Clinical Aspects of the Adrenal Gland Clinical Case & Discussion Flashcards
a
Aldosterone
b
Cortisol
c
Testosterone, Progesterone, Estrogen
d
Norepinephrine, Epinephrine
Name a Mineralocorticoids?
aldosterone
Name a Corticocorticoids
cortisol
Name Sex Steroids
Testosterone, Progesterone, Estrogen
Name adrenal medulla hormones?
Norepinephrine, Epinephrine
WHat are the different types of adrenal disorders that may be present?
What is the common approach to dealing with an adnrela disorder?
Clinical Suspicion
Test for assessing functional status - Is it functioning? Is it primary or secondary?
What is the aetiology?
If tumour: Can it be removed? Is additional Chemotherapy or radiotherapy required? How can we follow the course of the disease?
Endocrine deficiency may need correction
Aetiology specific treatment
What is this image showing?
Hypathalamo Hypopituitary Adrenal axis
how does primary hypofunction affect the hypothalamo hypopituitary adrenal axis
In hypofunction if primary then the adrenal gland is no producing enough cortisol and therefore no feedback so ACTH will rise to try produce more cortisol
If high ACTH then clue it is primary
How are the different hormones made in the different layers of the adrenal gland?
All steroid hormones are derived from cholesterol, but different enzymes are found in different adrenal zones, resulting in different end products e.g. enzymes needed to make aldosterone are found only in the zona glomerulosa
What are the different causes of hypofunction?
Adrenal dysgenesis – doesn’t form and incompatible with life
hyposecretion may be due to Primary Adrenal insufficiency which is caused by what?
Addisons disease
What are the causes of Addison’s disease?
Immune destruction (auto)
Invasion
Infiltration
Infection
Infarction
Iatrogenic
What are the causes of adrenal enzyme defects resuling in hyposecretion
congenital adrenal hyperplasia (most commonly 21-hydroxylase deficiency)
What is Autoimmune Addison’s?
>85% UK cases of adrenal failure
+ve adrenal autoantibodies (to 21-OHase) in 70% cases
lymphocytic infiltrate of adrenal cortex
associated autoimmune diseases are common:
- thyroid disease (20%)
- Type 1 diabetes mellitus (15%)
- premature ovarian failure (15%)
what are common symptoms seen in primary adrenal failure?
Weakness, fatigue, anorexia, weight loss 100%
Skin pigmentation or vitiligo 92%
Hypotension 88%
Unexplained vomiting or diarrhoea 56%
Salt Craving 19 %
Postural symptoms 12%
What are some possible clues to the diagnosis of adrenal failure?
- Disproportion between severity of illness & circulatory collapse/hypotension/dehydration
- Unexplained hypoglycaemia
- Other endocrine features (hypothyroidism, body hair loss, amenorrhoea)
- Previous depression or weight loss
What is the diagnosis of adrenal insufficiency?
Non-specific symptoms - so must think of the diagnosis in the first place!
Routine bloods: U&E, glucose, FBC
Early morning cortisol:
>450 nmol/l (not Addison’s)
<350 nmol/l (adrenal status uncertain)
Synacthen test (and basal ACTH)
If suspicion high & patient unwell, treat with steroids and do Synacthen test later
What is the Short Synacthen test?
The test is based on the measurement of serum cortisol before and after an injection of synthetic ACTH (The function of ACTH is to regulate levels of the steroid hormone cortisol, which released from the adrenal gland)
Summary diagram showing the process of working out if there is an adrenocorticol insufficiency
How is mineralocorticoid replacement carried out?
Synthetic steroid, fludrocortisone
Binds to mineralocorticoid (aldosterone) receptors
50-300 micrograms daily
Adjust dose according to:
- clinical status (postural BP, oedema)
- U&E
- plasma renin level
who needs special care when it comes to stress and steroids?
Hypoadrenal patients on replacement steroids
Patients on steroids in doses sufficient to suppress the pituitary adrenal axis (>7.5mg prednisolone daily, or equivalent)
Patients who have received such treatment during the previous 18/12 (HPA axis may still be suppressed)
what action should be taken in regards to minor short-lived illness or stress?
double glucocorticoid dose
What actions shoudl be taken in regards to major illness or operation?
(especially if nil by mouth or GI upset)
100mg hydrocortisone iv stat
50-100mg HC iv 8-hourly
as stress abates, reduce HC by 50% per day until back on usual replacement dose
What are three important ‘self-care’ rules
for patients on steroids?
- Never miss steroid doses
- Double the hydrocortisone dose in event of intercurrent illness (eg flu, UTI)
- If severe vomiting or diarrhoea, call for help without delay
(likely to need IM hydrocortisone - some patients or their partners are taught to inject)
what are endocrine caues of hypersecretion?
Primary hyperaldosteronism:
- unilateral adenoma
- bilateral hyperplasia
Rarer causes:
- Phaeochromcytoma
- Cushing’s syndrome
- Acromegaly
- Hyperparathyroidism
- Hypothyroidism
- Congenital Adrenal hyperplasia
what are adrenal disorders causing hypersecretion from the cortex?
Cushing’s syndrome
Conn’s syndrome
what are adrenal disorders causing hypersecretion from the medulla?
Phaeochromocytoma
what is cushings syndrome?
too much cortisol, androgens
caused by adenoma, carcinoma or bilateral hyperplasia
What is Conns syndrome?
too muchaldosterone
caused by adenoma or bilateral hyperplasia
What is Phaeochromocytoma?
too many catecholamines
Cushing’s syndrome = excess corticosteroids
Cortisol is a catabolic hormone causing what?
Tissue breakdown - causes weakness of skin, muscle & bone
Sodium retention - may cause hypertension & heart failure
Insulin antagonism - may cause diabetes mellitus
What are the side effects of glucocorticoid therapy?
what features may be seen in a person with cushings syndrome?
WHat is the chance of someone presenting with each sign or symptoms in cushings disease?
what are the different types of cushings syndrome?
ACTH-dependent:
75% cases: Pituitary tumour (Cushing’s disease)
5% cases: Ectopic ACTH secretion (eg lung carcinoid)
ACTH-independent
20% cases: Adrenal tumour (adenoma or carcinoma)
Corticosteroid therapy (eg for asthma, IBD)
What are the different possible sites of endocrine pathology in HPA and their effects?
Summary diagram showing the dfference between dependent and indepench ACTH cushings syndrome
what is the approach to dealing with hypercortisolism?
how do you screen for cushings syndrome?
24 hr Urinary free cortisol: normal 14- 135 nmol/24h
1mg overnight Dexamethasone suppression test taken at midnight: normal <50nmol/l (1.8 mg/dL) at 09.00h
cortisol suppression should happen and you should get a low level and if you don’t then you know something is wrong
How does cortisol and ACTH vary thoughout the day?
Cortisol & ACTH Diurnal variation
Surge in cortisol in preparation to waking up
Highest levels in morning and lowest when you go to bed so that’s why you check it in the morning
What happens to cortisol levels throughout the day if you have a hypersecretion problem?
describe what is seen
Tumour is ACTH independent and the body knows too much cortisol is there so switches of ACTH
Very high ACTH then more likely it is ectopic in origin
How do steroids affect cortisol production?
Highest amount of steroid seen at the top
Will switch off endogenous cortisol production
High does will make blue come down
what does aldosterone do?
Deals with water balance
Reabsorption of sodium and water and the excretion of potassium and hydrogen ions
What is the pathophysiology of primary hyperaldosteronism?
Less renin produced as alreadye nough aldosterone so the effect of angiotensin 2 which is meant to reduce the production of aldosterone but as the tumour is making it then it doesnt stop
A/R ratio is elevated
What would the screening results of plasma aldsterone to plasam renin activity show?
study this diagram
Someone with Conns also has what
hypertension
40-year-old woman
Hypertension
Hypokalaemia : K+ 2.7 mmol/l (N, 3.5-5)
Plasma aldosterone 1135 pmol/l (N, 100-500)
Plasma renin 1.8 (N, 2.8-4.5)
What is her diagnosis?
primary hyperaldosteronism
CT scan: 2cm left adrenal mass
iodocholesterol scan: increased uptake on the left
surgical removal of benign adenoma (mostly laparoscopically now)
post-op BP 120/80
no hypotensive drugs required
What is a pheochromocytoma?
Pheochromocytoma is a rare tumor of adrenal gland tissue. It results in the release of too much epinephrine and norepinephrine, hormones that control heart rate, metabolism, and blood pressure
What are the symptoms of a Phaeochromocytoma?
Hypertension (persistent in 70%)
Paroxysmal attacks:
headache
sweating
palpitations
tremor
pallor
anxiety/fear
30% of Phaeochromocytoma are caused by what?
30% inherited origin
How is an andrel mass often picked up and what questions are asked?
Adrenal mass often picked up incidentally
Is a mass functioning? Is it malignant? Does it ned treatment/surveillance?
WHat is congenital adrenal hyperplasia?
Congenital adrenal hyperplasia is any of several autosomal recessive diseases resulting from mutations of genes for enzymes mediating the biochemical steps of production of mineralocorticoids, glucocorticoids or sex steroids from cholesterol by the adrenal glands
Why does a deficit in 21-hydroxylase cause adrenal hyperplasia?
- Lack of 21-hydroxylase inhibits synthesis of cortisol
- This removes the negative feedback on ACTH and CRH release
- Increased ACTH secretion is responsible for enlargement of adrenal glands
- Negative feedback of ACTH on CRH synthesis remains
Congenital adrenal hyperplasia is due to what?
>90% cases due to 21-hydroxylase deficiency
Severe cases:
- neonatal salt-losing crisis
- ambiguous genitalia (girls)
Incomplete defects:
- pseudo-precocious puberty (boys) (early puberty)
- hirsutism (women) (developing features due to excess sex steroids)
a
conn syndrome
b
cushings syndrome
c
Phaemochromocytoma
d
addinsons disease
the main substrate for formation of adrenal cortical hormones is:
A) dopamine
B) very long chain fatty acids
C) metyrapone
D) abetaliporotein
E) cholesterol
E
abnormalities of which of the following hormones can cause abdnormalities in the serum sodium levels
A) cortisol
B) aldosterone
C) insulin
D) vasopressin
E) all of the above
F) none of the above
E
4
which of the following hormonal abnormalities can cause hypertension
A) increased cortisol
B) decreased aldosterone
C) decreased thyroxine
D) increased prolactin
E) decreased parathormone
A
