DISEASES OF ADRENAL GLANDS

BY: Getachew Tibebie

MD, Assistant Professor of Anesthesiology, Critical Care & Pain
Medicine
July, 2024

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 OUTLINES
• Brief anatomy & physiology of the adrenal gland
• Addison’s disease
• Cushing’s Syndrome
• Adrenocortical Tumors
• Pheochromocytoma

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Anatomy of the adrenal gland

• pyramid-shaped organs which lies just above the kidneys (also known as suprarenal glands).
• weigh 6–11 g each and averaging 3-5 cm in length.
• has two main parts
 Adrenal cortex(80%): Secretes steroid Hormones.
 Adrenal medulla(20%): Secretes Catecholamines.

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I. cortex: has 3 major anatomic Zones
1.Zona Glomerulosa(15%):
 outermost zone located immediately beneath the capsule.
 Synthesizes Aldosterone, the most potent natural mineralocorticoid
 essential for Na+ retention, intravascular volume & BP regulation .
 Aldosterone secretion is regulated by RAAS & serum K+ level
2.Zona Fasciculata(75%):
 middle Zone, the largest Zone
 Produces Cortisol the most Potent natural glucocorticoid .
 Cortisol secretion is regulated by ACTH which in turn regulated by CRH from Hypothalamus.
 Serum cortisol inhibits the secretion of both CRH and ACTH

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 3.Zona Reticularis(10%):
 the innermost zone, lying next to the adrenal medulla.
 synthesize Adrenal Androgens .
 ACTH and circadian partially regulates adrenal androgen secretion
II. Adrenal medulla
 Specialized neural crest (neuroendocrine) cells
 Part of the autonomic nervous system
 It secrets
• Epinephrine (80%)
• Norepinephrine (19%)
• Dopamine (1%)

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 physiology of the adrenal gland
• most important life-sustaining organ in human
A. Glucocorticoid B. mineralocorticoid
 Carbohydrate, protein, lipid metabolism.  primary endogenous mineralocorticoid is
aldosterone, others include progesterone and
 reduce bone growth
deoxycorticosterone.
 controls blood pressure.  Aldosterone secretion is mediated principally by
 responsible for the sleep/wake cycle. angiotensin II but also by ACTH and potassium
levels.
 secreted at times of stress to provide a  Aldosterone acts on the kidneys to provide active
burst of energy and assist it deal with reabsorption of sodium and an associated passive
reabsorption of water, as well as the active
an emergency scenario secretion of potassium in the principal cells

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C. Androgens
• hormones that exert masculinizing effects
• they promote anabolism and growth.
• The adrenal cortex in both sexes produces small amounts of sex hormone of the opposite sex.
• Adrenal androgens normally have little physiological effect.
• The ovaries and testes generate far more estrogens and androgens.
In males: Spermatogenesis, Inhibition of fat deposition, Muscle mass, regulation of human
aggression and libido, Masculinization of the developing male fetus
In females: Growth of pubic and axillary hair, Pubertal growth spurt, Development and maintenance
of female libido.

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 Adrenal gland Disorders
Classification of adrenal gland disorders could be;
1.Based on anatomy: Cortical vs medullar
2.Based on histology: Benign vs malignant
3.Based on hormone level: Hormonal deficiency vs hormonal excess
 Hormone deficiency
 inherited glandular or enzymatic disorders
 destruction of hypothalamus, pituitary or adrenal gland by autoimmune disorders, infection, infarction,
 iatrogenic events such as surgery or hormonal suppression.
 Hormone excess
 increased production of ACTH by the pituitary
 neuroendocrine ectopic ACTH producing cells or
 increased production of glucocorticoids, mineralocorticoids, or adrenal androgen precursors by adrenal
nodules.

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Adrenocortical Insufficiency(AI)

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primary AI
 lesions of the adrenal cortex prevent production of cortisol and often aldosterone.
 ACTH is elevated
 Acquired, chronic primary AI is termed Addison disease.
 is associated with both cortisol and mineralocorticoid deficiency.
secondary Adrenocortical insufficiency (central adrenal insufficiency)
 ACTH is decreased from anterior pituitary dysfunction
 If anterior pituitary doesn’t make enough ACTH, the adrenal glands don’t make enough cortisol.
Over time, the adrenal glands can shrink and stop working.
Tertiary adrenal insufficiency
 results from the impaired production or action of CRH from the hypothalamus which in turn
inhibits the secretion of ACTH from the pituitary gland.
 secondary and tertiary adrenal insufficiency are associated with cortisol deficiency, but not
mineralocorticoid deficiency. Why?
 This distinction accounts for the different clinical presentation and management of these disorders

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Continue….

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• Autoimmune destruction of adrenal cortex
 most common cause (in isolation/part of polyglandular autoimmune disorder).
 Hypothyroidism, Type 1 DM, alopecia, vitiligo, pernicious anemia, adrenal failure…
• Exogenous glucocorticoids — Prolonged administration of pharmacologic doses of synthetic
glucocorticoids is by far the most common cause of corticotropin (ACTH) deficiency and
consequent adrenal insufficiency.
• Critical illness - Subnormal corticosteroid production during critical illness in the absence of
structural defects in the hypothalamic - pituitary -adrenal axis has been termed "functional adrenal
insufficiency" or "relative adrenal insufficiency.“
• Drugs: Ketoconazole, etomidate, Mitotane …
• Other causes: Adrenal hemorrhage, infection(TB, HIV, syphilis), Neoplastic destruction,
 Waterhouse Friderichsen syndrome is a rare but life threatening disorder associated with bilateral
adrenal hemorrhage. Commonly caused by sever bacterial infection. Typically, caused by N.
meningitides but can also be caused by other organisms, including Pseudomonas spp.,
pneumococci, and Haemophilus influenzae.
 Fulminant infection from meningococcal bacteria in the bloodstream is a medical emergency and
requires emergent treatment with vasopressors, fluid resuscitation, and appropriate antibiotics.

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 Congenital Adrenal Hyperplasia
• Low cortisol production caused by a metabolic enzymatic abnormality in the cholesterol-steroid
biosynthesis pathway
• Autosomal recessive
• Deficiency in the enzyme 21-hydroxylase
• ACTH production by the pituitary gland is increased, resulting in hyperplasia of the adrenal
cortex and overproduction of adrenal androgens
• High propensity for developing benign adrenal cortical adenomas, but not malignancy

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 Addisonian(adrenal) Crisis

• is acute life-threatening form of adrenal insufficiency often preceded by hypotension

unresponsive to fluid resuscitation.
• Patients are easily and often misdiagnosed with an acute abdomen, whereas abdominal pain,
nausea, vomiting, and fever frequently accompany hypovolemia in these individuals.
• Pediatric patients can exhibit hypoglycemic seizures
Physical Examination
• Acute Dehydration signs • Hypotension (adrenal crisis)
• Orthostatic Hypotension • Tachycardia
• Symptomatic hypoglycemia • Altered mental status
• hyperpigmentation • Weight loss
• Public and axillary hair loose

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 Diagnostic Tests

Primarily made on clinical grounds, with a high index of suspicion

Morning serum cortisol and ACTH
Salivary cortisol and free serum cortisol in special occations
Exhibit abnormal aldosterone and renin levels
Confirmatory testing involves assessing the adrenal response to ACTH
stimulation in the form of the corticotropin test.
Serum electrolyte, blood sugar
 CBC (Normocytic anemia)
 Culture : Infection is a common cause of AI.
 CT Scan: helps to identify Adrenal hemorrhage, Calcification, and infiltrative
disease.

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 Continue…..

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 Treatment

• Fluid Resuscitation, Dextrose And Electrolyte Replacement (as patients

with adrenal insufficiency are hypovolemic, hypoglycemic,
hyponatremic and hyperkalemic ).
 1 to 3 liters of 0.9 percent saline solution or 5 percent dextrose in 0.9
percent saline (to correct possible hypoglycemia)/12 to 24 hours •
• Glucocorticoid Replacement is required in all forms of adrenal
insufficiency
 Patients with suspected adrenal crisis should undergo immediate
treatment with parenteral injection, 100mg Hydrocortisone IV bolus
after fluid resuscitation then 200mg/day (Continuous IV or 6-hourly
injection) OR 50 mg IV bolus administered every eight hours.
• Mineralocorticoid replacement is required only for patients with
primary adrenal insufficiency and is achieved with fludrocortisone

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 Prognosis
• With proper treatment Patients with adrenal insufficiency can live
a normal life span without limitations.
• Prognosis for untreated patient with adrenal insufficiency is poor.
Death is usually from hypotension or cardiac arrhythmia
secondary to hyperkalemia unless replacement steroid therapy.

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 Cushing’s syndrome
• clinical syndrome that result from chronic exposure to excess glucocorticoids of any
etiology.
• It is also called adrenal cortical hyper –function, Characterized by overproduction of adrenal
cortex hormones
• Non ACTH dependent- 15%
• ACTH dependent- 85%

What is difference between Cushing's

Syndrome vs Cushing disease?

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 causes

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 Diagnosis
Ix
• Adrenal imaging with U/S, CT, MRI,
Positron emission tomography (PET)
• Dexamethasone suppression test
• A corticotropin (ACTH) level :
Plasma ACTH concentrations are normally
between 20 and 80 pg/mL (4.5 and 18 pmol/L) at 8 AM.
• Corticotropin -releasing hormone (CRH) stimulation
• Other Blood Tests: CBC, RBS, RFT, LFT,
Serum electrolyte, ABG

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 Screening tests
1.low dose dexamethasone suppression test
• used to identify Cushing syndrome.
• 1 mg dexamethasone (DXM) administered at 11-12 PM.
 Serum cortisol is measured at 8- 9 AM. If Result: Cortisol < 50 nmol/L (suppression)→
exclude hypercortisolemia (Cushing Syndrome).
• Precuation: Drugs that induce hepatic microsomal enzymes (Phenobarbitone & phenytoin) →
↑ DXM metabolism and ↓ DXM blood level to achieve CRH suppression (false diagnosis of
Cushing).
2.24 Hour urinary free cortisol :if Cortisol < 250 nmol/day →exclude Cushing Syndrome.
Disadvantage: incomplete collection of urine →a false-negative result.
3.Midnight Salivary Cortisol : Result: if Cortisol < 100 ng/dL →exclude Cushing Syndrome

NB:Positive results of at least two screening tests would confirm the clinical diagnosis

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 • Serum ACTH >
• High> Pituitary Imaging
• Low> Abdominal imaging

• Ectopic ACTH syndrome for patients who have high serum ACTH levels, Normal
pituitary
• Direct measurements of ACTH in a downstream venous plexus —the inferior
petrosal sinus—after CRH stimulation has become the gold standard approach for
distinguishing ectopic ACTH production from Cushing disease.

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 CRH stimulation test
• The patient usually fasts for four hours or more.
• 100 mcg synthetic ovine CRH IV bolus given.
• Blood samples for corticotropin (ACTH) and cortisol are drawn 15 (or 5) and 0 minutes
before and as often as 5, 10, 15, 30, 45, 60, 90, and 120 minutes after CRH injection.
• ↑ ACTH and cortisol is consistent with pituitary Cushing disease.
• no response is consistent with ectopic Cushing
• Basal plasma ACTH concentrations increase 35 -900% (mean 400%) in normal subjects.

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 Algorism approach

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 Treatment

• Exogenous Cushing Syndrome- Gradual withdrawal

• Cushing Disease- trans-sphenoidal surgical resection, failed- bilateral
adrenalectomy
• Ectopic ACTH Syndrome- Resection of the primary ACTH-producing
tumor, if not possible- bilateral adrenalectomy
• ACTH-Independent Disease- Surgical resection of diseased Adrenal
• Medical Treatment of Hypercortisolism- if surgery fails/ impossible-
metyrapone, aminoglutethimide trilostane, ketoconazole, and
etomidate

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 Primary Aldosteronism

• Primary- aldosterone secretion is independent of the RAAS, and

plasma renin levels will be suppressed.
• Secondary- elevated renin levels are the cause of elevations in
aldosterone secretion

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 Investigation

• Screening test
• Morning (between 8 and 10 AM) Plasma Aldosterone Concentration (PAC)
• Plasma Renin Assay (PRA) or Direct Renin Concentration (DRC)
• PRA/DRC value be set at 0.2 ng/mL/h
• Confirmatory Testing
• 2 L of 0.9% sodium chloride IV over 4 hours, in the morning after an overnight
fast while the patient is in a recumbent position. PAC is measured; a level greater
than 5 ng/dL is diagnostic of primary aldosteronism, and levels greater than 10
ng/dL are suggestive of aldosterone producing adenomas
• Captopril suppression test, Furosemide-upright test and ACTH stimulation test –
low sensitivity

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 Treatment and Prognosis

• Surgically correctable subtype of primary aldosteronism can be

offered unilateral adrenalectomy
• Other patients can be managed effectively with medical therapy- The
aldosterone receptor antagonists spironolactone and eplerenone are
agents of choice

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Pheochromocytoma
 is Catecholamine -secreting tumors that arise from chromaffin cells of the adrenal medulla .
 Catecholamine -secreting tumors that arise from sympathetic ganglia are referred to
paragangliomas (extra -adrenal Pheochromocytoma).
 It is usually benign.
 In most cases, it originates in the medulla.
 The tumor causes increased function of the adrenal medulla and hyper secretion of its
hormones (epinephrine and norepinephrine).
 The tumor can be present without symptoms until triggered by pregnancy or other body
stressor

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 Rule of 10s of pheochromocytoma
• 10% of Pheochromocytoma with one of several familial are syndromes MEN -
2A and MEN -2B syndromes.
• 10% of Pheochromocytoma extra -adrenal (Known as Paragangliomas).
• 10% of non -familial adrenal Pheochromocytoma are bilateral; this figure may rise
to 70% in cases that are associated with familial syndromes.
• 10% of adrenal Pheochromocytoma are malignant
• 10% of adrenal Pheochromocytoma in childhood
• 10% can recur

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 Clinical presentation

• The triad of headache, episodic sudden perspiration, and tachycardia is a classic

hallmark of pheochromocytoma
• Hereditary pheochromocytomas- younger age and multifocal and/or bilateral at
presentation
• Malignant Pheochromocytoma- Metastatic disease is much more common in extra-
adrenal lesions, larger (>5 cm)
• HTN- most common sign. • Orthostatic hypotension
• palpitations • Diaphoresis (profuse sweating)
• Chest pain • Flank pain
• Nausea and vomiting • Nervousness
• Tremors • Elevated blood sugars
• Polyuria (increased urination)
 When it occurs with hereditary syndrome, other manifestation of the syndrome may be
noted

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 Investigations
• Plasma Metanephrine: 96% Sens. & 85% Spec.
• 24 -Hour urinary collection for Catecholamine & Metanephrines …86% sens & 99% spec.
• Computed Tomography (CT ): has accuracy of 85 -95% for detecting adrenal mass
• Magnetic Resonance Imaging (MRI): has sensitivity unto 100%. Preferred in children and
pregnant women

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 Treatment
• The gold -standard treatment in patients diagnosed with Pheochromocytoma is the surgical
removal of the tumor.
o Removal of tumor.
o Adrenalectomy (surgical removal of the effected adrenal gland ):
o Immunotherapy
• Preoperative preparation is very important and its goal is to decrease the incidence of
intraoperative cardiovascular complications.
 Start alpha blockade with Phenoxybenzamine 7-14 days preoperatively to allow for expansion
of blood volume.
 Volume expansion with isotonic saline, encourage liberal salt intake
 Initiate a beta blocker only after adequate alpha blockade (usually, 2 days). Why?

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 Complications

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 Prognosis
• The 5-year survival rate for people with non-malignant Pheochromocytoma is >95%.
• In patients with malignant Pheochromocytoma, the 5-year survival rate is <50%.
Follow up
• Test plasma free metanephrines 2 weeks post operatively.
• Obtain plasma metanephrines levels yearly for 10 years.
• Ensure blood pressure is under control
• Life long follow-up is mandatory if underlying genetic mutation.

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 Questions?
comments?

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