Internal Medicine Al Azhar university Faculty of Oral and Dental Medicine Lama El Banna

1. Dr. Suhail S. Kishawi
Consultant in Endocrinology and Diabetes
Consultant Internist
Diseases Of The Pituitary
Gland

3. THE ENDOCRINE SYSTEM
 It is of central importance to maintain stable internal
environment of the body.
 Such stability could be achieved only through the operation of
carefully coordinated physiological processes.
 The activities of cells, tissues, and organs must be regulated
and integrated with each other in such a way that any change
in the internal environment initiates a reaction to minimize the
change.
 HOMEOSTASIS denotes the stable conditions of the internal
environment that result from these compensating regulatory
responses.

4. THE ENDOCRINE SYSTEM
 Changes in the internal environment of the body
occur, but the magnitudes of these changes are
small and are kept within narrow limits through
multiple coordinated homeostatic processes.
 To achieve this, communication between cells, often
over relatively long distance is essential.
 The endocrine system is one of the body's two major
communicating systems, the nervous system being
the other

5. THE ENDOCRINE SYSTEM
 The endocrine system is oriented towards preservation of an
environment:
 That permits optimal efficiency of each individual physiologic
process
 That compensates for damage and stress from almost any
source of pathology.
 However when the precipitating pathology is actually within the
endocrine system itself, the ability of the system to self-correct
is extremely limited and the results can be disastrous.

6. THE ENDOCRINE SYSTEM
 The endocrine system is made up of secretory tissues
(ductless internal glands) whose secretions (hormones) are
discharged directlydirectly into the blood stream in response to a
stimulus.
 Hormones : are specialized chemical messengers produced by
a variety of specialized secretory cells of the endocrine system.
 They are carried via the circulation to other parts of the body
where they exert specific regulatory effects on their selected
target cells.
 These target cells possess particular recognition features
called hormone receptors (the classical endocrine effect).

7. Long Distance cell-to-cell Communication
Hormones And Neurotransmitters
• Hormones are secreted by
endocrine glands or cells into
the blood. Only target cells with
receptors for the hormone will
respond to the signal
• Neurotransmitters are
chemicals secreted by neurons
that diffuse across a small gap
to the target cell.
• Neurons use electrical signals
as well.

8. THE ENDOCRINE SYSTEM
• Endocrinology is the study of chemical
communication systems that provide the means to
control a huge number of physiologic processes.
• Like other communication networks, endocrine
system contains
Transmitters (hormone producing cells),
Signals or messengers (hormones) and
Receivers (receptors).

9. So what are hormones?
 Molecules secreted by specialized glands that function as a message
within an organism: their only function is to convey information.
 Travel from site of production (endocrine cell) to site of action (target
tissue) via blood
 Operate by binding to specific receptors only expressed at target cells

10. Hormones are categorized into five structural groups:
1) Large proteins like insulin, luteinizing hormone (LH) and PTH
2) Small neuropeptides like GnRH, TRH, somatostatin, and
vasopressin
HORMONE CHEMISTRY

11. HORMONE CHEMISTRY
1) Amino Acid Derivatives
There are two groups of hormones derived from the amino
acid tyrosine :
A. Thyroid hormones are basically a "double" tyrosine with
incorporation of 3 or 4 iodine atoms.
B. Catecholamines include epinephrine and norepinephrine, which
are used as both hormones and neurotransmitters.

12. HORMONE CHEMISTRY
4.Steroids are derivatives of
cholesterol. Like sex steroids such as
estrogen, testosterone and adrenal
steroids such as cortisol.
5. vitamin derivatives such as retinoids
(vitamin A) and vitamin D
As a rule :As a rule :
oAmino acid derivatives and peptide
hormones interact with cell-surface
membrane receptors.
oSteroids, thyroid hormones, vitamin D,
are lipid-soluble and interact with
intracellular nuclear receptors.

13. HORMONES, RECEPTORS AND TARGET CELLS
• Hormones are chemical messengers secreted into blood or
extracellular fluid by one cell that affect the functioning of other cells.
• Most hormones circulate in blood, coming into contact with
essentially all cells. However, a given hormone usually affects only a
limited number of cells, which are called target cells.
• A target cell responds to a hormone because it bears receptors for the
hormone.

14. BASIC MECHANISMS OF CHEMICAL SIGNALING

15. Hormone Binding protein(s)
Thyroxine(T4)
Thyroxine-binding globulin (TBG)
Thyroxine-binding prealbumin (TBPA)
Albumin
Cortisol Cortisol-binding globulin(CBG)
Testosterone
Estradiol
Sex hormone-binding globulin (SHBG)
Insulin-like growth
factor 1 (IGF-1)
IGF-binding protein 1-6 (IGF-BP 1-6)
PLASMA TRANSPORT

16. CONTROL OF SECRETION
NEGATIVE FEEDBACK : THYROID

17. CONTROL OF SECRETION
POSITIVE FEEDBACK
• Such a mechanism is less common, and tends
to increase rather than to stabilize the level of
circulating hormone.
• A hormone may facilitate its own release
directly, by acting on the anterior pituitary, or
indirectly by stimulating hypothalamic
hormones release.
• During the female menstrual cycle, a positive
feedback loop is activated when the level of
estrogen, released from the ovaries, attain a
certain high threshold level. At this point
estrogen stimulates (rather than inhibits)
the pulsatile release of gonadotrophic
hormones FSH and LH, and also the
hypothalamic GnRH.
• The resulting surge in gonadotrophin secretion
particularly LH leads to ovulation and abrupt
termination of the positive feedback.

18. PATTERNS OF SECRETION
Hormone secretion may be continuous or intermittent:
 Continuous secretion is shown by the thyroid hormones,
where T4, has a half-life of 7-10 days and T3 of about 6-10
hours. Levels over the day, month and year show very little
variation.
 In contrast, secretion of the gonadotrophins, LH and FSH, is
normally pulsatile, with major pulses released every 2 hours or
so.

19. BIOLOGICAL RHYTHMS
Circadian changes: mean changes over the
24 hours of the day-night cycle and is best
shown for the glucocorticoid cortisol axis. It
shows plasma cortisol levels measured over
24 hours - levels are highest in the early
morning and lowest overnight.
Additionally, cortisol release is pulsatile,
following the pulsatility of pituitary ACTH.
Thus normal' cortisol levels (stippled
areas) vary during the day and great
variations can be seen in samples taken only
30 mm apart
The menstrual cycle is the best example of
a longer (28-day) biological rhythm.

21. Endocrine System

22. Hypothalamus / Pituitary
The structure by gross anatomy as one gland (the pituitary) but actually two parts of
fundamentally different emryological origin.
1. The anterior pituitary is true endocrine tissue,
2. The posterior pituitary is neural tissue extending downward from the
region of the brain called the hypothalamus.

23. Pituitary Gland
• Lives in the skull base
in its own compartment
called Sella turcica

24. Pituitary - Relation to sphenoid sinus

25. The pituitary gland and its anatomical relations to
cavernous sinus and optic chiasm

26. The blood supply of the pituitary gland and its vascular
connection to the hypothalamus

27. Some hypothalamic
hormones are
transported to
capillaries in the
posterior pituitary
and released into
capillaries there for
transport to distant
tissues.
Other hypothalamic hormones
(releasing factors) enter
capillaries that merge into
portal veins which branch into
more capillaries in the anterior
pituitary to govern the release
of trophic hormones there.

28. Neurons extending from the
hypothalamus to the posterior
pituitary synthesize two
peptides that are packaged
into vesicles, transported
within the neurons to the
posterior pituitary, and
released there into the blood
to be carried by the circulation
to distant target tissues.
Therefore, these peptides,
vasopressin (antidiuretic
hormone, ADH) and oxytocin,
are classified as
neurohormones.

29. GROWTH
HORMONE

30. PITUITARY GLAND HORMONES

31. MECHANISMS OF ENDOCRINE DISEASE
• Endocrine disorders result from hormone deficiency,
hormone excess or hormone resistance
• Almost without exception, hormone deficiency
causes disease
– One notable exception is calcitonin deficiency
• Endocrine tumors: Hormone-secreting tumors can
occur almost in all endocrine organs, most
commonly pituitary, thyroid and parathyroid.

32. ANTERIOR PITUITARY HYPERFUNCTION
• What happens if:
– TOO much secretion of prolactin ( Prolactinoma)?
– Too much growth hormone secretion?
Anovulation; menstrual irregularities;
(Galactorrhea Amenorrhea Syndrome)
Gigantism In Children;
Acromegaly In Adults

33. Tumours of the anterior pituitary can
cause syndromes of hormone excess
• GH
• ACTH
• TSH
• LH/FSH
• PRL
Acromegaly
Cushing’s disease
Secondary thyrotoxicosis
(Non-functioning pituitary
tumour)
Prolactinoma

34. Pituitary MRI

35. Pituitary Tumor
Optic Chiasm
Pituitary Macroadenoma
(Sagittal MRI Scan(

36. TOO MUCH GROWTH HORMONE
• GIGANTISM IN CHILDREN
• ACROMEGALY IN ADULTS
– Enlarged feet/hands, thickening of bones, prognathism (jaw
projects forward), diabetes, HTN, wt. gain,
– Visual disturbances, diabetes mellitus

38. Acromegaly : Large Hands

39. A patient with marked macroglossia. This can cause severe
sleep apnea which can be associated with cardiac arrhythmias
and sudden death.
Acromegaly

40. Definitions
• Cushing’s Syndrome
– Excess cortisol in the blood
• Cushing’s Disease
– Excess cortisol in the blood due to an ACTH secreting
pituitary tumour

41. Cushing’s Syndrome
– Excess hair growth
– Irregular periods
– Problems conceiving
– Impotence
– High blood pressure
– Fluid retention
– Central obesity
– Moon face
– Buffalo hump
– Thin skin, easy
bruising
– Osteoporosis
– Diabetes

43. Cushing’s Syndrome

44. S & S Anterior Pituitary
Hypofunctioning
• GH
• FSH/LH
• Prolactin
• ACTH
• TSH
Define:
• Selective hypopituitarism
• Panhypopituitarism
ANTERIOR PITUITARY-
Hypofunction
•Etiology: (rare disorder)
may be due to disease,
tumor, or destruction of
gland.
•Diagnostic tests
•CT Scan
•Serum hormone
levels

45. Hypopituitarism
• Is usually gradual and may have single
hormone deficiency or multiple
hormone
• GH deficiency
 Deficiency In Children Lead To Short Stature
 Deficiency in adult lead to vague non specific
symptoms, fatigue decrease muscle mass, loss
of libido (somatopause)

46. GH Deficiency
– 1:3500
– Organic ~25% (congenital
or acquired)
– Idiopathic
GHD subject is 18 cm
shorter than her sister,
despite being one and a
half years older.

47. Gonadotrophin Deficiency (Hypogonadism)
• In women
a. Before puberty primary amenorrhea and failure of puberty
development
b. After puberty secondary amenorrhea and regression of
secondary sexual characteristic
C. Infertility

48. Gonadotrophin Deficiency (Hypogonadism)
• In men
A.Before puberty : failure of puberty development
B.After puberty : decrease libido or impotence, loss of
secondary sexual characteristic
C. Infertility

49. Treatment of hypopituitrism
DeficientDeficient
hormonehormone
TherapyTherapy
TSHTSH L-thyroxin .05-.02 mg/d POL-thyroxin .05-.02 mg/d PO
ACTHACTH Hydrocortisone 20 mg/ m-10mg /eHydrocortisone 20 mg/ m-10mg /e
LH and FSHLH and FSH Men :testosteroneMen :testosterone
Women :cyclic estrogen and progesteroneWomen :cyclic estrogen and progesterone
For fertility HCG,HMGFor fertility HCG,HMG
GHGH 0.05 mg/kg0.05 mg/kg

50. Posterior Pituitary-(Neurohypophysis(
• Name the hormones released by posterior pituitary
when signaled by hypothalamus!
ADH (vasopressin) and oxytocin

51.  Oxytocin is released from a
mother's posterior pituitary when
an infant is suckling, triggered by
stimulation of sensory nerves
leading from the nipples to the
paraventricular nuclei of the
hypothalamus.
 Elevation of oxytocin in blood
leads to contraction of smooth
muscle surrounding milk ducts in
the breasts.
 Oxytocin also stimulates
contraction of uterine muscle
during childbirth, in response to
cervical stretching.

52. Vasopressin ( Anti Diuretic Hormone : ADH (
 ADH is secreted in response to low blood pressure or
volume and to osmolarity of extracellular fluid, with ADH
secretion beginning at very low osmolarity and increasing
as osmolarity increases.
 ADH binds to a membrane receptor in the kidney and
increases H2O permeability of DCT and CD which leads to
reabsorbtion of free water and vasoconstriction

53. Posterior Hypopituitary-ADH disorders
• Diabetes Insipidus-(DI( (too
little ADH(
• Etiology:
– (50% idiopathic(
– Central- neurogenic- i.e.
brain tumors
– Nephrogenic - inability of
tubules to respond to ADH
– Psychogenic

54. What Clinical Manifestations-DI?
• Polydipsia
• Polyuria (10L in 24 hours(
• Severe fluid volume deficit
– wt loss
– tachycardia
– constipation
– shock

55. Medical Management-DI
• Identify etiology, H & P
• Treat underlying problem
• Desmopressin acetate (DDAVP(-
– Central DI; orally, nasally, IV
• Vasopressin (Pitressin(
• Diabenese, carbamazepine (Tegretol(
– Partial central DI
• Dietary, low Na etc if neprhogenic cause

56. Posterior Pituitary Disorders
• SIADH (Syndrome Of Inappropriate Anti Diuretic
Hormone = (TOO MUCH ADH!!(
• Numerous causes:
– Small cell lung cancer , other types cancer
– CNS disorders
– Medications as, thiazide diuretics, opioids, general
anesthetics, tricyclic antidepressants, others
– Miscellaneous

57. SIADH (TOO MUCH ADH!!(
Inappropriate secretion of ADH
Water excretion is impaired
Suppression of ADH is impaired
Functions of ADH
Increases permeability of water in the cells of the
distal tubules
Increases the permeability of collecting ducts to urea

58. SIADH - treatment
Treat the underlying cause, if known
Fluid Restriction – commonly 800-1000mL/d
Correct Na+ deficit – no more than 10mEq/L in 24
hours, 18mEq/L in 48 hours
0.9% NaCl
3% NaCl
NaCl enteral tablets – 2-3g TID
Add a loop diuretic

59. Key points
 The pituitary gland sits in the sella turcica in the
sohenoid bone and has close anatomical relations to
the optic chiasm and the cavernous sinus.
 Hypophyseal portal vessels transmit hypothalamic
releasing and inhibitory hormones to the anterior
pituitary.
 The anterior pituitary secretes at least six peptide
hormones : GH, prolactin, ACTH,TSH,LH and FSH.

60. Key points
 GH is secreted by somatotophs (stimulated by GH-
releasing hormone(,
 Prolactin is secreted by lactotophs (inhibited by
dopamine(,
 ACTH is secreted by corticotrophs (stimulated by
CRH(,
 TSH is secreted by thyrotrophs ( stimulated by TRH(

61. Key points
 LH and FSH are secreted by gonadotrophs
(stimulated by pulsatile GnRH(.
 The posterior pituitary secretes oxytocin and
vasopressin (also known as antidiuretic hormone(.
 Vasopressin secretion is stimulated by an increase
in serum osmolality and decreased extracellular
volume and blood pressure.

62. THANK YOUTHANK YOU