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Endochrinology Flashcards

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1
Q

What other function besides anti diuresis does ADH have?

A

V1 receptor - vasoconstriction
Stimulates ACTH in anterior pituitary

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2
Q

Describe the osmotic and non osmotic regulators of ADH

A

Osmotic - the organum vasculosum & subfornical organ around the third ventricle is highly vascularised and responds to systemic circulation (no BBB). The nerves project to the suppraoptic neurons allowing release of ADH during high osmolality.

Non osmotic- atrial stretch receptors in the right atria inhibits the secretion of ADH via baga; afferents to hypothalamus, when there is less stretch e.g during heamorrhage, the inhibition of ADH is reduced so more ADH secreted

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3
Q

What are the causes of Nephrogenic diabetes insipidus?

A

Drugs - Lithium
Mutation - V2 receptor, AQP2

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4
Q

What clinical investiations would you run following polyuria, nocturia , polydyspia once you’ve confirmed it isn’t diabetes mellitus?

A

Blood osmolarity- Hyper osmolar
Urine osmolarity - Hypo osmolar
Hypernatraemia
Glucose levels

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5
Q

How do you distinguish between psychogenic polydypsia and diabetes insipidus?

A

Water deprivation test - and you measure urine volume ,urine and blood osmolarity, you also have to weigh regularly if they lose > 3% of their weight then need to stop test but semi- confirms DI

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6
Q

Differentiate DI and PP in terms of plasma osmolarity

A

DI Hyperosmolar
PP hypo osmolar

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7
Q

How do you treat DI

A

CDI- demsopressin- intranasally or tablet
NDI- hard to tret, thiazide diuretics or

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8
Q

Signs of SIADH

A

Reduced urine output

High urine osmolality

Low plasma osmolality

Dilutional hyponatraemia

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9
Q

Causes of SIADH

A

CNS

Head injury, stroke, tumour,

Pulmonary disease

Pneumonia, bronchiectasis

Malignancy

Lung cancer (small cell)

Drug-related

Carbamazepine, Serotonin Reuptake Inhibitors (SSSRIs)

Idiopathic

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10
Q

What are the functional names for tumours of anteior pituitary cells?

A

Lactotrophs - Prolactinoma
Somatotrophs - Acromegaly
Corticotrophs - Cushings
Thyrotophs- TSHoma
Gonadotrophs - Gonadotrophinoma

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11
Q

What is the imaging modality for pituitary tumours and how are they decribed?

A

Size

-Microadenoma <1cm (10mm)
-Macroadenoma >1cm (10mm)

Sellar or suprasellar

Compressing optic chiasm or not

Invading cavernous sinus or not

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12
Q

What does benign and malignant pituitary tumours relate to?

A

Pituitary carcinoma very rare (<0.5% of pituitary tumours)
Mitotic index measured using Ki67 index – benign is <3%
Pituitary adenomas can have benign histology but display malignant behaviour

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13
Q

Causes of elevated prolactin levels

A

Physiological
-Pregnancy/breastfeeding
-Stress: exercise, seizure, venepuncture
-Nipple/chest wall stimulation

Pathological
-Primary hypothyroidism
-Polycystic ovarian syndrome
-Chronic renal failure

Iatrogenic
-Antipsychotics
-Selective serotonin re-uptake inhibitors
-Anti-emetics
-High dose oestrogen
-Opiates

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14
Q

What receptor do dopamine agonist like cabergoline work on?

A

D2 receptors

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15
Q

What are the symptoms of acromegaly?

A

Sweatiness
Headache
Coarsening of facial features
Macroglossia
Prominent nose
Large jaw - prognathism
Increased hand and feet size
Snoring & obstructive sleep apnoea
Hypertension
Impaired glucose tolerance/diabetes mellitus

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16
Q

How do we diagnose acromegaly?

A
  • Elevated serum IGF-1 helps
  • Failed suppression (paradoxical rise) of GH following oral glucose load- oral glucose tolerance test- we don’t know why
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17
Q

How do we treat acromegaly?

A

Trans-sphenoidal pituitary surgery
-Aim to normalise serum GH and IGF-1

Radiotherapy

If nto surgery or to reduce tumour size:
Somatostatin analogues eg octreotide – ‘endocrine cyanide’

Dopamine agonists eg cabergoline (GH secreting pituitary tumours frequently express D2 receptors)

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18
Q

Causes of Cushing’s syndrome

A

ACTH independent

  • Taking steroids by mouth (common)
  • Adrenal adenoma or carcinoma

ACTH dependent

  • Cushing’s disease (corticotroph adenoma)
  • Ectopic ACTH (lung cancer)
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19
Q

Diagnosis of Cushing’s syndrome

A
  • Elevation of 24h urine free cortisol- increased cortisol secretion
  • Elevation of late night cortisol- salivary or blood test- loss of diurnal rhythm
  • Failure to suppress cortisol after oral dexamethasone (exogenous glucocorticoid)- increased cortisol secretion

If high, measure ACTH, then if high, MRI

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20
Q

What do non functioning adenomas often present with?

A

Bitemporal hemianopia

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21
Q

What is it called in grave’s disease where the antibodies go behind the eye and push it out

A

exophthalmos

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22
Q

What is Toxic nodular goitre (Plummer’s disease)

A

Benign adenoma that is overactive at making thyroxine
- One cell has grown a lot on one side of the thyroid so that side is large
- This makes a lot of thyroxine which suppresses TSH and lack of TSH means the normal side of the gland atrophies and gets smaller

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23
Q

What are the effects of thyroxine on the sympathetic nervous system?

A
  • Sensitises beta adrenoceptors to ambient levels of adrenaline and noradrenaline
  • Thus there is apparent sympathetic activation
  • Causes tachycardia, palpitations, tremor in hands, lid lag
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24
Q

What is a thyroid storm?

A
  • Medical emergency- 50% mortality untreated
  • Blood results confirm hyperthyroidism
  • Need aggressive treatment
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25
Criteria for thyroid storm
- Hyperpyrexia >41°C - Accelerated tachycardia/arrhythmia - Cardiac failure - Delirium/frank psychosis - Hepatocellular dysfunction; jaundice
26
What classes of drugs are used in the treatment of hyperthyroidism?
The thionamides (thiourylenes; anti-thyroid drugs) - propylthiouracil (PTU) - carbimazole (CBZ) Potassium Iodide Radioiodine β-blockers
27
What is the function of thionamides and how does it work?
Daily treatment of hyperthyroid conditions - aim to stop after 18 months Inhibition of thyroid peroxidase Biochemical effect hours, cliical effect weeks so may use propanolol to reduce beta sympathetic activity related symptoms
28
What are the four steps of T4 synthesis
Uptake of iodide active transport Iodination Coupling reaction: Storage in colloid Endocytosis and secretion
29
Side effects of thionamide
Agranulocytosis (neutropenia) Rashes
30
What is the function of iodide treatment in hyperthyroidism and how does it work?
1a. preparation of hyperthyroid patients for surgery 1b. severe thyrotoxic crisis (thyroid storm) hyperthyroid symptoms reduce within 1-2 days vascularity and size of gland reduce within 10-14 days 2. Inhibits thyroid peroxidase, inhibits iodination of thyroglobulin using WOLFF–CHAIKOFF effect
31
Problems with surgery for hyperthyroidism
Risk of voice change (recurrent laryngeal nerve) Risk of also losing parathyroid glands Scar Anaesthetic
32
Radioiodine in hyperthyroidism
Swallow a capsule containing about 370 MBq (10 mCi) of the isotope I (131) Contraindicated in pregnancy Need to avoid children and pregnant mums for a few days For scans only (not treatment), 99-Tc pertechnetate is an option.
33
Symptoms of Viral (de Quervain's) thyroiditis
- Pyrexia (fever) - Malaise - Painful dysphagia - Hyperthyroidism - Thyroid inflammation - Tender + palpable thyroid - Thyroid gland visibly enlarged on one side
34
What is the biochemistry of primary hyperparathyroidism?
- High calcium - High PTH (not suppressed by hypercalcaemia negative feedback) - Low phosphate- increased renal phosphate excretion (inhibition of sodium-phosphate transporter in kidney)
35
What are the causes of secondary hyperparathyroidism?
- Most common cause is vitamin D deficiency due to diet, reduced sunlight - Less common, due to renal failure- can't make calcitriol in renal failure
36
What is the treatment for secondary hyperparathyroidism in people with and without kidney failure?
Without renal failure: 25 hydroxy vitamin D- inactive vit D They convert it to 1,25 dihydroxy vitamin D via 1alpha hydroxylase Can give ergocalciferol (25 hydroxy vitamin D2) or cholecalciferol (25 hydroxy vitamin D3) Can get at chemists/supermarket With renal failure: There's inadequate 1alpha hydroxylation, so can't activate 25 hydroxy vitamin D We give them alfacalcidol- 1alpha hydroxycholecalciferol- this is active vitamin D Reserved for renal failure patients so needs to be prescribed
37
What happens in tertiary hyperparathyroidism?
When you have chronic renal failure you can't make calcitriol so you have chronic vit D deficiency Parathyroid glands start secreting more PTH to make up for drop in calcitriol so calcium doesn't become low One or more of these glands enlarge (hyperplasia) to the point where they can't be switched off Autonomous PTH secretion happens causing hypercalcaemia
38
What happens in hypercalcaemia due to malignancy? (2)
- There is high calcium - There is low or suppressed PTH
39
Hormonal control of serum calcium
Increase - Vitamin D Parathyroid hormone (PTH) (secreted by parathyroid glands) Decrease - Calcitonin (secreted by thyroid parafollicular cells) Can reduce calcium acutely, but no negative effect if parafollicular cells are removed eg thyroidectomy
40
What is a good indicator of body vitamin D status
Serum 25-OH vitamin D
41
How does calcitrol regulate its own synthesis?
by decreasing transcription of 1 alpha hydroxylase
42
Effect of calcitrol
Kidney :Increase Ca2+ and PO43- reabsorption Gut: ↑ PO43- absorption ↑Ca2+ absorption Bone: Increase osteoclast activity
43
Actions of PTH
↑ Ca2+ reabsorption ↑ PO43- excretion ↑ 1-a-hydroxylase activity ↑ 1,25 (OH)2D3 synthesis Ca++ resorption from bone
44
Regulation of serum phosphate by FGF23
Phosphate is reabsorbed via sodium phosphate cotransporter channels in PCT PTH inhibits renal phosphate reabsorption by inhibiting these transporters FGF23 (from bone) inhibits phosphate reabsorption in the kidneys by inhibiting these transporters inhibits synthesis of calcitriol, causing less phosphate absorption from the gut
45
Hypocalcaemia symptoms & signs
CATs go numb Chvosteks’ sign – facial paresthesia Trousseau’s sign – carpopedal spasm
46
Causes of hypocalcaemia
Low PTH levels = hypoparathyroidism Surgical – neck surgery Auto-immune Magnesium deficiency Congenital (agenesis, rare) Low vitamin D levels Deficiency – poor diet/malabsorption, lack of UV light, impaired production (renal failure)
47
Hypercalcaemia signs and symptoms
Stones, abdominal moans and psychic groans
48
Causes of hypercalcaemia
Primary hyperparathyroidism Malignancy Vitamin D excess (rare)
49
What tests do we do following suspicion of Addisons?
(Addisons) - Morning 9am cortisol (low) and ACTH (high) - Short synacthen test: 1.cortisol blood test 2. synacthen IM 3. measure cortisol response if little response then we know its Addison's
50
What is the aldosterone treatment for Addisons, what's the issue with the standard treatment and how have we fixed it?
- Aldosterone replacement- problem is its half life is too short for safe once daily administration - We solve this by sticking a fluorine on aldosterone to make fludrocortisone - Fludrocortisone binds to both MR (mineralocorticoid) and GR (glucocorticoid) receptors - Its half life is 3.5h and effects are seen for 18h
51
What are the consequences of adrenocortical failure? (6)
- Fall in bp - Loss of salt in urine - Increased plasma potassium - Fall in glucose due to glucocorticoid deficiency - High ACTH resulting in increased pigmentation - Eventual death due to severe hypotension
52
Describe Congenital adrenal hyperplasia (CAH) - 3 + 1 disease
Most commonly caused by - 21-hydroxylase deficiency - Can be complete or partial deficiency Complete 21- hydroxylase deficiency: Aldosterone + Cortisol deficiency Sex steroids + testosterone in excess (girls may therefore present with ambiguos genitalia) Presents as a neonate - salt losing Addisonian crisis Partial 21 hydroxylase deficiency: Aldosterone + Cortisol scarse Sex steroids + testosterone in excess Presents at any age Girls - hirtulism and virilisation Boys - precocious puberty 11 hydroxylase deficiency: There's a build up of 11 deoxycorticosterone - behaves like aldosterone could cause hypertension / hypokalaemia Cortisol and aldosterone deficiency Excess 11 deoxycorticosterone, sex steroids and testosterone 17 hydroxylase deficiency - Cortisol and Sex steroid deficiency Excess 11 deoxycorticosterone, aldosterone
53
What two types of drugs can be given for cushings and when would they be used and what are we concerned about?
Metyrapone -inhibition of 11b-hydroxylase Control of Cushing’s syndrome prior to surgery. Control of Cushing’s symptoms after radiotherapy (which is usually slow to take effect) Hypertension on long-term administration Hirsutism Ketoconazole - blocks 17a hydroxylase treatment and control of symptoms prior to surgery Liver damage - possibly fatal - monitor liver function weekly, clinically and biochemically
54
Describe Conns; pathophysiology, diagnosis and management
- Benign adrenal cortical tumour (zona glomerulosa) - Aldosterone in excess (aldosterone controls bp, Na and lowers K remember) - Hypertension and hypokalaemia Diagnosis: renin - angiotensin pathway should be suppressed MR antagonist
55
Describe phaeochromocytoma, clinical features and management
tumours of the adrenal medulla which secrete catecholamines (adrenaline and noradrenaline) - Hypertension in young people- severe hypertension can cause myocardial infarction or stroke - Episodic severe hypertension (after abdominal palpitation) - High adrenaline can cause ventricular fibrillation & death- it's a medical emergency Management: - Eventually need surgery, but patient needs careful prep as anaesthetic can precipitate a hypertensive crisis - Alpha blockade is the first therapeutic step to block adrenaline effects for surgery - Patients may need intravenous fluid as alpha blockade commences (because blockade causes blood pressure crash so we need the fluid) - Beta blockade added to prevent tachycardia
56
What are the two types of infertility?
Primary - Have never had a live birth Secondary - has had a live birth > 12 months ago
57
What are the three categories of infertility causes in men?
Pre testicular Testicular Post testicular
58
What are pre testicular causes in men?
Congenital & Acquired Endocrinopathies Klinefelters 47XXY HPG, Testosterone, PRL issues
59
What are testicular causes in men?
Congenital Cryptorchidism Infections - STDs IMmunological - anti sperm AB Vascular Trauma/ Surgery Toxins
60
What are post testicular causes in men?
Congenital ( Absence of vas deferens) Obstructive Azoospermia Erectile dysfunction Iatrogenic - vasectomy
61
Describe Cryptorchidism
Undescended testis (90% in inguinal canal)
62
What are some categories of infertility causes in women?
Pelvic causes Tubal causes Ovarian causes Uterine causes Cervical causes Unexplained
63
Endometriosis: Description - Symptoms - Management-
1. Presence of functioning endometrial tissue outside of the uterus 2. Menstrual pain Menstrual irregularities Deep dyspareunia Infertility 3. Oestrogen
64
Fibroids: Descriptions - Symptoms - Management -
Benign tumours of the myometrium Usually asymptomatic - may present with deep dyspareunia, menstrual irregularities, increased menstrual pain, infertility
65
Kallmann Syndrome: Description Symptoms
Failure of migration of GnRH neurons with olfactory fibres Anosmia Failure of puberty INferitlity
66
Klinefelters syndrome: Symptoms
Tall stature Decreased facial hair Breast development Female - type pubic hair pattern Small penis and testes Infertility Mildly impaired IQ Narrow shoulders Reduced chest hair Wide hips Low bone density
67
Male infertility diagnostic overview
Key history: Duration, previous children, pubertal milestones, associated symptoms, meidcations/ drugs Key examination: BMI, sexual characteristics, testicular volume, anosmia Key investigations: Semen analysis, Blood tests, Imaging
68
Male infertility key investigations
Semen analysis - Volume Sperm concentration ( Azospermia, Oligospermia) Total motility Blood test- LH, FSH, PRL, morning fasting testosterone, karyotyping Imaging - Scrotal US/ Doppler MRI pituitary if indicated
69
Male infertility management
Treat treatable causes - hyperPRL General lifestyle - Optimise BMI, SMoking cessation, Alcohol reduction/ cessation Specific treatment - Gonadotrophin treatment for fertility Testosterone - if no fertility required Surgery - microtesticular sperm extraction
70
Premature ovarian insufficiency Description/ Diagnosis Causes
Conception may still happen, diagnosis high FSH > 25iU/ L ( x 2 at least 4 weeks apart) Autoimmune, Genetic, Cancer therapy
71
Polycystic Ovarian syndrome: Diagnosis -
Rotterdam PCOS Diagnostic criteria 2/3 1. Oligo or Anovulation 2. Clinical (Acne, Hirsutism, Alopecia) + Biochemical Hyperandrogenism 3. PCO using ultrasound
72
PCOS treatment
Metformin- Irregular menses/ amenorrhoea & increased insulin resistance IVF - infertility Oral contraceptive - Ireegular menses/ amenorrhea Anti- androgens (Spironolactone) - Hirsutism Creams, waxing - hirsutism Progesterone courses - Endometrial cancer risk
73
Turners Syndrome Description SYmptoms
One X chromosome Short stature, low hairline, shield chest, wide- spaced nipples, short 4th metacarpal, small fingernails, brown nevi, characteristic faces, webbed neck, coarction of aorta, poor breast development, elbow deformity, underdeveloped reproductive tract, amenorrhea
74
Female infertility diagnosis overview
Key history: Duration, Previous Children, Pubertal Milestones, Menstrual History, Medications/ Drugs Key examination: BMI, Sexual characteristics, Hyperandrogenism signs, Anosmia Key investigations: Blood test, pregnancy test, Imaging
75
Female inferitility key investigations
Blood test - LH, FSH, PRL, Oestrodial, Androgens, Mid - Luteal Prog, Karyotyping Pregnancy test Imaging - US (transvaginal) Hysterosalpingogram MRI pituitary if indicated
76

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