Pituitary Dysfunction: Hyper- and Hypopituitarism

Pituitary Dysfunction: Hyper- and Hypopituitarism

Understand pituitary dysfunctionApply to real clinical case

The case

Presented with:

• Crescendo headaches
• Vomiting

Likely diagnosis:

• Prolactinoma

Outcome:

• Symptoms resolved spontaneously

Question:

• What mechanisms cause pituitary dysfunction?

Contents

• Recap

• Hypopituitarism- features

• Back to the case

• Anterior pituitary

• Investigations

• Posterior pituitary

• Treatment

• Hyperpituitarism

• Hyperprolactinemia

• Conclusion

• Hypopituitarism

• Activity

Recap of the Pituitary

Hypophyseal portal circulationConnects hypothalamus → anterior pituitary Allows direct hormonal regulation

Rests in the sella turcica of the sphenoid bone beneath the optic chiasmConnected to hypothalamus via the pituitary stalk (infundibulum)

Key FunctionsPituitary = endocrine control centre Regulates:

• Thyroid axis
• Adrenal axis
• Gonadal axis
• Growth

Two divisionsAnterior pituitary → hormone production Posterior pituitary → hormone release Clinical Relevance Enlargement (e.g. adenoma) can compress optic chiasm → causes bitemporal hemianopia

Anterior pituitary

Overview

• Releases FSH, LH, ACTH, TSH, Prolactin, GH (FLAT PiG)
• Hypothalamus → Anterior pituitary → End organ

Growth hormone

• Hypothalamus → GnRH → anterior pituitary → LH, FSH→ Ovaries/ Testes
• Hypothalamus → GHRH → Anterior pituitary → Growth hormone → Liver → IGF- 1 → Tissue growth

Corticotropin-releasing hormone

• Hypothalamus → CRH → anterior pituitary → ACTH → adrenal cortex → Cortisol

Thyroid hormone

• Hypothalamus → Thyrotropin releasing hormone → anterior pituitary → TSH → thyroid → T3,T4
• Hypothalamus → Dopamine, TRH → Anterior pituitary → Prolactin → Breast → mik

Posterior pituitary

• Releases oxytocin, vasopressin (ADH)
• ↓ Volume, Angiotensin II, ↑ Osmolality → ↑ ADH release → ↑ Aquaporins collecting duct → ↑ H2O reabsorption
• Suckling → ↑ Oxytocin release → Milk let down
• Uterine stretch → ↑ Oxytocin release → ↑ Uterine contractions → Uterine stretch

Hyperpituitarism

↑ GH

↑ ACTH

↑GH

Gigantism: Occurs before perfusion of epiphyseal plates

Acromegaly: Occurs after perfusion of epiphyseal plates

Cushing disease: ACTH-secreting pituitary adenoma

↑ linear bone growth

↑ Cortisol → Bilateral adrenal hyperplasia

Usually benign pituitary adenoma → excess GH release → ↑ IGF-1 release → excess growth

Hyperprolactinemia

↑ Lactotrophs → ↑ Prolactin secretion

• ↑ Prolactin → ↑ Lactotroph activity
• ↑ Prolactin → ↓ GnRH → ↓ FSH, ↓ LH → ↓ Estrogen, ↓ Testosterone → Hypogonadotropic hypogonadism
• Lack of ovulation, vaginal atrophy in females, infertility/amenorrhea in women, ↓ spermatogenesis in males, osteoporosis
• Galactorrhea (nipple discharge), gynecomastia in men
• Bitemporal hemianopia: Loss of bitemporal peripheral vision due to compression of optic chiasm

Surgical resection if pituitary adenoma presentDopamine agonists (bbromocriptine, cabergoline

Prolactin level, TSH, T4, T3Brain MRI with contrast: Pituitary mass, enlargement of sella turcica

Hormone loss order

• GH → first
• LH/FSH
• TSH
• ACTH → last (but most dangerous)

Hypopitutarism

Deficiency of one or more pituitary hormones

Sheehan syndrome

Pituitary swells during pregnancy

Empty sella syndrome

Enlargement of Sella turcica

Pituitary Apoplexy

Hemorrhage or infarction of pituitary

Mass

Tumour compressing the pituitary

Clinical features of hypopituitarism

ADH

Diabetes Insipidus

ACTH

Fatigue, hypotension, risk of adrenal crisis

LH/FSH

Amenorrhoea, Infertility, low libido

TSH

Features of hypothyroidism

Biochemistry

GH/IGF-I

Interpretation

Clinical progression

Back to the Case

Improvement in hormone excess may reflect loss of tumour function, not recovery

So why did the symptoms resolve

Investigations!

Other test

Blood tests

Imaging

Prolactin Cortisol TSH IGF-1 LH/FSH

Visual field testing

MRI pituitary!!!!

Treatment

Hyperpituitarism

Treat cause: Medication (e.g. dopamine agonists) Surgery

Hypopituitarism

Hormone replacement: Steroids FIRST (important exam point) Then thyroid hormone Then sex hormones

Conclusions

Key take home points

• Anterior pituitary releases FSH, LH, ACTH, TSH, Prolactin, GH (FLAT PiG)
• Pituitary dysfunction = excess or deficiency
• Adenomas → most common cause of hyperpituitarism
• Compression/apoplexy → hypopituitarism
• Prolactinoma = most common functioning tumour

I hope you were paying attention

I think Im house

Start

House abducted you

A 32-year-old patient presents with:

• Progressive fatigue
• Irregular periods
• New headaches
• Intermittent blurred vision

Initial bloods show hormonal abnormalities across multiple axes. House thinks it’s a pituitary problem… but nothing fits neatly. He’s locked the diagnosis behind 4 missions. Solve the physiology. Solve the dysfunction. Solve the case.

Continue

Mission 1

Locked

Locked

Locked

House test

A pituitary tumour compresses the optic chiasm. What visual field defect occurs?

Homonymous hemianopia

Bitemporal hemianopia

Central scotoma

House test

Why is the hypophyseal portal system important?

Enables direct hypothalamic control of anterior pituitary

Allows posterior pituitary hormone release

Supplies blood to the optic chiasm

House test

A lesion damages the pituitary stalk. What is the most likely hormonal change?

Decreased prolactin

No change in prolactin

Increased prolactin

House test

Which statement best explains the difference between anterior and posterior pituitary function?

Anterior synthesises hormones, posterior stores them

Posterior synthesises hormones, anterior stores them

Both synthesise hormones independently

Mission 2

Completed

Locked

Locked

Which hormone is primarily under inhibitory control?

Prolactin

GH

TSH

Which sequence is correct for the thyroid axis?

TSH → TRH → T3/T4

TRH → TSH → T3/T4

TRH → T3/T4 → TSH

A patient has ↑ prolactin. What is the expected effect on gonadotropins?

↑ LH/FSH

↓ LH/FSH

No change

Which statement about CRH is correct?

Stimulates ACTH and related peptides from POMC

Directly stimulates cortisol release

Only stimulates ACTH

Mission 3

Completed

Completed

Locked

A patient has amenorrhoea and galactorrhoea. What is the most likely underlying mechanism?

Decreased prolactin

Suppression of GnRH

Increased GnRH

Which feature suggests acromegaly rather than gigantism?

Occurs after epiphyseal closure

Increased height

Increased IGF-1

Why is prolactin elevated in a non-functioning tumour?

Loss of dopamine inhibition

Increased GnRH

Increased production

A patient with a prolactinoma suddenly improves clinically. What is the most likely explanation?

Tumour haemorrhage/infarction

Increased dopamine production

Spontaneous immune resolution

A patient develops hypopituitarism after a pituitary tumour. What is the most likely mechanism?

Compression of normal pituitary tissue

Increased hypothalamic activity

Hormone overproduction

You’ve got the pieces. Now stop guessing and diagnose

Continue

Completed

Completed

Completed

Mission 4

Multiple hormone deficiencies suggest?

Peripheral endocrine disease

Pituitary dysfunction

Thyroid disease

Visual symptoms suggest compression of?

Occipital cortex

Optic chiasm

Optic nerve

Why is prolactin elevated?

Stalk compression

Prolactinoma

Increased TRH

What is the most important immediate management if hypopituitarism is suspected?

Start corticosteroids

Start dopamine agonist

Start thyroxine

What is the most likely diagnosis?

Non-functioning pituitary adenoma

Prolactinoma

Acromegaly

Completada

Completada

Completada

Completada

Completed

Completed

Completed

Completed

Continue

House walks in…‘You see a tumour and think hormones. That’s your mistake.’ ‘It’s not overproducing. It’s shutting everything down.’ Diagnosis: Non-functioning pituitary adenoma with stalk effect

House force fed you vicodin

He then performed experiments on you

Try again

Interpretation

Most consistent with:

• Pituitary apoplexy (haemorrhage into adenoma)

Explains:

• Sudden severe headache
• Tumour shrinkage
• Change in hormonal profile

Improvement in hormone excess may reflect loss of tumour function, not recovery

Pathophysiology: Hemorrhage or infarction of pituitary• Often with existing pituitary adenoma Presentation: Sudden-onset severe headache, bitemporal hemianopia, AMS Diagnostics: Head CT, intrasellar mass with hemorrhage Treatment: Corticosteroids, possible surgery

Pituitary adenoma/craniopharyngioma compressing pituitaryPresentation: Headaches, bitemporal hemianopia, can compress pituitary → Hypopituitarism Treatment: Surgical resection

Clinical Progression

Known pituitary lesion with hyperprolactinaemiaImaging:

• Haemorrhagic lesion abutting optic chiasm

Clinical course:

• Resolution of symptoms
• Evidence of tumour involution

Biochemistry

↑ IGF-1GH suppressed on OGTTFurther tests:

• MRI pituitary (follow-up)
• Synacthen test planned

Pituitary swells during pregnancy → Postpartum hemorrhage → Ischemia → Pituitary infarctPresentation: Prolactin deficiency → Lactation failure, amenorrhea • ↓ TSH → Hypothyroid symptoms • ↓ ADH → Diabetes insipidus Diagnostics: Infarction of pituitary on head MRI, empty sella turcica Treatment: Irreversible, treat with hormone replacement

Diagnosis + Management

Diagnostics:

• Low IGF-I levels
• Glucose challenge → ↑ GH levels (not suppressed)
• Pituitary mass, enlargement of sella turcica on Brain MRI/CT
• Cardiomegaly on CXR

Acromegaly: Old photo doesn’t look like same person Treatment:

• Surgical resection of pituitary adenoma
• Somatostatin analog → ↓ GH release
• GH receptor antagonist
• Dopamine analog, suppress GH release

Diagnostics and management

↑ 24-hr urine free cortisol, ↑ Late night salivary cortisol, ↑ ACTH High-dose dexamethasone suppression test: Adequate suppression CRH stimulation test: ↑ ACTH, ↑ Cortisol

• Pituitary MRI to identify lesion
• Surgical removal
• Radiation

GH / IGF-1

Now: Damaged tumour → reduced GH secretion IGF-1 still elevated (lags behind GH changes) So: Apoplexy → loss of GH hypersecretion → normal OGTT suppression

The findings:

• ↑ IGF-1
• GH suppressed on OGTT

This is not classic acromegaly What this likely means: Previously active GH excess (before apoplexy)

Presentations

Acromegaly:

• Occurs in adulthood → Disproportionate skeletal, tissue, organ growth
• Frontal bossing → Increased hat size, headaches in the morning
• Jaw enlargement → Prominent jaw with spaces between the teeth
• Large hands and feet, carpal tunnel syndrome, muscle weakness, HTN
• Coarse facies, deep voice, diaphoresis
• ↑ Risk colorectal polyps, cancer

Gigantism: Present from childhood → Increased stature Heart failure most common cause of death

Pathophysiology: Enlargement sella turcica → CSF leaks in → Atrophy/compression of pituitary• Associated idiopathic intracranial HTN Diagnostics: Pituitary fossa replaced by CSF, “empty” sella turcica No treatment if asymptomatic