Adrenocortical

disorders
By

AbdAlAziz AbdAllah,
MD

The adrenal gland is divided into two

.parts, adrenal cortex and medulla
The adrenal cortex secretes androgen,
mineralocorticoids (eg, aldosteron) and
.glucocorticoids (eg, crtisol)
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
I- 1ry hyper-aldosteronism (Conn
:syndrome)
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
unilateral aldosterone-producing adenoma ,( 1)
Conn syndrome, (50-60% of cases)

idiopathic hyperaldosteronism (IHA) or bilateral( 2)

. adrenal hyperplasia (40-50% of cases)
Rarely, aldosterone can be secreted by( 3)
.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
Hypertension, especially if left untreated for- 1
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(

Hypokalemia, especially if severe, causes -2

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 ascitis-
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 Care
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-

C\P
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

Cushing syndrome is caused by prolonged

exposure to elevated levels of either
endogenous glucocorticoids or exogenous
glucocorticoids

: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*

C\p
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

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

Investigations
Laboratory Studies
Hyperglycemia
Hypokalemic metabolic alkalosis

:Biochemical evaluation of Cushing syndrome

Urinary free cortisol excretion over 150 ug\-1
.day

dexamethasone suppression test;- 2

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

loss of circadian rhythm of cortisol secretion -3

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

A plasma ACTH of less than 5 pg/mL is- 4

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

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

Intaoperative
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 corticotropinreleasing 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
idiopathic autoimmune adrenocortical- 1
.insufficiency
Chronic granulomatous diseases; TB,- 2
. sarcoidosis, histoplasmosis
Hematologic malignancies; as Hodgkin- 3
. and non-Hodgkin lymphoma and leukemia

Metastatic malignant disease; as metastatic - 4

cancer of the lung, breast, colon or renal cell
.carcinoma
Infiltrative metabolic disorders; Amyloidosis -5
.and hemochromatosis
.AIDS- 6

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

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

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
corticosteroid: Prednisone 5-7.5 mg PO qd in am or 5- 1
.mg PO qd in am and 2.5 mg PO qd at 4-5 pm
mineralocorticoid: Fludrocortisone 0.05-0.1 mg PO qd;- 2
.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
mg of hydrocortisone phosphate every 8 h 100beginning 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

Intaoperative
.ensure adequate fluid
Postoperative
Continue the stress dose of steroids to gard
.against acute adrenal crisis

beta Hydroxylase Deficiency- 11

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