Endocrinology part 1:

Adrenal glands

Marcin Adamczak

 Adrenal glands physiology,

Adrenal cortex diseases,
Cushings syndrome
Mineralocorticoid excess
Adrenal insufficiency
Congenital adrenal hyperplasia

Adrenal medulla diseases,

Pheochromocytoma

Adrenal glands:

paired glands located retroperitoneally at the

upper pole of each kidney

Adrenals: Cross section

Cortex = yellow
Medulla= red to grey

Adrenal gland: Cross section

Adrenal glands:

include two distinct endocrine organs:

inner medulla part of sympathetic nervous
system, secretes catecholamines,
outer cortex sectretes numerous of different
steroid hormones;

Zona: reticularis, fasciculata, glomerulosa

Adrenocorticoids

HO
CH3

O
CH3

OH

OH

HO
CH3

O
CHO

O
Hydrocortisone

(11,17,21-trihydroxypregn-4-ene-3,20-dione)

Aldosterone

(11,21-dihydroxypregn-4-ene-3,18,20-trione)

OH

Hypothalamic-pituitary-adrenal axis

Pituitary - ACTH
39 AA; active 1-24 N-terminal fragment
proopiomelanocortin precursor (ACTH and
melanotropins, lipotropins and B-endorphin)
circadian rhythm peaks in the morning
Stimulus: CRF - stress, hypoglycemia,
CRF-feedback from glucocorticoids in circulation
action- adrenal cortex secrete glucocorticoids,
lesser aldosterone

Activation of Pathway=
Increased cholesterol utilisation
Cholesterol ester ==> free Cholesterol
Cholesterol synthesis
Cholesterol uptake by adrenals

Rate Limiting Step

ACTH stimulated
Mitochondrial step
2 hydroxylations
side chain cleavage
P450SCC( cholestrol 20,22-hydroxylase;
20-22 desmolase activity)

P450 C21 hydroxylase

(microsomal)
11-hydroxylase
(mitochondrial)
CORTISOL

Androgens
17 hydroxylase
17,20 desmolase
does not occur in
zona glomerulosa

18 hydroxylase
occur in zona glomerulosa only

18-OH steroid dehydrogenase

ALDOSTERONE

DHEA &
Androstendione
substrate for other
tissues

Adrenocorticoids
Biological Activities
1. Glucocorticoid Activity
1.1 Effects on Metabolism
1.1.1 Stimulation of gluconeogenesis, particularly in the liver
1.1.2 Mobilization of amino acids from extrahepatic tissues
1.1.3 Inhibition of glucose uptake in muscle and adipose tissue
1.1.4 Stimulation of fat breakdown in adipose tissue
1.2 Effects on Inflammation and Immune Function
1.2.1 Anti-inflammatory properties
1.2.2 Immunosuppressive properties
1.3 Other Effects of Glucocorticoids
1.3.1 Multiple effects on fetal development (promote maturation of the lung)
1.3.2 Miscellaneous effects (Excessive glucocorticoid levels affect many
systems, e.g., inhibition of bone formation, suppression of calcium
absorption and delayed wound healing.)
2. Mineralocorticoid Activity
2.1 Effect on Electrolytes
2.1.1 Increased re-absorption of sodium
2.1.2 Increased renal excretion of potassium
2.2 Effect on Water
2.2.1 Increased re-absorption of water

CORTISOL

reduce APC formation

of certain cytokines
(IL-1, IL-6, TNF)
reduce lymphocyte gene
activation for cytokine
synthesis

ACTH 15-70 pg/ml

Cortisol 5-25 g%

circadian rhythm peaks in the morning (6-8 am) the lowest plasma
concentration about midnight (60% lower)

Free cortisol in 24 h urine 50-125 g/24h

17 hydroksycorticosteroid in 24 h urine 3-16 mg/
24h (female) and 6-26 mg/24h (male)
Aldosteron 2-15 ng%
Aldosteron in 24 h urine 5-10 g/24h

 Adrenal glands physiology,

Adrenal cortex diseases,
Cushings syndrome
Mineralocorticoid excess
Adrenal insufficiency
Congenital adrenal hyperplasia

Adrenal medulla diseases,

Pheochromocytoma

Adrenal Cortex Disease

Clinical manifestations result from: Overproduction or deficiency of:
Glucocorticoids
Mineralocorticoids
Androgens

Hyper-secretion may present

differently depending on the disease
mechanism.
Hypo-secretion may only be apparent
at times of stress.

 Adrenal glands physiology,

Adrenal cortex diseases,
Cushings syndrome
Mineralocorticoid excess
Adrenal insufficiency
Congenital adrenal hyperplasia

Adrenal medulla diseases,

Pheochromocytoma

Overproduction of Glucocorticoids

Cushings syndrome refers to the

manifestation of glucocorticoids excess from any
cause (nonspecific designation).

Cushings disease excess production of

ACTH by pituitary gland causing manifestation of
adrenal hypercortisolism.

Cushings syndrome - causes:

- Cushings disease 80%
- Adrenal neoplasm (adenomas or carcinomas)
10-15%
- Ectopic ACTH-producting tumor
5-10%
- Bilateral adrenal hyperplasia with undetectable
ACTH less than 1%
- Iatrogenic Cushing syndrome

Cushing syndrome
ACTH
dependent

70%

independent

12%

10%
ACTH

ACTH

ACTH

Adenoma

Cortisol

8%
ACTH

Carcinoma

Hypothalamic-pituitary-etiology
(Cushings disease).
Stress
Diurnal rhythm

Hypothalamus

CRH

Pituitary

ACTH

Adrenal glands

Cortisol

Cushings disease:
- 90% - pituitary adenoma, 10% pituitary
hyperplasia,
- usually basophilic microadenoma,
- bilateral adrenal hyperplasia is due to increased
pituitary secretion of ACTH,
- more frequently in women than men (femalemale ratio 5:1); usually occurs during the
childbearing age,

A=
B=
C=

Addsions disease or long term corticosteroids

Normal
ACTH excess: Cushings disease or ectopic.
Idiopathic adrenal hyperplasia

Ectopic ACTH syndrome .

Stress

Hypothalamus

Pituitary

Adrenal glands

Diurnal rhythm

CRH

ACTH

Cortisol

Tumor

ACTH

Ectopic ACTH syndrome:

- Ectopic ACTH-production by tumours such as oat cell
carcinoma of the lung, carcinoma of the pancreas,
bronchial adenoma and others causes adrenal
hyperplasia.
- more frequent in men than in women (older age),
- In addition to increase of cortisol plasma level such
patients may have greatly increase level of
deoxycorticosterone (DOC) a potent mineralocorticoid.
That can result in severe hypertension, hypokalemia and
metabolic alkalosis.

Primary adrenal neoplasm

Stress

Diurnal rhythm

Hypothalamus

CRH

Pituitary

ACTH

Adrenal glands

Cortisol

Primary adrenal neoplasm:

- adenomas or carcinomas,
- Carcinomas are the most frequent spontaneus
Cushings syndrome in children.
- Carcinomas are usually large (> 6 cm).
- Adenomas secrete mainly cortisol. Carcinomas
produces usually variety of adrenal hormones
(glucocorticoids, mineralocorticoids, androgens
and estrogens).

Adrenal gland removed surgically in a patient with Cushing's

syndrome - adenoma. Some remaining atrophic adrenal is seen
at the right. Histologically, it is composed of well-differentiated
cells resembling cortical fasciculata zone. It is benign.

This is a large adrenal cortical

carcinoma which is displacing
the left kidney downward. Such
neoplasms are usually functional
(secreting corticosteroids or sex
steroids). They have a poor
prognosis.

Cushings syndromesymptoms (1):

- Central obesity

caused by effect of cortisol

on fat distribution. Fat
accumulates in the face,
neck, trunk, while the
limbs remain thin. The
moon face, Buffalo
hump (cervical fat pad),
supraclavicular fat pads.

Cushings syndrome- symptoms (1):

Buffalo hump
(cervical fat pad),

The moon face,

Cushings syndrome- symptoms (1):

Moon face; florid complexion (red face)

Cushings syndrome- symptoms (2):

2) Hypertension

Cushings syndrome- symptoms (2):

2) caused by increase cortisol-induced gluconeogenesis

and decreased peripheral glucose utilization; 20% of

patients have overt diabetes mellitus.
4) Symptoms of androgen excess (oligomenorrhea,
hirsutism and acne); in women with Cushings disease
stimultion of androgen secretion by ACTH,
5) Purplae striae linear marks on the abdomen where
the thin and wasted skin is stretched by underlying fat,

Purplae striae linear marks on the abdomen

Moon face

Central obesity
Purplae striae

Cushings syndrome- symptoms (3):

6) Muscle wasting and weakness caused by
catabolic effects of cortisol on muscle protein.

7) Osteoporosis caused by cortisols effects on

increased bone catabolism and inhibitory effects on

collagen synthesis and calcium absorption,

Cushings syndrome

Osteoporosis

Cushings syndromesymptoms (3):

8) Susceptibility to bruising
probably caused by enhanced
capillary fragility,

9) Psychiatric disturbances
especially depression.

Cushings syndrome- diagnosis (1):

The diagnostic approach in patients who are
suspected of having Cushings syndrome
consists of two phases.
1) Does the patients have Cushings syndrome?
2) If Cushings syndrome is present what is its
cause?

Cushings syndrome- diagnosis (2):

Does the patients have Cushings syndrome?
1) exclusion exogenous cause of Cushings syndrome by
the medical history,
2) high urine free-cortisol excretion rate,
3) low-dose dexametasone test
- 1 mg dexametasone orally between 11-12 p.m.,
- measure plasma cortisol level 8 a.m.
plasma cortisol < than 5 g/dl - normal supression,
> than 5 g/dl Cushings syndrome,
needs further study.
This test is sensitive but is not very specific mental and physical
stress may produce a false positive results

Cushings syndrome- diagnosis (3):

What is the cause of Cushings syndrome?
1) standard high-dose dexametasone test
The suppressibility of hypothalamic-pituitary-adrenal
axis is tested by the administration of dexamethasone
in high doses. Patients with Cushings disease behave as
though their feedback response to glucocoticoid is
intact but set a higher than normal level. They respond
to high but not to low doses of dexamethasone. Patients
with adrenal tumors and ectopic ACTH secretion
produce corticoid autonomously, without suppression
even by high doses of dexamethasone.

Cushings syndrome- diagnosis (4):

What is the cause of Cushings syndrome?
1) standard high-dose dexametasone test c.d.
- 8 mg (2 mg 4 times daily) dexametasone daily orally
during 2 days,
- measure plasma cortisol level, urinary free cortisol
and urinary 17-hydroxycorticosteroid exctretion rate,
before and in a second day of dexametazone
treatment.
healthy subjects suppression (decrease > 50 %),
Cushings disease - suppression (decrease > 50 %),
adrenal neoplasm no suppression,
ectopic ACTH syndrome no supression.

Cushings syndrome- diagnosis (5):

What is the cause of Cushings syndrome?

2) Plasma ACTH level

Cushings disease high normal or slightly elevated,
ectopic ACTH
markedly elevated,
adrenal neoplasm extremely low or undetectable.
3) Radiographic finding localize the primary
abnormality and confirm etiological diagnosis.
- skull X-ray (enlargement of sella turcica in case of
macroadenomas),
- MRI or computed tomography of pituitary,
- ultrasonography, MRI or computed tomography of
adrenal glands.

Cushings syndrome- diagnosis (6):

What is the cause of Cushings syndrome?

Petrosal sinus sampling : Pituitary or

ectopic?
Ratio Petrosal/peripheral
ACTH >2:1 if pituitary.
Lateralisation of
microadenoma : Localisation of microadenoma.
Ipsilateral ACTH release
of ACTH by adenoma

Pituitary not hypothalamic

via CRF: Both sides high ACTH if
CRH secreting tumour

Cavernous
Sinus
Inferior Petrosal
Sinus

Confluent
Pituitary
Veins
JUGULAR VEIN

 Adrenal glands physiology,

Adrenal cortex diseases,
Cushings syndrome
Mineralocorticoid excess
Adrenal insufficiency
Congenital adrenal hyperplasia

Adrenal medulla diseases,

Pheochromocytoma

P450 C21 hydroxylase

(microsomal)
11-hydroxylase
(mitochondrial)
CORTISOL

Androgens
17 hydroxylase
17,20 desmolase
does not occur in
zona glomerulosa

18 hydroxylase
18-OH steroid dehydrogenase
ALDOSTERONE

DHEA &
Androstendione
substrate for other
tissues

The renin-angiotensin-aldosterone system

ACTH

Serum K+

K+
excretion

BP

Renin "AI "AII "Aldosterone

Effective
ECF volume

Distal
nephron

H+
excretion
NaCl
reabsorption

Distal convoluted tubule cell

cytoplasmic mineralocorticoid receptor (MR)

Aldosterone
from blood
diffusion
into cell

CYTOPLASM
Mitochondrium

Tubular
lumen

homodimeric steroidreceptor complex

HRE
K+,H+
Na+
Apical
membrane

Interstitium

Nucleus

mRNA
Induced
gene
Permease
hypothesis

ATP
Metabolic
hypothesis

K+

K+

Pump
Aldosterone- Na+ pump
induced
hypothesis
+
Na+
proteins
Na
ADP + Pi
Na+
Na+ Na+ Na+
Basolateral
membrane

Mineralocorticoid Excess (1)

Primary hyperaldosteronism
(overproduction of aldosterone independent of its
normal chronic regulator Angiotensin 2)

Secondary hyperaldosteronism
(overproduction of aldosterone dependent of its
normal chronic regulator Angiotensin 2)

Primary hyperaldosteronism
Adenoma (50-90%)
Bilateral Adrenal
cortical Hyperplasia
(10%).
Sporadic or Familial
hyperaldosteronism
(Type FH2).
ACTH dependant
release
(dexamethasone
suppressible FH1).

Mineralocorticoid Excess (2)

Primary hyperaldosteronism
Diagnostic features:
1) High Aldosterone
2) Low Plasma Renin
3) High Aldosterone/Plasma Renin Ratio

Mineralocorticoid Excess (3)

Primary hyperaldosteronism:
Conn's syndrome (adrenal adenoma producing aldosterone)
- Conn's syndrome (50 - 90% of cases) is
hyperaldosteronism due to functional adenoma . The
normal feedback loops are intact so the renin is low. It
most commonly occurs from age 30-50 years and
presents as hypertension. It accounts for less than 1% of
hypertensive patients. In several of patients signs of renal
disease (50% develop proteinuria, 15% develop renal
failure).

Laboratory findings include low potassium and high

sodium serum concentration.

Conn's syndrome (adrenal adenoma producing aldosterone)

1.3 cm left adrenal adenoma in a patient with hypertension and

hypokalemia. Such adenomas are typically less than 2 cm in size and
yellow on cut surface.

Mineralocorticoid Excess (4)

Secondary hyperaldosteronism: Renal artery stenosis,
Renin secreting tumours,
Barters syndrome,
Diuretic and/or laxative abuse.

Diagnostic features:
1) High Aldosterone
2) High or Inappropriate Plasma Renin

Mineralocorticoid Excess (5)

Biochemical diagnosis
Primary hyperaldosteronism: Raised/Normal plasma aldosterone
concentration
Suppressed/low PRA
High plasma aldosterone concentration/
PRA ratio.

Secondary hyperaldosteronism: Raised plasma aldosterone concentration

Raised or normal (inappropriate) PRA.

Mineralocorticoid Excess (5)

Biochemical diagnosis

 Adrenal glands physiology,

Adrenal cortex diseases,
Cushings syndrome
Mineralocorticoid excess
Adrenal insufficiency
Congenital adrenal hyperplasia

Adrenal medulla diseases,

Pheochromocytoma

Primary adrenal insufficiency.

Stress

Hypothalamus

Pituitary

Adrenal glands

Diurnal rhythm

CRH

ACTH

Cortisol

MSH

Secondary adrenal insufficiency.

Stress

Hypothalamus

Diurnal rhythm

CRH

Pituitary

ACTH

Adrenal glands

Cortisol

Primary adrenal insufficiency (1):

- uncommon disorders, usually occured between ages 20
and 50
- female:male incidence ratio 2.6:1
- clinical symptoms are caused mainly by both cortisol
and aldosterone deficiencies
- clinical manifestations do not appear until at least 90%
of cortex has been compromised

Primary adrenal insufficiency (2):

causes:
- autoimmune (Addisons disease) (75%),
- tuberculosis (20%),
- others (5%); among them hemochromatosis, amyloidosis,
bilateral adrenal haemorrhage (in the WaterhouseFriederichsen syndrome or in patients during
anticoagulation), fungal and CMV infection in patients
with AIDS, metastatic malignancy, after bilateral
adrenadrelectomy, after aminoglutetymide treatment

A=
B=
C=

Addsions disease or long term corticosteroids

Normal
ACTH excess: Cushings disease or ectopic.
Idiopathic adrenal hyperplasia

Caseating granuloma of tuberculosis in the

adrenal gland.

Hemochromatosis in the adrenal gland.

Amyloidosis in the adrenal gland.

Primary adrenal insufficiency (3):

Symptoms of cortisol deficiency:
1) hyperpigmentation of skin - caused by MSH,
2) hypotension (often orthostatic) - caused by absence of
cortisols pressor effect on vasculature and decrease of
cardiac output,
3) anorexia, nausea, vomiting, weight loss,
4) hypoglycaemia - cortisol-induced gluconeogenesis,
5) mental symptoms lethargy and confusion,
6) intolerance to stress severe stress leads to exacerbation of
symptoms (patients can not to increase their steroid output
during the stress).

Primary
adrenal
insufficiency

Primary adrenal insufficiency

Primary adrenal insufficiency (3):

Symptoms of cortisol deficiency:
1) hyperpigmentation of skin - caused by MSH,
2) hypotension (often orthostatic) - caused by absence of
cortisols pressor effect on vasculature and decrease of
cardiac output,
3) weight loss, anorexia, nausea, vomiting, pain in the
abdomen
4) hypoglycaemia - cortisol-induced gluconeogenesis,
5) mental symptoms lethargy and confusion,
6) intolerance to stress severe stress leads to exacerbation of
symptoms.

Primary
adrenal
insufficiency

Primary adrenal insufficiency (4):

Symptoms of aldosterone deficiency:
1) sodium loss volume depletion, hypotension,

decrease of cardiac output, RBF with renal

insufficiency, weight loss,
2) potassium retention hyperkalemia and cardiac
arrhythmias. women loss of axillary and pubic hair

Primary adrenal insufficiency (5):

Symptoms of androgens deficiency in females:
1) women loss of axillary and pubic hair

Clinical Features of Primary Adrenal

Insufficiency
Gradual onset
Weakness & fatigue
Wt loss/anorexia
Hyperpigmentation
Hypotension / tachycardia
Hyponatremia
Hyperkalemia
Muscle, GI pain

>95%
100%
100%
92%
88%
88%
64%
56%

Primary adrenal insufficiency (6):

Diagnosis:
- Plasma cortisol, urinary free cortisol, urinary 17hydroxycorticosteroid are low (usually without circadian
rhythm).
- Plasma ACTH is high ( >200 N:20-100 ng/ml)
- Hyponatremia, hyperkalemia, hypoglycemia, chest X-ray
may revealed small heart.
- Short ACTH test: synacten (first 24 AA ACTH analog) 0.25mg i.v.
or i.m.. Cortisol is measured before injectionand after 30
minutes.
Normal response at least 7 g% increase in serum
cortisol concentration ans should reach 18 g%.
Lower response adrenal hypofunction

Aldosterone deficiency without glucocorticoid

deficiency:
Cause:
- deficient secretion of renin hyporeninemic
hypoaldosteronism (e.g. autonomic insufficiency, blocker therapy, injury of juxtoglomerular
apparatus),
- primary abnormality of zona glomerulosa
(autoimmune process, critically ill patients, ACEI
therapy, corticosterone methyloxidase deficiency).

Clinical features:
- usually asymptomatic,
- hyperkalemia.

Hyporeninic hypoaldosteronism
#Serum K+
K+
excretion

Renin " $ AI " $ AII " $Aldosterone

or N
BP

or N
Effective
ECF volume

Distal
H+
nephron excretion
or N
NaCl
reabsorption

Primary hypoaldosteronism
#Serum K+
K+
excretion
#Renin "#AI " #AII " Aldosterone

Distal
H+
nephron excretion

BP
Effective
ECF volume

NaCl
reabsorption

Secondary adrenal insufficiency.

Stress

Hypothalamus

Diurnal rhythm

CRH

Pituitary

ACTH

Adrenal glands

Cortisol

Secondary adrenal insufficiency (1):

Causes:
1) destructive lesions in the hypothalamic-pituitary axis,
2) isolated ACTH secretion defect,
3) prolonged suppression of pituitary-adrenal axis by
exogenous glucocorticoids.

Secondary adrenal insufficiency (2):

Clinical and diagnostic features:
Similar to those for primary glucocorticoid deficiency, but
with several important differences:
1) hyperpigmentation is absent (normal plasma MSH
concentration),
2) hyperkalemia and metabolic alkalosis did not occurred
(normal mineralocorticoid level),
3) clinical manifestations of hypogonadism and hypothyreosis
frequently occurred (in case of primary pituitary disease).

Secondary adrenal insufficiency (3):

Diagnosis:
Prolonged ACTH test:
synacten depot i.m. 0,5 mg twice daily during 4 days
Normal response three-five fold increase in urinary
cortisol, urinary 17-hydroxycorticosteroid excretion rate;
a 15-40 g/dl rise in serum cortisol level.
Primary adrenal insufficiency: lower response
Secondary adrenal insufficiency: normal but later than in
haelthy subjects response (lack of response during first
and second day, stepwise increase or normal response
during by the third or fourth day)

Clinical Features of Secondary Adrenal

Insufficiency
Gradual onset
Weakness & fatigue
Weight loss/anorexia
Pale
Hair loss
Anemia
Electrolytes usually normal

>95%
100%
100%
100%
<50%
<50%

Adrenal insufficiency treatment:

Glucocorticoid replacement is required in all patients

Daily dose: 37.5 mg cortisone or 30 mg hydrocortisone (2/3 of
dose in the morning)
Mineralocorticoid replacement is not required in all patients
Daily dose: Fludrocortison 0.05 0.2 mg in the morning
Stress, infection, surgery: dose of glucocorticoids should
be higher.
40-60 mg daily hydrocortisone during minor stress (e.g.
common cold or dental extraction)
100 mg daily hydrocortisone during moderate stress (e.g.
influenza or minor surgery)
300 mg or more daily hydrocortisone during major stress
(e.g. severe infection or major surgery)

Primary Acute Adrenocortical

Insufficiency
Occurs in a variety of clinical settings:
1) Addisonian crisis in patients with chronic
adrenal insufficiency who are subject to stress
2) Rapid withdrawal of steroids in patients on
therapy or failure to supplement patients on therapy
during acute stress
3) Massive adrenal hemorrhage

Adrenal crisis (Addisonian crisis):

Acute life-threating complication of Addisons disease in
which the manifestations of adrenal insufficiency are greatly
exaggerated. Adrenal crisis may occur in untreated
Addisons disease or in a treated patient following acute
stress if additional glucocorticoid replacement is not
provided.

Clinical features:
vascular collapse, shock (and as a consequence oliguria), low body
temperature in the initial phase and fever in the late phase,
vomiting, signs of dehydratation, abdominal pain
(pseudoperitonitis), altered mental status.
hypoglycemia, metabolic acidosis, hyperkalemia, hyponatremia
(in 90% of cases), plasma sodium/potassium ratio < 30

Adrenal crisis (Addisonian crisis) treatment:

NaCl and glucose i.v. infusion (up to 4 liters).
Hydrocortison i.v. 100 mg every 6 hours.

 Adrenal glands physiology,

Adrenal cortex diseases,
Cushings syndrome
Mineralocorticoid excess
Adrenal insufficiency
Congenital adrenal hyperplasia

Adrenal medulla diseases,

Pheochromocytoma

Congenital adrenal hyperplasia

Stress

Hypothalamus

Diurnal rhythm

CRH

Pituitary

ACTH

Adrenal glands

Cortisol

Androgens

Congenital adrenal hyperplasia (1):

Caused by a defect in one of the enzymes that are necessary
to synthesized cortisol (21-hydroxylase, 11-hydroxylase, 17hydroxylase deficiency, hydroxylase 3-steroid or 5,4
Isomerase deficiency). Cortisol deficiency stimulates ACTH
secretion which, causes hyperplasia adrenal cortex and
overproduction of ACTH dependent steroids (mainly
androgens).
Clinical manifestations depend mainly upon androgens
oversecretion (ambiguous genitalia or virilisation in
females, macrogenitosomia or precocious puberty in
males).

Congenital adrenal hyperplasia (2):

Diagnosis:
Low plasma cortisol and high plasma ACTH concentration
High blood testosterone concentration
Increase of steroid specific to the enzyme abnormality

Congenital adrenal hyperplasia (2):

21-hydroxylase deficiency
The most frequent syndrome (1:5000-1:15000 of newborn; 95% cases of
congenital adrenal hyperplasia ). High 17-OH progesterone plasma
concentration
11-hydroxylase deficiency
High 11-Deoxycorticosterone (DOC) and 11-Deoxycortisol plasma
concentration
17-hydroxylase deficiency
Low plasma cortisol, estrogens and androgens concentrations, high 11Deoxycorticosterone (DOC) (mineralocorticoid) plasma concentration.
hydroxylase 3-steroid or 5,4 Isomerase deficiency
Low plasma cortisol, estrogens and androgens concentrations, high 17-OH
pregnenolone and dehydroepiandrosterone (DHEA) plasma concentration

21-Hydroxylase Deficiency
Three distinct syndromes are known:
1) Classic, salt-wasting adrenogenitalism related to 21hydroxylase deficiency presenting at birth with
virilization in females; cryptorchidism and hypospadias in
males; salt wasting is due to concomitant aldosterone
deficiency
2) A simple virilizing variant with normal aldosterone
activity
3) A nonclassic variant with delayed onset of virilization
during late childhood or adolescence

Congenital adrenal hyperplasia (2):

21-hydroxylase deficiency
The most frequent syndrome (1:5000-1:15000 of newborn; 95% cases of
congenital adrenal hyperplasia ). High 17-OH progesterone plasma
concentration
11-hydroxylase deficiency
High 11-Deoxycorticosterone (DOC) and 11-Deoxycortisol plasma
concentration
17-hydroxylase deficiency
Low plasma cortisol, estrogens and androgens concentrations, high 11Deoxycorticosterone (DOC) (mineralocorticoid) plasma concentration.
hydroxylase 3-steroid or 5,4 Isomerase deficiency
Low plasma cortisol, estrogens and androgens concentrations, high 17-OH
pregnenolone and dehydroepiandrosterone (DHEA) plasma concentration.

Cholesterol

Review of congenital adrenal hyperplasia

syndromes caused by various defects in the
composite pathway of steroid hormone
biosynthesis .

StAR

salt loss/sexual infantilism

Cholesterol
Hypertension/sexual
infantilism

P-450scc ACTH
Pregnenolone

17-hydroxylase

17-OH pregnenolone

Dehydroepiandrosterone
(DHEA)

3-OHSD/5,4 Isomerase
salt loss + female: virilized; male: hypogonadal
Progesterone

17-hydroxylase

17-OH progesterone

salt loss/virilization

21-Hydroxylase
11-Deoxycorticosterone (DOC)
11-Hydroxylase

11-Deoxycortisol

hypertension/virilization

Corticosterone (ZF/ZR)
CORTICOSTERONE
CORTISOL
Cortisol

Aldosterone synthase
ALDOSTERONE

Aldosterone (ZG)

Androstenedione

initial salt loss

Testosterone
(made in peripheral
tissues by reduction of
androstenedione)

Congenital adrenal hyperplasia: 11- hydroxylase deficiency

prominent recession of the hairline characteristic of male baldness,

and the patient also has dark hair on the upper lip and acne.

Congenital adrenal hyperplasia (2):

21-hydroxylase deficiency
The most frequent syndrome (1:5000-1:15000 of newborn; 95% cases of
congenital adrenal hyperplasia ). High 17-OH progesterone plasma
concentration
11-hydroxylase deficiency
High 11-Deoxycorticosterone (DOC) and 11-Deoxycortisol plasma
concentration
17-hydroxylase deficiency
Low plasma cortisol, estrogens and androgens concentrations, high 11Deoxycorticosterone (DOC) (mineralocorticoid) plasma concentration.
hydroxylase 3-steroid or 5,4 Isomerase deficiency
Low plasma cortisol, estrogens and androgens concentrations, high 17-OH
pregnenolone and dehydroepiandrosterone (DHEA) plasma concentration.

Cholesterol

Review of congenital adrenal hyperplasia

syndromes caused by various defects in the
composite pathway of steroid hormone
biosynthesis .

StAR

salt loss/sexual infantilism

Cholesterol
Hypertension/sexual
infantilism

P-450scc ACTH
Pregnenolone

17-hydroxylase

17-OH pregnenolone

Dehydroepiandrosterone
(DHEA)

3-OHSD/5,4 Isomerase
salt loss + female: virilized; male: hypogonadal
Progesterone

17-hydroxylase

17-OH progesterone

salt loss/virilization

21-Hydroxylase
11-Deoxycorticosterone (DOC)
11-Hydroxylase

11-Deoxycortisol

hypertension/virilization

Corticosterone (ZF/ZR)
CORTICOSTERONE
CORTISOL
Cortisol

Aldosterone synthase
ALDOSTERONE

Aldosterone (ZG)

Androstenedione

initial salt loss

Testosterone
(made in peripheral
tissues by reduction of
androstenedione)

Congenital adrenal hyperplasia: 17- hydroxylase deficiency

Female with primary

amenorrhea,
disproportionately long
limbs relative to the trunk,
absent axillary and pubic
hair, infantile breast and
genitalia development, an
absent uterus, and an
incomplete vagina.

Cholesterol

Review of congenital adrenal hyperplasia

syndromes caused by various defects in the
composite pathway of steroid hormone
biosynthesis .

StAR

salt loss/sexual infantilism

Cholesterol
Hypertension/sexual
infantilism

P-450scc ACTH
Pregnenolone

17-hydroxylase

17-OH pregnenolone

Dehydroepiandrosterone
(DHEA)

3-OHSD/5,4 Isomerase
salt loss + female: virilized; male: hypogonadal
Progesterone

17-hydroxylase

17-OH progesterone

salt loss/virilization

21-Hydroxylase
11-Deoxycorticosterone (DOC)
11-Hydroxylase

11-Deoxycortisol

hypertension/virilization

Corticosterone (ZF/ZR)
CORTICOSTERONE
CORTISOL
Cortisol

Aldosterone synthase
ALDOSTERONE

Aldosterone (ZG)

Androstenedione

initial salt loss

Testosterone
(made in peripheral
tissues by reduction of
androstenedione)

Summary of Laboratory Findings

Cushing's
Syndrome

Cushing's
Disease

Conn's
Syndrome

Addison's
Disease

Na

high

high

high

low

low

low

low

high

glucose

high

high

normal

low

cortisol

high

high

normal

low

ACTH

low

high

normal

usually
high

 Adrenal glands physiology,

Adrenal cortex diseases,
Cushings syndrome
Mineralocorticoid excess
Adrenal insufficiency
Congenital adrenal hyperplasia

Adrenal medulla diseases,

Pheochromocytoma

Major hormones of adrenal

medulla:
Catecholamines:
norepinephrine,
epinephrine,
dopamine.

Pheochromocytoma:
- Uncommon but important

tumour of chromaffin cells.

- Occurs most commonly in
adrenal gland (90%), but can
be found in any sympathetic
ganglion. Bilateral or multiple
tumours in 5-10%. 10% of
pheochromocytoma are
malignant.

Pheochromocytoma

Note the grey-tan colour of the tumour compared to the yellow

cortex stretched around it and a small remnant of remaining adrenal
at the lower right. This patient had episodic hypertension.

Pheochromocytoma

chromaffin reaction
(dichromate fixation)

Pheochromocytoma

Pheochromocytoma:
Diagnosis:
1) Clinical manifestations depend upon catecholamines
oversecretion. Diagnosis is suggested by paroxysmal
nature of symptoms.
2) High urinary vanillylmandelic acid (VMA),
metanephrine, normetanephrine and free catecholamines
excretion rate. Hyperglycaemia.
3) Anatomic localization: ultrasonography, MRI or
computed tomography of adrenal glands, isotope scan
technique with 131I iodobenzylguanidine.

Pheochromocytoma

- noradrenaline (NA) , adrenaline (A),

- methoxyamines: normetanephrine (NMN) and metanephrine (MN).
- VMA (vanilmandelic acid)

Pheochromocytoma:
Diagnosis:
1) Clinical manifestations depend upon catecholamines
oversecretion. Diagnosis is suggested by paroxysmal
nature of symptoms.
2) High urinary vanillylmandelic acid (VMA),
metanephrine, normetanephrine and free catecholamines
excretion rate. Hyperglycaemia.
3) Anatomic localization: ultrasonography, MRI or
computed tomography of adrenal glands, isotope scan
technique with 131I iodobenzylguanidine.

Pheochromocytoma:

computed tomography of
adrenal glands,

MRI of
adrenal glands,

Pheochromocytoma:

isotope scan technique with 131I iodobenzylguanidine.