This document discusses disorders of the adrenal gland, including Addison's disease and Conn's syndrome. It covers symptoms, causes, diagnosis, and treatment of these conditions. Addison's disease is caused by insufficient production of cortisol and sometimes aldosterone by the adrenal glands. Symptoms include fatigue, weakness, weight loss, and dark skin pigmentation. Treatment involves replacing the missing hormones. Conn's syndrome is caused by excessive aldosterone production, leading to hypertension. It can be diagnosed through blood and urine tests showing elevated aldosterone levels. Treatment options include surgery or medications to suppress aldosterone.

1. Disorders of Adrenal gland
Dr.Uday Mahato
Lecturer -LMC

2. Addison's disease occurs when the adrenal glands
do not produce enough of the hormone cortisol and,
in some cases, the hormone aldosterone.
The disease is also called adrenal insufficiency, or
hypocortisolism.

3. Symptoms of ADDISON’S Disease
The symptoms of adrenal insufficiency usually begin gradually.
Characteristics of the disease are
worsening fatigue
muscle weakness
loss of appetite
weight loss
About 50 % of the time, one will notice
•nausea
•vomiting
•diarrhea

4. Other Symptom
low blood pressure that falls further when standing, causing dizziness or
fainting(postural hypotension)
skin changes in Addison's disease,
with areas of hyper-pigmentation, or dark tanning, covering exposed and
nonexposed parts of the body;
this darkening of the skin is most visible on scars; skin folds; pressure
points such as the elbows, knees, knuckles, and toes;
lips; and mucous membranes
Addison's disease can cause irritability and depression. Because of salt
loss, a craving for salty foods also is common. Hypoglycemia, or low
blood glucose, is more severe in children than in adults. In women,
menstrual periods may become irregular or stop.

5. Because the symptoms progress slowly, they are usually ignored until
a stressful event like an illness or an accident causes them to become
worse.
This is called an addisonian crisis, or acute adrenal insufficiency.
In most cases, symptoms are severe enough that patients seek
medical treatment before a crisis occurs.
However, in about 25% of patients, symptoms first appear
during an addisonian crisis.
Symptoms of an addisonian crisis include
 sudden penetrating pain in the lower back, abdomen, or legs
 severe vomiting and diarrhea
 dehydration
 low blood pressure
 loss of consciousness

6. Diagnosis
In its early stages, adrenal insufficiency can be difficult to
diagnose.
A review of a patient's medical history based on the symptoms,
especially the dark tanning of the skin, will lead a doctor to
suspect Addison's disease.
A diagnosis of Addison's disease is made by laboratory tests.
The aim of these tests is first to determine whether levels of
cortisol are insufficient and then to establish the cause.
X-ray exams of the adrenal and pituitary glands may be useful
in helping to establish the cause.

7. Diagnosis
ACTH Stimulation Test
This is the most specific test for diagnosing Addison's disease.
In this test, blood cortisol, urine cortisol, or both are measured
before and after a synthetic form of ACTH is given by
injection.
In the so-called short, or rapid, ACTH test, measurement of
cortisol in blood is repeated 30 to 60 minutes after an
intravenous ACTH injection.
The normal response after an injection of ACTH is a rise in
blood and urine cortisol levels. Patients with either form of
adrenal insufficiency respond poorly or do not respond at all.

8. Diagnosis
CRH Stimulation Test
When the response to the short ACTH test is abnormal, a
"long" CRH stimulation test is required to determine the cause
of adrenal insufficiency. In this test, synthetic CRH is injected
intravenously and blood cortisol is measured before and 30, 60,
90, and 120 minutes after the injection. Patients with primary
adrenal insufficiency have high ACTHs but do not produce
cortisol. Patients with secondary adrenal insufficiency have
deficient cortisol responses but absent or delayed ACTH
responses. Absent ACTH response points to the pituitary as the
cause; a delayed ACTH response points to the hypothalamus
as the cause.

9. Diagnosis
CRH Stimulation Test
In patients suspected of having an addisonian crisis, treatment
must begin with injections of salt, fluids, and glucocorticoid
hormones immediately. Although a reliable diagnosis is not
possible while the patient is being treated for the crisis,
measurement of blood ACTH and cortisol during the crisis and
before glucocorticoids are given is enough to make the
diagnosis. Once the crisis is controlled and medication has
been stopped, delay further testing for up to 1 month to obtain
an accurate diagnosis.

10. Causes
Failure to produce adequate levels of cortisol can occur for different
reasons.
The problem may be due to a disorder of the adrenal glands themselves
(primary adrenal insufficiency)
or to inadequate secretion of ACTH by the pituitary gland (secondary
adrenal insufficiency).

11. Primary Adrenal Insufficiency- Addison's disease
affects about 1 in 100,000 people.
Most cases are caused by the gradual destruction of the
adrenal cortex by the body's own
immune system.
About 70% of reported cases of Addison's disease are caused
by autoimmune disorders,
in which the immune system makes antibodies
that attack the body's own tissues or organs
and slowly destroy them.

12. Primary Adrenal Insufficiency- Addison's disease cause
Adrenal insufficiency occurs when at least 90% of the adrenal
cortex has been destroyed.
As a result, often both glucocorticoid (cortisol) and
mineralocorticoid (aldostertone) hormones are lacking.
Sometimes only the adrenal gland is affected, as in idiopathic
adrenal insufficiency; sometimes other glands also are affected,
as in the polyendocrine deficiency syndrome.

13. Causes
Tuberculosis
TB an infection which can destroy the adrenal glands,
accounts for about 20% of cases of primary adrenal
insufficiency in developed countries.
When adrenal insufficiency was first identified by Dr. Thomas
Addison in 1849, TB was found at autopsy in
70 -90% of cases.
As the treatment for TB improved, however, the incidence of
adrenal insufficiency due to TB of the adrenal glands has
greatly decreased.

14. Other Causes
Less common causes of primary adrenal insufficiency
are
•chronic infection, mainly fungal infections
•cancer cells spreading from other parts of the body to the
adrenal glands
•surgical removal of the adrenal glands

15. Secondary Adrenal Insufficiency
This form of adrenal insufficiency is much more common than
primary adrenal insufficiency and can be traced to a lack of
ACTH. Without ACTH to stimulate the adrenals, the adrenal
glands' production of cortisol drops, but not aldosterone.
A temporary form of secondary adrenal insufficiency may occur when a
person who has been receiving a glucocorticoid hormone such as
prednisone for a long time abruptly stops or interrupts taking the
medication.
WHY???
Glucocorticoid hormones
block the release of both
CRH and ACTH.

16. Treatment
Treatment of Addison's disease involves replacing, or substituting, the
hormones that the adrenal glands are not making.
Cortisol is replaced orally with hydrocortisone tablets, a synthetic
glucocorticoid, taken once or twice a day.
If aldosterone is also deficient, it is replaced with oral doses of a
mineralocorticoid called fludrocortisone acetate which is taken once a
day.
Patients receiving aldosterone replacement therapy are usually advised to
increase their salt intake. Because patients with secondary adrenal
insufficiency normally maintain aldosterone production, they do not
require aldosterone replacement therapy.

17. Treatment
During an addisonian crisis, low blood pressure, low blood glucose, and
high levels of potassium can be life threatening.
Standard therapy involves intravenous injections of hydrocortisone,
saline (salt water), and dextrose (sugar).
This treatment usually brings rapid improvement.

21. Conn’s Syndrome – Primary
Hyperaldosteronism
One etiology of Endocrine Hypertension
Consider in setting of resistant HTN, HTN &
hypokalemia, adrenal incidentaloma and HTN,
HTN onset at age <40, severe HTN (>or= 160
SBP or 100 DBP), or whenever considering sec.
HTN.
 Could be due to adenoma, bilateral adrenal
hyperplasia or carcinoma

22. • Aldosterone
• Aldosterone belongs to a class of hormones called
mineralocorticoids, also produced by the adrenal
glands(zona glomerulosa)
• It helps maintain blood pressure and water and salt balance
in the body by helping the kidney retain sodium and
excrete potassium

25. Work Up
 Get AM blood for:
Plasma aldosterone concentration (PAC)
Plasma renin activity (PRA or PRC)
 IF  PAC (≥15 ng/dL) + PRA or PRC AND
PAC/PRA ratio of ≥20 THEN you should investigate for
Primary Aldosteronism by doing a saline suppression test .

26. Work Up
.
Saline suppression- Measure Plasma aldosterone
level before and after 2L normal saline bolus or
measure 24 hour urine excretion of aldosterone
after an oral sodium loading test.
Elevated aldosterone levels are confirmatory of
primary Aldosteronism because in the normal
person, a sodium load should suppress aldosterone
levels.

27. Dx and Rx
Dx
CT imaging
Adrnal Venous sampling
Rx
Surgery
Spironolactone or epleronone to suppress
aldosterone