms/24 hr.
• Adolescent: 5-55 μg/24 hr.
• Child: 2-27 μg/24 hr.
87

88. Mineralocorticoids (aldosterone)
• Aldosterone: the principal mineralocorticoid hormone
• Target organs - kidneys, sweat and salivary glands and GI
tract
• Effects: Aldosterone regulates electrolyte balance and
extracellular fluid balance
– It regulates blood volume and blood pressure
– In the kidney, aldosterone causes active sodium
reabsorption, potassium and hydrogen excretion and
passive water reabsorption
88

89. Aldosterone release
• Three release stimulators
–Renin-angiotensin system (RAS) – primary
stimulation
–Extracellular potassium and sodium
–ACTH
89

90. Aldosterone
• Its production is primarily controlled by the renin-angiotensin
system.
• ACTH has a slight stimulatory effect on aldosterone synthesis, but
this is usually of no significance.
• Renin
• Protein produced by the juxtaglomerular apparatus of the
kidney in response to decreased renal pressure and/or
decreased serum sodium levels.
• Acts on angiotensinogen to produce angiotensin I which is
converted to angiotensin II by angiotensin converting enzyme.
• Angiotensin II is a potent vasoconstrictor and also stimulates
secretion of aldosterone by adrenal cortex.
90

91. Aldosterone control
• Atrial natriuretic peptide
• Plasma k+ level
• Role of ACTH
• Plasma Na+ level
• Renin- angiotensin system
• Aldosterone has negative feedback on the
juxtaglomerular apparatus of the kidney
91

92. 92

93. • Characteristics – poorly protein bound
• Only approximately 30% of aldosterone is bound to
plasma protein.
• The hormone is metabolized by the liver and
metabolites are excreted in the urine.
– The liver converts aldosterone into a glucuronide or a
tetrahydroglucuronide, which passes into the urine
• The kidney also inactivates aldosterone by
transformation into water-soluble glucuronides.
93

94. Hyperaldosteronism
• Primary hyperaldosteronism (conn’s syndrome)
– It is overproduction of aldosterone due to the presence of
an aldosterone secreting adrenal adenoma.
– These patients usually have elevated serum Na+
concentration, lowered K+ and hypertension.
• Secondary hyperaldosteronism
– It result from abnormalliteis in the renin-angiotensin
system
– It result from
• Excess production of renin→associated with increased
plasma renin 94

95. Hypoaldosteronism
• Aldosterone deficiency is most often due to
destruction of the adrenal glands
• If sodium intake is not adequate, the patient
will develop severe water and electrolyte
abnormalities and may die from vascular
collapse and/or hyperkalemia
95

96. Laboratory diagnosis
• Determination of aldosterone by RIA and FPIA
• Determination of sodium and potasium in serum and
urine
• Two blood samples are often drawn for aldosterone
evaluation, one in the early morning and one mid-
afternoon.
• Because a 24-hour urine specimen reflects hormone
production over an entire day, it will usually provide a
more reliable aldosterone measurement.
• Elevated blood levels should ideally be confirmed with a
24-hour urine test. 96

97. • Results will also vary between patients depending
upon average sodium intake, time of day, source of
specimen, age, sex, and posture.
• Reference ranges for blood plasma levels:
radioimmunoassay
– Supine: 3-10 ng/dL.
– Upright: Female: 5-30 ng/dL; Male: 6-22 ng/dL
– Urine: 2-80 micrograms/24 hr.
97

98. Adrenomedullary Hormone
98

99. Catecholamines
• Catecholamines – epinephrine, norepinephrine and
dopamine
– Epinephrine is the major adrenal catecholamine (80-
90%)
• Affects metabolism (mobilizes energy stores) and increases
heart rate and blood pressure in times of stress
• Functions as a neurotransmitter
– Norepinephrine (10-20%) and dopamine function
solely as neurotransmitters
• Catecholamine adrenal release is stimulated by stressors
such as fear and pain
99

100. Adrenal catecholamine synthesis
• The adrenal medullary catecholamines are
derived from the amino acid tyrosine
100

101. 101

102. 102

103. Thyroid hormones

104. Thyroid hormones
• Thyroid gland: small tissue situated in the neck just
below the larynx producing hormones that affect
metabolism and growth.
• Two types of cells from the thyroid:
– The follicular(or cuboidal) cells
• Secretory and produce thyroxine(T4) and triiodothyronine(T3)
• Each follicle surrounds a material called colloid, which is mainly
thyroglobin
– Perifollicular (or C) cells
• Situated inclusters along the interfollicular or intestinal space
• Produce calcitonin, which is involved in Ca2+ regulation(by
inhibiting bone resorption)

105. Thyroid Anatomy

106. Thyroid Anatomy: Cells
• The follicular cells
synthesize thyroglobulin
which is released into
the colloid.
• In the colloid iodine is
added.
• The thyroid hormones
are released to pass into
the capillary bed and
into the circulation.

107. Thyroid hormone cont’d
• Precursor hormones are:
– Monoiodotyrosine (MIT)
– Diiodotyrosine (DIT)
• Iodine and tyrosine derived
• Circulating thyroid
hormones are
– Thyroxine (T4)
– Triiodotyrosine (T3)

108. Steps of synthesis of Thyroid Hormone
1. The entry of inorganic iodide ion into the thyroid cell
2. Oxidation of iodide to iodine(reactive): by peroxidase
enzyme.
3. Iodination of tyrosine (activated iodine react with
tyrosine residue in thyroglobin) at 3’ and 5’ postion to
form monoiodo and diiodotyrosine
4. Oxidation coupling of MIT with DIT or DIT with DIT to
form T3 and T4 respectively, which are attached to
thyroglobin.
5. The stored iodinated thyroglobin is degraded by a
cellular protease to yield a mixture of free MIT, DIT, T3
and T4.

109. Thyroid hormones cont’d
• T4 is the principal iodinated hormone secreted by the thyroid;
• Peripheral tissues convert T4 to T3, the active hormonal entity that
enters tissue cells.
• About 70% of the plasma T3 is derived from the tissue
deiodination of T4, while the rest is of thyroidal origin.
• T3 is the most biologically active thyroid hormone and is three to
four times more potent than T4.
• Reverse T3 (rT3) is formed to a minor extent during the
deiodination process
– iodine molecules are in the 3, 3’, 5’ position instead of the 3, 5,
3’ position of T3,
– No hormonal activity

110. Transport of Thyroid Hormones
• T3 and T4 are poorly soluble in plasma
• Transported primarily by a thyroid-binding globulin
(TBG), a plasma protein that carries the majority (70 to
75%) of circulating T4 and T3.
• The remaining 25 to 30% of T4 is transported by
albumin and pre-albumin
• T3 has no affinity for prealbumin and circulates only
with TBG and albumin.
• TBG has a single binding site for T4 or T3, but in normal
individuals only about 30% of the binding sites are
occupied.

111. Thyroid hormone cont’d
• A very low concentration of free T4 and T3 exists in
plasma in equilibrium with the protein-bound forms.
• Only the free hormone (FT4 and FT3) can bind to
receptors on cell surfaces.
• They are the physiologically active thyroid hormones.
• The ratio of FT4 to total T4 is about 1:3,000; with a
corresponding figure of 1:300 for T3.
• the plasma distribution of thyroid hormones (>99.9%
bound) is approximately 97% T4, 2%T3 and <1% rT3

112. Biological Function
• A major function is their control of the basal metabolic rate and
calorigenesis through:
– Increased oxygen consumption via the effects on membrane
transport, Enhanced mitochondrial metabolism
• Thyroid hormones are indispensable for
– Growth, development, and sexual maturation, and
stimulation of heart rate and contraction,
– Stimulation of protein synthesis and degradation of
cholesterol and triglycerides,
– Increase in vitamin requirements and calcium and
phosphorus metabolism
– Enhancement of sensitivity of β–adrenergic receptors to
catecholamines.

113. Regulation of thyroid hormones
• Regulated by hypothalamic-pituitary-thyroid axis
• Hypothalamus releases TRH: stimulates release of TSH
• At pituitary, secretion of TSH regulated by:
– TRH and somatostatin interplay
– Free T4 and T3: stimulate secretion of somatostatin by
hypothalamus
• FT4 and FT3
– serve in a negative feedback to regulate the amount of TSH
and to stimulate hypothalamus to produce somatostatin.
– Enter target cell and bind to receptor sites in the cell
nuclei→synthesis of protein→effect

114. Thyroid disorder
• Hyperthyrodism: a disorder manifested by excessive
circulating levels of thyroid hormones.
• Symptoms:
– Increased heart rate and metabolism
– Problems with eyes
• Causes of hyperthyroidism
– Graves disease: an autoimmune disorder.
• Antibody against the thyroid TSH receptor that result in
overproduction of thyroid hormones by thyroid gland
– toxic multinodular goitor, Ingestion of thyroid hormones,
Secretion of thyrotropin by tumors

115. Hyperthyroidism
• Primary Hyperthyroidism (Grave’s disease)
– Disease of the primary organ (thyroid)
– Increased Free T4 and total T4 and T3
– Decreased TSH
• Secondary Hyperthyroidism
– Disease of the secondary organ (pituitary)
– Increased Free T4 and total T4 and T3
– Increased TSH

117. Hypothyroidism
• It is due to low serum levels of one or both thyroid
hormones with increased serum TSH levels
• Symptoms:
– Decreased heart rate and metabolism
– Failure to thrive and retardation in children
• The causes
– Hashimoto’s disease: it is chronic autoimmune thyroiditis in
which antithyroid antibody(antibody against T3 and T4) is
produced
– TSH deficiency due to anterior pituitary or
hypothalamus diseases.

118. Hypothyroidism
• Primary hypothyroidism
– Disease of the primary organ (thyroid)
– Decreased Free T4 and total T4 and T3
– Increased TSH
• Secondary Hypothyroidism
– Disease of the secondary organ (pituitary)
– Decreased Free T4 and total T4 and T3
– Decreased TSH (and other pituitary hormones)

119. Evaluation of thyroid function
• One or more of the following factors may be
abnormal, and these have to be sorted out and
evaluated:
– The concentration of thyroid-binding globin and its
degree of saturation with thyroid hormone
– The actual concentration of free (unbound) T4 and T3
– The response of the pituitary to TRH
– The response of thyroid to TSH

120. T4 and T3 immunoassay
• The serum T4 conc is a better indicator of the thyroid
secretory rate than T3
– Because T4 is the thyroid’s principal secretory
product.
• Total T4/T3 can be measured by RIA and FPIA
• Principles of Methods: Immunoassay Procedures
– Radioimmunoassay (RIA)
– Chemilumiscent Immunoassay
– Fluorescence Polarization Immunoassay (FPIA)

121. Increased total T4 and T3
• In hyperthyroidism
• In conditions that raise the plasma concentration of TBG
(pregnancy, taking of birth control pills or estrogens).
– No increase in the basal metabolic rate
• The extra T4 and T3 are bound to the newly
synthesized TBG as equilibrium between the free
and bound hormones is maintained.
– The person is euthyroid (normal thyroid function)

122. Decreased total T4 and T3
• In hypothyroidism
• In conditions that decrease TBG level
– Disease: nephrosis loss of TBG dring nephrosis, and
decreased TBG synthesis in liver disease
– Medications that reduce the synthesis of TBG (androgens,
anabolic steroids) or compete with T4 and T3 for binding sites
(aspirin, phenytoin, tolbutamide and others).
– No effect on the basal metabolic rate.
• Though the protein bound T4 and T3 are decreased, Free
T4 /T3 is normal so this is not a true hypothyroidism.
– Free T4 or Free T4 Index determined from T3 Uptake test
can help to determine when TBG is elevated/lowered

123. T3 uptake (T3U)/thyroid hormone binding ratio
• Alteration in plasma concentration of carrier proteins
usually cause misleadingly high or low results for the
measurement of thyroid hormones
• The T3 uptake (T3U) test provides an indirect estimate of
the binding capacity of the plasma thyroid-binding
proteins (TBG or TBG + albumin + prealbumin,
depending on the conditions of the assay).
• It is used to measure the number of available binding sites of
the thyroxine binding proteins, mostly TBG

124. T3 uptake (T3U) by RIA
• Patient sample + 125I-T3 (incubated)
• Resin added to remove excess 125I-T3
• G radiation is counted in count per minute(cpm)
• T3U is % of 125I-T3 taken up by resin
• Inversely proportion to free TBG binding sites
• High uptake of 125I-T3 means low levels of free TBG

125. T3 uptake (T3U)
• Typical value for %T3U are 25 to 30%
• Increased values:
– In hyperthyroidism
– in all situations in which there is a decrease in TBG conc
– Drugs that lower the serum T3 and T4 conc by competitive
binding of TBG
• Decreased values
– In hyperthyroidism
– Estrogens (increase in pregnancy, present in birth control pills)

126. Combination of total T4/T3 and T3U(THBR)
• If both are in concordance (deviation in the same
direction), indicate abnormalities in thyroid hormone
production
– Total ↑T4/T3 and ↑THBR→hyperthyroidism
– Total ↓T4/T3 and ↓THBR→hypothyroidism
• Deviation in opposite direction(discordant): indicate
change in concentration or affinity of circulating TBG
– Total ↑T4/T3 and ↓THBR→ increased TBG
– Total ↓T4/T3 and ↑THBR→ decreased TBG

127. Free thyroxin index(FT4)
• It is an indirect measure of free hormones concentration
from Total T4 and T3U
– FTI = T3 uptake X T4 concentration
• T3U test varies inversely with the T3 and T4 concentration
in a wide variety of conditions in which thyroid function is
normal, and directly with the T3 and T4 concentration in
hypothyroidism and hyperthyroidism
• Useful in correcting for euthyroid individuals who have
altered binding protein conc who have been misclassified
on basis of total T4

128. Free thyroxin index(FT4)
• The reference value : 4.5-12
• Normal FTI: in euthyroid subjects, pregnancy, women
taking estrogen, patients with nephrosis or hepatitis
and persons taking drug that elevates T3U
• Increased FTI: hyperthyroidism
• Decreaee FTI: hyporthyoudism

129. Free T4 and T3
• Better indicator of thyroid status than FTI
• Correlate much better with thyroid status than total
T4/T3, because they are not affected by abnormal
TBG concentration
• Method: the same as total T4 and T3 (RIA or
Chemiluminescent immunoassay)
– Except free T4 and T3 in serum is separated first from
protein bound hormone by dialysis and other separation
techniques.

130. TSH
• Measured by sensitive methods(RIA)
• Serum TSH levels are elevated in hypothyroidism
primary to the thyroid gland because of the absence
of the negative feedback control.
• TSH conc is decreased in hyperthyroidism but only
the most sensetive RIA methods are able to measure
it accurately at this level.
• Generally, TSH useful in the confirmation of
suspected primary hypo and hyperthyroidism.

131. T4 T3RU FTI
N N N N
Hypothy   
Hyperth
y
  
 TBG   N
 TBG   N
TSH
N


N
N
Free
T4
N


N
N
x =

132. Thyroid releasing hormone (TRH) stimulation test
• TRH stimulation detects residual TSH stores in the
pituitary glands
• TRH is injected intravenously and the output of TSH is
measured.
– In euthyroid: TSH will rise within 30 minutes.
– Primary hyperthyroidism: will not respond to the TRH
and their TSH will remain at base line levels,
– Primary hypothyroidism: will have an exagerated
response.

133. TRH stimulation test
• Used to differentiate secondary (pituitary) from
tertiary (hypothalamic) hypothyroidism.
– In both conditions, the patient have a low FT4/T3
with borderline or inappropriately normal TSH.
– when TRH is injected
• In a patient with secondary hypothyroidism, the TSH will
not increase or will be blunted,
• In patients having tertiary hypothyroidism the TRH
stimulation will have a response.

134. Specimens for Thyroid Analysis
• Serum
• Heparinized or EDTA plasma
• Whole blood from Capillary
– Dried blood spot

135. Interpretation of Results
Thyroid Hormone Reference Ranges
• T4: adult 5.1 to 11.0 µg/dL(66 -142 nmol/L)
• T3 adult 70 to 200 ng/dL (1.08 to 3.08 nmol/L)
• %T3U: 25 to 35%.
• Free T4: adult 5.6-11.7 mg/dL
• Free T3: adult 80-210 ng/dL
• Ranges are method dependent and age
adjusted.

136. Gonadal hormones(Sex steroids)
• Predominately produced by the adult male testes and
female ovaries
• Adrenal cortex also produces small amounts of sex
steroids
• Responsible for
– manifestation of primary and secondary sex characteristics
– Human reproduction
• Characteristics – steroid, lipid-soluble, slow effects, bound
to carrier proteins (SHBG, albumin)
• Their secretion is under hypothalamus-pituitary-gonadal
axis control 136

137. Classes of female sex steroids
• Androgens
– Dehydroepiandrosterone (DHEA), DHEAS, testosterone,
dihydrotestosterone (DHT), androstenedione
• The predominate adrenal androgens are DHEA and DHEAS
• Estrogens
– Estradiol, estrone
• Progestins
– Progesterone
137

138. Female sex hormones
• Function of female gonad, or ovary,
– produces and secretes the female sex hormones
– it is the site of production and maturation of the ova.
• One mature ovum is released every 4 or 5 weeks by a non
pregnant woman during the years between the onset of
menstruation and the menopause.
• The reproductive system of females is far more
complicated than that of males
– Due to cyclical events that take place during the
menstrual cycle and changes that occur during
pregnancy.
138

139. Female sex hormones cont’d
• Two different chemical types of steroid hormones are
produced and secreted by the ovary in non pregnant
women.
– Estrogen and progesterone
• During pregnancy, the same hormones are produced by the
ovary, but in different proportion.
• The placenta also makes the hormones that are necessary
for the maintenance of pregnancy.
– Estrogen, progesterone, HCG, lactogen
• This production is under control of
– hypothalamus(GnRH)→Pituitary(FSH,LH)→ovary/placenta
(female sex steroids)
139

140. Estrogen
• Originate in the ovarian follicles and in the placenta
during pregnancy
• Function
– Participate in the menstrual cycle
– development and maintenance of the reproductive
organs and secondary sex characteristics.
• Three clinically important estrogens: C18 steroid
– Estradiol(E2): major hormone in non-pregnant
– Estrone(E1)
– Estriol(E3): major hormone in pregnant
140

141. Estradiol
• The principal and most potent estrogen
• It exists in a reversible state with estrone (with weaker
biologic action), but it must be converted into E1 before
it is degraded.
– Estradiol(E2) ↔ Estrone (E1) → Estriol(E3) → degradation
• Plasma E2 levels
– Useful for the investigation of women with menstrual
difficulties
• To ascertain wether a problem is of pituitary or
ovarian origin.
– Measurement of pituitary tropic hormones, FSH and LH
141

142. Estriol(E3)
• It has no hormonal activity
• Produced in relatively large quantity during the last
trimester of pregnancy by the placental conversion
of fetal adrenal steroids.
• Its concentration in urine or plasma of pregnant
women provides indication of fetal well being
(fetoplacental viability)
– Sudden drop in estriol concentration or output is a
danger signal of fetoplacental dysfunction.
142

143. Progesterone
• It is a C21 compound and chemically more closely related
to the adrenal steroids.
• It is an intermediate in the production of adrenal
steroids.
• Formed in the corpus luteum, the body that develops
from the ruptured ovarian follicle.
• Function
– Stimulates the uterus to undergo changes that prepare it for
implantation of the fertilized ovum,
– Suppresses ovulation and secretion of pituitary LH.
– If pregnancy occurs, the secretion of progesterone by the
corpus luteum and by the placenta suppresses menstruation
for the duration of the pregnancy. 143

144. Placental hormones
• Function of placenta: providing nutrients to the
developing embryo and removing its waste products
• Additionally in the pregnant women it serves as an
endocrine organ
– Produce
• Estrogen
• Progesteron
• chorionic gonadotropin (hCG)
• lactogen.
144

145. Human chorionic gonadotropin (hCG)
• It is a glycoprotein composed of 2 chains, alpha and
beta.
• Alpha polypeptide chain is identical to the alpha chain
on many other hormones including TSH, LH and FSH.
• The beta chain is unique in hCG so is the speciificity for
immunoassay techniques.
• The action of hCG is similar to that of LH
– It stimulate the corpus luteum to produce progesterone.
• Progesterone helps to maintain the pregnancy by
preventing menstruation.
145

146. Clinical significance of hCG
• For diagnosis of pregnancy
– The detection of hCG in urine or serum is the basis
of current tests for pregnacy.
– The most sensetive can detect pregnacy with in 5
to 7 days after conception.
– The antibody used for quantitation of serum hCG
should be specific to β-hCG in order to avoid cross
reactions,
146

147. Clinical significance cont’d
• Other significance
– Diagnosis of ectopic pregnancy: implantation of fertilized
ovum in a site other than the uterus (fallopian tube)
– Prediction of spontaneous abortion: lower or failure of
HCG to increase appropriately in the first few weeks of
pregnancy indicates that the placenta is not developing
correctly and associated with increased incidence of
spontaneous abortion.
– Detection of multiple pregnacies: HCG level in women
carrying multiple fetuses are higher than in woman
carrying only one
– Detection and follow up of HCG-producing tumors
– Diagnosis of testicular cancer in males. 147

148. Human placental lactogen
• It is a protein hormone that is structurally,
immunologically and functionally very similar to growth
hormone and prolactin
• HPL appears to act in concert with HCG to stimulate
estrogen and progesterone synthesis by the corpus
luteum.
• It stimulates development of the mammary gland
(similar to prolcatin)
• Has somatotropin actions similar to those of growth
hormone.
– it increases maternal plasma glucose levels and mobilization of
free fatty acids and promotes positive nitrogen balance.
148

149. Male sex hormones
• The male gonads are the testes.
• They have a double function:
– To produce and secrete the male hormone, testosterone
– To produce the spermatozoa
• Essential for fertilization of the ovum in the reproductive
process.
• The testes are part of a hypothalamic-pituitary-gonadal axis.
– FSH stimulate spermatogenesis,
– LH stimulate the production of testestrone by interstitial
(Leydig’s) cells.
– Both LH and FSH suppressed by high levels of testosterone
149

150. Testosterone
• The most potent naturally occurring androgen.
• Function
– Promote growth of secondary sex organs
• It causes growth and development of the male
reproductive system, prostate, and external genitalia.
– Promotes muscular and skeletal growth and is protein
anabolic.
• Transport
• 80% by plasma globulin
• 17% by albumin
• < 3% unbound, active hormone. 150

151. Testosterone cont’d
• All of the testosterone in males is derived from the
testes; the contribution of the adrenal cortex is
negligible.
• Plasma testosterone levels are much lower in women,
usually only 5% of those found in men.
– Testosterone in women arise from the tissue conversion of
androgens.
• Plasma testosterone concentration is a good way of
studying hypogonadism and hypergonadism.
• The role of the pituitary has to be assessed to
determine whether an abnormality is primary to testes
or secondary to an LH deficiency or excess.
151

152. Testosterone cont’d
• Increased concentration of testosterone
– Testicular carcinomas
– Abnormalities of pituitary gonadotropin of males
– In female
• Virilism: development of male physical characteristics(depening of
voice, breast atrophy, increased hair growth)
• Hirsutism: growth of body hair in male like pattern
• Decreased plasma testosterone can be due to:
– Defects associated with testis
– Defects associated in pituitary
– Chromosomal abnormalities of sex hormones. 152

153. Methods of Sex Steroid Analysis
Estrogens and testosterol
– RIA
– Reference Ranges vary with method and timing of
female cycle
• More useful if tested along with FSH and LH
153

154. Hormones Regulating Mineral Metabolism
• Principal minerals: Calcium, phosphorus, magnesium
• mineral ions are important for normal cellular
physiology as well as skeletal integrity.
• They are under powerful endocrine control
mechanisms:
– Parathyroid hormone, vitamin D , calcitonin
• Disturbances in their homeostasis have been linked to
pathophysiological disorders
154
on calcium

155. Parathyroid Hormone
• It is 84- aa linear peptide
• secreted by the 4 parathyroid glands on or near the
thyroid gland capsule
• PTH is synthesized as a precursor pre-pro-PTH
155

156. Regulation of PTH Secretion and Biosynthesis
• ionized calcium concentration in ECF
– the only physiologically significant regulator of minute-to-
minute changes in PTH secretion (acute Vs chronic change)
• 1,25-dihydroxyvitamin D3
– High levels of 1,25-dihydroxyvitamin D inhibit transcription
of the PTH gene
• Plasma phosphate levels
– Elevated phosphate level increase PTH secretion
• Plasma Mg2+ concentrations
– PTH release can be stimulated by a decrease in plasma Mg2+
156

157. Biological Action of PTH
• PTH influences both calcium and phosphate homeostasis
– direct actions on bone and kidney ,indirectly on intestinal
• Effects on the Kidney
– increases calcium reabsorption in DCT
– decreases reabsorption of phosphate by the proximal tubule,
• Effect of PTH on intestine
– The action of PTH on intestinal Ca2+ absorption is indirect.
– PTH stimulates the 1α-hydroxylase in the kidney → production
1,25(OH)2D →stimulates intestinal Ca2+ absorption.
• Effects of PTH on bone
– Increase bone resorption→release of Ca2+ to plasma
157

158. Fig: Effects of PTH on calcium and phosphate 158

159. Pathophysiology of PTH
• Due to : hormone excess, hormone deficiency or hormone
resistance
• Hyperparathyroidism:
– Primary hyperparathyroidism: caused by parathyroid adenoma
secretes excessive PTH
• Result in increased bone resorption, increased Ca2+
reabsorption from kidney and absorption from intestine, and
decreased phosphate reabsorption (phosphaturia)
• Leads to hypercalcemia and hypophosphatemia
– Secondary hyperparathyroidism: parathyroid glands secrete
excessive PTH secondary to hypocalcemia (from chronic renal
failure or vitamin D deficiency)
• circulating levels of PTH are elevated and plasma Ca2+ levels
are either low or normal, but never high
159

160. Pathophysiology of PTH cont’d
• Hypoparathyroidism
– Characteristics: low circulating levels of PTH,
decreased bone resorption, decreased renal
reabsorption and intestinal absorption of Ca2+, and
increased phosphate reabsorption
• Result in: hypocalcemia and hyperphosphatemia
• Pseudohypoparathyroidism
– the defect lies in the end organs (bone and kidney)
– Characteristics:
• hypocalcemia and hyperphosphatemia
• circulating levels of PTH are increased, not decreased
160
t/f

161. Clinical significance of PTH
• Determination of PTH is useful for
– differential diagnosis of both hypercalcemia &
hypocalcemia
– assessing parathyroid function in the renal failure
– evaluating parathyroid function in bone and mineral
disorders
• Measurement of PTH
– Serum or EDTA plasma
– Two-site or sandwich immunoassays
– Typical reference intervals are 10 to 65 pg/ml
161

162. Vitamin D
• Vitamin D and its metabolites may be categorized as:
– Cholecalciferol(vitamin D3)
• parent cpd of the naturally occurring family
• produced in the skin from 7-dehydrocholesterol on UV
exposure
– Ergocalciferol(vitamin D2)
• manufactured by irradiation of ergosterol produced by yeasts
• differs from vit D3 by the double bond between carbon 22
and carbon 23 and a methyl group on carbon 24
• Both are inactive, undergo a series of transformations
(hydroxylation) in the liver and kidneys
– 25(OH)D → 1, 25-dihydroxycholecalciferol(calcitriol)
162

163. Fig: vitamin D metabolism 163

164. Vitamin D cont’d
• In blood, bound principally to vitamin D-binding protein
(DBP) (85%) and albumin (15%)
• Regulation: by PTH, phosphate, calcium, and 1,25-
(OH)2 D
– PTH and hypophosphatemia
• increases the synthesis of 1,25-(OH)2 D by
increasing 25(OH)D-1α-hydroxylase
– hypocalcemia acts indirectly by stimulating the
secretion of PTH
– Hypercalcemia, hyperphosphatemia, and 1,25(OH)2D
reduce 25(OH)D-1α-hydroxylase and 1,25-(OH)2 D
164

165. Biological action of vit D
• primarily influences the GI tract, also on kidneys and
bones
• Action on intestine: increases both Ca2+ and phosphate
absorption by the small intestine →↑plasma conc
• Action on the kidney: weak and minor effect
– stimulates both Ca2+ and phosphate reabsorption,
promoting the retention of both ions in the body
• Actions on bone: act synergistically with PTH to
stimulate osteoclast activity and bone resorption
– promotes the resorption of ‘‘old’’ bone, bringing more
Ca2+ and phosphate in to the extracellular fluid
165

166. Fig: Effects of 1,25-dihydroxycholecalciferol 166

167. Pathophysiology of Vitamin D
• Vitamin D deficiency causes
– Rickets in children
• insufficient Ca2+ and phosphate to mineralize growing bones
– Osteomalacia in adult
• failure to mineralize new bone results in bending and
softening of the weight-bearing bones.
• Vitamin D resistance
– caused by absence of 1α-hydroxylase or by chronic renal failure
• C-1 hydroxylation step in the kidney is impaired or missing
– kidney is unable to produce the active Vit D
167

168. Clinical significance
• Conc of 25(OH) D is useful in evaluating hypocalcemia, vitamin D
status, bone disease, confirming intoxication with vitamin D
• 1,25(OH)2D in the evaluation of hypercalcemia, hypercalciuria,
hypocalcemia, and bone and mineral disorders
• Measurement
– Require deproteinization or extraction, purification, quantification
– Serum 25(OH) D: immune assay,
– Serum 1,25(OH)2D : immune assay
– Reference Intervals
• 25(OH)D: 10 to 65 ng/ml
• 1, 25(OH)2D: 15 to 60 pg/ml
168

169. Calcitonin (thyrocalcitonin)
• A 32 aa peptide produced by parafollicular cells of the
thyroid gland
• It fine-tunes the calcium regulatory system, but not in
the minute-to- minute regulation
• overall action: decrease plasma Ca and phosphate
169

170. Calcitonin (thyrocalcitonin) cont’d
• The primary target of CT is bone
– CT opposes the action of PTH on osteoclasts by
inhibiting their activity
• This leads to decreased bone resorption and an
overall net transfer of calcium from plasma into
bone
• lesser effects in the kidneys
– decreases the tubular reabsorption of Ca &
phosphate
• little or no direct effect on the GI tract
170

171. Fig Effects of calcitonin (CT) on calcium and phosphate metabolism
 serves as a tumor marker
 Calcitonin is secreted by medullary carcinoma of the thyroid 171

172. Other hormones
• Pancreatic Hormones
– Insulin,
– Glucagon
• Gastrointestinal Hormones
– Gastrin
– Secretin
– Somatostatin
– Vasoactive intestinal peptide
172

173. MATCHING
1 TSH A.adrenal cortec
2 FSH b. adrenal medulla
3 LH c. kidney
4 Aldosterol d. ovary
5 cathecolamine e. testes
6 progestrone F. anterior pitutary
7 testerone G. POSTIRIOR pitutary
8 estrogen H .thyroid gland
9 calcitone
10 thyroxine
11 ACTH