Adrenal Gland

Disorders
Priya Losshini Manokar
Year 5 MBBS
Newcastle University Medicine Malaysia
 Learning Outcomes

Adrenal Gland and its Cushing syndrome Addison’s disease Conn’s syndrome
Hormones

Congenital Adrenal
Phaeochromocytoma
Hyperplasia
What is adrenal gland? Adrenal Gland and its
Hormones

§ Also called as suprarenal glands

§ Comprises an outer cortex and inner
medulla
§ The cortex has 3 zones :
üZona Glomerulosa (G) – salt
üZona Fasciculata (F) – sugar
üZona Reticularis (R) – sex

§ The inner medulla synthesizes, stores

& secretes catecholamines (flight-or-
fight’ response)
 Lets discuss the
conditions that disrupts
these hormones!!!
 Cushing Syndrome
q Clinical condition resulting from prolonged
exposure to excessive glucocorticoid
hormones.
q Causes :
ACTH dependent ACTH independent

Pituitary adenoma Exogenous

(Cushing’s glucocorticoid
disease)

Adrenal
Ectopic ACTH adenoma/carcinoma
producing tumor

Adrenal
hyperplasia Clinical features of Cushing syndrome

Cushing Syndrome
 Investigation of Cushing syndrome
2 Stages Work-up
1. Confirm whether it’s a Cushing syndrome

ü 24-hr urinary free cortisol

ü Low dose dexamethasone suppression test (most sensitive)
ü Late night salivary cortisol

2. Determine the cause

ü Serum ACTH (ACTH-independent or ACTH-dependent cause)

Cushing Syndrome
 How to manage Cushing syndrome?
Drug treatment : Gradually taper down their steroid dose, Metyrapone
(blocks cortisol synthesis)
Pituitary adenoma : trans-sphenoidal adenectomy (remove the tumor)
Adrenal adenoma : adrenalectomy
Ectopic secretion by lung cancer : treat the lung cancer
(surgery/medical treatment)

Cushing Syndrome
 Addison’s disease
Primary adrenal failure
q Destruction of adrenal cortex leads to
glucocorticoid (cortisol) and
mineralocorticoid (aldosterone) deficiency.
q Causes : autoimmunity (UK), TB (world),
HIV, lymphoma, breast/lung cancer, • Hyperpigmentation in buccal mucosa,
amyloid, Waterhouse-Friedrichsen palmar creases (common in primary adrenal
syndrome failure)
• Fatigue, Weight loss
• Hypoglycemia
Secondary adrenal failure • Abdominal pain
q Inadequate ACTH production (resulting • Diarrhoea
from acute steroid withdrawal) • Postural hypotension
q Pituitary disorder (tumors) Clinical features of Addison’s disease
q Adrenal cortex is still intact.
Addison’s Disease
How to Investigate & Manage Addison’s disease?
ACTH stimulation test (short Synacthen test) Electrolyte abnormalities seen in
Addison’s disease
• Measure plasma cortisol 30min before
• Given Synacthen 250microgram IM • Hyperkalemia
• Measure plasma cortisol 30min after giving • Hyponatremia
Synacthen • Hypoglycemia
• Cortisol should rise to > 550 nmol/l : failure to • Metabolic acidosis
do so (ADRENAL INSUFFICIENCY)
Management
9am serum cortisol
Primary adrenal failure
Mx : replace Hydrocortisone and Fludrocortisone
• > 500 nmol/l makes Addison's very unlikely
• < 100 nmol/l is definitely abnormal Secondary adrenal failure
• 100-500 nmol/l should prompt a ACTH stimulation Mx: Replace hydrocortisone only
test to be performed

Cushing Syndrome
 Conn’s syndrome
Features
Primary hyperaldosteronism
• Excess aldosterone - Refractory hypertension
• Independent of RAAS system - Hypokalemia (weakness, cramps,
• Due to aldosterone-producing adenoma (Conn’s fatigue, polyuria)
syndrome) (2/3) & bilateral adrenocortical - Metabolic alkalosis
hyperplasia (1/3)

Secondary hyperaldosteronism How to investigate?

• Due to low renal perfusion à high renin
v plasma aldosterone: renin ratio (primary
(activates RAAS system)
vs secondary)
• What are the conditions that can cause low
v Serum aldosterone level
renal perfusion?
v High-resolution CT abdomen
• Eg : renal artery stenosis, CCF, diuretics,
v Adrenal vein sampling (done after
accelerated hypertension
hyperaldosteronism is proven)
Aldosterone Renin
Primary ↑ ↓/normal
hyperaldosteronism
Conn’s Syndrome
Secondary ↑ ↑
hyperaldosteronism
 How to Manage Hyperaldosteronism?
Primary hyperaldosteronism

Conn’s syndrome : Laparoscopic adrenalectomy

Bilateral adrenocortical hyperplasia : Aldosterone antagonist (spironolactone or amiloride)

Secondary hyperaldosteronism

Treat the underlying cause (renal artery stenosis, stop diuretics, treat the CCF)

Cushing Syndrome
Break time!
LET'S TAKE A 2 MINUTE BREAK TO RECHARGE...

Any questions? Drop them in the Q and A!

Coming up…..
v Phaeochromocytoma
v CAH
 Congenital Adrenal
Hyperplasia 21-hydroxylase deficiency features (90%)
ü virilisation of female genitalia
ü precocious puberty in males
• Group of autosomal recessive disorders ü 60-70% of patients have a salt-losing
• Affect the adrenal steroid biosynthesis crisis at 1-3 wks of age
• Low cortisol, aldosterone à anterior pituitary
secretes more ACTH à more stimulation of
adrenal androgens à virilization
• Symptoms depend on which gene is defective in
your body
• Features : vomiting, diarrhoea, ambiguous
genitalia

Cause
21-hydroxylase deficiency (90%)
11-beta hydroxylase deficiency (5%)
Congenital Adrenal
17-hydroxylase deficiency (very rare)
Hyperplasia
 Phaeochromocytoma
• Catecholamine-producing tumor (adrenal
medulla) Tachycardia High BP
• Extra-adrenal tumor (paraganglioma)
• 10% rule : bilateral, malignant, extra-adrenal,
familial.

Investigations headaches Palpitation

• 24hr urine metanephrines
• Abdominal CT/MRI to localize the tumor

Management!!!
• Stabilize the patient first (alpha blocker- Anxiety Sweating
phenoxybenzamine, then after 2 weeks
give beta blocker-propranolol)
• Definitive : surgery
Phaeochromocytoma
Too much cortisol : Too many catecholamines :
Cushing syndrome Phaeochromocytoma
Too little cortisol : Too many sex hormones :
Addison’s disease Congenital adrenal
hyperplasia
Too many Aldosterone :
Conn’s syndrome
 Mentimeter :
1. A 37-year-old lady presents with weight gain and bruising. On
examination, she is hypertensive and has proximal myopathy. A low
dose dexamethasone suppression test showed a lack of appropriate
suppression of plasma cortisol. However, cortisol was suppressed
during a high dose dexamethasone suppression test. Plasma ACTH was
elevated. A pituitary MRI was normal.

What is the most likely diagnosis?

A. Cushing’s disease D. Conn’s syndrome

B. Exogenous steroid use E. Adrenal hyperplasia
C. Small cell lung cancer
2. A 41-year-old man presents with recurrent headaches. These
typically occur 2-3 times a day and are associated with sweating and
palpitations. As he was concerned that it may be due to blood pressure
he borrowed his father’s home monitor. During these episodes his BP is
around 210/110 mmHg. Given the likely diagnosis, what is the most
appropriate next test?

A. Ultrasound of adrenal glands

B. Phenoxybenzamine suppression test
C. 24-hour blood pressure monitoring
D.24-hour urinary collection of metanephrines
E. 24-hour urinary collection of catecholamines
3. A 53-year-old male presents to A&E with palpitations, sweating and
intermittent headaches. On examination, his blood pressure is
162/112. He is later diagnosed with a phaeochromocytoma and
advised it should be operated on. What is the 1st-line management
that should be initially started?

A. Alpha blockade (Phenoxybenzamine)

B. Calcium-channel blocker
C. High salt diet
D.Beta-blockade (Propranolol)
E. Chemotherapy
4. A 14-year-old girl sees you in the outpatients department with a
variety of troubling symptoms. She has suffered with bullying at school
due to facial hair and large stature. She also reports menarche was at
10 years old. You organize some investigations which show;
What is the most likely diagnosis?

Na+ 131 mmol/l (low)

K+ 6.1 mmol/l (high)
A. Turner's syndrome
Dexamethasone
B. Polycystic ovarian syndrome
8am cortisol <50nmol/l
suppression test C. Addison’s disease
Testosterone 2 nmol/l (0.7-3 nmol/l) D.Congenital adrenal hyperplasia
Plasma 17-
2 mg/l (0.2-1 mg/l) E. Cushing’s syndrome
hydroxyprogesterone
5. A 55 year old woman has Cushing’s syndrome. She has previously
treated with a bilateral adrenalectomy. She then starts to develop
headaches and blurred vision with increasing skin pigmentation. What
is this syndrome described?

A. Nelson’s syndrome
B. Carcinoid syndrome
C. Multiple Endocrine Type 1 (MEN1) Syndrome
D.Polycystic Ovarian Syndrome
E. Nephrotic syndrome
 Summary
1 2 3 4
Lesson Recap 1 Lesson Recap 2 Lesson Recap 3 Lesson Recap 4
Cushing’s syndrome causes: Managing
Addison's disease is the Phaeochromocytoma
ACTH-independent primary adrenal failure The most common
(adrenal adenoma & and the most common deficiency of CAH is
Alpha blocker first, after 2
exogenous steroid) cause in the UK is
autoimmunity, and TB weeks, give beta blocker 21-hydroxylase
ACTH-dependent worldwide before going for surgery deficiency
(pituitary adenoma & (prevent unopposed
ectopic ACTH by SCLC) alpha-receptor mediated
vasoconstriction
 Additional Resources
https://www.endoc
rinology.org/clinical-
Oxford Handbook practice/clinical-
guidance/society-
10th Edition pg Passmedicine for-endocrinology-
224-230 guidance/
Society for
Endocrinology UK
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