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Endocrinology > Endo > Flashcards

Endo Flashcards

1
Q

What are the major endocrine systems?

A

Pituitary
Thyroid
Parathyroid
Adrenal
Pancreas
Ovary
Testes

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2
Q

What is a basic definition of hormone

A

To excite

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3
Q

What do we mean by Endocrine?

A

Within/separate - glands ‘pour’ secretions into blood stream (thyroid, adrenal, beta cells of pancreas)

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4
Q

What do we mean by Exocrine?

A

Outside - glands ‘pour’ secretions through a duct to site of action (pancreas - amylase, lipase)

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5
Q

What does hormone action depend on?

A

blood level of hormone
numbers of target cell receptors
affinity for receptors

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6
Q

What are the different types of hormone action?

A

Endocrine
Paracrine
Autocrine

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7
Q

What does Endocrine mean?

A

blood-borne, acting at distant sites

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8
Q

What does paracrine mean?

A

acting on adjacent cells

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9
Q

What does autocrine mean?

A

feedback on same cell that secreted hormone

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10
Q

What are the crucial mediators of body homeostasis?

A

reproduction, sexual differentiation development and growth

maintenance of the internal environment regulation of metabolism and nutrient supply

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11
Q

What are the features of water-soluble hormone?

A

Transport : Unbound - dont need to bind
Cell interaction: Bind to surface receptor of organ or whatever its working on
Half life : short
Clearance : fast
Eg : peptides, monoamines

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12
Q

What are the features of fat hormone?

A

Transport : Protein bound
Cell interaction: Diffuse into cell
Half life : long
Clearance : slow
Eg : Thyroid hormone, steroids

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13
Q

Where are peptides/ monoamines stored in?

A

Vesicles

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14
Q

Whats the difference between peptide and steroid hormone production?

A

Steroids are synthesised on demand

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15
Q

Features of Peptide hormones:

A

-Vary in length – TRH: 3 amino acids, Gonadotrophins: 180 amino acids
-Linear or ring structures
-Two chains and may bind to carbohydrates e.g LH,FSH
-Stored in secretory granules, hydrophilic, water soluble
-Released in pulses or bursts
-Cleared by tissue or circulating enzymes
-E.g insulin

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16
Q

How are peptides granularly stored?

A

Synthesis: Preprohormone> prohormone
Packaging: Prohormone>hormone
Storage: Hormone
Secretion: Hormone

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17
Q

How does the insulin receptor work?

A
  1. Insulin binds to insulin receptor
  2. Causes phosphorylation of insulin receptor > Tyrosine kinase now active
  3. Signal molecules becomes phosphorylated > cascade of effects > glucose uptake and anabolic reactions
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18
Q

Where is insulin released/ secreted from?

A

Pancreas - beta cell islets of langerhans

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19
Q

What are the features of Amine hormones?

A

Amines: water soluble, stored in secretory granules, release pulsatile, rapid clearance,
Bind to alpha and beta receptors or D1 and D2

E.g Adrenaline / Noradrenaline

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20
Q

What happens when amine hormones bind to alpha adrenoreceptors?

A

vasoconstriction, dilated pupil, alertness, contraction of stomach, bowel, anal sphincter

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21
Q

What happens when amine hormones bind to beta adrenoreceptors?

A

Beta adrenoceptors: vasodilatation, increased heart rate, bronchial and visceral smooth muscle relaxation

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22
Q

What are the features of phenylalanine derivatives?

A

Secreted by medulla
Neurotransmitters
Rate limiting step is the conversion to l-DOPA
Cortisol potentiates conversion of norepinephrine to epinephrine
Look back “the endocrine system and functional anatomy and physiology” lecture slide on amine ask if relevant

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23
Q

Where is adrenaline released from?

A

Adrenal medulla

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24
Q

What hormones are produced from adrenal cortex?

A

aldosterone (a mineralocorticoid)
cortisol (a glucocorticoid) androgens
estrogen (sex hormones)

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25
Q

What stimulates the secondary messenger system?

A

Hormone is primary messenger – stimulates secondary messenger system – could lead to inhibitory effect or stimulatory effect

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26
Q

What are the features of Iodothyronine hormones? (Thyroid hormones)

A

-Not water soluble; 99% is protein bound
-Only 20% of T3 in the circulation is secreted directly by thyroid
-Secretory cells release thyroglobulin into colloid – acts as base for thyroid hormone synthesis
-Incorporation of iodine on tyrosine molecules to form iodothyrosines
-Conjugation of iodothyrosines gives rise to T3 and T4 and stored in colloid bound to thyroglobulin
-TSH stimulates the movement of colloid into secretory cell, T4 and T3 cleaved from thyroglobulin

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27
Q

What makes up follicles?

A

Secretory cells + colloid

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28
Q

Thyrosine comes from…?

A

Thyroglobulin

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29
Q

Iodine comes from…?

A

Iodide

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30
Q

Thyroid hormones will bind to what protein?

A

thyroid binding globulin

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31
Q

Synthesis of Thyroxine T4 and T3

A
  1. Thyroglobulin synthesised and discharged in the follicle lumen - goes through RER and GA and forms Tyrosines
  2. Iodide (I-) actively transported into follicle lumen
  3. Iodide oxidised to iodine
  4. Iodine attached to tyrosine in colloid to forming DIT and MIT
  5. Iodinated tyrosines (DIT and MIT) linked together to form T3 and T4
  6. Thyroglobulin colloid is endocytosed and combined with a lysosome
  7. Lysosomal enzymes cleave T4 and T3 from thyroglobulin and hormones diffuse into bloodstream
    3,4,5 - happens in colloid
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32
Q

What are 3 hormone receptor locations ?

A

Cell membrane
Cytoplasm
Nucleus

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33
Q

What hormones work on cell membranes?

A

Peptides

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34
Q

What hormones work on cytoplasm?

A

Steroids

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35
Q

What is the steroid receptor family?

A

Glucocorticoids - cortisol
Mineralocorticoids - aldosterone
Androgens - testosterone
Progesterone

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36
Q

What hormones work on the nucleus?

A

Thyroid hormones

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37
Q

What is the nuclear receptor family?

A

Oestrogen
Thyroid Hormone
Vitamin D

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38
Q

What are the features of cholesterol derivatives and steroid hormones (Vitamin D)

A

Fat soluble
Enters cells directly to nucleus to stimulate mRNA production
Transported by Vitamin D binding protein

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39
Q

What are the features of cholesterol derivatives and steroid hormones (Adrenocortical and gonadal steroids)

A

-95% protein bound
After entering cell:
-Pass to nucleus to induce response
-Altered to active metabolite
-Bind to a cytoplasmic receptor

Not too rapid inactivation
- In liver by reduction and oxidation, or conjugation to glucoronide and sulphate groups

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40
Q

How do we get the Vitamin D we need?

A

Sunlight > 7-dehydrocholesterol > Cholecalciferol (Vit D3) > Liver > Converted to 25-hydroxyvitamin D3> Kidney> converted to 1,25-dihydroxyvitamin D3 WHICH maintains calcium balance in the body

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41
Q

Where is progesterone secreted?

A

Corpus luteum of ovaries

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42
Q

Where is testosterone secreted from?

A

Leydig cells of testes

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43
Q

Where is estradiol secreted from?

A

Follicles of ovaries

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44
Q

What is the intracellular pathway for steroid action?

A
  1. Steroid hormone diffuses through plasma membrane and binds to receptor
  2. Receptor hormone complex enters nucleus
  3. Receptor hormone complex binds to GRE
  4. Binding initiates transcription of gene to mRNA
  5. mRNA directs protein synthesis
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45
Q

What are the different ways of controlling hormone secretion?

A

-Basal secretion – continuously or pulsatile

-Superadded rhythms e.g day-night cycle – ACTH, prolactin, GH and TSH

-Release inhibiting factors – dopamine inhibiting prolactin, sum of positive and negative effects (GHRH and somatostatin on GH)

-Releasing factors

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46
Q

Why should we know the time of day when we measure hormone levels?

A

range will vary depending on time of day
Cortisol level – at 4pm its 100 9am could be different
This is due to circadian rhythm of hormones

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47
Q

What is hormone metabolism?

A

increased metabolism to reduce function

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48
Q

What is hormone receptor induction?

A

Induction of LH receptors by FSH in follicle

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49
Q

What is Hormone receptor down regulation?

A

Hormone secreted in large quantities cause down regulation of its target receptors

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50
Q

What is synergism in hormones?

A

Combined effects of 2 hormones amplified ( glucagon with epinephrine-

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51
Q

What is antagonism in hormones?

A

One hormone opposes another hormone (glucagon antagonises insulin)

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52
Q

Negative feedback loop?

A

Initial stimulus > Response > Decrease in stimulus > Response loop shuts off

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53
Q

Positive feedback loop?

A

Initial stimulus > response > Increase in stimulus
Outside factor is required to shut off

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54
Q

If we saw an MRI of a pituitary gland what would we see?

A

Anterior and posterior pituitary gland
Optic chiasm
Hypothalamus
Pituitary stalk

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55
Q

What does the pituitary stalk do?

A

Carries hormones

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56
Q

What does the optic chiasm do?

A

carries optic nerves over pituitary gland

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57
Q

What does the hypothalamus do?

A

Stimulates production of hormones

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58
Q

What could happen if we have a pituitary gland tumour?

A

– press on optic chiasm – present with visual problems – bitemporal hemianopeia

Cavernus sinuses – get cranial nerve – CN 4 and CN6 are P and P2 of trigeminal nerve – patient will present with double vision

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59
Q

Features of posterior pituitary gland?

A

1.Hypothalamic neurons synthesis oxytocin or ADH in hypothalamus and paraventricular nucleus
2. Oxytocin and ADH are transported down the axons of the hypothalamic-hypophyseal tract to the posterior pituitary.
3. Oxytocin and ADH are stored in axon terminals in posterior pituitary.
4. When hypothalamic neurons activated, hormones released.

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60
Q

ADH

A

ant diuretic hormones – controls blood volume and sodium levels
Osmolality – conc of fluid in circulation – if increased ADH will reabsorb water from kidneys and prevent sodium levels get too high
Have conditions where you lose ADH – diabetes insipidus

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61
Q

What hormones does the anterior pituitary release?

A

Adrenocorticotrophic hormone (ACTH)
Thyroid-stimulating hormone (TSH)
Luteinising hormone (LH)
Follicle-stimulating hormone (FSH)
Prolactin (PRL)
Growth hormone (GH)
Melanocyte-stimulating hormone (MSH)

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62
Q

What hormones do PPG release?

A

Oxytocin and ADH

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63
Q

What happens if you have pituitary dysfunction?

A

Tumour mass effects
Hormone excess
Hormone deficiency
Headaches
Eye problems
Blindness – ignore initial problems
Acromegaly – young but very tall
Cushings syndrome - excess ATCH – excess cortisol

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64
Q

How do we get acromegaly?

A

Excess growth hormone

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65
Q

Growth hormone axis

A

Hypothalamus secretes growth hormone releasing hormone (GHRH) (as well as somatostatin which is GHIH)
GH released from anterior pituitary - inhibits GRHR release and stimulates GHIH release - inhibits GH synthesis and release

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66
Q

Hypothalamo-pituitary-thyroid axis

A

Hypothalamus releases thyroid releasing hormone > Ant pituitary releases TSH > Thyroid gland releases thyroid hormones

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67
Q

What important artery is next to thyroid artery?

A

Common carotid artery

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68
Q

Thyroid hormone functions

A

Accelerates food metabolism
Increases protein synthesis
Stimulation of carbohydrate metabolism
Enhances fat metabolism
Increase in ventilation rate
Increase in cardiac output and heart rate
Brain development during foetal life and postnatal development
Growth rate accelerated

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69
Q

Hypothalamo-pituitary-adrenal axis & Cortisol Actions

A

Hypothalamus secretes corticotropin releasing hormone (CRH) > AP releases Adrenocorticotropic hormone (ACTH) > Acts on Adrenal cortex causing cortisol release > causes negative feedback on ant pituitary and hypothalamus to not release ACTH and CRH

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70
Q

Adrenal gland zones

A

Capsule
Zona glomerulosa
Zona fasciculata
Zona reticularis
Adrenal medulla

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71
Q

Whats released from zona glomerulosa?

A

aldosterone
mineralcorticoids

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72
Q

Whats released from zona fasciculata?

A

cortisol
glucocrticoids

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73
Q

Whats released from zona reticularis?

A

sex hormones
Androgens
androstenedione
- dihydroepiandrosterone
(DHEA)

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74
Q

Cortex of adrenal gland?

A

Epinephrine
Norepinephrine

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75
Q

RAAS

A

relearn this

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76
Q

Short term stress response

A

Heart rate increases
BP increases
Bronchioles dilate
Liver converts glycogen to glucose and releases glucose into blood
Metabolic rate increases

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77
Q

Long term stress response

A

Kidneys retain sodium and water
Blood volume and blood pressure rise
Proteins and fats converted to glucose or broken down for energy
blood glucose increases
Immune system suppressed

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78
Q

Hypothalamo – pituitary - gonadal axis

A

Gonadotropin releasing hormone released from hypothalamus > Acts on FSH and LH to release testosterone and progesterone > negative feedback reduces FSH and LSH producion GnRH production

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79
Q

What does FSH do?

A

FSH – stimulates puberty to start and start producing sperm – supported by LH

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80
Q

Prolactin

A

Look it up and edit this

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81
Q

What is satiety?

A

feeling of fullness -
disappearance of appetite after a meal

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82
Q

BMI

A
  • wt (kg)/ht (m2)
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83
Q

What are the scales of BMI?

A

<18.5 underweight
18.5 - 24.9 normal
25.0 - 29.9 overweight
30.0 - 39.9 obese
>40 morbidly obese

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84
Q

Risks of obesity?

A

Type II diabetes
Hypertension
Coronary artery disease
Stroke
Osteoarthritis
Obstructive sleep apnoea
Carcinoma - breast, prostate, colon

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85
Q

Obesity in the UK

A

In excess of 20% of population are obese and 40% overweight; uk economy costs exceed 3 billion per year; 40% of children are obese or overweight and are the first generation at risk to die before parents

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86
Q

Link between obesity and shift work?

A

HSE 2013 25% of population carry out shift work; outside 7am to 7pm; more likely to report ill health and be diabetic or obese

Affect your rhythyms
When sleeping in day and waking up at night – glucose levels and insulkin levels higher – cortisol level is high when it should be low – body is not made up to work in that sort of situation

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87
Q

What does weight regulation depend on?

A

Environment
Genes
Maintenance (homeostasis) systems
Normal fat mass

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88
Q

Which hormone makes you lose appetite and stop eating?

A

Leptin

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89
Q

What is the main organ that controls appetite?

A

Hypothalamus
Lateral hypothalamus - hunger centre
Ventromedial hypothalamic nucleus (satiety center)

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90
Q

Features of Leptin

A

Expressed in white fat
Binds to leptin receptor
- cytokine receptor family
- in hypothalamus
Switches off appetite and is
immunostimulatory

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91
Q

What happens if you are deficient in leptin?

A

hyperphagic
hyperinsulinaemic
very obese
Blood levels increase after meal
Blood levels decrease after fasting
Continue eating without stopping

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92
Q

What are the important peptides in appetite suppression?

A

NPY - Neuro peptide Y

AgRP - Agouti-related peptide

POMC - Pro-opiomelanocortin

CART - cocaine and amphetamine regulated
transcript

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93
Q

How does leptin work

A

Increase in fat cell mass > increase in leptin action expression and action on hypothalamus >
1. inhibits NPY/AgRP neuron > decreased expression and release of these peptides > decreased food intake
2. Activates POMC neuron > increased alpha-MSH expression and release > increased alpha MSH binding and activation of melanocortin receptors > decreased food intake

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94
Q

Where are the NPY/AgRP neurons found

A

Arcuate nucleus

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95
Q

What does decreased AgRP release do?

A

Decreased inhibition of melanocortin receptors

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96
Q

What is peptide YY

A

36 amino acids
Structurally similar to NPY
Binds NPY receptors
secreted by neuroendocrine cells in ileum, pancreas and colon
in response to food
inhibits gastric motility
reduces appetite

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97
Q

What can PYY do?

A

Infusion of PYY diminishes appetite
Likely action by pre-synaptic Inhibitory Y2 receptors on NPY Neurones
- so less NPY released and hence hunger diminished

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98
Q

What does cholecystokinin (CCK) do?

A

Receptors in pyloric sphincter
- delays gastric emptying
- gall bladder contraction
- insulin release

and via vagus - satiety

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99
Q

What is Ghrelin?

A

28 amino acid
Acyl side chain
Expressed in stomach

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100
Q

What is the action of Ghrelin?

A

Growth hormone release
appetite - orexigenic
Blood levels high when fasting, fall on re-feeding
Levels lower after gastric bypass surgery

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101
Q

What will happen if you have a Proopiomelanocortin (POMC) deficiency?

A

Pale skin
Adrenal insufficiency
Hyperphagia and obesity

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102
Q

What are the effects of leptin and insulin together?

A
  1. Stimulate- POMC/CART neurons > increase CART and alpha-MSH levels
  2. Inhibit NPY/AgRP neurons > decrease NPY and AgRP

Net effect : ↑ Satiety and decreased Appetite

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103
Q

What are the effects of ghrelin?

A

stimulates NPY/AgRP > increases NPY and AgRP secretion

			      ↑ Appetite
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104
Q

What is PYY 3-36?

A

homolog of NPY
Binds to an inhibitory receptor on NPY/AgRP > decreased secretion of NPY and AgRP > decreased Appetite

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105
Q

What are incretins?

A

gut hormones that are secreted from enteroendocrine cells into the blood within minutes after eating.

Augment the secretion of insulin released from beta cells by a blood-glucose–dependent mechanism

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106
Q

What is the incretin effect on glucagon?

A

Blunting of GLUCAGON, in a glucose-dependent fashion.

means that glucagon is only blunted with normal or high glucose levels

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107
Q

What is the incretin effect on insulin?

A

Beta-cell stimulation of INSULIN production, in a glucose-dependent fashion.

Means that insulin is stimulated only when glucose levels are high.

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108
Q

What do sulfonylurea agents do?

A

stimulate beta cells to produce insulin, but continue to stimulate the beta cell even when hypoglycemia is present, hence worsening or prolonging the hypoglycvemia

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109
Q

What is the incretin effect on satiety?

A

Because weight control is an issue for the majority of T2DM patients, improved satiety enhances the ability to maintain diet and weight goals.

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110
Q

What is the incretin effect on gastric motility?

A

Decreased GASTRIC MOTILITY delivers smaller, less frequent amounts of calories to the small intesting per unit time.

Although not widely recognized, early diabetes is associated with an INCREASE in the rate of gastric motility.
Slowing the rate of delivery of gastric contents to the small intesting reduces the rate of rise of post-prandial glucose, hence the observed effects on postprandial glucose measurements.

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111
Q

Other effects of incretin?

A

Increased glucose uptake by muscles
Decreased glucose production
Increased glucose-dependent insulin release
Increased beta cell regeneration
Decreased glucose dependent glucagon release from alpha cell

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112
Q

What receptors in the stomach increase satiety?

A

Stretch

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113
Q

What are the actions of parathyroid hormone?

A

Increased calcium reabsorption because of increased 1,25 (OH) vit D
Decreased phosphate reabsorption
Decreased serum phosphate
Decreased FGF-23
Increased 1,25 (OH)2vit D
Increased bone remodelling + bone reabsorption > Bone formation

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114
Q

What is parathyroid hormone response to decreased serum calcium?

A

serum Ca2+ decreases > increased PTH > increased urinary phosphate excretion (increased bone resorption + increased Ca2+ reabsorption) > due to increased u-phos > decreased serum phosphate> increased 1,25-(OH)2 vit D>Increased Ca2+ absorption

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115
Q

Where do we find calcium detecting receptors?

A

Parathyroid glands

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116
Q

Calcium homeostasis is an example of what type of feedback?

A

Negative
Return serum ionised calcium back to the set point of about 1.1 mmol/l

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117
Q

What is the normal relationship between serum calcium and PTH?

A

Usually both at the same level

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118
Q

What happens if you have a low serum calcium?

A

Get very high PTH

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119
Q

What happens if you have a high serum calcium?

A

Get very low PTH

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120
Q

Why is calcium very important?

A

Functioning of nerves and muscles

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121
Q

Why would changes in PTH be appropriate?

A

To maintain calcium balance however could be inappropriate as it could cause calcium imbalance

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122
Q

What is hypocalcaemia?

A

Low total serum calcium + low albumin
(Not low ionised calcium)
Calcium bound to albumin
If albumin is outside normal range will effect calcium levels

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123
Q

What is the corrected calcium formula?

A

total serum calcium + 0.02 * (40 – serum albumin)

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124
Q

What are the consequences of hypocalcaemia ?

A

Parasthesia
Muscle spasm
-Hands and feet
-Larynx
-Premature labour
Seizures
Basal ganglia calcification
Cataracts
ECG abnormalities
o Long QT interval

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125
Q

Vitamin D is made from what?

A

the action of UVB on cholesterol on the skin

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126
Q

What are the uses of 1,25-dihydroxyvitamin D3 ?

A

Intestines - increases absorption of Ca2+
Bones - increases bone mineralisation
Immune cells - induces differentiation
Tumour microenvironment - Inhibits proliferation and angiogenesis, induces differentiation

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127
Q

How can hypoparathyroidism be caused?

A

Surgical radiation
Syndromes
Genetic
Surgical
Radiation
Autoimmune
Infiltration
Magnesium deficiency

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128
Q

What are some syndromes assosciated with hypoparathyroidism?

A

Di George
HDR
Kenney-Caffey

129
Q

What happens in Di George syndrome?

A

Developmental abnormality of third and fourth branchial pouches

130
Q

What are the genetic reasons for hypoparathyroidism?

A

Recessive
Dominant
X-linked

131
Q

How can autoimmune conditions cause hypoparathyroidism?

A

isolated
polyglandular type 1

132
Q

How can infiltration cause hypoparathyroidism?

A

Haemochromatosis
Wilson’s disease

133
Q

What is Pseudohypoparathyroidism?

A

Resistance to parathyroid hormone
Type 1 Albright hereditary osteodystrophy
– mutation with deficient Gα subunit

134
Q

What are the features Type 1 Albright hereditary osteodystrophy?

A

Short stature
Obesity
Round facies
Mild learning difficulties
Subcutaneous ossification
Short fourth metacarpals
Other hormone resistance

135
Q

What are symptoms of hypercalcaemia?

A

Thirst, polyuria
Nausea
Constipation
Confusion > coma
Renal stones
ECG abnormalities
Short QT

136
Q

What are the main reasons (90% of the time) hypercalcaemia is caused?

A

Malignancy
- bone mets, myeloma, PTHrP, lymphoma
Primary hyperparathyroidism

137
Q

What are some other reasons/ causes of hypercalcaemia?

A

Thiazides
Thyrotoxocosis
Sarcoidosis
Familial hypocalciuric / benign hypercalcaemia
Immobilisation
Milk-alkali
Adrenal insufficiency
Phaeochromocytoma

138
Q

What happens in malignancy of hypercalcaemia?

A

Increased serum calcium> Decrease in PTH > Decreased bone resorption, Decreased calcium absorption, decreased calcium reabsorption

139
Q

What are the consequences of Primary Hyperparathyroidism?

A

Bones
Osteitis fibrosa cystica
Osteoporosis

Kidney stones

Psychic groans
confusion

Abdominal moans
Constipation
Acute pancreatitis

140
Q

What is the optic chiasm?

A

Crossover of the optic nerve

141
Q

How does the anterior pituitary receive blood?

A

The anterior pituitary has no arterial blood supply but receives blood through a portal venous circulation from the hypothalamus
Has portal blood supply
Doesn’t have its own arteriole blood supply
Gets blood supply from hypothalamus

142
Q

What hormone is somatostatin?

A

inhibitory hormones – works with growth hormone releasing hormone
Corticor

143
Q

What is the pituitary thyroid axis?

A

Negative feedback loop
Hypothalamus releases TRH which stimulates TSH production fron anterior pituitary which causes production of T4 and T3
They feed back at the hypothalamus and pituitary

144
Q

If you remove the thyroid gland what will happen?

A

TSH will increase – use this as marker for underactive thyroid

145
Q

What does luteinising hormone (LH) do in men and women?

A

In men stimulates release of testosterone (which feedsback negatively)
releases oestradiol in women

146
Q

Why is Follicle stimulating hormone (FSH) important in men and women?

A

important for fertility and sperm

147
Q

What happens in menopause?

A

Menopause is failure of ovaries – stop secreting oestrogen no negative feedback so lh and fsh go up – measure lh and fsh to test for menopause

148
Q

What is released by the hypothalamus?

A

GHRH & SMS
GnRH
CRH
TRH
Dopamine

149
Q

What is released from pituitary?

A

GH
LH & FSH
ACTH
TSH
Prolactin

150
Q

What are some diseases of the pituitary?

A

Benign pituitary adenoma
Craniopharygioma
Trauma
Apoplexy / Sheehans
Sarcoid / TB

151
Q

What are the 3 vital points of pituitary tumour presentation?

A

1.Pressure on local structure e.g. optic nerves
-Bitemporal hemianopia – most common – tumours press on optic chiasm

2.Pressure on normal pituitary
hypopituitarism

3.Functioning tumour
Prolactinoma
Acromegaly
Cushing’s disease

152
Q

What can you have with a functioning pituitary tumour?

A

Prolactinoma
Acromegaly - big hands and big jaws – heart gets big - sleep apnoea
Cushing’s Disease - rounded face
Gigantism - not enough testosterone and and oestrogen

153
Q

What is the most common tumour in pituitary?

A

Prolactin microadenoma

154
Q

What are features of prolactin microadenoma?

A

No prolactin cant really breast feed
Mildly contraceptive – doesn’t guarantee that whilst breastfeeding you wont get pregnant
Women presents with infrequent periods – check prolactin levels

155
Q

Features of prolactinoma?

A

More common in women
Present with galactorrhoea / amenorrhoea
/ infertility
Loss of libido
Visual field defect

Treatment dopamine agonist eg Cabergoline or bromocriptine.

156
Q

What is the percentage of women who will get graves disease in their lifetime?

A

2% - 5-10 times more than men

157
Q

Where are thyroid autoantibodies found?

A

Thyroglobulin and thyroid peroxidase (TPO) antibodies found in almost all patients with autoimmune hypothyroidism

158
Q

What is the mechanism for thyroid cell destruction?

A

Cytotoxic (CD8+) T cell-mediated

Thyroglobulin and TPO antibodies may cause secondary damage, but alone have no effect

Uncommonly antibodies against the TSH-receptor may block the effects of TSH

159
Q

What are the causes of Graves disease?

A

Thyroid stimulating antibodies
Some TSH-R antibodies do not stimulate the receptor; instead they block the effects of TSH - these (rarely) can cause hypothyroidism

160
Q

What is the biggest risk factor for thyroid autoimmunity?

A

Being female

161
Q

What other risk factors are their for thyroid autoimmunity?

A

Genetic and environmental factors in varying proportion
HLA-DR3 and other immunoregulatory genes contribute (25% monozygotic twins concordant)
Environmental factors include stress, high iodine intake, smoking

162
Q

What are the autoimmune diseases assosciated with thyroid autoimmunity?

A

Type 1 diabetes mellitus
Addison’s disease
Pernicious anaemia
Vitiligo
Alopecia areata
Coeliac disease/ dermatitis herpetiformis
Chronic active hepatitis
Rheumatoid arthritis/ SLE/ Sjogren’s syndrome
Myasthenia gravis (Graves’ disease)

163
Q

What is thyroid associated ophthalmopathy?

A

Present in most Graves’ and some autoimmune hypothyroidism patients

Swelling in extraocular muscles

Most likely due to an autoantigen in the extraocular muscle that cross reacts with, or is identical to, a thyroid autoantigen

Current favourite candidate is the TSH receptor

Know its swelling
Due to TSH receptor antibodies interfering with extra ocular muscles with cytokines

164
Q

What is a GOITRE?

A

Palpable & visible thyroid enlargement
Variety of causes
Commonly sporadic or autoimmune
Endemic in iodine deficient areas

165
Q

What is a sporadic non-toxic GOITRE?

A

Commonest endocrine disorder
8.6% prevalence thyroid enlargement
Euthyroid
Goitre: diffuse, multinodular, solitary nodule, dominant nodule
Differentiate benign from malignant
Not throwing out excess thyroid hormone
Both lobes of the thyroid are swollen
Most often benign

166
Q

What is the definition of Hyperthyroidism?

A

Excess of thyroid hormones in blood

167
Q

What are the 3 mechanism for increased levels of Thyroid hormone?

A

a. overproduction thyroid hormone
b. leakage of preformed hormone from thyroid
c. ingestion of excess thyroid hormone

168
Q

What are most common causes of hyperthyroidism?

A

Graves’ disease (75- 80% of all cases)
Toxic multinodular goitre – cause excess thyroid hormone
Toxic adenoma – one nodule that secretes extra hormone

169
Q

What are some other causes of hyperthyroidism?

A

Congenital (neonatal) hyperthyroidism
Non autoimmune hereditary hyperthyroidism
Metastatic differentiated thyroid Ca
Struma ovarii
etc

170
Q

What drugs can cause drug-induced hyperthyroidism?

A

Iodine
Amiodarone
Lithium
Radiocontrast agents

171
Q

What are the clinical features of hyperthyroidism?

A

Wt loss
Tachycardia
Hyperphagia
Anxiety
Tremor
Heat intolerance
Sweating
Diarrhoea
Lid lag + stare
Menstrual disturbance

172
Q

What are specific clinical features of Graves disease?

A

Diffuse goitre
Thyroid eye disease (infiltrative)
Pretibial myxoedema
Acropachy
Clubbing
Something on the shin

173
Q

What are clinical features of a pituitary adenoma?

A

Solitary nodule

174
Q

What are the investigations we do for hyperthyroidism?

A

Thyroid function tests to confirm biochemical hyperthyroidism

Diagnosis of underlying cause important because treatment varies

Clinical history, physical signs usually sufficient for diagnosis

Supporting investigations

175
Q

Thyroid function tests: primary hyperthyroidism

A

increased [free T4], increased [free T3], suppressed TSH
in primary hyperthyroidism as it suppresses thyroid and hypothalamus – primary hyperthyroidism

176
Q

Thyroid function tests: secondary hyperthyroidism

A

(In secondary hyperthyroidism increased [free T4], increased [free T3] but inappropriately high TSH) – doesn’t respond to negative feedback mechanism leads to excess TRH production

177
Q

What are the different treatments for hyperthyroidism?

A

Antithyroid drugs (course or long-term)

Radioiodine 131I

Surgery (partial, subtotal thyroidectomy)

178
Q

What are examples of antithyroid drugs?

A

Thionamides-
carbimazole, propylthiouracil (PTU), methimazole

179
Q

What do thionamides do?

A

Decrease synthesis of new thyroid hormone
PTU also inhibits conversion T4 > T3
Do not treat underlying cause of hyperthyroidism BUT:
Immune modifying effects are seen(decrease IL-6) and reduction in antibody titres

180
Q

Which thionamide should pregnant ladies use?

A

propylthiouracil (PTU) - not just pregnant young women too

181
Q

What is the regiment for thionamides?

A

TITRATION regimen (12-18months)
BLOCK AND REPLACE regimen with T4 (6-12mths) for Graves’ disease
OR
short course to render euthyroid before 131I and surgery
OR
long-term treatment in patients unwilling to have131I or surgery

182
Q

What are the remission rates for antithyroid drugs?

A

Remission rates 30 - 50%

183
Q

What are some poor prognostic factors for antithyroid drug remission?

A

severe biochemical hyperthyroidism
large goitre
TRAb +ve at end of course of ATD
male sex
young age of disease onset

184
Q

Side effects of thionamides?

A

Generally well tolerated
Common side effect: Rash
Less common:
arthralgia
hepatitis
neuritis
thrombocytopenia
vasculitis
Usually occur within first few months
Resolve after stopping drug

185
Q

What is the most serious side effect of thianomides ?

A

Agranulocytosis
most serious side effect
occurs in 0.1% to 0.2%
manifests as sore throat, fever, mouth ulcers
MUST warn patients before starting ATD
STOP if patients develops symptoms and check FBC

186
Q

What is the definitive treatment for hyperthyroidism?

A

Radioiodine

187
Q

What is essential for thyroid hormone production?

A

Iodine
taken up by thyroid gland and used to make thyroid hormone
I actively transported by Na/I symporter into thyroid follicular cells

188
Q

How does surgery work in hyperthyroidism?

A

Near total thyroidectomy for Graves’ disease and MNG
Near total thyroidectomy / lobectomy for toxic adenoma

189
Q

What is hypothyroidism?

A

Thyroid hormones levels abnormally low

190
Q

What are the 3 types of hypothyroidism?

A

Primary, secondary, tertiary

191
Q

What is primary hypothyroidism?

A
  • absence / dysfunction thyroid gland
  • most cases due to Hashimoto’s thyroiditis
192
Q

What is secondary/ tertiary hypothyroidism?

A

pituitary / hypothalamic dysfunction – problem with pituitary

193
Q

Whats more common, hyper or hypothyroidism?

A

Hypothyroidism

194
Q

What are the primary causes of hyperthyroidism?

A

Hashimoto’s thyroiditis- autoimmune
131 I therapy
Thyroidectomy
Postpartum thyroiditis
Drugs
Thyroiditides
Iodine deficiency
Thyroid hormone resistance

195
Q

What are the secondary/tertiary causes of hyperthyroidism?

A

Pituitary disease
Hypothalamic disease

196
Q

What are the drugs that cause hyperthyroidism?

A

Iodine, inorganic or organic
iodide
iodinated agents
amiodarone
Lithium
Thionamides
Interferon alpha

197
Q

Causes of hyperthyroidism in neonate/ children?

A

Neonatal hyperthyroidism:
Thyroid agenesis
Thyroid ectopia
Thyroid dyshormonogenesis
Others

Resistance to thyroid hormone – need to remember this
Isolated TSH deficiency

198
Q

What are the clinical features of hyperthyroidism?

A

Fatigue
Wt gain
Cold intolerance
Constipation
Menstrual disturbance
Depression
Low mood
Bradycardia
Dry, rough skin
Periorbital oedema

199
Q

What is the investigation for primary hyperthyroidism?

A

Increased TSH (most sensitive marker),usually decreased [free T4], decreased [free T3]
T4/ T3 may be low normal in mild hypothyroidism
positive titre of TPO antibodies in Hashimoto’s

Elevated TSH is first line investigation
Most common cause is autoimmune

200
Q

What is the investigation for secondary/tertiary hyperthyroidism?

A

TSH inappropriately low for reduced T4 / T3
levels

201
Q

What is the main treatment for hypothyroidism?

A

synthetic L-thyroxine (T4)

202
Q

How do you monitor treatment primary hypothyroidism?

A

dose titrated until TSH normalises
T4 half-life is long - check levels 6-8 weeks after dose adjustment

203
Q

How do you monitor treatment in secondary/ tertiary hypothyroidism?

A

TSH will always be low
T4 is monitored

204
Q

What are some metabolic changes that happen during pregnancy?

A

Increased erythropoetin, cortisol, noradrenaline
High cardiac output
Plasma volume expansion
High cholesterol and triglycerides
Hyperventilation

205
Q

What are some gestational syndromes you can have in pregnancy?

A

Postnatal depression
Postpartum thyroiditis
Postnatal autoimmune disease
Gestational Diabetes
Obstetric cholestasis
Gestational Thyrotoxicosis

206
Q

What are the thyroid hormone changes during pregnancy for a mother?

A

Thyroxine binding globulin, Total T4
HCG
Free T4, thyrotropin (TSH)

207
Q

What are the thyroid hormone changes during pregnancy for a fetus?

A

TBG, Total T4
Thyroptropin (TSH), FT4 and FT3

Importance of Iodine

208
Q

What is the structure of glycoprotein hormones?

A

alpha and beta subunits

209
Q

What happens to women with normal thyroid function in the first trimester of pregnancy?

A

Increase in thyroxine (T 4 ) and triiodothyronine (T 3 ) production, which results in inhibition of thyroid-stimulating hormone (TSH) in the first trimester of pregnancy

Due to a high human chorionic gonadotropin (hCG) level that stimulates the TSH receptor because of partial structural similarity

210
Q

Why is there higher thyroxine requirements in pregnancy?

A

large plasma volume and thus an altered distribution of thyroid hormone
increased thyroid hormone metabolism
increased renal clearance of iodide
higher levels of hepatic production of thyroxine-binding globulin (TBG) in the hyperestrogenic state of pregnancy

211
Q

What is they prevalence of hypothyroidism in pregnancy?

A

2-3%

212
Q

What are the signs and symptoms of hypothyroidism in pregnancy?

A

Usually predate the pregnancy
Weight gain, cold intolerance, poor concentration, poor sleep pattern, dry skin, constipation, tiredness

213
Q

What happens if you have inadequate treatment of of hypothyroidism in pregnancy?

A

Gestational hypertension and pre-eclampsia
Placental abruption
Post partum haemorrhage

214
Q

What happens if you leave they hypothyroidism untreated in pregnancy?

A

Low birth weight
Preterm delivery
Neonatal goitre
Neonatal respiratory distress

215
Q

What do you do if the women has rpre existing hypothyroidism in pregnancy?

A

Preconception counselling
ideal pre-conception TSH <2.5 mIU/L

Increase dose by 30 %

Arrange TFT early pregnancy and titrate

Women require a dose increase in their thyroxine during pregnancy

216
Q

Who are the women who are targeted for screening for hypothyroidism?

A

Age >30
BMI >40
Miscarriage preterm labour
Personal or family history
Goitre
Anti TPO
Type 1 DM
Head and neck irradiation
Amiodarone, Lithium or contrast use

217
Q

What is the prevalence of hyperthyroidism in pregnancy?

A

Prevalence in pregnancy is 0.1-0.4 %
85-90% due to Graves disease

218
Q

How does hyperthyroidism affect pregnancy if inadequately treated?

A

IUGR
Low birth weight
Pre-ecclampsia
Preterm delivery
Risk of stillbirth
Risk of miscarriage

219
Q

How does the pregnancy affect the hyperthyroidism?

A

Tends to worsen in the first trimester
Improves latter half of pregnancy

220
Q

What are the symptomatic treatments for hyperthyroidism?

A

B-blockers are safe eg propranolol 10-20 mg tds

221
Q

What are some anti-thyroid medications you can use for hyperthyroidism in pregnancy?

A

PTU or Carbimazole
prevent thyroid peroxidase enzyme coupling and iodinating tyrosine residues on thyroglobulin reduce T3 and T4

222
Q

When can surgical interventions be done for hyperthyroidism in pregnancy?

A

Surgical interventions- if intolerant optimal timing 2nd trimester

223
Q

What are some anti-thyroid medications in pregnancy?

A

Carbimazole:
Increased risk of congenital abnormalities
-Aplasia cutis
-Choanal atresia
-Intestinal anomalies

Propylthiouracil
Rare hepatotoxicity

224
Q

What are the thyroid autoantibodies that cause thyroid problems?

A

TSH-R antibodies (TRAB/TBII):
Are measured at 22-26 weeks
Can cross the placenta
If raised 2-3 fold or present
fetal/neonatal thyrotoxicosis risk increased and surveillance needed

225
Q

Who do we test for thyroid autoantibodies?

A

Current Graves’, past Graves’, previous neonate with Graves’, etc

226
Q

What happens in Fetal Thyrotoxicosis?

A

Transplacental transfer of TSH-R antibodies
Occurs in 0.01 % of cases
Management options: anti-thyroid medication
Associated with:
IUGR
Fetal goitre
Fetal tachycardia
Fetal hydrops
Preterm delivery
Fetal demise

227
Q

What is gestational thyrotoxicosis?

A

Limited to the first half of the pregnancy
Raised FT4, low/suppressed TSH
Absence of thyroid autoimmunity
Associated with hyperemesis gravidarum
5-10 cases/1000 pregnancies
Multiple gestation
Hydatidaform mole
Hyperplacentosis
Choriocarcinoma

228
Q

What is post partum thyroiditis?

A

Prevalence 7 %
High risk women are
-Type 1 diabetics
-Graves disease in remission
-Chronic viral hepatitis
Measure TSH 3 months post partum

229
Q

What are the common drugs for thyroid?

A

Amiodarone
Lithium
Interferon
Immune therapies (oncology, rheumatology)

230
Q

Amiodarone

A

Dirty drug
Potent anti-arrhythmic- AF
37 % iodine by weight
200mg tablet 75 mg iodide
Lipid soluble
Long elimination half life
14-18 % get abnormalities
Amiodarone Induced Hypothyroidism (AIH) or Amiodarone Induced Thyrotoxicosis (AIT)

231
Q

What is amiodarone-induced hypothyroidism?

A

Susceptibility
Inhibitory effect on thyroid hormone synthesis
Inability of gland to escape Wolf-Chaikoff effect
Accelerate Hashimotos trend
Reduction in thyroid hormone synthesis
Downregulation of peripheral receptors

232
Q

What is amiodarone induced thyrotoxicosis? (Type 1)

A

Latent pre-existing
Low iodine areas
Iodine induced excess
Thyroid hormone release
Jode-Basedow phenomenon

233
Q

What is amiodarone induced thyrotoxicosis? (Type 2)

A

Normal Thyroid
Destructive

234
Q

Immune therapies and the thyroid

A

Immune checkpoint inhibitors
CTLA-4 and PD-1 inhibitors
Ipilimumab and Nivolumab ➜ melanoma

Thyrosine kinases inhibitors
Sunitinib

Immune reconstitution therapy
Alemtuzumab ➜ multiple sclerosis

235
Q

Ipilimumab

A

Licenced for advanced melanoma
Mode of action: monoclonal antibody, activates immune system by inhibiting CTLA-4 which normally downregulates immune system
Target CTLA-4 – keeps T Cell active to destroy cancer cells

236
Q

Nivolumab

A

Licensed for advanced melanoma, renal cell carcinoma
Mode of action: monoclonal antibody that blocks PD-1 activity and promotes antitumor immunity

237
Q

Side effects of Ipilimumab ?

A

Associated endocrinopathies- new entity
Most common:
Hypophysitis 0-17 %
Hypothyroidism (thyroiditis related) 2.7 %
Hyperthyroidism (thyroiditis related) 0.3 %
Primary Adrenal Insufficiency 2.1 %

More frequent with increased usage given overall survival benefit
Strategies for early detection

238
Q

What is Ipilimumab Hypophysitis?

A

Headache and fatigue common presentation
Can occur as early as 3 weeks but most 11 weeks
Males>Females (unlike lymphocytic hypophysitis)
Diagnosis with low levels of pituitary hormones (ACTH, TSH, LH, FSH)
Thyroiditis and primary adrenal insufficiency ACTH and TSH are high
If doubt take bloods and give steroids
Discuss with Endocrine
MRI pituitary
Visual fields
Recovery may occur over time

239
Q

Where are vasopressin and oxytocin made?

A

Paraventricular nucleus
Supraoptic nucleus
2 nuclei which are just posterior and superior to optic chiasm – these make hormones
Via axonal transport conduct down to the posterior pituitary

240
Q

Where are osmoreceptors found?

A

In the hypothalamus have osmoceptor – senses concentration in blood It has singles that fire to these 2 nuclei
Down in the brainstem is vagal nuclei and baroreceptor – which senses very rapid changes in circulatory volume

241
Q

Features of Vasopressin/ ADH?

A

Binds to G-protein coupled 7 transmembrane domain receptors

V1a - vasculature
V2 - renal collecting tubules - reabsorption of water V1b – pituitary – anterior – firing and release of ATCH from anterior pituitary

Release controlled by
osmoreceptors in hypothalamus - day to day baroreceptors in brainstem and great vessels - emergency

242
Q

Water in 70kg man

A

Extracellular fluid 1/3 total body water (14L)
- Intravascular fluid
1/4 ECF (3.5L)
- Interstitial fluid
3/4 ECF (10.5L)

Intracellular fluid 2/3 total body water (28L)

60% of total body weight = 42L

243
Q

What is the feedback loop for water balance? (Water excess)

A

Decreased (D) Increased (I)
Ingestion of water > D Plasma osmolality > I cellular hydration > D Thirst + D Vasopressin secretion > D Water intake + I Urine water excretion by kidney > D Total body water > Ingestion of water

244
Q

What is the feedback loop for water balance? (Water deficit)

A

Decreased (D) Increased (I)
Water loss > I Plasma osmolality > D cellular hydration > I Thirst + I Vasopressin secretion > I Water intake + D Urine water excretion by kidney > I Total body water > Water loss

245
Q

Vasopressin features

A

Synthesised in hypothalamus
Released from PPG into bloodstream
Binds to V2 receptors on renal collecting duct principle cells - allows aquaporin channels to be inserted for increased reabsorption of water

246
Q

How much water do we metabolise if we take in a litre to a litre and half of water a day?

A

500mls

247
Q

Urine concentration takes place where in the kidney?

A

Nephron

248
Q

What is the action of vasopressin in the kidney?

A

Vasopressin activates the vasopressin V2 receptors in the renal collecting ducts, leading to increased reabsorption of water via the kidneys

249
Q

Vasopressin action steps:

A

1.Vasopressin binds to the vasopressin V2 receptors
2. This stimulates an intracellular cascade
3. Aquaporin-2 proteins are synthesised and inserted into the apical membrane, increasing the permeability of the renal collecting duct
4. Water is reabsorbed from the renal collecting duct and returned to the blood stream, decreasing the plasma osmolality 2,4

250
Q

What is concentration in plasma?

A

Osmolality (mOsmol/kg)

Measured by an osmometer - by freezing point

251
Q

What is osmolality?

A

Concentration per kilo
size of particle not important, number is important
sodium, potassium, chloride, bicarbonate, urea and glucose present at high enough concentrations to affect osmolality
alcohol, methanol, polyethylene glycol or manitol - exogenous solutes that may affect osmolality

252
Q

Where can plasma osmolality be appropriately calculated?

A

At the bedside

253
Q

Normal serum sodium vs hyponatremia serum sodium

A

Normal Hyponatraemia
Na 137x2 125x2
Glucose 4.5 4.5
Urea 6 6
Total 284.5 260.5 All in mmol/l

254
Q

Relationship of plasma AVP concentration and urine concentration

A

When vasopressin level 6pmol/l urine osmolality so high you cant concentrate urine anymore

255
Q

Examples of pituitary mass lesions

A

Non-Functioning Pituitary Adenomas
Endocrine active pituitary adenomas
Malignant pituitary tumors
Pituitary cysts
Vascular tumors

256
Q

Embryology of pituitary gland?

A

Anterior pituitary comes from roof of mouth in development – from rathkes pouch
Posterior pituitary – totally separate and different

257
Q

Features of Craniopharyngioma?

A

Arise from squamous epithelial remnants of Rathke’s pouch
-Adamantinous: cyst formation and calcification
-Squamous papillary: well circumscribed

Benign tumour although infiltrates surrounding structures

Peak ages: 5 to 14 years; 50 to 74 years

Solid, cystic, mixed, extends into suprasellar region

Raised ICP, visual disturbances, growth failure, pituitary hormone deficiency, weight increase

258
Q

Features of Rathke’s cyst?

A

Derived from remnants of Rathke’s pouch

Single layer of epithelial cells with mucoid, cellular, or serous components in cyst fluid

Mostly intrasellar component, may extend into parasellar area

Mostly asymptomatic and small

Present with headache and amenorrhoea, hypopituitarism and hydrocephalus

259
Q

Features of meningioma

A

Commonest tumour of region after pituitary adenoma

Complication of radiotherapy

Associated with visual disturbance and endocrine dysfunction

Usually present with loss of visual acuity, endocrine dysfunction and visual field defects

T1 MRI images similar to grey matter, hypointense to pituitary and enhance with contrast

260
Q

Features of Lymphocytic Hypophysitis

A

Inflammation of the pituitary gland due to an autoimmune reaction
Incidence 1 per 9 million based on pituitary surgery

LAH commoner in women - 6:1

Age of presentation of LAH women: 35 years; men: 45 years
Pregnancy or postpartum
Can inflammation of all or just anterior or pituitary
If inflammation is big can hit optic nerves and patient will have visual problems
More common in women

261
Q

What is a Non-Functioning Pituitary Adenoma (NFPA)?

A

Pituitary adenomas account for <10 – 15% of primary intracranial tumours
NFPA account for 14 - 28% of clinically relevant pituitary adenomas and 50% of pituitary macroadenomas
Most NFPA express gonadotropins or subunits
30% of NFPA are classified as null cell adenomas
More common in autopsies – not functioning usually present late

262
Q

Pituitary dysfunction can lead to:

A

Tumour mass effects
Hormone excess
Hormone deficiency

263
Q

Investigations of pituitary dysfunction

A

Hormonal tests
If hormonal tests abnormal or tumour mass effects perform MRI pituitary

264
Q

What are the local mass effects

A

CSF rhinorrhoea - Leakage of CSF out of nose – fluid coming out of nose – reflection of a hole – can get infection there which can cause meningitis
Headaches
Cranial Nerve Palsy and Temporal Lobe Epilepsy
Visual Field Defects

265
Q

Features of non-functioning tumours:

A

No specific test but absence of hormone secretion
Test normal pituitary function
Trans-sphenoidal surgery if threatening eyesight or progressively increasing in size

266
Q

Why is testing pituitary function complex?

A

Many hormones: GH, LH/FSH, ACTH, TSH and ADH
May have deficiency of one or all and may be borderline
Circadian rhythms and pulsatile

267
Q

What is the guiding principle for testing pituitary function?

A

If the peripheral target organ is working normally the pituitary is working

268
Q

Testing for primary hypothyroid

A

Raised TSH low Ft4

269
Q

Testing for Hypopituitary

A

Low Ft4 with normal or low TSH

270
Q

Testing for Graves disease

A

Suppressed TSH high Ft4

271
Q

Testing for TSHoma (very rare)

A

High Ft4 with normal or high TSH

272
Q

Testing for hormone resistance

A

High Ft4 with normal or high TSH

273
Q

Testing primary hypogonadism

A

Low T raised LH/FSH

274
Q

Testing primary Hypopituitary

A

Low T normal or low LH/FSH

275
Q

What happens with anabolic use

A

Low T and suppressed LH
T makes pituitary gland produce less LH – testes produce less testosterone – get suppressed LH and suppressed testosterone – testes become smaller – no more money for analbolic steroids and stop them – gonadal axis doesn’t wake up immediately – sometimes it doesn’t wake up – low LH and low testosterone and have hypergonadism

276
Q

Why is testing women b4 puberty hard?

A

Oestradiol very low/undectable with
low LH and FSH although FSH slightly higher than LH

277
Q

Testing women in puberty

A

Pulsatile LH increases and oestradiol increases

278
Q

Post menarche testing

A

Monthly menstrual cycle with LH/FSH, mid-cycle surge in LH and FSH and levels of oestradiol increase through cycle

279
Q

Primary ovarian failure

A

High LH and FSH with FSH greater than LH and low oestradiol

280
Q

Hypopituitary in women

A

Oligo or amenorrhoea with low
oestradiol and normal or low LH and FSH

281
Q

When do we measure cortisol and synacthen

A

9am
Due to circadian rhythm

282
Q

What happens in primary AI

A

Low cortisol, high ACTH, poor response to Synacthen

283
Q

What happens in hypopituitarism

A

Low cortisol, low or normal ACTH, poor response to synacthen

284
Q

How is growth hormone secreted

A

in pulses with greatest pulse at night and low or undetectable levels between pulses
GH levels fall with age and are low in obesity

285
Q

Prolactin is under negative control of what?

A

Dopamine

286
Q

What type of hormone is prolactin?

A

Stress hormone

287
Q

What can prolactin be raised by?

A

Stress
Drugs: antipsychotics
Stalk pressure
Prolactinoma

288
Q

HPA Axis

A

Hypothalamus controls the release of ACTH from the pituitary through the release of corticotrophin-releasing hormone which stimulates ACTH which stimulates the release of cortisol which has a classical negative feedback loop

289
Q

Where is cortisol released from?

A

Cortex of adrenal glands

290
Q

What is the cortisol circadian rhythm?

A

Fundamental rhythm in body

Important for behaviour and how we feel

Low at 10pm, builds up at 3am for energy for the day, over the day cortisol level falls, 6pm 7pm when we go home cortisol level falls

291
Q

What is corticotropin-releasing hormone also known as?

A

Anxiety hormone

292
Q

Why do many hormones have circadian rhythms?

A

Reflect our metabolic needs
Fine-tune physiology and behaviour to the varying demands of activity and rest

293
Q

What is the central clock?

A

Suprachiasmatic nucleus
Manage the rhythms in our body

294
Q

The central clock controls what?

A

Peripheral clocks

295
Q

What are glucocorticoids in the context of “clocks”

A

Glucocorticoids are a secondary messenger from central to peripheral clocks

296
Q

What is primary adrenal insufficiency?

A

Addison’s disease
TB big cause of Addisons disease – causes skin pigmentation – now its autoimmune – antibodies causes destruction of adrenal gland
Autoimmune
Adrenoleukodystrophy
Mets, haemorrhage, infection
Infection (TB), infiltration (Amyloid)

297
Q

What is secondary adrenal insufficiency?

A

Hypopituitarism (150-280/M)
Pituitary macroadenoma/Cranio
Apoplexy
Hypophysitis
Mets, infiltration, infection
Radiotherapy
Congenital

298
Q

What is tertiary adrenal insufficiency?

A

– Suppression of HPA
Steroids, oral, inhaler, creams

299
Q

What is the commonest cause of adrenal insufficiency?

A

Steroids
Anti-inflammatory drug
2nd most common is benign pituitary tumour

300
Q

What is the history for a possible adrenal diagnosis?

A

Symptoms: fatigue, weight loss, poor recovery from illness, adrenal crisis, headache
Past History: TB, post partum bleed, cancer
Family History: Autoimmunity, congenital disease
Treatment: Any steroids! Etomidate, Ketoconazole

301
Q

What are the signs for a possible adrenal diagnosis?

A

Pigmentation and pallor
Hypotension
Fatigue

302
Q

What is the biochemistry for a potential adrenal diagnosis?

A

Low Na, high K
Eosinophilia
Borderline elevated TSH

303
Q

When is adrenal insufficiency usually diagnosed?

A

Adrenal insufficiency only diagnosed when they present with intercurrent illness
Poor recovery from illness is common
No cortisol will become very sick with intercurrent illness – can acc die

304
Q

Why is ACTH important?

A

Works on melanocortin receptor and stimulates pigmentation – if you excess ACTH get too much pigmentation

305
Q

What is the key point about sodium?

A

Low sodium is sign of adrenal insufficiency – always check cortisol level – low sodium with high potassium – highly suggestive of adrenal insufficiency

306
Q

Why is cortisol important for water?

A

cortisol important for excreting water load – another hormone from adrenal gland which is aldosterone important for sodium retention and potassium excretion – low aldosterone and low cortisol get low sodium and high potassium

307
Q

9am cortisol and ACTH

A

Cortisol > 500 nmol/l AI unlikely
Cortisol < 100 nmol/l AI likely
ACTH > 22 pmol/l primary
ACTH < 5 pmol/l secondary

308
Q

When do we get elevated renin/ aldosterone?

A

Elevated renin in primary

309
Q

Synacthen test

A

In adrenal insufficiency is synacthen test – synthetic ACTH and we measure cortisol response for adrenal
If ACTH – if its high suggests primary adrenal insufficiency

250ug IV measure 0’ & 30’
> 500-550 nmol/l AI unlikely

310
Q

What are the causes of primary adrenal insufficiency?

A

Adrenal antibodies
Very long chain fatty acids
17-OHP
Imaging
Genetic

311
Q

What are the causes of secondary adrenal insufficiency?

A

Any steroids???
Imaging
Genetic

312
Q

What is the treatment for adrenal insufficeincy?

A

Hydrocortisone (pharmaceutical name for cortisol) twice or three times daily at a dose to replace cortisol levels 15-25mg

In primary adrenal insufficiency also replace aldosterone with fludrocortisone

313
Q

What is the management of adrenal crisis?

A

Take bloods if possible for cortisol and ACTH
Immediate hydrocortisone 100mg IV, IM, (SC)
Fluid resuscitation (1L N/Saline 1 hour)
Hydrocortisone 50-100mg IV/IM every 6 hours – don’t wanna give too much could give Cushings disease – have to wean them off
In primary start fludrocortisone 100-200ug (when HC
<50mg)

314
Q

How can you know if someone is having a adrenal crisis?

A

If someone presents with low Na and High K, hypotensive, could be having adrenal crisis
Someone on steroids and stopped taking them and has the same symptoms
Normal adrenal glands – your adrenals produce a lot of cortisol
Without cortisol you will die of an adrenal crisis if you have an infection
Intercurrent illness is when your really in trouble

315
Q

What are the sick day rules?

A

Always carry 10 x 10mg tablets hydrocortisone
If unwell with fever or flu like illness double dose of steroids
If in doubt double dose of steroids
If vomiting or increasingly unwell take emergency injection of hydrocortisone 100mg IM (SC)
If unable to have injection take hydrocortisone 20mg and repeat if vomit
Go to emergency room / ring ambulance

316
Q

Glucocorticoid replacement

A

Daily production of cortisol 5-6 mg/m2 BSA
Usually hydrocortisone 15-25 mg in 2-3 divided doses
Could use prednisolone 3-5mg/d administered orally once or twice

317
Q

Mineral corticoid replacement

A

Usual dose 50-300 ug once or twice daily
Start with 100 -150 ug
Aim for renin in upper half normal range
Monitor: U&E, BP, SALT CRAVING

318
Q

What happens when amine hormones bind to alpha receptors?

A

W

Endocrinology (17 decks)

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