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UG Biochemistry > 7. Pituitary Gland > Flashcards

7. Pituitary Gland Flashcards

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

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?

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
Q

What stimulates + inhibits GH?

A

Stimulated by;

  • stress
  • exercise
  • fall in glucose (blood)
  • fasting
  • specific amino acids

Inhibited by rise in blood glucose

26
Q

Do GH levels remain constant in the body?

A

GH levels in blood vary throughout the day - may be undetectable with current assays

Secretion occurs in bursts throughout day: mainly during sleep

27
Q

Describe the GH pathway

A

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
Q

What are the signs + symptoms of GH excess?

A

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
Q

What are the metabolic effects of excess GH?

A

Hypercalcemia
Hyperphosphatemia (PO4)
Glucose intolerance (diabetes mellitus may be seen)

30
Q

What causes excess GH disorders?

A

95% cases due to excess secretion of GH by pituitary tumour

31
Q

How is an excess GH disorder usually diagnosed?

A

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
Q

List the causes of GH deficiency

A

Congenital

Acquired;

  • pit/hypo damage
  • psychosocial deprivation
  • idiopathic

Children: most secondary to GHRH deficiency
Adults: most pit adenoma/irradiation

33
Q

Describe the signs + symptoms of GH deficiency in adults + children

A

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
Q

How is GH deficiency diagnosed?

A

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
Q

What is vasopressin and what is its function?

A

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
Q

What regulates ADH production?

A

ADH secretion from post pit regulated by sodium conc in ECF;

- via osmoreceptors in hypothalamus

37
Q

What non-osmotic factors stimulate ADH release?

A

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
Q

What two disorders are linked to ADH?

A

Deficiency of ADH action = diabetes insipidous

Excess ADH secretion = syndrome of inappropriate ADH secretion (SIADH)

39
Q

What is diabetes insipidous?

A

Disorder where kidneys cannot retain water due to deficiency in ADH action

40
Q

List the signs + symptoms of DI

A

Uncontrolled excretion of water (polyuria)

Leads to thirst + polydipsia (excessive thirst/drinking)

41
Q

Describe the two main types of DI

A

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
Q

Describe the rarer types of DI

A

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
Q

How is DI diagnosed?

A

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
Q

What is SIADH + with what conditions is it associated?

A

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
Q

What are the symptoms of SIADH?

A

Pts usually asymptomatic as develops over days/weeks

46
Q

How is SIADH treated?

A

Restriction of fluid intake

47
Q

How is SIADH diagnosed?

A

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
Q

What is the function of prolactin + how is it regulated?

A

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
Q

Does prolactin remain steady in the blood?

A

Prolactin secretion is pulsatile

Increases;

  • with stress
  • during sleep
  • increased levels during pregnancy + breastfeeding (main stimulus = suckling)
50
Q

Describe prolactin deficiency

A

Rare

Only symptom = failure of lactation

51
Q

What factors affect prolactin secretion?

A

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
Q

What is hyperprolactinemia?

A

A common endocrine abn of the ant pit that causes overproduction of prolactin

53
Q

What causes hyperprolactinema?

A

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
Q

What are the signs + symptoms of hyperprolactinemia?

A

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
Q

What is the treatment for a prolactinoma?

A

Surgery

Dopamine agonist drugs can be used to shrink, e.g. bromocriptine

56
Q

Why are falsely high prolactin levels sometimes detected in the lab? How can this be fixed?

A

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

UG Biochemistry (14 decks)

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