MEH session 8 Flashcards
Where is the hypothalamus located?
At the base of the brain beneath the thalamus
Where is the pituitary gland located?
Beneath the hypothalamus in a socket of bone called the sella turcica
What is the infundibulum?
(pituitary stalk)- axons from the hypothalamus pass down here and terminate in the posterior pituitary.
The anterior and posterior pituitary gland have distinct embryonic origins. What are they?
Anterior pituitary
Arises from invagination of oral ectoderm (primiative gut tissue) rathke’s pouch
Posterior pituitary
Originates from neuroectoderm
(Primitive brain tissue)
Is the anterior or posterior pituitary gland physically connected to the hypothalamus?
Posterior pituitary via infundibulum
Where are hormones that are released from the posterior pituitary gland synthesised?
Hypothalamus
Which hypothalamic nuclei are involved in the control of:
- Appetite
- Biological clock
- Milk secretion
- Blood pressure
- Arcuate nuclei
- Suprachiasmatic nuclei
- Supraoptic nuclei and paraventricular
- Paraventricular nuclei and supraoptic
Which hormones are synthesised in the hypothalamus and transported to the posterior pituitary? How?
ADH
Oxytocin
Neurocrine secretion
How are hormones synthesised in the hypothalamus and transported to the anterior pituitary?
Transported down axons and released into the median eminence by neurocrine secretion.
Enter the hypothalamic-hypophyseal portal to reach target cells in the anterior pituitary gland
What effect to the hormones synthesised in the hypothalamus have on target cells in the anterior pituitary?
They are tropic hormones.
They either stimulate or inhibit target cells in the anterior pituitary gland.
What methods of communication do hormones synthesised and secreted by the anterior pituitary gland use?
Autocrine
Paracrine
Endocrine
What are the seven tropic hormones synthesised and released by the hypothalamus?
- TRH - thyrotropin releasing hormone
- PRH - prolactin releasing hormone
- PIH - prolactin release-inhibiting hormone (dopamine)
- CRH - corticotropin releasing hormone
- GnRH - gonadotropin releasing hormone
- GHRH - growth hormone releasing hormone
- GHIH - growth hormone inhibitory hormone (also called somatostatin)
The hormones produced by nerve cells of the hypothalamus act via two distinct neurocrine pathways. What are they?
- direct effects on distant target tissues via oxytocin and ADH from the posterior pituitary
- hormones secreted exclusively into the hypophyseal portal system via the median eminence to affect endocrine cells in the anterior pituitary
What is the difference between tropic and trophic hormones?
Tropic hormones affect the release of other hormones in the target tissue.
Trophic hormones affect growth
What is the hypothalamic stimulating and inhibitory hormone for the release of TSH from thyrotropes in the anterior pituitary?
What does TSH do?
Thyrotropin releasing hormone
Growth hormone inhibiting hormone (somatostatin)
TSH stimulates secretion of thyroid hormones from the thyroid gland.
What is the hypothalamic stimulating and inhibitory hormone for the release of prolactin from lactotropes in the anterior pituitary?
What does prolactin do?
Prolactin releasing hormone (minor stimulatory control on prolactin)
Prolactin release-inhibiting hormone
Growth hormone-inhibiting hormone (somatostatin)
Prolactin stimulates milk production in mammary glands
What is the stimulating hormone for the release of ACTH from corticotropes in the anterior pituitary?
What does ACTH do?
Corticotropin releasing hormone (CRH)
ACTH stimulates glucocorticoid (mainly cortisol) secretion from the adrenal cortex
What is the hypothalamic stimulatory and inhibitory hormones for the release of growth hormone from somatotropes in anterior pituitary gland?
What does growth hormone do?
Growth hormone releasing hormone (GHRH)
Growth hormone inhibiting hormone (GHIH)
Growth hormone stimulates IGF production by the liver. It also has direct growth effects on some target cells.
What is the hypothalamic stimulating hormone for the release of LH and FSH from gonadotropes in the anterior pituitary?
What do LH and FSH do?
Gonadotropin releasing hormone (GnRH)
LH - stimulates progesterone and oestrogen production in females and testosterone in males. Initiates ovulation.
FSH - stimulates gamete production (egg in female, sperm in male)
Which hormones are produced by the anterior pituitary?
TSH - thyroid stimulating hormone ACTH - adrenocorticotropic hormone LH - luteinising hormone FSH - follicle stimulating hormone PRL - prolactin GH - growth hormone
Which hormones that are produced and secreted by the anterior pituitary are tropic hormones?
F-L-A-T
TSH stimulates release of thyroid hormones from thyroid gland
ACTH stimulates release of cortisol from adrenal cortex
LH stimulates release of oestrogen and progesterone in females, and testosterone in males
FSH stimulates gamete production
In the ultra-short loop, what produces the negative feedback and what does it inhibit the production of?
What produces the negative feedback?
Hypothalamic releasing hormone
Inhibits production of?
Hypothalamic releasing hormone
How?
Autocrine
In the short loop, what produces the negative feedback? What does this influence the production of?
What produces the negative feedback?
Anterior pituitary hormone released in response to hypothalamic releasing hormone
Inhibits production of?
Hypothalamic releasing hormone
Stimulates production of?
Hypothalamic inhibiting hormone
In the direct long loop, what produces the negative feedback and what does this influence the production of?
What produces the negative feedback?
Peripheral effector hormone
Inhibits production of?
Anterior pituitary hormone
In the indirect long loop, what produces the negative feedback? What does this influence the production of?
What produces the negative feedback?
Peripheral effector hormone
Inhibits production of?
Hypothalamic releasing hormone
Stimulates production of?
Hypothalamic inhibiting hormone
What is growth influenced by?
Nutrition
Genetics
Environment
Hormones - growth hormone is the most important endocrine regulator of postnatal growth
Where is growth hormone produced?
Somatotrope cells in the anterior pituitary gland
Is growth hormone orally active?
No- it is a protein hormone so is denatured
Only steroid hormones are biologically active when taken orally.
How does growth hormone exert a majority of its effects?
In response to growth hormone, liver and skeletal muscle produce insulin-like growth factors.
IGFs act on target cells through their own specific receptor which shows similarities to the insulin receptor (tyrosine kinase).
Why is growth hormone essential for normal growth during childhood and teenage years?
Growth hormone stimulates long bone growth.
- length and width prior to epiphyseal plate closure
- width after epiphyseal closure
IGFs stimulate both bone and cartilage growth
What does growth hormone do in adults?
Growth hormone and IGFs:
- maintain muscle mass
- maintain bone mass
- promote healing and tissue repair
- modulate metabolism (promote anabolic processes)
What principally controls the release of growth hormone?
Hypothalamus
Growth hormone releasing hormone
Growth hormone inhibiting hormone (somatostatin)
What factors stimulate the release of growth hormone?
Endocrine:
• Hypothalamic hormone - GHRH (growth hormone releasing hormone)
• Ghrelin
Metabolic:
• A decrease in plasma glucose or plasma free fatty acid concentrations
• Fasting
Central nervous system-inputs into hypothalamus affecting GHRH and GHIH levels
• Surge in GH secretion after onset of deep sleep
• Stress eg. Trauma, surgery fever
• Exercise
What factors inhibit the release of growth hormone?
Endocrine:
• Hypothalamic hormone - Somatostatin/GHIH (growth hormone inhibiting hormone)
Metabolic:
• An increase in plasma glucose or plasma free fatty acid concentrations
• Obesity
Central nervous system-inputs into hypothalamus affecting GHRH and GHIH levels
• Light sleep (Rapid Eye Movement REM) sleep
In childhood, what does growth hormone deficiency result in?
Pituitary dwarfism
- proportionate type of dwarfism
- complete or partial deficiency
- height below third percentile on standard growth charts
- growth rate slower than expected for age
- delayed or no sexual development
Responds well to GH therapy
In childhood, what does growth hormone excess result in?
What is it often caused by?
Gigantism
This is often caused by a pituitary adenoma
In adulthood, what does excess growth hormone result in?
Acromegaly
Large extremities:
Hands, feet, lower jaw
What kind of receptor is the growth hormone receptor?
What does activation of this receptor cause?
Kinase-linked receptor, Janus kinases (JAK)
Coupled to janus kinase
This results in activation of a transcription factor that turns on production of IGFs
What kind of cell communication are IGFs involved in?
Paracrine
Autocrine
Endocrine
What effects to IGFs have?
Hypertrophy
Hyperplasia
Increased protein synthesis
Increased lipolysis in adipose tissue
IGF1 can produce a hybrid receptor with which type of receptor?
Insulin receptor
Which hormones other than growth factor influence growth?
Insulin - influences somatic growth by interacting with IGF receptors
Thyroid hormones - promote CNS development and enhance GH secretion
Androgens - accelerate pubertal growth spurt, increase muscle mass, promote closure of epiphyseal plate
Oestrogens - decrease somatic growth, promote closure of epiphyseal plates
Glucocorticoids - inhibit somatic growth
What effect would a superior growth of a pituitary tumour have on vision?
Bitemporal hemi-anopia (vision is missing on outer half of left and right field)
How do pituitary tumours present?
—>Mass of tumour on local structures leading to:
Visual loss
Headache
—>Abnormality of pituitary function
Hyposecretion
Hypersecretion
Which anterior pituitary hormone is under tonic inhibitory control by the hypothalamus and which hormone mediates this?
Prolactin
Prolactin inhibitory hormone (dopamine)
How can a pituitary tumour cause hyposecretion of hormones from the anterior pituitary gland?
The pituitary tumour may block the hypothalamic tropic hormones from reaching target cells in the anterior pituitary. Therefore, hormones that are usually under stimulatory/inhibitory influence change in concentration:
FSH/LH decreases
ACTH decreases
TSH decreases
Growth hormone decreases
Prolactin increases
How can you tell whether hypothyroidism is due to a tumour in the pituitary gland (secondary hypothyroidism) or due to a problem in the thyroid gland itself (primary hypothyroidism)?
Primary hypothyroidism
T3 and T4 is low
TSH is high
Secondary hypothyroidism
T3 and T4 is low
TSH is low
What does growth hormone deficiency cause in adults?
Reduced quality of life - fatigue, muscle weakness
What does LH/FSH deficiency present as?
In children, this results in delayed puberty
In adults, this results in loss of secondary sexual characteristics in adults (males develop breasts, loss of periods is an early sign in women).
What does ACTH deficiency present as?
Low cortisol
Tired, dizzy, low blood pressure, low sodium, can be life threatening
Pituitary tumours can result in hyposecretion of which hormones…
TSH
ACTH
FSH/LH
Growth hormone
Pituitary tumours commonly results in hypersecretion of which hormones?
Commonly,
Prolactin
Growth hormone
ACTH
What processes are involved in the investigation and diagnosis of a pituitary tumour?
- Delineation of the anatomy, size and topographical location of the pituitary or parapituitary mass (usually by MRI scan)
- Assessment of visual field defects
- Assessment of endocrine function determine whether there is a hormonal excess/deficiency
In biochemical assessment of pituitary disease, which axes is a basal blood test sufficient for?
Thyroid axis
Gonadal axis
Prolactin axis
The levels of these hormones do not fluctuate significantly throughout the day.
In the biochemical assessment of pituitary disease, which axes require dynamic blood tests?
HPA axis - levels of cortisol vary throughout the day (diurnal rhythm)
GH axis - growth hormone released in a pulsatile fashion
How is the dynamic assessment of the adrenal axis carried out?
Suspected hormone deficiency —> stimulation test
- direct stimulation of adrenals by ACTH
- response to hypoglycaemic stress (insulin stress test)
Suspected hormone excess —> suppression test
-suppress ACTH axis with steroids
How is dynamic assessment of the GH axis carried out?
Suspected hormone deficiency—> stimulation test
-Response to hypoglycaemic stress (insulin stress test)
Suspected hormone excess—> suppression test
-suppress GH axis with glucose load (glucose tolerance test)
How are prolactinomas treated?
Dopamine receptor agonists such as cabergoline are usually the first line of treatment. The tumour will shrink.
Prolactin secretion from the anterior pituitary is mainly under the negative influence of dopamine.
Give some signs of hyperprolactinaemia in women.
Galactorrhoea - unexplained milk production
higher level of dopamine in the hypothalamus resulting from negative feedback of increased plasma prolactin which inhibits GnRH secretion from the hypothalamus and therefore FSH and LH secretion from the anterior pituitary. This results in:
Menstrual disturbance
Fertility problems
What are the symptoms of hyperprolactinaemia in men?
Men present later than women
Usually larger tumours
Symptoms of low testosterone are non-specific eg. Loss of libido
May present with mass symptoms such as visual loss
Which hormone of the anterior pituitary gland is the only hormone which would show an increase in a non-functional or functional tumour of the pituitary gland if pituitary function is affected and why?
Prolactin
It is the only anterior pituitary hormone under tonic inhibitory control by dopamine from the hypothalamus so is the only one that would be raised in a non-functional tumour that affects pituitary function.
How can you tell if prolactinaemia is due to a non-functional tumour or a functional tumour?
If prolactin is <5000, high prolactin may be due to disinhibition rather than active secretion
If prolactin is >5000, high prolactin is likely to be due to active prolactin secretion (prolactinoma)
Why is it important to recognise whether a prolactinaemia is caused by a functional or non-functional pituitary adenoma?
prolactinomas are treated with dopamine agonists
non functioning pituitary tumours are treated surgically
Why is it important to check if anyone with hyperprolactinaemia is taking any anti-sickness or anti-psychotic drugs?
These could be dopamine antagonists.
Dopamine inhibits prolactin release.
Therefore, the drug may be the cause of high prolactin in the blood.
What is the treatment for acromegaly?
Surgical removal of the tumour
Radiotherapy
Drugs:
dopamine receptor agonists have some efficacy is reducing GH levels but a much higher dose than that used for prolactin-secreting pituitary adenoma is required
somatostatin - the hypothalamic hormone which limits GH secretion has limited use due to its very short half-life but the synthetic somatostatin analogs have been developed which produce a prolonged suppression of GH secretion
Pegvisomant - antagonists of the GH receptor
What are the symptoms of Cushing’s disease?
Round pink face with round abdomen
• Skinny and weak arms and legs
• Thin skin and easy bruising
• Red stretch marks (‘striae’) on abdomen
• High blood pressure and diabetes
• Osteoporosis (thin bones)
What is the difference between Cushing’s disease and Cushing’s syndrome?
Cushing’s disease is due to a pituitary tumour.
Cushing’s syndrome may be caused by other pathologies.
What causes diabetes insipidus?
ADH deficiency
Less expression of aquaporins in collecting ducts of kidney nephrons
Less water reabsorbed into the blood
What are the symptoms of diabetes insipidus?
Excess secretion of dilute urine
Dehydration
Increased thirst sensation
If untreated, can result in:
Reduced consciousness
Coma
Death
Do standard pituitary tumours affect both the anterior and posterior pituitary?
No.
They usually just affect the anterior pituitary
If they affect the posterior pituitary, it is due to some other sort of pathology:
- inflammation
- infiltration
- malignancy
- infection
What is the treatment for cranial diabetes insipidus?
synthetic vasopressin
Desmopressin nasal spray, tablets or injection
What is pituitary apoplexy?
Sudden vascular event within a pituitary tumour.
Haemorrhage with in the tumour (bleeding)
Infarction within the tumour (blood supply cut off)
What is the clinical presentation of pituitary apoplexy?
Sudden onset headache Double vision Cranial nerve palsy Hypopituitarism - cortisol deficiency most dangerous Visual field loss
In which nuclei of the hypothalamus are the neurones that synthesis oxytocin located?
Supraoptic and paraventricular nuclei
Describe the embryonic origin of the anterior lobe of the pituitary gland.
The anterior lobe of the pituitary gland arises from an up-growth of ectodermal cells from the roof of the primitive pharynx
Which organ releases IGF-1 into the blood in response to growth hormone stimulation?
Liver
Which disease results from excess growth hormone secretion occurring after puberty after the epiphyseal plates have closed?
Acromegaly
Why might a patient with a pituitary adenoma develop visual field loss?
Growth of the adenoma can cause physical compression of the optic chiasma.
(Mass-effect)
What is galactorrhoea?
Milky secretion from the breasts not due to breastfeeding which can be caused by hyperprolactinaemia
Which biochemical finding would you expect in. Patient with acromegaly?
Plasma growth hormone above the normal range
Plasma IGF-1 above the normal range as liver and muscle is stimulated to release more
Which term is used to describe a sudden vascular event such as haemorrhage or infarction to a pituitary tumour?
Pituitary apoplexy
Patients with pituitary apoplexy may show sudden onset headache, double vision, cranial nerve palsy, visual field loss and hypopituitarism (cortisol deficiency is the most dangerous). Apoplexy needs prompt diagnosis and treatment
Which of the following is a typical clinical consequence of untreated central diabetes insipidus?
Glucosuria
Hypernatraemia
Hyperkalaemia
Hypocalcaemia
Hypernatraemia -dehydration can develop in patients when they do not drink adequately
Which pattern of plasma cortisol concentration is normal?
Highest at midnight, lowest level in the morning
Constant throughout the day
Highest in the morning, lowest level at midnight
Plasma cortisol reaches its peak at around 7:00 to 8:00 AM and then gradually declines throughout the day to a lowest levels at around midnight before gradually increasing again through the night. For this reason it is essential to always record the time a blood sample for cortisol measurement was taken and to take repeated samples the same timne of day. Typically cortisol is measured in the morning.
What is the role of LH in men?
Control of the production of testosterone by the testis by acting on the Leydig cells
Name the type of surgical procedure that can be used to remove a pituitary tumor by inserting an endoscope and/or surgical instruments through the nose.
Transphenoidal surgery
