Hypothamalus/Pituitary Flashcards
What is the piuitary gland divided into
- Anterior pituitary(adenohypophysis)
- Posterior pituitary (neurophysis)
Where does the pituitary gland lie in the skull?
bony hollow of the sphenoid bone(sella turcica) and covered by diaphragma sella
Where is the hypothalamus located?
Diencephalon
Regions of the hypothalmus
Mammillary region, tuberal region , supraoptic region, preoptic region
Mammary region
- adjacent ot midbrain , most posterior part of the hypothalamus
- mammary bodies (two small rounded projections and the posterior hypothalamic nuceli
Tuberal region
widest part of the hypothalmus
includes:
- dorsomedial nucleus, ventromedial nucleus, arcuate nucleus,
- infundibulum (connecs pituitary to the hypothalamus
- median eminence (encircles infundibulum)
Supraoptic region
superior to the optic chiams
includes:
- paraventicular nucleus, supraoptic nucleus, anterior hypothalamic nucleus, suprachiasmatic nucleus
Pre-optic region
medial and lateral pre-optic nuclei
Cells of the anterior pituitary and what they secrete
o Somatotrophs- growth hormone (GH)
o Gonadotrophs- luteinising hormone (LH) and follicle-stimulating hormone (FSH)
o Corticotrophs- adrenocorticotrophic hormone (ACTH)
o Thyrotrophs- thyroid-stimulating hormone (TSH)
o Lactotrophs- prolactin
o Chromophobes- inactive secretory cells
Anterior pituitary is divided into three regions?
o Pars distalis- the majority of the gland
o Pars tuberalis- a layer of mostly functionally inactive gonadotroph cells around the pituitary stalk in humans
o Pars intermedia- a thin layer of corticotroph cells between the anterior and posterior pituitary. It is poorly developed in humans
Hormones secreted from the posterior pituitary>
ADH and oxytocin
Blood vessels that link the hypothalamus to the anterior pituitary
hypophyseal portal system
Growth Hormone axis
The hypothalamus produces Growth hormone releasing hormone (GHRH) to stimulate the anterior pituitary gland to produce growth hormone (GH). This has multiple physiological effects mostly in childhood which has direct effects on the liver, bone(increase bone growth), adipose tissue(breakdown fatty tissue) and on metabolism or indirect effects via production of Insulin-like growth factor (IGF-1) from liver.
Example of a negative feedback loop
GH secretion is pulsatile, mainly overnight so usually IGF-1 are usually produced
Female Hypo-gonadal axis
The hypothalamus stimulates the production of GNRH which stimulates the anterior pituitary to produce Lutenising hormone (LH) and Follicular-stimulating hormone (FSH). This stimulates the ovaries to produce Oestradiol (luteal phase of menstruation) and progesterone (in the follicular phase of menstruation). These hormones then negatively feedbacks to the anterior pituitary, except in the late luteal phase when oestradiol and progesterone positively feedback (leading to LH surge in ovulation). The production of FSH leads to the production of inhibin from the ovarian stromal cells which negatively feeds back to the anterior pituitary
Male hypo-gonadal axis
The hypothalamus stimulates the production of GNRH, stimulating the anterior pituitary to produce LH and FSH. LH acts on the leydig cells on the testes to produces testosterone. Testosterone and LH act on the sertoli cells in the testes to produce sperm. FSH stimulates the sertoli cells to produce inhibin which negatively feeds back to the anterior pituitary to switch off production.
lactotroph axis
In normal physiological action the pituitary is under negative hypothalamic control by dopamine. In pregnancy and in the post-partum period, dopamine release is decreased and this results in a surge in prolactin enhancing lactation and allowing development of the mammary glands.
AVP/ADH axis
Osmoreceptors in hypothalamus trigger release of ADH from the hypothalamus. ADH results in increased permeability from the collecting ducts and results in increased H20 reabsorption to increase H20 reabsorption and increase plasma osmolarity.
- Main role is in regulating water status
- Produced in response to:
o Decreased plasma volume (sensed by baroreceptors in atria/veins/carotids)
o Increase in plasma osmolality (sensed by osmoreceptors in hypothalamus)
Action of AVPR1
g-coupled protein receptor
- vascular smooth muscle, platelets
- vasoconstriction
platelet adhesion/release
Action of AVPR2
found in collectind ducts
- basolateral membrane of kidney collecting ducts, inserts aquaporin channels to increase renal water reabsorption
Action of AVPR3
g-protein
- anterior pituitary corticotroph cells
- increased ACTH release
Definition of Diabetes inspidus
Passage of large volume (>3l/day) of dilute urine due to a deficiency, or lack of effective ADH (vasopressin) secretion
Clinical features of diabetes inspidus
• Polyuria
• Polydipsia
• Nocturia
Must exclude DM and hypercalcaemia
Causes of Diabetes insipidus
Cranial (posterior pituitary is not producing ADH)
• Deficiency of ADH
• Can be genetic
• Trauma, tumors. Infections, inflammatory conditions of the posterior pituitary
Nephrogenic (pituitary is producing but nephrons are resistant)
• Resistance to ADH
• Genetic
• Or secondary to drugs (e.g Lithium), metabolic upset, renal disease
Diagnosis of diabetes insipidus
ADH stimulation/ water deprivation test is used to distinguish between deficient ADH and unresponsive kidneys.
Deprive patients of fluid for 8h, then measure plasma and urine osmolality every 2-4hr
Normal = If you deprive a normal patient of water, kidneys will respond by producing a small volume of concentrate urine, plasma osmolarity remains unchanged
DI
If you deprive a patient of water, kidneys will not care and will continue to produce large volumes of dilute urine and plasma volume continues to rise
To assess between cranial and nephrogenic give synthetic ADH (ddAVP) and reassess urine osmolality
Cranial= if you give synthetic ADH you immediately solve the problem and produce concentrated urine
Nephrogenic DI= If you give synthetic ADH, the kidneys will not respond and still produce dilute urine
*if urine is dilute osmolality is low
management of diabetes insipidus
Cranial • Desmopressin (vasopressin/ADH analogue) • Can be given orally/nasal spray/ Injection • Monitor plasma sodium and osmolality Nephrogenic • Treat underlying cause • High doses of ddAVP • Very difficult
Definition of SIADH
Excess production of ADH or inappropriate ADH for plasma osmolality, causes hyponatraemia
Causes of SIADH
General illness will cause ADH excess • Cancer: lung/lymphoma/leukaemia • Chest disease: pneumonia • CNS disorder: infections, injury • Drugs: opiates, thiazides, anti-convulsants, proton pump inhibitors, anti-depressants
Diagnosis of SIADH
Excess ADH, brings down plasma osmolality, brings down sodium
• Urine osmolality > plasma osmolality high urinary osmolality
• Urine sodium >20 mmol/l - high urinary sodium
• Absence of hypotension, hypovolaemia and oedematous states
• Normal renal and adrenal function
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Treatment
- Treat underlying cause
- Fluid restrict (1-1.5l/day)
- Use ADH (AVPR2) anatagonists (vaptans)
Hyperpituitarism definition
excess pituitary hormone secretion
Hypopituitarism
insufficient pituitary hormones secretion
Compression of the surrounding structures of pituitary
space-occupying lesions
Pituitary tumours are classified into
functioning and non-functioning
Pituitary tumours can present with
visual field defects from compresion of optic chiasm (bitemporal hemianopia)
- headaches
- eye movement problems
- inappropriate hormone secretion e.g prolactin, ACTG, GH
- hormone hypo/hypersecretion
- amenorrhoea and or loss of libido
features of functioning/secretory pituitary tumours
- Present early, while still very small
- Cause disease by excess hormone release
- Fatal if untreated
Types of functioning/secretory pituitary tumours
- Prolactin (prolactinoma) –>Commonest: 30%
- GH (acromegaly) ~ 15%
- ACTH (Cushings disease) ~20%
- TSH (TSHoma) ~
Features of prolactinoma
- Commonest secretery pituitary tumour
- Pituitary tumours releasing prolactin
- Micro 1cm
Clinical features of prolactinoma
- Galactorrhoea (milk secretion)
- Headaches
- Mass effect
- Visual field defect
- Amenorrhoea
- erectile dysfunction
Investigations of prolactinoma
- serum prolactin >6000
- MRI pituitary
- Test remaining pituitary function
o Gonadal function and thyroid hormones most affected
treatment of prolactinoma
- Medical
o Dopamine agonists
o E.g cabergoline/bromocriptine/quinagolide - Surgery
o Surgery if large tumour with visual field effects
o VF compromise
o Failure of medical therapy
Definition of acromegaly
Excess production of GH (and IGF-1) in adults (in children- gigantism)
Cause of acromegaly
pituitary adenoma
Clinical features of acromegaly
“growth plates fuse after puberty, however tissue size can increase” - Symptoms o Sweats o Headache o Tiredness o Increase in ring or shoe size, joint pains - Signs o Coarse facial appearance o Enlarged tongue o Enlarged hands and feet o Visual field loss
Complications of Acromegaly
- Impaired glucose tolerance (40%), DM (15%)
- Vascular: BP increases, left ventricular hypertrophy (+/- dilation/CCF) cardiomyopathy
- Increased risk of bowel cancer
- Heart failure
Diagnosis of acromegaly
“if you think a hormone is being produced in excess you suppress it”
- Glucose suppresses GH therefore do a glucose tolerance test
o Glucose load fails to suppress GH
o May reveal underlying GM IGT
- IGF-1 level
o Long half life, protein bound
o So more useful than plasma GH which is pulsatile
- Pituitary MRI
o Tumour usually large (macroadenoma >1cm) and often extends into surrounding structures
Treatment of Acromegaly
- Surgical o By transphenoidal route o Often not curative - Medical therapy o Before and after surgery o Somatostatin analogues to inhibit GH secretion - Pituitary radiotherapy o To treat residual tumour o Risk of hypopituitarism and long term problems
Hypopituitarism definition
failure of anterior pituitary function-
Can affect single hormonal axis (FSH/LH most commonly) or all hormones (Panhypopiuitarism)
Leads to secondary gonadal/thyroid/adrenal failure
Causes of hypopituitarism
- Tumours
- Radiotherapy
- Infarction /haemorrhage (apoplexy)
o Associated headache/visual disturbance
o Assoc PPH (Sheehans syndrome) - Infiltration (e.g sarcoid)
- Trauma
Diagnosis of hypopituitarism
- Diagnosis of hypopituitarism involves the same as for hyperpituitarism. However, stimulation tests are used instead of suppression
- Visual field assessment
- Basal hormone levels in the blood
- Stimulation tests
- MRI or CT scan
The main stimulation tests for anterior pituitary levels are to measure - GH in response to an insulin tolerance test, which normally increases GH levels
- Cortisol in response to hypoglycaemia or the ACTH analogue synacthen
- LH and FSH in response to GnRH or the anti-oestrogen clomifene
Treatment for hypopituitarism
- The main treatment of hypopituitarism is hormone replacement, which requires frequent monitoring. All major anterior pituitary hormones can be replaced, though prolactin is not readily available since it is rarely needed:
- ACTH – hydrocotrison
- TSH- thyroxine
- FSH/LH – testosterone (males), Oestrogen (females)
- GH – growth hormone
- PRL – no replacement
Insulinoma defintion
Rare tumour of islet cells
Symptoms of insulinoma
Sweats
Weakness
Confusion
Seizure
Initial investigations of insulinoma
Urine sulphonylurea screen Overnight fast (glucose/insulin/ c-peptide) Medical imaging (CT abdo/endoscopic USS)
Treatment of insulinoma
Surgery
95% benign
