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1. .
Adrenal Disorders
PREPARED
BY
MARRAH

2. .
Agenda
•Physiology of adrenal
•Causes of adrenal insufficiency
•Addison Disease
•Adrenal crisis
•Congenital adrenal hyperplasia
•Cushing Syndrome

5. Aldosterone
•Mineralocorticoid
•Regulates concentration of Na+ and K+.
–Kidney conserves Na+.
–Kidney excretes K+.
–Therefore, decreased aldosterone will lead to hyperkalemia and
hypornatremia.
•Responds to changes in composition of plasma.
•Regulated by renin-angiotensin system of kidney

6. Regulation of
adrenal gland
secretion
ACTH
Cortisol
Cortisol

7. Aldosterone is regulated by the renin angiotensin system
while cortisol is regulated by the hypothalamic pituitary
axis.
Random cortisol measurement is not useful, ACTH
stimulating test to stimulate the adrenals must be done to
measure it. If it’s still low after stimulation, then it suggests
adrenal insuffeciency.

8. Pattern of cortisole level during the day

9. Adrenal Dysfunction
Decrease function
•Adrenal insufficiency
•Low cortisol, aldestrone
Eg Addison disease
Increase function
•Cushing syndrome
High Cortisol
•Hyperaldosteronism
High aldestrone
•Pheochromocytoma
High catecholamine
.

10. Causes of Adrenal insufficiency
1.Congenital adrenal hyperplasia
2.Addison disease most common cause and it’s
acquired.
3.Infection (TB, sepsis)
4.Adrenoleukodystrophy very rare.
.

11. Addison disease
1.Autoimmune
2.Isolated or associated with other autoimmune disease
3.Presents with tiredness, weight loss, skin pigmentation
4.Hypotension, hyponatremia, hyperkalemia
5.Aldestrone & cortisol low, high ACTH, high renin
6.Low sodium , high potasium
7.ACTH stimulation test: diagnostic test by giving synthetic ACTH
(IV or IM) and measuring the serum cortisol at 30 and 60
minutes. In normal individuals the baseline cortisol should be
doubled after the test whereas in adrenal insufficiency, the
baseline (which is low) is only increased to 25% after the test.
8.Adrenal antibodies
9.Treatment : cortisol + aldosterone
.

13. Hyperpigmentation
A Color Atlas of Endocrinology p97

14. Addisonian crisis
•Life threatening complication
•Severe vomiting and diarrhoeafollowed by
dehydration
•Low blood pressureand shock
•Hypoglycemia
•Loss of consciousness
•Treatment: IV fluids + IV hydrocortisone

15. Adrenal
insufficiency with
echomosis is
suggestive of
meningeococcal
septicemia.

16. Congenital Adrenal Hyperplasia
•Family of inherited disorders of adrenal
synthesis
•Autosomal Recessive (M=F)
•Each disorder results from a deficiency of one
of the five enzymes necessary for steroid
synthesis
•21-hydroxylase is the commonest form
(90–95% of CAH cases)

17. Steroid biosynthetic enzymes
1)Cholesterol side chain cleavage=
desmolase)
2) 3-Hydoxysteroid dehydrogenase
3) 17 hydroxylase
4) 21-Hydroxylase
5) 11-Hydroxylase

18. Minerlocorticoid Glucocoticiod Sex Steroid
17 OH Pregnenlolone
17 OH Progesterone
11 Desoxycortisol
Cortisol
3 B HSD
21 OH
11 OH
DeHydroEpiAndrosterone
Androstendione
TestosteroneEstradiol
3 B HSD
Pregnenlolone
Progesterone
Desoxycorticosterone
Corticosterone
18 OH Corticosterone
Aldosterone
Cholesterol
Desmolase
3 B HSD
21 OH
11 OH
18 OH
17,20 lyase

19. •Desmolase is the first step in the pathway and if deficient all three
pathways will be stopped. Only female genitalia because no androgens at
all.
•3BHSD deficiency: all 3 enzymes will be absent but will also present
with ambiguous genitalia because of high levels of DHEA
•17aOH: cortisol and androgens are deficient and males will present with
ambiguous genitalia. Aldosterone is present; therefore, they will not
develop adrenal crisis and will have hypertension due to the excess
aldosterone levels.

20. •21aOH: is the commonest cause of CAH, both cortisol and aldosterone
will be missing, the pathway will be shifted to the production of
androgens which will be manifested as ambiguous genitaliain females
and hyper-pigmentation and virilization in males.
•11aOH: both cortisol and aldosteronewill be deficient, but there will be
accumulation of the Desoxycorticosterone which has an aldosterone like
activity, therefore they will present hypertension, hypernatremia and
hypokalemia), but it similar to 21OH in that they both present with
ambiguous genitaliaand low cortisol levels.
•Hypertension is only present in 11 And 17 OH deficiency.

21. Congenital Adrenal Hyperplasia
.

22. Congenital Adrenal Hyperplasia

23. 21-OH CAH: Clinical phenotypes
1.“Classic, severe”salt-wasting (SW) form: it is
the life-threatening form.
2.“Classic, less severe”simple-virilizing (SV)
3.“Mild, non-classic”forms

24. Pregnenlolone
Progesterone
Desoxycorticosterone
Corticosterone
18 OH Corticosterone
Aldosterone
17 OH Pregnenlolone
17 OH Progesterone
11 Desoxycortisol
Cortisol
DeHydroEpiAndrosterone
Androstendione
TestosteroneEstradiol
Cholesterol
Desmolase
3 B HSD
21 OH
11 OH
18 OH
Desmolase
3 B HSD
3 B HSD
21 OH
11 OH
Treatment
Hydrocortisone
Fludrocortisone
For life
21-OHCAH:
90 % of CAH
50-70 % salt wasting
Female =
ambiguous, Hyperpig
Male =
Virlization and
hyperpigmentation

25. Salt wasting form
•Salt wasting form
–Adrenal crisis in the 1
st
-4
th
weeks of life, peaking at 3
rd
–Poor feeding, vomiting, diarrhea, FTT
•Dehydration
•Shock
•Electrolytes imbalance
–Hyponatremia
–Hyperkalaemia
•Hypoglycemia
•Hyperpigementations
–If untreated circulatory collapse shock death
–Permanent brain injury due to shock and hypoglycemia lower
IQ

26. Simple virilizing form 21-OH CAH
•Simple virilizing form
–No adrenal-insufficiency symptoms unless subjected to severe
stress but exhibit virilization
–Girls present with ambiguous genitaliaat birth
–Males usually not diagnosed until later (virilization, precocious,
growth acceleration)
–Advanced skeletal age diagnosed late short adult stature

27. Prader Classification of Virilization

28. •Type 1: increase in the size of the clitoris.
•Type 2: more increase in the size of the clitoris.
•Type 3: one opening, the vagina and clitoris opens in the same
opening.
•Type 4: one opening and more increase in the size, starts
looking as a penis.
•Type 5: looks like male genitalia with no testis.
Newborn Screening

29. .
Prader 1

30. .Prader 2

31. Prader 3
•.

32. Prader4

33. Prader5

34. Nonclassical CAH
Residual enzyme activity.
Non-salt losing CAH
Presents late in childhood with precocious
pubic hair and/or clitoromegaly and
accelerated growth.
Present in adolescence or adulthood with
varying virilizing symptoms ranging from
oligomenorrhea to hirusutism and
infertility.

35. Non classic
CAH
.

36. Diagnosis of CAH
Serum electrolytes & glucose
Low Na & high K
Fasting hypoglycemia
Elevated serum urea due to associated dehydration
Elevated plasma Renin & ACTH levels
Low Cortisol
High 17 –OHP
High androgens especially testosterone level
Low Aldosterone
Urinary steroid profile
Chromosomal study and US of external genitalia if
they present with ambiguous genitalia.
Pelvic US

37. Management
•Hydrocortisone
•Fludrocortisone 0.05 -0.2 mg/day
•Triple dose of hydrocortisone and mineralcorticoids
during stress or very sick.
•During adrenal crisis intravenous hydrocortisone and
IV fluid
•Surgery for female external genitalia can be done in
the 1st year of life.
•Antenatal diagnosis and treatment

38. Newborn screening for CAH
•Neonatal screening by filter paper on 3
rd
day of life
•17 Hydroxyprogestrone blood level (17 OHP)
.

39. Pregnenlolone
Progesterone
Desoxycorticosterone
Corticosterone
18 OH Corticosterone
Aldosterone
17 OH Pregnenlolone
17 OH Progesterone
11 Desoxycortisol
Cortisol
DeHydroEpiAndrosterone
Androstendione
TestosteroneEstradiol
Cholesterol
Desmolase
3 B HSD
21 OH
11 OH
18 OH
Desmolase
3 B HSD 3 B HSD
21 OH
11 OH
11 Hydroxylase Deficiency:
5 % of CAH
HTN
Female =
ambiguous, Hyperpig
Male =
virlization

40. Pregnenlolone
Progesterone
Desoxycorticosterone
Corticosterone
18 OH Corticosterone
Aldosterone
17 OH Pregnenlolone
17 OH Progesterone
11 Desoxycortisol
Cortisol
DeHydroEpiAndrosterone
Androstendione
TestosteroneEstradiol
Cholesterol
Desmolase
3 B HSD
21 OH
11 OH
18 OH
Desmolase
3 B HSD 3 B HSD
21 OH
11 OH
17 Hydroxylase Deficiency: (adrenal crisis doesn’t occur)
HTN
Hypokalemic alkalosis
Female =
Normal
Male =
Ambiguous

41. Pregnenlolone
Progesterone
Desoxycorticosterone
Corticosterone
18 OH Corticosterone
Aldosterone
17 OH Pregnenlolone
17 OH Progesterone
11 Desoxycortisol
Cortisol
DeHydroEpiAndrosterone
Androstendione
TestosteroneEstradiol
Cholesterol
Desmolase
3 B HSD
21 OH
11 OH
18 OH
Desmolase
3 B HSD 3 B HSD
21 OH
11 OH
Survival is rare due to more proximal enzyme bloke
3 BHydroxy steroid DH Deficiency:. Weak Androgen; therefore, ambiguous
genitalia in females only.

42. Congenital Lipoid Adrenal Hypoplasia
•Inability to convert cholesterol to pregnenolone
thus all 3 classes of steroids are absent (1
st
step
is inhibited due to the absence of desmolase)
•Clinical Manifestations:
–Salt-losing crisis
–XX and XY have female genitalia
–Massive cholesterol accumulation in adrenal cortex
–Absent puberty in males
–Females may have puberty

43. Harvey Williams Cushing (1869-1939)

44. Definitions
•Cushing’s Syndrome
–Excess cortisol in the blood
•Cushing’s Disease most common
–Excess cortisol in the blood due to an ACTH secreting pituitary
tumour, due to pituitary adenoma.

45. ACTH
ADRENAL
CORTEX
PITUITARY
HYPOTHALAMUS
CRH
CORTISOL

46. Cushing’s syndrome
•Cushing’s Syndrome
–Results from increased adrenocortical secretion of
cortisol
–Causes include:
•ACTH-secreting tumor of the pituitary
(Cushing’s disease)
•excess secretion of cortisol by a neoplasm
within the adrenal cortex
•ectopic secretion of ACTH by a malignant
growth outside the adrenal gland
•excessive or prolonged administration of
steroids

48. •Cushing’s Syndrome
–Characterized by:
•truncal obesity
•moon face
•buffalo hump
•acne, hirsutism
•abdominal striae
•hypertension
•psychiatric disturbances
•osteoporosis
•Amenorrhea
•Diabetes
Cushing’s syndrome

49. www.saadmedical.com

52. Establishing the Cause
•Serum ACTH, cortisol and urine free cortisol
(urine free cortisol is so sensitive, if high you do
the suppression test)
•Dexamethasone Suppression testing
•Localisation of the ACTH source
–Imaging (MRI) for pit pathologies
–CT scan for adrenal pathologies.

53. Treatment of Cushing’s syndrome
•Treatment of underline cause
•Surgery for neoplasia
.

54. Data interpretation
A 2 week old infant presents to hospital with 1 week history of
persistent vomiting and lethargy. On examination the infant is
10% dehydrated and unwell. He has normal male genitalia and
both gonads are palpable blood results are:
Sodium 115 mmol/L
Glucose 3.8 mmol/L; hypoglycemic <2.7mmol/L
Potassium 7.2 mmol?L
What two investigations would be most likely to confirm the
diagnosis?
How do you treat?

55. •This case could be CAH or hyponatremic dehydration, so
now we added the presence of hyperpigmentation to the
scenario to confirm CAH.
•The most important 2 investigations are: A. 17
hydroxyprogesterone as a screening test, it will be high
(blockage of 21OH will lead to its accumulation of substrate
before. B. ACTH stimulation test to confirm the diagnosis.
•DNA study (CYP21) for 21 OH deficiency is done at the
end.
•Treatment: I.V fluid and I.V hydrocortisone for the
treatment of the crisis, and replacement of cortisol and
aldosteronefor life.
•Not addisons because it doesn’t present in the first few
months of life.
Newborn Screening