adrenal gland disorders ii-14 - Copy.ppt

Adrenal gland disorder

1. ADRENAL GLANDADRENAL GLAND
DISORDERSDISORDERS
Dr Magda A Latif Dr Magda A Latif
Oct 2020Oct 2020

2. ANATOMYANATOMY

The The adrenal glandsadrenal glands are endocrine are endocrine
organs consisting of both cortex organs consisting of both cortex
and medullaand medulla..

3. ANATOMYANATOMY

Adrenal cortex:Adrenal cortex:

the narrow layer of zona glomerulosathe narrow layer of zona glomerulosa
( mineralocorticoids)( mineralocorticoids)

Intervening is the broad zona Intervening is the broad zona
fasciculata, which makes up about fasciculata, which makes up about
75% of the total cortex75% of the total cortex
( glucocorticoids) ( glucocorticoids)

The narrow layer of The narrow layer of zona reticularis zona reticularis
abuts the medullaabuts the medulla (sex steroids) (sex steroids)

4. ANATOMYANATOMY

The The adrenal medullaadrenal medulla is composed of is composed of
chromaffin cells, which synthesize chromaffin cells, which synthesize
and secrete and secrete catecholaminescatecholamines, mainly , mainly
epinephrine. epinephrine.

6. ANATOMYANATOMY

The The adrenal cortexadrenal cortex synthesizes three different synthesizes three different
types of steroids:types of steroids:

(1) (1) glucocorticoidsglucocorticoids (principally cortisol), which are (principally cortisol), which are
synthesized primarily in the zona fasciculata and synthesized primarily in the zona fasciculata and
to a lesser degree in the zona reticularis;to a lesser degree in the zona reticularis;

(2) (2) mineralocorticoidsmineralocorticoids, the most important being , the most important being
aldosterone, which is generated in the zona aldosterone, which is generated in the zona
glomerulosa; glomerulosa;

(3) (3) sex steroidssex steroids (estrogens and androgens), which (estrogens and androgens), which
are produced largely in the zona reticularisare produced largely in the zona reticularis

7. ADRENOCORTICAL HYPERFUNCTION ADRENOCORTICAL HYPERFUNCTION
(HYPERADRENALISM(HYPERADRENALISM ))

TThere are three basic types of here are three basic types of
hyperadrenal syndromes:hyperadrenal syndromes:

(1) (1) Cushing syndromeCushing syndrome, characterized by an , characterized by an
excess of cortisol;excess of cortisol;

(2) (2) hyperaldosteronismhyperaldosteronism; ;

(3) (3) adrenogenitaladrenogenital or virilizing syndromes or virilizing syndromes
caused by an excess of androgens. caused by an excess of androgens.

8. Hypercortisolism Hypercortisolism
(Cushing Syndrome)(Cushing Syndrome)

Cushing syndrome can be broadly Cushing syndrome can be broadly
divided into divided into exogenousexogenous and and
endogenousendogenous causes. causes.

The vast majority of cases of Cushing The vast majority of cases of Cushing
syndrome are the result of the syndrome are the result of the
administration of exogenous administration of exogenous
glucocorticoidsglucocorticoids ("iatrogenic" Cushing ("iatrogenic" Cushing
syndrome).syndrome).

9. Hypercortisolism Hypercortisolism
(Cushing Syndrome)(Cushing Syndrome)

The endogenous causes can, in turn, The endogenous causes can, in turn,
be divided into those that are be divided into those that are ACTH ACTH
dependentdependent and those that are and those that are ACTH ACTH
independentindependent

10. Hypercortisolism Hypercortisolism
(Cushing Syndrome)(Cushing Syndrome)

ACTH-DEPENDENTACTH-DEPENDENT

Cushing disease (pituitary adenoma; rarely CRH-dependent pituitary Cushing disease (pituitary adenoma; rarely CRH-dependent pituitary
hyperplasia)hyperplasia)

Ectopic corticotropin syndrome (ACTH-secreting pulmonary small-cell Ectopic corticotropin syndrome (ACTH-secreting pulmonary small-cell
carcinoma, bronchial carcinoid)carcinoma, bronchial carcinoid)

ACTH-INDEPENDENTACTH-INDEPENDENT

Adrenal adenomaAdrenal adenoma

Adrenal carcinomaAdrenal carcinoma

Macronodular hyperplasia (ectopic expression of hormone receptors, Macronodular hyperplasia (ectopic expression of hormone receptors,
including GIPR, LHR, vasopressin and serotonin receptors)including GIPR, LHR, vasopressin and serotonin receptors)

Primary pigmented nodular adrenal disease (Primary pigmented nodular adrenal disease (PRKARIAPRKARIA and and PDE11PDE11 mutations) mutations)

McCune-Albright syndrome (McCune-Albright syndrome (GNASGNAS mutations) mutations)
  

11. Cushing's Syndrome Cushing's Syndrome
MMiddle-aged 3F/1M iddle-aged 3F/1M
4 main causes: 4 main causes:
1.1.Pituitary adenoma - secretes ACTHPituitary adenoma - secretes ACTH
2.2.Adrenal tumors - secrete cortisol Adrenal tumors - secrete cortisol
3.3.Ectopic production of ACTH Ectopic production of ACTH
4.4.Iatrogenic Cushing's Syndrome Iatrogenic Cushing's Syndrome

12. 1.1.Pituitary adenomaPituitary adenoma
-- secretes ACTH secretes ACTH
-- 60-70% of cases of pathologic 60-70% of cases of pathologic
causescauses
-- adrenal glands are hyperplastic adrenal glands are hyperplastic
-- Biochemistry Biochemistry: : Increased ACTH and Increased ACTH and
cortisolcortisol

13. 2. 2. Adrenal tumorsAdrenal tumors
-secrete cortisolsecrete cortisol
-20-25% of cases of Cushing's20-25% of cases of Cushing's
-adrenal adenoma (50%), carcinoma adrenal adenoma (50%), carcinoma
(50%)(50%)
 atrophy of contralateral gland atrophy of contralateral gland
-BiochemistryBiochemistry: : low ACTH and high low ACTH and high
cortisolcortisol

14. 3. 3. Ectopic production of ACTH Ectopic production of ACTH
-by tumorsby tumors
-lung cancerlung cancer, ,
-bronchial and thymic carcinoids, bronchial and thymic carcinoids,
-medullary thyroid carcinoma, medullary thyroid carcinoma,
-islet cell cancerislet cell cancer
-10-15% of cases10-15% of cases
-adrenals are hyperplasticadrenals are hyperplastic
-BiochemistryBiochemistry: : Increased ACTH and Increased ACTH and
cortisolcortisol

15. 4. 4. Iatrogenic Cushing's SyndromeIatrogenic Cushing's Syndrome
-commonest cause overallcommonest cause overall
-ddue to long-term corticosteroid ue to long-term corticosteroid
therapy for treatment of:therapy for treatment of:
- connective tissue diseases- connective tissue diseases
- - asthmaasthma
- rheumatoid arthritis - rheumatoid arthritis
- - cancercancer
- transplant rejection- transplant rejection
- Biochemistry- Biochemistry: : High cortisol and High cortisol and
ACTH suppressedACTH suppressed

16. Clinical findings inClinical findings in Cushing's Cushing's
SyndromeSyndrome

  OOccurs as a ccurs as a
consequence of consequence of
excess plasma excess plasma
glucocorticoid levels glucocorticoid levels
otruncal obesity, buffalo truncal obesity, buffalo
hump and moon face hump and moon face
due to fat deposition due to fat deposition
ohypertension hypertension
ohirsutism - due to hirsutism - due to
increased testosterone increased testosterone
omuscle weakness and muscle weakness and
breakdown breakdown
omenstrual irregularity menstrual irregularity
oosteoporosis - decreased osteoporosis - decreased
calcium absorption, calcium absorption,
increased bone increased bone
resorption and resorption and
suppression of bone suppression of bone
formation formation
oimpaired glucose impaired glucose
tolerance or diabetes tolerance or diabetes
mellitus - due to insulin mellitus - due to insulin
resistance resistance
oabdominal striae - due to abdominal striae - due to
inhibition of protein inhibition of protein
synthesis and abnormal synthesis and abnormal
collagen maturation collagen maturation
omental symptoms are mental symptoms are
common; depression and common; depression and
psychosis psychosis

17. AdenomaAdenoma

18. Primary Primary
HyperaldosteronismHyperaldosteronism

HyperaldosteronismHyperaldosteronism is the generic is the generic
term for a group of closely related term for a group of closely related
conditions characterized by chronic conditions characterized by chronic
excess aldosterone secretion. excess aldosterone secretion.

19. Primary Primary
HyperaldosteronismHyperaldosteronism

Hyperaldosteronism may be primary, or it may Hyperaldosteronism may be primary, or it may
be secondary to an extra-adrenal cause.be secondary to an extra-adrenal cause.

Primary hyperaldosteronismPrimary hyperaldosteronism stems from an stems from an
autonomous overproduction of aldosterone, autonomous overproduction of aldosterone,
with resultant suppression of the renin-with resultant suppression of the renin-
angiotensin system and angiotensin system and decreased plasma renin decreased plasma renin
activityactivity. .

Blood pressure elevation is the most common Blood pressure elevation is the most common
manifestation of primary hyperaldosteronism, manifestation of primary hyperaldosteronism,
which is caused by one of three mechanismswhich is caused by one of three mechanisms::

20. Primary Primary
HyperaldosteronismHyperaldosteronism

Bilateral idiopathic Bilateral idiopathic
hyperaldosteronismhyperaldosteronism (IHA), (IHA),

Adrenocortical neoplasmAdrenocortical neoplasm,,

Glucocorticoid-remediable Glucocorticoid-remediable
hyperaldosteronismhyperaldosteronism

21. Bilateral idiopathic Bilateral idiopathic
hyperaldosteronismhyperaldosteronism (IHA) (IHA)

Bilateral idiopathic hyperaldosteronismBilateral idiopathic hyperaldosteronism (IHA), (IHA),
characterized by bilateral nodular hyperplasia of characterized by bilateral nodular hyperplasia of
the adrenal glands, is the most common the adrenal glands, is the most common
underlying cause of primary underlying cause of primary
hyperaldosteronismhyperaldosteronism, accounting for about 60% , accounting for about 60%
of cases. of cases.

Individuals with IHA tend to be older and to have Individuals with IHA tend to be older and to have
less severe hypertension than those presenting less severe hypertension than those presenting
with adrenal neoplasms. with adrenal neoplasms.

22. Adrenocortical neoplasmAdrenocortical neoplasm

EEither an aldosterone-producing adenoma (the most ither an aldosterone-producing adenoma (the most
common cause) or, rarely, an adrenocortical common cause) or, rarely, an adrenocortical
carcinoma. carcinoma.

In approximately 35% of cases, primary In approximately 35% of cases, primary
hyperaldosteronism is caused by a solitary hyperaldosteronism is caused by a solitary
aldosterone-secreting adenoma, a condition referred aldosterone-secreting adenoma, a condition referred
to as to as Conn syndromeConn syndrome..

This syndrome occurs most frequently in adult middle This syndrome occurs most frequently in adult middle
life and is more common in women than in men (2 : 1).life and is more common in women than in men (2 : 1).

Multiple adenomas may be present in an occasional Multiple adenomas may be present in an occasional
patient.patient.

23. Primary Primary
hyperaldosteronismhyperaldosteronism

low-renin hyperaldosteronismlow-renin hyperaldosteronism

too much mineralocorticoidtoo much mineralocorticoid

not due to excess ACTHnot due to excess ACTH

0.5% of hypertensives have primary 0.5% of hypertensives have primary
hyperaldosteronism hyperaldosteronism

Patients exhibit hypokalemia, alkalosis, and Patients exhibit hypokalemia, alkalosis, and
low renin, low renin,

Low potassium is likely to cause muscle Low potassium is likely to cause muscle
weakness, and even paralysis. weakness, and even paralysis.
–these patients can die from hypokalemia if you these patients can die from hypokalemia if you
give them thiazide diuretics to treat their high give them thiazide diuretics to treat their high
blood pressure. blood pressure.

24. Secondary aldosteronismSecondary aldosteronism

In In secondary hyperaldosteronismsecondary hyperaldosteronism, in contrast, aldosterone , in contrast, aldosterone
release occurs in response to activation of the renin-release occurs in response to activation of the renin-
angiotensin system.angiotensin system.

It is characterized by It is characterized by increased levels of plasma reninincreased levels of plasma renin and is and is
encountered in conditions such as the following: encountered in conditions such as the following:

Decreased renal perfusion (arteriolar nephrosclerosis, Decreased renal perfusion (arteriolar nephrosclerosis,
renal artery stenosis)renal artery stenosis)

Arterial hypovolemia and edema (congestive heart failure, Arterial hypovolemia and edema (congestive heart failure,
cirrhosis, nephrotic syndrome)cirrhosis, nephrotic syndrome)

Pregnancy (due to estrogen-induced increases in plasma Pregnancy (due to estrogen-induced increases in plasma
renin substrate)renin substrate)

25. Hypofunction of Hypofunction of
adrenaladrenal cortex cortex
PrimaryPrimary causes causes

Loss of Cortex:Loss of Cortex:
–aautoimmuneutoimmune
–bacterialbacterial
–hhemorrhageemorrhage
–amyloidosisamyloidosis
–sarcoidosissarcoidosis
–hhemochromatosisemochromatosis
–metastatic diseasemetastatic disease
–surgical ablation.surgical ablation.

Metabolic Failure:Metabolic Failure:
–Primary failure of Primary failure of
adrenal glandsadrenal glands, ,
–DDrug induced rug induced
inhibition of inhibition of
adrenocortical adrenocortical
function.function.

26. SecondSecondaryary causes causes

hhypothalamic / pituitary ypothalamic / pituitary
disease disease

nneoplasm eoplasm

infection infection

hhypothalamic / pituitary ypothalamic / pituitary
suppression: suppression:
–long term steroid long term steroid
administration. administration.

27. AAdrenocorticaldrenocortical InsufficiencyInsufficiency
((Hypoadrenocorticism)Hypoadrenocorticism)
Primary Acute Adrenal Primary Acute Adrenal
Insufficiency:Insufficiency:

Precipitated by stress Precipitated by stress
in a patient with in a patient with
Addison's. Addison's.

Precipitated by Precipitated by
withdrawal of steroids withdrawal of steroids
in an adrenalectomized in an adrenalectomized
patient. patient.

In patients with acute In patients with acute
bilateral hemorrhagic bilateral hemorrhagic
necrosis of adrenals. necrosis of adrenals.
Chronic insufficiencyChronic insufficiency::

Addison's diseaseAddison's disease

28. Acute InsufficiencyAcute Insufficiency
Acute Hemorrhagic Necrosis of AdrenalsAcute Hemorrhagic Necrosis of Adrenals

Waterhouse-Friedricksen SyndromeWaterhouse-Friedricksen Syndrome
–DDue particularly to meningococcal septicemia,ue particularly to meningococcal septicemia,

less commonly Staph, pneumococcus, or Haemophilus less commonly Staph, pneumococcus, or Haemophilus
–Newborns due to perinatal trauma.Newborns due to perinatal trauma.

DICDIC

adrenal glands are hemorrhagic with cortical adrenal glands are hemorrhagic with cortical
necrosisnecrosis

purpuric rashpurpuric rash

vascular collapse vascular collapse  shock: shock: due to endotoxin and due to endotoxin and
vomiting, decreased vomiting, decreased steroids and steroids and NaNa
++
, increased K, increased K
++

in blood and dehydrationin blood and dehydration..

29. Waterhouse-Friedricksen SyndromeWaterhouse-Friedricksen Syndrome

30. Primary cPrimary chronic hronic adrenal adrenal insufficiencyinsufficiency

Addison's diseaseAddison's disease
–60-60-75% due to 75% due to auto-immune destructionauto-immune destruction of adrenal of adrenal
cortex with lymphocytic and plasma cell infiltratecortex with lymphocytic and plasma cell infiltrate
–normal medullanormal medulla
–TuberculosisTuberculosis ( (2nd commonest cause2nd commonest cause))
–more than 90% of cortex needs to be destroyedmore than 90% of cortex needs to be destroyed
–ClinicallyClinically
Lethargy, muscle weakness, anorexia, nausea & Lethargy, muscle weakness, anorexia, nausea &
vomiting, wt loss, hypotension, hyperpigmentation vomiting, wt loss, hypotension, hyperpigmentation
of skin and mucous membranes.of skin and mucous membranes.

31. Addison’s disease:Addison’s disease: H Hyperpigmentation of yperpigmentation of
mucous membranesmucous membranes

32. 
Primary:Primary:
–due to adrenal insufficiencydue to adrenal insufficiency
–sshould be suspected when there is hould be suspected when there is
marked skin pigmentation due to high marked skin pigmentation due to high
ACTH levels.ACTH levels.

Secondary:Secondary:
–ppituitary or hypothalamic ituitary or hypothalamic iinsufficiency nsufficiency
(no skin pigmentation).(no skin pigmentation).
–Addison's disease is rare.Addison's disease is rare.

33. Causes of Addison'sCauses of Addison's Disease Disease
1. 1. Autoimmune Autoimmune

most cases of Additions show anti-most cases of Additions show anti-
adrenal Antibodies adrenal Antibodies ((60-75%60-75%) ) Two types Two types
exist. exist.

34. 
2. 2. TTuberculosisuberculosis ( (~~25% of cases). 25% of cases).

3. 3. Other causes:Other causes:
–hhistoplasmosisistoplasmosis
–amyloidamyloid
–sarcoidsarcoidosisosis
–mmetetastasesastases
- congenital hypoplasia
- hemochromatosis
- CMV infection (in AIDS)
- adrenal leukodystrophy

35. Addison'sAddison's Disease Disease

37. Adrenal Medulla Adrenal Medulla
PathologyPathology
Adrenal MedullaAdrenal Medulla

Synthesizes and secretes Synthesizes and secretes "adrenalin" "adrenalin"
(epinephrine, norepinephrine)(epinephrine, norepinephrine)

The only diseases are two tumors which The only diseases are two tumors which
may arise here or at the other chromaffin may arise here or at the other chromaffin
tissue massestissue masses
–pheochromocytomapheochromocytoma (well-differentiated, adults) (well-differentiated, adults)
–neuroblastomaneuroblastoma (poorly-differentiated, children). (poorly-differentiated, children).

38. 
Can present as Can present as Paroxysmal attacksParoxysmal attacks
which may precipitate which may precipitate
–congestive cardiac failure, congestive cardiac failure,
–coronary thrombosis, coronary thrombosis,
–cerebral hemorrhagecerebral hemorrhage
–may be brought on by stress, pressure, may be brought on by stress, pressure,
exercise exercise  acute release of acute release of
catecholamine catecholamine
–Biochemistry:Biochemistry: increased urinary and increased urinary and
serum metanephrinsserum metanephrins

39. 
Most (90%) occur in the adrenal Most (90%) occur in the adrenal
medullamedulla

Other sites (10%)Other sites (10%)
–the organs of Zuckerkandl: chromaffin the organs of Zuckerkandl: chromaffin
tissue at the origin of the tissue at the origin of the

inferior mesenteric artery and/or aortic inferior mesenteric artery and/or aortic
bifurcationbifurcation

paravertebral sympathetic chainparavertebral sympathetic chain

urinary bladder. urinary bladder.

40. 
Ten percent of pheo cases involve Ten percent of pheo cases involve
both adrenals, and many of these are both adrenals, and many of these are
also among the 10% that are familial. also among the 10% that are familial.
Syndromes include: Syndromes include:

MEN IIa or IIb MEN IIa or IIb

von Recklinghausen's neurofibromatosis von Recklinghausen's neurofibromatosis
(NF-I) (NF-I)

von Hippel-Lindau von Hippel-Lindau

succinic dehydrogenase mutation succinic dehydrogenase mutation

41. PheochromocytomaPheochromocytoma

42. Pheochromocytoma:Pheochromocytoma:
Signs & SymptomsSigns & Symptoms

HTNHTN
–> 115 mmHG > 115 mmHG
diastolicdiastolic
–IntermittentIntermittent
–UnstableUnstable

TachycardiaTachycardia

Unrelenting H/AUnrelenting H/A

Profuse diaphoresisProfuse diaphoresis

PalpitationsPalpitations

43. Pheochromocytoma:Pheochromocytoma:
Signs & SymptomsSigns & Symptoms

Visual Visual disturbancesdisturbances

N/VN/V

Feeling of Feeling of
apprehensionapprehension

Elevated blood Elevated blood
glucoseglucose levels levels

44. Pheochromocytoma:Pheochromocytoma:
ComplicationsComplications

StrokeStroke

RetinopathyRetinopathy

Heart diseaseHeart disease

Kidney damageKidney damage

45. Pheochromocytoma:Pheochromocytoma:
Medical Management / SurgicalMedical Management / Surgical

Treatment of choice Treatment of choice
is…is…
–SurgerySurgery

46. THANK YOUTHANK YOU