3. Overview of Adrenal Glands
• The adrenal glands (suprarenal glands) are paired endocrine glands
situated over the medial aspect of the upper poles of each kidney. They
secrete steroid and catecholamine hormones directly into the blood.
• The adrenal cortex produces 3 main types of steroid hormones namely
1. Mineralocorticoids- (such as aldosterone)-help in the regulation of blood
pressure and electrolyte balance.
2. The glucocorticoids cortisol and cortisone-help in regulation of
metabolism and immune system suppression.
3. The androgens that are converted to fully functional sex hormones in
the gonads and other target organs]
The Chromaffin cells of the medulla produce Catecholamine namely
adrenaline and noradrenaline which produce a Rapid response throughout
the body in stress situations. The adrenal medulla is driven by
the sympathetic nervous system.
4. Adrenal Hormones related
disorders
CORTICOSTEROID OVERPRODUCTION
Cushing's syndrome- is the manifestation of glucocorticoid excess.
• It can be the result of a prolonged treatment with glucocorticoids or
be caused by an underlying disease which produces alterations in
the production of cortisol.
Primary aldosteronism
Results when the zona glomerulosa produces
excess aldosterone.
• Causes for this condition are bilateral hyperplasia (excessive tissue
growth) of the glands, or aldosterone-producing adenomas (a
condition called Conn’s Syndrome). Primary aldosteronism produces
hypertension and electrolyte imbalance, increasing
potassium depletion and sodium retention.
5. Adrenal Hormonesrelated disorders
.ADRENAL INSUFFICIENCY
• Diseases are classified as primary adrenal insufficiency (including Addison’s Disease and
genetic causes) directly affect the adrenal cortex. If a problem that affects the HPA axis arises
outside the gland, it is a secondary adrenal insufficiency.
Addison's disease
• Addison's disease refers to primary hypoadrenalism, which is a deficiency in
glucocorticoid and mineralocorticoid production by the adrenal gland
Congenital adrenal hyperplasia is a congenital disease in which mutations of
enzymes that produce steroid hormones result in a glucocorticoid deficiency and
malfunction of the negative feedback loop of the HPAaxis. In the HPAaxis, cortisol (a
glucocorticoid) inhibits the release of CRH and ACTH, hormones that in turn stimulate
corticosteroid synthesis. As cortisol cannot be synthesized, these hormones are
released in high quantities and stimulate production of other adrenal steroids instead.
The most common form of congenital adrenal hyperplasia is due to 21-
Hydroxylase deficiency. 21-hydroxylase is necessary for production of both
mineralocorticoids and glucocorticoids, but not androgens. Therefore, ACTH
stimulation of the adrenal cortex induces the release of excessive amounts of adrenal
androgens, which can lead to the development of ambiguous genitalia and secondary
sex characteristics.
6. CUSHINGSYNDROME
It’s a constellation of symptoms associated with cortisol excess
(glucocorticoid). Cushing disease is caused by a pituitary gland tumor (usually
benign) that over-secretes the hormone ACTH, thus overstimulating the
adrenal glands' cortisol production. Cushing syndrome refers to the signs and
symptoms associated with excess cortisol in the body, regardless of the cause.
7.
8. Diagnosisof Cushing’sSyndrome
• Obtain a careful history to exclude exogenous glucocorticoid use.
• Tests to obtain the diagnosis are:
• Urine free cortisol (UFC) (at least two measurements) - 24-hr urine sample
• Late-night salivary cortisol (two measurements)- Cortisol levels in blood are
normally elevated at 8 A.M. and decrease to less than 50% by midnight
except in infants and young children in whom a diurnal rhythm is not
always established. In patients with Cushing syndrome this circadian
rhythm is lost, and cortisol levels at midnight and 8 A.M. are usually
comparable
• Serum ACTH level ,FBC
• Tests to diagnose –Hyperglycemia, Hyperlipidemia ,• Hypokalemia,
Metabolic alkalosis
• U/E – low K
• DST( Dexamethasone suppression test) Dexamethasone is an exogenous
steroid that provides negative feedback to the pituitary to suppress the
secretion of ACTH. Dexamethasone binds to glucocorticoid receptors in the
pituitary gland resulting in regulatory modulation. The test is given at low
(usually 1–2 mg) and high (8 mg) doses of dexamethasone, and the levels
of cortisol are measured to obtain the results.
10. Addison’s Disease
• Addison's disease is serious chronic disease, caused
by partial or absolute abnormality of hormonal
function of the adrenal cortex .
• Arises when cortisol levels are not sufficient to meet
the needs of the body.
• Causes
• Autoimmune: - Isolated autoimmune adrenalitis (30- 40%)
• Polyglandular syndrome 1 &2 (60- 70%)
• Infection:TB, HIV, CMV, cryptococcosis, histoplasmosis,
coccidioidomycosis
• AIDS
• Metastases
• Bilateral adrenalectomy
11.
12. Diagnosis & Management
DIAGNOSIS
• In the blood analysis:
lymphocytosis, eosinophilia,
erythrocyte sedimentation rate is
decreased, Hypoglycemia
• The electrolyte: hyponatremia,
hypochloremia, hyperkaliemia
• Baseline Cortisol and ACTH levels
should be obtained in the early
morning The content of ACTH is
increased; The content of cortisol
is decreased
• Narrow cardiac silhouette on
CXR, Low voltage EKG
MEDICAL MANAGEMENT
• Glucocorticoid therapy-
Hydrocortisone therapy
• Mineralocorticoid
replacement-fludrocortisone
• Adrenal androgen
replacement -in patients with
lack of energy, and in women
with loss of libido.
13. Addisonian Crisis
Clinical Manifestations
• Severely low blood pressure
(shock)
• Hyperkalemia
• Hyponatremia
• Hypoglycemia
• Hypercalcemia
• Unexplained fever, diarrhea,
vomiting
• Coma and death
• Precipitated by infection,
surgery or intercurrent disease
Management of Addisonian Crisis
• It is a medical emergency
• IV fluid (normal saline 1 L/h with
continuous cardiac monitoring and
10% dextrose)
• Hydrocortisone 100 mg bolus
followed by 100–200 mg
hydrocortisone over 24 h infusion or
i.v doses until GI symptoms improve
then start oral therapy
• Mineralocorticoid replacement can
be initiated once the daily
hydrocortisone dose has been
reduced to <50 mg
• Treat precipitating cause
14. Adrenal tumor
• An adrenal tumor or adrenal massis any benign or malignant
neoplasms of the adrenal gland, with a usual tendency to
overproduce endocrine hormones.
• When adrenal gland tumor produce too much of hormone it is
called a “functioning tumor” and when it does not produce
hormones is called a “nonfunctioning tumor.”
Types of Adrenal Tumors
Incidentalomas
•Is an adrenal tumor found by
coincidence without clinical
symptoms or suspicion.
15. Types of adrenal gland tumors-
Tumors of the adrenal cortex
• Adrenocortical adenoma/Benign adenomas
• are encapsulated, well-circumscribed, solitary tumors with solid,
homogeneous yellow-cut surface .
• are relatively small, usually less than 2 inches in diameter and most
people with this type of tumor have no symptoms. These tumors
usually occur on only one adrenal gland, but they can appear on both
glands in rare instances.
• Functional adrenocortical adenomas are surgically curable.
• Adrenocortical carcinomas
• are usually much larger than benign adenomas.
• They frequently invade large vessels, such as the renal
vein and inferior vena cava, as well as metastasizing via the
lymphatic and through the blood to the lungs and other organs. The
most effective treatment is surgery, although this is not feasible for
many patients, and the overall prognosis of the disease is
poor. Chemotherapy, radiation therapy and hormonal therapy may
also be employed in the treatment of this disease.
16. Typesofadrenalglandtumors-Tumorsoftheadrenalmedull
Neuroblastoma
• is an aggressive cancer of immature neuroblastic cells ; one of the most common
pediatric cancers and typically presents with a rapidly enlarging abdominal mass.
• Although the tumor has often spread at the time of diagnosis, this cancer is unusual
in that many cases are highly curable when the spread is limited to the liver,skin
and/or bone marrow.
• Related, but less aggressive tumors are ganglioneuroblastoma and ganglioneuroma.
• Treatment of neuroblastoma includes surgery and radiation for localized disease, and
chemotherapy for metastatic disease.
Pheochromocytoma
• is a neoplasm composed of cells similar to the chromaffin cells
• Occur in patients of all ages, and may be sporadic, or associated with a hereditary
cancer syndrome. The most clinically important feature of Pheochromocytoma is
their tendency to produce large amounts of the catecholamine hormones leading to
potentially life-threatening high blood pressure or cardiac arrhythmias and numerous
other symptoms.
• Only 10% are malignant. Signs and symptoms are
The five P’s:-Pressure (HTN) , Pain (Headache), Perspiration, Palpitation, Pallor,
Paroxysms (6th P!)
17. Adrenal Tumors
CAUSES
• Medullary thyroid
carcinoma
• Parathyroid Hyperplasia
• Emotional and physical
stress.
• General factor
• Increased or Decreased
secretion of Hormone.
SIGN AND SYMPTOMS
• Hypertension
((320/200mm.Hg)
• Hypermetabolism
• Hyperglycaemia
• Head ache, Visual
Disturbances, Nervousness
• Abdominal pain
• Polyuria
• Psychotic Behavior,
Depression and Emotional
Upset.
• Allergic Reactions
18. Adrenal Tumors
Staging of Adrenal
Carcinoma The WHO
classification of 2004
is based on the
McFarlane
Classification &
defines four stages:
• I stage –Tumor <
5 cm
• II stage – Tumor
>5 cm
• III stage – Locally
invasive tumors
• IV Stage – Tumor
with distant
metastasis
• DIAGNOSTIC EVALUATION
• History collection andPhysical examination
• Biochemical evaluation- Morning &
midnight plasma cortisol measurement
• Dexamethasone suppression test(DST) is
used to assess adrenal gland function by
measuring how cortisol levels change in
response to an injection of dexamethasone.
• 24 hr urinary cortisol measurement
• Serum potassium, plasma aldosterone &
plasma renin activity
• Abdominal imaging, CT scan,MRI scan
• Adrenal vein catheterization
19. MANAGEMENT of Adrenal
Tumors
MEDICAL
• Alpha- Adrenergic Blocking Agents: Inhibit the effects of
Catecholamines on blood pressure.
• Catecholamine Synthesis Inhibitor: Used pre operatively or for long
term management of in operable tumors.
• Beta Adrenergic blocking agent: Propranolol - Used for patient with
cardiac dysarhythmias or those not responsive to alpha adrenergic
blocking agent.
• Corticosteroid replacement: To prevent adrenal insufficiency
SURGICAL MANAGEMENT
• Unilateral or Bilateral Adrenalectomy
Chemotherapy and Radiation Therapy in case of neoplasms
20. Hereditary disorders associated
with adrenal tumors
• Von Hippel–Lindau disease, a mutation of the VHL1 tumor-
suppression gene associated with many types of tumor,
including pheochromocytoma.
• Multiple Endocrine Neoplasia, a family of syndromes in which
genetic abnormalities contribute to the development of
endocrine tumors
