The thyroid gland secretes thyroxine (T4) and triiodothyronine (T3) which are formed through a process involving iodine trapping, oxidation, tyrosine iodination, and hormone coupling/release from thyroglobulin stored in thyroid follicles. Thyroid hormones increase metabolism, growth, and metabolic processes. Their secretion is regulated through thyroid stimulating hormone (TSH) feedback from the pituitary gland. Abnormalities include hyperthyroidism and hypothyroidism. The endocrine pancreas secretes insulin and glucagon from beta and alpha cells respectively within pancreatic islets. Insulin regulates glucose metabolism and storage through genomic and non-genomic actions.

1. Presented by/
Dr/ dina hamdy merzeban

2. THYROID GLAND
• The thyroid gland, located immediately below the larynx on each side
and anterior to the trachea, is one of the largest of the endocrine glands,
• The thyroid secretes two major hormones, thyroxine and triiodothyronine,
commonly called T4 and T3 , respectively. Triiodothyronine is about four
times as potent as thyroxine, but it is present in the blood in much
smaller quantities and persists for a much shorter time than does
thyroxine.
• The thyroid gland also secretes Thyro-calcitonin (TCT), an important
hormone for calcium homeostasis.

3. THYROID GLAND
The thyroid gland is composed of large
numbers of closed follicles filled with a
secretory substance called colloid and
lined with cuboidal epithelial cells that
secrete into the interior of the follicles.
The major constituent of colloid is the
large glycoprotein thyroglobulin.

4. THYROID GLAND
• To form normal quantities of thyroxine, about 50 milligrams of ingested iodine in
the form of iodides are required each year, or about 1 mg/week.
• To prevent iodine deficiency, common table salt is iodized
• Fate of ingested iodides. Iodides ingested orally are absorbed from the
gastrointestinal tract into the blood in about the same manner as chlorides.
• Normally, about one fifth are absorbed by the cells of the thyroid gland and used
for synthesis of the thyroid hormones.
• Thyroid gland has a large storage of Thyroid hormone that covers the
needs of the body for months.

5. Steps of formation of
thyroid hormone:
1-Thyroglobulin synthesis (colloid
formation):
glycoprotein produced by the follicular cells
of the thyroid and used entirely within the
thyroid gland to form T3 and T4.
Thyroglogulin is stored in the follicles in large
amounts for long periods of time.

6. Steps of formation of
thyroid hormone:
2-Iodide trapping (Iodide pump) :
-The basal membrane of the thyroid cell has the
specific ability to pump the iodide actively
sodium-iodide symporter (NIS),
The energy for transporting iodide against a
concentration gradient comes from the sodium-
potassium ATPase pump, which pumps sodium
out of the cell, thereby establishing a low
intracellular sodium concentration and a gradient
for facilitated diffusion of sodium into the cell.
Iodide is transported out of the thyroid cells
across the apical membrane into the follicle by a
chloride-iodide ion counter-transporter
molecule.

7. Steps of formation of
thyroid hormone:
2-Iodide trapping (Iodide pump) :
-The basal membrane of the thyroid cell has the
specific ability to pump the iodide actively
sodium-iodide symporter (NIS),
The energy for transporting iodide against a
concentration gradient comes from the sodium-
potassium ATPase pump, which pumps sodium
out of the cell, thereby establishing a low
intracellular sodium concentration and a gradient
for facilitated diffusion of sodium into the cell.
Iodide is transported out of the thyroid cells
across the apical membrane into the follicle by a
chloride-iodide ion counter-transporter
molecule.

8. Steps of formation of
thyroid hormone:
3-Oxidation:
The first essential step in the formation of the
thyroid hormones is conversion of the iodide ions
to an oxidized form of iodine, that is then
capable of combining directly with the amino acid
tyrosine. This oxidation of iodine is promoted by
the enzyme peroxidase.

9. Steps of formation of
thyroid hormone:
4-Iodination of Tyrosine and Formation
of the Thyroid Hormones
“Organification” of Thyroglobulin:
The binding of iodine with the thyroglobulin
molecule is called organification of the
thyroglobulin.
Oxidized iodine even in the molecular form
will bind directly but slowly with the amino
acid tyrosine through thyroid peroxidase
enzyme.
Tyrosine is first iodized to monoiodotyrosine
(MIT) and then to diiodotyrosine (DIT).
Then final formation of the two important
thyroid hormones, thyroxine and
triiodothyronine occurs.

10. Steps of formation of
thyroid hormone:
4-Iodination of Tyrosine and
Formation of the Thyroid Hormones
“Organification” of Thyroglobulin:
-through thyroid peroxidase enzyme.
5-COUPLING : ( of MIT and DIT) :
-Thyroxine (T4 ),(DIT + DIT)
–Triiodothyronine (T3 ), (DIT + MIT)

11. Steps of formation of
thyroid hormone:
6- Release of Thyroxine and Triiodothyronine from the
Thyroid Gland:
Thyroglobulin itself is not released into the circulating
blood in measurable amounts; instead, thyroxine and
triiodothyronine must first be cleaved from the
thyroglobulin molecule, and then these free hormones
are released. This process occurs as follows:
The apical surface of the thyroid cells sends out
pseudopod extensions that close around small
portions of the colloid to form pinocytic vesicles that
enter the apex of the thyroid cell. Then lysosomes in
the cell cytoplasm immediately fuse with these vesicles
to form digestive vesicles containing Protease enzyme
digests the thyroglobulin molecules and release
thyroxine and triiodothyronine in free form.

12. Steps of formation of
thyroid hormone:
The thyroid hormones are stored in the follicles in an amount
sufficient to supply the body with its normal requirements of thyroid
hormones for 2 to 3 months.
Therefore, when synthesis of thyroid hormone ceases, the
physiologic effects of deficiency are not observed for several months.
-Daily Rate of Secretion of Thyroxine and Triiodothyronine: About 93
percent of the thyroid hormone released from the thyroid gland is
normally thyroxine and only 7% is triiodothyronine.
-about one half of the thyroxine is slowly deiodinated to form
additional triiodothyronine. Therefore, the hormone finally delivered
to and used by the tissues is mainly triiodothyronine.
Level of thyroid hormones in blood:
Total T4: 8 μg/dl Free T4: 2 ng/dl
Total T3: 0.15 μg/dl Free T3: 0.3 ng/dl

13. Mechanism of Action:
• Genomic Actions: Thyroid Hormones Increase the Transcription
of Large Numbers of Genes
• Non-Genomic Actions: include the regulation of ion channels and
oxidative phosphorylation and appear to involve the activation of
intracellular secondary messengers such as cyclic AMP or protein kinase
signaling cascades.

14. Mechanism of Action:
Genomic Actions: Thyroid Hormones Increase the Transcription of Large
Numbers of Genes
Thyroid Hormones Activate Nuclear Receptors. The thyroid hormone
receptors are either attached to the DNA genetic strands or located in
proximity to them.
The thyroid hormone receptor usually forms a heterodimer with
retinoid X receptor (RXR) at specific thyroid hormone response
elements on the DNA. On binding with thyroid hormone, the receptors
become activated and initiate the transcription process. Then large numbers
of different types of messenger RNA are formed, followed within another
few minutes or hours by RNA translation on the cytoplasmic ribosomes to
form hundreds of new intracellular proteins.
Therefore, in virtually all cells of the body, great numbers of protein
enzymes, structural proteins, transport proteins, and other substances are
synthesized.
The net result is generalized increase in functional activity throughout the
body.

15. PHYSIOLOGICAL FUNCTIONS OF THE THYROID
HORMONES
calorigenic
acyion Growth Metabolism
Carbohydrate
Metabolism:
(Anti-insulin
action)
plasma lipids
Sexual Function
Increased
Requirement for
Vitamins
Body Weight CVS
CNS

16. PHYSIOLOGICAL FUNCTIONS OF THE
THYROID HORMONES
1-Increase the metabolic activities of almost all the tissues of the body (calorigenic acyion).
The basal metabolic rate can increase to 60 to 100 percent above normal when large quantities of the
hormones are secreted.
Thyroid Hormones Increase the Number and Activity of Mitochondria. That in turn increases the rate of
formation of adenosine triphosphate (ATP) and energy production in the cell.

17. PHYSIOLOGICAL FUNCTIONS OF THE
THYROID HORMONES
2-Effect of Thyroid Hormone on Growth
 Thyroid hormone has both general and specific effects on growth.
 manifest mainly in growing children. In those who are hypothyroid, the rate of growth is greatly
retarded.
 An important effect of thyroid hormone is to promote growth and development of the brain during
fetal life and for the first few years of postnatal life.
 If the fetus does not secrete sufficient quantities of thyroid hormone, growth and maturation of the
brain both before birth …… mentally retarded.

18. PHYSIOLOGICAL FUNCTIONS OF THE
THYROID HORMONES
3-Effects of Thyroid Hormone on Metabolism:
, -A: Carbohydrate Metabolism: (Anti-insulin action)
• Stimulation of Carbohydrate Metabolism. Thyroid hormone stimulates almost all aspects of carbohydrate
metabolism, including
• rapid uptake of glucose by the cells
• enhanced glycolysis,
• enhanced gluconeogenesis
• increased rate of absorption from the gastrointestinal tract.
B- Stimulation of Fat Metabolism.
• Essentially all aspects of fat metabolism are also enhanced under the influence of thyroid
hormone.
• lipids are mobilized rapidly from the fat tissue, which decreases the fat stores of the body to a greater extent.
• On plasma lipids: thyroid hormones decrease plasma cholesterol and increase its secretion in bile and
stool.

19. PHYSIOLOGICAL FUNCTIONS OF THE
THYROID HORMONES
Effect on CVS :
A- Increased blood flow and cardiac output.
B- Increased heart rate.
C- Increased force of heart contraction.
D- Elevated systolic and decreased diastolic blood pressure with greater pulse pressure. The mean
arterial blood pressure is minimally changed.

20. PHYSIOLOGICAL FUNCTIONS OF THE
THYROID HORMONES
• Effect of Thyroid Hormone on Sexual Function :
• For normal sexual function, thyroid secretion needs to be approximately normal
• In men, lack of thyroid hormone is likely to cause loss of libido.
• In women, lack of thyroid hormone often causes Menstrual disturbances.
• Increased Requirement for Vitamins
• On Body Weight: Greatly increased thyroid hormone almost always decreases the body weight, and
greatly decreased thyroid hormone almost always increases the body weight
• On plasma lipids: thyroid hormones decrease plasma cholesterol and increase its secretion in bile
and stool
• On CNS : Thyroid has an excitatory effect on the CNS functions : A- Muscle tremors
• Other endocrine glands: thyroid hormone increases the levels of insulin, cortisol and parathyroid
hormone

21. PHYSIOLOGICAL FUNCTIONS OF THE THYROID
HORMONES
calorigenic
acyion Growth Metabolism
Carbohydrate
Metabolism:
(Anti-insulin
action)
plasma lipids
Sexual Function
Increased
Requirement for
Vitamins
Body Weight CVS
CNS

22. REGULATION OF THYROID HORMONE
SECRETION
TSH Feedback
mechanism
Effect of
change in
temperature

23. REGULATION OF
THYROID HORMONE
SECRETION
• TSH : Increases Thyroid Secretion
Through c AMP
• Increased proteolysis of the thyroglobulin
that has already been stored in the follicles
• Increased activity of the iodide pump, which
increases the rate of “iodide trapping” in the
glandular cells
• Increased iodination of tyrosine to form the
thyroid hormones
• Increased size and increased secretory
activity of the thyroid cells

24. REGULATION OF
THYROID HORMONE
SECRETION
• N.B. Anterior Pituitary Secretion
of TSH Is Regulated by
Thyrotropin-Releasing Hormone
from the Hypothalamus
• through activation of the
phospholipase second messenger
system

25. Feedback
mechanism

26. Effect of change in
temperature
Exposure to cold weather >> increases
TRH secretion >> increases TSH.
Exposure to hot weather >> Decrease
TRH secretion >> decrease TSH.

27. ABNORMALITIES OF THE THYROID
HORMONE

28. Hyperthyroidism
• Graves’ disease
• the most common form of hyperthyroidism, is an autoimmune disease in which
antibodies called thyroid-stimulating immunoglobulins
• Thyroid Adenoma

29. Hyperthyroidism
Symptoms of Hyperthyroidism :
• Nervousness and high excitability (Inability to
sleep).
• Intolerance to heat and increased sweating (due
to increase the metabolic rate 60-100% leading to
warm, flushed and sweaty skin).
• Weight loss (despite increased appetite and
hyperphagia).
• Tremors of the hands.
• Exophthalmos (protrusion of eye balls).
• Tachycardia and palpitations.

30. Hypothyroidism
Causes of Hypothyroidism:
Chronic iodine
deficiency
Iatrogenic due to
over surgical
removal of thyroid
tissue or excessive
anti-thyroid drugs
chronic thyroiditis
(autoimmune)
leading to
destruction of
thyroid tissue.

31. Hypothyroidism
Myxedema: Hypothyroidism in adult life,
characterized by cold intolerance, depressed
mental and sexual functions, husky voice, and
weight gain
Cretinism: Hypothyroidism in the neonatal period,
lead to irreversible mental, physical and sexual
growth retardation

32. ENDOCRINE PANCREAS
• The acini, which secrete digestive juices into the duodenum

33. ENDOCRINE PANCREAS
• The islets of Langerhans, which secrete insulin and glucagon directly into
the blood

34. ENDOCRINE PANCREAS
The beta cells, constituting about 60 percent of all the cells of the
islets, lie mainly in the middle of each islet and secrete insulin
The alpha cells, about 25 percent of the total, secrete glucagon
The delta cells, about 10 percent of the total, secret somatostatin
The PP cell, is present in small numbers in the islets and secretes a
hormone called pancreatic polypeptide

35. INSULIN
Insulin receptor is a combination
of four subunits held together by
disulfide linkages: two alpha
subunits that lie entirely outside
the cell membrane and two beta
subunits that penetrate through
the membrane, protruding into
the cell cytoplasm
NB: Overlap in the secretions of
androgens and glucocorticoids
exist between the fasciculata
and reticularis
Being lipophilic, the
adrenocortical hormones are all
carried in the blood extensively
bound to plasma proteins
Cortisol is bound mostly to a
plasma protein specific for it
called corticosteroid binding
globulin , about 15% is bound to
albumin, only 10% is free

36. INSULIN
• Rapid : Cell membrane becomes more permeable to Glucose, K+

37. • GLUT4 is insulin dependent, it’s contained in vesicles in the cytoplasm,
these vesicles move to the cell membrane once Insulin binds to its
receptor
• Non- insulin dependent tissues , have glucose transporters on the cell
membrane in absence of Insulin
• EXERCISE increases the movement of GLUT4 vesicles towards cell
membrane through the action of 5’AMP activated kinase

38. INSULIN
• Intermediate : Change the activity of intracellular enzymes
• Secondary Active transport: – SGLT1, SGLT2; SGLT2 inhibitors are widely used for lowering blood glucose as they increase glucose loss in
urine
• Facilitated Diffusion: GLUT 1- GLUT7
• Zona glomerulosa
• Zona fasciculata
• Zona reticularis
• Hormones produced by the adrenal cortex are steroids derived from the common precursor cholesterol
• These comprise mineralocorticoids, glucocorticoids and sex hormones
• The three categories of adrenal steroids are produced in anatomically distinct portions of the adrenal cortex as a result of differential distribution
of the enzymes required to catalyze the different biosynthetic pathways leading to the formation of each of these steroids
• Zona Glomerulosa

39. INSULIN
• Intermediate : Change the activity of intracellular enzymes
• Outermost zone – just below the adrenal capsule is very thin and secretes mineralocorticoids
• They maintain Na+ and K+ balance and ECF volume
• Mineralocorticoid of most importance is aldosterone
• Zona Fasciculata
• It is the middle widest zone – between the glomerulosa and reticularis
• Primary secretion is glucocorticoids
• Glucocorticoids play a major role in glucose metabolism, as well as protein and lipid metabolism
• Zona Reticularis

40. MECHANISM OF INSULIN SECRETION
• The beta cells have a large number of glucose transporters that permit a rate of glucose influx that is proportional to the
blood concentration in the physiological range
• Glucose is phosphorylated to glucose-6-phosphate by glucokinase
• The glucose-6-phosphate is subsequently oxidized to form adenosine triphosphate
• ATP inhibits the ATP-sensitive potassium channels of the cell
• Opening voltage-gated calcium channels, which are sensitive to changes in membrane voltage
• Influx of calcium that stimulates fusion of the docked insulin- containing vesicles with the cell membrane and secretion of
insulin into the extracellular fluid by exocytosis
• ON CARBOHYDRATE METABOLISM
• N.B: There is Lack of Effect of Insulin on Glucose Uptake and Usage by the Brain

41. MECHANISM OF INSULIN SECRETION
• ON LIPID METABOLISM
• Insulin has several effects that lead to fat storage in adipose tissue
• Increases Fat synthesis in the liver, the glucose is first split to pyruvate in the glycolytic pathway, and the
pyruvate subsequently is converted to acetyl coenzyme A , the substrate from which fatty acids are
synthesized
• Most of the fatty acids are then synthesized within the liver and used to form triglycerides, the usual form
of storage fat
• Insulin inhibits the action of hormone-sensitive lipase
• Insulin promotes glucose transport through the cell membrane into the adipose tissue cells in the same
way that it promotes glucose transport into muscle cells

42. MECHANISM OF INSULIN SECRETION
• ON PROTEIN METABOLISM AND GROWTH
• Insulin stimulates transport of many of the amino acids into the cells
• Insulin increases the translation of messenger RNA, thus forming new proteins
• Over a longer period of time, insulin also increases the rate of transcription of selected DNA genetic
sequences in the cell nuclei, thus forming increased quantities of RNA and still more protein synthesis
• Insulin inhibits the catabolism of proteins, thus decreasing the rate of amino acid release from the cells,
especially from the muscle cells
• In the liver, insulin depresses the rate of gluconeogenesis
• Insulin and Growth Hormone Interact Synergistically to Promote Growth

43. MECHANISM OF INSULIN SECRETION
• Promotes Muscle Glucose Uptake and Metabolism to produce energy during exercise
• Promotes glucose uptake and oxidation by all tissues
• Storage of Glycogen in Muscle
• Insulin Promotes Liver Uptake, Storage, and Use of Glucose
• Insulin inactivates liver phosphorylase, the principal enzyme that causes liver glycogen to split into glucose
• Increases the activity of the enzyme glucokinase, which is one of the enzymes that causes the initial phosphorylation of
glucose
• Promotesglycogensynthesis,includingespeciallyglycogen synthase
• Insulin Promotes Conversion of Excess Glucose into Fatty Acids and Inhibits Gluconeogenesis in the Liver

44. CONTROL OF INSULIN SECRETION
Insulin causes K+ to enter the cells through its activation of
Na+-K+ ATPase
K+ depletion causes inhibition of Insulin secretion , this
happens in 1ry Hyperaldosteronism and patients treated with
thiazide diuretic)

45. INSULINOMA—HYPERINSULINISM
About 10 to 15 percent of these adenomas are malignant, In case of
high levels of insulin cause blood glucose to fall to low values, the
metabolism of the central nervous system becomes depressed
Consequently, in patients with insulin-secreting tumors or in patients
with diabetes who administer too much insulin to themselves, the
syndrome called insulin shock may occur as follows
Proper treatment for a patient who has hypoglycemic shock or coma is
immediate intravenous administration of large quantities of glucose

46. GLUCAGON
• Breakdown of liver glycogen
• Increased gluconeogenesis in the liver

47. PHYSIOLOGICAL ACTIONS OF
GLUCAGON
• Increased Blood Glucose Concentration
• Glucagon activates adenylyl cyclase in the hepatic cell membrane
• Which causes the formation of cyclic adenosine monophosphate
• Which activates protein kinase regulator protein
• Which activates protein kinase
• Which activates phosphorylase b kinase
• Which converts phosphorylase b into phosphorylase a
• Which promotes the degradation of glycogen into glucose-1- phosphate
• Which is then dephosphorylated; and the glucose is released from the liver cells

48. Glucagon Increases Gluconeogenesis
• Stimulates lipolysis, Keogenesis and fat utilization for energy production

49. Regulation of Glucagon Secretion
• Increased Blood Glucose Inhibits Glucagon Secretion

50. Regulation of Glucagon Secretion
• Increased Blood Amino Acids Stimulate Glucagon Secretion
• Exercise Stimulates Glucagon Secretion

51. SOMATOSTATIN
Somatostatin acts locally within the islets of Langerhans in a
paracrine way to depress the secretion of both insulin and glucagon
Somatostatin decreases the motility of the stomach, duodenum, and
gallbladder
Somatostatindecreasesbothsecretionandabsorptioninthe
gastrointestinal tract

52. SUMMARY OF BLOOD GLUCOSE REGULATION
The liver acts as a Glucostat : That is, when the blood glucose rises to a high concentration after
a meal and the rate of insulin secretion also increases, as much as two thirds of the glucose
absorbed from the gut is almost immediately stored in the liver in the form of glycogen
Both insulin and glucagon function as important feedback control systems for maintaining a
normal blood glucose concentration
Also, in severe hypoglycemia, a direct effect of low blood glucose on the hypothalamus
stimulates the sympathetic nervous system
And finally, over a period of hours and days , both growth hormone and cortisol are secreted in
response to prolonged hypoglycemia

53. Importance of Blood Glucose
Regulation
• In case of hypoglycemia: Glucose is the only nutrient that normally can
be used by the brain, retina, and germinal epithelium of the gonads in
sufficient quantities to supply them optimally with their required energy

54. In case of hyperglycemia
Glucose can exert a large amount of osmotic pressure in the extracellular fluid, and if the glucose
concentration rises to excessive values, this can cause considerable cellular dehydration
An excessively high level of blood glucose concentration causes loss of glucose in the urine
Loss of glucose in the urine also causes osmotic diuresis by the kidneys, which can deplete the
body of its fluids and electrolytes
Long-term increases in blood glucose may cause damage to many tissues, especially to blood
vessels

55. DIABETES MELLITUS
Type I diabetes, also called
insulin-dependent diabetes
mellitus , is caused by lack
of insulin secretion
Type II diabetes, also called
non-insulin-dependent
diabetes mellitus , and is
initially caused by decreased
sensitivity of target tissues to
the metabolic effect of
insulin

56. DIABETES MELLITUS
Microvasularcomplications:retinopathy,pe
ripheralneuropathy, Nephropathy
Macrovasular complications:
Atherosclerosis, Ischemic heart
diseases, cerebrovascular Strokes
Fasting blood glucose more than: 126
mg/dl
HBA1C more than: 6.4 %
Homeostatic model assessment index:
evaluates B-cell function and Insulin
resistance

57. Adrenal gland
There are two adrenal glands, one at the superior
pole of each kidney
The adrenal glands are essential for life
Severe illness results from their atrophy and death
follows their complete removal

58. Mineralocorticoids
¯It regulates the electrolyte concentrations of extracellular
fluids
¯Mineralocorticoids include mainly aldosterone and
deoxy-corticosterone
¯Mineralocorticoids are essential for life, without
aldosterone, a person rapidly dies from circulatory shock

59. Action of aldosterone
• NB: Aldosterone also increases Na+ absorption from other body fluid as
well as from GIT mucosa
• Angiotensin II stimulates conversion of corticosterone to aldosterone in
the zona glomerulosa cells and secretion of aldosterone from these cells
• Direct stimulation of adrenal cortex by a rise in plasma K+ concentration

60. Glucocorticoids
• Physiological actions of glucocorticoids

61. GLUCOCORTICOIDS
Effect on metabolism

62. Glucocorticoids
Stimulation of
gluconeogenesis by the liver
Decrease the utilization of
glucose by muscle and
adipose tissue and lowers
their sensitivity to insulin
Increase protein degradation
in many tissue especially
muscle, increases the blood
amino acid concentration,
thus providing more amino
acids to liver or for tissue
repair
Decreased protein synthesis
Increase lipolysis (the
mobilized fatty acids are
available as an alternative
metabolic fuel for tissues that
can use this energy source
as an alternative to glucose,
conserving glucose for the
brain
In diabetics, it increases
ketone body formation
Permissive action
Role in adaptation to stress

63. Glucocorticoids
Gluconeogenesis
Rises in blood
glucose, fatty
acids, and amino
acids

64. Glucocorticoids
Other effects
Cortisol has a very slight mineralocorticoid activity
During fetal life, cortisol accelerates the maturation of surfactant in the lung
When cortisol or synthetic cortisol like compounds are administered to yield higher than physiologic concentrations of
glucocorticoids during treatment of certain diseases; or in case of its hypersecretion by adrenal cortex
Corticosteroids are anti-inflammatory and immunosuppressive
It suppress the inflammatory reaction by reducing phagocytic action of white blood cells , inhibiting release of the lysosomal
enzymes and decreasing capillary permeability
Suppresses allergic reactions by preventing release of histamine from the mast cells

65. Glucocorticoids
Other undesirable effects may be observed with prolonged exposure to
higher than normal concentrations of glucocorticoids
Cortisol increases the production of red blood cells by mechanisms
that are unclear
The administration of large doses of cortisol causes significant atrophy
of all the lymphoid tissue throughout the body, which in turn decreases
the output of both T cells and antibodies from the lymphoid tissue

66. Glucocorticoids
• NB: This occasionally can lead to fulminating infection and death from
diseases that would otherwise not be lethal, such as fulminating
tuberculosis in a person whose disease had previously been arrested

67. Glucocorticoids
• Hypothalamic control is via CRH
• CRH is secreted into the hypothalamic-hypophyseal portal blood and sent to the anterior pituitary
• CRH binds to receptors causing synthesis of POMC a precursor of ACTH
• POMC is a large precursor of MSH, and β- endorphin
• ACTH being tropic to zona fasciculata and zona reticularis
• Negative feedback system involving the hypothalamus and anterior pituitary
• Diurnal rhythm: The plasma cortisol concentration display a characteristic diurnal rhythm, with the highest level occurring in
the morning and lowest level at mid night
• Stress: The magnitude of the increase in plasma cortisol concentration is proportional to intensity of the stressful stimuli

68. THE ADRENAL SEX
HORMONES
Adrenal androgen “Dehydroepiandrosterone” and androstenedione

69. The adrenal sex hormones
Development
and
maintenance of
female sex drive
Have no
masculinizing
effect in their
normal amount

70. The adrenal sex hormones
ACTH controls
adrenal androgen
secretion
Adrenal androgens
feedback outside
the hypothalamus
pituitary adrenal
cortex loop
Instead of
inhibiting CRH, it
inhibits
gonadotropin
releasing
hormone, just as
testicular
androgen do
Adrenal androgen
secretion
undergoes a
marked surge, at
the time of
puberty, and peaks
between the ages
25 and

71. Disorders of the adrenal cortex
Is most commonly caused by autoimmune destruction of the adrenal cortex by erroneous production of adrenal cortex – attacking antibodies
Characterized by deficiency of all adrenocortical hormones and hyper- pigmentation
Pituitary or hypothalamic abnormality
Does not exhibit hyper-pigmentation
Aldosterone levels are normal
Decreased sodium
Decrease ECF volume
Hyperkalemia → disturbs cardiac rhythm and metabolic acidosis
Patient dies in shock if untreated
Disruption in glucose concentration

72. Disorders of the adrenal cortex
Reduction in metabolism of fats and proteins
Decreased resistance to different types of stress
Pigmentation of mucous membranes, pressure areas of skin areola & nipple due to
increased ACTH secretion
Loss of pubic and axillary hair in females
Anemia

73. NB: Addisonian crisis
Primary hyperaldosteronism
Caused by over activity of the zona glomerulosa as a result of
hypersecreting adrenal tumor
Caused by inappropriately high activity of the renin – angiotensin
system
The symptoms of both are related to exaggerated effects of
aldosterone

74. NB: ADDISONIAN
CRISIS
High blood pressure

75. NB: Addisonian crisis
Metabolic alkalosis , decreases the plasma Ca++
Overstimulation of the adrenal cortex by excessive amount of CRH or ACTH
Adrenal tumors that uncontrollably secrete cortisol independent of ACTH
ACTH secreting tumors located in places other than the pituitary, most commonly in
the lung
Administration of pharmacological doses of glucocorticoids

76. NB: Addisonian crisis
↑ Cortisol and androgen levels
↑ ACTH , ↓ ACTH
Hyperglycemia, glucosuria
Central obesity , round face supraclavicular fat
↑ Protein catabolism leads to muscle wasting and fatigue
Poor wound healing and easy bruisability
Hypertension
Osteoporosis
The protein poor thin skin of the abdomen becomes over overstretched by the excessive underlying fat deposits forming irregular reddish purple linear streaks
Virilization of women

77. Adrenogenital syndrome
Male pattern of
body hair
Deepening of
the voice and
more muscular
arms and legs

78. Adrenogenital syndrome
• The breast become smaller, and menstruation may cease , and sterility
occur
• Female infants born with a male – type external genitalia

79. ADRENOGENITAL
SYNDROME
Pre-pubertal males: Precocious pseudo-puberty

80. Adrenogenital syndrome
Over activity of adrenal androgens in adult males has no apparent
effect
The adrenogenital syndrome is most commonly caused by enzymatic
defect in the cortisol steroidogenic pathway
The decline in cortisol secretion removes –ve feedback effect on the
hypothalamus and anterior pituitary →↑ CRH and ACTH →↑ androgen
pathway

81. Adrenal medulla
The adrenal medulla forms about 20% of the adrenal gland
It is a modified postganglionic sympathetic neuron where the
neurons have lost their axons and become secretory cells
Controlled by preganglionic sympathetic innervation
Secretes epinephrine and norepinephrine

82. Adrenal medulla
• Hormones are secreted and stored in the adrenal medulla and released in response to appropriate stimuli by
exocytosis
• Epinephrine is primarily a hormone produced by the adrenal medulla, whereas norepinephrine is also a
neurotransmitter of major importance in sympathetic nervous system
• Adrenomedullary hormones are not essential for life, but virtually all organs in the body are affected by these
catecholamines
• The effects of epinephrine and norepinephrine are brought about by actions on two classes of and β
adrenergic receptors
• Epinephrine and norepinephrine exert similar effects in many tissues, with epinephrine generally reinforcing
sympathetic nervous activity
• Both hormones increase the force and rate of contraction via β1 receptors

83. Adrenal medulla
Both hormones also increase myocardial excitability
Increase arterial blood pressure
Norepinephrine produces vasoconstriction in almost all organs via a1
Epinephrine promotes vasodilation of the blood vessels that supply skeletal muscle and the heart through β2 receptor activation
Epinephrine constricts blood vessels which have α-adrenergic receptors in their smooth muscle
A central role of epinephrine is to increase the availability of metabolites for the intensive physical activity involved in the acute
stress situation described
The release of glucose from the liver to the blood is increased by epinephrine in several ways: it increases glycogenolysis, and
stimulates gluconeogenesis

84. Adrenal medulla
Epinephrine stimulates glycogenolysis in skeletal muscles, leading to the formation of
lactic acid
In pancreatic beta cells, epinephrine inhibits the production of insulin, and stimulates
glucagon
In adipose tissue, epinephrine stimulates the lipolysis
Epinephrine increases the overall metabolic rate
Catecholamines affect the central nervous system to promote a state of arousal and
increased CNS alertness