Transcript ADRENAL INSUFFICIENCY BY DR UMENZEKWE CHUKWUDI

ADRENAL INSUFFICIENCY
BY
DR UMENZEKWE CHUKWUDI
OUTLINE
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INTRODUCTION
ANATOMY AND PHYSIOLOGY
EPIDEMIOLOGY
AETIOLOGY
TYPES OF ADRENAL INSUFFIENCY
TREATMENT
CONCLUSION
Intro cont
• They are lobulated retroperitoneal glands
• Greyish yellow in color, soft, pyramidal in
shape
• Cortex is 90% of the gland, made of 3 layers Z.
glomerulosa, Z. fasciculata and Z. reticularis.
HORMONES OF ADRENAL CORTEX
• ZONA GLOMERULOSA……ALDOSTERONE,11
DEOXYCORTICOSTERONE.
• ZONA FASICULATA -------CORTISOL
• ZONA RETICULARIS………ANDROGENS.
CORTISOL
• A glucocorticoid
• Frequently referred to as the ‘stress hormone’
• Released in response to physiological or
psychological stress: exercise, illness, injury,
starvation, extreme dehydration, electrolyte
imbalance, emotional stress, surgery, etc.
FXNS OF CORTISOL
• Critical actions on many physiologic systems,
including:
• Maintains cardiovascular function
• Provides blood pressure regulation
• Enables carbohydrate metabolism
• acts on the liver to maintain normal glucose
levels
• Immune function actions
• Reduces inflammation
• Suppresses immune system
FXNS OF CORTISOL CONT
• When cortisol is not produced or released by
the adrenal glands, humans are unable to
respond appropriately to physiologic stressors
• Rapid deterioration resulting in organ damage
and shock/coma/death can occur, especially in
children
ALDOSTERONE
• A mineralocorticoid
• Regulates body fluid by influencing sodium
balance
• The human body requires certain amounts of
sodium and water in order to maintain normal
metabolism of fats, carbohydrates and
proteins
ALDOSTERONE CONT
• Water/sodium balance is maintained by
aldosterone
• Without aldosterone, significant water and
sodium imbalances can result in organ
failure/death
ALDOSTERONE CONT
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Aldosteron secretion is stimulated by;
-Renin-angiotensin system.
-ACTH.
-Hyperkalemia.
-Hypovolemia.
-Hypotension.
-congestive heart failure.
-Surgery.
PHYSIOLOGY OF THE GLAND
ADRENAL INSUFFICIENCY
• Adrenal glands produce inadequate amount of
steroid hormones,primarily cortisol.
• Also there is inadequacy of aldosterone that
regulate Na retention,potasium secretion and
water retention.
TYPES OF ADRENAL INSUFFICIENCY
• Basicaly three types;
• 1’ Primary adrenal insufficiency;
-idiopathic or of unknown cause.
-80% due to autoimmune disease(addisons or
autoimmune adrenalitis.
-Congenital adrenal hyperplasia or adenoma of
adrenal gland.
2; 2ndry adrenal insufficiency (pituiitory)
• Examples;exogenous steroid use,
- pituitary adenoma/microadenoma
----Sheehans syndrom;
3 Tertiary adrenal insufficiency is due to
hypothalamic disease.
CLINICAL PRESENTATION
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HYPOGLYCEMIA
DEHYDRATION
WT LOSS
DISORIENTATION
WKNESS,TIREDNESS,LOW BP,ORTHOSTATI
HYPOTENSION,CVS COLLAPSE,MUSCLE
ACHES,NAUSEA,VOMITING,DIARHOEA
• TANNING of the skin that may be patchy or
generalised.seen commonly on the hands and buccal
mucosa.
• GOITER AND VERTILIGO MAY BE PRESENT.
C/P CONT
• CHRONIC ADRENAL INSUFFICIENCY
• ACUTE ADRENAL INSUFFICIENCY PPTED BY;
-Waterhouse-friderickson syndrom.
-Sudden withdrawal of long term steroid
therapy
Stress;surgery,infection,emotional sress
ADDISONS DISEASE
• Thomas Addison first described the clinical presentation of
primary adrenocortical insufficiency (Addison disease) in
1855 in his classic paper, On the Constitutional and Local
Effects of Disease of the Supra-Renal Capsules.
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Pathophysiology of addisons dx
• Addison disease is adrenocortical insufficiency
due to the destruction or dysfunction of the
entire adrenal cortex. It affects glucocorticoid
and mineralocorticoid function. The onset of
disease usually occurs when 90% or more of
both adrenal cortices are dysfunctional or
destroyed.
EPIDEMIOLOGY OF ADDISONS DX
• Age;The most common age at presentation in
adults is 30-50 years.
• Sex;Idiopathic autoimmune Addison disease
tends to be more common in females and
children.
• Incidence;3-4/million/year.
• Prevalence;40-60/million/year.
Aetiology cont
• 1- idiopathic autoimmune adrenocortical insufficiency.
• 2- Chronic granulomatous diseases; TB, sarcoidosis, histoplasmosis.
• 3- Hematologic malignancies; as Hodgkin
• and non-Hodgkin lymphoma and leukemia.
• Haemorhage/infarctiion
-meningococcal septisaemia
-venography
Aetiology cont
• 4- Metastatic malignant disease; as metastatic
cancer of the lung, breast, colon or renal cell
carcinoma.
• 5-Infiltrative metabolic disorders; Amyloidosis
and hemochromatosis.
• Schilders dx(adrenal leucodystrophy)
. AIDS.
• Surgical removal
• Type 2 polyglandular syndrom
CF OF ADDISONS DISEASE
• C\P
• Patients usually present with features of both glucocorticoid and
mineralocorticoid deficiency. The predominant symptoms vary
depending on the duration of disease.
• -Hyperpigmentation of the skin and mucous membranes due to
high ACTH.
• - vitiligo, which most often is seen in idiopathic autoimmune
Addison disease.
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• -clinical manifestations due to aldosteron
deficiency; hyponatremia, hypovolemia,
hypotension, hyperkalemia and metabolic
acidosis
• -clinical manifestations due to cortisol
deficiency; weakness, fatigue, hypoglycemia,
hypotension, and weight loss.
CF CONT
• Prominent gastrointestinal symptoms may
include nausea, vomiting, and occasional
diarrhea.
• - acute adrenal crisis;a life threatening
emergency.may be pri or sec.presents basicaly
as hypotension resistant to catecholamine and
IVF resuscitation.
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INVESTIGATIONS
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Laboratory Studies;
Single cortisol measurement;100nmol/l is suggestive but when >550nmol/l makes
the diagnosis unlikely.
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-Short ACTH(tetracosactide) stimulation test; In patients with Addison disease,
both cortisol and aldosterone show minimal or no change in response to ACTH.
Am plasma ACTH levels;>80ng/l with low/lownormal cortisol>pri
hypoaldosteronism.
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-hyponatremia
Hyperkalemia
metabolic acidosis
INVEST CONT
• -elevated (BUN) and creatinine due to the
hypovolemia with decreased glomerular
filtration rate.
• -Hypoglycemia
• -adrenal autoantibodies may be present
• Plasma renin levels >very high due to low
aldosterone
TREATMENT
• ACUTE;
• IV HYDROCORT 100mg(bolus),then200mg in
infusion over 24hours.
• Correct volume deficit and hypoglycaemia.
ADDISON DISEASE AND PREGNANCY
• Addison Disease and Pregnancy
• -Before glucocorticoid replacement therapy
became available, pregnancy in patients with
adrenal insufficiency was associated with a
maternal mortality rate of 35-45%.
• -The usual glucocorticoid and mineralocorticoid
replacement dosages are continued throughout
pregnancy.
ADDISONS AND PREGNANCY CONTD
• During labor, adequate saline hydration and
25 mg of intravenous cortisol (ie,
hydrocortisone sodium succinate) should be
administered every 6 hours.
• At the time of delivery or if the labor is
prolonged, high-dose parenteral
hydrocortisone should be administered (100
mg q6h or as a continuous infusion).
ADDISONS AND PREGNANCY CONTD
• After delivery, the dosage can be quickly
tapered to a maintenance dose in 3 days.
CONGENITAL ADRENAL HYPERPLASIA
• An autosomal recessive deficiency of enzyme in
the cortisol synthetic pathway.
• 5 major Enzymes deficiency are clinically
important
• 21-Hydroxylase
• 11-b-Hydroxylase
• 17-a-Hydroxylase
• 3-b-Hsteroid hydrogenese
• 20,22 Desmolase deficiency
Result of a 21-Hydroxylase Deficiency
21 HYDROXYLASE DEFICIENCY
• Most common type, accounts for >80% of
cases.
• Incidence is 1:5000 to 1:15000 live birth.
• Gene is located on the short arm of
chromosome 6 near the C4 locus in close
association with HLA genes.
• Heterozygous carriers can be detected by
ACTH stimulation test.
21 OHLASE DEF CONT
• It is characterized by reduced production of
cortisol and aldosterone and increased
production of progesterone;
17-OH-progesterone, and sex steroids.
• The urinary steroid metabolites
(17-ketosteroids and pregnanetriol) are
elevated above normal levels.
21 OHLASE DEF CONT
• 2 forms, classic early virilization type with or
without salt-losing crisis and non-classic type
with late-onset virilization.
• Male babies with non salt-losing non-classic
type remains asymptomatic till late childhood
when they may show signs of sexual precocity.
11-b-Hydroxylase Deficiency
• Accounts for 5-10% of cases of CAH.
• Gene is located on the long arm of chromosome 8.
• It is characterized by low plasma renin activity &
elevation of serum 11-Deoxycortisol and 11deoxycorticosterone.
• Because of the strong mineralocorticoid activity of
deoxycorticosterone, the condition is characterized by
salt retention, hypertension & hypokalemic alkalosis.
• The elevated plasma androgens may cause virilization
of the female fetus.
17-a-Hydroxylase deficiency
• Genetic defect is on chromosome 10.
• Presents with similar features of those of 11Hydroxylase deficiency except that Androgens
are low, so no virilization in girls & genitalia is
ambiguous in boys.
3-b-hydroxysteroid dehydrogenase
deficiency
• This is a very rare disorder that results in
accumulation of DHEA, which is converted to
testosterone in peripheral tissues.
• It can cause virilization of female fetus and
leads to ambiguous genitalia in the newborn.
C/F
• The clinical phenotype depends upon the nature
and severity of the enzyme deficiency.
• Approximately 50% of patients with classic
congenital adrenal hyperplasia due to 21hydroxylase (CYP21) deficiency have salt wasting
due to inadequate aldosterone synthesis.
• Girls are usually recognized at birth because of
ambiguous genitalia.
GIRLS WITH CAH
• Have ambiguous genitalia at birth:
• complete fusion of the labioscrotal folds and a
phallic urethra. clitoromegaly and partial
fusion of the labioscrotal folds
• In less severe forms, genitalia is normal at
birth. Precocious pubic hair & clitoromegaly
and excess facial or body hair appear later in
childhood, often accompanied by tall stature.
BOYS WITH CAH
• Are unrecognized at birth because their genitalia are
normal.
• They are not diagnosed until later, often with a salt wasting
crisis resulting in dehydration, hypotension, hyponatremia
and hyperkalemia or later in childhood with early pubic hair
& phallic enlargement accompanied by accelerated linear
growth and advancement of skeletal maturation.
• High blood pressure & hypokalemia may occur in those
with 11-b-hydroxylase deficiency and 17-a-hydroxylase
deficiency due to the accumulation of the
mineralocorticoid desoxycorticosterone
INVESTIGATION
• BASAL ACTH LEVELS ARE RAISED.
• 17-HYDROXYPROGESTERONE LEVELS ARE
RAISED.
• URINARY PREGNANTRIOL EXCRETION IS
INCREASED.
• ALDOSTERONE LEVELS ARE RAISED.
IMAGING STUDIES
• A pelvic ultrasound: in the infant with ambiguous
genitalia to demonstrate the presence or absence
of a uterus or associated renal anomalies
• A urogenitogram is often helpful to define the
anatomy of the internal genitalia.
• A CT scan of the adrenal gland to R/O bilateral
adrenal hemorrhage in the patient with signs of
acute adrenal failure
• A bone age study is useful in the evaluation of the
child who develops precocious pubic hair,
clitoromegaly, or accelerated linear growth.
TREATMENT PRINCIPLE
• Treatment is life-long
• Treatment goals are:
• to maintain growth velocity & skeletal
maturation.
• to normalize electrolytes & hormone levels using
the smallest dose of glucocorticoids that will
suppress the ACTH to normal. Mineralocorticoid
replacement may be needed to sustain normal
electrolyte homeostasis.
ACUTE MEDICAL MGT
• Fluid therapy in babies with salt losing crisis
0.9% sodium chloride 20 ml/kg as IV bolus,
followed by a continuous IV infusion of 0.9%
or 0.45% saline 3200 ml/m2/day.
• If the patient is hypoglycemic, 2-4 ml of 10%
dextrose will correct the hypoglycemia.
• Patients with 11-b-hydroxylase and 17-alphahydroxylase deficiency, may be hypokalemic
and require potassium.
LONG TERM THERAPY
• Glucocorticoids Replacement
• Hydrocortisone 10-15 mg/m2/day divided in 3
oral doses. Dose should doubled during crisis &
stressful conditions. The goals of therapy are:
• To replace the body's requirement under normal
conditions and during stress.
• To suppress ACTH secretion, which drives the
adrenal gland to overproduce adrenal androgens
in virilizing forms of congenital adrenal
hyperplasia.
LONG TERM THERAPY CONT
• Mineralocorticoids Treatment
• Fludrocortisone acetate 0.05-0.2 mg once
daily orally is indicated for patients who have
salt-wasting forms of CAH to replace the
aldosterone that is insufficiently produced by
the adrenal cortex. It will restore the sodiumpotassium balance.
SURGICAL MGT
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• Infants with CAH may require surgical
evaluation and, if needed, corrective surgery.
• Traditional approach is clitroplasty early in life,
followed by vaginoplasty after puberty.
• Some female infants with adrenal hyperplasia
are only mildly virilized and may not require
corrective surgery if they receive adequate
medical therapy to prevent further virilization.
PATIENT EDUCATION
• Educate the caretakers and patients about the
nature of the disease.
• Patients & parents must understand the need
for additional glucocorticoids in times of
illness and stress in order to avoid an adrenal
crisis which may be life-threatening.
PROGNOSIS
• Is good and complications like short stature,
sexual precocity & metabolic effects are not
seen with early adequate therapy.
• However, children with CAH are at risk of
developing mesodermal tumours e.g.
osteogenic sarcoma, pulmonary liposarcoma,
uterine leiomyomata and brain tumours.
PROGNOSIS 2
• Late diagnosis & inadequate therapy may
cause:
• Death of newborns with salt-losing types & if
patients are not provided with stress doses of
glucocorticoid in times of illness, trauma, or
surgery.
• Psychological problems in girls with
ambiguous genitalia.
• Short stature and infertility.