2. Acquired
 Autoimmune
 AIDS
 Tuberculosis
 Bilateral injury
◦ Hemorrhage
◦ Necrosis
◦ Metastasis
 Idiopathic
 Iatrogenic
Congenital
 Congenital adrenal
hypoplasia
Syndromes
 Autoimmune
polyglandular
syndrome
1. APS1
2. APS2

3. Decrease function Increase function
 Adrenal insufficiency
 CAH
 Low cortisol, aldestrone
Addison disease
 Cushing syndrome
High Cortisol
 Hyperaldosteronism High
aldestrone
 CAH
 Pheochromocytoma
High catecholamine
.

4.  Glucocorticoids are essential for life and have mutiple
pysiological effects.
 Metabolic actions include enhanced gluconeogenesis
and inhibition of peripheral glucose utilization.
 Glucocorticoids are required for vascular and bronchial
smooth muscle to be responsive to catecholamines.
 Glucocorticoids are structurly related to aldosterone, so
they have aldosterone like action.

5.  ACTH is the principal regulator of Glucocorticoids
secretion.
 Secretion of ACTH and glucocorticoids exhibit a
diurnal rhythm, stimulated by stress and inhibited
by circulating glucocorticoids.
 Endogenous production of cortisol averages 20
mg day.

7. Mineralocorticoid excess
 I- Primary hyperaldosteronism (Conn
syndrome):
 Conn syndrome is characterized by increased
aldosterone secretion from the adrenal glands, it
was first described in 1955 by J. W. Conn in a
patient who had an aldosterone-producing
adenoma.

8.  Pathophysiology
 Primary hyperaldosteronism is caused by increased
aldosterone excretion from the adrenals, which results
primarily from 2 major subtypes:
 (1) unilateral aldosterone-producing adenoma , Conn
syndrome, (50-60% of cases)
(2) idiopathic hyperaldosteronism (IHA) or bilateral adrenal
hyperplasia (40-50% of cases).
(3) Rarely, aldosterone can be secreted by adrenocortical
carcinomas and ovarian tumors.

9.  Aldosterone, by inducing renal distal tubular
reabsorption of sodium, enhances secretion of
potassium and hydrogen ions, causing
hypernatremia, hypokalemia.

10. Conn syndrome, is primarily related to;
 1- Hypertension, especially if left untreated for
many years, can lead to many complications,
including heart disease (eg, coronary artery
disease, congestive heart failure), stroke, and
intracerebral hemorrhage (with very high blood
pressure).
 2-Hypokalemia, especially if severe, causes
cardiac arrhythmias, which can be fatal.

11.  II- Secondary hyperaldosteronism:
 There is increased renin-angiotensin with
increased aldosteron secretion;
 Causes:
 -CHF
 -Liver cirrhosis and ascitis
 -Nephrotic syndrome
 -Renal artery stenosis

12. Clinical manifestations
 -Hypertension;
 -Hypokalemia;
 patients with severe hypokalemia report fatigue, muscle
weakness, cramping, headaches, and palpitations. They
can also have polydypsia and polyuria from hypokalemia
induced nephrogenic diabetes insipidus.
 -Metabolic alkalosis;
will lower ionized calcium levels and can cause tetany.


13.  Investigations:
 Laboratory Studies
 Hypernatremia
 Hypokalemia; normokalemia does not exclude
primary hyperaldosteronism. Several studies
have shown that 7-38% of patients with
primary hyperaldosteronism have normal
baseline serum levels of potassium

14.  metabolic alkalosis
 Renin levels are suppressed to less than 1
ng/mL/h in patients with primary
hyperaldosteronism.
 A 24-hour aldosterone excretion rate of greater
than 14 ug is diagnostic of primary
hyperaldosteronism

15.  Imaging Studies
 -CT scanning
 -MRI

16.  Treatment
 Medical
 medical therapy is used preoperatively to prevent
the morbidity and mortality associated with
hypertension and hypokalemia, thus decreasing
surgical risk.
 Sodium-restricted diet (<80 mEq or <2 g of
sodium per day.
 Potassium-sparing agent (first-step agent) such as
spironolactone100 mg initially, increase to 400
mg/d for control of blood pressure.

17.  Potassium supplementation should not be
routinely administered with spironolactone
because of the potential for the development of
hyperkalemia.
 Second-step agents include thiazides diuretics,
ACE inhibitors, calcium channel antagonists, and
angiotensin II blockers.

18. 
Mineralocorticoid deficiency
 Hypo-aldosteronism
 Atrophy or destruction of both adrenal glands
results in a combined deficiency of
Mineralocorticoid and glucocorticoid ( addison
disease) .
 Isolated Mineralocorticoid deficiency;
 Unilateral adrenalectomy
 Congenital

19.  CP
 *Hypotension; due to hypovolemia
 *Metabolic acidosis
 *Hyperkalemia; any increase in Sr. potassium
without renal impairment, hypoaldosteronism
should be considered.
 *hyponatremia

20.  Glucocorticoid excess
 Cushing syndrome
 Cushing syndrome is caused by prolonged
exposure to elevated levels of either
endogenous glucocorticoids or exogenous
glucocorticoids

21.  Causes:
 Exogenous steroid administration
Symptoms of glucocorticoid excess generally
occur with the administration of oral steroids;
however, occasionally injections of steroids into
joints and the use of steroid inhalers can cause
Cushing syndrome.


22.  Patients at risk to develop cushing syndrome
includes:
 rheumatological, pulmonary, neurological, and
nephrologic diseases that respond to steroid
therapy.
 Patients who have undergone organ transplants
due to exogenous steroids required as part of
graft antirejection medication regimens.

23.  Endogenous glucocorticoid administration
 ACTH-producing pituitary adenoma ( Cushing
disease).
 Primary adrenal lesions; Overproduction of
glucocorticoids may be due to an adrenal
adenoma, adrenal carcinoma, or macronodular or
micronodular adrenal hyperplasia.
 Ectopic ACTH is sometimes secreted by oat cell or
small-cell lung tumors or by carcinoid tumors.

24.  Amino acid catabolism (muscle wasting)… gluconeogenesis in
the liver.. Hyperglycemia… increased insulin output… eventual
beta cell failure… fat deposition… diabetes
 Ca resorption, impairment of Ca absorbtion, increased renal
Ca excretion…. osteoporosis
 Increased gastric acidity… ulcer formation or aggravation
 K loss and Na retention… edema and hypertension
 Initially increased antibody release.. Eventually decreased
antibody production, lymphocytopenia, eosinopenia,
neutrophelia, polycythemia… susceptibility to infections
 Maintenance of arteriolar tone and blood pressure

25. Obesity
-moon facies
-buffalo hump
-Central obesity, increased waist-to-hip ratio
greater than 1 in men and 0.8 in women

27. Skin
Facial plethora
abdominal striae
facial hair
Hirsutism and Steroid acne

29. Cardiovascular and renal
Hypertension and possibly edema may be present
due to cortisol activation of the mineralocorticoid
receptor leading to sodium and water retention
Gastroenterologic
Peptic ulceration may occur with or without
symptoms.

30. endocrine
Galactorrhea and menstrual disturbances
decreased libido and impotence in men.
Skeletal/muscular
Proximal muscle weakness
Osteoporosis and osteopenia
Avascular necrosis of the hip

31. Neuropsychological
emotional liability, fatigue, and depression

32.  Investigations
 Laboratory Studies
 Hyperglycemia
 Hypokalemic metabolic alkalosis
Biochemical evaluation of Cushing syndrome:
 1-Urinary free cortisol excretion over 150 ug day.

33.  2- dexamethasone suppression test;
glucocorticoids inhibit secretion of hypothalamic
CRH and pituitary ACTH but do not directly affect
adrenal cortisol production.
The overnight 1-mg dexamethasone suppression
test requires administration of 1 mg of
dexamethasone at 11 PM with subsequent
measurement of cortisol level at 8 am.
In healthy individuals, the serum cortisol level
should be less than 2-3 ug/dL.

34.  3-loss of circadian rhythm of cortisol secretion
 Normal values, 10-25 ugml in the morning, 2-10
ugml in the evening, elevated serum cortisol at
11 PM can be an early finding.
 Recently, measuring salivary cortisol level has
gained interest, as it is a simple and convenient
way of obtaining a night time sample. Levels less
than 1.3-1.5 ng/mL exclude Cushing syndrome.


35.  4- A plasma ACTH of less than 5 pg/mL is
suggestive of a primary adrenal tumor. An ACTH
level greater than 10-20 pg/mL is consistent with
ACTH-dependent Cushing syndrome.
 Imaging studies
CT or MRI brain and abdomen

36.  Pathophysiology
Addison disease is adrenocortical insufficiency
due to the destruction or dysfunction of the entire
adrenal cortex. It affects glucocorticoid and
mineralocorticoid function. The onset of disease
usually occurs when 90% or more of both adrenal
cortices are dysfunctional or destroyed.

37.  Causes
 1- idiopathic
 2- Chronic granulomatous diseases; TB,
histoplasmosis.
 3- Hematologic malignancies; Hodgkin
and non-Hodgkin lymphoma and leukemia.

38. 4- Metastatic malignant disease; as metastatic
cancer of the lung, breast, colon or renal cell
carcinoma.
 5-Infiltrative metabolic disorders; Amyloidosis and
hemochromatosis.
 6- AIDS.

39.  Secondary adrenal insufficiency is a result of
inadequate ACTH secretion by the pituitary, the
most common cause of secondary adrenal
insufficiency is iatrogenic, the result of the
administration of exogenous glucocorticoids.

40.  CP
 Patients usually present with features of both
glucocorticoid and mineralocorticoid deficiency.
The predominant symptoms vary depending on
the duration of disease.
 -Hyperpigmentation of the skin and mucous
membranes due to high ACTH.
 - vitiligo, which most often is seen in idiopathic
autoimmune Addison disease.

41.  -clinical manifestations due to cortisol deficiency;
weakness, fatigue, hypoglycemia, hypotension,
and weight loss.
 -Prominent gastrointestinal symptoms may include
nausea, vomiting, and occasional diarrhea.
 - Patients with secondary insufficiency have a
history of taking cortisol.
 clinical manifestations due to aldosterone
deficiency; hyponatremia, hypovolemia,
hypotension, hyperkalemia.

49.  Investigations
 Laboratory Studies
 -ACTH stimulation test; In patients with Addison
disease, both cortisol and aldosterone show
minimal or no change in response to ACTH.
 Hyponatremia
 Hyperkalemia

50.  elevated (BUN) and creatinine due to the
hypovolemia with decreased glomerular filtration
rate.
 Hypoglycemia
 adrenal autoantibodies may be present

51.  Imaging study
 Chest x-ray TB
 CT abdomen

52. .

53.  Congenital adrenal hyperplasia (CAH) is a general
term used to describe a group of inherited
disorders in which a defect in cortisol biosynthesis
is present with consequent overproduction of
(ACTH) and secondary adrenal hyperplasia as a
consequence.

55.  Patients with 11-beta-hydroxylase deficiency
present with features of androgen excess,
including masculinization of female newborns and
precocious puberty in male children.
 Approximately two thirds of patients also have
hypertension, which may or may not be
associated with mineralocorticoid excess,
hypokalemia, hypernatremia and metabolic
alkalosis.

56.  The hypertension is initially responsive to
glucocorticoid replacement, but it may become a
chronic condition subsequently requiring standard
antihypertensive therapy.

57.  Ambiguous genitalia in girls
 Hyperpigmentation
 Dehydration
 Salt-loss presentations with electrolytes
imbalance
◦ Hyponatremia
◦ Hyperkalaemia
 Hypoglycemia
 Shock

58. Are unrecognized at birth because their genitalia are normal.
 Present early with salt wasting
crisis resulting in dehydration, hypotension,
hyponatremia and hyperkalemia
Or present later in childhood with early pubic hair,
precocious puberty and accelerated growth

59. Neural Crest
Sympathoadrenal Progenitor Cell
(Neuroblasts)
Chromaffin Cell Sympathetic Ganglion Cell
Intra-adrenal Extra-adrenal
Pheochromocytoma
Ganglioneuroma
Neuroblastoma

60.  Pheochromocytoma
 Paraganglioma (extra-adrenal pheo)
 Originate in extra-adrenal sympathetic chain/chromaffin
tissue
 Ganglioneuroma
 Behave like paraganglioma biochemically

61.  Neuroblastoma
 Common malignancy in children, adrenal or sympathetic
chain.
 Rapid growth & widespread metastasis
 Some differentiate and spontaneously regress
 Rx complex (surgery, RT, chemotherapy)
 Cheodectoma
 Carotid body, behave like paraganglioma biochemically
 Glomus jugulare tumor
 Intracranial branch of CN IX and X
 Behave like paragangliomoa biochemically

62.  Neuroendocrine tumour of the medulla of the
adrenal glands
 Originates from the chromaffin cells along the
paravertebral sympathetic chain extending from
pelvis to base of skull
 >95% are abdominal
 >90% in adrenal medulla
 Secretes excessive amounts of adrenaline and
noradrenaline
 80% occur unilateral

63.  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

64. Tyrosine L-Dopa Dopamine
Norepinephrine
Epinephrine
Catecholamines
Normetanephrine
Metaneprine
PNMT
DBH
COMT
COMT
Metabolites
Homovanillic acid
(HVA)
MAO, COMT
Vanillymandelic Acid
(VMA)
MAO
MAO
TH

65.  Alpha-Adrenergic Receptors
 α1: vasoconstriction, intestinal relaxation, uterine
contraction, pupillary dilation
 α2: ↓ presynaptic NE (clonidine), platelet aggregation,
vasoconstriction, ↓ insulin secretion
 Beta-Adrenergic Receptors
 β1: ↑ HR/contractility, ↑ lipolysis, ↑ renin secretion
 β2: vasodilation, bronchodilation, ↑ glycogenolysis
 β3: ↑ lipolysis, ↑ brown fat thermogenesis

66.  0.01-0.1% of HTN population
 Found in 10% of those screened
 M = F
 3rd
to 10th
decades of life
 Rare, investigate only if clinically suspicion:
 Signs or Symptoms
 Severe HTN, HTN crisis
 Refractory HTN (> 4drugs)
 Adrenal lesion found on imaging (ex. Incidentaloma)

67.  The five P’s:
 Pressure (HTN)9%
 Pain (Headache) 80%
 Perspiration 71%
 Palpitation 64%
 Pallor 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

68. Diagnosis
1. Biochemical
2. Localization

69. Positive results (> 2-3 fold elevation):
 24h Ucatechols > 2-fold elevation
 ULN for total catechols 591-890 nmol/d
 24h Utotal metanephrines > 1.2 ug/d (6.5 umol/d)
 24h UVMA > 3-fold elevation
 ULN 35 umol/d for most assays
 Detected by high performance liquid chromatography

70.  Test Characteristics:
 24h urinary catechol Sen 83% Spec 88%
 24h U total metanephrines Sen 76% Spec 94%
 24h Ucatechols + Utotal metanephrines Sen 90% Spec 98%
 24h UVMA Sen 63% Spec 94%
 Sensitivity increased if 24h urine collection begun at
onset of a paroxysm
 Serum creatinine measured for all collections of urine
to determine adequacy of collection

71.  Plasma free metanephrines sen 99%
spec 89%
 Plasma catecholamines sen 84%
spec 81%