Endo 9.5 Flashcards
(83 cards)
1
Q
Causes of thyrotoxicosis?
A
Graves 50-60% toxic multinodular goitre acute phase subacute de Quervains thyroiditis acute phase postpartum thyroiditis acute phase Hashimoto's thyroiditis amiodarone Rx
2
Q
triiodothyronine thyrotoxicosis - small subset who have isolated T3
Rx?
A
carbimazole
3
Q
Drivers on insulin/sulfonylureas - who can drive?
A
HGV: - no severe hypo in 12m - full hypo awareness - has adequate control/monitoring - understands risks of hypo Car: - hypo awareness, not more than 1 hypo episode requiring assistance, no relevant visual impairment
4
Q
Hypothyroidism Rx
- starting dose of thyroxine?
- therapeutic goal?
- in pregnancy?
- when is levothyroxine & liothyronin (T3) used?
A
- 50-100mcg OD but lower at 25mcg OD if elderly/have IHD and slowly titrate up
- check TFTs 8-12wks after a change in thyroxine
- TSH 0.5-2.5 i.e. normalisation of TSH
- increase dose by at least 25-50mcg thyroxine in pregnancy, monitor carefully
- Myxoedema coma: T3 has a greater biologic activity & faster onset than T4 so can be used until there’s clinical improvement (can also give steroid as often there’s coexistent adrenal insufficiency)
5
Q
Side-effects of thyroxine Rx?
Interactions?
A
- osteoporosis
- worsening of angina
- AF
- hyperthyroid due to over-Rx
- iron reduces absorption of thyroxine - give 2h apart
6
Q
Pathophys of DKA?
Dx criteria?
A
- uncontrolled lipolysis -> XS free fatty acids -> ketone bodies
- BM >11
- pH <7.3
- HCO3 <15
- ketones >3
7
Q
Rx of DKA?
A
- isotonic saline
- correction of hypokalaemia
- FRII 0.1unit/kg/hr - start 5% dextrose once BM<15
- continue long-acting insulin
- may need to be slower rate in young as at risk of cerebral oedema - usually occurs 4-12h after starting but can occur at any time - if any suspicion, needs CT head & senior R/V
- If K 3.5-5.5 give 40mm KCl
- if <3.5 needs urgent senior R/V
8
Q
Complications of DKA and its Rx?
A
- gastric stasis
- thromboembolism
- arrhythmias 2ry to high K/low K
- iatrogenic due to incorrect fluid Rx: cerebral oedema, low K, hypoglycaemia
- ARDS
- AKI
9
Q
Congenital adrenal hyperplasia:
- autosomal rec disorders affecting adrenal steroid biosynthesis
- low cortisol -> high ACTH -> adrenal androgens -> virilise female infant
- enzyme deficiencies?
A
21-hydroxylase deficiency (90%) -> reduced cortisol & aldosterone -> high ACTH -> adrenal hyperplasia -> XS androgen: ambiguous genitalia, salt wasting, hypovolaemia, shock
-> can also be aSx with androgen XS a problem in later childhood: premature pubarche, accelerated bone age, acne, hirsutism, oligomenorrhoea, mimicking PCOS
11-beta hydroxylase deficiency (5%) - raised BP, raised androgens
17-hydroxylase deficiency (very rare) - raised aldosterone, low androgens
10
Q
Hypopituitarism - adult GH deficiency - low peak GH levels in response to insulin-induced hypoglycaemia
- features?
A
- low ACTH: tired, postural hypotension
- low gonadotrophins: amenorrhoea
- low TSH: constipated
- can happen after e.g. pituitary mass removal
- assess dynamic pituitary function: insulin stress test (measure cortisol surge) BUT inducing hypoglycaemia in some is C/I
- next best test = glucagon stimulation test which mimics hypoglycaemia causing fake stress on pituitary
11
Q
Onset/peak/duration of rapid-acting insulin analogues?
A
Onset 5mins Peak 1h Duration 3-5h - insulin aspart Novorapid - insulin lispro Humalog
12
Q
Onset/peak/duration of Short-acting insulin?
A
Onset 30mins
Peak 3h
Duration 6-8h
- Actrapid, Humulin S
13
Q
Onset/peak/duration of Intermediate-acting insulin?
A
Onset 2h
Peak 5-8h
Duration 12-18h
- isophane insulin
14
Q
Onset/peak/duration of Long-acting insulin analogues?
A
Onset 1-2h Flat profile Duration upto 24h - insulin determir Levemir - insulin glargine Lantus
15
Q
BM aim for T1DM?
A
5-7 on waking
4-7 pre-meal
5-9 90mins post-meal
16
Q
Acromegaly Rx
1st line?
Drugs?
What may be used in older pts or if the above fails?
A
- trans-sphenoidal surgery
- Somatostatin analogue e.g. Octreotide directly inhibits GH release effective in 50-70% may be used as adjunct
- DA agonist eg Bromocriptine effective in only a minority
- SC PEGVISOMANT OD = GH receptor antagonist prevents dimerisation of GH receptor - v effective at decreasing IGF-1 levels in 90% to normal, but doesn’t reduce tumour volume
- external irradiation in older
- monitor IGF-1 every 6months (long half-life)
17
Q
Addison’s Rx?
A
- glucocorticoid hydrocortisone eg BD/TDS 20-30mg/day
- mineralocorticoid
- do not miss doses, consider bracelet/steroid card
- sick day rules: double glucocorticoid
- take doses from waking if doing night shift/travelling as cortisol highly linked to diurnal rhythm
18
Q
Kallmann’s syndrome: hypogonadotrophic hypogonadism -> delayed puberty
- X-linked recessive
- failure of GnRH-secreting neurons to migrate to hypothalamus
Features?
A
- delayed puberty
- hypogonadism, cryptorchidism
- anosmia
- low sex hormones
- LH, FSH inappropriately low/normal
- typically normal/above average height
- check HCG & FSH then IVF to restore ovulation/try for pregnancy
19
Q
Features of Addisonian crisis?
A
hypotension hypothermia hypoglycaemia - classic hyponatraemia/hyperkalaemia doesn't often happen -> give IV hydrocortisone
20
Q
Causes of hypokalaemia with alkalosis?
A
- vomiting
- thiazide & loop
- Cushings
- Conns
21
Q
Hypokalaemia with acidosis?
A
- diarrhoea
- RTA
- acetazolamide
- partially Rx DKA
22
Q
DDx with hypokalaemia, metabolic alkalosis & normal-low BP?
Next best Ix?
A
diuretic abuse
Bartter’s syndrome
Gitelman’s syndrome
- diuretic assay
23
Q
hypokalaemia, metabolic alkalosis & normal-low BP
- triangular facies, polyuria, polydipsia, renal failure
high renin & aldosterone despite this
- urine calcium may be raised
- renal stones common
Dx?
A
Bartters syndrome
24
Q
hypokalaemia, metabolic alkalosis & normal-low BP
- hypomagnaesaemia, hypocalciuria
Dx?
A
Gitelman’s syndrome
25
Hypercalcaemia Rx
IV fluids
bisphosphonates - take few days to work, max effect at day 7
(also calcitonin, steroids)
26
Tests to confirm Cushings syndrome?
- most sensitive is overnight dexamethasone suppression test
| - screening 24h urinary free cortisol
27
Localisation tests for Cushing's syndrome?
1st line 9am & midnight plasma ACTH & cortisol (if ACTH suppressed then ectopic i.e. non-ACTH-dependent cause likely)
2nd low/high dose dexamethasone suppression test
- if cortisol suppressed by high dose but not by low dose, then Cushing disease
- if cortisol not suppressed by low dose then Cushings syndrome e.g. 2ry to steroids
- if cortisol not suppressed by low/high then ectopic ACTH most likely
CRH stimulation: if pituitary source then cortisol rises
- if ectopic/adrenal then no change in cortisol
- petrosal sinus sampling of acth can help differentiate between pituitary & ectopic ACTH secretion
28
What is pseudo-cushings?
common in XS ETOH
- idiopathic
- diurnal variation is maintained
- elevated 24h urinary cortisol and will also fail to suppress serum cortisol with a low dose dexamethasone suppression test
29
Subacute granulomatous de Quervain's thyroiditis post-viral
4 phases?
Ix?
Rx?
1. hyperthyroid, tender goitre, raised ESR, 3-6wks
2. euthyroid 1-3wks
3. hypothyroid wks-months
4. thyroid structure & function normalise
- thyroid scintigraphy: globally reduced uptake of iodine-131
- usually self-limiting, NSAIDs etc, steroids if severe
30
```
Pathophys of thyroid eye disease?
Prevention?
Features?
Rx?
Monitoring established eye disease?
```
- autoimmune response against autoAg, possibly TSH receptor -> retro-orbital inflammation -> glycosaminoglycan & collagen deposition in muscles
- stop smoking
- RADIOIODINE WORSENS it
- can be eu/hypo/hyperthyroid at presentation
- exophthalmos, conjunctival oedema, optic disc swelling, opthalmoplegia, exposure keratopathy
- topical lubricants, steroids, RT, surgery
- IV Methylpred if severe
Urgent R/V if:
- unexplained worsening vision, change in intensity/quality of colour vision, subluxation, corneal opacity, cornea visible when eyes closed, disc swelling
31
MEN type I?
```
PTH hypeprlasia 95%
Pituitary 70% eg prolactinoma
Pancreas eg insulinoma/gastrinoma/rec peptic ulcer
also: adrenal & thyroid
MEN1 gene
commonest presentation = hypercalcaemia
```
32
MEN type IIa?
Medullary thyroid ca 70%
PTH 60%
Phaeochromocytoma
RET oncogene
33
MEN type IIb?
```
Medullary thyroid ca
Phaeochromocytoma
Neuromas
Marfanoid body habits
RET oncogene
```
34
Orlistat indications? MoA?
pancreatic lipase inhibitor
- causes fecal urgency/incontinence/flatulence
- BMI 28 with RFs or
- BMI 30
- cont weight loss 5% at 3months
- use <1year
35
Commonest thyroid cancer, often young females with best prognosis?
Papillary
- papillary projections & pale empty nuclei
- LN metastasis
36
2nd commonest thyroid ca?
Follicular
- may appear encapsulated macro and micro capsular invasion (without this is an adenoma)
- vascular invasion
37
Thyroid cancer of parafollicular C cells that secrete calcitonin, part of MEN-2?
Medullary
- c cells from neural crest (not thyroid tissue)
- raised serum calcitonin
- familial genetic disease 20%
- LN & blood spread, poor prognosis
38
Thyroid cancer not responsive to Rx, can cause pressure Sx?
Anaplastic
- elderly females
- local invasion
- resect where possible
- chemo doesn't work
39
Rarest thyroid ca, ass with Hashimoto's?
Lymphoma
40
Work-up for thyroid nodule?
check TSH
- if normal/high then do thyroid USS
- if suspicious then do FNAC
- if TSH suppressed do thyroid uptake scan -> do FNAC if cold nodule
41
Type 1 RTA
- complications
- causes
Distal - can't generate acidic urine
- low K
- renal stones/calcinosis
- idiopathic, RA, SLE, Sjogren's, analgesic nephropathy
42
Type 2 RTA
- complications
- causes
Proximal - decreased HCO3 reabsorption
- low K
- osteomalacia
- idiopathic, Fanconi's, Wilson's, cystinosis, acetazolamide/topiramate
43
Type 4 RTA
| - causes
RAAS - fall in aldosterone -> reduced ammonium excretion
- high K
- hypoaldosteronism, diabetes
44
T2DM HbA1c target if on any hypoglycaemic, or if HbA1c has risen to 58?
53
| 7%
45
T2DM Rx?
1. Metformin
2. +sulfonylurea/gliptin/pioglitazone/SGLT-2 inhibitor
3. 3x therapy with metformin + 2 of the above but not gliptin+pio or gliptin+SGLT2
*can't give SGLT2 inhibitor without metformin
46
When can you give metformin + sulfonylurea+ GLP1 mimetic?
BMI 35 with comorbidity ass with obesity
or BMI<35 for whom insulin has significant implications/weight loss would benefit other comorbidities
- only continue if reduction of at least 11mmol/1% in HbA1c and weight loss at least 3%, in 6 months
47
Toxic multinodular goitre = thyroid gland containing number of autonomously functioning thyroid nodules -> hyperthyroid
- Ix?
- Rx?
Nuclear scintigraphy = patchy uptake
| Rx = Radioiodine Rx (Nb exacerbated thyroid eye disease)
48
In hyperthyroidism, if TSH Ab are negative - what scan can help distinguish between types of hyperthyroidism?
Radionuclide uptake scan
- Graves: diffuse high uptake
- thyroiditis: low uptake
- nodules: uneven uptake
49
Autoimmune polyendocrinopathy syndrome
| type 2?
- much more common than type 1
- polygenic inheritance, linked to HLA DR3/DR4
- Addison's + T1DM/AI thyroid disease
50
Autoimmune polyendocrinopathy syndrome
| type 1?
```
= MEDAC
- v rare, auto rec, mutation of AIRE1 gene on chr 21
2 of 3 of:
- Addison's
- 1ry hyPOparathyroid
- chronic mucocutaneous candida
```
51
HHS
- higher mortality than DKA
- can be complicated by vast e.g. MI, stroke, peripheral arterial thrombosis
- can occur over many days, so more extreme disturbance
- pathphys?
- clin features?
- Dx?
- hyperglycaemia -> osmotic diuresis with ass loss of Na & K
- severe volume depletion -> v high osmolarity -> hyper viscosity of blood
- severe electrolyte losses & body volume depletion
- fatigue, lethargy, nausea, vomit
- altered GCS, headaches, papilloedema, weakness
- hyperviscosity/pro-thrombotic
- dehydration, hypotension, tachycardia
1. hypovolaemia
2. BM>30 without signif ketonaemia/acidosis
3. osmolarity >320
52
Rx of HHS?
- key parameter is osmolality (glucose, Na - plot hourly with osmolality)
- do not use insulin unless significant ketonaemia/acidosis
1. gradually normalise osmolality - 0.9% NaCl already hypotonic in comparison, 0.45% if not working
2. replace fluid & electrolyte losses (est loss 100-220ml/kg)
3. normalise BM gradually
- Insulin treatment prior to adequate fluid replacement may result in cardiovascular collapse as the water moves out of the intravascular space, with a resulting decline in intravascular volume
- give insulin if significant ketonaemia 0.05u/kg/hr
- K deplete but less acidotic than DKA
53
calculated osmolarity?
2Na + glucose + urea
54
Insulinoma = neuroendocrine tumour mainly from pancreatic islets of langerhans cells
- commonest pancreatic endocrine tumour
- 10% malignant 10% multiple of which 50% have MEN-1
- features?
- Dx?
- Rx?
- hypo esp on waking, rapid weight gain
- high C-peptide
- high insulin & pro:insulin
Dx = supervised prolonged 72h fast + CT pancreas
Rx = surgery; Diazoxide + somatostatin if not a candidate
55
low Na
normal serum osmolarity
low calculated osmolarity -> raised osmolar gap
Pseudohyponatraemia
| - proteins, lipids etc
56
low Na
| low plasma osmolarity
true hypotonic hyponatraemia
57
low Na
| high serum osmolarity
hypertonic hyponatraemia
| - check solutes e.g. BM
58
Hyponatraemia causes if spot urinary Na >20?
Renal loss (hypovolaemic)
- thiazide/loops
- Addison's
- diuretic stage of renal failure
Euvolaemic
- SIADH urine osmolality>550
- hypothyroid
59
Hyponatraemia causes if spot urinary Na <20?
Extra-renal loss
- D&V, sweating, burns
- rectal adenoma
Oedematous
- 2ry hyperaldosteronism: heart failure, liver failure
- renal failure
- IV dextrose
- polydipsia
60
Radioiodine Rx can destroy thyroid gland and other thyroid cells that take up iodine, with little effect on rest of body
- Indications?
- C/I?
- method?
- differentiated thyroid ca
- toxic multinodular goitre
- Graves disease refractory to medical Rx
- radiation exposure: potassium iodide used to help individuals exposed to radiation by reducing harmful accumulation of radioactive substances in thyroid
C/I = pregnancy, breastfeeding, active thyroid eye disease unless steroid cover
Avoid until 8wks after CT contrast (competes for binding sites, reducing the uptake, less effective)
1. increase TSH levels to stimulate thyroid levels into taking up radioactive iodine (stop thyroxine or give recombinant human TSH)
2. ingest radioactive iodine capsule
3. once ingested, pt can leave isotopes unit
- > keep away from babies, young children, pregnant women, pets for 2-3wks
- > M/F: no pregnancy for at least 6months
61
Complications of radio iodine Rx?
| F/U?
- thyroid eye pain
- hypothyroid
- Graves flare
- monitor thyroid function
- monitor THYROGLOBULIN for thyroid cancers (if initially elevated than it's likely it can be used as a tumour marker)
62
Thyroid requirement in pregnancy
- increase in thyroxine-binding globulin -> increase in total thyroxine (but doesn't affect free thyroxine level)
63
Thyrotoxicosis in pregnancy
- risks if untreated?
- Graves is commonest cause
- what happens with HCG?
- Rx?
- monitoring?
- fetal loss, maternal heart failure, prem labour
- HCG can transiently activate TSH receptor - hug levels fall in 2nd & 3rd trimester
- Propylthiouracil in 1st trimester (but inc risk of severe hepatic injury)
- carbimazole inc risk of congenital abnormalities, can be used unto 20mg OD
- keep maternal free thyroxine in upper 1/3 of normal to avoid fetal hypothyroidism
- check thyrotrophin receptor stimulating Ab at 30-36/40 to help determine risk of neonatal problems
64
Hypothyroidism in pregnancy
| - Rx?
Thyroxine safe - often need inc dose
- measure TSH every trimester & 6-8wks postpartum
- breastfeeding safe
65
Advantage of GLP-1 agonist e.g. LIRAGLUTIDE
Have been shown to reduce HbA1c by similar levels to basal insulin, without increasing the risk of hypoglycaemia, and promote approximately 3% weight loss over a 6 month period
66
Low urinary calcium in the presence of hypercalcaemia is suggestive of?
Familial hypocalciuric hypercalcaemia
| Or thiazide diuretic use
67
Familial benign hypocalciuric hypercalcaemia
- rare autosomal dominant disorder
- defect in the calcium-sensing receptor & decreased sensitivity to increases in extracellular calcium
- Dx?
aSx hypercalcaemia
- PTH often normal/not suppressed due to decreased sensitivity to increases in extracellular calcium
- no Rx required
- low urinary Ca
- phosphate normal/high
68
Features specific to Graves disease?
| Ab?
- eye signs: exophthalmos & ophthalmoplegia
- thyroid acropachy
- pretibial myxoedema
90% TSH-R Ab
75% anti-thyroid peroxidase Ab
69
Features of 1ry hyperaldosteronism?
| Causes?
BL idiopathic adrenal hyperplasia is commonest cause
- also adenoma
- carcinoma v rare
- HTN
- low K
- ALKALOSIS
70
1st line Ix for suspected Conns syndrome?
| Rx?
1st plasma aldosterone:renin ratio (low renin)
Then CT also with adrenal vein sampling to differentiate UL & BL sources of XS aldosterone
Aldosterone antagonist for hyperplasia
Surgery for adenoma
71
Familial hypercholesterolaemia = Auto dom mutation in gene encoding LDL-R protein
- high LDL
Dx?
Rx?
Adults TC>7.5 LDL>4.9
+ tendon xanthoma or DNA-based evidence = definite
or + FHx MI<50yrs in 2nd degree or <60yrs in 1st degree or FHx raised cholesterol = possible FH
- specialist lipid clinic referral
- high-dose statins
- screen 1st degree relatives inc children by age 10
- discontinue statins 3months before conception (risk of congenital defects)
Heterozygous present later
Homozygous present before age 30 with early CVD
72
Causes of hypoglycaemia?
- insulinoma - inc rate of proinsulin:insulin
- self-admin of insulin: low c-peptide
- self-admin sulfonylurea: high c-peptide
- liver failure
- Addison's
- ETOH
- beta cell hyperplasia in kids
73
Thyrotoxicosis features?
| What drug must be stopped?
- weight loss, manic, restless, heat intolerance
- palpitations
- inc sweating, pretibial myxoedema, thyroid acropachy
- diarrhoea
- oligomenorrhea
- anxiety, tremor
STOP ASPIRIN as it can worsen the storm by displacing T4 from thyroid-binding globulin (inc free T4)
74
Progesterone in pregnancy?
- first 2wks stimulates flap tubes to secrete nutrients the zygote requires
- placenta starts producing at6wks and takes over at 12wks
- inhibits uterine contractions by inhibiting PGs & decreasing sensitivity to oxytocin
- stimulates development of lobules & alveoli
75
Oestrogen in pregnancy?
- oestriol is main one
- stimulated continued growth of myometrium
- stimulates growth of ductal system of breasts
76
Prolactin in pregnancy?
- increases during pregnancy due to oestrogen rise
- initiates & maintains milk secretion of mammary gland
- essential for expression of mammotropic effects of oestrogen & progesterone
- O & P directly antagonises the stimulating effects of PRL on milk synthesis
77
HCG in pregnancy?
- secreted by syncitiotrophoblast, stimulated by GnRH produced in adjacent cytotrophoblast
- can be detected within 9days, peak secretion 9wks
- mimcs LH -> rescuing corpus lute from degenerating & ensuring early O & P secretion
- stimulates relaxin production
- may inhibit contractions induced by oxytocin
78
Relaxin in pregnancy?
suppresses myometrial contractions and relaxes the pelvic ligaments & pubic symphysis
79
hPL in pregnancy?
has lactogenic actions (insignificant with respect to prolactin) - antagonises insulin, therefore making less glucose available to the mother - enhances protein metabolism
80
SGLT-2 inhibitors
- examples
- MoA
- adverse effects
- benefits?
- reduce glucose reabsorption & increase urinary glucose excretion
- empagliflozin, dapagliflozin, canagliflozin
- UTI, genital infection, inc risk LL amputation
- normoglycaemic ketoacidosis
- weight loss/good in heart failure
81
Prolactin secreted by anterior pituitary (dopamine is main inhibitory factor)
- features of XS prolactin?
- causes of raised PRL?
- impotence, loss of libido, galactorrhoea
- amenorrhoea, galactorrhoea
- Pregnancy, Prolactinoma, Physiological, PCOS, Primary hypothyroid (TRH), Oestrogens
- metoclopramide, domperidone, phenothiazines, haloperidol, SSRIs, opioids
82
Rx for SIADH resistant to fluid restriction?
Demeocycline - reduces responsiveness of collecting tubule cells to ASH
83
Causes of SIADH?
- SCLC, pancreas ca, prostate ca
- stroke, SAH, SDH, meningitis/encephalitis/abscess
- TB, pneumonia
- sulfonylureas, SSRIs, TCAs, carbamazepine, cyclophosphamide, vincristine
- PEEP, porphyrias
