Adrenocortical

disorders
 Adrenal Gland
Anatomy was first described in 1563.
Is located above (or attached to) the upper pole
of the kidney.
Is pyramidal in structure and weighs ~ 4 g.
Consists of the adrenal cortex and adrenal
medulla
Activities are regulation of fluid volume and
stress response
The Adrenal
Gland:
Anatomy
Adrenal Histology

The adrenal gland is divided into two parts, adrenal cortex and medulla.

The adrenal cortex secretes androgen, mineralocorticoids (eg,

aldosteron) and glucocorticoids (eg, cortisol).

The adrenal medulla secretes catecholamines (eg, epinephrine,

norepinephrine, dopamine).
 Aldosteron is primarily involved with fluid and
electrolyte balance.

 Aldosteron secretion causes sodium reabsorption

in the distal renal tubule in exchange for
potassium and hydrogen ions.

 The net effects are, fluid retention, decrease in

plasma potassium and metabolic alkalosis.
Aldosteron secretion is stimulated by;
-Renin-angiotensin system.
-ACTH.
-Hyperkalemia.
-Hypovolemia.
-Hypotension.
-congestive heart failure.
-Surgery.
Glucocorticoids are essential for life and have
mutiple pysiological effects.

Metabolic actions include enhanced

gluconeogenesis and inhibition of peripheral
glucose utilization.

Glucocorticoids are required for vascular and

bronchial smooth muscle to be responsive to
catecholamines.

Glucocorticoids are structurly related to

aldosteron, so they have aldosteron like action.
ACTH is the principal regulator of Glucocorticoids
secretion.

Secretion of ACTH and glucocorticoids exhibit a

diurnal rhythm, stimulated by stress and inhibited by
circulating glucocorticoids.

Endogenous production of cortisol averages 20 mg \

day.
 Mineralocorticoid excess
(Conn syndrome)
I- 1ry hyper-aldosteronism :

Conn syndrome is characterized by increased

aldosterone secretion from the adrenal glands, it
was first described in 1955 by J. W. Conn in a
patient who had an aldosterone-producing
adenoma.
 Pathophysiology
 Primary hyperaldosteronism is caused by
increased aldosterone excretion from the
adrenals, which results primarily from 2 major
subtypes:
 (1) unilateral aldosterone-producing adenoma ,
Conn syndrome, (50-60% of cases)
 (2) idiopathic hyperaldosteronism (IHA) or
bilateral adrenal hyperplasia (40-50% of cases
 (3) Rarely, aldosterone can be secreted by
adrenocortical carcinomas and ovarian tumors.
Aldosterone, by inducing renal distal
tubular reabsorption of sodium,
enhances secretion of potassium and
hydrogen ions, causing
hypernatremia, hypokalemia, and
metabolic alkalosis.
Frequency:
Prevalence for Conn syndrome; 0.05-2% of the
population.
Mortality/Morbidity:
The morbidity and mortality associated with
Conn syndrome, are primarily related to;
1- Hypertension, especially if left untreated for
many years, can lead to many complications,
including heart disease (eg, coronary artery
disease, congestive heart failure), stroke, and
intracerebral hemorrhage (with very high blood
pressure).
2-Hypokalemia, especially if severe, causes
cardiac arrhythmias, which can be fatal
Age
Peak incidence occurs in the third to sixth
decades of life.
Sex
Primary hyperaldosteronism is twice as common
in women as in men.
 II- 2ry hyperaldosteronism:

There is increased renin-angiotensin with

increased aldosteron secretion;
-CHF
-Liver cirrhosis and ascites
-Nephrotic syndrome
-Renal artery stenosis
Clinical manifestations
- Hypertension;
- Hypokalemia;
patients with severe hypokalemia report fatigue, muscle
weakness, cramping, headaches, and palpitations. They
can also have polydipsia and polyuria from hypokalemia-
induced nephrogenic diabetes insipidus.
Metabolic alkalosis;
will lower ionized calcium levels and can cause tetany.


Investigations:
Laboratory Studies
- hypernatremia
- hypokalemia; normokalemia does not exclude
primary hyperaldosteronism. Several studies have
shown that 7-38% of patients with primary
hyperaldosteronism have normal baseline serum
levels of potassium
metabolic alkalosis
-Renin levels are suppressed to less than 1 ng/mL/h
in patients with primary hyperaldosteronism.
-A 24-hour aldosterone excretion rate of greater than
14 ug is diagnostic of primary hyperaldosteronism
Imaging Studies :
- CT scanning

- MRI
Treatment
Medical
Medical therapy is used preoperatively to prevent
the morbidity and mortality associated with
hypertension and hypokalemia, thus decreasing
surgical risk.
Sodium-restricted diet (<80 mEq or <2 g of
sodium per day.
Potassium-sparing agent (first-step agent) such
as spironolactone100 mg initially, increase to 400
mg/d for control of blood pressure.
Potassium supplementation should not be
routinely administered with spironolactone
because of the potential for the development of
hyperkalemia.
Second-step agents include thiazides diuretics,
ACE inhibitors, calcium channel antagonists,
and angiotensin II blockers.
Surgical treatment
Surgery is the main therapy for Conn
syndrome. A laparoscopic adrenalectomy is
favored, when possible

• Anesthetic considerations
Preoperative correction of hypertension, CHF and
volume and electrolytes imbalance specially potassium
is mandatory.
 Mineralocorticoid deficiency
( Hypo-aldosteronism )
Atrophy or destruction of both adrenal glands results in a
combined deficiency of Mineralocorticoid and glucocorticoid
( addison disease) .
-Isolated Mineralocorticoid deficiency;
-Unilateral adrenalectomy
-DM -Heparine therapy
-congenital
Clinical Presentasi
Hypotension; due to hypovolemia
Metabolic acidosis
Hyperkalemia; any increase in s. potassium without renal
impairment, hypoaldosteronism should be considered.
Hyponatremia
 Anesthetic management
 Preoperative preparation includes;
 correction of fluid and electrolyte imbalance
 exogenous mineralocorticoid, fludrocortison 0.1-0.3
mg\ day.
 Glucocorticoid excess
( Cushing syndrome/ disease )

Cushing syndrome is caused by prolonged

exposure to elevated levels of either endogenous
glucocorticoids or exogenous glucocorticoids
 Cushing’s Disease

William’s Textbook of Endocrinology. 8th Ed. Foster, DW, Wilson, JD (Eds), WB Saunders, Philadelphia, 1996
Cushing’s Syndrome vs. Cushing’s
Disease
• Cushing’s syndrome is a syndrome
due to excess cortisol from pituitary,
adrenal or other sources (exogenous
glucocorticoids, ectopic ACTH, etc.)

• Cushing’s disease is hypercortisolism

due to excess pituitary secretion of
ACTH (about 70% of cases of
endogenous Cushing’s syndrome)
Increased ACTH:Cushing’s Disease
Cushing's is a disorder in which the adrenal glands
are producing too much cortisol (hypercotisolism).
If the source of the problem is the pituitary gland,
then the correct name is Cushing's Disease
whereas, if it originates anywhere else (adrenal
tumors, long term steroid administration) then the
correct name is Cushing's Syndrome.
Cushing’s Disease is caused by pituitary
hypersecretion of ACTH.
Causes:
Exogenous steroid administration
 Symptoms of glucocorticoid excess generally occur
with the administration of oral steroids; however,
occasionally injections of steroids into joints and the
use of steroid inhalers can cause Cushing syndrome.
 Patients at risk to develop cushing syndrome includes:
 -rheumatological, pulmonary, neurological, and
nephrologic diseases that respond to steroid therapy.
 -Patients who have undergone organ transplants due
to exogenous steroids required as part of graft
antirejection medication regimens.
Endogenous glucocorticoid administration

 ACTH-producing pituitary adenoma ( Cushing

disease).
 Primary adrenal lesions; Overproduction of
glucocorticoids may be due to an adrenal adenoma,
adrenal carcinoma, or macronodular or micronodular
adrenal hyperplasia.
 Ectopic ACTH is sometimes secreted by oat cell or
small-cell lung tumors or by carcinoid tumors
Frequency
Most cases of Cushing syndrome are due to exogenous
glucocorticoids. Endogenous Cushing syndrome has
been estimated at 13 cases per million individuals.
Age
The peak incidence of Cushing syndrome due to either
an adrenal or pituitary adenoma is in persons aged 25-
40 years
Ectopic ACTH production due to lung cancer occurs
later in life
Sex
The female-to-male incidence ratio is approximately 5:1
for Cushing syndrome due to an adrenal or pituitary
tumor
Mortality/Morbidity
Morbidity and mortality associated with Cushing
syndrome are related primarily to the effects of excess
glucocorticoids. However, a large primary pituitary
tumor may cause panhypopituitarism and visual loss.
Adrenocortical carcinomas are associated with a 5-
year survival rate of 30% or less.
Multiple medical problems, including hypertension,
obesity, osteoporosis, fractures, impaired immune
function, impaired wound healing, glucose intolerance,
and psychosis.
Adrenal crisis
Clinical Presentation
Obesity
Moon facies
Buffalo hump
Central obesity, increased waist-to-hip ratio
greater than 1 in men and 0.8 in women

Skin
Facial plethora
abdominal striae
lanugo facial hair
Hirsutism and Steroid acne
 Cushing’s Syndrome
Moon facies •Proximal muscle
Facial plethora weakness
•Easy bruising
Supraclavicular fat
•Hirsutism
pads
•Hypertension
Buffalo hump •Osteopenia
Truncal obesity •Diabetes mellitus/IGT
Weight gain • Impaired immune
function/poor wound
Purple striae healing
 Central Obesity in Cushing’s Disease

William’s Textbook of Endocrinology. 8th Ed. Foster, DW, Wilson, JD (Eds), WB Saunders, Philadelphia, 1996
 Progressive Obesity of Cushing’s
Disease

Age 6 Age 7 Age 8 Age 9 Age 11

William’s Textbook of Endocrinology. 8th Ed. Foster, DW, Wilson, JD (Eds), WB Saunders, Philadelphia, 1996
 Buffalo Hump in Cushing’s Disease

Orth, D. UpToDate
 Striae in Cushing’s Disease

Orth, D. UpToDate
 Proximal Muscle Wasting in
Cushing’s Syndrome

William’s Textbook of Endocrinology. 8th Ed. Foster, DW, Wilson, JD (Eds), WB Saunders, Philadelphia, 1996
Cardiovascular and renal
Hypertension and possibly edema may be present
due to cortisol activation of the mineralocorticoid
receptor leading to sodium and water retention
Gastroenterologic
Peptic ulceration may occur with or without
symptoms. 
Endocrine
Galactorrhea and menstrual disturbances
decreased libido and impotence in men.

Skeletal/muscular
Proximal muscle weakness
Osteoporosis and osteopenia
Avascular necrosis of the hip
Neuropsychological
Emotional liability, fatigue, and depression
Visual-field defects, often bitemporal, and blurred
vision

Adrenal crisis
Diagnosis of Cushing’s Syndrome

 ACTH, AM cortisol
 24 hour urine cortisol
 Dexamethasone suppression testing
 Midnight salivary cortisol
 Dexamethasone Suppression
Test

http://www.endotext.com/neuroendo/neuroendo7/neuroendoframe7.htm
 Circadian Studies of Serum Cortisol
Levels

http://www.endotext.com/neuroendo/neuroendo7/neuroendoframe7.htm
Investigations
Laboratory Studies
 Hyperglycemia
 Hypokalemic metabolic alkalosis
 Biochemical evaluation of Cushing syndrome:
1-Urinary free cortisol excretion over 150 ug\ day.
 2- dexamethasone suppression test; glucocorticoids
inhibit secretion of hypothalamic CRH and pituitary
ACTH but do not directly affect adrenal cortisol
production. The overnight 1-mg dexamethasone
suppression test requires administration of 1 mg of
dexamethasone at 11 PM with subsequent measurement
of cortisol level at 8 am.4 In healthy individuals, the
serum cortisol level should be less than 2-3 ug/dL.
3-loss of circadian rhythm of cortisol secretion
Normal values, 10-25 ug\ml in the morning, 2-10 ug\ml
in the evening, elevated serum cortisol at 11 PM can
be an early finding.
Recently, measuring salivary cortisol level has gained
interest, as it is a simple and convenient way of
obtaining a nighttime sampl. levels less than 1.3-1.5
ng/mL exclude Cushing syndrome.


4- A plasma ACTH of less than 5 pg/mL is
suggestive of a primary adrenal tumor. An ACTH
level greater than 10-20 pg/mL is consistent with
ACTH-dependent Cushing syndrome.

Imaging studies
CT or MRI brain and abdomen
 Diagnosis
 24 hr urine cortisol levels
 Serum sodium levels
 Serum potassium levels
 Serum glucose
 Serum ACTH in Cushing Disease
 ACTH suppression test to identify cause
 Dexamethasone supression test: cause pituitary or
adrenal
 Radiological exam to reveal pituitary or adrenal tumor
 Treatment
Transphenoidal surgery if the condition is due
to a pituitary tumor
Where surgery is contraindicated or fails to
reduce cortisol levels, adrenalectomy and/or
pituitary radiation may be necessary.
Adrenocortical Inhibitors: (metapyrone,
aminogluthimide) are only effective short-term.
Diet: low calorie, carbohydrate & salt. High
potassium.
Treatment
Hypopysectomy for pituitary tumors, or adrenalectomy for
adrenal tumors.
Pituitary irradiation is employed when transsphenoidal
surgery is not successful or not possible
Patients with endogenous Cushing syndrome who
undergo resection of pituitary, adrenal, or ectopic tumors
should receive stress doses of glucocorticoid in the
intraoperative and immediate postoperative period
Lifelong glucocorticoid and mineralocorticoid replacement
is necessary in those patients who undergo bilateral
adrenalectomy.
Anesthetic considerations
Preoperative management
From the C\P those pt. Tend to be volume
overloaded, hypertensive and hypokalemic, so
Preoperative correction of these factors are
essential by potassium and spironolactone.
Intraoperative
Patients with osteoprosis are at risk for fracture
during positioning.
Preoperative weakness may indicate an increased
sensitivity to muscle relaxants.
Supplemental steroids are indicated for patients
with Cushing syndrome due to exogenous
glucocorticoids
patients undergoing adrenalectomy
Dose; I.V. hydrocortisone succinate 100 mg
every 8 h beginning the evening before surgery
or on the morning of surgery.
Other complications of adrenalectomy include
significant blood loss and unintentional
pneumothorax.
Pseudo-Cushing Syndrome
In 1976, Smalls and associates described 3
alcoholic patients who had the physical and
biochemical abnormalities of Cushing syndrome.
Most of the abnormalities disappeared with 1-3
weeks of alcohol abstinence. About 30 cases have
been reported.
Pathophysiology
The mechanism remains unclear. Most evidence
suggests central stimulation of a corticotropin-
releasing hormone, either at the hypothalamic or
suprahypothalamic level.
Persistence of abnormalities may lead to
complications such as hypertension, glucose
intolerance, diabetes mellitus, and osteoporosis.
The most important part of the history is the
extent and duration of alcohol abuse.
 Glucocorticoid deficiency
( Addison 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.
Pathophysiology
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.
Frequency
The prevalence of Addison disease is 40-60 cases
per 1 million population.
Causes
1. Idiopathic autoimmune adrenocortical
insufficiency.
2. Chronic granulomatous diseases; TB,
sarcoidosis, histoplasmosis.
3. Hematologic malignancies; as Hodgkin and
non-Hodgkin lymphoma and leukemia.
4. Metastatic malignant disease; as metastatic
cancer of the lung, breast, colon or renal cell
carcinoma.
5. Infiltrative metabolic disorders; Amyloidosis and
hemochromatosis.
6. AIDS.
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.

Secondary adrenal insufficiency is a result of inadequate

ACTH secretion by the pituitary, the most common cause
of secondary adrenal insufficiency is iatrogenic, the
result of the administration of exogenous glucocorticoids.
Clinical Presentasi
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.
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.
Prominent gastrointestinal symptoms may
include nausea, vomiting, and occasional
diarrhea.
Patients with secondary adrenal insufficiency have a
history of tacking cortisol.
Acute adrenal crisis
Investigations
Laboratory Studies
ACTH stimulation test; In patients with Addison
disease, both cortisol and aldosterone show
minimal or no change in response to ACTH.
Hyponatremia
Hyperkalemia
Metabolic acidosis
Elevated (BUN) and creatinine due to the
hypovolemia with decreased glomerular filtration
rate.
Hypoglycemia
Adrenal autoantibodies may be present
Imaging study
Chest x-ray TB
CT abdomen
Treatment
The goals of pharmacotherapy are to reduce morbidity and to
prevent complications e.g adrenal crisis;
1. Corticosteroid: Prednisone 5-7.5 mg PO qd in am or 5 mg PO qd in
am and 2.5 mg PO qd at 4-5 pm.
2. Mineralocorticoid: Fludrocortisone 0.05-0.1 mg PO qd; some
patients may only require alternate-day dosing.
Anesthetic considerations
Preoperative management
 Ensure adequate replacement therapy
 Correct fluid and electrolytes disturbaces
for all patients who have received potentially suppressive doses of
steroids, the daily equivalent of 5 mg of prednisone, by any route of
administration- topical, inhalational or oral-, for a period of more than
2 weeks any time in the previous 12 months may be unable to
respond appropriately to surgical stress.
Adults normally secrete 20mg of cortisol daily,
this may increase to over 300 mg under maximal
stress.
- 100 mg of hydrocortisone phosphate every 8 h
beginning the evening before or on the morning
of surgery.
an alternative low dose regimen, 25 mg of
hydrocortisone phosphate at the time of
induction followed by an infusion of 100 mg
during the subsequent 24 h, and this might be
appropriate for diabetic pt.
Intraoperative
ensure adequate fluid.
Postoperative
Continue the stress dose of steroids to gard
against acute adrenal crisis.
 11- beta Hydroxylase Deficiency
Congenital adrenal hyperplasia (CAH) is a general
term used to describe a group of inherited disorders in
which a defect in cortisol biosynthesis is present with
consequent overproduction of (ACTH) and secondary
adrenal hyperplasia as a consequence.
Causes
An autosomal recessive disease.
 Patients with 11-beta-hydroxylase deficiency
present with features of androgen excess, including
masculinization of female newborns and precocious
puberty in male children.
Approximately two thirds of patients also have
hypertension, which may or may not be
associated with mineralocorticoid excess,
hypokalemia, hypernatremia and metabolic
alkalosis.
The hypertension is initially responsive to
glucocorticoid replacement, but it may become a
chronic condition subsequently requiring
standard antihypertensive therapy.
 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. Some patients may require slightly
more glucocorticoid in the third trimester.
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).
After delivery, the dosage can be quickly
tapered to a maintenance dose in 3 days.
 Cushing Syndrome and Pregnancy
The risk of maternal morbidity and a poor fetal
outcome is significant when Cushing syndrome
coexists with pregnancy.
Maternal hypertension may antedate the pregnancy
but becomes worse in two thirds of patients.
Preeclampsia or pregnancy-induced hypertension is
noted in approximately 10% of patients.
Gestational DM occurs in approximately one third.
Congestive heart failure associated with severe
hypertension occurs in 10%.
Wound breakdown after surgery is possible.
Severe proximal myopathy and mental problems
ranging from emotional lability to profound
psychosis should be added to the list of medical
problems that may occur.
 Primary Hyperaldosteronism and
Pregnancy
Patients present with hypertension, hypokalemia,
and elevated urine potassium levels.
The goals of medical therapy should be adequate
control of blood pressure and replacement of
potassium
Spironolactone and angiotensin-converting enzyme
inhibitors, are contraindicated in patients who are
pregnant.
Methyldopa, beta-blockers, and calcium channel
blockers have been used with variable outcomes