The Hypothalamic Pituitary axis Flashcards
Where does the hypothalamus sit?
In a socket of bone called sella turcica
Infundibulum
Pituitary stalk
Where do the anterior and posterior pituitary arise from?
Anterior - Arises from evagination of oral ectoderm (primitive gut tissue)
Posterior - Originates from neuroectoderm
Anterior and posterior pituitary glands are also called:
Adenohypophysis and neurohypophysis
Which two hormones are secreted by the pituitary gland? And where are they produced?
Oxytocin and ADH.
Produced by neurosecretory cells in the supraoptic and paraventricular nuclei of the hypothalamus.
Anterior pituitary function
- Hormones synthesised in hypothalamus are transported down axons and stored in the median eminence
- These hormones stimulate (or inhibit) target endocrine cells in the anterior pituitary gland
- Has endocrine, paracrine and autocrine function
Tropic hormones of the hypothalamus (6)
- Thyrotropin releasing hormone (TRH)
- Prolactin release inhibiting hormone (Dopamine, PIH)
- Corticotropin releasing hormone (CRH)
- Gonadotropin releasing hormone (GnRH)
- Growth hormone releasing hormone (GHRH)
- Growth hormone inhibiting horome (Somatostatin, GHIH)
Tropic hormone definition
Affect the release of other hormones in the target tissue
Hormones produces by the anterior pituitary
- Thyroid stimulating hormone (TSH)
- Adrenocorticotropic hormone (ACTH)
- Luteinising hormone (LH)
- Follicle stimulating hormone (FSH)
- Prolactin (PRL)
- Growth hormone (GH)
Growth hormone
- Produced in the anterior pituitary
- Stimulated by hypothalamic GHRH
- Inhibited by somatostatin
- Contains signal peptide
- In response to GH cells of the liver and skeletal muscle produce and secrete IGFs
When is there a increase or decrease in GH secretion?
Increase:
- Onset of deep sleep
- Stress
- Exercise
- Decrease in glucose or fatty acids
- Fasting
Decrease:
- REM sleep
- Obesity
- Increase in glucose
Long and short loop negative feedback
Long:
- Mediated by IGFs
- Inhibits release of GHRH from hypothalamus
- Stimulates release of somatostatin
- Inhibit release of GH from anterior pituitary
Short:
- Mediated by GH via stimulation of somatostatin release
Growth hormone deficiency
- Proportionate dwarfism
- Respond to GH therapy
- Delayed or no sexual development
Growth hormone deficiency
- In childhood esults in gigantism
- Often caused by pituitary adenoma
- In adulthood results in acromegaly
How does GH exert its effects on cells?
- GH receptors activate Janus kinases (JAKs)
- Tyrosine kinase receptors activate intracellular kinases which leads to transcription factor activation and IGF production
Insulin-like growth factors: two different types, actions, what do they modulate?
- IGF1 major growth factor in adults
- IGF2 mainly involved in fetal growth
- Binding proteins modulate their availability
- Actions can be paracrine, autocrine and endocrine
- Modulate hypertrophy, hyperplasia, increase in the rate of protein synthesis, increase in the rate of lipolysis in adipose tissue
IGF and insulin receptors
There is cross activation of signalling pathways due to similarities in the receptors
Other hormones that also influence growth and their actions
- Insulin (enhances somatic growth)
- Thyroid hormones (promotes CNS development and enhance GH secretion)
- Androgens (accelerate pubertal growth spurt, increase muscle mass, promote closure of epiphyseal plated)
- Estrogens (decrease somatic growth, promote closure of epiphyseal plates)
- Glucocorticoids (inhibit somatic growth)
Upwards growth of pituitary tumour causes:
Visual field loss due to pressure on optic chiasm (bitemporal hemianopia)
Lateral growth of pituitary tumour causes:
Pain and double vision. Left sided eye compression (tumour invading left side)
Hypopituitarism
Signal from hypothalamus does not reach pituitary gland. No control over hormone release and production
Hormone deficiencies with pituitary tumours
- Growth hormone, short stature in children, reduced quality of life in adults
- Gonadotropin (LH and FSH), loss of secondary sexual characteristics, loss of periods
- TSH and ACTH deficiency, late features of pituitary tumours, cold, weight gain, tiredness, low T4. Low cortisol, tired, dizzy, low BP, can be life threatening
Hormone excess with pituitary tumours
Common:
- Prolactin
- GH
- ACTH
Rare:
- TSH
- LH/FSH
Biochemical assessment of pituitary disease
- Thyroid axis, fT4 and TSH
- Gonadal axis, LH, FSH, testosterone and oestradiol
- Prolactin axis, serum prolactin
Dynamic assessment - Cortisol
- GH
Adrenal axis dynamic tests
Deficiency:
- Direct stimulation by synACTHen
- Response to hypoglycaemia stress (insulin stress test)
Excess:
- Suppress ACTH axis with steroids (dexamethasone)
GH axis dynamic tests
Deficiency:
- Response to hypoglycaemic stress (insulin stress test)
Excess:
- Suppress GH axis with gluc,ose load (glucose tolerance test)
Prolactinoma
- Prolactin secreting pituitary tumour
- Treated with dopamine agonist tablets (dopamine inhibits prolactin and shrink tumour)
Hyperprolactinaemia symptoms in women and men
- Prolactin directly inhibits LH secretion
Women: - Menstrual disturbance
- Fertility problems
- Galactorrhoea (milky discharge)
Men: - Present later than women (why? Lecture 8.2 slide 29)
- Usually large tumours
- Symptoms of low testosterone are non specific
- May present with mass symptoms such as visual loss
Likely diagnosis if prolactin levels are higher or lower than 5,000?
< 5,000 - disinhibition (stalk effect)
> 5,000 - active prolactin secretion (prolactinoma)
Non functioning pituitary adenoma: clinical features, blood hormone levels
- Clinical features are due to mass effect (bitemporal hemianopia) or symptoms of low pituitary hormones
- Low testosterone, LH, FSH, cortisol, GH, IGF
- High prolactin
Long term complications of acromegaly
- Premature cardiovascular death
- Increased risk of colonic tumours
- Hypertension
- Diabetes
Biochemical tests to confirm acromegaly
- Oral glucose tolerance test with GH response
- Elevated IGF-1 level (age related reference range
- Growth hormone day curve
Treatment of acromegaly
- Surgical removal of tumour
- Reduce GH secretion (dopamine agonist, somatostatin analogues)
- Block GH receptor
- Radiotherapy
Cushing’s disease classical change in appearance
- Round pink face with round abdomen
- Skinny and weak arms and legs
- Thin skin, easy bruising
- Stiae on abdomen
- High blood pressure and diabetes
- Osteoperosis
Difference between Cushing’s disease and Cushing’s syndrome
Cushing’s disease is due to a pituitary tumour, whereas Cushing’s syndrome may be caused by other pathologies e.g. adrenal tumour, ectopic ACTH or steroid medication
What does antidiuretic hormone do?
Retains water in the body and constricts blood vessels (at high concentrations). Diuresis means increased urine.
Diabetes insipidus types
- Neurogenic and nephrogenic
- Unusual in standard pituitary tumours as those just affect anterior pituitary
Consequences of untreated diabetes insipidus
- Severe dehydration
- Very high sodium levels
- Reduced consciousness, coma and death
Treatment of diabetes insipidus
Synthetic vasopressin
Clinical presentation of pituitary apoplexy (stroke)
- Sudden onset headache
- Double vision
- Visual field loss
- Cranial nerve palsy
- Hypopituitarism (cortisol deficiency most dangerous)
