7. Pituitary Gland Flashcards
Describe anatomy of pit gland
Located at base of skull in pituitary fossa
Beneath hypothalamus - connected via pit stalk
2 lobes, close prox but functionally distinct;
- ANTERIOR pituitary
- POSTERIOR pituitary
Describe general function of pit gland
Each lobe contains unique cells + releases diff hormones
Generally, controls several vital functions including;
- release of hormones for growth
- thyroid, adrenal, reproductive function
- water homeostasis
Describe the function + regulation of the anterior pituitary
Secretes several different peptide/glycopeptide hormones
- inc trophic hormones that stimulate activity of other endocrine glands
Secretion of ant pit hormones controlled by;
- hypothalamus hormones: reach via system of portal BVs
- feedback from stimulated hormones in other organs
Describe the regulation of hypothalamic hormone production
Secretion of hypothalamic hormones controlled by higher centres in the brain;
- signal by neurotransmitters e.g noradrenaline, serotonin, acetylcholine
- reflects internal (e.g. glucose levels) + external environmental (e.g. stress, light/dark) signals
Negative feedback control on hypothalamic hormone release is inhibited by some ant pit + target organ secretions;
- neg feedback from pit = short loop
- neg feedback from target organ = long loop
Describe the different structures of hormones released by the anterior pituitary
Peptides/polypeptides: GH, prolactin, ACTH
Glycoproteins: TSH, FSH, LH
- composed of 2 glycoprotein chains
- alpha + beta subunits in LH
How can ant pit hormones be measured in the lab?
All routinely measured by immunoassay
List the ant pit hormones, their target organ + function (also include regulating hypothalamus hormone)
GHRH = GH; (inhib: somatostatin)
- liver = IGF
- others = metabolic regulation
Prolactin; (inhib: dopamine)
- breast = lactate
TRH = TSH;
- thyroid = thyroid hormone synthesis + release
GnRH = FSH;
- ovary = estrogen synth + oogenesis
- testes = spermatogenesis
GnRH = LH;
- ovary = ovulation + corpus luteum = progesterone production
- testes = testosterone synth
CRH = ACTH;
- adrenal cortex = GC (cort) synth + release
- skin = pigmentation
List the hormones released by the ant pit
2 hormones;
- arganine vasopressin/anti-diuretic hormone = water reabsorption at kidney tubule
- oxytocin = uterus contractility + lactation
Both produced in hypo + pass down nerve axons into post pit
How is hypothalamus + pituitary disease classified?
Primary = caused by target organ hypo/hyperfunction
e.g. primary hypothyroidism
Secondary = caused by pituitary hypo/hyperfunction
Tertiary = hypothalamus problem
What are the main causes of hypothalamus/pituitary disease?
Hormone deficiency/excess may arise from damage to pit/hypothala or target organs
Causes;
- tumours, e.g. pit adenoma, prolactinoma
- infection, e.g. encephalitis
- trauma, e.g. head injury
- iatrogenic, e.g. surgery, radiation, prolonged treatment with thyroxine or GC causing TSH + ACTH suppression
- genetic, e.g. hereditary deficiency
- hypothalamic functional disturbances, e.g. stress, starvation, anorexia, intense athletic training causing reversible hypogonadotrophic hypogonadism
What are the illnesses associated with the hypothalamic-pituitary-thyroid axis + how are they measured?
Thyroid function tests to detect hypo/hyperthyroidism
- random serum TSH + fT4 (free thyroxine) measured
- indicates primary or secondary (pit problem)
Hypo: TRH > Pit: TSH > Thyroid: T4/thyroxine
1 HYPOthyroidism = decreased fT4/increased TSH
2 HYPOthyroidism = decreased fT4/decreased TSH
1 HYPER thyroidism = increased fT4/decreased TSH
2 HYPER thyroidism = increased fT4/increased TSH
Also note clinical features: proptosis/goitre = Grave’s
What are the illnesses associated with the hypothalamic-pituitary-gonadal axis + how are they measured?
To detect primary/secondary hypo/hypergonadism
- affects the gonadotrophins LH + FSH
Male: hypo:GnRH > pit: FSH + LH > testes: sperm + testosterone
Female: hypo:GnRH > pit: FSH + LH > ovaries: estrogen = ovulation, menstruation, etc
Hypopituitarism typically causes;
MALE:
- decreased testosterone, decreased/normal LH/FSH
FEMALE:
- premenopausal: amenorrhea, decreased estradiol, decreased/normal LH/FSH
- postmenopausal (normally v high LH/FSH + low estradiol): decreased estradiol, decreased/normal LH/FSH
What are the illnesses associated with the hypothalamic-pituitary-adrenal axis + how are they measured?
To detect primary/secondary hyper/hypo adrenalism;
- measures ACTH + cortisol
- cortisol usually measured first to assess axis
Hypo:CRH > pit:ACTH > adrenal:cortisol
- HYPERadrenalism (Cush syn) = increased cortisol/decreased ACTH
- HYPERadrenalism (Cush dis) = increased cortisol/ increased ACTH
- HYPOadrenalism (Add) = decreased cortisol/increased ACTH
- HYPOadrenalism = decreased cortisol/decreased ACTH
What type of pituitary tumours are there?
- Purely destructive/space occupying
2. Functional i.e. produce excess pit hormone
What are the general symptoms associated with any pituitary tumour?
As tumour takes up more intercranial space;
- headache
- vomiting
- visual field defects
What kind of tests can be performed to assess pituitary tumours?
Biochem tests for hormone production
Imaging techniques e.g. CT/MRI scans to look for tumour
What is the most common hormone produced by pituitary tumours?
Prolactin - prolactinoma
What is hypopituitarism?
Diminished hormone secretion by pit
List the causes of hypopituitarism
Destruction of pituitary tissue
Hypothalamic/pituitary disease
What is the most common cause + type of hypopituitarism?
Most common cause = pit tumour
Partial hypopituitarism more common than complete/panhypopituitarism
How does hypopituitarism present?
Depends on;
- extent + severity of hormone deficiency
- age of pt (growth problems more obv in child)
If secreting tumour;
- symptoms of excess may also be present
Haemorrhage into pituitary (usually by tumour);
- can cause pituitary apoplexy
- sudden onset: headache, signs of meningism, visual problems, loss of consciousness
- urgent treatment req’d
Isolated deficiency of an ant pit hormone can occur but usually congenital
How is hypopituitarism investigated?
Stimulatory tests - assess ability to produce hormones
Visual field exam - blind spots?
Skull radiography, imaging (CT/MRI)
Describe the use of stimulatory tests to investigate hypopituitarism
Assess ability to produce hormones
Protocol;
- measure basal hormones
- give insulin, TRH + GnRH
- measure hormone response over 120 mins
- use immunoassay
Insulin-induced hypoglycemia should increase GH + cortisol
TRH should increase TSH
GnRH should increase LH/FSH
What is growth hormone + what is its function?
GH = hormone essential for normal growth
Mainly acts via stimulating liver to produce insulin-like growth factor 1 (IGF-1)
Metabolic effects;
- increased lipolysis (ketogenesis)
- increased liver glucose production
- decreased tissue glucose uptake
- increased protein synthesis (anabolic)
What stimulates + inhibits GH?
Stimulated by;
- stress
- exercise
- fall in glucose (blood)
- fasting
- specific amino acids
Inhibited by rise in blood glucose
Do GH levels remain constant in the body?
GH levels in blood vary throughout the day - may be undetectable with current assays
Secretion occurs in bursts throughout day: mainly during sleep
Describe the GH pathway
CNS signals hypothalamus by neurotransmitters;
- stimulated by stress, exercise, sleeping
Hypothalamus releases;
- GHRH: stimulates ant pit to release GH
- increased by fasting, hypoglycemia, arganine
- Somatostatin: inhibits ant pit release of GH
- decreased by hyperglycemia
GH released by ant pit;
- metabolic effects e.g. increase blood glucose
- stimulate IGF-1 in liver = anabolic growth
Negative feedback of IGF-1 + GH on pituitary + hypothalamus
What are the signs + symptoms of GH excess?
Causes excess growth of soft tissues + bone
Children;
- before bone epiphyses fixed
- causes GIGANTISM due to growth of long bones
Adults;
- bone epiphyses fixed
- causes ACROMEGALY
- increased growth of soft tissues, hands, feet, jaw + inner organs are characteristic
E.g. Charles Byrne 1761-1783
- “Irish giant”: skeletal evidence places at 7ft 7in
- acromegaly, died at 22
What are the metabolic effects of excess GH?
Hypercalcemia
Hyperphosphatemia (PO4)
Glucose intolerance (diabetes mellitus may be seen)
What causes excess GH disorders?
95% cases due to excess secretion of GH by pituitary tumour
How is an excess GH disorder usually diagnosed?
Random serum GH usually raised BUT secretion episodic: need confirmation
Confirm by oral glucose tolerance test (OGTT)
- GH fails to suppress to <2mU/L in GH excess
Serum IGF-1 also high
List the causes of GH deficiency
Congenital
Acquired;
- pit/hypo damage
- psychosocial deprivation
- idiopathic
Children: most secondary to GHRH deficiency
Adults: most pit adenoma/irradiation
Describe the signs + symptoms of GH deficiency in adults + children
Rare but significant cause of growth retardation in children
- majority secondary to GHRH deficiency
Most cases in adults due to pituitary adenoma/irradiation
- not of major clinical significance
- can cause fatigue/lack of muscle strength
How is GH deficiency diagnosed?
Random GH concentration of >20mU/L
- excludes significant deficiency
- BUT random levels often undetectable = need stim test
Stimulation tests: various pharmacological/physiological stimuli can be used to assess pit GH reserves;
- insulin hypoglycemia test: should stim GHRH + GH
- exercise
- arganine
- glucagon
- sleep
What is vasopressin and what is its function?
Post pit hormone aka ADH/AVP
Essential to maintain fluid + electrolyte balance = controls tonicity + concentration of ECF in body
Functions by regulating water permeability of renal collecting tubule + ascending loop of Henle
- reduces water loss in urine by reabsorption
What regulates ADH production?
ADH secretion from post pit regulated by sodium conc in ECF;
- via osmoreceptors in hypothalamus
What non-osmotic factors stimulate ADH release?
Non-osmotic stimuli for ADH release;
- reduction in circulating blood volume/hypotension
- nausea/vomiting
- hypoglycemia
- pain
Non-osmotic stimuli override osmotic regulation = water retention can be non-specific finding in illness
What two disorders are linked to ADH?
Deficiency of ADH action = diabetes insipidous
Excess ADH secretion = syndrome of inappropriate ADH secretion (SIADH)
What is diabetes insipidous?
Disorder where kidneys cannot retain water due to deficiency in ADH action
List the signs + symptoms of DI
Uncontrolled excretion of water (polyuria)
Leads to thirst + polydipsia (excessive thirst/drinking)
Describe the two main types of DI
Cranial (central) DI;
- failure of ADH secretion
- e.g. due to pit tumour, meningitis, trauma/surgery, familial
Nephrogenic DI
- failure of kidney to respond to ADH
- e.g. due to CKD, familial, drugs
Describe the rarer types of DI
Dipsogenic DI;
- inappropriate excess fluid intake
- defect/damage to thirst mechanism in hypothalamus
- generally manifestation of primary hyperdipsia (psychogenic: psychiatric disease/non-psychogenic: autoimmune chronic hep with severely increased Ig)
- secondary hyperdipsia (drug effects)
Gestational DI;
- only during pregnancy
- enzyme made by placenta destroys ADH in mother (vasopressinase)
How is DI diagnosed?
Exclude other causes of polyuria + polydipsia
- DM, chronic renal failure, hypercalcemia, low K+
- simple blood tests exclude these
Psychogenic polydipsia (compulsive) = polyuria - difficult to distinguish from true DI
Diagnosis confirmed with fluid deprivation test;
- in normal subjects urine = concentrated + serum osmolality will not exceed 295mmol/L
- in DI urine will fail to concentrate = increased osmolality
Cranial/nephrogenic DI can be distinguished in a final stage of fluid deprivation test;
- pt given synthethic analogue of ADH (desmopressin)
- cranial DI = urine concentrated
- nephrogenic DI = urine remains dilute as kidneys still insensitive to ADH
What is SIADH + with what conditions is it associated?
Syndrome of Inappropriate ADH secretion;
- pts have dilutional hyponatremia due to impairment of water excretion
Seen in many conditions;
- infections, e.g. pneumonia
- malignancy, e.g. carcinoma of bowel/lung
- trauma, e.g. abdominal surgery
- drug induced, e.g. carbamazepine
What are the symptoms of SIADH?
Pts usually asymptomatic as develops over days/weeks
How is SIADH treated?
Restriction of fluid intake
How is SIADH diagnosed?
Exclude other causes of hyponatremia;
- diuretic treatment
- heart failure, liver disease = edema
- thyroid/adrenal disease
- kidney disease
- low Na assoc with volume depletion, e.g. vomiting, diarrhea (take history, assess fluid status)
Water loading test can be used;
- pts fail to dilute urine in SIADH
- dangerous! can overload with water
What is the function of prolactin + how is it regulated?
Main action = initiate + sustain lactation
Secretion of prolactin from ant pit controlled by hypothalamus through dopamine;
- dopamine inhibits prolactin secretion from pit
- no known hypothalamus releasing hormone for prolactin
Does prolactin remain steady in the blood?
Prolactin secretion is pulsatile
Increases;
- with stress
- during sleep
- increased levels during pregnancy + breastfeeding (main stimulus = suckling)
Describe prolactin deficiency
Rare
Only symptom = failure of lactation
What factors affect prolactin secretion?
Dopamine from hypo: inhibits prolactin secretion from ant pit
Dopamine inhibited by;
- some antipsychotic drugs, antidepressants, signals from spinal cord
- supracellular + infundibular lesions
Prolactin secretion stimulated by;
- prolactinomas
- some GH-secreting adenomas
- estrogen
- in experimental settings TRH + VIP (from hypothala via hypophyseal portal system)
Renal clearance of prolactin inhibited by renal insufficiency + failure
What is hyperprolactinemia?
A common endocrine abn of the ant pit that causes overproduction of prolactin
What causes hyperprolactinema?
Pit tumour secreting prolactin (prolactinoma)
Pit tumour blocking blood from hypothalamus;
- stops inhibition via dopamine
Pit stalk damage/surgery;
- stops dopamine inhibition
Drugs reducing dopamine levels/blocking dopamine receptors in pituitary
Hyperthyroidism;
- TRH stimulates prolactin secretion (not v significant)
What are the signs + symptoms of hyperprolactinemia?
Important cause of infertility in males + females;
- thought to be due to high prolactin interference in GnRH release
Impotence in males + menstrual irregularities/galactorrhoea in females
What is the treatment for a prolactinoma?
Surgery
Dopamine agonist drugs can be used to shrink, e.g. bromocriptine
Why are falsely high prolactin levels sometimes detected in the lab? How can this be fixed?
Falsely high prolactin levels seen in small proportion of individuals with macroprolactin in their blood;
- physiologically inactive complex of Ig + prolactin
Polyethylene glycol (PEG) can be used to ppt out macroprolactin - sample can be reanalysed to measure prolactin not bound to Ig
