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ADRENAL FUNCTION TESTS
Adrenal glands
 Two small organs located above the
kidneys.
 Have two functionally distinct parts
◦ Outer cortex(with three zones)
◦ Inner medulla – Catecholamines
HORMONES
Adrenal cortex zone Adrenocorticosteroid
hormone
Zona Glomerulosa Mineralocorticoids
Zona Fasciculata Glucocorticoids
Zona reticularis Androgens
 Cyclopentanoperhydrophenanthrene
nucleus as their basic structure
 All steroid hormones are derived from
cholesterol(major source -
circulation)
 Most reactions catalyzed by enzymes
of Cyt P450 family.
 Liver is the major site for steroid
catabolism
Glucocorticoids
 21C steroids
 Secreted in response to ACTH (secreted by
pituitory), which is in turn controlled by CRH.
 Cortisol (also known as hydrocortisone) is
the predominant glucocorticoid
 Mainly involved in the regulation of
carbohydrate, lipid and protein metabolism.
 Powerful anti-inflammatory hormone.
 Cortisol exerts negative feedback on CRH
and
ACTH secretion
 Diurnal variation – highest in early morning,
lowest near midnight.
Mineralocorticoids
 21 C steroid
 Aldosterone is the most potent
naturally occurring mineralocorticoid.
 Have effects on water and electrolyte
balance.(sodium conservation,
potassium and H ion excretion )
 Regulated by renin –angiotensin
system
Sex steroid hormones
 Secreted by zona reticularis.
 Dehydroepiandrosterone,
dehydroepiandrosterone
sulfate(DHEA-S), Androstenedione-
Peripheral conversion to
testosterone.
 Estrogen production negligible in
adrenal cortex.
 Regulation not well understood yet
ADRENAL HYPERFUNCTION ADRENAL
HYPOFUNCTION
Cushing’s syndrome: Primary defect
in adrenal gland (Adrenal adenoma,
adrenal carcinoma etc)
Addison’s disease(primary
adrenal insufficiency)
Cushing’s disease/
Hyperpituitarism:Excess ACTH from
pituitary –pituitary adenoma
Secondary adrenal
insufficiency:hypothalamic/
pituitary disorder -
impaired secretion of
CRH/ACTH
Androgen-secreting tumors of
Ovaries, Testes, Ectopic ACTH by
other tumors
Administration of ACTH
Primary hyperaldosteronism/Conn’s
syndrome
Adrenal function tests
 Help in diagnosis and monitoring of
adrenal hypo/hyperfunction disorders.
 DHEA may be measured to determine
cause of hirsuitism, amenorrhoea,
infertility or precocious puberty in
females.
Adrenal function tests
 Plasma Cortisol level
 Plasma ACTH level
 ACTH stimulation test/ CoSyntropin
test
 Corticotropin-releasing hormone(CRH)
stimulation test
 Dexamethasone Suppression Test
 17-Hydrocortisol level
 Urinary free Cortisol
 Estimation of aldosterone in blood
Adrenal function tests
contd…
 Urinary excretion of steroids
 Serum electrolytes
 Estimation of plasma renin activity
 Insulin induced hypoglycemic
stimulation test.
 17 alpha- Hydroxyprogesterone levels
 DHEA estimation
Plasma Cortisol level
 Diurnal rhythm
◦ Secretion maximum in morning
◦ Minimum at midnight
 Normal range
◦ 5-25 microgm/dl in morning(8 am)
◦ 2-5 microgm/dl in night(10 pm)
 Determined by immunoassay
(ELISA/CLIA/RIA)
 Loss of diurnal rhythm may be an early
indication of lesion at any point in
hypothalamic –pituitary- adrenal axis
Plasma ACTH
ACTH CORTISOL PROBABLE
DISORDER
Low High Primary
hyperadrenalism
Low Low Secondary
adrenal
insufficiency
High Low Primary
adrenocortical
insufficiency
High High Pituitory
adenoma
(Cushings
Synacthen test/ACTH stimulation
tests
 Used to assess adrenal reserve
capacity
 Used to demonstrate the failure of
adrenal gland to produce cortisol in
response to ACTH
 Stimulation of adrenal cortex by
synthetic
ACTH(eg:synacthen/cosyntropin)inject
 Normal response shows a rise in
serum cortisol > 18microg/dl within
60mts of i.v administration of
synacthen
 A person with primary adrenal failure
doesnot respond.( rise <18microg/dl)
 Confirms the diagnosis of Addison’s
disease
CRH Stimulation tests
 Definitive to differentiate pituitary
causes from other causes
 Rise in ACTH secretion and cortisol
levels following injection
 If there is no ACTH response after
CRH stimulation tests, the disease is
of pituitary origin
Dexamethasone Suppression Tests
 Used in diagnosis of Cushing’s syndrome.
Low dose Dexamethasone Suppression Tests
 Dexamethasone is a potent suppressor of
pituitary ACTH secretion and thereby cortisol
level,causing 50% fall in serum cortisol with a
dose as low as 1mg
 Patient takes dexamethasone tab at night and
plasma cortisol is determined at 8 am the
following morning
 Morning cortisol <5microgm/dl rules out
adrenal tumors.
High dose dexamethasone
suppression test
 Done to confirm Cushings disease
 Administer 2mg dexamethasone every
6 hrs for 2 days & cortisol measured
next day morning.
 This dose suppresses plasma cortisol
in Cushings disease.(drop atleast
50%)
 If plasma cortisol level is not
suppressed, adrenal tumors producing
high levels of cortisol or ectopic ACTH
producing tumors are usually the
Urinary excretion of steroids
 Urinary steroids are 17 ketosteroids
and 17 hydroxy steroids
 17 ketosteroids are derived from both
adrenal steroids and androgen from
gonads, major contribution by cortisol
and cortisone
 17 hydroxy steroids are derived mainly
from adrenal steroids
 Diagnostic value to assess functional
status of adrenal cortex, particularly in
females
Estimation of aldesterone in
blood
 Increased levels are seen in primary
hyperaldosteronism /Conn’s syndrome
and bilateral adrenal hyperplasia
 Decreased aldosterone levels are
seen in Addison’s disease
Estimation of plasma renin
activity
 Helps to differentiate between primary
and secondary hyperaldosteronism
 Enzyme activity is high in secondary,
low in primary hyperaldosteronism
Urinary free Cortisol
 In plasma 70% cortisol is bound to
cortisol binding globulin/transcortin
 20% cortisol is bound to albumin
 Rest is free,which is the biologically
active form
 A definite fraction of unbound/free
cortisol is exreted in urine unchanged
 24 hr urine sample is collected
 Estimation of urinary free cortisol is a
sensitive index of adrenal activity:
Hyper/Hypofunction.
Lab findings in Adrenal
hyperfunction
Cause Plasma
cortisol
Urinary
cortisol
Plasma
ACTH
Dexamethasone
suppression
Adrenal
adenoma
Increased Increased decreased No suppression
Adrenal
carcinoma
Increased Increased decreased No suppression
Pituitory
adenoma
Increased Increased Increased Suppression with
high dose
Ectopic ACTH Increased Increased Increased No suppression
Lab findings in Adrenal
hypofunction
Cause for
adrenal
insufficienc
y
Plasma
cortisol
Urinary
cortisol
Plasma
ACTH
ACTH
stimulation
CRH
stimulation
Primary low low High No effect No effect
Secondary low low Low Normal/
exaggerate
d
No effect
Lab findings in Conn’s
syndrome
 Plasma Aldosterone levels are high
 Plasma renin activity is decreased due
to feedback
 Serum electrolytes-hypernatemia,
hypokalemia
 pH is elevated(hypokalemic alkalosis)
 Osmolality is elevated
Sex hormones & investigations
in Infertility
Commonly measured hormones for
evaluation of infertility are:
 FSH
 LH
 Testosterone
 Prolactin
 Estradiol
 Anti-Mullerian Hormone
 TSH
 Progesterone
 Inhibin-B
Assignment Questions( 5*4 =
20 marks)
1. List the adrenal function test with
significance of each.
2. List the lab findings in adrenal
hyperfunction.
3. List the lab findings in adrenal
hypofunction.
4. In tabular form, give the pattern of
hormone levels in various endocrine
abnormalities in males and females.
Thank you

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Adrenal Function Tests-3.pptxwhfbdqbfwwfjgwngnegenhndngssfb

  • 1. ADRENAL FUNCTION TESTS Adrenal glands  Two small organs located above the kidneys.  Have two functionally distinct parts ◦ Outer cortex(with three zones) ◦ Inner medulla – Catecholamines
  • 2. HORMONES Adrenal cortex zone Adrenocorticosteroid hormone Zona Glomerulosa Mineralocorticoids Zona Fasciculata Glucocorticoids Zona reticularis Androgens
  • 3.  Cyclopentanoperhydrophenanthrene nucleus as their basic structure  All steroid hormones are derived from cholesterol(major source - circulation)  Most reactions catalyzed by enzymes of Cyt P450 family.  Liver is the major site for steroid catabolism
  • 4. Glucocorticoids  21C steroids  Secreted in response to ACTH (secreted by pituitory), which is in turn controlled by CRH.  Cortisol (also known as hydrocortisone) is the predominant glucocorticoid  Mainly involved in the regulation of carbohydrate, lipid and protein metabolism.  Powerful anti-inflammatory hormone.  Cortisol exerts negative feedback on CRH and ACTH secretion  Diurnal variation – highest in early morning, lowest near midnight.
  • 5. Mineralocorticoids  21 C steroid  Aldosterone is the most potent naturally occurring mineralocorticoid.  Have effects on water and electrolyte balance.(sodium conservation, potassium and H ion excretion )  Regulated by renin –angiotensin system
  • 6. Sex steroid hormones  Secreted by zona reticularis.  Dehydroepiandrosterone, dehydroepiandrosterone sulfate(DHEA-S), Androstenedione- Peripheral conversion to testosterone.  Estrogen production negligible in adrenal cortex.  Regulation not well understood yet
  • 7. ADRENAL HYPERFUNCTION ADRENAL HYPOFUNCTION Cushing’s syndrome: Primary defect in adrenal gland (Adrenal adenoma, adrenal carcinoma etc) Addison’s disease(primary adrenal insufficiency) Cushing’s disease/ Hyperpituitarism:Excess ACTH from pituitary –pituitary adenoma Secondary adrenal insufficiency:hypothalamic/ pituitary disorder - impaired secretion of CRH/ACTH Androgen-secreting tumors of Ovaries, Testes, Ectopic ACTH by other tumors Administration of ACTH Primary hyperaldosteronism/Conn’s syndrome
  • 8. Adrenal function tests  Help in diagnosis and monitoring of adrenal hypo/hyperfunction disorders.  DHEA may be measured to determine cause of hirsuitism, amenorrhoea, infertility or precocious puberty in females.
  • 9. Adrenal function tests  Plasma Cortisol level  Plasma ACTH level  ACTH stimulation test/ CoSyntropin test  Corticotropin-releasing hormone(CRH) stimulation test  Dexamethasone Suppression Test  17-Hydrocortisol level  Urinary free Cortisol  Estimation of aldosterone in blood
  • 10. Adrenal function tests contd…  Urinary excretion of steroids  Serum electrolytes  Estimation of plasma renin activity  Insulin induced hypoglycemic stimulation test.  17 alpha- Hydroxyprogesterone levels  DHEA estimation
  • 11. Plasma Cortisol level  Diurnal rhythm ◦ Secretion maximum in morning ◦ Minimum at midnight  Normal range ◦ 5-25 microgm/dl in morning(8 am) ◦ 2-5 microgm/dl in night(10 pm)  Determined by immunoassay (ELISA/CLIA/RIA)  Loss of diurnal rhythm may be an early indication of lesion at any point in hypothalamic –pituitary- adrenal axis
  • 12. Plasma ACTH ACTH CORTISOL PROBABLE DISORDER Low High Primary hyperadrenalism Low Low Secondary adrenal insufficiency High Low Primary adrenocortical insufficiency High High Pituitory adenoma (Cushings
  • 13. Synacthen test/ACTH stimulation tests  Used to assess adrenal reserve capacity  Used to demonstrate the failure of adrenal gland to produce cortisol in response to ACTH  Stimulation of adrenal cortex by synthetic ACTH(eg:synacthen/cosyntropin)inject
  • 14.  Normal response shows a rise in serum cortisol > 18microg/dl within 60mts of i.v administration of synacthen  A person with primary adrenal failure doesnot respond.( rise <18microg/dl)  Confirms the diagnosis of Addison’s disease
  • 15. CRH Stimulation tests  Definitive to differentiate pituitary causes from other causes  Rise in ACTH secretion and cortisol levels following injection  If there is no ACTH response after CRH stimulation tests, the disease is of pituitary origin
  • 16. Dexamethasone Suppression Tests  Used in diagnosis of Cushing’s syndrome. Low dose Dexamethasone Suppression Tests  Dexamethasone is a potent suppressor of pituitary ACTH secretion and thereby cortisol level,causing 50% fall in serum cortisol with a dose as low as 1mg  Patient takes dexamethasone tab at night and plasma cortisol is determined at 8 am the following morning  Morning cortisol <5microgm/dl rules out adrenal tumors.
  • 17. High dose dexamethasone suppression test  Done to confirm Cushings disease  Administer 2mg dexamethasone every 6 hrs for 2 days & cortisol measured next day morning.  This dose suppresses plasma cortisol in Cushings disease.(drop atleast 50%)  If plasma cortisol level is not suppressed, adrenal tumors producing high levels of cortisol or ectopic ACTH producing tumors are usually the
  • 18. Urinary excretion of steroids  Urinary steroids are 17 ketosteroids and 17 hydroxy steroids  17 ketosteroids are derived from both adrenal steroids and androgen from gonads, major contribution by cortisol and cortisone  17 hydroxy steroids are derived mainly from adrenal steroids  Diagnostic value to assess functional status of adrenal cortex, particularly in females
  • 19. Estimation of aldesterone in blood  Increased levels are seen in primary hyperaldosteronism /Conn’s syndrome and bilateral adrenal hyperplasia  Decreased aldosterone levels are seen in Addison’s disease
  • 20. Estimation of plasma renin activity  Helps to differentiate between primary and secondary hyperaldosteronism  Enzyme activity is high in secondary, low in primary hyperaldosteronism
  • 21. Urinary free Cortisol  In plasma 70% cortisol is bound to cortisol binding globulin/transcortin  20% cortisol is bound to albumin  Rest is free,which is the biologically active form  A definite fraction of unbound/free cortisol is exreted in urine unchanged  24 hr urine sample is collected  Estimation of urinary free cortisol is a sensitive index of adrenal activity: Hyper/Hypofunction.
  • 22. Lab findings in Adrenal hyperfunction Cause Plasma cortisol Urinary cortisol Plasma ACTH Dexamethasone suppression Adrenal adenoma Increased Increased decreased No suppression Adrenal carcinoma Increased Increased decreased No suppression Pituitory adenoma Increased Increased Increased Suppression with high dose Ectopic ACTH Increased Increased Increased No suppression
  • 23.
  • 24. Lab findings in Adrenal hypofunction Cause for adrenal insufficienc y Plasma cortisol Urinary cortisol Plasma ACTH ACTH stimulation CRH stimulation Primary low low High No effect No effect Secondary low low Low Normal/ exaggerate d No effect
  • 25.
  • 26. Lab findings in Conn’s syndrome  Plasma Aldosterone levels are high  Plasma renin activity is decreased due to feedback  Serum electrolytes-hypernatemia, hypokalemia  pH is elevated(hypokalemic alkalosis)  Osmolality is elevated
  • 27. Sex hormones & investigations in Infertility
  • 28. Commonly measured hormones for evaluation of infertility are:  FSH  LH  Testosterone  Prolactin  Estradiol  Anti-Mullerian Hormone  TSH  Progesterone  Inhibin-B
  • 29.
  • 30.
  • 31. Assignment Questions( 5*4 = 20 marks) 1. List the adrenal function test with significance of each. 2. List the lab findings in adrenal hyperfunction. 3. List the lab findings in adrenal hypofunction. 4. In tabular form, give the pattern of hormone levels in various endocrine abnormalities in males and females.

Editor's Notes

  1. Cytoplasmic receptor