Adrenal Gland :
Adrenal Insufficiency,
Addison Disease,
Cushing Syndrome
Ruswana Anwar, Tita Husnitawati M
ADRENAL INSUFFICIENCY
Primary adrenal insufficiency
Secondary adrenal insufficiency :
-(CRH) secretion from the
hypothalamus
-(ACTH) secretion from the
pituitary
Pathophysiology:
renin-angiotensin system , increased
serum potassium concentrations :
regulate Aldosterone secretion
ACTH regulate Cortisol secretion and
Adrenal androgen
Frequency:
90% of cases are attributed to
autoimmune disease ,
Worldwide, the most common cause
is tuberculosis (TB).
Mortality/Morbidity
Onset is gradual.
Hyperpigmentation : ACTH, contains the MSH
sequence, which stimulates melanocytes.
Complain of fatigue, anorexia, asthenia, weight loss,
abdominal pain, nausea, vomiting, and weakness.
Hypoglycemia, and most have hypotension.
Orthostatic changes in BP and pulse are cardinal signs
of adrenal insufficiency.
Hyponatremia and hyperkalemia due to deficient
aldosterone secretion.
Death usually results from hypotension or cardiac
arrhythmia secondary to hyperkalemia.
History:
in the context of a serious illness such as
sepsis, as the result of prolonged and
difficult labor, or from a traumatic delivery.
Autoimmune may be exacerbated by an
acute adrenal crisis
on long-term pharmacologic doses of
glucocorticoids , when they are stressed
by an illness or trauma
Physical:
hyperpigmentation
hyperpigmentation
surrounding vitiligo
(autoimmune destruction
of melanocytes)
Causes:
Primary/Central adrenal insufficiency
exposure to pharmacological doses
of glucocorticoids can cause CRH-ACTH-
adrenal axis suppression.
an inactivating mutation of the ACTH
receptor that renders the adrenal glands
unresponsive to ACTH
Acquired primary adrenal insufficiency
autoimmune destruction of the adrenal cortex
Type 2 autoimmune consists of diabetes mellitus,
autoimmune thyroid disease, and adrenal failure.
o Less common causes of adrenal failure include the
following:
o Adrenal hemorrhage
o Infections (eg, TB)
o Neoplastic destruction
Hemachromatosis in thalassemia patients
Congenital primary adrenal
insufficiency
Congenital disease may occur from
adrenal hypoplasia or hyperplasia
Lab Studies:
laboratory studies help
establish the diagnosis:
o Electrolytes
o Fasting blood sugar
o Serum ACTH
o Plasma renin activity
o Serum cortisol
o Serum aldosterone
serum cortisol concentration less than 18
mcg/dL in a sick and stressed patient
highly suggests adrenal insufficiency.)
Antibodies to 1 or more steroidogenic
enzymes, particularly 21-hydroxylase,
found in autoimmune adrenal disease.
If the test are negative, search for TB,
adrenal hemorrhage, or
adrenoleukodystrophy.
Imaging Studies
Abdominal radiographs : bilateral
adrenal calcifications
CT is the imaging study of choice and
helps identify adrenal hemorrhage,
calcifications, or infiltrative disease
Medical Care
Patients are hypovolemic, and hypoglycemic,
hyponatremic, or hyperkalemic. Initial therapy consists of
IV saline and dextrose.
If hypotensive, a 20 mL/kg bolus of isotonic sodium
chloride solution over the first hour
Once electrolytes, blood sugar, cortisol, and ACTH
concentrations are obtained, treat patients suspected of
having adrenal insufficiency with glucocorticoids.
dexamethasone may be administered prior to cosyntropin
without interfering with results.
Treat patients with adrenal insufficiency requiring
surgery with stress doses of glucocorticoids (eg,
50-75 mg/m2 hydrocortisone IM or IV "on call"
prior to surgery).
o Treat the patient with additional hydrocortisone
during the procedure, using either a
hydrocortisone drip of 2-4 mg/m2/h or as an
additional push of 10-25 mg/m2 IV every 6 hours
throughout the procedure.
o Continue hydrocortisone administration in the
immediate postoperative period.
ADDISON DISEASE
Pathophysiology:
Addison disease is adrenocortical
insufficiency due to the destruction
or dysfunction of the entire adrenal
cortex.
It affects both glucocorticoid and
mineralocorticoid function.
Presentation of acute Addison disease
o nausea, vomiting, and vascular collapse.
They may be in shock and appear cyanotic
and confused.
o Abdominal symptoms : acute abdomen.
o Patients may have hyperpyrexia, and may be
comatose.
o In acute adrenal hemorrhage, sudden
collapse, abdominal or flank pain, and
nausea with or without hyperpyrexia.
Presentation of chronic Addison disease
history of amenorrhea due to the
combined effect of weight loss and
chronic ill health or secondary to
premature autoimmune ovarian failure.
Steroid-responsive hyperprolactinemia
may contribute to the impairment of
gonadal function and to the amenorrhea
Causes:
Idiopathic autoimmune
adrenocortical atrophy and
tuberculosis (TB) account for nearly
90% of cases of Addison disease.
Causes of acute Addison disease
Stress:
Failure to increase steroids
Bilateral adrenal hemorrhage
Lab Studies:
rapid ACTH stimulation test : An
increase in the plasma cortisol and
aldosterone levels above basal levels
after ACTH injection reflects the
functional integrity of the adrenal
cortex.
Lab Studies:
rapid adrenocorticotrophic hormone
test : In patients with Addison
disease, both cortisol and
aldosterone show minimal or no
change in response to ACTH
Addison disease and in patients with secondary
adrenocortical insufficiency
Thyroid-stimulating hormone
Modest hyperprolactinemia :
hyperresponsiveness of the lactotroph
to thyrotropin-releasing hormone (TRH)
in the absence of the steroid-induced or
steroid-enhanced hypothalamic
dopaminergic tone.
Figure 10. Schematic representation of the main factors interacting in the regulation of TSH synthesis and
secretion (DA: dopamine; SS: somatostatin; a-AD: a adrenergic pathways). Solid arrows: stimulation; open
arrows: inhibition.
Estrogen biosynthesis
A single reaction P450 arom convert
androstenedion to estrone or
testosterone to 17-estradiol.
Cushing syndrome
Cushing syndrome is caused by
prolonged exposure to elevated levels
of either endogenous or exogenous
glucocorticoids.
Sign :
moon facies, facial plethora,
supraclavicular fat pads, buffalo
hump, truncal obesity, and purple
striae
Symtoms
proximal muscle weakness, easy
bruising, weight gain, hirsutism, and,
in children, growth retardation.
Hypertension, osteopenia, diabetes
mellitus, and impaired immune
function may occur.
Pathophysiology
Endogenous glucocorticoid
overproduction or hypercortisolism that is
independent of adrenocorticotropic
hormone (ACTH) due to a primary
adrenocortical neoplasm
ACTH-secreting neoplasms cause ACTH-
dependent Cushing syndrome, due to an
anterior pituitary tumor, ie, classic
Cushing disease (80%).
Table 1. Etiology of Cushing's syndrome
ACTH-dependent
•Pituitary-dependent Cushing's syndrome (Cushing's disease)
•Ectopic ACTH syndrome
•Ectopic CRH syndrome
•Exogenous ACTH administration
ACTH-independent
•Adrenal adenoma
•Adrenal carcinoma
•Macronodular adrenal hyperplasia (partially ACTH dependent)
•Pigmented micronodular adrenal hyperplasia
•Adrenal hyperplasia secondary to abnormal hormone receptor
expression/function
The majority of cases of Cushing
syndrome are due to exogenous
glucocorticoids
Mortality/Morbidity :
Related primarily to the effects of
excess glucocorticoids
Primary pituitary tumor may cause
panhypopituitarism and visual loss.
Exposure to excess glucocorticoids
results in multiple medical
problems, including :
hypertension, obesity,
osteoporosis, fractures,
impaired immune function,
impaired wound healing, glucose
intolerance, and psychosis.
Endocrine in Cushing syndr
o Hypothyroidism may occur
from anterior pituitary tumors,
o Galactorrhea may occur when
anterior pituitary tumors
compress the pituitary stalk,
leading to elevated prolactin
levels.
Endocrine in Cushing syndr
o Menstrual irregularities, amenorrhea, and infertility may
occur due to inhibition of pulsatile secretion of LH and FSH,
due to interruption of luteinizing hormone-releasing
hormone (LHRH) pulse generation.
o Low testosterone levels in men may lead to decreased
testicular volume from inhibition of LHRH and LH/FSH
function.
o Low estrogen levels in women may result from inhibition of
LHRH and LH/FSH function.
Adrenal crisis
occur in patients on steroids who
stop taking their glucocorticoids or
neglect to increase their steroids
during an acute illness.
have recently undergone resection
of an ACTH-producing or cortisol-
producing tumor.
Adrenal crisis
Physical findings : hypotension,
abdominal pain, vomiting, and
mental confusion (secondary to low
serum sodium or hypotension).
Other findings include hypoglycemia,
hyperkalemia, hyponatremia, and
metabolic acidosis.
Lab Studies:
The diagnosis of Cushing syndrome
due to endogenous overproduction
of cortisol
Two common screening tests are the
24-hour UFC (urinary free cortisol)
test and the overnight (ON) 1-mg
dexamethasone suppression test.
Imaging Studies:
CT scan: adrenal mass larger than 4-
6 cm raises the possibility that the
mass is an adrenal carcinoma
contrast-MRI study of the pituitary
Medical Care:
Agents that inhibit steroidogenesis,
such as mitotane, ketoconazole,
metyrapone, aminoglutethimide,
trilostane, and etomidate, have been
used to cause medical
adrenalectomy.
radiation therapy of the pituitary
o Ketoconazole acts on several of the P450
enzymes in cortisol synthesis, and inhibit
ACTH secretion when used at therapeutic
doses (200-400 mg bid-tid).
o Metyrapone blocks 11-beta-hydroxylase
activity (the final step in cortisol
synthesis)
Mifepristone (RU 486) is an
antiprogestational agent,
competitively binds to the
glucocorticoid and
progesterone receptors
Agents that decrease CRH or
ACTH release : bromocriptine,
Surgical Care :
Transsphenoidal surgery
Bilateral adrenalectomy
