2. Adrenal Glands
e
Suprarenal glands
• Paired organ each weight
about 4 grams, pyramidal in
shape, located on the top of
the kidneys, one on each sid
at the level ofthe T12
• It enclosed by fibroelastic
connective tissue capsule.
3. Adrenal glands
• Eachgland is divided into tow parts:
– Cortex– outer part of gland
• Part of hypothalamus – pituitary – adrenalaxis
• Secrete avariety of steroid hormones
– Medulla – inner part of gland, (20%ofgland)
• Part of sympathetic nervoussystem
• Secrete catecholamines
– Both parts are structurally and functionallydifferent
5. Adrenal cortex
• Thelarge cortical cells are arranged into three
layers or zones:
– Thezona glomerulosa,
• Thethin outermost layer
• Constitute about 15%of cortex
– Thezona fasciculata,
• Themiddle and largest portion
• Constitute about 75%of cortex.
– Thezona reticularis,
• Theinnermost zone.
6. Adrenal cortex
• Zonaglomerulosa:
– Produce meniralocorticods
– Mainly aldosterone (because it containenzyme
aldosterone synthase)
Hormones that help control the balance of
minerals (Na+ and K+)and water in theblood
8. Adrenal cortex
• Zonafasciculata:
– Produce glucocorticods
– Mainly cortisol andcorticosterone
– Thehuman adrenal glands produce the equivalent
of 35–40 mg of cortisone acetate perday
– Thesecretion of these cells is controledby
hypothalamic-pituitary axis viaACTH
Hormone that play amajor role inglucose
metabolism aswell asin protein and lipid
metabolism
9. Adrenal cortex
• Zonareticularis:
– Theinnermost layer of the adrenal cortex, lying
deep to the zonafaciculata and superficial tothe
medulla.
– Thesecells produce androgens
10. Adrenal cortex
• Zonareticularis:
– Theandrogens produced includes
• Dehydroepiandrosterone (DHEA)
• Androstenedione
– Synthesizedfrom cholesterol
• DHEAis further converted to DHEA-sulfate viaa
sulfotransferase
11. Adrenal cortex
• Zonareticularis:
– Theandrogens produced are released into the
blood stream and taken up in the testis and
ovaries to produce testosterone and theestrogens
respectively.
12. Disordersof adrenal cortex
• Patient with adrenal disorders canpresent
with features relatedto:
• HYPOFUNCTIONOFTHEGLAND
• HYPERFUNCTIONOFTHEGLAND
18. Adrenal Hypofunction
• Other causes
– ACTHblockingantibodies
– Mutation in ACTHreceptor gene
– Adrenal hypoplasiacongenita
– Familial adrenal insufficiency
19. Addison disease
Autoimmune
Isolated or associated with other autoimmune
disease
Presents with tiredness, weight loss, skin
pigmentation
Aldestrone & cortisol low, high ACTH, high renin
Low sodium , high potasium
ACTH stimulation test
Adrenal antibodies
Treatment : cortisol + aldestrone
.
20. • Progressivedestruction of entire adrenal cortex,
Thisis usually autoimmune based.
• Most likely the result of cytotoxicTlymphocytes,
although 50%of patients have circulatingadrenal
antibodies.
Adrenal Hypofunction
Addison’s disease
Primary hypoaldosteronism
Addison’s disease: pathogenesis
21. Addison’s disease: Clinical features
Common Lesscommon
Tiredness, generalized Hypoglycemia
weakness, lethargy
Anorexia, nausea, vomiting Depression
Hyponatremia
Hyperkalemia ,Hypercalcemia
Convulsions
Dizzinessand postural
hypotension
Pigmentation
Lossof body hair (woman)
24. ADRENALCRISIS
• Acuteadrenal insufficiency
• Medical emergency
• Acute in onset; can be fatal if not promptly
recognized and treated
• Clinicalfeatures :
• Severehypovolaemia
• Dehydration
• Shock
• Hypoglycaemia
• possible mental confusion and lossof consciousness
25. ADRENALCRISIS
• Causes:
• Precipitated by stress
• infection, trauma or surgery in patients with incipient
adrenal failure/treated with glucocorticoids if dosage is
not increase
• Adrenal haemorrhage
• due to cxof anticoagulanttreatment
• Meningococcal septicaemia
26. INVESTIGATIONS (HORMONAL)
• Plasmacortisol concentration
• <50nmol/L at 0900H →effectively diagnostic
• >550nmol/L excludes the Dx
• ACTHstimulation test / Synacthentest
• Measurement of plasmaACTH
• Metyrapone test
• CRHstimulation test
• Plasmarenin and aldosterone levels
28. INVESTIGATIONS(HORMONAL)
• ACTHstimulation test / Synacthentest
SHORTTEST LONGTEST
Takebloodsampleat 0900H Day1 : inject 1 mgdepotACTH
for measurement ofcortisol IM im
Inject 250µgACTHim oriv Days2 and3 : repeat
Takefurther blood sample Day4 : perform shortACTH
after 30 and60 minfor cortisol test
measurement
29. METYRAPONETEST
• Measures the ability of the pituitary gland to
release ACTHin response to decreased blood
cortisol levels.
• Metyrapone inhibits cortisol production by
blocking the conversion of 11-deoxycortisolto
cortisol by 11-beta-hydroxylase
32. PLASMARENINAND ALDOSTERONE
• Give an indication of mineralocorticoid
activity.
• Adrenal insufficiency
– Low aldosterone level with highrenin
33. Management
• Hormonereplacement
• Life-long replacement therapy
• Hydrocortisone and 9α-fludrocortisone
• Secondaryadrenocortical insufficiency
• Hormone replacement
• may also require more definitive treatmente.g.
surgical removal of apituitary tumour.
34. Management
• Adrenal crisis:
• Adequate resuscitation e.g. IVfluids, IVglucose.
• IVhydrocortisone 100mg which should be
continued four times daily afterwards untilthe
patient can take oralmedication.
37. Hyperaldosteronism
• A medical condition where too much
aldosterone is produced by the adrenal glands,
which can lead to sodium retention and
potassium loss.
• Types:
– Primary hyperaldosteronism
– Secondary hyperaldosteronism
43. Conn’ssyndrome
• Clinical features:
– Hypertension : aldosterone induced Na retention
with increase in ECF volume
– Muscle weakness: Due to decrease K+
– Muscle paralysis: severe hypokalaemia
– Latent tetany andparaesthesiae
– Polydipsia, polyuria and nocturia: due to
hypokalaemic nephropathy
45. INVESTIGATION
• Plasma aldosterone :renin activityratio
– Sensitive screening test
– No need to standardizeposture
Ratio Interpretation Action
<800 Diagnosis excluded Seek other cause
>1000,<2000 Diagnosis possible Confirmatory test
>2000 Diagnosis very likely Establish cause
46. Diagnosis
• Perform saline infusion test (sodiumloading)
– Method :
infusion of 1.25Lof 0.9%saline over 2 hrs
– Result:
plasmaaldosterone remains >240 pmol/l confirm
Conn’s syndrome
63. Cont..
• Back pain ( osteoporosis and vertebral collapse) –
inhibit bone formation
• Psychiatric disturbances – euphoria, mania,
depression
64.
65. Laboratory
investigations
There are two diagnostic steps in the investigation
of patient suspected of having Cushing's syndrome
Screening test
for identification of Cushing's syndrome.
the demonstration of high plasma cortisol level
Identification of cause
66. 1. Demonstration of increased
cortisol
Assessment of circadian rhythm in cortisol secretion
24-Hour urinary free cortisol excretion
Overnight / low dose dexamethasone suppression
test
67. Laboratory
investigations
1. Assessment of circadian rhythm in cortisol
secretion.
Measure 8 am and 11 pm serum cortisol
level
Normal : Serum value @ midnight is 50% less than value
@ 8 am
Cushing’s syndrome : rhythum is loss
Pseudo-Cushing : normal circadian.
68. Laboratory
investigations
2. Measuring 24-hour urinary free cortisol
Level (umol/ 24 h )
< 300
Interpretation
Normal
300 - 700 Severe depression
Stress
Diagnostic of
Cushing's syndrome
> 700
69. Laboratory
investigations
3. Low dose Dexamethasone suppression test :
0.5 mg Dexametason (oral) given 6 hourly for 2 days
blood for plasma cortisol collected 6 hour after last dose
urine for UFC is collected before & on the 2nd day of
Dexa
Result:
UFC suppress by 50% ( < 70nmol/24h)
plasma cortisol suppress < 140 nmol/L
Cushing
no suppression of UFC & Pl. cortisol
normal
pseudo-
Cushing's synd
70. Elucidation of the
cause
• High dose Dexamethasone suppression test
• Normal individuals suppress plasma cortisol to
<50 nmol/L.
• Patients with Cushing's syndrome fail to show
complete suppression of plasma cortisollevels.
Thistest is highly sensitive (>97%).
71. 2. Elucidation of the
cause
• PlasmaACTH
– Normal <50 ng/L
– Low – adrenal causes
– Elevated
• Slight – pituitary dependent Cushing’s
• Gross– ectopic secretion ofACTH
72. Elucidationof the cause
• CRHTest
– Differentiate ectopicACTHsecretion and
Cushing’s disease.
– Cushing’s disease – plasmaACTHincreases 50%
over baseline and cortisol increase by20%
– EctopicACTHor adrenal tumour – no response
73. Elucidation of the
cause
• Imaging
– CTscanof adrenal gland: TROadrenaltumor
– MRI of pituitary gland: majority microadenoma
( <10mm). MRI reveal lesion in 50 - 60%of cases
– CTscan/MRI of thorax & abdomen: ectopicACTH
producing tumor
