Hypopituitarism Flashcards

1
Q

General overview of structure of the pituitary?

A

Anterior - glandular

Posterior - neural

Sits on sella turcica

Optic chains above

Anterior blood supply through hypophyseal portal system. Hypothalamic releasing or inhibitory factors travel in this to regulate anterior pituitary production

Posterior has no blood supply

Hypothalamus hormones -> anterior pituitary-> glands

Best way to view is with MRI

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2
Q

What are the anterior pituitary hormones?

A

Growth hormone (Somatostatin, GhRH)

Prolactin (dopamine)

TSH (TRH)

LH and FSH (GnRH)

ACTH (CRH)

(Hypothalamus hormones in brackets)

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3
Q

What are the effects of the anterior pituitary hormones?

A

GH -> liver and bones, growth and IGF-1

Prolactin -> breast, milk production (oxytocin is ejection)

LH and FSH -> gonads, oestrogen, progesterone and testosterone

TSH -> thyroid, T3 and T4

ACTH -> adrenal cortex, cortisol

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4
Q

What are primary and secondary diseases?

A

Effect glands: thyroid, adrenal, gonads

Low home be levels from these can be primary or secondary

Primary: problem is with the last gland

Secondary: problem is with the anterior pituitary

Eg.

Thyroid:

1° - high TSH, low T3 and T4

2° - low TSH, low T3 and 4

Adrenal:

1° - high ACTH, low cortisol

2° - low both

Gonads:

1° - high LH and FSH, low testosterone/oestrogen/progesterone

2° - both low

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5
Q

What are primary and secondary hypothyroidism?

A

Thyroid:

1° - high TSH, low T3 and T4

May be autoimmune destruction of thyroid gland

TRH would also be high but this can’t be measured

2° - low TSH, low T3 and 4

May be pituitary tumour damaging thyrotrophs

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6
Q

What are primary and secondary hypoadrenalism?

A

NB cortisol is regulated by ACTH so this is effected. Aldosterone is not (renin-angiotensin)

Adrenal:

1° - high ACTH, low cortisol

May be auto immune destruction of adrenal cortex

2° - both low

May be pituitary tumour damaging corticosteroids

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7
Q

What are primary and secondary hypogonadism?

A

Gonads:

1° - high LH and FSH, low testosterone/oestrogen/progesterone

May be destruction of testes by mumps or ovaries by chemo

2° - both low

May be pituitary tumour damaging gonadotrophs

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8
Q

What are the two categories of hypopituitarism (give examples of both)?

A

CONGENITAL:

Rare,
Usually due to mutations of transcription factor genes needed for normal anterior pituitary development (eg. PROP1 mutation)

They will be deficient in GH and at least one other ant pit hormone

They will have a short stature

Hypoplastic pituitary gland on MRI

ACQUIRED:

More common

Tumours (adenomas, metastases, cysts)

Radiation (hypothalamic/pituitary damage)

Infection (eg. Meningitis)

Traumatic brain injury

Pituitary surgery

Inflammation (hypophysitis)

Pituitary apoplexy (haemorrhage, or less commonly infarction)

Peri-partum infarction (sheehans syndrome)

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9
Q

What is panhypopituitarism?

A

Total loss of anterior and posterior pituitary function

Hypopituitarism usually only describes anterior dysfunction, but certain processes such as inflammation (hypophysitis) and surgery can cause posterior dysfunction too.

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10
Q

What is radiotherapy induced hypopituitarism?

A

Radiotherapy , either directly to pituitary due to acromegaly eg, or indirectly to surrounding structures such as a nasopharyngeal carcinoma, causes hypopituitarism

Extent of damage depends on dose of radiotherapy

Growth hormone and gonadotrophins are most sensitive

Prolactin can increase after radiotherapy is the hypothalamus is damaged, as dopamine has an inhibitory effect on prolactin

The risk of damage persists up to 10 years after therapy, so annual assessment is needed

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11
Q

How does hypopituitarism present?

A

GH - reduced quality of life, short stature only in children

FSH and LH - reduced libido, secondary amenorrhoea, erectile dysfunction, reduced pubic hair

TSH - fatigue (may also be weight gain)

ACTH - fatigue (NB not a salt losing crisis as renin-angiotensin is not affected)

Prolactin - inability to breastfeed

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12
Q

What is Sheehan’s syndrome? (Including symptoms)

A

Post-partum hypopituitarism secondary to hypotension (due to haemorrhage - PPH). Leads to pituitary infarction

More common in developing countries

Anterior pituitary enlarges during pregnancy due to lactotroph hyperplasia

Symptoms:
Lethargy, anorexia, weight loss - TSH/ACTH deficiency

Failure of lactation - prolactin deficiency

Failure to resume menses post delivery - LH/FSH deficiency

Posterior pituitary is usually not affected coz it has no blood supply

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13
Q

What is pituitary apoplexy?

A

Intra pituitary haemorrhage or les commonly infarction

Often has a dramatic presentation in patients who already have a pituitary tumour (adenoma). It may be the first presentation of an adenoma

Can be precipitated by anticoagulants

Symptoms:
Severe sudden onset headache
Visual field defect (compressed optic chias - bitemporal hemianopia)

Involvement of the cavernous sinus (contains internal carotid arteries and cranial nerves) may lead to Diplopia (IV, VI) and ptosis (III)

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14
Q

How is hypopituitarism diagnosed?

A

Biochemically:
by measuring hormone levels. But caution must be taken

Cortisol - diurnal rhythm, high around 9am

T4 - circulating half life of 6days

FSH/LH - cyclical in women

GH/ACTH - pulsatile

Radiologically: 
Pituitary MRI (CT can’t delineate pituitary gland well)

This may reveal specific pituitary pathology (eg. Haemorrhage (apoplexy) or adenoma)

In an MRI you may see the haemorrhage or a tumour, or congenitally the sella may look empty as there is only a thin rim of pituitary tissue

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15
Q

How is dynamic pituitary function used in hypopituitarism diagnosis?

A

ACTH and GH are stress hormones (act when the body is stressed)

So

Insulin is injected to induce hypoglycaemia (<2.2mM). This is the stress

Insulin induced hypoglycaemia stimulates GH and ACTH (cortisol is measured) release

An increase in both of these would be normal. They would remain low in hypopituitarism

You can also inject TRH and GnRH to see if it has any effect on TSH and LH/FSH levels

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16
Q

How is hypopituitarism treated?

A

Hormone replacement

Only one you can’t fix is low prolactin, no substitute, and not really enough demand

17
Q

How is the GH deficiency treated?

A

Confirmation of GH deficiency must be confirmed by dynamic pituitary function test

Assess quality of life using a specific questionnaire

Then daily injections

A response is measured by seeing whether there is an improvement in quality of life and plasma IGF-1

I think the injections are stopped if there is no effect

18
Q

How is TSH deficiency treated?

A

Replace with once daily levothyroxine

The dose must be adjusted. TSH will be low, I like in primary hypothyroidism so TSH levels can’t be used to adjust dose.
Aim for T4 levels above the middle of the reference range

19
Q

How is ACTH deficiency treated?

A

Replace cortisol rather than cortisol

It is difficult to mimic the diurnal variation of cortisol

Prednisolone- once daily (3mg)

OR

Hydrocortisone- three times daily (10mg->5mg-> 5mg)

These are both glucocorticoids

20
Q

What must be taken into account with ACTH deficiency?

A

Sick day rules

Also patients with addisons (primary adrenal failure)

Because these people are at risk of adrenal crisis: dizziness, hypotension, vomiting, weakness.
Can result in collapse and death

Sick day rules:
Steroid alert bracelet
Double steroid dose if fever/intercurrent illness
Unable to take tablets (vomiting) inject IM or come to a and e

21
Q

How is FSH/LH deficiency treated in men?

A

No fertility required:

Replace testosterone (topical/IM)

Measure plasma T

This does not restore sperm production - this is dependant on FSH

Fertility requires:

Induction of spermatogenesis by gonadotropin injections

Best response If secondary hypogonadism has developed after puberty

Measure T and semen analysis

Sperm production may take 6-12 months

22
Q

How is FSH/LH deficiency treated in women?

A

No fertility required:

Replace oestrogen (oral or topical)

Will need additional progestogen (fake progesterone) if uterus is intact to prevent endometrial hyperplasia (no periods)

Fertility required:

Can induce ovulation by carefully timed gonadotropin injection