Endo 7.5 Flashcards
(250 cards)
1
Q
What is type 3c diabetes?
A
2ry to pancreatic disease e.g. inflammation
2
Q
When to consider bariatric surgery for people with severe obesity?
A
- BMI >40 OR
- BMI >35 with other significant disease that could be improved by weight loss
AND: - all non-surg measures have failed to achieve/maintain adequate beneficial weight loss at least 6m
- intensive specialist Rx
- gen fit for anaesthesia & surgery
- they commit to need for long-term follow-up
3
Q
When to consider bariatric surgery as a 1st line?
A
BMI > 50 & sugical intervention appropriate
- consider orlistat before if waiting time is long
4
Q
What are the types of bariatric surgery?
A
1rily restrictive: laparoscopic adjustable gastric banding (LAGB) or sleeve gastrectomy
- LAGB less weight loss than the others but fewer complications, so usually 1st line if vmi 30-39
1rily malabsorptive: classic biliopancreatic diversion (BPD) but with duodenal switch - usually reserved for v obese
mixed: Roux-en-Y gastric bypass surgery
5
Q
Causes of thyrotoxicosis?
A
Graves (50-60%) toxic nodular goitre acute phase of subacute de Quervain's thyroiditis acute phase of post-partum thyroiditis acute phase of Hashimoto's thyroiditis amiodarone Rx
6
Q
How do thiazolidinediones work?
A
PPAR-gamma agonists
- reduce peripheral insulin resistance
- intracellular nuclear receptor - it’s natural ligands are free fatty acids & thought to control adipocyte differentiation & function
7
Q
Adverse effects of thiazolidinediones ?
C/I?
increased risk of what?
A
- weight gain
- liver impairment - monitor LFTs
- fluid retention - therefore C/I in heart failure
- increased risk of fractures
- increased risk bladder cancer with pioglitazone
8
Q
Causes of Cushing’s syndrome?
A
ACTH-dependent:
Cushing’s disease
ectopic ACTH
ACTH-independent: steroids commonest adrenal adenoma adrenal carcinoma - rare Carney complex: syndrome inc cardiac myxoma micronodula adrenal dysplasia - v. rare
Pseudo-Cushing’s
- mimics often etoh XS or severe depression
- causes false +ive dexamethasone suppression/24h urinary free cortisol
- insulin stress test can be used to differentiate
9
Q
Causes of 1ry hyperaldosteronism - what is the commonest?
A
70% BL idiopathic adrenal hyperplasia
adrenal adenoma (Conn’s)
adrenal carcinoma - extremely rare
10
Q
Features of 1ry hyperaldosteronism?
A
HTN
hypokalaemia (muscle weakness etc)
alkalosis
11
Q
1st line Ix in suspected 1ry hyperaldosteronism?
A
plasma aldosterone:renin ratio
- high aldosterone
- low renin
12
Q
How to differentiate between UL & BL sources of aldosterone XS?
A
high-resolution CT abdomen
adrenal vein sampling
13
Q
Management of 1ry hyperaldosteronism?
A
adrenal adenoma -> surgery
BL adrenocortical hyperplasia -> AA e.g. spironolactone
14
Q
1ry site of absorption of iron & calcium?
A
duodenum
15
Q
1st line antihypertensive in PHaeochromocytoma?
A
PHenoxybenzamine
= non-selective alpha blocker
16
Q
Associations of a phaeochromocytoma?
A
MEN type II
neurofibromatosis
von-Hippel-Lindau syndrome
17
Q
Features of phaeochromocytoma?
A
episodic HTN headaches palpitations sweating anxiety
18
Q
Most sensitive test for phaeochromocytoma?
A
24h urinary metanephrine collection
19
Q
Rx of phaeochromocytoma?
A
- alpha-blocker phenoxybenzamine
- then beta-blocker propranolol
- surgery when stable
20
Q
Features of metabolic syndrome?
A
- inc waist circumference/central obesity
- raised triglycerides
- reduced HDL cholesterol
- HTN
- impaired fasting glucose/T2DM
- microalbuminuria
- raised uric acid levels
- nafld
- pcos
21
Q
Test to confirm / screen for Cushing’s syndrome?
A
OVERNIGHT dexamethasone suppression test (LOW dose) = most sensitive = DIAGNOSTIC
24h urinary free cortisol - screen
22
Q
1st line localisation test for Cushing’s syndrome?
A
9am & midnight plasma ACTH & cortisol levels
- if ACTH suppressed then a non-ACTH dependent cause is likely e.g. adrenal adenoma
23
Q
What does high-dose dexamethasone suppression test confirm?
A
If it suppresses cortisol, then it confirms a pituitary source of Cushing’s (it can’t suppress adrenal/ectopic cortisol)
24
Q
What does CRH stimulation test show in Cushing’s syndrome?
A
It it shows a rise in cortisol then confirms a pituitary source
If no change in cortisol, it is ectopic/adrenal
25
How differentiate ectopic ACTH & pituitary ACTH?
Petrosal sinus vein sampling
26
Which gland secretes prolactin?
| What is the 1ry prolactin releasing Inhibitory factor?
Anterior pituitary
| Dopamine so DA agonists can be used to control galactorrhoea
27
Features of XS prolactin?
M: impotence, galactorrhoea, loss of libido
F: amenorrhoea, galactorrhoea
28
Drugs causing raised prolactin?
metoclopramide, domperidone
phenothiazines
haloperidol
v rarely: SSRIs, opioids
29
Causes of raised Prolactin?
```
Pregnancy
Prolactinoma
Pcos
Primary hypothyroid (TRH stimulates prolactin release)
Phys: stress, exercise, sleep
Oestrogens
Acromegaly (1/3)
```
30
Definite Ix for suspected Addison's disease?
short synACTHen test
- measure plasma cortisol
- can also check adrenal autoAb e.g. anti-21-hydroxylase
31
9am cortisol in Addison's?
<100 abnormal think Addisons
100-500 borderline - do synacthen test
>500 normal, Addisons v unlikely
32
Electrolyte abnormalities in Addison's?
hyponatraemia
hyperkalaemia
HYPOGLYCAEMI
metabolic Acidosis
33
Side-effects of mineralocorticoids?
HTN
| fluid retention
34
Side-effects of glucocorticoids?
MSK: osteoporosis, proximal myopathy, AVN femoral head
immunosuppression: inc infections risk, TB reactivation
endocrine: impaired glucose, increased appetitie/weight gain, hirsutism, hyperlipidaemia, Cushing's syndrome
GI: peptic ulcers, acute pancreatitis
psych: insomnia, mania, depression, psychosis
ophthalmic: glaucoma, cataract
intracranial HTN
growth suppression in children
35
MoA of Mirabegron?
Beta-3 agonist used for urge incontinence if others have failed or C/I
36
Urge incontinence Rx
- minimum 6wks bladder retraining
- 1st line antimuscarinic as a bladder stabiliser; oxybutynin IR (avoid in frail older women), tolterodine IR or darifenacin OD
- If above fail, mirabegron (beta3 agonist)
37
Stress incontinence Rx?
pelvic floor muscle training: Min 3months of 8 contractions 3x/day
surgery: retropubic mid-urethral tape procedures
38
MEN type 1
- features?
- gene?
- most common presentation?
```
Parathyroid 95% (hyperplasia)
Pituitary 70%
Pancreas 50% e.g. insulinoma, gastrinoma (rec peptic ulcers)
- MEN1 gene
- hypercalcaemia
```
39
MEN type IIa
- features?
- gene?
Medullary thyroid ca 70%
Parathyroid 60%
Phaeochromocytoma
- RET oncogene
40
MEN type IIb
- features?
- gene?
```
Medullary thyroid cancer
Phaeochromocytoma
Marfinoid body habitus
Neuromas
- RET oncogene
```
41
Causes of 1ry hyperPTH?
solitary adenoma 80%
hyperplasia 15%
multiple adenoma 4%
carcinoma 1%
42
Features of 1ry hyperPTH?
```
polydipsia, polyuria
peptic ulcer, constipation, pancreatitis
bone pain/fracture
renal stones
depression
hypertension
```
43
Xray showing pepper pot skull - Dx?
hyperparathyroidism
44
Ix in 1ry hyperPTH?
- low phosphate, high Ca
- PTH raised or normal
- technetium-MIBI subtraction scan
45
Rx for 1ry hyperPTH?
- definitive = total parathyroidectomy
- cons Rx ok if Ca++ < 0.25 above ULN + pt>50yrs + no evidence of end-organ damage
- calcimimetics e.g. Cinacalcet can be used if surgery unsuitable
46
Indications for considering parathyroidectomy in 1ry hyperparathyroidism?
- age < 50
- adj Ca2+ 0.25+ above ULN
- eGFR<60
- renal stones/nephrocalcinosis
- osteoporosis/osteoporotic fracture
- Sx disease
47
Pt with HTN + low K + metabolic alkalosis - what is the Dx? best Ix?
1ry hyperaldosteronism
| renin:aldosterone
48
What is an insulinoma?
= most common pancreatic endocrine tumour; is a neuroendocrine tumour mainly derived from islets of Langerhans
- 10% malignant, 10% multiple (1/2 of which have MEN-1)
49
Dx of insulinoma?
| Rx?
- supervised, prolonged fasting upto72h
- can do insulin & C-peptide levels DURING attack
- CT pancreas but doesn't always show up
- surgery
- Diazoxide & Somatostatin if pts not candidates
50
Features of insulinoma?
- hypo usually ***early in AM or just before meals
- rapid weight gain
- high insulin, raised proinsulin:insulin ratio
- high C-peptide
51
high renin & high aldosterone think ?
BL renal artery stenosis
52
MoA of Acarbose?
| commonest side effect?
- inhibitor of intestinal alpha-glucosidases -> decreased absorption of starch & sucrose
- therefore increased carb load delivered to colon where bacteria digest complex carbs -> GI side-effects e.f. flatulence & diarrhoea
- XS flatulence
53
What is measured in an insulin stress test?
When is it used?
What would happen normally?
What are the contraindications?
- IV insulin -> measure GH & cortisol
- Ix hypopituitarism
- GH & cortisol should rise with normal function
- C/Is = epilepsy, IHD, adrenal insufficiency
54
Which drugs can cause false negative renin:aldosterone ratio results in 1ry hyperaldosteronism?
ACE-I
ARBs
direct renin inhib e.g. aliskiren
AAs
55
What is acromegaly?
XS growth hormone
95% pituitary adenoma
minority ectopic GHRH or GH production by tumours e.g. pancreatic
56
Features of acromegaly?
- coarse facies, spade hands, inc shoe size
- large tongue, prognathism, interdental spaces
- XS sweating (gland hypertrophy), oily sin
- features of pituitary tumour e.g. hypopituitarism, headaches, bitemporal hemianopia
- 1/3 raised prolactin -> galactorrhea
- 6% MEN-I
57
Complications of acromegaly?
- HTN
- diabetes >10%
- CARDIOmyopathy
- BOWEL ca (initial colonoscopy age 40, then surveillance)
58
Definitive test for acromegaly?
| Screening/monitoring?
OGTT with serial GH measurements
- IGF-1 may be used as a screening test, & sometimes for monitoring
- MRI pituitary may show a tumour
59
OGTT in acromegaly?
- in acromegaly, there is no GH suppression (may also show impaired glucose tolerance)
- normally, GH is suppressed < 2 with hyperglycaemia
60
Acromegaly Rx:
what is 1st line Rx?
what may be used in older pts or following failed medsurg Rx?
1st line: trans-sphenoidal surgery
| if everything fails external irradiation sometimes used
61
Medical Rx options in acromegaly?
SOMATOSTATIN analogue e.g. OCTREOTIDE (50-70% efficacy) 1st line
- can be used as an adjunct to surgery
Dopamine agonist e.g. BROMOCRIPTINE - 1st effective med Rx, effective in only a minority
GH receptor antagonist that prevents dimerisation of the GH receptor e.g. PEGVISOMANT OD SC
- v effective, reduces IGF-1 levels in 90% to normal
- surgery still needed if mass effect because doesn't reduce tumour volume
62
Features of Addison's disease?
- lethargy, weakness, anorexia, N&V, weight loss, 'salt craving'
- hyperpigmentation (esp palmar creases), vitiligo, loss of pubic hair in women, hyPOtension
- crisis: collapse, shoch, pyrexia
63
Causes of Hypoadrenalism/Addison's?
80% autoimmune destruction of adrenal glands
1ry: TB, mets, meningococcal septicaemia, HIV, antiphospholipid syndrome
2ry: pituitary disorders
64
Causes of Addisonian crisis?
- sepsis/surgery causing an acute exacerbation of an chronic insufficiency
- adrenal haemorrhage e.g. fulminant meningococcaemia Waterhouse-Friderichsen syndrome
- steroid withdrawal
65
Rx of Addisonian crisis?
- 100mg IM/IV hydrocortisone
- 1L fluid over 30-60mins
- cont hydrocortisone 6hrly if pt stable
- oral replacement can start after 24h and be reduced to maintenance over 3-4days
- hydrocortisone has weak mineralocorticoid action
66
Causes of 1ry amenorrhoea?
- Turner's syndrome
- Testicular feminisation
- CAH
- congenital malformations of genital tract
67
Causes of 2ry amenorrhoea i.e. when menses has previously occurred but has not stopped for 6+months?
(after excluding pregnancy)
- hypothalamic amenorrhoea e.g. stress, XS exercise
- PCOS
- hyperPRL
- premature ovarian failure
- thyrotoxicosis(/hypothyroid)
- Sheehan's syndrome
- Asherman's syndrome
68
Initial Ix in amenorrhoea?
- exclude pregnancy
- TFTs, prolactin
- oestradiol, androgen levels
- gonadotrophins (if low often hypothalamic cause, if high then suggests ovarian problem)
69
What is androgen insensitivity syndrome?
What are the features ?
How do you Dx?
Rx?
- X-linked recessive condition due to end-organ resistance to testosterone causing genotypical males to have a female phenotype (46XY)
- testicular feminisation syndrome = complete andogen insensitivity
1. '1ry amenorrhoea'
2. undescended testes causing groin swellings
3. breast development may occur (testosterone converted to estradiol)
Dx = buccal smear or chromosomal analysis (46XY)
Rx =
- counselling (raise as female)
- oestrogen therapy
- BL orchidectomy (undescended testes increases risk of testicular cancer)
70
How is hyperaldosteronism, caused by cortisol activating the mineralocorticoid nuclear receptor, prevented?
cortisol -> inactive cortisone
| by 11-hydroxysteroid dehydrogenase type 2 at the renal parenchyma
71
What is apparent mineralocorticoid XS?
often inherited
autosomal recessive
mutation in 11-hydroxysteroid dehydrogenase type 2 (which normally converts cortisol to inactive cortisone)
rarely, XS liquorice can inhibit this enzyme -> xs cortisol -> AME
72
What is autoimmune polyendocrinopathy/polyglandular syndrome: APS?
What can occur in both types?
What is type 1 (v rare)?
What is type 2?
- Where addison's disease/autoimmune hypoadrenalism is associated with other endocrine deficiencies (10%)
- Vitiligo in both
APS type 1 aka MEDAC = multiple endocrine deficiency autoimmune candidiasis
- V. rare a. recessive
- mutation of AIRE1 gene on chr 21
- Need 2/3 of:
1. Addison's disease
2. 1ry hypoPTH
3. chronic mucocutaneous candidiasis (typically 1st feature as young child)
```
APS type 2 - much more common
- polygenic inheritance linked to HLA DR3/DR4
Addison's disease
+ T1DM OR
+ autoimmune thyroid disease
```
73
What is Bartter's syndrome?
'think lots of furosemide'
What are the features?
- usually inherited cause of severe HYPOKALAEMIA due to defective chloride absorption at the Na/K/2Cl- cotransporter (NKCC2) in ascending loop of Henle
- failure to thrive in childhood (presentation)
- polyuria, polydipsia
- hypokalaemia
- weakness
- NORMOtension (unlike conns/cushings/liddles)
74
What are the 3 enzyme deficiencies that can cause congenital adrenal hyperplasia, and what are their features?
21-hydroxylase deficiency:
- virilisation of female genitalia
- precocious puberty in males
- !60-70% pts have a salt-losing crisis at 1-3weeks of age
11-beta hydroxylase deficiency:
- virilisation of female genitalia
- precocious puberty in males
- hyPOkalaemia, HTN
17-hydroxylase deficiency:
- Non-virilising in females
- inter-sex in boys
- HTN
75
Which steroids have the highest glucocorticoid activity with minimal mineralocorticoid?
Dexamethasone
| Betmethasone
76
Which steroid has very high mineralocorticoid activity with minimal glucocorticoid?
Fludrocortisone
77
Which steroid is predominantly glucocorticoid, with low mineralocorticoid activity?
Prednisolone
78
Which steroid has high mineralocorticoid activity, with some glucocorticoid activity?
Hydrocortisone
79
What is a dynamic pituitary function test for?
What is given?
What is measured at intervals?
What would be normal?
Used to assess pts with suspected 1ry pituitary dysfunction
- > Given insulin, TRH & LHRH
- > Measure glucose, cortisol, GH, TSH, LH, FSH +/- PRL
```
Normally
GH rises > 20
Cortisol rises > 550
TSH rises > 2 from baseline
LH & FSH double
```
80
Disorder of sex development:
46XX or 47XXY
both ovarian & testicular tissue present
v rare
True hermaphroditism
81
Disorder of sex development:
46XX
ovaries present but male/ambiguous external genitalia (virilised)
may be 2ry to CAH
Female pseudohermaphroditism
82
Disorder of sex development:
46XY
testes present but external genitalia are female/ambiguous
may be 2ry to androgen insensitivity syndrome
Male pseudohermaphroditism
83
```
Disorder of sex development:
46XY
ambiguous genitalia in newborn period
hypospadias common
virilisation in puberty
autosomal recessive
results in inability of males to convert testosterone -> DHT
```
5-alpha-reductase deficiency
84
Disorder of sex development:
46XY
genotypical male has a female phenotype
rudimentary vagina & testes present but no uterus
elevated testosterone, oestrogen & LH
X-linked recessive
Androgen insensitivity syndrome
85
RFs for endometrial cancer?
- nulliparity, early menarche, late menopause
- unopposed oestrogen (adding a progestogen reduces risk, eliminates it if prog given continuously)
- Tamoxifen (ER+ breast ca)
- obesity, DM, PCOS
86
Ix for endometrial cancer?
1st line TVUS: normal endometrial thickness <4mm has a high NPV
if thick will probably have hysteroscopy with endometrial biopsy
87
Rx of endometrial cancer?
Localised -> TAH with BSO
If high-risk, may have post-op RT
Progestogen Rx sometimes used in frail elderly not suitable for surgery
88
What is Gitelman's syndrome?
| What are the features?
Defect in thiazide-sensitive Na/Cl transporter in the dct
Low K & Mg
Low Ca2+ in urine
NORMOtension
Metabolic ALKAlosis
89
Causes of gynaecomastia inc drugs?
| Usually caused by increased oestrogen:androgen
- phys: puberty
- liver disease
- syndromes with androgen deficiency: Kallman's, Klinefelter's
- testicular failure e.g. mumps
- testicular ca e.g. seminoma secreting hCG
- ectopic tumour secretion
- hyperthyroidism
- haemodialysis
Drugs:
- spironolactone commonest
- digoxin
- cimetidine
- cannabis
- finasteride
- gonadorelin analogues e.g. goserelin, buserelin
- oestrogens, anabolic steoirds
90
What is HRT composed of?
Small dose of oestrogen
| (WITH progestogen in women with a uterus) to help alleviate menopausal vasomotor Sx
91
Side effects of HRT?
Potential complications/increased risks?
- nausea
- breast tenderness
- fluid retention & weight gain
- increased risk of VTE, stoke, & IHD (10yrs after menopause)
- increased risk of breast & endometrial ca
Adding a progestogen increases risk of breast cancer & VTE further, but reduces risk of endometrial cancer
92
Causes of hypercalcaemia?
- 1ry hyperPTH
- Malignancy: bone mets, myeloma, PTHrP, any ca
- in malignancy, 80% due to PTHrP, remaining due to osteolysis, some due to calcitriol-mediated high Ca & ectopic PTH secretion
Others:
- dehydration
- drugs: thiazides, vitamin d toxicity, calcium-containing antacids
- endocrine: acromegaly, thyrotoxicosis, addison's disease
- granulomas: sarcoid, TB
- milk-alkali syndrome
- can occur with prolonged immobilisation in Paget's bone disease
93
What is 1ry hypoPTH?
Cause?
Rx?
- decrease in PTH secretion leading to low Ca, high phosphate
- e.g. 2ry to thyroid surgery
- Rx with Alfacalcidol
94
Sx of hypoPTH?
usually 2ry to hypocalcaemia
tetany - muscle twitch, cramp, spasm
perioral paraesthesia
Trousseau: carpal spasm if brachial artery occluded by maintaining BP cuff above systolic
Chvostek: tapping parotids causes facial muscle twitch
ecg - prolonged QT interval
chronic - depression, cataracts
95
```
What is pseudohypoPTH?
type I?
type II?
features?
how to Dx?
```
- target cells are insensitive to PTH, due to mutation in a G protein, leading to high PTH, low Ca, high phosphate
I: complete receptor defect
II: cell receptor intact
- low IQ
- short stature
- short 4th & 5th metacarpals
- obesity, round face
- Dx: PTH infusion -> measure urinary cAMP & phosphate levels
(hypoPTH will cause increase in cAMP & phosphate)
- In pseudohypoPTH type I, neither increase; in type II cAMP rises
96
What is pseudopseudohypoPTH?
similar phenotype to pseudohypoPTH but normal biochemistry
97
What is Kallmann's syndrome?
Failure of GnRH-secreting neurons to migrate to the hypothalamus
X-linked recessive
Cause of delayed puberty 2ry to hypogonadotrophic hypogonadism
98
Features of Kallmann's syndrome?
- 'delayed puberty'
- hypogonadism, cryptorchidism (undesc testes)
- anosmia
- low sex hormone levels
- LH & FSH inappropriately low/normal
- pts typically of normal/above average height
- sometimes cleft lip/palate & visual/hearing defects
99
What is Klinefelter's syndrome?
Dx?
Features?
Karyotype 47XXY
Dx by chromosomal analysis
- often taller than average
- lack of 2ry sexual characteristics
- small, firm testes
- infertile
- gynaecomastia - inc incidence of breast ca
- elevated gonadotrophin levels
100
What is Liddle's syndrome?
| Rx?
- rare a dominant condition causing HTN & hypokalaemic alkalosis
- thought to be caused by disordered sodium channels in distal tubules -> inc reabsorption of sodium
Rx with amiloride/triamterene
101
What is neuroblastoma?
| Features?
- childhood malignancy median onset 20m
- tumour arises from neural crest tissue of adrenal medulla & sympathetic nervous system
Features:
- abdo mass
- pallor, weight loss
- bone pain, limp
- hepatomegaly
- paraplegia
- proptosis
102
Ix of neuroblastoma:
urine?
AXR?
- raised urinary VMA & HVA
- calcification can be on AXR
- can Bx the tumour
103
What is MoA of Orlistat?
What are the adverse effects?
What are the NICE criteria for using it?
Pancreatic lipase inhibitor
Fecal urgency/incontinence, flatulence
```
Should only be prescribed as part of an overall plan for managing obesity in adults with:
- BMI 28+ with ass RFs or
- BMI 30+
- cont'd weight loss e.g. 5% at 3months
It is normally used <1yr
```
104
What is MoA of Sibutramine?
Why was it withdrawn in 2010?
What are the adverse effects?
When is it C/I?
Centrally acting appetite suppressant (inhibits uptake of serotonin & noradrenaline at hypothalamic sites that regulate food intake)
- Withdrawn due to increased risk of cardiovascular events
- HTN, constipation, headache, dry mouth, insomnia, anorexia
- C/I: in psych illness, HTN, IHD, stroke, arrythmias
105
Commonest cell type of ovarian cancers?
70-80% serous carcinomas (90% are epithelial in origin)
106
Clinical features for ovarian cancer?
RFs?
Rx?
- abdo pain, pelvic pain
- abdo distension, bloating, diarrhoea, early satiety
- urinary Sx
- FHx: BRCA1 & 2 gene mutations
- many ovulations
Rx usually combo of surgery & platinum-based chemo
107
What is PID?
What is the commonest causative organism?
What are the complications of it?
= infection & inflammation of female pelvic organs inc uterus, fallopian tubes, ovaries & surrounding peritoneum
Commonest cause = chlamydia trachomatis
Complications:
- chronic pelvic pain
- infertility (10-20% after single episode)
- ectopic pregnancy
108
Features of PID?
Rx?
- lower abdo pain, fever
- deep dyspareunia
- vaginal/cervical discharge
- cervical excitation
- dysuria & menstrual irregularities can happen
- perihepatitis: Fitz-Hugh Curtis syndrome (RUQ pain)
Have low threshold for Rx
po OFLOXACIN + po METRONIDAZOLE
or im CEFTRIAXONE + DOXYCYCLINE po + METRONIDAZOLE po
If mild, IUCD can be left in but removal should still be considered (better short term clinical outcomes)
109
What is Pendred's syndrome?
Features?
Dx?
Rx?
- a recessive disorder of
1. BL sensorineural deafness
2. mild hypothyroidism
3. goitre
- pts tend to present with progressive HL & delay in academic progression
- often head trauma makes the HL worse so avoid contact sports
- defect in iodine organification -> dyshormonogenesis
- but thyroid Sx often mild, can be clinically euthyroid with goitre, TFTs often normal requiring perchlorate discharge test to aid Dx
Dx via genetic testing (PDS gene chr 7), audiometry & MRI to look for characteristic ***1.5 turns*** in cochlea (vs normal 2.5)
Rx with thyroid hormone replacement & cochlear implants
110
How to classify pituitary adenomas?
Commonest types?
DDx?
1. Size (micro adenoma <1cm & macro adenoma >1cm)
2. Hormonal status (secretory/functioning adenoma that secretes XS of a hormones vs non-secretory/functioning)
Incidence 10% of people, usually aSx, 10% of adult brain tumours
Prolactinomas = commonest
then non-secreting adenomas
then GH-secreting
then ACTH-secreting
DDx = pituitary hyperplasia, craniopharyngioma, meningioma, brain mets, lymphoma, hypophysitis, vasc malformation
111
How do pituitary adenomas cause Sx?
Ix?
Rx?
- XS hormone
- depletion of hormone (compression of pituitary)
- stretching dura within/around pituitary fossa (headaches)
- optic chiasm compression (bitemporal hemianopia)
- bloods inc GH, PRL, ACTH, FH, LSH, TFTs
- formal visual field testing
- MRI brain with contrast
Rx with combo of:
- hormonal Rx (e.g. bromocriptine for prolactinoma)
- surgery
- RT e.g. transsphenoidal transnasal hypophysectomy
112
PCOS:
aetiology?
features?
Ix?
- not well understood but hyperinsulinaemia & high levels LH are seen, and some overlap with metabolic syndrome
- menstrual disturbance: oligo/amenorrhoea
- acne, hirsutism (hyperandrogenism)
- obesity
- subfertility & infertility
- acanthosis nigricans (insulin resistance)
Ix:
- pelvic US: multiple cysts on ovaries
- FSH, LH, prolactin, TSH, testosterone. Can have raised LH:FSH, PRL can be normal/mildly raised, testosterone is normal/mildly raised
- check impaired glucose tolerance
113
Rx of PCOS?
Gen - weight reduction, cocp can help regulate cycle
Acne & hirsutism:
- 3rd gen cocp or co-cyprindiol (anti-androgen) but both increase risk of VTE
- topical eflornithine
- spironolactone/flutamide/finasteride under specialist supervision
Infertility: weight reduction
- anti-oestrogen e.g. clomifene to help stimulate ovulation
- &/or metformin, esp in obese
- gonadotrophins
Nb potential risk of multiple pregnancies with anti-oestrogen therapies, which work by occupying hypothalamic oestrogen receptors without activating them -> interferes with binding of estradiol -> preventing negative feedback inhibition of FSH secretion
114
What is premature ovarian failure?
Causes?
Features?
- menopausal Sx & elevated gonadotrophins in <40yrs. 1/100 women
- idiopathic commonest
- chemo
- autoimmune
- radiation
- climacteric Sx
- infertility
- 2ry amenorrhoea
- raised FSH, LH
115
What is remnant hyperlipidaemia?
What are the features?
What is the Rx?
aka broad-beta disease, dysbetalipoproteinaemia
= rare cause of mixed hyperlipidaemia (raised cholesterol & triglyceride levels)
- thought to be caused by impaired removal of intermediate density lipoprotein from circulation by the liver
- ass with apo-e2 homozygosity
- high incidence IHD & PVD
- yellow palmar creases
- palmer xanthomas
- tuberous xanthomas
Rx 1st line Fibrates
116
What is Sheehan's syndrome?
| What are the features?
Postpartum pituitary necrosis caused by hyopituitarism due to hypovolaemia with postpartum haemorrhage
- failure to lactate
- breast involution
- amenorrhoea
117
Rx of papillary & follicular thyroid cancer?
- total thyroidectomy
- then radio iodine (I-131) to kill residual cells
- yearly thyroglobulin levels to detect early recurrent disease
118
Commonest thyroid cancer, often young females, v good prognosis?
Papillary carcinoma
- usually contains a mixture of papillary & colloidal filled follicles
- histologically: papillary projections & pale empty nuclei
- seldom encapsulated
- LN metastasis predominate
- haematogenous metastasis rare
119
Thyroid growth that usually presents as a solitary thyroid nodule, and malignancy can only be excluded on formal histological assessment?
Follicular adenoma
120
2nd commonest thyroid cancer, where vascular invasion predominates?
Follicular carcinoma
- multifocal disease is rare
- macroscopically encapsulated, microscopically capsular invasion is seen (without this, it would be adenoma)
121
Thyroid cancer of parafollicular C cells that secrete calcitonin, and is part of MEN-2?
Medullary carcinoma
- C cells derived from neural crest (not thyroid tissue)
- raised serum calcitonin
- familial 20%
- both lymphatic & haem metastasis can be seen; nodal disease ass with v poor prognosis
122
Commonest thyroid cancer in elderly females, where local invasion is a common feature causing pressure Sx?
Anaplastic carcinoma
- Rx by resection where possible
- palliation through isthmusectomy & RT
- chemo ineffective
- not v responsive to Rx
123
Rarest thyroid cancer, ass with Hashimoto's?
Lymphoma
124
Ix for diabetes insipidus?
| Features?
- high plasma osmolality
- low urine osmolality
- can do a water deprivation test
- polyuria, polydipsia, nocturia, dehydration
125
What is cranial diabetes insipidus?
| Causes?
Deficiency of ADH/vasopressin
- reduced circulating ADH
- so kidneys excrete lots of dilute urine (low urine osmolality)
- mutation
- idiopathic
- post-HI trauma
- pituitary surgery
- meningitis
- tumours
- histiocytosis X
- DIDMOAD: DI, DM, optic atrophy & deafness
126
What is nephrogenic diabetes insipidus?
| Causes?
Anything which leads to insensitivity to ADH/interferes with binding
- mutation: in the receptor gene, more common than gene encoding aquaporin 2 channel
- metabolic: hypercalcaemia, hypokalaemia
- drugs: lithium, demeocycline
- CKD
- tubulo-interstitial disease: post-obstructive uropathy, sickle cell, pyelonephritis
127
```
Water deprivation test - how is it done?
what happens it it is normal?
psychogenic polydipsia?
cranial DI?
nephrogenic DI?
```
- give fluid overnight -> measure plasma & urine osmolality -> deprive of water for at least 8h -> measure urine osmolality -> administer vasopressin/ADH -> measure again
normal: normal plasma osmolality, then urine osmolality >600, again >600 after ADH
psychogenic: low starting pl. osmolality, then urine ism >400 after deprivation, and >400 after ADH
cranial DI: high pl osmolality, urine osm < 300 after deprivation, urine osm > 600 after ADH
nephrogenic DI: high pl osmolality, urine osm < 300 after deprivation, urine osm < 300 after ADH (can't respond to any ADH)
128
Dx of diabetes with fasting & OGTT:
Sx?
aSx?
fasting glucose 7.0+
OGTT/random glucose 11.1+
If aSx, then 2x separate readings
129
Dx of diabetes with HbA1c:
Sx?
aSx?
HbA1c 48+ or 6.5%+
If without Sx, then repeat to confirm Dx
- HbA1c less than this doesn't exclude diabetes (i.e. less sensitive than fasting etc sample)
130
What can lead to misleading lower HbA1c result?
Conditions where HbA1c can't be used for Dx?
Increased red cell turnover
- e.g. blood loss, sub/clinical haemolysis, Hbopathies & red cell disorders like sickle cell, myelodysplastic disease
- above, untreated IDA, suspected gestational DM, children, HIV, people on steroids etc
131
MoA of Metformin?
| C/I?
- increases insulin sensitivity & decreases hepatic gluconeogenesis
- 1st line in T2DM but C/I if eGFR < 30
132
```
MoA of sulfonylureas?
On a molecular level?
Common adverse effects?
When to avoid?
Rare adverse effects?
```
- stimulate pancreatic beta cells to secrete insulin therefore only effective if functional B cells present
- they bind to an ATP-dependent K+ channel on the cell membrane of the pancreatic beta cells
- hypos & weight gain
- avoid in pregnancy & breastfeeding
Rarely:
- SIADH/low Na
- BM suppression
- cholestatic liver damage
- peripheral neuropathy
133
MoA of thiazolidinediones?
- activate PPAR-gamma receptor in adipocytes to promote adipogenesis & fatty acid uptake
134
MoA of DPP-4 inhibitors i.e. gliptins?
How is it given?
When might it be preferable to pioglitazone?
What do they increase the risk of?
- increase incretin levels -> inhibit glucagon secretion
- oral, well tolerated, no increased risk of hypo, no weight gain
- preferable to pioglitazone if further weight gain would cause significant problems, it is C/I or pt has had poor response
135
MoA of SGLT-2 inhibitors i.e. gliflozins?
- they reversibly inhibit sodium-glucose co-transporter 2 in the renal pct to inhibit glucose reabsorption, and increase glycosuria
136
MoA of GLP-1 agonists i.e.-tides?
- incretin mimetic -> inhibits glucagon secretion & increases insulin secretion
137
What is impaired fasting glucose?
| What should people be offered if they have impaired fasting glucose?
6.1 =< fasting glucose < 7.0
Offer ogtt to rule out Dx
Due to hepatic insulin resistance
138
What is impaired glucose tolerance?
fasting glucose < 7.0 AND After OGTT:
7.8 =< glucose < 11.1
Due to muscle insulin resistance
139
What is pre diabetes?
Impaired fasting glucose i.e.
HbA1c 42-47 (6-6.4%) or
fasting glucose 6.1-6.9
140
Abs & Ag involved in T1DM?
| What about in LADA?
- HLA DR4 > HLA DR3
- Ab against beta cells of pancreas
- anti-IAA: islet-ass Ag Ab, anti-GAD: glutamic acid decarboxylase
141
T1DM:
HbA1c target & monitoring?
self-monitoring or blood glucose?
BG targets?
- monitor HbA1c every 3-6m, target 48mmol/6.5% or lower where possible
- do BG at least 4x/day inc pre-meals & pre-bed; more frequent if having hypos, unwell, sports, pregnancy etc
- BG target 5-7 on waking, otherwise 4-7
142
T1DM in adults:
what is insulin regimen of choice?
what is an example?
what type of insulin should be offered for mealtime replacement?
when can you consider adding metformin in T1DM adults?
- basal-bolus regimens
- e.g. insulin detemir/levemir BD, or can be OD, or glargine OD
- rapid-acting insulin Analogues before meals
- If BMI 25+, can add metformin
143
HbA1c target if:
lifestyle+/- metformin Rx?
if on any drug that may cause hypoglycaemia?
if on Rx but HbA1c has risen to 58mmol/7.5%?
- 48mmol/6.5%
- 53mmol/7.0%
- 53mmol/7.0%
144
T2DM Drug Rx if someone can tolerate Metformin?
1. Metformin if HbA1c 48/6.5% +
2. Add 2nd drug if HbA1c 58/7.5% + : sulfonylurea/gliptin/pioglitazone/SGLT2inhibitor
3. Triple therapy if HbA1c rises/still 58/7.5% + :
- sulfonylurea can have any of the other drugs added/vice versa
- or metformin + pioglitazone + SGLT2inhibitor
- or insulin Rx should be considered
145
What are the criteria for GLP1 mimetic e.g. exenatide in T2DM if triple therapy not effective/tolerated/C/I?
The combo of metformin + sulfonylurea + GLP1 mimetic if:
1. BMI 35+ & specific med/psych problem ass with obesity OR
2. BMI < 35 & in whom insulin would have significant occupational implications/weight loss would benefit other significant obesity-related conditions
AND
3. ONLY continue if there is a reduction of at least ***11mmol/1.0%*** HbA1c AND weight loss 3% in 6months
146
T2DM Rx if someone cannot tolerate Metformin or C/I?
1. If HbA1c 48/6.5% then: sulfonylurea/gliptin/pioglitazone
2. If HbA1c rises to 58/7.5% then double therapy combo of any 2 of the 3 is ok
3. If it persists at 58/7.5% then consider insulin Rx
147
Starting with insulin Rx in T2DM:
what should be continued?
what insulin can be started initially?
- > Continue metformin. Others would be reviewed for continued need
- > ***Start with human NPH insulin (=isophane, intermediate-acting). ON or BD according to need***
- > can add a short-acting insulin if HbA1c v high e.g. 75mmol/9%
- > use insulin deter/glargine as alternative to NPH if pt needs assistance with injection or lifestyle warrants it if it reduces frequency of injections
148
What is target BP in people with T2DM?
What is 1st line antihypertensive?
When to offer anti platelets?
When to offer a statin & what?
- target BP < 140/80
- <130/80 if end-organ damage
- ACE-I 1st line
- anti-platelets only if existing CVD
- 1ry prevention atorvastatin 20mg od if Qrisk 10% + (uptitrtte if non-HDL doesn't fall by at least 40%)
- 2ry prevention atorvastatin 80mg od (ihd/cvd/pad)
149
Which groups to offer lipid-modification Rx i.e. statin without a formal risk assessment, and what are the criteria?
CKD (All, i.e. eGFR < 60 &/or ACR >3)
Familial hypercholesterolaemia
T1DM 1ry prevention atorvastatin 20 if:
- aged 40+
- has had DM for > 10 yrs
- has established nephropathy or
- has other CVD RFs e.g. obesity & HTN
- for all other adults, still consider it... & 80mg if 2ry prevention
150
If a pt with T2DM decides to fast during Ramadan:
- what should they eat before sunrise/suhoor?
- monitoring?
- metformin dose adjustment?
- sulfonylurea dose adjustment?
- pioglitazone dose adjustment?
- before sunrise eat meal with long-acting carbs
- BG monitor to use, esp if they feel unwell
- 1/3 metformin before sunrise, 2/3 metformin after sunset/iftar
- take sulfonylura after sunset. if BD prep e.g. gliclazide, take larger proportion of dose after sunset
- pioglitazone no adjustment needed
151
Precipitating factors of DKA?
| Clinical features?
- infection, infarction, iatrogenic (missed insulin), ischaemia
- abdo pain
- polyuria, polydipsia, dehydration
- Kussmaul resp (deep hyperventilation)
- acetone-smelling breath
152
Dx criteria for DKA?
- hyperglycaemia of glucose > 11/known DM
- ketonaemia > 3 or ketonuria ++
- acidaemia: pH < 7.3, bicarb < 15
- N.b. if anion gap not raised, consider another cause for the acidosis
153
DKA Rx: 4 things?
fluid rate?
electrolyte replacement?
- IV fluids (most deplete at least 5L)
- IV insulin fixed rate 0.1unit/kg/h - can start 5% dextrose when glucose < 15
- correction of hypokalaemia
- Rx underlying cause!!!
- rate can be 1L bags over 1/2/2/4/4/6hrs etc, slower if young adult <26yrs as greater risk of cerebral oedema... 1:1 nursing, neuro-obs etc - usually occurs 4-12h after Rx but can be any time. If concerned consider CT head & get senior r/v
K level in first 24h:
- > 5.5, no KCl
- 3.5-5.5 give 40mmol KCl
- < 3.5 senior review for additional KCl
154
Complications of DKA and its Rx?
- thromboembolism
- gastric stasis
- AKI
- ARDS
- arrhythmias 2ry to hyperkalaemia/iatrogenic hypokalaemia
- iastrogenic inc: cerebral oedema, hypokalaemia, hypoglycaemia (if no glucose bag ran alongside insulin!)
155
Diabetic foot disease occurs 2ry to which 2 main factors?
How to screen for both?
What are their presentations?
What are complications?
1. neuropathy: loss of protective sensation, Charcot's arthropathy, dry skin
- 10g monofilament at least annually
- loss of sensation
2. peripheral arterial disease: micro & macrovascular ischaemia
- palpate both distal pulses at least annually
- absent pulses, intermittent claudication, reduced ABPI
Complications inc: calluses, ulceration, Charcot's, cellulitis, osteomyelitis, gangrene
156
How to risk stratify diabetic foot disease:
low?
moderate?
high?
Low risk: no RFs except callus
Moderate risk:
- deformity/neuropathy/non-critical limb ischaemia
High risk:
- previous ulceration/amputation or
- on RRT or
- neuropathy + non-critical ischaemia or
- neuropathy + callus/deformity or
- non-critical ischaemia + callus/deformity
i. e. 2 of 3 or RRT or previous critical ischaemia
All mod/high risk pts should have regular F/u in local diabetic foot centre
157
Diabetic neuropathic pain Rx ladder?
localised?
rescue?
resistant?
1. duloxetine/amitriptyline/pregabalin/gabapentin
2. if 1st doesn't work, trial 1 of the other 3
localised neuropathic pain e.g. post-herpetic neuralgia: Topical Capsaicin
rescue therapy/exacerbations: Tramadol
If resistant: pain clinic
158
Sx & Rx for Gastroparesis as a result of diabetic neuropathy?
- erratic BMs, bloating, vomiting
Rx = prokinetics e.g. metoclopramide/domperidone/erythromycin
159
DVLA rules of diabetes:
Driving HGV if on insulin/hypoglycaemics?
Driving a car (group 1) on insulin/hypoglycaemics?
if on exenatide/other tablets/diet-controlled?
HGV driver on insulin/hypoglycaemics:
- no severe hypo in last 12m, driver has hypo awareness, adequate BM monitoring, driver understands risks of hypo, no other debarring complications
Car driver on insulin/hypos:
- can drive if they have awareness, max 1 episode of hypo requiring assistance in past 12m, no relevant visual impairment
on exenatide/tablets/diet:
- no need to inform dvla
160
HbA1c = glycosylated Hb
How is it produced?
What is it dependent on?
Equation for calculating plasma glucose from HbA1c?
- Produced by glycosylation of Hb at a rate proportional to glucose conc
Depends on:
1. RBC lifespan
2. average blood glucose concentration
average plasma glucose = (2 X HbA1c) - 4.5
161
What conditions can lead to lower than expected HbA1c?
Reduced RBC lifespan i.e. increased red cell turnover e.g.
- sickle cell
- GP6D deficiency
- hereditary spherocytosis
162
What conditions can lead to higher than expected HbA1c?
Increased RBC lifespan e.g.
- vit B12/folic acid deficiency
- IDA
- splenectomy
163
Important adverse effects of SGLT2 inhibitors?
- urogenital infections 2ry to glycosuria
- increased risk DKA!!! - euglycaemic
- nb they increase total cholesterol (HDL & LDL), significance unclear
164
5 RFs for gestational DM?
Screening for gestation DM?
1. BMI > 30
2. prev macro baby 4.5kg +
3. prev gestational DM
4. 1st degree relative with DM
5. family origin with high prevalence
- if pre gest DM then OGTT asap after booking + at 24-28wks if normal - can also self-monitor early
- OGTT at 24-28wks if any other RF
165
Dx thresholds for gestational DM?
Targets for self-monitoring of pregnancy women (inc those with pre-existing DM)?
fasting glucose 5.6+
OGTT 2h glucose 7.8+
fasting target max 5.3
1h post-meal 7.8 or
2h post-meal 6.4
166
Management of pre-existing diabetes during pregnancy:
- conservative?
- medicines?
- supplement?
- monitoring?
- if BMI > 27 then weight loss
- stop oral hypoglycaemics, continue metformin, start insulin
- folic acid 5mg OD from pre-conception to week 12/40
- wk 20/40 detailed anomaly scan inc 4 chamber view of heart & outflow tracts
- treat retinopathy (can worsen during pregnancy)
- tight glycaemic control reduces complication rates
167
```
Management of gestational diabetes:
Cons?
When to start metformin?
When to start insulin?
When to offer Glibenclamide?
```
Cons:
- joint diabetes & antenatal clinic within 1wk, teach self-monitoring of BG, diet & exercise advice
- trial diet & exercise if fasting glucose < 7
Start metformin:
- if glucose targets not met within 1-2wks of altering diet/exercise
Start insulin if:
- fasting glucose 7+ at time of Dx
- fasting glucose 6-6.9 + evidence of complications e.g. macrosomia/hydramnios
- glucose target not met by diet/exercise/metformin
Only offer glibenclamide if:
- can't tolerate metformin or
- BG target not met by metformin, and declines insulin Rx
168
What is MODY?
inheritance?
features?
- T2DM development in <25yrs old typically
- autosomal dominant, >6 different genetic mutations identified, usually FHx of early onset DM
- insulin not usually necessary
- ketosis not a feature at presentation
169
MODY 3 prevalence?
gene defect?
increased risk of what?
- 60% of MODY cases
- defect in HNF-1 alpha gene
- inc risk of hepatocellular cancer
170
MODY 2 prevalence?
| gene defect?
- 20% of MODY cases
| - defect in glucokinase gene
171
What are meglitinides?
When are they usually used?
Adverse effects?
e. g. repaglinide, nateglinide
- insulin secretagogues that bind to ATP-K+ channel like sulfonylureas
- pts with erratic lifestyle
- weight gain & hypo (less than sulfonylureas)
172
Commonest causes of hypoglycaemia?
- insulin/sulfonylureas
- etoh, liver failure
- Addison's disease
- insulinoma, increased pro:insulin
Sulfonylureas are long-acting anti-glycaemics so can cause recurrent hypoglycaemia
Low glycogen stores in chronic alcoholism prevents glucagon from being an effective Rx for hypoglycaemia
Wernicke's encephalopathy
173
Hyperosmolar hyperglycaemic state:
presentation?
complications?
- often in elderly T2DMs where hyperglycaemia results in severe dehydration, osmotic diuresis & electrolyte deficiencies. HHS often occurs over days, so disturbances more extreme
- higher mortality than DKA, and can be complicated by e.g. MI, stroke, peripheral arterial thrombosis
- uncommon but documented tic: seizures, cerebral oedema, CPM
174
Pathophysiology of HHS?
- hyperglycaemia -> osmotic diuresis with ass loss of Na & K
- severe volume depletion -> significantly raised serum osmolarity > 320 -> hyper viscosity of blood
- hypertonicity leads to preservation of intravascular volume so pt usually doesn't look as severely dehydrated as they are
175
Dx of HHS?
Clinical features?
1. hypovolaemia
2. marked hyperglycaemia > 30 without significant ketonaemia/acidosis
3. significantly raised serum osmolarity > 320
Gen: fatigue, lethargy, nausea & vomiting
Neuro: altered GCS, headaches, papilloedema, weakness
Haem: hyper viscosity that can result in MIs, stroke, peripheral arterial thrombosis
CVS: dehydration, hypotension, tachycardia
176
3 goals of HHS Rx?
Fluid replacement?
Monitoring response?
1. normalise osmolality gradually
2. replace fluid & electrolyte losses
3. normalise BG gradually
- estimated fluid losses 100-220ml/kg
- caution rehydration rate in elderly/comorbidities
- hypotonic 0.9% NaCl
- aim of Rx should be to replace at least 3-6L or 50% of losses by 12h, remaining losses within next 12h
- key parameter is osmolality to which glucose & Na are the main contributors (rapid change in osmolality can lead to CV collapse & CPM)
- plot osmolarity, Na & glucose on a graph initially hourly
- rough best of serum osmolarity = 2Na + glucose + urea
- fluid replacement gradually lowers glucose which will reduce osmolality
- fall in osmolarity -> shift of water into intracellular space -> rise in Na of 2.4 for every fall in BG of 5.5
- safe rate of fall of glucose if 4-6mmol/hr
- target BG 10-15
- normalisation of electrolytes & osmolality may take 72h
177
Insulin in HHS?
ONLY if significant ketonaemia, is insulin indicated e.g. mixed DKA/HHS e.g. fixed rate 0.05u/kg/h
- otherwise, insulin can lead to rapid decline of serum glucose, therefore osmolarity, and if before fluids can cause CV collapse as water moves out the intravascular space -> fall in intravascular volume
178
Potassium in HHS?
- HHS pts are K deplete but less acidotic than DKA
- can have hyperkalaemia with AKI
- pts on diuretics may be profoundly hypokalaemic
- therefore K monitoring & fixing as nec is required
179
What is GLP-1?
glucagon-like peptide-1
- hormone released by the small bowel in response to an oral glucose load
- an oral glucose load results in a greater release of insulin than if the same load is given IV = incretin effect; this effect is largely mediated by GLP-1, and known to be decreased in T2DM
180
How is Exenatide (a GLP-1 mimetic) administered?
Advantage of Liraglutide (another GLP-1 mimetic) over exenatide?
SC within 60minutes before Am & evening meal - should NOT be given after a meal
Liraglutide only OD
181
Main side effects of GLP-1 mimetics?
| What adverse effect has exenatide been linked to in some patients?
Nausea & vomiting
***Severe pancreatitis***
182
Overweight taxi driver has started Metformin, HbA1c has come down but still high at 75 - next step?
Add DPP-4 inhibitor e.g. sitagliptin (no risk of hypo - driver - and weight neutral)
183
What is MoA of Pegvisomant?
GH receptor antagonist
- used in Acromegaly
- effectively decreases IGF-1 levels in 90% but doesn't shrink tumour
184
What is the chromosomal abnormality ass with Klinefelter's syndrome?
47 XXY
185
Hashimoto's thyroiditis is associated with which thyroid cancer?
Lymphoma
186
What is the most abundant circulating adrenal steroid?
DHEA: dehydroepiandrosterone
| Adrenals are main source of DHEA in females therefore in Addison's, Sx can be as a result of androgen deficiency
187
When would you start Metformin in pre diabetes?
For high risk adults e.g. 'whose blood glucose measure (fasting plasma glucose or HbA1c) shows they are still progressing towards type 2 diabetes, despite their participation in an intensive lifestyle-change programme'
e.g. their BT is in pre-diabetes range despite lifestyle interventions
188
What does endometrial histology show during menstrual cycle:
follicular phase?
luteal phase?
```
Follicular = endometrial proliferation
Luteal = endometrium changes to secretory lining under influence of progesterone
```
189
What does ovarian histology show during menstrual cycle:
follicular phase?
luteal phase?
Follicular: follicles develop; one becomes dominant around mid-follicular phase
Luteal: becomes the corpus luteum
190
What happens to hormone levels during menstrual cycle:
follicular phase?
luteal phase?
Follicular:
- FSH rise -> follicular development -> secrete Oestradiol
- when egg has matured, it secretes enough estradiol to trigger acute release of LH
- LH surge leads to ovulation
Luteal:
- Progesterone secreted by corpus lute rises throughout the luteal phase
- Corpus luteum degenerates if fertilisation doesn't happen -> progesterone levels fall
- Oestradiol levels also rise again
191
What happens to the cervical mucus during menstrual cycle:
follicular phase?
luteal phase?
Follicular: after menses, mucus is thick, forming a plug at the external os
- just before ovulation it becomes clear, acellular, low viscosity & stretchy ('spinnbarkeit')
Luteal: becomes thick, scant, tacky under influence of progesterone
192
Hypoglycaemia with raised insulin, normal proinsulin, & low C-peptide levels?
Insulin abuse
193
How do non-functioning pituitary tumours usually present?
Hypopituitarism & pressure effects
194
2ry amenorrhoea with lower FSH, PRL & estradiol?
hypothalamic causes e.g. stress/exercise
195
What causes overactive bladder/urge incontinence?
Detrusor over-activity
196
1st line for overactive bladder/urge incontinence in older man?
Tolterodine
| oxybutynin greater risk of confusion
197
What happens biochemically in DKA?
Low insulin stimulates lipolysis -> production of ketone bodies, beta-hydroxybutyrate & acetoacetate for metabolic fuel
198
Which type of thyroid cancer is ass with RET oncogene?
Medullary mainly
(also papillary)
RET oncogene encodes tyrosine kinase receptor ass with MEN type 2
199
MoA of Carbimazole?
How is it usually dosed?
Adverse effects?
- blocks thyroid peroxidase from coupling & iodinating the tyrosine residues on thyroglobulin -> reducing thyroid hormone production
Usually high doses for 6wks until pt is euthyroid then reduced
Agranulocytosis
- crosses placenta, ok in low doses in pregnancy
200
Features of congenital hypothyroidism?
- prolonged neonatal jaundice
- delated mental & physical milestones
- short stature, puffy face, macroglossia, hypotonia
- irreversible cognitive impairment if not Dx & Rx within first 4wks
201
Graves' disease:
Presentation?
Specific signs limited to it?
- features of thyrotoxicosis in females aged 30-50
- commonest cause of thyrotoxicosis in pregnancy
- 25-50% risk of developing eye disease
- eye signs 30%: exophthalmos, ophthalmoplegia
- pretibial myxoedema
- thyroid acropachy
202
Commonest autoAb in Graves' disease?
| 2nd commonest?
TSH receptor stimulating Ab 90%
| anti-thyroid peroxidase Ab 75%
203
Anti-thyroid drug Rx in Graves' disease?
Carbimazole high dose 40mg at least 6wks until euthyroid then reduced gradually to maintain
- typically continued 12-18months
- fewer side-effects than block&replace regime
204
Block & replace Rx in Graves' disease?
Carbimazole 40mg started to block
- Thyroxine added when pt is euthyroid
- usually lasts 6-9months
205
Radioiodine Rx in Graves' disease:
what are the contra-indications?
Thyroxine supplementation?
C/I:
- age < 16yrs
- pregnancy (avoid conception 4-6m after Rx)
- relative: thyroid eye disease as it may worsen
Majority will require thyroxine after 5yrs
(hypothyroidism is most likely side effect)
206
What is Hashimoto's thyroiditis?
who does it typically affect?
What are the clinical features
Which Ab may be present?
Autoimmune disorder typically associated with hypothyroidism; there may be a transient thyrotoxicosis in acute phase
- 10x more common in women
- commonest cause of hypothyroidism
- ass with other AI disease e.g. IDDM, Addisons, pernicious anaemia
1. firm, non-tender goitre
2. hypothyroidism features
1. anti-thyroid peroxidase Ab
2. anti-Tg Ab
207
Causes of 2ry hypothyroidism?
Rare
- pituitary failure
- Downs, Turners syndromes, coeliac disease
- Give steroids before thyroxine
208
Causes of 1ry hypothyroidism?
1. Hashimoto's thyroiditis
2. Subacute thyroiditis (de Quervain's)
3. Riedel thyroiditis
4. After thyroidectomy/radioiodine Rx
5. Drug Rx
6. Dietary iodine deficiency
209
Features of hypothyroidism?
Gen: weight gain, lethargy, cold intolerance
Skin: dry, cold, yellow skin
- non-pitting oedema
- dry, coarse scalp hair, loss of lateral aspect eyebrows
GI: constipation
Gynae: menorrhagia
Neuro: reduced deep tendon reflexes, carpal tunnel
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4 Side effects of thyroxine therapy?
Interaction?
1. reduced bone mineral density
2. worsening of angina
3. AF
4. hyperthyroidism due to overRx
Iron reduces absorption of levothyroxine, so take at least 2h apart
211
Starting dose of thyroxine?
When should initial dose be reduced?
When to check TFTs after a change in thyroxine dose?
What is the therapeutic goal?
- 50-100mcg OD
- Lower e.g. 25mcg od in over 50s, severe hypothyroidism, & those with IHD
- check 8-12wk after change
- normalisation of TSH e.g. 0.5-2.5
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Hypothyroidism in pregnancy:
thyroxine dose?
when to measure TSH?
- many women require increased thyroxine dose in pregnancy, it is safe in breastfeeding as well
- measure TSH each trimester (aim low-normal) & 6-8wks postpartum
213
What happens to thyroxine level in pregnancy?
Pregnancy increases levels of thyroxine-binding globulin -> increase in levels of total thyroxine (but NO effect in free thyroxine level)
214
What are the 3 risks of untreated thyrotoxicosis in pregnancy?
1. inc risk fetal loss
2. premature labour
3. maternal heart failure
215
What is transient gestational hyperthyroidism?
When HCG activates the TSH receptor
| - HCG levels fall in 2nd & 3rd trimester
216
Rx of thyrotoxicosis in pregnancy:
what is the antithyroid regimen of choice?
free thyroxine level target?
which Ab should be checked & when?
- Propylthiouracil in 1st trimester (because carbimazole has inc risk of congenital abnormalities)
- Switch back to Carbimazole at start of 2nd trimester (as propylthiouracil has inc risk of severe hepatic injury
- keep maternal free thyroxine levels in upper 1/3 limit of normal to avoid fetal hypothyroidism
- check thyrotrophin-receptor stimulating Ab at wks 30-36/40 gestation to help determine risk of neonatal thyroid problems
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What is Riedel's thyroiditis?who does it usually affect?
clinical features?
main association?
Rare cause of hypothyroidism characterised by DENSE FIBROUS tissue replacing the normal thyroid parenchyma
- usually seen in middle-aged women
1. hypothyroidism features
2. hard, fixed, painless goitre
Ass with retroperitoneal fibrosis
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What is sick euthyroid syndrome?
| What is shown on bloods?
Non-thyroidal illness, reversible on recovery from a systemic illness
- low T3 & thyroxine
- low/normal TSH
219
Skin manifestations of hypothyroidism?
- dry, cold, yellow skin
- non-pitting oedema
- dry, coarse scalp hair, loss of lateral 1/3 eyebrow
- eczema
- xanthomata
- pruritus (both)
220
Skin manifestations of hyperthyroidism?
- increased sweating
- scalp hair thinning
- thyroid acropachy: clubbing
- pretibial myxoedema: erythematous, oedematous lesions above lateral malleoli
- pruritus (both)
221
What is subacute de Quervain's (granulomatous) thyroiditis?
What are the 4 phases?
Thyroid imbalance thought to over after a viral infection, usually presenting with hyperthyroidism
1. 3-6wks of hyperthyroidism, painful goitre, raised ESR
2. 1-3wks euthyroid
3. wks-months of hypothyroid
4. thyroid structure & function back to normal
222
Ix of subacute de Quervain's thyroiditis?
Globally reduced uptake on iodine-131 scan
223
Rx of subacute de Quervain's thyroiditis?
- usually self-limiting, not requiring Rx
- aspirin/nsaids for thyroid pain
- steroids if severe- esp if hypothyroidism develops
224
What is subclinical hyperthyroidism?
What are the causes?
Why is it important to recognise it?
Rx?
- low TSH < 0.1
- but normal T3 & free thyroxine
1. multinodular goitre, esp in elerly females
2. XS thyroxine can give a similar biochemical picture
Due to the potential adverse effects on heart & bone. Can also impact QoL & inc risk of dementia.
Rx:
- e.g. therapeutic trial low-dose anti-thyroid agent for 6months to try reduce remission
- BUT TSH often normalises - so levels should be persistently low to warrant intervention
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What is subclinical hypothyroidism?
| What is the significance?
- raised TSH
- normal T3, T4
- no obvious Sx
- risk of progressing to overt hypothyroidism 2-5%/yr, esp men
- risk increased by presence of thyroid autoAb
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Rx of subclinical hypothyroidism:
- if TSH is 4-10 & free thyroxine level normal?
- if TSH>10 & free thyroxine normal?
TSH 4-10, normal thyroxine:
- <65yrs with Sx, trial levothyroxine, but if no improvement then stop
- in older esp >80yrs, watch & wait gen avoiding hormonal strategy
- if aSx, observe & repeat thyroid function in 6months
TSH > 10, normal thyroxine:
- =<70 yrs start Rx with levothyroxine, even if aSx
- in older eso >80yrs, again watch & wait
227
What is the basic feedback loop of the hypothalamus-pituitary-end organ system that produces thyroxine hormones?
Hypothalamus secretes Thyrotropin-RH
- > stimulates anterior pituitary to secrete TSH
- > acts on thyroid gland inc T4 & T3 (triiodothyronine), the main hormones
- > they act on a wide variety of tissues helping to regulate use of energy sources, protein synthesis & controlling boys sensitivity to other hormones
228
How to classify hypothyroidism problems?
Congenital: problem with thyroid dyshormonogenesis/dysgenesis
1ry: problem with thyroid gland
2ry: usually disorder or pituitary, or lesion compressing pituitary
229
Painful goitre + raised ESR + recent viral illness?
Subacute de Quervain's thyroiditis
230
Features of hyperthyroidism?
Gen: weight loss, 'manic'/restlessness, heat intolerance
Cardiac: palpitations/arrhyhtmis e.g. AF
Skin: sweating, pretibial myxoedema, acropachy
GI: diarrhoea
Gynae: oligomenorrhoea
Neuro: anxiety, tremor
231
TSH-receptor Ab?
90-100% of Graves' disease pts
232
anti-TPO Ab?
90% of Hashimoto's thyroiditis pts
233
Nuclear scintigraphy: patchy uptake?
Toxic multinodular goitre
234
What drug is often given initially to block adrenergic effects in Graves'?
Propranolol
| e.g. for tremor
235
Low TSH, normal free T4?
Subclinical hyperthyroidism
OR
Steroid Rx
236
Causes of thyrotoxicosis?
Graves'
Toxic multinodular goitre
Amiodarone
Acute phases of: subacute thyroiditis, post-partum thyroiditis, or Hashimoto's thyroiditis
237
What is the pathophysiology of thyroid eye disease?
How to prevent it?
Autoimmune response against an autoAg, possibly the TSH-receptor
- > retro-orbital inflammation
- > glycosaminoglycan & collagen deposition in the muscles
- Smoking = most important modifiable RF
- Radioiodine can worsen the inflammatory Sx - Prednisolone may help reduce this risk
238
Features of thyroid eye disease?
Rx?
What features would need urgent ophthalmology review?
- pt thyroid status can be low/eu/high
- exophthalmos, conjunctival oedema
- optic disc swelling, ophthalmoplegia
- sore, dry eyes if they can't close eyelids
Rx with topical lubricants (corneal inflammation)
- steroids
- RT, surgery
Urgent R/V:
- unexplained deteriorating vision
- awareness of change in intensity/quality of colour vision in 1/both eyes
- Hx of eye suddenly 'popping out' = globe subluxation
- obvious corneal opacity
- cornea still visible when eyelids closed
- disc swelling
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What are the clinical features of a thyroid storm?
Rx?
Life-threatening complication of thyrotoxicosis; rarely presenting feature or due to iatrogenic thyroxine
- nausea & vomiting, confusion & agitations
- fever > 38.5, tachycardia, hypertension
- abnormal LFTs
- heart failure
- Sx Rx e.g. paracetamol
- Rx underlying precipitant
- Propranolol
- anti-thyroid drugs e.g. propylthiouracil/methimazole
- Lugol's iodine
- dexamethasone e.g. 4mg IV qds - blocks conversion of T4 -> T3
240
What is a toxic multi nodular goitre?
Ix of choice?
Rx of choice?
Thyroid gland containing a number of autonomously functioning thyroid nodules -> hyperthyroidism
Ix: nuclear scintigraphy reveals patchy uptake
Rx: Radioiodine Rx
241
What is the pathophysiological mechanism is causing apparent mineralocorticoid excess?
11-hydroxylase dehydrogenase type 2 inhibition
242
HTN not responding to drugs + hypokalaemia metabolic alkalosis?
1ry hyperaldosteronism
243
Hypothyroidism + hard, fixed, painless goitre?
Riedel thyroiditis
244
Hypothyroidism + firm non-tender goitre?
Hashimoto's thyroiditis
245
Myxoedemic Coma/thyrotoxic storm: confusion, bradycardia, hypotension
initial Rx?
Hydrocortisone (to Rx adrenal insuffienciency)
& levothyroxine (to replace low thyroid hormone levels causing pts Sx)
- beta blocker if tachycardia
- Risk of hypopituitarism due to the location of the lesion -> therefore treat as presumed adrenal insufficiency until it has been ruled out.
246
autosomal dominant disorder that mimics hyperaldosteronism, resulting in hypokalaemia associated with hypertension?
Liddle's syndrome
247
Causes of hypokalaemia with hypertension?
Cushing's syndrome
Conn's syndrome (1ry hyperaldosteronism)
Liddle's syndrome
11-beta hydroxylase deficiency
248
Causes of hypokalaemia without hypertension?
- diuretics
- GI loss
- renal tubular acidosis type 1 & 2
- Bartter's syndrome
- Gitelman syndrome
249
what class of drugs are chlorpropamide & tolbutamide?
sulfonylurea
250
When to offer HPV vaccine to men?
MSM under age of 45 to protect against anal, throat & penile cancers
