Session 9: Hypothalamus & Pituitary Gland, and Their Disorders

Vital regulatory functions of the hypothalamus

- Temperature

- Heart rate

- Blood pressure

- Blood osmolarity

- Goal-seeking behaviour

- Emotional behaviour

- Visceral nervous system

- Sexual activity

- Food & water intake

- Aggression

Pituitary gland is ___ fused glands...

Pituitary is two fused glands...

- Anterior pituitary (adenohypophysis)

- Posterior pituitary (neurohypophysis)

Anterior pituitary

adenohypophysis

Posterior pituitary

neurohypophysis

The pituitary gland lies just below the ___ in the brain

hypothalamus

The pituitary gland is connected by a stalk to the hypothalamus. This stalk is known as the ___ ___ stalk

median eminence

Describe development of pituitary gland in utero

Anterior lobe (adenohypophysis)

- Upgrowth of ectodermal cells from roof of primitive pharynx (buccal cavity)

- Arises from Rathke's Pouch

Posterior lobe (neurohypophysis)

- Down-growth of neural tissue from hypothalamus

- Arises from neuroectoderm

These two tissues fuse to form the pituitary gland

Identify anterior and posterior pituitary on this brain MRI

Name the artery connecting pituitary gland to the hypothalamus

Hypophyseal portal artery

The hypothalamus controls the ___ pituitary gland secretion by releasing hormones (neurohormones) from the ___ ___

The hypothalamus controls the anterior pituitary gland secretion by releasing hormones (neurohormones) from the median eminence

The anterior pituitary is connected to the hypothalamus via the ___-___ circulation

The anterior pituitary is connected to the hypothalamus via the hypophyseal-portal circulation

The anterior pituitary is made up of hormone producing glandular cells.

It produces six peptide hormones - these hormones are...

1) Prolactin

2) Growth Hormone (GH)

3) Adrenocorticotropic hormone (ACTH)

4) Lutenizing Hormone (LH)

5) Follicle Stimulating Hormone (FSH)

6) Thyroid Stimulating Hormone (TSH)

Name the TWO gonadotrophins secreted by anterior pituitary

1) Follicle Stimulating Hormone (FSH)

2) Lutenizing Hormone (LH)

These gonadotrophins are produced by gonadotrophs and act on gonads to control reproduction

Thyroid Stimulating Hormone (TSH) is produced by ___

thyrotrophs

TSH stimulates the ___ gland to secrete hormone

thyroid

Glycoprotein hormones secreted by anterior pituitary

- Gonadotrophins = FSH, LH

- TSH

Polypeptide hormones secreted by anterior pituitary

- GH

- ACTH

- Prolactin

Growth Hormone (GH) is produced by ___

somatotrophs

Adrenocorticotropic hormone (ACTH) is produced by ___

corticotrophs

Prolactin is produced by ___

lactotrophs

Role of ACTH

Stimulates adrenal cortex to release glucocorticoids (cortisol)

Role of GH

Influences growth and metabolism

Role of prolactin

Controls milk production (from breasts) and other reproductive processes

Gonadotropes are controlled by GnRH (___).

This hormone stimulates both LH and FSH secretion.

Gonadotropin Releasing Hormone (GnRH)

Thyrotropes are controlled by TRH (___).

This hormone stimulates Thyroid Stimulating Hormone (TSH) - stimulates thyroid gland to provide thyroid hormones

Thyrotropin Releasing Hormone (TRH)

Somatotropes are controlled by GHRH (___).

This hormone stimulates Growth Hormone (GH) release.

Growth Hormone Releasing Hormone (GHRH)

Lactotropes controlled in a different way.

The hypothalamus secretes ___.

___ inhibits prolactin secretion from the anterior pituitary.

Dopamine

What environmental factors influence the Hypothalamus - Pituitary Gland Axis

- Cold

- Stress (HPA)

- Metabolic status

- Dehydration

- Exercise

- Time of day

- Menstruation

- Sleep

- Growth

- Breastfeeding

- Pregnancy

- Puberty

Examples of some physiological effects elicited by the pituitary gland in the Hypothalamus - Pituitary Gland Axis?

- ACTH = adrenal function

- TSH = thyroid function

- FSH/LH = gonadal function

- Prolactin = lactation

- GH = growth/metabolism

- Water balance

- Parturition

HPA axis

hypothalamic-pituitary-adrenal axis

HPA axis responds to ___

Stress

What are the metabolic effects of the stimulation of the HPA axis?

- Energy stores mobilised

- Lipolysis and proteolysis

- Vasoconstriction

- Reproduction is suppressed

- Altered stress-related behaviours

- Bronchodilation

- Increased heart rate & blood pressure

- Blood flow to muscles is increased (fight/flight)

Increased risk of cognitive, emotional and behavioural dysfunctions as an effect of increased HPA axis stimulation.

Some examples of these dysfunctions...

- Major depression disorder

- Anxiety disorders

- Memory problems

Increased risk of cardiovascular dysfunctions as an effect of increased HPA axis stimulation.

Some examples of these dysfunctions...

- Cardiac hypertrophy (hypertension)

- Vascular damage

Increased risk of other diseases as an effect of increased HPA axis stimulation.

Some examples of these dysfunctions...

- Cancer

- Diabetes

- Cushing's syndrome (hypercortisolism)

- Obesity

Increased risk of immune system dysfunction as an effect of increased HPA axis stimulation.

Some examples of these dysfunctions...

- Increased risk of autoimmune disorders

- Increased levels of circulating cytokines

- Chronic/low-grade inflammation throughout body

Mechanism of fever

- Exogenous pyrogens (e.g., bacterial LPS) stimulate leukocytes (monocytes, macrophages, Kupffer cells) to release cytokines

- Cytokines lead to release of prostaglandins from hypothalamus (prostaglandin E)

- Prostaglandins cause increase of temperature set point causing fever

- Fever is regulated by negative feedback

Give two examples of pituitary gland disorders

1) Hypopituitarism

2) Pituitary Adenoma

Hypopituitarism

Deficient pituitary gland activity

- Decreased synthesis of one or more pituitary or hypothalamic hormones

- Rare

- Most commonly = FSH/LH deficiency

- Mostly due to = tumours, surgical, radiotherapy treatment

- Symptoms/signs depend on the severity of deficiency

Name some causes of Hypopituitarism

bacterial/viral
subaracnoid hemorage

snake bite
TBI

Symptoms of gonadal deficiencies in Hypopituitarism

- Loss of libido

- Secondary sexual hair loss

- Amenorrhoea

- Erectile dysfunction

- Menstrual cycle deficiencies

Symptoms of GH deficiency in Hypopituitarism

- Growth failure in children

- Impaired wellbeing in adultd

Symptoms of TSH deficiency in Hypopituitarism

- Weight gain

- Dry skin

- Cold intolerance

Symptoms of ACTH deficiency in Hypopituitarism

- Mild hypotension

- Hyponatraemia (low serum sodium)

Case study

36 year old male referred by GP with 5 day history of headache that has been progressively increasing in severity and a 1 day history of visual disturbance. Further history reveals a one month history of lethargy, dizziness on standing up too quickly, loss of libido and some loss of chest hair.

Clinical Findings

• Decreased serum cortisol, TSH, LH, FSH and testosterone

• Increased prolactin

• MRI: large pituitary tumour compressing the optic chiasm

Diagnosis = Pituitary Adenoma

Pituitary adenoma can be associated with ___ hormonal secretion which causes effects. This is called a ___ adenoma

Pituitary adenoma can be associated with excess hormonal secretion which causes effects. This is called a functional adenoma

- Hyperprolactinaemia

- Gigantism

- Acromegaly

- Cushing's disease

Gigantism

Pituitary adenoma secreting excess GH in childhood (before epiphyses have fused)

- Accelerated growth of bone, muscle and connective tissue

- Enlargement of organs

Gigantism symptoms

- Joint pain

- Delayed puberty

- Pain and limited joint mobility

- Vision problems

- Headaches

Acromegaly

Pituitary adenoma secreting excess GH during adulthood (after epiphyses have fused)

Symptoms and signs of Acromegaly

- Enlarged hands and feet

- Enlarged facial features (facial bones, lips, nose, tongue)

- Fatigue

- Joint/muscle weakness

- Pain and limited joint mobility

- Vision problems

- Headaches

- Menstrual cycle irregularities

- Erectile dysfunction

- Reduced libido

Cushing's disease

Pituitary adenoma secreting ACTH; increased cortisol, increased ACTH

Symptoms of Cushing's disease

- Weight gain and increase in body fat on abdomen/chest

- Thin arms and legs

- Build-up of fat on back of neck and shoulders

- Moon face/rounded face, puffiness, redness

- Easy bruising

- Large purple stretch marks

- Skin ulcers (poor wound healing)

- Amenorrhea

- Purpura

- Abdominal striae

- Osteoporosis

Management of Cushing's disease

- Pituitary adenoma/tumour =

Surgery, radiotherapy, medical therapy

- Pituitary hormonal secretion deficiency or excess

Hormonal therapy, medical therapy

Name the pituitary gland cells that release thyroid stimulating hormone (TSH).

Thyrotrophs

Which hypothalamic hormone regulates secretion of TSH?

Thyrotropin releasing hormone (TRH)