Adrenal disorders

1. W.O. Balogun
Endocrinology Unit
Dept. Of Medicine, UCH

2. About anatomy
 Paired glands located supra renal
 Divided anatomically and functionally into 2 parts:
adrenal cortex and adrenal medulla
 Adrenal cortex:
 -zona glomerulosa
 zona fascilculata, and
 zona reticularis

3. Histological divisions

4. Anatomical location

5. Adrenal medulla
 Derived from embryonic neural crest ectoderm (same
tissue that produces the sympathetic ganglia).
 Synthesizes and secretes:
 Catecholamines (mainly Epinephrine but some NE).

6. Adrenal cortex
 Secretes corticosteroids
 Controlled by ACTH
 Zona glomerulosa: Mineralocorticoids
 Zona fasciculata: Glucocorticoids
 Zona Reticularis: Sex steroids

8. Mechanism of action of steroid
hormones
1) The steroid h. enters the cytoplasm of the cell
where it binds with a specific receptor ( protein
in nature).
2) The combined hormone receptor diffuse into
the nucleus.
3) Then it activates the transcription process of
specific genes to form a messenger RNA.
4) The messenger RNA diffuse to ‘ cytoplasm to
promote synthesis of specific protein &
enzymes within ribosomes’.

9. Actions of Glucocorticoids
 Intermediary metabolism
Acts in a concerted way to maintain or increase blood
glucose level
 Liver: Increase expression of gluconeogenic enzymes
 Adipocytes: mobilises FFA for gluconeogenesis
 Degrade muscle proteins for gluconeogenesis
 Causes low serum Ca by ↑ calcium
absorption/reabsorption from GI and kidneys; also ↑ bone
resorbption
 Inhibits pancreatic insulin secretion
 Blunts gonadotrophs sensitivity to GnRH

10. Actions of Glucocorticoid (2)
 Depresses immune system:
 Causes thymus atrophy
 Decreases IL-1 production
 Inhibits monocytes proliferation; decreases lymphocytes and
eosinophils concentration, increases neutrophils but
suppreses their activities
 Inhibits inflammation

11. Actions of glucocorticoid (3)
 Antiproliferative actions on fibroblasts and keratinocytes
 Stimulation of surfactant production in the lungs
 CVS: Increased cardiac contractility; increase vascular
reactivity to vasoconstrictors and decreased endothelia
permeability
 Kidneys: Causes increased GFR to excrete excess water load

12. Actions of glucocorticoid (4)
 Psychologic /CNS:
 Maintains emotional balance
 Suppression of REM sleep
 Acts on hippocampus to facilitate memory,
concentration and intellectual performance
 Eye: causes increased ocular prssure

13. Actions (5)
 Effects during stress:
 Increases lipolytic actions directly and via
cathecolamines, providing FFA for stress
 Counterregulates hypoglycaemia by increasing
gluconeogesis

15. MINERALOCORTICOIDS
ALDOSTERONE
 ELECTROLYTE BALANCE
 BLOOD PRESSURE
 RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM

16. Actions and control of aldosterone

17. Functions of adrenal medulla
 The cathecolamines:
 Increase respiratory rate.
 Increase HR and cardiac output.
 Vasoconstrict blood vessels, thus increasing venous return.
 Stimulate glycogenolysis.
 Stimulate lipolysis.

18. SEX HOMONES
 ANDROGENS (TESTOSTERONE)
 ESTROGENS
LESS THAN GONADS

19. Function tests

20. Disorders of function
 Excess: Hypercotisolism; hyperaldosteronism;
 Deficiency: Hypoadrenalism

21. Regulation of
adrenal gland
secretion ACTH
Cortisol
Cortisol

22. REGULATION OF CORTISOL SECRETION
HYPOTHALAMUS
CRH
ANTERIOR PITUITARY
ACTH
ADRENAL CORTEX
TARGET ORGANS
CORTISOL
STRESS
DIURNAL
RHYTHM
+ +
-
-
INCREASED
BLOOD GLUCOSE
BLOOD AA
BLOOD FATTY ACIDS

23. Concept of circadian rhythm
Group of hormones with pulsatile patterns of secretion
and well-defined amplitude, frequency and rhytmicity
within the circadian

24. Pattern of cortisole and ACTH level during
the day

25. Tests of Hypercortisolism
Plasma cortisol assays: limited usefulness. Episodic
secretions, affected by stress, ↑oestrogen, depression,
starvation, alcoholism, CKD
Urinary free cortisol:
Urine collected for 24 hrs to measure unbound cortisol-
fraction excreted unchanged. Provides an integrated
measure of serum cortisol. Very useful to confirm
Cushing syndrome
17-hydroxycorticosteroids measurement
Late night salivary cortisol

26. Tests of hypercorticolism (2)
Dexamethasone suppresion tests: dexamethasone, a potent
steroid is used
Principle: suppress HPA axis; normally, ACTH decreases,
causing low plasma or urinary corticosteroids. Fail to suppress in
cushing
 Low-Dose (overnight): given oral 1 mg. 80-99% with C.S.
showed abnormal response. False positive in hospitalised,
alcohol, depression, anxiety, uraemia, high oestrogen states
High-Dose:- can be overnight (8mg) or for 2 days (2mg 6-
hourly). The supraphysiologic dose given to distinguish
Cushing disease from ectopic ACTH or adrenal tumours;
cortisol suppresses to about 50%. Fairly useful

27. Test of Pituitary-adrenal reserve
Principle: stress or challenge HPA to provoke rise in
cortisol
ACTH: to stimulate release of cortisol
Metyrapone: inhibits cortisol release , causing ↑ACTH
CRH: direct stimulation of pituitary corticotrophs
Insulin –induced hypoglycaemia testing

28. Androgens: Tests
 Direct measurement better than dynamic testing
 Measure assays of hormones directly, e.g DHEA,
DHEA sulphate, androstenedione, testrosrone

29. Tests for Hypoadrenalism
ACTH stimulation test/Synacthen test
250µg of tetracosactrin administered; plasma
cortisol>550nm/l after 30 min normally
Subnormal responses in hypoadrenalism
Plasma ACTH level. Helps distinguish primary from
secondary hypoadrenalism
Insulin-induced hypoglycaemia stress test

30. Others:
Electrolytes
Low Na and high potassium in hypoadrenalism
Hypokalemia in Heprcorticolism
FBC: anaemia; leukocytosis
Radiodiagnosis for localisation
Inferior petrosal sinus sampling of ACTH to
distinguish Cushing disease from ectopic

31. Hyperaldosteronism
Serum K: Hypokalemia
Confirmation is by demonstrating subnormal supine and
erect plasma renin activity and elevated plasma
aldosterone
NB: Patient not on diuretic therapy for ≥3 weeks
 Aldosterone: Renin >30 in Primary aldosteronism
24-hour urinary aldosterone (especially when plasma
aldosterone not elevated but suppressed renin)
Saline infusion test: aldosterone fails to suppress with
expansion of ECF
Oral salt loading test for 3 days: aldosterone fails to
suppress

32. Adrenal medulla function tests
In phaeochromocytoma:
Screening by 24 hr urine metabolites e.g VMA or
metanephrines of cathecolamines. Useful.
NB: VMA less subject to drug interference but less
sensitive to metanephrines
Plasma or urinary free cathecolamines. More
specialised

33. THANK YOU