3. THE ADRENAL GLAND
• The pair located in the posterior abdomen between the superomedial
kidney and the diaphragm.
• Retroperitoneal, with parietal peritoneum covering their anterior
surface only.
• The right gland is pyramidal in shape, contrasting with the semi-lunar
shape of the left gland.
• Perinephric (or renal) fascia encloses the adrenal glands and the
kidneys. This fascia attaches the glands to the crura of the diaphragm.
They are separated from the kidneys by the perirenal fat.
4.
5. • The adrenal glands consist of an outer connective tissue capsule,
a cortex and a medulla. Veins and lymphatics leave each gland via
the hilum, but arteries and nerves enter the glands at numerous sites.
• The outer cortex and inner medulla are the functional portions of the
gland. They are two separate endocrine glands, with different
embryological origins:
• Cortex – derived from the embryonic mesoderm.
• Medulla – derived from the ectodermal neural crest cells.
6. • The cortex is yellowish in colour. It secretes two cholesterol derived
hormones – corticosteroids and androgens. Functionally, the cortex
can be divided into three regions (superficial to deep):
• Zona glomerulosa – produces and secretes mineralocorticoids such as
aldosterone.
• Zona fasciculata – produces and secretes corticosteroids such as
cortisol. It also secretes a small amount of androgens.
• Zona reticularis – produces and secretes androgens such
as dehydroepiandrosterone (DHES). It also secretes a small amount of
corticosteroids.
7.
8.
9. • The medulla lies in the centre of the gland, and is dark brown in
colour. It contains chromaffin cells, which secrete catecholamines
(such as adrenaline) into the bloodstream in response to stress.
• These hormones produce a ‘flight-or-fight‘ response. Chromaffin cells
also secrete enkephalins which function in pain control.
10. • The adrenal glands have a rich blood supply via three main arteries:
• Superior adrenal artery – arises from the inferior phrenic artery
• Middle adrenal artery – arises from the abdominal aorta.
• Inferior adrenal artery – arises from the renal arteries.
• Right and left adrenal veins drain the glands. The right adrenal vein
drains into the inferior vena cava, whereas the left adrenal vein drains
into the left renal vein.
11. • The adrenal glands are innervated by the coeliac plexus and greater
splanchnic nerves.
• Sympathetic innervation to the adrenal medulla is via myelinated pre-
synaptic fibres, mainly from the T10 to L1 spinal cord segments.
• Lymph drainage is to the lumbar lymph nodes by adrenal lymphatic
vessels. These vessels originate from two lymphatic plexuses – one
deep to the capsule, and the other in the medulla.
12. ADRENAL INSUFFICIENCY
• This is a chronic medical condition in which the adrenal glands don’t
produce enough essential hormones in response to a physiological or
psychological stressor. It could be as a result of congenital conditions,
tumours, non-functional adrenal glands, long-term steroid
administration, head trauma, loss of circulation to the adrenal glands,
and bilateral adrenalectemy, infections, etc.
• could be primary (damage to the adrenal glands, or drugs blocking
cortisol synthesis); Secondary; or Tertiary (the latter 2 as a result of
reduced ACTH from Pituitary or hypothalamic causes respectively.
13. • Cortisol is secreted in response to stressors. It is under the mediation
of the Hypothalamo-Pituitary-Adrenal (HPA) Axis. The stressors could
include exercise, illness, injury, starvation, electrolyte imbalances,
emotional stress or surgery among others.
• It’s actions include maintenance of cardiovascular function, blood
pressure regulation, carbohydrate metabolism, growth suppression,
immune functions and alteration of sleep pattern and awareness.
14.
15.
16.
17. ADDISON’S DISEASE
• Also known as Primary Adrenal Insufficiency. In this case, the there is
a reduction in production of Adrenal steroids. Onset occurs when 90%
or more of both adrenal cortices are dysfunctional or destroyed. Due
to reduced adrenal steroids, vascular smooth muscles become
nonresponsive to effects of catecholamines in stressful situations.
• This results in vasodilation and capillary leaking and the patient is
unable to maintain adequate blood pressure. Hence, the there is
cardiovascular collapse. The liver is also unable to metabolise
carbohydrates leading to reduced glucose levels which is difficult to
reverse unless cortisol is replaced.
18. ADDISONIAN CRISIS
• Addisonian crisis is a life threatening condition in which the adrenal
glands are almost nonfunctional. It is an acute presentation of
adrenocortical insufficiency.
• The Society of Critical Care Medicine recommends that the condition
be called CRITICAL ILLNESS-RELATED CORTICOSTEROID INSUFFICIENCY
(CIRCI).
• Hence, the diagnosis of Addisonian crisis is considered in critically ill
patients with refractory hypotension even while on vasopressors,
with adequate fluid Resuscitation.
19. • In 1855, Thomas Addison described a syndrome of long-term adrenal
insufficiency that develops over months to years, with weakness,
fatigue, anorexia, weight loss, and hyperpigmentation as the primary
symptoms. In contrast, an acute adrenal crisis can manifest with
vomiting, abdominal pain, and hypovolemic shock.
• The clinical definition involves:
1. Acute deterioration with absolute (Systolic Pressure < 100mm) or
relative hypotension (fall in Systolic Pressure by > 20mm)
2. Resolution within 1-2 hours of IV steroid administration.
20. EPIDEMIOLOGY
• A prevalence of adrenal crisis ranging from 5.2 to 8.3 per 100 patient
years has been reported.
• The incidence of adrenal crisis appears to increase with age with one
study reporting a rate of 24.3 admissions per million per year in
patients aged 60–69 years.
21. • A postal survey of over 1000 patients with PAI from four countries
reported an 8% annual frequency of adrenal crisis.
• Hahner and colleagues reported 8.3 adrenal crises per 100 patient-
years, with a mortality rate from adrenal crisis of 0.5/100 patient
years.
22. PRECIPITANTS
• Severe stress (eg, infection, trauma, surgery, hyperthyroidism, or
prolonged fasting), or minor stress (vaccinations) in patients with
latent or treated adrenal insufficiency;
• Hyperthyroidism or prescription of thyroid hormone to patients with
untreated adrenal insufficiency
• Nonadherence to glucocorticoid replacement or sudden withdrawal
of adrenocortical hormone in patients with chronic primary or
secondary adrenal insufficiency
23. • Bilateral adrenalectomy or removal of functioning adrenal tumor that
had suppressed the other adrenal gland
• Sudden destruction of the pituitary gland (pituitary necrosis) or
damage to both
• administration of intra- venous etomidate
24. PATHOPHYSIOLOGY
• Impaired suppression of inflammation leads to systemic inflammation
(fever, malaise, anorexia)
• Hemodynamic Effects: loss of permissive vasoconstriction support of
catecholamines
25. • Metabolic effects: reduction of gluconeogenesis in the liver, free fatty
acid production and amino acid release (Hypoglycemia,
hypocholesterolemia and hypoproteinemia).
• Renal Effects: sodium wasting with retention of potassium and
protons (hyponatrenia, hyperkalemia and NAGMA).
26.
27. • It could present in Chronic adrenal insufficiency in the presence of a
stressor or an acute adrenal insufficiency in the context of an acute
illness.
• NB: 2-4 weeks of daily oral corticosteroid administration is sufficient
to reduce response to stressor in the adrenal glands. Steroids are
always tapered off and an abrupt withdrawal is a potential trigger. It
takes up to about a year for a person’s adrenal glands to become fully
functional after tapering off steroids.
28. HISTORY
• GI: Anorexia, nausea, vomiting, abdominal pain, diarrhea
• CNS: Seizure, headache, confusion, psychosis, slurred speech
• MSS: Severe pain in the back and legs, flank pain, muscle weakness and
cramping
• CVS: Syncope
• Fever, Coma
29. • Prior steroid use: Use involves at least 20 mg daily of prednisone or its
equivalent for at least 5 days within the past 12 months. Patients
receiving doses close to normal physiologic levels require only 1
month to recover normal adrenal function.
• History of infection with organisms associated with adrenal crisis (eg,
Haemophilus influenzae, Staphylococcus aureus, Streptococcus
pneumonia, fungi)
• History suggestive of Meningococcemia
30.
31. • Adrenocorticotropin therapy, known primary or secondary
adrenocortical insufficiency
• AIDS
• Invasive or infiltrative disorders
• Tuberculosis
33. INVESTIGATION
• CAVEAT EMPTOR!!!
• BE SURE TO RESUSCITATE PATIENT (ABCs + IV Bolus Steroid) before
fully investigating.
• E/U/Cr
Hyponatremia is common (although not diagnostic); hyperkalemia, and
normal anion gap metabolic acidosis may be present.
• RBG: Hypoglycemia
34. • Serum cortisol: Less than 20 mcg/dL in severe stress or after ACTH
stimulation is indicative of adrenal insufficiency.
• ACTH test (diagnostic): Determine baseline serum cortisol, then
administer ACTH 250 mcg intravenous push (IVP), and then draw
serum cortisol 30 and 60 minutes after ACTH administration. An
increase of less than 9 mcg/dL is considered diagnostic of adrenal
insufficiency.
35. • FBC: Anemia (mild and nonspecific), lymphocytosis, and eosinophilia
(highly suggestive) may be present.
• Serum thyroid levels: Assess for autoimmune, infiltrative, or multiple
endocrine disorders.
• Cultures: Perform blood and other cultures as clinically indicated.
Infection is a common cause of acute adrenal crisis.
36. • Chest radiography: Assess for tuberculosis, histoplasmosis, malignant
disease, sarcoid, and lymphoma.
• Abdominal CT scanning: Visualize adrenal glands for hemorrhage, atrophy,
infiltrative disorders, and metastatic disease. Adrenal hemorrhage appears
as hyperdense, bilaterally enlarged adrenal glands.
• Electrocardiography
Prolongation of the QT interval can induce ventricular arrhythmias, Deep
negative T waves have been described in acute adrenal crisis.
37.
38. • Histology depends on the cause of the adrenal failure. In primary
adrenocortical failure, histologic evidence of infection, infiltrative
disease, or other condition may be demonstrated. Secondary
adrenocortical insufficiency may cause atrophy of the adrenals or no
histologic evidence at all, especially if due to exogenous steroid
ingestion. Appearance of bilateral adrenal hemorrhage may be
striking, as if bags of blood are replacing the glands.
39. TREATMENT
• Administration of glucocorticoids in supraphysiologic or stress doses
is the only definitive therapy. Other medications, such as pressors (eg,
dopamine, norepinephrine) or antibiotics, are administered as
clinically indicated.
40.
41. • The following are essential in the management of the patient post-
Resuscitation
• Endocrinologist
• Infectious disease specialist
• Critical care physician
• Cardiologist
• Surgeon
• Other consultations as clinically indicated
42. • A short ACTH stimulation test may be performed during resuscitation.
• 1L Normal Saline over 30 to 60 minutes with 100mg of IV Bolus
Hydrocortisone is administered (or 40mg IV methylprednisolone)
• Continue infusion of 2-3L saline within 24 hours in addition to 100mg
of IM Hydrocortisone 6 hourly (or 50mg IV Hydrocortisone)
43. • Continue IV saline at a slower rate for the next 24 to 48 hours.
• Based on patient’s response, change to oral Hydrocortisone 20mg 8
hourly, and owed by a gradual reduction to 20-30mg in divided doses
over the next few days.
• Fludrocortisone 0.1mg is administered orally daily when saline
infusion is stopped.
• Search for and treat possible infections with empiric antibiotics,
pending culture and sensitivity pattern determination
44. • Dehydroepiandrosterone 50mg daily can be given to boost libido in
women
• Pressors (eg, dopamine, norepinephrine) may be necessary to combat
hypotension
• Ensure vitals, glucose and urine output monitoring every 1-2 hours
• Salt in diet
• Patient education
45. • Treat any underlying or precipitating disorder as clinically indicated.
• Carefully monitor growth and development in pediatric patients.
• Recommend medical tag or bracelet that alerts emergency personnel
to adrenal gland insufficiency.
46. • If exposed to chickenpox, prophylaxis with varicella-zoster immune
globulin is indicated.
• If exposed to measles, prophylaxis with immune globulin is indicated.
• Closely observe for reactivation of tuberculosis in patients with latent
disease.
48. PATIENT EDUCATION
• Instruct patients regarding the importance of careful attention to
health and fluid intake and to double maintenance doses when ill
until medical attention is obtained.
• Educate them on how to avoid exposure to chickenpox or measles; if
exposed, they should seek medical advice without delay.
• They ought to notify physician or seek medical attention for persistent
nausea and vomiting, fatigue, and abdominal pain.
50. REFERENCES
• 2022 Current Medical Diagnosis and Treatment. Papadakis MA, McPhee SJ,
Rabow MW. Chapter 26I – Endocrine disorders, pg 1171. McGraw Hill. New
York.
• Medscape (2022). Addison’s Disease. Retrieved from
https://www.google.com/url?sa=t&source=web&rct=j&url=https://emedici
ne.medscape.com/article/116467-
overview&ved=2ahUKEwiAutqesK_6AhWh_7sIHQpYAlIQFnoECA4QAQ&usg
=AOvVaw3vEAVLFzNfdNFiK-nm7PWj.
• Medscape. Adrenal Crisis. Retrieved from
https://www.google.com/url?sa=t&source=web&rct=j&url=https://emedici
ne.medscape.com/article/116716-
overview&ved=2ahUKEwihlv_ssK_6AhWlgf0HHebUCAgQFnoECAsQAQ&usg
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51. • Joersjö P, Block L. BMJ Case Rep 2019;12:e231858. doi:10.1136/bcr-
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• Smans LC, Van der Valk ES, Hermus AR, et al. Incidence of adrenal
crisis in patients with adrenal insufficiency. Clin Endocrinol (Oxf)
2016; 84: 17–22.
• Hahner S, Spinnler C, Fassnacht M, et al. High incidence of adrenal
crisis in educated patients with chronic adrenal insufficiency: a
prospective study. J Clin Endocrinol Metab 2015; 100: 407–416.
52. • Rushworth RL and Torpy DJ. A descriptive study of adrenal crises in
adults with adrenal insufficiency: increased risk with age and in those
with bacterial infections. BMC Endocr Disord 2014; 14: 79.
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