adrenal The gland
Abdulmoein E Al-Agha; MBBS,DCH,CABP,MRCP(UK)
Pediatric Endocrinologist
Adrenal Gland
Adrenal Cortex
Zona Glomerulosa
mineralocorticoid production,
aldosterone
Zona Fasciculata
glucocorticoid production, cortisol
Zona Reticularis
androgen production, including
testosterone
Medulla
catecholamines epinephrine and
norepinephrine
Regulation Cortisol
Regulation of
adrenal gland
secretion
ACTH
Cortisol
Cortisol
Aldosterone
Mineralocorticoid
Regulates concentration of Na+ and K+.
Kidney conserves Na+.
Kidney excretes K+.
Responds to changes in composition of
plasma.
Linked to renin-angiotensin system of
kidney
Aldosterone Functions
Func tio ns o fth e
a ld o s te ro ne :
ANP
escape phenomenon
Plasma
Tubular reabsorption of Na+
Tubular secretion of K+ or H+
Na+
(Kaliuresis)
K+
Hypokalemia & muscle paralysis
Hyperkalemia & cardiac toxicity
Increase tubular H+ secretion
alkalosis
Circulatory function
absence of aldosterone secretion
EC F volume
Blood pressure
Control of Aldosterone
ACTH
Low Blood Pressure, Low Na+.
Juxtaglomerula cells release renin.
Renin converts angiotensinogen to
angiotensin I.
Angiotensin I to angiotensin II by ACE.
Angiotensin II stimulates adrenal gland to
release aldosterone.
Aldosterone acts on kidney.
Disease States
DiseaseStates
Addison's disease: Affects about 1 in 100,000
people; caused by adrenal in-sufficiency (90%);
typical by auto-immune disorders; both cortisol and
aldostertone hormones are lacking.
Cushing's disease: Affects about 10 to 15 million
people / yr; caused by adrenal hyper-activity
(cortisol); typical because of tumor growth exposure
to prednisone for asthma, rheumatoid arthritis,
lupus or other inflammatory diseases
Conn's syndrome: May affect 15% of patients with
high blood pressure; caused by hyper production of
aldosterone; inability of adrenal cortex to carry out
17 -hydroxylation; hypertension, loss of potassium
in the urine, muscle weakness and passing of large
volumes of urine (polyuria)
Congenital Adrenal Hyperplasia
The first case was described in 1865
Family of inherited disorders of adrenal
steroidogenesis
Each disorder results from a deficiency of one of
several enzymes necessary for steroid synthesis
Autosomal Recessive (M=F)
21-OH is the commonest form
Gene CYP21 on Chromosome 6
Neonatal screening by filter paper on 3rd day of
life (17 OHP)
Steroid biosynthetic enzymes
The pathway from cholesterol to cortisol,
aldosterone and adrenal androgens requires
the action of five cytochrome P450 enzymes
and one dehydrogenase enzyme as following:
1) Cholesterol side chain cleavage=scc (20,22
desmolase)
2) 3-Hydoxysteroid dehydrogenase
Steroid biosynthetic enzymes
3) 17 hydroxylase and 17,20 lyase
4) 21-Hydroxylase
5) 11-Hydroxylase
6) Aldosterone synthetase (11,18
hydroxylase & 18 oxidase)
Congenital Adrenal Hyperplasia
CAH due to 21-Hydroxylase Deficiency
9095% of CAH cases are caused by 21- OHD
Females affected with severe, classic 21- OHD
are exposed to excess androgens prenatally and
are born with virilized external genitalia
First described in the mid -19th century
A more thorough understanding of this disease
was not forthcoming until the mid -20th century,
when the recessive nature of the genetic trait
and identification of hormonal abnormalities
were recognised
Presentations of CAH
Ambiguous genitalia
FTT
Dehydration
Shock
Salt-loss presentations with electrolytes
imbalance
Hyponatremia
Hyperkalaemia
Hypoglycemia
Hyperpigementations
Is it a boy or a girl ?
Is it a boy or a girl ?
Non-Classical CAH
Presentations
Childhood
Pubarche and advanced growth
Adolescent girls
Oligo- Amenorrhoea, acne, hirsutism,
androgenic alopaecia
Adolescent boys
early beard growth, acne and early growth
spurt
Adult
Infertility
Non-Classical CAH
Diagnosis
A review of a patient's medical history
Thorough clinical examination (B.P)
Serum electrolytes & glucose
Low Na & high K
Fasting hypoglycemia
Elevated serum urea due to associated dehydration
Elevated plasma Renin & ACTH levels
Low Cortisol
High 17 OHP
High androgens especially testosterone level
Low Aldosterone ( in salt losing types only)
Urinary steroid profile
Treatment
Acute Adrenal Insufficiency
Chronic Adrenal Insufficiency
Management
Hydrocortisone 10-20 mg/m2/day divided into three
doses
In and infancy early childhood, sodium replacement
is required
Fludrocortisone 0.05 - 0.2 mg/day
Monitor growth, signs of androgen excess, pubertal
development and blood pressure
During adrenal crisis intravenous hydrocortisone
therapy 6 hourly with hydration with normal saline
and dextrose
During fever or sickness 2-3 fold increment in
hydrocortisone dose
In vomiting or diarrhea, parental therapy is indicated
Prenatal diagnosis
21-Hydroxylase deficiency
By 8-11 weeks gestation
Amniotic fluid for 17-OHP
Karyotype
CVS for genotype
DNA mutation analysis on chromosome 6
Primary acquired adrenal insufficiency
Autoimmune
80%
Drugs
Infection
Hemorrhage
Metastases
Addisons disease
Described by Dr Thomas Addison in 1849
Rare endocrine disorder
incidence 1 in 100,000
Autoimmune destruction of adrenal gland
TB was the commonest pathology in 70-90%
Occurs in all age groups
Males and females are equally affected
Adrenal insufficiency occurs when 90 % of the
adrenal cortex has been destroyed
Adrenal Insufficiency:
Clinical Manifestations
Clinical Features
Fatigue
Generalized Weakness
Anorexia
Weight Loss
Diffuse Myalgia & Arthralgia
Fasting hypoglycemia
Nausea, vomiting & diarrhea
Fasting hypoglycemia
Hyperpigmentation
Hypotension Shock Death
Clinical Features
Addisonian crisis
Sudden penetrating pain in the lower back,
abdomen, or legs
Severe vomiting and diarrhoea followed by
dehydration
Low blood pressure and shock
Hypoglycemia
Loss of consciousness
Fatal, if left untreated
Biochemical features
Low Na & high K with metabolic acidosis
Elevated serum urea due to associated
dehydration
Fasting hypoglycemia
Elevated plasma Renin & ACTH levels
Low serum Cortisol & Aldosterone level
Low adrenal androgen including 17hydroxyprogestrone
Adrenal autoantibodies are positive
Highest Cortisol Concentration at 8:00 am
ACTH Stimulation Test
This is the most specific test for diagnosing
Addison's disease
Short ACTH test, Cortisol measurement 30 and
60 minutes after an intravenous ACTH injection
"long" ACTH stimulation test, synthetic ACTH is
given over 48- 72-hour period, and blood and
urine cortisol are measured the day before and
during the 2 to 3 days of the test
Primary Adrenal Insufficiency
Summary:
Hyperpigmentation
Dehydration
Hypotension
Hyperkalemia
Hyponatremia
Hypoglycemia
Abnormalitiesofadrenocorticalsecretion
Hyp o a d re n a lis m Ad d is o n s Dis e a s e
Ad d is o ns C ris is
Pigmentatio
n
Secretion of MSH
along with ACTH
H yp e rp ig m e n ta tio n
A Color Atlas of Endocrinology p97
H yp e rp ig m e n ta tio n
A Color Atlas of Endocrinology p91
H yp e rp ig m e n ta tio n
A Color Atlas of Endocrinology p97
Secondary Adrenal Insufficiency:
Causes
Exogenous Corticosteroids
Isolated ACTH Deficiency
Isolated CRH Deficiency
Lesions of the Hypothalamus or Pituitary
Gland (Tumor, Infection, Granuloma)
Postpartum (Sheehan Syndrome)
Steroid Preparations
Steroid
Steroid
Half Life
Potency
Hydrocortisone
Cortisone
Prednisolone
Prednisone
Dexamethasone
Glucocorticoid Mineralocorticoid
(minutes)
Potency
90
30
230
60
1.0
0.8
4.0
3.5-4.0
1.0
0.8
0.8
0.5
280
25.0-30.0
0.0
Primary aldosteronism
Primary aldosteronism
Cause of Hyperaldosteronism
Primary aldosteronism (Conn's Syndrome)
-Aldosteron-producing adenoma : Conns disease
-Idiopathic bilateral adernal hyperplasia
-Adrenal carcinoma
65-70%
30%
< 1%
Symptoms and Signs
Hypersecretion of aldosterone may result in:
Hypernatremia
Hyperchlorhydria
Hypervolemia
Hypokalemic alkalosis manifested by:
episodic weakness
Paresthesias
transient paralysis
tetany
Diastolic hypertension with headache
Hypokalemic nephropathy with polyuria &
polydipsia
Signs, Symptoms, and Laboratory Data
in Primary Hyperaldosteronism
Summary slide
Hypertension
Headache
Weakness/ Fatigue
Paresthesia
Muscle Cramps
Polyuria/ Polydepsia
Arrhythmias
Hypokalemia
No Other Cause For
Hypertension Or
Hypokalemia
Metabolic Alkalosis
Hyperaldosteronism
Hyporeninemia
Aldosterone / Renin Ratio
Normal & Patients With Essential
Hypertension < 20
Primary Aldosteronism > 30
> 90% Sensitivity & Specificity
Overproduction of aldosterone
treatment
surgical for adenoma
medical for hyperplasia with sprionolactone
Aldosterone-producing
adenoma
Tx : Unilateral adrenalectomy