7 - Hypoadrenal Disorders Flashcards by Anisha Malli

Outline the hypothalamo-pituitary-adrenal axis.

Hypothalamus
- Corticotrophin Releasing Hormone (CRH)

Pituitary
- AdrenoCorticoTrophic Hormone (ACTH)

Adrenal Glands
- Cortisol

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What happens to the adrenal glands in the presence of ACTH?

They hypertrophy (ACTH is a trophic hormone)

They release cortisol

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What molecule is the starting point for all steroid hormones?

Cholesterol

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What cells in the body make cholesterol?

All human cells

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What does each part of the adrenal gland synthesise?

ADRENAL CORTEX
Zona glomerulosa = aldosterone
Zona fasciculata = cortisol
Zona reticularis = androgens

ADRENAL MEDULLA
adrenaline and noradrenaline

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What are the overall effects of steroid hormones?

Some are anabolic
= grow

Some are catabolic
= break down
= lose protein

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What happens in the hypothalamo-pituitary-adrenal axis when a person is stressed?

Greater release of ACTH

ACTH goes to the adrenal gland

Enzymes (3,11,17,21) for cortisol production are switched on by the ACTH

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Outline the pathway for aldosterone synthesis from cholesterol

Cholesterol
- desmolase

Pregnenolone
- 3-beta-hydroxysteroid dehydrogenase

Progesterone
- 21-hydroxylase

11-Deoxy-Corticosterone
- 11-beta hydroxylase

Corticosterone
- 18-hydroxylase

Aldosterone

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Outline the pathway for cortisol synthesis from cholesterol

Cholesterol
- desmolase

Pregnenolone
- 3-beta-hydroxysteroid dehydrogenase

Progesterone
- 17-alpha-hydroxylase

17-Alpha-Hydroxyprogesterone
- 21-alpha-hydroxylase

11-Deoxycortisol
- 11-beta-hydroxylase

Cortisol

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Outline the pathway for sex steroid synthesis from cholesterol

Cholesterol
- desmolase

Pregnenolone

Progesterone
- 17-alpha hydroxylase

17- Hydroxyprogesterone

Sex Steroids

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What are the 4 causes of hypoadrenalism?

ADRENAL GLANDS DESTROYED

Tuberculous - Addison’s Disease
Autoimmune Addison’s Disease
Congenital Adrenal Hyperplasia

ENZYMES IN THE STEROID SYNTHETIC PATHWAY NOT WORKING

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What is the most common cause of adrenocortical failure worldwide?

Tuberculosis causing:

Tuberculous - Addison’s Disease

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What is the most common cause of adrenocortical failure in the UK?

Autoimmune Addison’s Disease

[Not Tuberculous-Addison’s Disease due to relative lack of poverty in the UK]

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What are the 3 causes of adrenocortical failure?

ADRENAL GLANDS DESTROYED

Tuberculous - Addison’s Disease
Autoimmune Addison’s Disease
Congenital Adrenal Hyperplasia

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What are the signs and symptoms of Addison’s Disease?

Loss of weight
Increased pigmentation (due to high MSH)
- in mouth
- freckles
- hair
- skin
Hypotension
Exhaustion (tiredness)
Vitligo (autoimmune diseases go together)

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What are the consequences of adrenocortical failure?

Fall in blood pressure

Loss of salt in the urine

Increased plasma potassium

Fall in glucose due to glucocorticoid deficiency

High ACTH resulting in increased pigmentation

Eventual death due to severe hypotension

[LOW SODIUM, HIGH POTASSIUM!!]

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Why do people in adrenocortical failure have increased pigmentation?

No cortisol

No negative feedback

Pituitary releases lots of ACTH to try and increase cortisol levels

ACTH and MSH come from same precursor molecule called POMC. Therefore, when lots of ACTH is released so is lots of MSH

MSH causes increased pigmentation

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What is POMC?

Study These Flashcards

Pro-Opio MelanoCortin

Synthesised in the pituitary and broken down to ACTH and MSH (as well as into endorphins, enkephalins and other peptides)

What are the tests for Addison’s and what would the results be if the patient does have the disease?

Study These Flashcards

9am Cortisol [blood test]
- low

ACTH [blood test]
- high

Short Synacthen Test
- low

Why must cortisol be measured at 9am?

Study These Flashcards

This is because cortisol release is diurnal

Therefore, if you test it at night it will be low in any person regardless of whether or not they have Addison’s

How do you carry out Short Synacthen Test?

Study These Flashcards

Give 250 μg I.M. synacthen (synthetic ACTH)

Measure cortisol response

high in normal person
low in Addison’s Disease

What is a normal cortisol level at 9am compared to that of an Addison’s patient?

Study These Flashcards

270-900

Addison’s = 100

What would be the normal response to a short synacthen test compared to that of an Addison’s patient?

Study These Flashcards

Cortisol at 9am

Normal = 270-900
Addison’s = 100

I.M injection of synacthen

Cortisol at 9:30am

Normal = >600
Addison’s = 150

What is Congenital Adrenal Hyperplasia?

Study These Flashcards

A group of rare inherited autosomal recessive disorders characterized by a deficiency of one of the enzymes needed to make specific hormones.

Commonest form is caused by 21-hydroxylase deficiency [recessive condition]

Can be complete or partial

What would happen in a person with Congenital Adrenal Hyperplasia due to complete 21-hydroxylase deficiency?

No aldosterone or cortisol Due to lack of enzyme, all the precursor for steroid hormones goes into making sex steroids. Therefore, their adrenal glands make lots of testosterone. Excess testosterone and sex steroids. Will have a salt-losing Addisonian Crisis as soon as they are born The neonates are hypotensive and virilised at birth. Can survive less than 24 hours without treatment.

Why does Congenital Adrenal Hyperplasia not affect foetuses in utero?

This is because they are provided with the enzyme they cannot synthesise for themselves from their mother

Why is Congenital Adrenal Hyperplasia called by this name?

This is because back in the time when this was not diagnosed before birth, on post-mortem the neonates had extremely large adrenal glands. Hyperplasia had occurred within the adrenal glands because ACTH had been increased in large amounts to try and stimulate cortisol release from the adrenal glands due to lack of negative feedback. ACTH is a trophic hormone so this would have caused the adrenal glands to grow.

What is virilisation?

It is the biological development of sex differences, changes that make a male body different from a female body. Most of the changes of virilization are produced by androgens.

What is the age of presentation for a person with Congenital Adrenal Hyperplasia due to complete 21-hydroxylase deficiency?

As a neonate with a salt losing Addisonian Crisis | before birth, foetus gets steroids across placenta from mother

What is a particular consequence for girls with Congenital Adrenal Hyperplasia due to complete 21-hydroxylase deficiency?

May have ambiguous genitalia (virilised by excess adrenal testosterone)

Why can a family history of Congenital Adrenal Hyperplasia help a doctor in prevention of symptoms in the next child of the family?

Check for CAH - Girl: give mother steroids so foetus doesn't synthesise lots of ACTH and then testosterone causing inappropriate virilisation - Boy: lots of testosterone would lead to appropriate virilisation so this is less important to treat

What would happen in a person with Congenital Adrenal Hyperplasia due to partial 21-hydroxylase deficiency?

In order to produce enough cortisol and aldosterone, levels of 17-hydroxyprogesterone will be high as 21-hydroxylase is only partially active. Therefore, more sex steroids will also be produced In girls, puberty will occur early and then they will develop hirtuism

What is the age of presentation for a person with Congenital Adrenal Hyperplasia due to partial 21-hydroxylase deficiency?

Any age as they survive Present as symptoms present such as lack of period at 18, hirtuism development etc.

What are the symptoms associated with Congenital Adrenal Hyperplasia due to partial 21-hydroxylase deficiency?

Hirtuism (in girls) Precocious Puberty (early false puberty in boys) Virilisation in Girls = DUE TO HIGH LEVELS OF TESTOSTERONE Slight Hypotension = DUE TO SLIGHT LACK OF ALDOSTERONE Some Fatigue = DUE TO SLIGHT LACK OF CORTISOL

What are the symptoms associated with Congenital Adrenal Hyperplasia due to complete 21-hydroxylase deficiency?

Hypotensive Virilised at birth High testosterone and sex steroids Salt losing Addisonian Crisis at birth

What are the overall symptoms of Congenital Adrenal Hyperplasia due to 21-hydroxylase deficiency?

Virilisation in Girls - small breasts Precocious Puberty in boys Hypotension Fatigue High testosterone and sex steroids Low cortisol Some pigmentation Baldness Acne Large adrenal glands

What occurs in Congenital Adrenal Hyperplasia due to 11-beta hydroxylase deficiency?

ALDOSTERONE ARM Increased levels of 11-deoxycorticosterone (this doesn't normally circulate) This acts as aldosterone and binds to the aldosterone receptor Clinically, it looks like there is too much aldosterone - hypertension - hypokalaemia It is the opposite of a salt losing Addisonian crisis CORTISOL ARM They make no cortisol Increased ACTH Slightly hypoglycaemia Adrenal gland hyperplasia SEX STEROID ARM Increased sex steroids due to large amounts of precursors accumulating Virilisation occurs

Which hormones are deficient and which are in excess for patients with Congenital Adrenal Hyperplasia due to 11-beta hydroxylase deficiency?

DEFICIENT - Cortisol - Aldosterone EXCESS - Sex steroids (especially Testosterone) - 11 - Deoxycorticosterone

How would you spot Congenital Adrenal Hyperplasia due to 11-beta hydroxylase deficiency?

A child with high blood pressure who is virilised

What occurs in Congenital Adrenal Hyperplasia due to 17 hydroxylase deficiency?

Lots of aldosterone Cortisol and Sex Steroid synthesis cannot occur

Which hormones are deficient and which are in excess for patients with Congenital Adrenal Hyperplasia due to 17 hydroxylase deficiency?

DEFICIENT - Cortisol - Sex Steroids EXCESS - 11-Deoxycorticosterone - Aldosterone (mineralocorticoids)

What are the consequences for patients with Congenital Adrenal Hyperplasia due to 11-beta hydroxylase deficiency?

Hypertension - high aldosterone Hypokalaemia - high aldosterone Prepubertal - sex steroid deficiency Low Glucose - glucocorticoid Deficiency

What is the treatment for Addison's Disease?

Hydrocortisone (to replace cortisol) Fludrocortisone acetate (to replace aldosterone)

What is the treatment for an Addisonian Crisis?

I.V. Saline Glucose Corticosteroids

7 - Hypoadrenal Disorders Flashcards

(44 cards)