adrenal

1. ADRENAL
By
WAN MUHAMMAD GHAZI BIN WAN ZAWAWI

2. Position and location
■ The adrenal glands located on the upper poles of
each kidney on the right and left sides
■ They are covered by peritoneum on the
posterior abdominal wall they are embedded
into pre renal fat
■ The left one is larger and higher than the right

3. The right adrenal gland
■ It is triangular in shape located on the upper
pole of the right kidney behind the inferior vena
cava
■ It is related anterior to the inferior vena cava and
the right lobe of the liver
■ Posterior it is related to the right cruse of
diaphragm

4. The left adrenal gland
■ It is crescent in shape located on the upper pole
of the left kidney behind the stomach
■ Anterior it is related to the stomach, the tail of
pancreas and the lesser sac
■ Posterior it is related to the left cruse of
diaphragm

5. The blood supply
■ Each adrenal gland supply by three arteries superior
,middle and inferior suprarenal arteries
■ The superior supra renal artery branch from inferior
■
phernicarterywhichisbranchfromthe aorta, the
middle supra renal artery branch from the aorta and the
inferior supra renal artery branch from the renal artery
Thevenousdrainagebythesuprarenalveinonthe
right side at the inferior venacavaand on the left side
at the left renal vein

6. Arterial supply

7. Structure of adrenal gland
■ The adrenal gland formed of outer cortex which
isyellowformingthe main mass of the gland
and inner medulla completely enclosed by the
cortex except at the hilum the gland enclosed by
capsule of connective tissue
■ The cortex has mesodermdevelopment while
the medulla developed from the neural crest

8. The cortex and capsule

9. The adrenal cortex
■ The cortex of the adrenal cortex consist of three layers
arrangedfromouterto innerthezonaglomerulosa,
fasciculata, and reticularis
■ Zona glomerulosa : it is the outer layer located close
to the capsule .
■ itiscellsstimulatedbyACTH andangiotensin2to
secretmineralocorticoidshormoneswhicharethe
aldesterone , they control thefluid and electrolytes
balance in the body by affecting the renal tubules

10. Zona fasciculata
■ It is the middle largest layer of the cortex
■ thecellsof thislayersecrettheglucocorticoids
which are the cortisol and hydrocortisone which
are maintain the carbohydrate balance

11. Zona reticularis
■ It is the inner layers it is cells secret the
gonadocorticoids hormone which are the
estrogen and androgen which supplemented the
sex hormones for both men and women

12. Adrenal Histology

13. Structure of the cortex

14. Adrenals produces:
1. Mineralcorticoids
(Aldosterone)
2. Glucocorticoids
(Cortisol)
3. Gonadocorticoids
(Androgen)
4. Epinephrine (Adrenaline)

15. Aldosterone
■ Target Cell:
■ Kidneys!
■ Exocrine Glands
■ Effect of Hormone:
■ Maintains balance of Na+in the bloodstream
■ aldosterone conservation of Na+

17. Cortisol
■ Produced when ACTH levels are high!
■ Act as negative feedback for the pituitary gland
■ Converts adipose tissue
to glucose!
■ Occurs during high
stress periods
■Emotional distress
■Physical distress
(exercise,
hemorrhage)

19. Androgens
■ “male” sex hormone
■ Converted to Testosterone in Males !
■ Convertedto Estrogen in Females!

20. Adrenal medulla
■ The adrenal medulla developed from the neural crest it
isformedof groupandcolumnsof cellscalled
chromaffin cells
■ The chromaffin cells secreted the adrenalin and
noradrenalin which they activated the sympathetic
stimulation

21. Chromaffin cell

22. Epinephrine
■ Stimulated by Sympathetic Nervous System
to initiate “fight or flight” response!
■ Stored in adrenal gland until needed!
■ Effects of Epinephrine
■
■
■
blood sugar
heart rate
blood flow to brain, heart, muscles

23. Clinical problems
■ Variousclinicalconditiondueto thelesionof the
adrenalcortexormedullaaffect thesecretionof the
adrenal hormone hyper secretion of the hormones of
the adrenal cortex result in Cushing syndrome which
characterized by redistribution of fat the spindle limbs,
swollen face, diabetes mellitus and slow of wound
heeling the
■ HyposecretioncausetheAddisondiseasewhichis
characterized by weight loss muscular weakness and
hypoglycemia, low blood pressure and dehydration

24. CUSHING SYNDROME

25. CUSHING SYNDROME
Definition
•Cushing’s syndrome: constellation of symptoms
associated with cortisol excess.
•Cushing's syndrome develops when the level of a
glucocorticoid in the body is too high over a long
period of time.
•Too much glucocorticoid can occur from an
exogenous or endogenous source
•described by Harvey Cushing in 1932

26. Etiology

27. Differential Diagnosis
• Pseudo-Cushingoid:
• Chronic severe anxiety and/or
depression
• Prolonged excess alcohol
consumption
• Obesity
• Poorly controlled diabetes
• HIV infection
• Malnutrition
• Anorexia nervosa

28. Clinical presentations
Findings are more obvious in infants
• ⚫Children with adrenal tumors
Signs of abnormal masculinization
• ⚫Growth impairment
Short stature
• Decreased collagen cause purplish striae on soft tissues of
the body
• They are prone to infections due to compromised immune
system
• Decreased linear growth

31. Diagnosis of Cushing’s Syndrome
• Obtain a careful history to exclude exogenous glucocorticoid
use.
• Perform at least two first-line biochemical tests to
obtain the diagnosis:
• Urine free cortisol (UFC) (at least two measurements)
• Late-night salivary cortisol (two measurements)
• In +ve tests Morning and midnight plasma cortisol levels are
elevated
• Serum ACTH level
• Bloods tests
- FBC
- U/E – low K

32. Diagnosis
•Cortisol levels in blood are normally elevated at 8
A.M. and decrease to less than 50% by midnight
•In patients with Cushing syndrome this circadian
rhythm is lost, and cortisol levels at midnight and 8
A.M. are usually comparable.
• Urinary excretion of free cortisol is increased. This
is best measured in a 24-hr urine sample and is
expressed as a ratio of micrograms of cortisol
excreted per gram of creatinine

33. Dexamethasone suppression test
• Given low dose of dexamethasone (which is
exogenous steroid that suppress ACTH
production of th epitituary gland)
• Normally should cause decrease in cortisol
level
• If cushing syndrome cause by endogenous
cortisol production, the the serum cortisol
should remain unchanged.
• If that test is positive the next step is to
determine the exact cause of endogenous
cortisol and acth production

34. ACTH Plasma Level
• Low ACTH can be seen in adrenal adenoma
and carcinoma
• High ACTH level can be seen in cushing
disease and ectopic ACTH production
• If ACTH level high, the next step is to give
high dose of dexamethasone
• Unlike pitituary adenoma, ectopis site of
ACTH won’t response to high dose of
dexamethasone and the serum cortisol will
remain high

35. IMAGING
• An MRI of the pitituary gland in the
case of cushing disease
• CT scan of the adrenal when adrenal
pathology is suspected
• Ct of chest, abdomen and pelvis if
the seems to be an ectopic site of
ACTH production

36. Algorithm for testing

37. •Dx of Cushing syndrome has been established
then,the next step is to find out the cause
↓
Serum ACTH level
•If low or undetectable– ACTH independent
cause [Adrenal cause likely]
•If high– Cushing’s disease or Ectopic ACTH
syndrome
•Two differentiate between these two: High dose DST
is to be done

39. Others tests;
Effects of hypercortisolism include:
• Hyperglycemia
• Hyperlipidemia
• Hypokalemia(excrete K+)
• Metabolic alkalosis(excrete H+)

41. Medical therapy
Purpose
• Correct metabolic abnormalities before attempted
surgical cure
• Palliate surgically non curable disease
• Achieve remission in patients for whom surgery is
unlikely to achieve satisfactory long term results

42. EXOGENOUS MEDICATION
 Drug is gradually decrease
 Avoid sudden withdrawal, can lead to Addisonian crisis
Pitituary adenoma
Surgical excision

43. Surgical tx
Cushing’s disease
◦Trans sphenoidal
microadenomectomy
◦Pituitary radiation
◦Bilateral total adrenalectomy
Adrenal adenoma and
carcinoma
◦Surgical removal
Ectopic ACTH Syndrome
◦Surgical removal of the
ectopic tumor
◦Radiotherapy

44. Adrenal Insufficiency
• Primary Adrenal Insufficiency is also known asAddison’s Disease in
honor of Dr. ThomasAddison
• Dr.Addison is also credited with the discovery of PerniciousAnemia
• Addison's disease is serious chronic disease, caused by partial or
absolute abnormality of hormonal function of the adrenal cortex due
to its two-sided disorder (first it was described by Tomas Addison in
1855).

45. Adrenal Insufficiency
•Arises when cortisol levels are not sufficient
to meet the needs of the body
•May be primary or secondary
•May be congenital or acquired
•It develops at the age of 20-40 years old
•Can be fatal if left untreated

46. Primary adrenal insufficiency
(high ACTH) (Addison’s
disease)
Autoimmune:
Isolated autoimmune adrenalitis
(30- 40%)
Polyglandular syndrome 1 &2 (60-
70%)
Infection:TB, HIV, CMV,
cryptococcosis, histoplasmosis,
coccidioidomycosis
AIDS
Metastases
Bilateral adrenalectomy

47. • Hypothalamic or pituitary disease:
- Chronic glucocorticoid excess (endogenous or exogenous)
- Pituitary tumors (active and inactive adenomas,
carcinoma)
- Mass lesions affecting the hypothalamic-pituitary region:
Craniopharyngioma meningioma, metastases
- Pituitary irradiation
- Autoimmune hypophysitis
- Pituitary apoplexy/hemorrhage
- Pituitary infiltration (TB, actinomycosis, sarcoidosis,
histiocytosis X, Wegener's granulomatosis, metastases
Secondary (low ACTH)

48. Etiology
•Most commonly is of an autoimmune
etiology, resulting from chronic destruction
of the adrenal cortex
•Typical histologic feature is lymphocytic
infiltration
•Antibodies to adrenal cortical antigens are
present early in the disease process
•Patients with autoimmune adrenal disease
are more likely to have polyglandular
autoimmune systems causing deficiency of
other endocrine glands

49. Clinical Presentation
•Symptoms may include weakness, weight loss, nausea,
vomiting, anorexia, and postural
hypotension,Hyperpigmentation,Hypotension,
Orthostatic changes,Weak pulses,Shock
•Loss of axillary/pubic hair (women)
•Increased skin pigmentation can be seen with primary
adrenal insufficiency secondary to melanocyte
stimulating activity associated with ACTH
•Hyponatremia and Hyperkalemia may develop
secondary to a lack of aldosterone

51. LABORATORY DIAGNOSTICS
In the blood analysis: lymphocytosis, eosinophilia,
erythrocyte sedimentation rate is decreased, when the active
tuberculosis is present this rate is increased;
The electrolyte: hyponatremia, hypochloremia,
hyperkaliemia;
Baseline Cortisol and ACTH levels should be obtained in the
early morning
The content of ACTH is increased;
The content of cortisol is decreased;
The concentration of glucose in the blood is decreased;
The glucose tolerance test – flat with marked
hypoglycemic phase in three hours;
The potassium flow with urine is decreased, the natrium
and chlorine flow is increased.

52. Primary adrenal insufficiency:
Laboratory findings
•Hyponatremia
•Hyperkalemia
•Hypoglycemia
•Narrow cardiac
silhouette on CXR
•Low voltage EKG

53. Treatment
•Replacement ( always need glucocorticoids and
usually mineralcorticoid therapy)
•Hydrocortison orally 15 mg at morning and 5 mg
at evening
•Doses change according to lifestyle:
-doubling the routine oral dose in the case
of intercurrent illness with fever
-IV hydrocortisone injection at a daily dose of 100
mg in cases of prolonged vomiting, surgery, or
trauma
•Have to carry emergency injection of
hydrocortisone and card/bracelet indentifying
their condition

54. •Mineralocorticoid replacement in primary AI
(100–150 g fludrocortisone). The adequacy
of treatment can be evaluated by measuring
BP, sitting and standing to detect a postural
drop indicative of hypovolemia, serum Na, k,
and plasma renin should be measured
regularly.
•Adrenal androgen replacement is an option in
patients with lack of energy, and in women
with loss of libido.
- It can be achieved by once-daily
administration of 25–50 mg DHEA. Treatment
is monitored by measurement of DHEAS,
androstenedione, testosterone.

55. Treatment
Special precautions
•During intercurrent illness,trauma,surgery, esp in
fever, the dose of hydrocortisone should be
doubled
•Increase the dose of fludrocortisone and to add
salt in strenuous exercise with sweating, extremely
hot weather, gastrointestinal upsets such as diarrhea
•Pts receiving long term steroid therapy have
two deficits
1.adrenal atrophy secondary to the loss of
endogenous ACTH
2.failure of pituitary ACTH release have low blood
cortisol, ACTH levels, and abnormal ACTH stimulation
test

56. ADDSONIAN CRISIS (ACUTE
PRIMARY ADRENAL INSUFFIENCY)
•Severely low blood pressure (shock)
•Hyperkalemia
•Hyponatremia
•Hypoglycemia
•Hypercalcemia
•Unexplained fever, diarrhea, vomiting
•Coma and death
•Precipitated by infection, surgery or
intercurrent disease

57. Management
• It is a medical emergency
• IV fluid (normal saline 1 L/h with continuous cardiac monitoring
and 10% dextrose)
• Hydrocortisone 100 mg bolus followed by 100–200 mg
hydrocortisone over 24 h infusion or i.v doses until GI symptoms
improve then start oral therapy
• Mineralocorticoid replacement can be initiated once the daily
hydrocortisone dose has been reduced to <50 mg
• Treat precipitating cause

58. Pheochromocytoma
•Is a are neuroendocrine tumor of the medulla of
the adrenal glands (originating in the chromaffin
cells), or extra-adrenal chromaffin tissue that
secretes excessive amounts of Catecholomines
(epinephrine and norepinephrine) --hormones
that regulate heart rate and bloodpressure

59. •May occur as a single tumor or as
more than one growth. It usually
develops in the center (medulla) of
one or both adrenal glands.
•Sometimes this kind of tumor occurs
outside the adrenal gland but 90% are
in the adrenal glands .The
extramedulary sites are;
•Within the sympathetic nervechain
along the spinal cord
•Overlying the distal aorta
•Within the ureter
•Within the urinary bladder

60. Factors associated with
pheochromocytoma include
•A family history of pheochromocytoma
•Tumors in other glands of the body
•Other hormonal disorders
•Genetic diseases including:
• Von Hippel-Lindau disease
• Multiple endocrine neoplasia type 2
• Neurofibromatosis type 1
• Paraganglioma syndromes

61. Pheo: Signs & Symptoms
• The five P’s:
• Pressure (HTN) 90%
• Pain (Headache)
• Perspiration
• Palpitation
• Pallor
80%
71%
64%
42%
• Paroxysms (the sixth P!)
• The Classical Triad:
• Pain (Headache), Perspiration, Palpitations
• Lack of all 3 virtually excluded diagnosis of pheo in a series of > 21,0000 patients

62. Pheo: Signs & Symptoms
• N/V, abdo pain, severe constipation (megacolon)
• Chest-pains
• Anxiety
• Angina/MI with normal coronaries:
• Catecholamine induced:  myocardial oxygen consumption or coronary vasospasm
• CHF
• HTN  hypertrophic cardiomyopathy  diastolic dysfn.
• Catechols induce dilated cardiomyopathy  systolic dysfn.
• Cardiac dysrhythmia & conduction defects
• Postural hypotension,Lypolisis[VLDL synthesis]

63. Cont..
• Hyperglycemia
• Tachycardia
• Anxiety
• Chest pain
• Palpitations
• Refractory hypertension
• Abdominal pain
• Increased appetite
• Weight loss

64. Pheo: ‘Rule of 10’
• 10% extra-adrenal (closer to 15%)
• 10% occur in children
• 10% familial (closer to 20%)
• 10% bilateral or multiple (more if familial)
• 10% recur (more if extra-adrenal)
• 10% malignant
• 10% discovered incidentally

65. Exams and Tests
• 24 hr Urine Sample
• Plasma levels of Catecholamines
• Glucose test
• Adrenal biopsy
• Abdominal CT scan
• MRI of abdomen
• ultrasonography

66. Treatment
Pharmacologic Therapy
• Decrease BP:
•Alpha-adrenergic blocking agents.-eg. Phentolamine (Regitine)
•Smooth muscle relaxants.-eg. Na nitroprusside (Nipride
• Before and During Surgery:
Long-acting alphablocker.-Phenoxybenzamine
Ca Channel Blockers.-Nifedipine
Beta-adrenergic blocking agents.-Propranolol
Cathecholamine synths. inhibitors.-Methyrosine

67. Surgical Management
• Adrenalectomy

68. Prognosis
• •1/3 Patients continue to be hypertensive:
1)Not all tissue removed
2)Recurrence
3)Blood vessels damaged by severe & prolonged hypertension
•The tumors come back in less than 10% of these patients.
• Release of the hormones norepinephrine and epinephrine returns
to normal after surgery.
• Less than 50% of patients who have cancerous tumors that spread
to the bones, liver, or lung are alive after 5 years.

69. Assessments
• Blood sugar
- Hypoglycemia (after surgery)
- Hyperglycemia (before and during surgery)
• Blood pressure
- Hypertension (before and during surgery)
- Hypotension (after surgery)

70. HYPERALDOSTERONISM

71. People with primary Hyperaldosteronism have
a problem within the adrenal gland that causes
it to release too much aldosterone.
Primary Hyperaldosteronism
(Conn’s disease)

72. ⦁ Most cases are caused by a noncancerous
(benign) tumor of the adrenal gland.
⦁ Cases due to bilateral adrenal hyperplasia (The
enlargement of an organ caused by an increase in the
reproduction rate of its cells).

73. Secondary Hyperaldosteronism is when the
excess aldosterone is caused by something
outside the adrenal gland that mimics the
primary condition.

74. ⦁ May result from conditions that induce
hypertension through increased renin production,
ingestion of oral contraceptives, and pregnancy.
⦁ Conditions such as congestive heart failure, liver
failure, kidney disease, and dehydration, or
caused by certain medicines such as diuretics or
fludrocortisone.
⦁ It is likely that many cases of secondary
Hyperaldosteronism are never detected.
*Renin - An enzyme secreted by and stored in the kidney area that
stimulates aldosterone and therefore, raises blood pressure

76. ⦁ Moderate hypertension, or high blood pressure
⦁ Similar symptoms of Primary Hyperaldosteronism
⦁ Most individuals have no other specific symptoms.
However, some may have:
◦ Muscle weakness
◦ Cramping
◦ Headaches
◦ Low potassium level
◦ Tingling
◦ Muscle spasms
◦ Fatigue

77. ⦁ Secondary Hyperaldosteronism is treated by
treating the underlying cause.
⦁ Typically medicines and diet (but not surgery)
are used to treat secondary Hyperaldosteronism.
⦁ Untreated Hyperaldosteronism can lead to
uncontrolled hypertension (can become a risk
factor for stroke or heart disease).

78. ⦁ Elevated aldosterone levels can be measured
in the blood or urine.
◦ A blood test, PRA (Plasma renin activity), is used to
distinguish between primary (low PRA) and
secondary Hyperaldosteronism (high PRA).

79. Virilization
• Virilization is a condition that causes a female to
develop male-pattern hair growth and other
masculine traits.
• Women with virilization often have an
imbalance in the sex hormones estrogen and
testosterone.
• Virilization is caused by an overproduction of
testosterone or use of anabolic steroids,
synthetic substances that act like the male
hormone testosterone.

80. Causes of Virilization
Any underlying medical condition that causes an imbalance in sex
hormone levels can result in virilization. These conditions are
likely to cause adrenal hyperplasia, an overproduction of
hormones in the adrenal cortex. In some cases, the
overproduction of adrenal hormones is caused by an adenoma
(cancerous tumour). This type of tumour is normally located
within the adrenal glands.
Other causes of virilization include:
•Use of male hormone supplements
•Use of steroids to increase muscle mass
•Development of ovarian cysts (normally seen in patients with
polycystic ovary syndrome)

81. Symptoms of Virilization
 Women with this condition often experience male-
pattern baldness. They also tend to have an eruption of
acne on the chest, back, face, hairline, underarms and
groin.
 Other symptoms of virilization include:
•Excessive facial hair (normally located on the cheeks, chin, and upper lip)
Deepening of the voice
Increased sex drive
Smaller than normal breasts
Enlarged clitoris
Irregular menstrual cycles

82. Diagnoses of Virilization
The blood sample will be tested for the presence of
testosterone, estrogen, progesterone, and other hormones.
If the level is very high, a dexamethasone suppression test
can help determine if the problem is coming from the adrenal
glands and whether the problem is an adenoma or adrenal
hyperplasia.
If cancerous adenoma is suspected, an imaging test, such as a
computed tomography (CT) scan will be performed to obtain
a view of the adrenal gland.

83. Treatments of Virilization
Removal of an adrenal gland that contains an adenoma is the
most common treatment for virilization. This is normally done
surgically. However, chemotherapy or radiation treatments will
be chosen if the tumour is in a dangerous area or is difficult to
reach. These therapies help shrink the growth before it’s
removed.
If a tumour is not the cause, an oral contraceptives will help
balance the hormone levels.
oral contraceptive will blocks testosterone production
completely.

84. THANK YOU