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UG Biochemistry > 7. Pituitary Gland > Flashcards

7. Pituitary Gland Flashcards

(56 cards)

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1
Q

Describe anatomy of pit gland

A

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
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2
Q

Describe general function of pit gland

A

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
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3
Q

Describe the function + regulation of the anterior pituitary

A

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
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4
Q

Describe the regulation of hypothalamic hormone production

A

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
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5
Q

Describe the different structures of hormones released by the anterior pituitary

A

Peptides/polypeptides: GH, prolactin, ACTH

Glycoproteins: TSH, FSH, LH

  • composed of 2 glycoprotein chains
  • alpha + beta subunits in LH
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6
Q

How can ant pit hormones be measured in the lab?

A

All routinely measured by immunoassay

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7
Q

List the ant pit hormones, their target organ + function (also include regulating hypothalamus hormone)

A

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
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8
Q

List the hormones released by the ant pit

A

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

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9
Q

How is hypothalamus + pituitary disease classified?

A

Primary = caused by target organ hypo/hyperfunction
e.g. primary hypothyroidism

Secondary = caused by pituitary hypo/hyperfunction

Tertiary = hypothalamus problem

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10
Q

What are the main causes of hypothalamus/pituitary disease?

A

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
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11
Q

What are the illnesses associated with the hypothalamic-pituitary-thyroid axis + how are they measured?

A

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

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12
Q

What are the illnesses associated with the hypothalamic-pituitary-gonadal axis + how are they measured?

A

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
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13
Q

What are the illnesses associated with the hypothalamic-pituitary-adrenal axis + how are they measured?

A

To detect primary/secondary hyper/hypo adrenalism;

  • measures ACTH + cortisol
  • cortisol usually measured first to assess axis

Hypo:CRH > pit:ACTH > adrenal:cortisol

  1. HYPERadrenalism (Cush syn) = increased cortisol/decreased ACTH
  2. HYPERadrenalism (Cush dis) = increased cortisol/ increased ACTH
  3. HYPOadrenalism (Add) = decreased cortisol/increased ACTH
  4. HYPOadrenalism = decreased cortisol/decreased ACTH
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14
Q

What type of pituitary tumours are there?

A
  1. Purely destructive/space occupying

2. Functional i.e. produce excess pit hormone

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15
Q

What are the general symptoms associated with any pituitary tumour?

A

As tumour takes up more intercranial space;

  • headache
  • vomiting
  • visual field defects
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16
Q

What kind of tests can be performed to assess pituitary tumours?

A

Biochem tests for hormone production

Imaging techniques e.g. CT/MRI scans to look for tumour

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17
Q

What is the most common hormone produced by pituitary tumours?

A

Prolactin - prolactinoma

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18
Q

What is hypopituitarism?

A

Diminished hormone secretion by pit

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19
Q

List the causes of hypopituitarism

A

Destruction of pituitary tissue

Hypothalamic/pituitary disease

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20
Q

What is the most common cause + type of hypopituitarism?

A

Most common cause = pit tumour

Partial hypopituitarism more common than complete/panhypopituitarism

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21
Q

How does hypopituitarism present?

A

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

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22
Q

How is hypopituitarism investigated?

A

Stimulatory tests - assess ability to produce hormones
Visual field exam - blind spots?
Skull radiography, imaging (CT/MRI)

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23
Q

Describe the use of stimulatory tests to investigate hypopituitarism

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A

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

24
Q

What is growth hormone + what is its function?

Study These Flashcards
A

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)
25
What stimulates + inhibits GH?
Stimulated by; - stress - exercise - fall in glucose (blood) - fasting - specific amino acids Inhibited by rise in blood glucose
26
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
27
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
28
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
29
What are the metabolic effects of excess GH?
Hypercalcemia Hyperphosphatemia (PO4) Glucose intolerance (diabetes mellitus may be seen)
30
What causes excess GH disorders?
95% cases due to excess secretion of GH by pituitary tumour
31
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
32
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
33
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
34
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
35
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
36
What regulates ADH production?
ADH secretion from post pit regulated by sodium conc in ECF; | - via osmoreceptors in hypothalamus
37
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
38
What two disorders are linked to ADH?
Deficiency of ADH action = diabetes insipidous Excess ADH secretion = syndrome of inappropriate ADH secretion (SIADH)
39
What is diabetes insipidous?
Disorder where kidneys cannot retain water due to deficiency in ADH action
40
List the signs + symptoms of DI
Uncontrolled excretion of water (polyuria) | Leads to thirst + polydipsia (excessive thirst/drinking)
41
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
42
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)
43
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
44
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
45
What are the symptoms of SIADH?
Pts usually asymptomatic as develops over days/weeks
46
How is SIADH treated?
Restriction of fluid intake
47
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
48
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
49
Does prolactin remain steady in the blood?
Prolactin secretion is pulsatile Increases; - with stress - during sleep - increased levels during pregnancy + breastfeeding (main stimulus = suckling)
50
Describe prolactin deficiency
Rare | Only symptom = failure of lactation
51
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
52
What is hyperprolactinemia?
A common endocrine abn of the ant pit that causes overproduction of prolactin
53
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)
54
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
55
What is the treatment for a prolactinoma?
Surgery | Dopamine agonist drugs can be used to shrink, e.g. bromocriptine
56
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 ```

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