2. Endocrine System
Pituitary Gland
- The main endocrine gland.
- Called the “master” gland.
- Acts as the control center
for the endocrine system which
controls all the hormones
produced by other glands in the
body.

3. PITUITARY FOSSA

5. Some of the neurons within the
hypothalamus - neurosecretory
neurons - secrete hormones that
strictly control secretion of hormones
from the anterior pituitary.
The hypothalamic hormones are
referred to as releasing hormones
and inhibiting hormones, reflecting
their influence on anterior pituitary
hormones.

6. Hypothalamic releasing
and inhibiting hormones
are carried directly to the
anterior pituitary gland
via hypothalamic-
hypophyseal portal veins
.
Specific hypothalamic
hormones bind to
receptors on specific
anterior pituitary cells,
modulating the release
of the hormone they
produce.

8. Anterior
Pituitary
Posterior
pituitary Stimulates milk
ejection and uterine
contractions
Ovary and testisOxytocin
Conservation of
body water
KidneyAntidiuretic hormone
Control of reproductive
function
Ovary and testisFollicle stimulating
hormone
Control of reproductive
function
Ovary and testisLuteinizing hormone
Milk productionMammary glandProlactin
Stimulates secretion of
glucocorticoids
Adrenal gland cortexAdrenocorticotrophic
hormone
Stimulates secretion of
thyroid hormones
Thyroid glandThyroid stimulating
hormone
Promotes growth (indirectly),
control of protein, lipid and
carbohydrate metabolism
Liver, adipose tissueGrowth hormone
Major physiologic
effects
Major target organsHormone

9. • The portion of the adenohypophysis known as the pars tuberalis
contains cords of epithelial cells and is filled with hypophyseal portal
vessels. It reportedly contains gonadotropes and thyrotropes, plus
other secretory cells of unknown function.
• The pars intermedia is closely associated with pars nervosa and
separated from the pars distalis by the hypophyseal cleft.
Melanocyte-stimulating hormone is the predominant hormone
secreted by the pars intermedia.
The pituitary gland has two distinct
parts, the anterior and the posterior
lobes, each of which releases
different hormones.

10. • Histology of the Adenohypophysis
• The bulk of the adenohypophysis is
pars distalis. That tissue is composed
of winding cords of epithelial cells
flanked by vascular sinusoids.
• In sections stained with dyes such as
hematoxylin and eosin, three distinct
cell types are seen among epithelial
cells:
• Acidophils have cytoplasm that stains
red or orange
• Basophils have cytoplasm that stains
a bluish color
• Chromophobes have cytoplasm that
stains very poorly

11. • Histology of the Adenohypophysis
• The bulk of the adenohypophysis is
pars distalis. That tissue is composed
of winding cords of epithelial cells
flanked by vascular sinusoids.
• In sections stained with dyes such as
hematoxylin and eosin, three distinct
cell types are seen among epithelial
cells:
• Acidophils have cytoplasm that stains
red or orange
• Basophils have cytoplasm that stains
a bluish color
• Chromophobes have cytoplasm that
stains very poorly

12. Acidophils: contain the polypeptide hormones:
– Somatotropes which produce growth hormone
– Lactotropes which produce prolactin
Basophils: contain the glycoprotein hormones:
– Thyrotropes which produce thyroid stimulating hormone
– Gonadotropes which produce luteinizing hormone or
follicle-stimulating hormone
– Corticotropes which produce adrenocorticotrophic hormone
Chromophobes
• These are cells that have minimal or no hormonal content.
– may be acidophils or basophils that have degranulated and thereby
are depleted of hormone
– may also represent stem cells that have not yet differentiated into
hormone-producing cells.

13. • Although classification of cells as acidophils or
basophils is useful in some situations, specific
identification of anterior pituitary cells requires
immunostaining for the hormone in question.
• In addition to differential staining characteristics, the
size of secretory granules varies among different
types of cells in the anterior pituitary.
Somatotropes and lactotropes tend to have the
largest size granules.

14. Hyperpituitarism and
Pituitary Adenomas

15. Pituitary tumor causes symptoms by any of
three mechanisms:
1. By producing too much of one or more
hormones.
2. By compressing the pituitary gland, and thus
making it produce too little of one or more
hormones.
3. By compressing the optic nerves or (less
commonly) the nerves controlling eye
movements, and thus causing either loss of part
or all of the visual field, or double vision.

17. ENLARGING PITUITARY MASS

19. Type of Adenoma Secretion Staining Pathology
Corticotrophic
adenomas
Secrete adrenocotrophic
hormone (ACTH) and
Proopiomelanocortin
(POCM)
Basophilic Cushing’s disease
Somatotrophic
adenomas
Secrete growth hormone
(GH)
Acidophilic Acromegaly
(Gigantism)
Thyrotrophic
adenomas (rare)
Secret thyroid stimulating
hormone (TSH)
Basophilic Occasionally
hyperthyroidism
usually does not cause
symptoms
Gonadotrophic
adenomas
Secrete luteinizing
hormone (LH), follicle
stimulating hormone (FSH)
Basophilic Usually does not cause
symptoms
Prolactinomas Secret prolactin Acidophilic Galactorrhea,
hypogonadism,
amenorrhea, infertility
and impotence
Null cells adenomas Do not secrete hormones May stain positive for
synaptophysin

20. By producing too much of one or more hormones
• Growth hormone: causes ACROMEGALY
– a syndrome that includes:
• excessive growth of soft tissues and bones
• high blood sugar
• high blood pressure
• heart disease
• sleep apnea
• excess snoring
• carpal tunnel syndrome
• pain symptoms (including headache).

21. By producing too much of one or more hormones
• Thyroid stimulating hormone:
– causes high production of thyroid hormone
– Thyroid hormone:
• leads to nervousness and irritability
• fast heart rate and high blood pressure
• heart disease
• excess sweating and thin skin
• and weight loss.

22. By producing too much of one or more hormones
• Prolactin:
– causes inappropriate secretion of breast milk (even in
men)
– osteoporosis (bone weakening)
– loss of sex drive
– Infertility
– irregular menstrual cycles
– and impotence

23. By producing too much of one or more hormones
• Adrenocorticotropic hormone:
– causes weight gain (particularly in the body’s trunk,
not the legs or arms)
– high blood pressure
– high blood sugar
– brittle bones
– emotional changes
– stretch marks on the skin
– easy bruising.

24. By producing too much of one or more hormones
• Gonadotropins (FSH and LH):
– usually not elevated enough to produce direct
symptoms
– but in extreme cases can cause infertility (inability to
have a child)
– irregular menstrual cycles in women.

25. Cushing’s Syndrome
• Definition
– a condition that occurs when your body is exposed
to high levels of the hormone cortisol for a long time.
– Referred to as hypercortisolism
– use of oral corticosteroid medication (most common
cause)
– The condition can also occur when your body
makes too much cortisol.

26. Hallmark signs of Cushing's syndrome:
- fatty hump between shoulders
- rounded face
- pink or purple stretch marks on your skin
- can also result in high blood pressure, bone loss and, on
occasion, diabetes.

27. By compressing the pituitary gland, and thus making it produce
too little of one or more hormones.
• Growth hormone: causes poor muscle strength, irritability,
weakening of bone strength, and overall feeling of malaise (feeling
unwell). DWARFISM in children.
Thyroid stimulating hormone: causes fatigue, low energy, and
weight gain.
• Prolactin: causes inability to breastfeed after a woman gives birth to
a baby.
• Adrenocorticotropic hormone: causes fatigue and low energy, low
blood pressure, low blood sugar, and upset stomach.
• Gonadotropins (FSH and LH): cause infertility, decrease in sex
drive, impotence, and irregular menstrual cycles.

28. Histology of the Neurohypophysis
• The neurohypophysis is known also as the pars
nervosa.
• Three areas of this organ, starting closest to the
hypothalamus:
– the median eminence
– infundibular stalk
– infundibular process
• The infundibular - bulk of the neurohypophysis (usually
referred to as the posterior pituitary)
• Composed on largely unmyelinated axons from
hypothalamic neurosecretory neurons.
• These neurons secrete oxytocin and antidiuretic
hormone.

29. • The neurohypophysis shown here resembles neural
tissue, with glial cells, nerve fibers, nerve endings, and
intra-axonal neurosecretory granules.
• The hormones vasopressin (antidiuretic hormone, or
ADH) and oxytocin made in the hypothalamus
(supraoptic and paraventricular nuclei) are transported
into the intra-axonal neurosecretory granules where they
are released.

30. Anterior pituitary Posterior pituitary

31. • Oxytocin increases uterine contractions and
stimulates milk secretion.
• Underproduction of ADH results in a disorder called
diabetes insipidus characterized by inability to
concentrate the urine. The consequence is excess
urination leading potentially to dehydration.
• Antidiuretic hormone (ADH) increases reabsorption
of water by the tubules of the kidney.

32. Syndrome of Inappropriate ADH Secretion
(SIADH)
= Excess resorption of water -> hyponatremia
= CAUSES:
Secretion of ectopic ADH (small cell ca of the lung)
Injury to hypothalamus or pituitary or both.

33. Parathyroid Gland
They are hard to differentiate from the thyroid or fat.
The parathyroid glands are four or more small glands, about the size of a
grain of rice, located on the posterior surface (back side) of the thyroid
gland.
The parathyroid glands are named for their proximity to the thyroid but serve
a completely different role than the thyroid gland.
They are quite easily recognizable from the thyroid as they have densely
packed cells, in contrast with the follicle structure of the thyroid.

34. Thyroid Gland: colloid-filled follicles Parathyroid Gland

35. The sole purpose of the parathyroid glands is to control calcium
within the blood in a very tight range between 8.5 and 10.5.
Parathyroid hormone (PTH)
- mobilizes calcium release from bone when there is a decrease the
blood level of calcium.
- enhances intestinal absorption of calcium.
PARATHYROID HORMONE

36. Hyperparthyroidism
• The most common cause of excess hormone
production (hyperparathyroidism) is the
development of a benign tumor in one of the
parathyroid glands.
• Over-production of parathyroid hormone.
• Occur in 94 percent of all patients with primary
hyperparathyroidism.

37. Parathyroid adenoma

38. Hyperprathyroidism
Symptoms of Parathyroid Disease
• Loss of energy.
• Don't feel like doing much. Tired all the time.
• Just don't feel well; don't quite feel normal. Hard to explain but just feel kind of bad.
• Feel old. Don't have the interest in things that you used to.
• Can't concentrate, or can't keep your concentration like in the past.
• Depression.
• Osteoporosis and Osteopenia. Bones hurt; typically it's bones in the legs and arms but
can be most bones.
• Don't sleep like you used to. Wake up in middle of night. Trouble getting to sleep.
• Tired during the day and frequently feel like you want a nap.
• Spouse claims you are more irritable and harder to get along with (cranky, bitchy).
• Forget simple things that you used to remember very easily.
• Gastric acid reflux; heartburn; GERD.
• Decrease in sex drive.
• Thinning hair (predominately in older females).
• Kidney Stones.
• High Blood Pressure (sometimes mild, sometimes quite severe; up and down a lot).
• Recurrent Headaches (usually patients under the age of 40).
• Heart Palpitations (arrhythmias). Typically atrial arrhythmias.

40. Adrenal Glands

41. • Located immediately anterior to the
kidneys, encased in a connective tissue
capsule and usually partially buried in an
island of fat.
• Retroperitoneal.

43. Adrenal Gland
Adrenal cortex
- secretes several classes of steroid hormones (glucocorticoids and
mineralocorticoids)
- with three concentric zones of cells that differ in the major steroid
hormones they secrete.

44. Adrenal Gland
Adrenal medulla
- source of the catecholamines epinephrine and norepinephrine.
- chromaffin cell is the principle cell type.
- The medulla is richly innervated by preganglionic sympathetic fibers and
is, in essence, an extension of the sympathetic nervous system.

45. HORMONE SYNTHESIS:
– Corticosteroid.
– Androgen such as testoterone.
– Aldosterone.
– Function is regulated by the neuroendocrine hormones from the
pituitary, hypothalamus and renin-angiotensin system.
– Adrenal medulla is regulated by direct innervation.
ADRENAL CORTEX

46. The adrenal cortex comprises three zones each produces and secretes
distinct hormones.
• Zona glomerulosa (outer)
– for production of mineralocorticoids, mainly aldosterone, which is largely
responsible for the long-term regulation of blood pressure.
• Zona fasciculata
– responsible for producing glucocorticoids, chiefly cortisol in humans.
• Zona reticularis (innermost)
– produces androgens, mainly dehydroepiandrosterone (DHEA) and
DHEA sulfate (DHEA-S) in humans.
ADRENAL CORTEX

47. Adrenal Medullary Hormones
– Cells in the adrenal medulla synthesize and secrete
epinephrine and norepinephrine.
Adrenergic Receptors and Mechanism of Action
– The physiologic effects of epinephrine and
norepinephrine are initiated by their binding to
adrenergic receptors on the surface of target cells.

48. Receptor Effectively Binds Effect of Ligand
Binding
Alpha1
Epinephrine,
Norepinephrine
Increased free calcium
Alpha2 Epinephrine,
Norepinephrine
Decreased cyclic AMP
Beta1 Epinephrine,
Norepinephrine Increased cyclic AMP
Beta2 Epinephrine Increased cyclic AMP

49. Adrenal cortical hyperplasia.
causes:
- due to a pituitary
adenoma secreting ACTH
(Cushing's disease)
- Cushing's syndrome from
ectopic ACTH production
- idiopathic adrenal
hyperplasia.
Adrenal atrophy (with either
Addison's disease or long-
term corticosteroid therapy).
Normal adrenal glands

50. Adrenal adenoma with Cushing's syndrome
- remaining atrophic adrenal is seen at the right.
- composed of yellow firm tissue just like adrenal cortex.
- well-circumscribed.
Histologically
- composed of well-differentiated cells resembling
cortical fasciculata zone. It is benign.

51. Hallmark signs of Cushing's syndrome:
- fatty hump between shoulders
- rounded face
- pink or purple stretch marks on your skin
- can also result in high blood pressure, bone loss and, on occasion,
diabetes.

52. PRIMARY HYPERALDOSTERONISM
• Generic term for a closely related, uncommon
syndromes characterized by chronic excess
aldosterone secretion independent of the RA system.
• Characterized by suppression of plasma renin activity.
• Secondary increased aldostrerone due to renal
ischemia (2ndary hyperladosteronism)

53. Causes of Primary Hyperaldosteronism
1. Conn’s Syndrome:
-solitary aldosterone-secreting adenoma
2. Bilateral Idiopathic Hyperplasia of adrenals.
3. Glucocorticoid-suppressible hyperaldosteronism
4. Adrenal Cortical Carcinoma

54. Solitary aldosterone secreting adenoma - Conn’s Syndrome
- patient had hypokalemia.
- with high serum aldosterone and a low serum renin,
- This lesion accounts for about two-thirds of cases of primary
hyperaldosteronism (PHA)
- Bilateral adrenal hyperplasia accounts for about 30% of PHA.

55. • Microscopically, the adrenal cortical adenoma at
the right resembles normal adrenal fasciculata.
The capsule is at the left. There may be some
cellular pleomorphism.

56. • This is a large adrenal
cortical carcinoma which
is displacing the left
kidney downward.
• Such neoplasms are
usually functional
(secreting corticosteroids
or sex steroids).
• They have a poor
prognosis.

57. • High power microscopic appearance of an adrenal cortical carcinoma
• loosely resembles normal adrenal cortex
• It is difficult to determine malignancy in endocrine neoplasms based upon
cytology alone.
• Thus, invasion (as seen here in a vein) and metastases are the most
reliable indicators.
• Luckily, most endocrine neoplasms are benign adenomas.
BV
TC

58. • Here is an adrenal cortical carcinoma seen microscopically at high
power to demonstrate cellular pleomorphism with nuclear
hyperchromatism.
• Both benign and malignant endocrine neoplasms demonstrate some
degree of cellular pleomorphism, so it is not easy to tell benign from
malignant on histologic grounds alone. The larger the neoplasm, the
more likely it is malignant, but the best indicators are invasion and
metastasis.

59. ADRENAL MEDULLA
A. PHEOCHROMOCYTOMA:
- associated with catecholamine-induced
hypertension.
- occassionally, this tumor produces other
biogenic steroids or peptides asociated with
Cushing’s Syndrome.
-morphology: - ave . weight of 100 gms
- Zellballen appearance

60. • This large adrenal neoplasm has been sectioned in half.
Note the grey-tan color of the tumor compared to the
yellow cortex stretched around it and a small remnant of
remaining adrenal at the lower right. This patient had
episodic hypertension. This is a tumor arising in the
adrenal medulla--a pheochromocytoma.
T
N

61. • There is some residual adrenal cortical tissue at
the lower center right, with the darker cells of
pheochromocytoma seen above and to the left.

62. HYPOADRENALISM
• Caused by any anatomic or metabolic lesion of the
adrenal cortex that impairs output of the cortical steroids.
• Primary Acute Adrenal Insufficiency
- Waterhouse Friderichsen Syndrome
due to overwhelming septicemic
infection caused by meningococci
but occasionally other virulent
organism such as gonococci,pneumococi
and staphylococci.
morphology: massive bilateral adrenal hemorrhage

63. HYPOADRENALISM
• Primary Chronic Adrenal Insufficiency:
- Addison’s Disease
- caused by any destructive process in the
adrenal cortex.
a. Autoimmune Adrenalitis
b. Infection
c. Metastatic Ca to the adrenal cortex