Endocrinology Flashcards
(258 cards)
1
Q
Prediabetes Impaired fasting glucose
A
due to hepatic insulin resistance (more likely to develop T2DM than IGT).
fasting glucose 6.1-7.0 (need to do OGTT to rule out T2DM dx)
2
Q
Impaired glucose tolerance
A
due to muscle insulin resistance.
OGTT 2hrs 7.8 to 11.1
3
Q
Rx for prediabetes (IFG/IGT)
A
lifestyle mod, yearly f/u, metformin if heading towards T2DM despite participation
4
Q
Which form of prediabetes (IFG or IGT) is one more likely to develop T2DM with
A
IFG
5
Q
Dx for T2DM
A
Fasting glucose >7. Random glucose/2hrs post OGTT >11.1. Symptomatic x1, asymptomatic x2
6
Q
Metformin MOA
A
biguanide, activates AMPK, reduces hepatic gluconeogenesis, increases peripheral insulin sensitivity
7
Q
How to titrate metformin up
A
slowly (1wk before increasing dose)
8
Q
What to do if meformin SE unacceptable
A
convert to MR
9
Q
metformin SE
A
lactic acidosis, reduced B12 absorption, GI upset
10
Q
Contraix for metformin
A
ckd, tissue hypoxia, iodine contrast, ETOH
11
Q
Sulfonylurea moa
A
binds to ATP-dependent K (atp) channel on pancreatic beta cells (closes them), increases pancreatic insulin secretion.
12
Q
sulfonylurea SE
A
hypo, weight gain, SIADH, cholestatic liver dysf, peripheral neuropathy.
13
Q
Sulfonylurea contraix
A
pregnancy
breastfeeding
14
Q
Meglitinides MOA
A
like sulfonylureas
15
Q
When to give meglitinides instead?
A
for erratic lifestyles
16
Q
Meglitinide SEs
A
weight gain, hypoglycaemia (less than sulfonylureas)
17
Q
Glitazones SE
A
weight gain, fluid retention, liver dysfunction, fractures
18
Q
Glitazones MOA
A
PPAR gamma and alpha agonism
19
Q
Gliptins MOA
A
DPP-4 inhibitor, increases peripheral incretin levels
20
Q
Gliptins SE
A
pancreatitis
21
Q
Acarbose MOA
A
intestinal alpha glucosidase inhibitor
22
Q
Acarbose SE
A
increased delivery of carbs to colon –> flatulence, diarrhoea
23
Q
GLP-mimetics - when to give and how
A
exenatide (must be given within 60 mins pre-morning/evening meals), liraglutide (just OD). Must be combined with metformin + sulfonylurea.
Indicated if BMI>35, or if insulin is unacceptable
24
Q
GLP- mimetics SE
A
nausea, vomiting, pancreatitis, renal impairment
25
Do gliptins cause weight gain?
no
26
Do gliptins cause hypoglycaemia
no
27
SGLT-2 inhibitor action
reversible inhibition of sodium glucose contransporter at PCT
28
SGLT-2 inhibitor SEs
urinary/genital infections
Fournier's gangrene
ketoacidosis
lower-limb amputations
weight loss
29
Thiazolidinediones MOA
PPAR-gamma agonism,
act on intracellular nuclear receptors, reduce peripheral insulin resistance
30
Thiazoliniediones SE
weight gain, LFT derangement, fluid retention (worsened with insulin which itself has potential of causing fluid retention), fractures, bladder Ca
31
Contraix for thiazolinediones
HF
32
HbA1c % to mmol/mol conversion
(Average BM=2*HBA1c (%) -4.5).
6%=42mmol/mol, add 11mmol/mol for every %
33
What causes lower-than-expected HbA1c?
(dependent on RBC lifespan, so anything causing shortened RBC lifespan)
Sickle cell, G6PD def, hereditary spherocytosis, haemodialysis
34
What causes higher than expected HbA1c?
Vit B12/folate def, IDA, splenectomy
35
At what HbA1c do you add a 2nd drug for pts on metformin?
58 (7.5%)
36
How often do you monitor HbA1c after adding 2nd drug on top of metformin?
every 6 months, 3-6 months until stable
37
What HbA1c target do you go for when on a drug causing hypoglycaemia?
53 (7%)
38
When to give SGLT-2 in T2DM
As 2nd line, if QRISK>10%, CVD/IHD, HF
39
When to give GLP-1 mimetic?
4th line in T2DM, switch one of 3 drugs with GLP-1 mimetic
40
How to start insulin for T2DM on metformin?
continue metformin,
start with human NPH insulin (isophane, intermediate-acting), taken at bed-time/twice daily
41
Rules for metformin during ramadan?
metformin doses should be split 1/3 before sunrise, 2/3 after sunset
42
Rules for sulfonylureas in Ramadan
give for after sunset
43
Food with high glycaemic index
white rice, baked potato, white bread
44
Food with medium glycaemic index
couscous, boiled new potato, digestive biscuits, brown rice, porridge
45
Food with low glycaemic index
fruit, veg, peanuts
46
How to treat peripheral neuropathy
Amitriptyline, duloxetin, gabapentin, pregabalin (try 3 other 3 drugs if 1st is ineffective)
Tramadol as rescue therapy for severe neuropathic pain
topical capsaicin for localised pain
pain management clinics
47
T2DM related gastroparesis sx
erratic blood glucose control, bloating, vomiting
48
Rx for T2DM relatedd gastroparesis
metoclopramide, domperidone, erythromycin
49
Forms of GI autonomic neuropathy in diabetes
gastroparesis
chronic diarrhoea (at nigh)
GORD (reduced lower oesophageal sphincter pressure)
50
Diabetic foot disease Rx
screening on annual basis for ischaemia (by palpation of DP, PT pulses) and neuropathy (10g monofilament)
51
Mortality in HHS
20%
52
precipitants of HHS
intercurrentillness
dementia
sedatives
53
HHS sx
over many days, dehydration, polyuria, polydipsia, lethargy, N&V, reduced GCS, focal neuro, hyperviscosity.
54
Dx for HHS
hyperglycaemia (>30),
hyperosmolality (>320)
no ketoacidosis.
55
HHS Rx
fluids
insulin only if BMs don't fall to IVF
VTE prophylaxis
56
HHS complications
hyperviscosity-related (infarcts etc)
57
When to add metformin in T1DM?
if BMI>25 as likely to have insulin resistance too
58
how are ketones produced in DKA
by uncontrolled lipolysis → excess free fatty acids → ketone bodies (beta hydroxybutyrate, acetoacetate).
59
Precipitants of DKA
infection, missed insulin, MI
60
DKA sx
abdo pain, polyuria, polydipsia, dehydration, Kussmaul respiration, acetone-smelling breath
61
Dx for DKA
glucose>11
pH<7.3
bicarb<15
ketones>3/ketonuria++
62
Rx for DKA
IVF 1st
0.1unit/kg/hr fixed rate insulin
once BM<14, 10% dextrose at 125ml/hr with saline
Monitor K (may need KCL if K 3.5-5.5)
63
DKA resolution
pH>7.3
ketones<0.6
bicarb>15
Eating and drinking
(should resolve within 24hrs)
Switch to SC insulin
64
Compl of DKA
gastric stasis, VTE, arrhythmias (2ndarly to hyperK/hypoK), cerebral oedema (children esp vulnerable with IVF esp 4-12hrs post fluids), hypoK, hypoglycaemia, ARDS, AKI
65
Causes of hypoglycaemia
insulinoma (increased ratio of proinsulin to insulin), insulin/sulfonylureas, liver failure, addison’s, alcohol (exaggerated insulin secretion, effect of alcohol on pancreatic microcirculation, redistribution of pancreatic blood flow from exocrine into endocrine parts), nesidioblastosis (beta cell hyperplasia)
66
Hormones in response to hypoglycaemia
reduced insulin, increased glucagon, GH, cortisol later released, increased SNS.
67
Rx for hypoglycaemia
in community, oral glucose 10-20g/glucogel/dextrogel. In hospital, if alert as community, if unconscious/no swallow, IV 20% glucose or IM/SC glucagon
68
Insulinoma sx, assx
neuroendocrine tumour from pancreatic islets of langerhans cells. Most common pancreatic endocrine tumour. 10% malignant, 10% multiple. 50% MEN1 assx.
Sx: Hypoglycaemia early in morning, just before meal, rapid weight gain, high insulin, raised proinsulin:insulin ratio, high C-peptide.
69
Dx of insulinoma
supervised, prolonged fasting (up to 72hrs)
CT pancreas
70
Rx for insulinoma
surgery
diazoxide, somatostatin if not for surgery
71
Addison's sx
Sx: lethargy, weakness, anorexia, N&V, weight loss, ‘salt-craving’, hyperpigmentation (palmar creases), vitiligo, loss of pubic hair in women (DHEA deficiency due to loss of functioning adrenal tissue and androgen deficiency), hypotension, hypoglycaemia, hypoNa, hyperK
72
Causes of Addison's
autoimmune 80% in UK.
Primary: TB, mets, meningococcal septicaemia (Waterhouse-Friderichsen syndrome), HIV, antiphospholipid, Nelson’s syndrome (post-b/l adrenalectomy)
Secondary: pituitary disorders (tumours, irradiation, infiltration). Exogenous steroids.
73
Addisonian crisis sx:
collapse, shock, pyrexia
74
Causes of Addisonian crisis
sepsis/surgery, adrenal haemorrhage (Waterhouse-Friderichsen), steroid withdrawal.
75
Addisonian crisis Rx
IV/IM Hydrocortisone 100mg 6hrly until stable then oral replacement after 24hrs, Fluids.
76
List steroids from Most MR/least GR activity to least MR/most GR activity
fludrocortisone, hydrocortisone, prednisolone, dexamethasone/betmethasone
77
SE of steroids
DM, weight gain, hirsutism, hyperlipidaemia, Cushing’s, osteoporosis, proximal myopathy, avascular necrosis of femoral head, infection, TB reactivation, psychosis, depression, mania, insomnia, peptic ulcers, pancreatitis, glaucoma, cataracts, growth suppression, intracranial HTN, neutrophilia, fluid retention, HTN.
78
When to do gradual withdrawals for steroids
if >40mg OD for >1wk/ >3wks Rx/ repeated courses
79
How common is a pituitary adenoma
10% of pop
80
How to classify pituitary adenomas
Micro <1cm, macro >1cm.
Functioning/non-functioning.
81
Rx for pituitary adenomas
dopamine agonists for prolactinomas
somatostatin analogues for GH-secreting adenomas
cortisol synthesis inhibitors for ACTH-secreting adenomas.
Transsphenoidal surgery, radiotherapy.
82
Where is prolactin produced
anterior pituitary
83
What inhibits prolactin
dopamine
84
Causes of high prolactin
prolactinoma, pregnancy, oestrogens, physiological (stress, exercise, sleep), acromegaly (⅓), PCOS, primary hypothyroidism (TRH stimulates prolactin release), dopaminergic antagonists (metoclopramide, domperidone), antipsychotics (phenothiazines, haloperidol), SSRIs, opioids
85
Acromegaly sx
coarse facial features, spade-like hands, increased shoe size, macroglossia, prognathism, interdental spaces, excessive sweating, oily skin (sweat gland hypertrophy), features of pituitary tumour, raised prolactin in ⅓ (with galactorrhoea), 6% MEN1.
86
Acromegaly complications
HTN, DM (>10%), CDM, colorectal Ca (colonoscopy at 40 + surveillance)
87
Acromegaly ix
IGF-1 levels,
then OGTT to confirm diagnosis (GH should be suppressed in normal, but no suppression in acromegaly, IGT also assx with acromegaly)
88
Acromegaly Rx:
trans-sphenoidal surgery.
somatostatin analogue (octreotide, directly inhibits GH release, effective 50-70%, as adjunct to surgery or used if inoperable)
pegvisomant OD SC (GHr antagonist, reduces IGF-1 levels in 90%, no size reduction)
dopamine agonists (bromocriptine, only in minority), external irradiation (for older patients)
89
MODY inheritance pattern
autosomal dominant
90
Dx of MODY
genetic testing
91
MODY Rx
sulfonylureas
92
MODY 3
(60%): HNF1A, progressive, higher risk for complications, Rx: low-dose sulfonylureas
93
MODY1
HNF4A, progressive, reduced endogenous insulin secretion, higher risk for complications
94
MODY 2
(20%): GCK, stable, fasting hyperglycaemia. Rx: none required
95
MODY4 gene
PDX1
96
MODY5 gene
HNF1B
97
LADA sx + dx
often misdiagnosed as t2dm, presents younger in life, without increased body habitus, insulin not required in early stages. Often with other autoimmune diseases.
Dx: Glutamic acid decarboxylase autoantibodies.
98
Causes of cranial DI
idiopathic
post head injury
pituitary surgery
craniopharyngiomas
infiltrative
histiocytosis X
sarcoidosis
DIDMOAD is the association of cranial Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy and Deafness (also known as Wolfram's syndrome)
haemochromatosis
99
Causes of nephrogenic DI
genetic:
more common form affects the vasopression (ADH) receptor
less common form results from a mutation in the gene that encodes the aquaporin 2 channel
electrolytes
hypercalcaemia
hypokalaemia
lithium
lithium desensitizes the kidney's ability to respond to ADH in the collecting ducts
demeclocycline
tubulo-interstitial disease: obstruction, sickle-cell, pyelonephritis
100
Rx for nephrogenic DI
thiazides, low salts
101
What does prolactin do
stimulates breast development, milk production, reduces GnRH pulsatility at hypothalamus, blocks action of LH on ovary/testes.
102
What is prolactin stimulated by
TRH, pregnancy, oestrogen, breastfeeding, sleep, stress, metoclopramide, antipsychotics
103
PTH actions
increases Ca, reduces PO4, increases renal Ca reabsorption, osteoclast activity (indirectly), renal 1 alpha hydroxylation of 25-hydroxycholecalciferol, reduces renal PO4 reabsorption
104
1, 25 dihydroxycholecalciferol actions
increases Ca, PO4, increases renal tubular reabsorption, gut absorption of Ca, increases osteoclast activity, increases renal PO4 reabsorption in proximal tubule
105
1,25 dihydroxycholecalciferol actions
increases Ca, PO4, increases renal tubular reabsorption, gut absorption of Ca, increases osteoclast activity, increases renal PO4 reabsorption in proximal tubule
106
Where is calcitonin from?
C cells in thyroid
107
Calcitonin actions
inhibits osteoclasts
inhibits renal tubular Ca absorption
108
Sx of hypoCa
Tetany, perioral paraesthesia, depression, cataracts, prolonged QTc, Trosseau’s sign (95%), Chvostek’s sign (70%) (Trousseau’s more sensitive)
109
Causes of hypoCa
Vit D def, CKD, hypoPTH (post-surgery), pseudohypoparathyroidism (target cells insensitive to PTH), rhabdomyolysis (initial stages), hypoMg (end-organ PTH resistance), massive blood transfusions, acute pancreatitis
Hungry Bone Syndrome:
110
What is hungry bone syndrome
rare, post-parathyroidectomy. Long-standing hyperPTH → high pre-op PTH levels → constant osteoclast activity + hyper Ca, bone demineralisation → parathyroidectomy + PTH falls rapidly → bones re-mineralise rapidly → hypoCa
111
How to treat for hypoCa
IV Ca Gluconate (10ml 10% 10mins) if severe with sx, with ECG changes
112
Causes of hyperCa from malignancy
PTHrP from tumour (eg squamous cell lung ca)
Bone mets
Myeloma (osteoclastic bone resorption by cytokines released from myeloma cells)
113
Comonest cause of hyperCa in hospitalised and non-hospitalised
hospitalised: primary hyperPTH
non-hospitalised: malignancy
114
causes of hyperCa
HyperPTH
Malignancy
granulomas (sarcoidosis, TB, histoplasmosis)
vit D intoxication
acromegaly
thyrotoxicosis
addison’s
milk-alkali syndrome
chronic Paget’s (with prolonged immobilisation)
dehydration
thiazides
calcium-containing antacids
115
Rx of hyperCa
rehydration with saline (3-4l/day), then bisophosphonates (max effect at 7 days), consider calcitonin (quicker than bisphosphonates), steroids (if sarcoidosis), furosemide (esp if cannot tolerate fluid rehydration)
116
Causes of primary hyperPTH
85% solitary adenoma, 10% hyperplasia, 4% multiple adenoma, 1% carcinoma
117
Assx of primary hyperPTH
HTN, MEN I and II, peptic ulceration (hyperCa stimulates gatrin secretion, increases gastric acid production)
118
Ix of primary hyperPTH
low PO4
urine calcium:creatinine clearance ratio>0.01
technetium-MIBI subtraction scan
XR: pepperpot skull, osteitis fibrosa cystica
119
Rx for primary hyperPTH
Surgery (total parathyroidectomy) if: Ca>1 above normal, calciuria>400, creat clearance <30% of normal, life threatening hyperCa, nephrolithiasis, age<50, neuromuscular sx, bone mineral density reduction in femoral neck, lumbar spine, distal radius with T score <-2.5
Give cinacalcet if not for surgery (calcimimetic with allosteric activation of Ca-sensing receptor)
120
PO4 and vitD levels in secondary hyperPTH
high PO4, low vit D
121
Indications for surgery in secondary hyperPTH
bone pain
persistent pruritis
soft tissue calcifications
122
What happens in tertiary hyperPTH
ongoing hyperplasia of PTH glands after correction of underlying renal disorder.
123
PO4 in primary hyperPTH vs tertiary hyperPTH
PO4 low in primary, high in tertiary
124
Rx for tertiary hyperPTH
allow 12 months post-transplant for resolution by itself, then consider surgery
125
Benign familial hypocalciuric hypercalcaemia
Aut Dom
urine Ca:creatinine clearance ratio <0.01
126
Cause of hypoPTH
2ndary to surgery
127
Rx for hypoPTH
alfacalcidol
128
PseudohypoPTH - what causes it
target cells insensitive to PTH, due to G protein abnormality
Aut Dom.
129
Types of pseudohypoPTH
Type I: complete receptor defect
Type II: receptor still intact
130
Sx for pseudohypoPTH
low IQ
short stature
shortened 4th, 5th metacarpals
obesity
round face
low Ca
high PO4
high PTH
131
Dx and Ix for peudohypoPTH
urinary cAMP, PO4 levels post PTH infusion. Rises in true hyperPTH. PseudohypoPTH type I: neither cAMP/PO4 rises. PseudohypoPTH type II: cAMP rises
132
PseudopseudohypoPTH
normal biochemistry but just phenotypes of pseudohypoPTH
133
Hashimoto's
(chronic autoimmune thyroiditis), may be acutely transiently hyperthyroid. 10x more common in women. Sx: firm, non-tender goitre. anti-TPO and thyroglobulin abs. Assx: autoimmune, MALT lymphoma
134
Riedel's thyroiditis
rare, dense fibrous tissue replacing normal parenchyma. Sx: hard, fixed, painless goitre, middle-aged women, retroperitoneal fibrosis
135
Pendred's syndrome genetics
aut rec, SLC26A4 mutation in PDS gene, Chr 7.
136
Pendred's syndrome sx
Defect in iodine organification. b/l sensorineural deafness, progressive, delay in academic progression, exacerbated by head trauma (avoid contact sports). Mild hypothyroid/euthyroid with goitre.
137
Ix for pendred's syndrome
perchlorate discharge test (TFTs often normal), genetic testing, auudiometry, MRI (one and a half turns in cochlea instead of two and a half turns).
138
Rx for Pendred's syndrome
Thyroid hormones
Cochlear implants
139
Subclinical hypoThyroidism TFTs
raised TSH
normal T3, T4
Risk of progressing to hypothyroidism, which is increased with presence of autoantibodies
140
Rx for subclinical hypothyroidism
If TSH>10: Start levothyroxine if TSH >10 on 2 separate occasions 3 months apart.
If TSH 5.5-10:
6-month trial of levothyroxine on 2 separate occasions 3 months apart + age <65yrs + symptomatic
Age >65yrs watch and wait
Asymptomatic → observe + rpt TFTs in 6 months
141
When to start levothyroxine on lower starting doses (25mcg OD) in hypothyroidism
elderly
IHD
142
How often do you check TFTs when treating for hypothyroidism
8-12 wks
143
In pregnancy how much do you increase levothyroxine dose
at least 25-50mcg
144
SE of levothyroxine
hyperthyroidism, reduced bone mineral density, angina worsening, A fib. Iron, calcium carbonate reduces absorption so give at least 4 hrs apart.
145
Skin manifestations of hypothyroidism
dry (anhydrosis), cold, yellowish skin, non-pitting oedema, dry, coarse scalp hair, loss of lateral aspect of eyebrows, eczema, xanthomata, pruritis (in hyperthyroid too)
146
Commonest cause of hyperthyroidism
Grave's
147
Grave's disease sx
most common, 30-50 yr old women. Triad: eyes (exopthalmos, opthalmolplegia), shins (pretibial myxoedema), Acropachy (clubbing, soft tissue swelling of hands/feet, periosteal new bone formation).
148
Abs in Grave's
anti-TSH receptor (90%), anti-TPO (75%).
149
Ix in Grave's
thyroid scintigraphy shows diffuse, homogenous, increased uptake
150
Thyroid eye disease sx
25-50%, due to anti-TSHr → inflammation
Sx: exophthalmos, conjunctival oedema, optic disc swelling, ophtalmoplegia, exposure keratopathy
151
RF for thyroid eye disease
Smoking, radioiodine.
152
Rx for thyroid eye disease
stop smoking
topical lubricants
steroids
radiotherapy
surgery
153
Compl of thyroid eye surgery
exposure keratopathy (commonest)
optic neuropathy (most serious, compression of optic nerve at apex of orbit by extraocular muscles, requiring urgent intervention)
strabismus
diplopia
154
When to get urgent ophthalm r/v in thyroid eye disease
(3Ds, 3Cs) deterioration in vision, disc swelling, de-eye (eye pop out), corneal opacity, cornea visible when eye closed, colour vision change.
155
Rx for Grave's disease
propanolol initially for sx control
anti-thyroid drug therapy
block-and-replace
radioiodine
156
Describe Anti-thyroid drug therapy
start carbimazole 40mg OD, reduce gradually, for 12-18 months
fewer SE than block-and-replace
157
Describe Block-and replace therapy
carbmazole 40mg OD, thyroxine added when euthyroid, lasts 6-9 months
158
When to use radioiodine for Grave's?
if relapse/resistant to ATD
159
Contraix for radioiodine
pregnancy (avoid conception 4-6 months post Rx)
Age<16yrs
Thyroid eye disease (relative contraix)
160
Carbimazole MOA
blocks TPO from coupling and iodinating tyrosine residues on thyroglobulin
161
carbimazole SE
agranulocytosis
crosses placenta
162
Toxic multinodular goitre
autonomously functioning nodules.
Ix: nuclear scintigraphy showing patchy uptake.
Rx: radioiodine.
163
subacute (de quervain's) thyroiditis:
post-viral infection, raised ESR
4 phases: Hyperthyroid (3-6wks) → euthyroid (1-3wks) → hypothyroid (wks-months) → normal.
Ix: scintigraphy shows globally reduced uptake.
Rx: self-limiting. Steroids if severe (esp if hypothyroid). aspirin/NSAIDs for pain
164
Thyroid storm precipitants
thyroid/non-thyroidal surgery, trauma, infection, acute iodine load (eg contrast)
165
Sx of thyroid storm
fever, tachycardia, confusion, N&V, HTN, HF, jaundice, LFTs deranged
166
Rx for thyroid storm
treat underlying + IV propranolol + propylthiouracil/methimazole + Lugol’s iodine + IV dexamethasone (4mg QDS)/hydrocortisone (blocks T4 conversion to T3)
167
Sick euthyroid syndrome TFTs
Either all TSH, T4, T3 low or TSH normal + others low
168
Forms of thyroid cancer
Papillary 70%
Follicular 20%
Medullary 5%
Anaplastic 1%
Lymphoma
169
Papillary thyroid cancer
70%, young females, excellent prognosis. Mixture of papillary and colloidal filled follicles. Histology: papillary projections, pale empty nuclei. Seldom encapsulated. LN mets predominate, haematogenous mets rare. Rx: total thyroidectomy + radioiodine, yearly thyroglobulin levels
170
Follicular thyroid cancer
May be macroscopically encapsulated, microscopically capsular invasion seen (adenoma has no capsular invasion). Vascular invasion predominates. Rare multifocal disease. Rx: total thyroidectomy, radioiodine, yrly thyroglobulin levels
171
Follicular thyroid adenoma
Follicular adenoma - usually solitary thyroid nodule, need histological assessment to exclude carcinoma
172
Medullary thyroid cancer
C cells (parafollicular) from neural crest (not thyroid tissue), raised calcitonin, MEN2 assx (familial 20%). Both LN + haematogenous mets. Nodal disease - poor prognosis.
173
Anaplastic thyroid cancer
Elderly females. Local invasion common. Often Not responsive to chemo, can cause pressure sx. Rx by resection. Palliation via isthmusectomy, radiotherapy. Histology: spindle, giant cells
174
Thyroid lymphoma
rare, Hashomito’s assx (chronic infiltration of thyroid gland with B-lymphocytes, which undergo clonal proliferation, predisposing to MALT thyroid lymphoma). Histology: extranodal marginal B-cells
175
Thyroid changes in pregnancy
increased TBG, causing increased total thyroxine (free thyroxine unaffected)
176
HCG action on TSHr
can activate, causing transient gestational hypothyroidism
HCG falls in 2nd/3rd trimester
177
Rx fo thyrotoxicosis in pregnancy
propylthiouracil in 1st trimester
carbimazole in 2nd trimester
T4 should be kept in upper third of normal
Thyrotrophin receptor stimulating abs should be checked at 30-36 wks
Radioiodine and block-and-replace regimes contraindicated
178
Is thyroxine safe in pregnancy and breastfeeding?
yes to both
179
How to screen for hypothyroidism in pregnancy
TSH measured each trimester and 6-8 weeks post-partum
180
How much more thyroxine is required in pregnancy
by up to 50% as early as 4-6 wks
181
How common is gestational DM
1 in 20 pregn
182
RF for gestational DM
BMI <30, previous macrosomic baby >4.5kg, previous gestational diabetes, 1st deg relative with diabetes, ethnicity (South Asian, black Caribbean, Middle Eastern).
183
How to screen and dx gestational dm
GTT (women with past GDM get OGTT after booking + at 24-28wks, others get it at 24-28wks).
Dx: 5678 fasting glucose >5.6, 2-hr glucose >7.8.
184
Rx of gestational DM
if fasting glucose <7, diet → metformin if target not met within 1-2 wks → insulin. If fasting glucose >7, insulin. If 6-6.9 but complications such as macrosomia/hydramnios, give insulin. Glibenclamide as alternative to insulin
185
Targets for BM management in gestational DM
Targets: (7.8 becomes post-1hr, add .3, .4 to 5,6 for fasting + post-2hrs) fasting 5.3, 1hr post meal 7.8, 2hrs post meal 6.4
186
Rx for pre-existing diabetes in pregnancy
weight loss if BMI>27, stop oral hypoglycaemics, start insulin. Folic acid 5mg/day from pre-conception to 12 wks, detailed anomaly scan at 20 wks (including 4-chamber view of heart and outflow tracts), tight glycaemic control, treat retinopathy
187
Hypertriglyceridaemia causes
DM, obesity, ETOH, Chronic renal failure, thiazides, non-selective beta blockers, unopposed oestrogen, liver disease
188
Hypercholesterolaemia causes
nephrotic syndrome, cholestasis, hypothyroid
189
When to assess for familial hypercholesterolaemia
cholesterol >7.5 or PMHx/1st deg FHx of premature IHD (<60yrs), if children of affected parents.
190
Mutation in familial hypercholesterolaemia
Aut Dom. Mutations in LDL receptor protein mutations
190
Dx of familial hypercholesterolaemia
Simon Broome criteria (cholesterol>7.5 + LDL-C>4.9, cholesterol>6.7 + LDL>4 in children, + possible/definite FHx
191
Rx for familial hypercholesterolaemia
lipid clinic, high dose statins, screening for 1st deg relatives.
192
Remnant hyperlipidaemia
rare cause of mixed hyperlipidaemia (high cholesterol + triglycerides) (Friedrickson type III hyperlipidaemia/broad-beta disease/dysbetalipoproteinaemia)
assx with apo-e2 homozygosity.
High IHD, PVD rates.
Impaired removal of intermediate density lipoprotein from circulation by liver.
Sx: yellow palmar creases, palmar xanthomas, tuberous xanthomas.
Rx: fibrates
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Hyperuricaemia assx
hyperlipidaemia
HTN
metabolic syndrome
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Causes of hyperuricaemia
Increased synthesis: Lesch-Nyhan, myeloproliferative disorders, purine-rich diet, exercise, psoriasis,cytotoxics
Reduced excretion: low-dose aspirin, diuretics, pyrazinamide, pre-eclampsia, ETOH, renal failure, lead
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Klinefelter's
47 XXY, taller than average, lack of secondary sexual characteristics, small, firm testes (no cryptorchidism), infertile, gynaecomastia (breast Ca risk), elevated gonadotrophin levels, low testosterone. Dx by karyotype
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Kallman's
X recessive. Failure of GnRH neurons to migrate to hypothalamus. Sx: delayed puberty, hypogonadism, cryptorchidism, anosmia, low sex hormones, low gonadotrophins, normal/above-average height, cleft lip/palate, visual/hearing defects. Rx: testosterone and gonadotrophin supplementation
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RF for urinary inncontinence
age, past pregnancy/childbirth, high BMI, hysterectomy, FHx.
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Ix for urinary incontinence
bladder diaries 3 days, vaginal exam, urine dip + MSU, urodynamic studies
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Describe urge incontinence
detrusor overactivity, urge followed by uncontrollable leakage from few drops to complete emptying
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Rx for urge incontinence
bladder retraining 6 wks min. Antimuscarinics - oxybutynin, (immediate release, contraix in frail, due to risk of delirium, impairment of daily functions), tolterodine (immediate release), darifenacin (OD preparation). Mirabegron (beta 3 agonist, caution in frail)
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Describe stress incontinence
leakage when coughing/laughing
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Rx for stress incontinence
pelvic floor training >8 contractions TDS min 3 months, surgical (retropubic mid-urethral tape procedures), duloxetine (SNRI, increases synaptic conc of noradrenaline and serotonin within pudendal nerve, → increases urethral striatal muscle stimulation in sphincter → enhanced contraction)
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what causes overflow incontinence
bladder outlet obstruction
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Functional incontinence
comorbidities impair ability to get to bathroom in time. Causes: dementia, sedation, injury/illness affecting ambulation
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Autoimmune polyendocrinopathy syndromes
Type 1: Multiple Endocrine Deficiency Autoimmune Candidiasis (MEDAC), Aut rec AIRE1 gene mut, Chr 21. ⅔ of Chronic mucocutaneous candidiasis (in young child), Addison’s, primary hypoparathyroidism
Type 2: Schmidt’s syndrome, more common, polygenic, HLA DR3/4 assx, Addison’s + T1DM + autoimmune thyroid.
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Multiple Endocrine Neoplasia
MEN Type I: MEN1 gene, hyperCa most common presentation. 3Ps: hyperPTH (95%), Pituitary tumours (70%), Pancreatic tumours (50%, insulinoma/gastrinomas), adrenal, thyroid tumours
MEN Type IIa: RET oncogene, 1 M, 2Ps: Medullary thyroid Ca (70%, papillary also assx), hyperPTH, Phaeochromocytoma
MEN Type IIb: RET, 2Ms, 1P: Medullary thyroid Ca, Marfanoid body habitus, Phaeochromocytoma
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Phaeochromocytoma assx
MEN II
NF
von Hippel-Lindau
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Phaeo sx
10% rule: bilateral, malignant, familial, extra-adrenal (most common site: organ of Zuckerkandl, adjacent to aortic bifurcation)
Sx: HTN (90%), headaches, palpitations, sweating, anxiety
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Phaeo dx
24-hr urinary metanephrines
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Rx for phaeo
alpha (phenoxybenzamine) then beta blockade + surgery
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Dynamic pituitary function testing
: Give insulin, TRH, LHRH, record glucose, cortisol, GH, TSH, LH, FSH, sometimes prolactin. Rises: GH>20, cortisol>550, TSH>2, LH, FSH double
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Insulin stress test
to investigate hypopituitarism. IV insulin → measure GH, cortisol (should rise normally, due to hypoglycaemia).
Contraix: epilepsy, IHD, adrenal insufficiency
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Causes of hyponatraemia with urinary Na >20
Hypovolaemic: thizides, loop diuretics, Addison’s, diuretic stage of renal failure
Euvolaemic: SIADH, hypothyroidism
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SIADH causes
Cancer (small cell lung, pancreas, prostate), Neuro (stroke, SAH, SDH, meningitis/encephalitis/abscess), Infections (TB, pneumonia), Drugs (VASCC - Vincristine, anti-depressants (TCAs, SSRIs), sulfonylureas, carbamazepine, cyclophosphamide), PEEP, prophyrias.
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Ix for SIADH
high urinary Na + osmol
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Rx for SIADH
slow correction, fluid restrict, demeclocycline (reduces collecting tubule responsiveness to ADH), ADH receptor antagonists
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How to Rx for hypoNa
Chronic without severe sx: fluids if hypovolaemic. Fluid restrict if euvolaemic, + democlocycline, vaptans (V2 antagonists). Fluid restrict + diuretics/vaptans if hypervolaemic.
Acute with severe (<120)/symptomatic: HDU monitoring, hypertonic saline (3% NaCl)
Compl: central pontine myelinolysis: astrocyte apoptosis, demyelination. Locked in syndrome
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Causes of hypoNa with urinary Na<20
Extra-renal losses: diarrhoea, vomiting, sweating, burns, rectal adenoma
Water excess (Hypervolaemic): HF, cirrhosis, nephrotic syndrome, IV dextrose, psychogenic polydipsia
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Causes of hypoK with HTN
Cushing's
Primary hyperaldosteronism
Liddle's
11 beta hydroxylase def
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Causes of hypoK without HTN
diuretics
GI loss
RTAs
Bartter's
Gitelman's
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Causes of hypoK with alkalosis
vomiting
diuretics
Cushing's
Conn's
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Causes of hypoK with acidosis
diarrhoea
RTA
acetazolamide
patially treated DKA
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Causes of Cushing's syndrome
ACTH-dependent: Cushing’s disease (80% - ACTH secreting pituitary tumour), ectopic (5-10%, small cell lung ca commonest cause, with very low K levels)
ACTH-independent: iatrogenic (commonest, steroids), adrenal adenoma (5-10%), adrenal carcinoma (rare), micronodular adrenal dysplasia
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Pseudo-Cushing's
mimics Cushing’s, due to ETOH excess/severe depression, false +ve dexamethasone suppression test/24hrs urinary free cortisol. Ix: insulin stress test required
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Carney's syndrome
cardiac myxoma with pituitary adenoma
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Ix for Cushing's syndrome
low-dose (overnight) dexamethasone suppression test (no suppression in Cushing’s syndrome), 24-hr urinary cortisol x2, bedtime salivary cortisol x2.
Localisation tests:
9am and midnight plasma ACTH + cortisol levels: if ACTH suppressed, non-ACTH dependent cause likely
High-dose dexamethasone suppression test: If cortisol suppressed, Cushing’s disease (pituitary adenoma). If ACTH suppressed, Ectopic ACTH syndrome. If ACTH suppressed but cortisol not suppressed, Cushing’s syndrome due to other causes (eg adrenal adenomas)
CRH stimulation: if pituitary source, cortisol rises. If ectopic/adrenal then no change
Petrosal sinus sampling of ACTH to differentiate between pituitary and ectopic ACTH secretion
Insulin stress test: differentiate between Cushing’s and pseudo-Cushing’s
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Causes of primary hyperaldosteronism
b/l idiopathic adrenal hyperplasia (60-70%), adrenal adenoma (Conn’s - 20-30%), unilateral hyperplasia, familial hyperaldosteronism, adrenal carcinoma
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Ix for primary hyperaldosteronism
high aldosterone/renin ratio (-ve feedback due to Na retention lowers renin), high-res CT abdo, adrenal being sampling (differentiates unilateral and b/l sources).
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Rx for primary hyperaldosteronism
surgery for Conn’s, spironolactone for b/l adrenocortical hyperplasia
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Liddle's syndrome
aut dom, DCT epithelial Na channel defect causing increased Na reabsorption, hyperNa, hypoK, alkalosis, HTN. Low renin+low aldosterone.
Rx: amiloride/triamterene (K-sparing)
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What kind of acidosis does RTA cause?
hyperchloraemic metabolic acidosis, with normal AG
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Type 1 RTA
(A for ACID) cannot generate acid urine in distal tubule. hypoK. Compl: nephrocalcinosis/stones (Ca PO4 stones have increased tendency to be deposited at higher pHs). Causes: (A for Autoimmune causes) idiopathic, Rh arth, SLE, Sjogren’s, amphotericin B toxicity, analgesic nephropathy
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Type 2 RTA
(B for BICARB) reduced HCO3- reabsorption in proximal tubule. hypoK. Compl: (B for Bones) osteomalacia. Causes: idiopathic, Fanconi’s syndrome, Wilson’s disease, cystinosis, outdated tetracyclines, carbonic anhydrase inhibitors
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Type 3 RTA
mixed. Extremely rare, carbonic anhydrase II deficiency. HypoK
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Type 4 TA
hyperK. Reduced aldosterone → reduced proximal tubular ammonium excretion. Causes: hypoaldosteronism, DM
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Barrter's syndrome
Aut rec, defective Cl absorption at Na/K/Cl co-transporter (NKCC2) in ascending loop of Henle (like furosemide) Sx: normotensive, childhood presentation, polyuria, polydipsia, hypoK, weakness
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Gitelman's
aut rec, def in thiazide-sensitive Na/Cl transporter in DCT (like thiazides). Sx: normotension, hypoK, hypocalciuria, hypoMg, metabolic alkalosis
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Bartter's vs Gitelman's sx
Bartter’s has more polyuria, polydipsia, Gitelman’s has more hypoMg, hypocalciuria (with hyperCa)
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ECG for hyperK
tented T, small P, broad QRS, sinsoidal pattern, asystole.
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Causes of hyperK
AKI, K sparing diuretics, ACEi, ARBs, ciclosporin, beta blockers, heparin (inhibits aldosterone), metabolic acidosis, Addison’s, rhabdomyolysis, massive transfusions. Foods (bananas, oranges, kiwi fruit, avocado, spinach, tomatoes)
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Pseudohyperkalaemia
excessive K leakage from cells during or after blood being taken.
Causes: haemolysis during venepuncture (excessive vacuum, prolonged tourniquet use, needle gauge too small), delay in processing specimen, high platelet, leukocyte, RBC count, familial.
Rx: get ABG or request slow spin
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Galactosaemia
Aut rec. Galctose-1-phosphate uridyl transferase absence → galactose-1-phosphate. Sx: jaundice, failure to thrive, hepatomegaly, cataracts, hypoglycaemia post galactose exposure, Fanconi’s syndrome. Dx: urine reducing substances. Rx: galactose-free diet
242
Primary amenorrhoea definition
no periods by 15yrs with normal 2ndary sexual characteristics/13yrs with no 2ndary sexual characteristics
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Causes of primary Amenorrhoea
gonadal dysgenesis (Turner's)
Androgen insensitivity syndrome
Congenital genital tract malformations
Functional hypothalamic amenorrhoea
Congenital adrenal hyperplasia
Impeforate hymen
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Androgen insensitvity syndrome
X recessive. 46XY.
Sx: primary amenorrhoea, little/no axillary/pubic hair. Groin swellings. Breast development.
Dx: buccal smear/chromosomal analysis. High-normal testosterone for post-pubertal.
Rx: counselling, b/l orchidectomy (increased testicular Ca risk), oestrogen therapy
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Congenital adrenal hyperplasia
aut rec disorders. Low cortisol, high ACTH, high androgens. 21-hydroxylase def (90%), 11-beta hydroxylase def (5%, HTN due to excess deoxycorticosterone), 17-hydroxylase def (very rare, low androgens, mineralocorticoid excess). Sx: virilization, salt-wasting (75%), precocious puberty, infertility. Dx: ACTH stimulation testing (increased 17-hydroxyprogesterone). Rx: steroid replacement
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Rx for primary amenorrhoea and SE
Hormone replacement therapy (HRT)
SE: nausea, breast tenderness, fluid retention, weight gain.
Compl: breast Ca risk (increased with progestogen), endometrial Ca (reduced with progestogen), VTE (increased with progestogen), stroke, IHD
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Secondary amenorrhoea definition
periods stop for 3-6 months with normal menses/6-12 months with oligomenorrhoea
248
Causes of secondary amenorrhoea
hypothalamic (2ndary to stress/excessive exercise)
PCOS
Hyperprolactinaemia
premature ovarian insufficiency
hypo/hyperthyroid
Sheehan's
Asherman's
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PCOS Rx
Rx: weight reduction, COCP.
Hirsutism/acne Rx: COCP, topical eflornithine, spironolactone, flutamide, finasteride under supervision.
Infertility Rx: weight loss, clomifene, metformin (esp if obese), gonadotrophins
250
Premature ovarian insufficiency
elevated gonadotrophins, low oestradiol, menopausal sx, pre-40yrs, 1 in 100 women. Causes: idiopathic (most common, FHx assx), b/l oophorectomy, radiotherapy, chemotherapy, infection (mumps), autoimmune, resistant ovary syndrome (FSH receptor abnormalities). Rx: HRT/COCP until menopause age
251
Metabolic syndrome
likely due to insulin resistance. Dx: waist circumference (men>102, women>88cm), high triglycerides (>1.7mmol/L), reduced HDL (<1.03 men, <1,29 women), raised BP (>130/85/HTN), fasting BM >5.6/T2DM.
Other assx: microalbuminuria, raised uric acid, PCOS, NAFLD
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HypoPO4 causes
ETOH, liver failure, DKA, refeeding syndrome, hyperPTH, osteomalacia.
253
HypoPO4 consequences
haemolysis, WBC/pltlt dysfunction, muscle weakness, rhabdo, CNS dysfunction
254
DVLA HGV licensing in relation to BM control
HGV licence possible if they are hypo aware, no hypos in last yr, demonstrate adequate control with regular BM monitoring at least BD and at times relevant to driving, demonstrate hypo risk awareness, no debarring complications
255
Orlistat
pancreatic lipase inhibitor. SE: faecal urgency/incontinence/flatulence
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Evolocumab
prevents PCSK9-mediated LDLr degradation
