Endocrinology Flashcards
(188 cards)
1
Q
What are the most likely causes of acromegaly?
A
GH secreting pituitary adenoma
GH secreting ganglioneuroma, GH-secreting bronchial CA or GH secreting pancreatic CA
2
Q
What are some signs and symptoms of acromegaly?
A
sweating
headaches
carpal tunnel syndrome
thick, greasy skin
prominent eyebrow ridge + cheeks, thick lips, broad nose, large tongue, husky voice
enlarged feet
if due to pituitary adenoma -> bitemporal hemianopia
3
Q
what are the pharmacological management options for patients wtih acromegaly?
A
subcut somatostatin analogues = octreotide, lanreotide
oral dopamine agonists = cabergoline, bromocriptine
GH antagonists = pegvisomant
4
Q
what are the common causes of adrenal insufficiency?
A
iatrogenic (after stopping long term steroid therapy or bilateral adrenalectomy)
in developing worlds -> adrenal TB
in the UK -> primary due to addison’s (autoimmune)
5
Q
what are RF for adrenal insufficiency?
A
autoimmune conditions
female
damage or pathology of adrenals
steroid therapy (long term)
6
Q
what is an adrenal crisis?
A
an acute adrenal insufficiency attack precipitated by stress (infection, surgery, emotional)
leads to major haemodynamic collapse -> hypotensive shock, tachycardia, pale, cold, oliguria, clammy
7
Q
A woman presents to the GP with a history of anorexia, weight loss, lethargy + weakness. She has had some dizzy episodes as well as diarrhea + vomiting with abdominal pain.
On examination you notice some increased pigmentation on her gums and hand creases. Her BP drops on standing indicating postural hypotension
what is the likely diagnosis?
A
adrenal insufficiency
possibly due to Addison’s (autoimmune)
KEY FEATURES: anorexia, weight loss, tired, weak, dizzy, diarrhoea and vomiting, abdo pain, depression, postural hypotension, skin pigmentation
8
Q
what electrolyte abnormality might be seen on blood results from a patient with adrenal insufficiency?
A
hyponatraemia
hyperkalaemia
9
Q
what investigations would you perform to diagnosis adrenal insufficiency?
A
9am serum cortisol (low)
short-synACTHen test -> no rise in cortisol
long synACTHen test -> just monitor for longer, no rise
bloods - autoantibodies (anti-21 hydroxylase), TFT, U&E
abdo CT, adrenal biopsy
10
Q
how do you manage an addisonian crisis?
A
- rapid IV fluid rehydration
- 50mL 50% dextrose
- IV 200mg hydrocortisone - followed by 6hr 100ml bolus till BP is stable
treat underlying cause
11
Q
how do you manage a patient with adrenal insufficiency in the long term?
A
replace glucocorticoids with HYDROCORTISONE
replace mineralocorticoids with FLUDROCORTISONE
advise: medic alert, increase dose in acute illness/stress
12
Q
what is carcinoid syndrome?
A
where a carcinoid tumour secretes serotonin, histamine and/or bradykinin leading to excess of these hormones. these high levels lead to a cluster of symptoms
13
Q
what symptoms do patients with carcinoid syndrome commonly experience?
A
diarrhoea
SOB
flushing
itching
often worse after alcohol and emotional stress
14
Q
what is a carcinoid crisis?
A
PC: profound flushing, bronchospasm, tachycardia, fluctuating BP, pyrexial
15
Q
what causes a carcinoid crisis?
A
tumour releases an overwhelming amount of the active substances usually due to tumour manipulation (e.g. surgery, biopsy) or in the induction of anaesthesia
16
Q
What is the most common cause of Cushing’s syndrome?
A
exogenous corticosteroid exposure (steroid therapies)
17
Q
ACTH dependent causes of Cushing’s?
A
cushing’s disease = ACTH secreting pituitary adenoma
ectopic ACTH production (small cell Lung CA or carcinoid tumours)
18
Q
What are ACTH independent causes of Cushing’s?
A
adrenal adenoma/cancer
adrenal nodular hyperplasia
iatrogenic (steroid therapy)
carney complex and mccune-albright syndrome [RARE]
19
Q
what are the features of cushings?
A
glucose intolerance, dyslipidaemia, weight gain (central obesity), striae, proximal myopathy, facial plethora, moon face
depression, easy bruising, hirsutism, lethargy
20
Q
what investigations would you order if you suspect cushings?
A
bloods: glucose, U&Es
late night salivary cortisol (raised)
low dose dexamethasone suppression test
24 hour urinary free cortisol
scans for tumours
21
Q
what medical therapies may be used to treat cushings?
A
stop steroids if possible
metyrapone or ketoconazole prevents cortisol synthesis
otherwise surgical intervention to remove tumour or radiotherapy
22
Q
what is the management for cranial diabetes inspidus?
A
desmopressin
23
Q
what is the management for nephrogenic DI?
A
salt +/- protein restriction
thiazide diuretics
stop any causative medications if possible e.g. lithium
24
Q
how do you manage DKA?
A
give bolus insulin then use a sliding scale infusion until ketones are <0.3, pH > 7.3, bicarb >18
fluid resuscitation with saline
potassium replacement and monitoring
close monitoring, broad spec Abx if infection suspected, thromboprophylaxis
25
what is the pathophysiology of graves disease?
TSH receptor antibodies which stimulate the receptor causing T3 and T4 production
26
how do you manage acute hypercalcaemia?
IV fluids
avoid exacerbating factors e.g. thiazides or anything dehydrating
27
what medication can be used to increase parathyroid sensitivity to calcium?
cinacalcet
28
what order are the pituitary hormones lost?
Usually lost in this order: GH → gonadotrophins (FSH + LH) → ACTH and TSH
29
what order are the pituitary hormones lost?
Usually lost in this order: GH → gonadotrophins (FSH + LH) → ACTH and TSH
30
what are the signs of hypothyroidism?
BRADYCARDIC
Bradycardia
Reflexes relax slowly
Ataxia
Dry thin hair/skin
Yawn, drowsy, coma
Cold hands and low temperature
Ascites + non pitting oedema
Round puffy face, double chin, obese
Defeated demeanor (depression)
Immobile + ileus (constipation)
Congestive cardiac failure
31
what are some causes of hypothyroidism?
```
autoimmune thyroiditis (hashimoto's disease)
thyroidectomy/radiotherapy/iodine therapy for hyperthyroidism
```
amiodarone or lithium (iatrogenic)
secondary - Sheehan's, pituitary apoplexy, head trauma
32
how do you treat hypothyroidism?
levothyroixine sodium to replace T4
if elderly or known heart disease start at a lower starting dose and titre up slowly to prevent exacerbating CVD
33
how do you treat myxoedema coma?
liothyronine sodium (T3 replacement)
hydrocortisone
correct glucose
fluids
if hypothermic warm slowly
34
what tumours are associated with MEN1?
parathyroid tumours
pituitary tumours
pancreatic tumours
35
what tumours are associated with MEN 2a?
parathyroid tumours
medullary thyroid cancer
phaeochromocytoma
36
what tumours are associated with MEN 2b?
medullary thyroid cancer
phaeochromocytoma
marfanoid appearance
37
what are the features of a phaechromocytoma?
episodes of sweating, palpitations and headaches
sporadic hypertension
38
what is osteomalacia?
a disorder of bone matrix mineralisation
39
what are RF for osteomalacia?
renal phosphate loss (excessive wasting)
vitamin D deficiency
40
what are the osteoporosis RF?
SHATTERED
Steroid use
Hyperthyroid, hyperparathyroid, hypercalciuria
Alcohol + tobacco
Thin
Testosterone low
Early menopause
Renal or liver failure
Erosive/inflammatory bone disease
Diet (low Ca2+), DM1
41
what is the origin of cells involved in a phaeochromocytoma?
catecholamine producing chromaffin cells
ADRENAL MEDULLA
42
what is Conn's syndrome?
an aldosterone producing adenoma which leads to a primary hyperaldosteronism
43
what electrolyte imbalance are patients with primary aldosteronism vulnerable to?
hypokalaemia
may become hypernatraemic
44
what diuretic is appropriate for use in patients with primary aldosteronism?
a potassium sparing diuretic such as spironolactone
45
what medication is used to manage prolactinomas?
dopamine AGONISTS
e.g. cabergoline or bromocriptine
46
what is carbemazepine used for?
it is an anti-epileptic and to treat neuropathic pain
47
what is carbimazole used for?
carbimazole is used to treat hyperthyroidism
it acts by preventing iodination of molecules so reduces the amount of T3 and T4 produced
48
what is cabergoline used for?
to treat prolactinomas as it is a dopamine agonist
it may also be used to treat excess GH (i.e. acromegaly)
49
what are the features of SIADH?
inappropriate and excessive ADH
hypotonic hyponatraemia
concentrated urine
euvolaemic state
50
what are the causes of SIADH
drugs: SSRI, amiodarone, carbamazepine, amitriptyline, NSAIDs, chemo
infections or malignancy
porphyria, alcohol withdrawal
51
what would results would one expect from investigations for a patient with SIADH?
serum sodium \< 135 (low)
serum osmolality \< 280 {low}
urine osmolality \> 100 and urine sodium \> 40 if euvolaemic
52
What are other causes of hyponatraemia that must be ruled out prior a diagnosis of SIADH?
hypovolaemia
oedema
renal failure
adrenal insufficiency
hypothyroidism
53
what is the management of SIADH?
if severe hyponatraemia (\<125) give hypertonic saline but only to stop seizures not to normalise sodium
fluid restriction
furosemide
vasopressin receptor antagonist (talvaptan)
54
what are the types of thyroid cancer?
papillary
follicular
anaplastic
medullar
55
what is the most common type of thyroid cancer?
papillary
56
where does a papillary thyroid cancer usually spread?
lymph nodes
57
how does a follicular thyroid cancer spread?
haematologically
58
what is the tumour marker for papillary and follicular thyroid cancer?
thyroglobulin
59
what is thyroglobulin a marker for?
follicular and papillary thyroid cancer
60
what is the marker for medullary thyroid cancer?
calcitonin
61
what is calcitonin a marker of?
medullary thyroid cancer
62
what are drugs that commonly cause drug-induced thyroiditis?
amiodarone, lithium and interferons
63
what is riedel's thyroiditis?
chronic thyroiditis where normal thyroid tissue is replaced with fibrotic tissue
64
what are the complications of diabetes?
microvascular = retinopathy, neuropathy, nephropathy
macrovascular = MI, stroke, PVD
metabolic = DKA, HHS, hypoglycaemia
65
What drug is used to treat prolactinoma?
cabergoline
66
zones of adrenal + hormones produced
zone glomerulosa → aldosterone
zona fasciculata → cortisol
zone reticularis → sex steroid hormones
medullar → catecholamines (e.g. NA)
67
zones of adrenal + hormones produced
zone glomerulosa → aldosterone
zona fasciculata → cortisol
zone reticularis → sex steroid hormones
medullar → catecholamines (e.g. NA)
68
acromegaly - definition + causes
excess GH in adults leading to overgrowth of all organs, bones and soft tissue
causes:
* _pituitary adenoma_
* ectopic GH (rare)
* ectopic GnRH (rare, ganglioneuroma, bronchia CA, pancreatic CA
69
key features of acromegaly presentation
* headaches
* sweating
* carpal tunnel syndrome
* visual disturbance - bitemporal hemianopia
* thick greasy skin
* prominent eyebrow ridge, broad nose bridge, prognathism
* enlarged hands + feet
70
investigations for acromegaly
* bedside
* BP, ECG (LVH), CN/visual fields
* bloods
* IGF-1 (screening)
* oral glucose tolerance test (diagnostic)
* pituitary status - TFTs, LH + FSH, Test/Oes, prolactin
* CoD screen - HbA1c/glucose, lipids, bone profile
* imaging
* MRI pituitary
* CT chest - assess for CA ectopic cause
* ECHO - LVH + cardiomegaly
71
complications of acromegaly
structural are usually irreversible so early treatment ESSENTIAL
* HTN, cardiomyopathy (LVH)
* OSA
* colon + thyroid cancer
* raised calcium, phosphate
* raised lipids
* DM/glucose intolerance
* renal stones
72
treatment of acromegaly
1. **transphenoidal hypophysectomy**
1. CoM: nasoseptal perf, hypopituitarism, recurrence, infection. CSF leak
2. medical Mx
1. SC somatostatin analogue (octreotide)
2. PO DA agonist (bromocriptine, cabergoline)
3. GH antagonist (Pegvisoman)
3. screening - monitor for DM/cardiac, colonoscopy if \> 40 and every 5 years
73
definition and causes of adrenal insufficiency
*inadequate production of cortisol _+_ mineralocorticoids from adrenal cortex*
**primary** - Addison's disease (AI destruction of cortex)
**secondary**
* infection - TB, post-meningococcal sepsis (Waterhouse-Friederichesen syndrome)
* infiltration - mets, amyloidosis, lymphoma
* infarction
* inherited - ACTH receptor mutation
* iatrogenic - bilateral adrenalectomy, _long term steroid use_
74
investigations for adrenal insufficiency
* bloods
* **9am cortisol** - \< 100nmol/L essential Ddx, 100-500 more tests, \> 500 unlikely
* autoAb - anti 21-hydroxylase, adrenal cortex Ab
* U&Es, glucose
* imaging
* CT adrenals + contrast - infection/infiltration
* specialist
* short synACTH, \< 550nmol at 30 = adrenal failure
* adrenal biopsy
75
electrolyte abnormality in adrenal insufficiency
hyponatraemia
hyperkalaemia
76
acute management of adrenal insufficiency
* fluid resuscitation 0.9% saline (bolus if needed or 1L in 1 hour)
* IM 100mg hydrocortisone
* another 100mg over 8 hours in 5% dextrose
* treat hypoglycaemia
* treat hyperkalaemia
* treat precipitating cause
77
what is carcinoid syndrome?
pathology + site
carcinoid tumours secreting vasoactive compounds e.g. serotonin
* ⅔ of neuroendocrine gastroenteropancreatic tumours
* most are _serotonin producing enterochromaffin cells_
* most common sites is liver and small intestine
78
presentation of carcinoid syndrome
* paroxysmal flushing
* diarrhoea
* palpitations
* sweating
* wheeze
* telangiectasis
* **right sided murmur**
* **carcinoid crisis** = profound flush, bronchospasm, tachy, fluctuating BP, pyrexia
79
key carcinoid syndrome Ix
* plasma chromagranin A - screening
* **24 hour urine 5-HIAA collection** (serotonin metabolic), \> 25mg strong evidence
* CT or MRI with radiolabelled somatostatin analogue (localise tumour)
80
treatment of carcinoid syndrome
1. surgical resection if possible
2. somatostatin analogue - octreotide
81
causes of cushing's syndrome
* **ACTH dependent**
* Cushing's disease → pituitary adenoma (suppressed with high dose)
* Ectopic ACTH → SCLC, carcinoid tumour, high dose fails to suppress
* **ACTH independent**
* adrenal adenoma/cancer
* adrenal nodular hyperplasia
* iatrogenic/exogenous
* Carney complex
* McCune-Albright syndrome
82
Key investigations for Cushings
diagnosis + cause
* late night 11pm salivary cortisol - screening, raised abnormal
* low dose dexamethasone suppression test (0.5mg, +ve \> 50 nanomol/L)
* inferior petrosal sinus sampling - confirm pituitary
* pituitary adenoma
* Adrenal CT
* CXR/chest CT - ectopic lung CA
complications
* BP - HTN
* glucose, lipids, U&Es
* DEXA scan
83
treatment of Cushing's syndrome
* **Iatrogenic** → stop meds, reduce dose, steroid sparing
* **Medical treatment**
* Cortisol synthesis inhibition
* **Metyrapone** or **ketaconazole**
* Enzyme inhibitors, rapid effect
* Usually ineffective long term in Cushing's disease but bridge to surgery
* **Mitotane** - adrenolytic drug
* Delayed onset, long-lasting action, effective long-term
* Optimise/manage any comorbidities
* Osteoporosis preventing - calcium + vitamin D levels, consider bisphosphonates
* **Surgical treatment**
* Trans-sphenoidal resection of pituitary adenoma
* resect/treat ectopic tumour
* Bilateral adrenalectomy
* Adrenal lesions
* May require lifelong steroid hormone replacement
84
causes of cranial DI
* Surgery (pituitary)
* Trauma
* Tumours - primary or metastases (CNS, pituitary, breast mets)
* Granulomatous infiltration
* Vascular (aneurysm's, Sheehan's syndrome)
* Inherited - AD mutation in vasopressin gene
85
causes of nephrogenic DI
* Inherited channelopathies (Rare)
* Lithium
* Demeclocycline
* Hypercalcaemia
* Post-obstructive uropathy
* Pyelonephritis
* DM - osmotic diuresis
86
key feature of pathophysiology of diabetes insipidus
Failure to respond to ADH or to produce ADH → impaired water reabsorption in the kidneys → production of large amounts of dilute urine, concentrated serum.
87
what electrolyte abnormality do DI patients have?
hypernatraemia (lethargy, thirst, irritable, confusion, coma, fits)
88
key Ix for DI
* urine osmolality - \< 2, very dilute urine
* 24 hour collection - \> 3 hours
* U&Es
* plasma osmalality - raised
* HbA1c - must exclude DM
* calcium - must exclude high calcium
* **water deprivation test**
* restrict H2O for 8 hrs
* normal - concentrate \> 600 mOsmol/kg
* primary polydipsia - 400-600
* cranial - only after desmopression
* nephrogenic - never concentrates
89
management of cranial DI
DDVAP (desmopressin) replacement
* monitor sodium every 1-3 months
90
manage of nephrogenic DI
* thiazide diuretic
91
what is the sign of active Grave's disease?
lid lag
92
what is Grave's disease?
Graves' disease is an _autoimmune condition_ whereby auto-antibodies bind to and stimulate the TSH receptors on the thyroid → overproduction of T3 and T4 → hyperthyroidism.
93
what are the ophthalmological features of Grave's?
* exophthalmos (bulging eyes)
* ophthalmoplegia (weakness/paralysis of eye muscles)
* lid lag
* gritty sensation in eyes
* papilloedema, conjunctival oedema
94
extra features of Grave's (not usual hyperthyroid)
* eye signs
* proximal myopathy
* pretibial myoedema (above lateral malleolus)
* hyper-reflexia
* thyroid acropachy (thick nails)
95
key Ix of Grave's
* thyroid examine + eye examination
* ECG
* TFT - low TSH, high T4/T3
* TSH-receptor antibodies
* thyroid USS - enlarged and vascularised thyroid
* technetium scan - raised uptake, not needed for diagnosis
96
management of thyroid storm
1. Admit + discuss with ITU/HDU
2. **Propranolol** - 60mg QDS IV _+_ digoxin
1. Diltiazem if beta-blockers CI e.g. asthma
3. **Carbimazole** - inhibits TPO, 15-25mg, QDS, PO
4. **Steroids** - Hydrocortisone 100mg QDS IV or dexamethasone 2mg, QDS, PO
5. **Treat precipitant** e.g. Abx for infection
6. **Supportive** - as required consider cooling, IV fluids, further circulatory support
7. Ongoing management
* 4 hours after 1st carbimazole dose give **Lugol's iodine** for 10 days (TDS)
* After 5 days ↓ carbimazole to 15mg TDS, PO
* After 10 days stop propranolol and iodine, adjust carbimazole as required
97
management of Graves
* refer to endo
* symptom control - beta-blocker or CCB
* **radioactive iodine**
* 1st line in adults
* realistically medical tried first
* CI: compression concern, ?CA, pregnant, active thyroid eye disease
* **anti-thyroid drugs -** 12-18 months, either _block + replace_, or _dose titrate to TFTs_
* carbimazole
* propylthiouracil - safe for pregnancy
* monitor TFT every 6/52 until in range then very 3/12 rest of treatment
* **total thyroidectomy**
* 1st line if compression concern, ?CA, other methods CI/unsuccessful
98
treatment of primary hyperparathyroidism
* mild - increase fluid intake, thiazide diuretics
* **total parathyroidectomy**
* if high calcium (\>2.85), bone disease, osteoporosis, renal stones, declining eGFR, \< 50
* **conservative** - not appropriate for surgery
* Ca2+ \< 2.85, \> 50, no end organ damage
* correct vitamin D
* **calcium lowering meds**
* calcitonin
* cinacalcet (calcimimetic)
* desonumab
* bisphosphonates
99
treatment of acute hypercalcaemia
treat if 3-3.5 + acute/symptomatic _or_ \> 3.4 even if asymptomatic
1. **IV fluids** - 0.9% NaCl, 1L in 1st hour, 4-6L total in 24 hours
2. **Consider IV bisphosphonate**s (e.g. zoledronic acid 4mg over 15 minutes)
* mainly used in malignancy related
3. Address exacerbating factors e.g. thiazide diuretics
4. Moderate calcium and vitamin D intake
100
treatment of secondary hyperparathyroidism
* calcium + vitamin D supplements as required
* treat underlying cause
* phosphate restriction _+_ binders
* cinacalcet (calcimimetic if ESRF and refractory to treatment)
101
treatment of tertiary hyperparathyroidism
* Total or subtotal parathyroidectomy
* Cinacalcet
102
**biguanides**
example medication
mechanism of action
**metformin**
complex mechanism but helps patient's utilise insulin better
* **decreases hepatic glucose production**
* decreases intestinal absorption of glucose
* improves insulin sensitivity by increasing peripheral glucose uptake and utilization
103
**_metformin_**
**class:**
**SE:**
**Cautions/risk:**
**benefit:**
**metformin**
**class**: biguanide
**SE**: GI upset, altered taste, rare (hepatitis, skin reaction, reduced B12 absorption, _lactic acidosis)_
**Cautions/risks**: contraindicated → acute metabolic acidosis, eGFR \< 30; caution → other RF for acidosis
**benefit**: cardio + renal protection, not linked with weight gain
104
**_Empagliflozin, Dapaglifozin, etc_**
**class:**
**SE:**
**Cautions/risk:**
**benefit:**
**_Empagliflozin, Dapaglifozin_**
* **class:** SGLT 2 inhibitors
* **SE:**
* serious - DKA
* Common – thirst, urinary disorders, urosepsis, ↑ infection, hypo if + insulin or sulfonyl
* Uncommon – dehydration, dizzy, hypotension, renal failure, syncope
* **Cautions/risk:** DKA, increased risk of lower limb amputation, _necrotising fasciitis of groin_ (Fournier's)
* **benefit:** weight loss, **cardioprotective**
105
MOA of SGLT2 inhibitors and examples
* Sodium-glucose co-transporter 2 inhibitor → reduced glucose resorption in kidney inducing glycosuria
* “gliflozin”
* Canagliflozin
* Dapagliflozin
* Empagliflozin
* Ertugliflozin
106
**_pioglitazone etc_**
**class:**
**SE:**
**Cautions/risk:**
**_pioglitazone etc_**
* **class:** thiazolidinediones
* **SE:**
* weight gain (common)
* #, infection, numbness visual impairment
* **Cautions/risk:**
* increased risk of HF, _bladder cancer_, bone #
* avoid if other RF for this
107
**_gliclazide etc_**
**class:**
**SE:**
**Cautions/risk:**
**benefit:**
**_gliclazide etc_**
* **class:** sulphonylurea
* **SE:**
* _hypoglycaemia_
* weight gain
* GI disturbance
* liver dysfunciton
* agranulocytosis (rare)
* **Cautions/risk:**
* CI: high BMI, elderly, G6PD deficiency
108
**_alogliptin, sitagliptin etc_**
**class:**
**SE:**
**Cautions/risk:**
**benefit:**
**_alogliptin, sitagliptin etc_**
* **class:** DDP-4 inhibitor
* **SE:** headache, constipation, dizzy, skin reaction
* **Cautions/risk:**
* CI - *ketoacidosis*
* hypersensitivity reaction (SJS)
* **benefit:**
* weight loss
* reduced CVD deaths
109
**_Exenatide, liraglutide etc_**
**class:**
**SE:**
**Cautions/risk:**
**benefit:**
**_Exenatide, liraglutide etc_**
* **class:** glucagon-like-peptide-1 mimetic (GLP-1 analogue)
* **SE:**
* GI disturbance
* Interacts with _warfarin_
* Common - ↓ appetite, dizzy, skin reactions
* Uncommon – alopecia, drowsy, hyperhidrosis, renal impairment, change in taste
* **Cautions/risk:**
* Exenatide + liraglutide are weekly SC injection
* CI – ketoacidosis, severe GI disease
* Caution – elderly, pancreatitis
* **benefit:**
* prevents weight gain, may cause weight loss → good if BMI \> 35
110
Thiazolidinediones MOA and example
Bind to PPARs (PPAR-gamma) in adipocytes to promote adipogenesis and fatty acid take up
* “glitazones”
* Pioglitazone
111
sulfonylurea MOA and examples
* **Insulin secretagon**
* Augment insulin secretion, requires some residual beta cell function
* Bind + close ATP-sensitive channels so beta-cells depolarise opening Ca2+ channels and release of insulin granules
* May inhibit hepatic glucose production
* *gliclazide*
112
MOA of DDP-4 inhibitors and examples
**secretagon**
Inhibitor DDP-4 which increases insulin secretion and decreases glucagon secretion by preventing DDP-4 breakdown of incretins (e.g. GLP-1)
* “gliptin”
* Alogliptin
* Linagliptin
* Saxagliptin
* Sitagliptin
* Vildagliptin
113
what is the diagnostic criteria for DM?
Symptomatic + 1 biochemical test indicating hyperglycaemia
* Fasting glucose _\>_ 7
* Oral glucose tolerance test with 75g glucose - 2hr blood sugar _\>_ 11.1
* Random glucose _\>_ 11.1
* HbA1c \> 48 (\> 6.5%) → _only for T2DM_
* Normal \< 42, pre-diabetes is 42-47 (6-6.4%)
Asymptomatic + 2 biochemical tests indicating hyperglycaemia
114
what are the genetic + autoantibody associations in T1DM?
* Associated with HLA DR3 _+_ HLA DR4
* Associated autoantigens: glutamic acid decarboxylase (GAD), insulin, insulinoma-associated protein 2, efflux zinc transporter
115
management of T1DM
* **Conservative**
* Structure education program (DAFNE course)
* Advice: reduce CVD risk, foot care advice, DVLA
* **Medical**
* Aim for sugars of: **4-7 pre-meal, \< 9 post-meal**
* Blood sugar monitoring - 1st and last thing in the day, prior to each meals.
* **Insulin therapy**
* Short acting - dose calculated using insulin unit: carbohydrate ratio
* Long-acting
* Optimise health - statins if ↑ lipids, anti-hypertensives if ↑ BP
* **Monitoring**
* HbA1c every 3-6 months
* Annual review: retinopathy (annual), nephropathy, vascular disease, diabetic foot (at clinic), CVD risk factors
116
Types of insulin regime
* Types of regimes
* **Basal-bolus regime** - 1st line
* **Twice daily regime** - biphasic insulin given pre-breakfast and pre-evening meal
* Mixed of intermediate acting with rapid or short acting
* **Pump therapy** - continuous SC insulin infusion
117
what are the target BM in DM if on insulin (T1DM mainly)?
Aim for sugars of: 4-7 pre-meal, \< 9 post-meal
118
management of hypoglycaemia
75ml 20% dextrose
150ml 10% dextrose
119
when can HbA1c not be used for diagnosis of DM?
**Inappropriate** to use HbA1c in paediatrics, ?T1DM, \< 2/12 of symptoms, medications impairing glucose metabolism, significant pancreatic damage, pregnancy
120
epidemiology + RF of T2DM
* UK prevalence is 5-10%
* T2DM \> T1DM
* Asians, African, Hispanic, men and elderly are more commonly diagnosed.
* **RF** - FHx, Afro-Caribbean, Black African, South Asian, HTN, overweight/obese
121
stages and treatment of diabetic retinopathy
122
Meeran's guide for T2DM medical treatment (step 1+2)
* Diet + exercise + lifestyle
* Metformin = everyone unless CI
* Step 2 → consult diabetes team for recommendation
* Guidelines have changed to say you can use anything.
* GLP-1 agonist if _obese_
* Expensive, currently only injectable, but new ones coming orally
* SGLT2 if _ischaemic heart disease_
* Very good if heart failure
* Gliclazide for _everyone else_/money important
* Used to be gliclazide as always second line
123
What are the NICE targets for T2DM?
**NICE targets:**
* 48 mmol/mol HbA1c = diagnostic + target
* if drug associated hypoglycaemia aim for 53 mmol/mol
* If HbA1c not adequately controlled by single drug and rises to over 58 mmol/mol consider intensifying treatment and aim for \< 53 mmol/mol
124
what is the management of T2DM
* **conservative**
* education program
* Advice: diet, exercise, reduce CVD risk, foot care, DVLA
* **medical**
* Conservative – diet and exercise advice, weight loss
* **Metformin - monotherapy**
* r/v if eGFR \< 45, stop if \< 30
* **CI**: eGFR \< 30, tissue hypoxia (MI, surgery), iodine contrast (stop 24 hrs prior → 48hrs after), alcohol abuse (relative)
* **dual therapy**:
* DDP-4 inhibitor (gliptins, e.g. sitagliptin) Good if _overweight_
* pioglitazone (thiazolidinedione)
* CI: HF, hepatic impairment, DKA, bladder cancer, un-Ix macroscopic haematuria
* sulfonylurea (glibenclamide, gliclazide)
* SGLT2 inhibitor (e.g. empagliflozin)
* only if sulfonylurea CI/not tolerated or high risk of hypoglycaemia
* **triple therapy**
* can consider GLP-1 analogue if BMI \> 35, or BMI \< 35 with occupational consequences of insulin treatment
* **Insulin based treatment**
* continue metformin for cardio + renal protection
if metformin CI or not tolerated as 1st drug use another for mono → dual → insulin
125
criteria for DKA
* pH \< 7.3 and bicarbonate \< 15
* Plasma glucose \> 11mM
* Blood ketones \> 3 mM or ++ in urine
126
treatment of DKA
127
how do you calculate osmolarity?
* **Osmolarity = 2(Na+ + K+) + urea + glucose**
* Osmolarity is in mmol/L
128
what is normal serum and urine osmolality?
* Normal **serum osmolality** is **275-295** mmol/kg
* Normal urine osmolality 50-1200 mmol/kg
osmolality is lab measure, osmolarity is calculated
129
diagnostic criteria for HHS
**Diagnostic criteria** - patient is clinically hypovolaemic
* pH \> 7.3 (no acidosis)
* Serum osmolarity \> 320 mosmol/kg
* Blood glucose \> 30mM
130
complications of HHS
* Fluid overload, cerebral oedema, central pontine myelinosis
* Ischaemic events including MI, cerebrovascular
* VTE
* ARDS, DIC, multi-organ failure, rhabdomyolysis
131
Ix for HHS
* **Bedside**
* Weight - guide fluid resuscitation
* GCS/AVPU
* Urine dipstick - glucose +++, ketones may be mildly ↑ (+)
* ECG
* **Bloods**
* VBG - ↑ glucose, normal pH (pH \> 7.3, bicarbonate \> 15)
* Serum osmolality - \> 320 mmol/L, normal 290 _+_ 5
* U&Es (Na+ often ↑)
* FBC, CRP - exclude infection
* CK - screen for rhabdo
* **Specialist or scoring**
* Calculate osmolarity
* **assessing for infection** - urine/blood MC&S, CXR
132
management of HHS
1. **Aggressive fluid replacement**
* **0.9% NaCL** _+_ K+ as indicted by U&Es
* Swap to **0.45% NaCl** if osmolality is not ↓ with adequate fluid resuscitation
* Initial ↑ in Na+ is expected, should not prompt change of fluid
* Aim for 3-6L by 12 hours depending on weight and extent of dehydration
* Aim to ↓ glucose by no more than 5mM/h and sodium by 10mM/24 hours
* Encourage oral intake as soon as safe to do so
2. **IV insulin infusion**
* Only required if glucose no longer falling with fluid resuscitation alone or significant ketonuria (++)
* _0.05 IU/kg/hour_ fixed rate
3. **Treat the underlying precipitate**
4. **VTE prophylaxis**
5. **Monitoring** - serial glucose, U&E, neuro obs
133
indications for HDU in HHS
Consider **HDU care** for those with osmolality \> 350, sodium \> 160, PH \< 7.1, K+ abnormalities, GCS \< 12, ↓ O2 sats, SBP \< 90, tachy or bradycardic, evidence of significant AKI.
Intubation and ventilation required for severely unwell especially if ↓ GCS
134
what is hypopituitarism + it's causes
Hypopituitarism is a deficiency in **one or more pituitary hormones**. The deficiency may be partial or complete.
**Panhypopituitarism** is a deficiency in all pituitary hormones.
causes
* neoplastic - pit. adenoma (most common), craniopharyngioma (kids), mets (rare)
* vascular - pituitary apoplexy, Sheehan's, SAH, intrasellar aneurysm
* inflammatory + infiltrative - haemochromatosis, sarcoid, TB
* hypothalamic dysfunction - anorexia, starvation, over exercise
* infection - abcess, TV, fungal (AIDS)
* congenital
* TBI
* radiotherapy or pituitary surgery
135
what are dynamic pituitary function tests?
**Contraindications:**
* Ischaemic heart disease.
* Epilepsy.
* Untreated hypothyroidism (impairs the GH and cortisol response).
**Procedure:** Administration of LHRH (GnRH), TRH and insulin Measure the 0, 30, 60, 90 + 120 mins the pituitary hormones
**Interpretation:** Involves interpreting three aspects
1. **Insulin Tolerance test**
* Adequate cortisol response = ↑ greater than 170 nmol/l to above 500nmol/l.
* Adequate GH response = ↑ greater than 6mcg/L
2. Thyrotrophin Releasing Hormone Test
* The normal result is a TSH rise to \>5 mU/l (30 min value \> 60 min value)
* Hyperthyroidism = TSH remains suppressed
* Hypothyroidism = exaggerated response.
* With the current sensitive TSH assays basal levels are now adequate and _dynamic testing is not usually needed to diagnose hyperthyroidism._
3. Gonadotrophin Releasing Hormone Test
* Normal peaks can occur at either 30 or 60 minutes
* LH should \> 10 U/l and FSH should \> 2 U/l.
* Gonadotrophin deficiency is diagnosed on the basal levels rather than the dynamic response.
136
management of hypopituitarism
**Acute pituitary failure**
* Resuscitation with IV fluids
* IV hydrocortisone → IV infusion
* Replacement of other hormones subsequently
**Hormone replacement**
* Order of replacement therapy:
* hydrocortisone → thyroxine → oestrogen/T → GH
* Desmopressin - Central DI seen if pathology affects the posterior pit.
**Surgical** - apoplexy emergent decompression, SOL - resection
137
causes of hypothyroidism
* **Primary hypothyroidism**
* Autoimmune thyroiditis (**Hashimoto’s disease**) is a common cause.
* Thyroid atrophy
* Congenital - thyroid aplasia or dysplasia
* Thyroidectomy
* radioactive iodine Tx
* radiotherapy to head/neck
* Severe iodine deficiency or iodine excess
* **_Drug causes:_** lithium, amiodarone
* **_Secondary_**_:_ pituitary adenomas, sheehan’s syndrome, pituitary apoplexy, head trauma, surgical complication.
138
Ix for hypothyroidism
* * **Bloods**
* TFT - TSH will be ↑ or ↓ depending on whether primary or secondary, T3/4 ↓
* Anti-TPO and anti-thyroglobulin antibodies
* Lipids - often raised
* HbA1c or fasting glucose
* **Imaging**
* Thyroid USS - if asymmetrical or suspicious thyroid mass
* CT/MRI head - if suspicion of CNS cause
139
management of myoxedema coma
* Features: hypothermia, ↓ RR, ↓ Na+, ↓ glucose, heart failure, confusion, ↓ GCS/coma, hyporeflexia
1. IV T3/T4) - loading dose + then maintenance
* Loading doses - T4 500mch, T3 10mcg
2. IV hydrocortisone (50-100mg)
3. Supportive
* Mechanical ventilation
* Oxygen, warming blankets, fluid (cautiously), Abx if infective trigger
4. Treat precipitant
140
management of hypothyroidism
**Clinical hypothyroidism**
* **levothyroxine sodium (25-200mcg/day)** replacement for T4.
* 50-100mcg starting, increase till TSH in range or in secondary when T4 in mid-range
* if CAD or \> 60 start 25mcg
* Monitoring
* TFT 8-12 weeks after dose change
* Aim to normalise TSH (0.5-2.5)
141
management of subclinical hypothyroidism
* ↑ TSH but normal T3/T4
* TSH 4-10 and normal T4
* \< 65 and symptomatic - trial levothyroxine, stop if no improvement
* Elderly - consider watch and wait approach
* Asymptomatic - repeat TFT in 6/12
* TSH \> 10 and normal T4
* Start levothyroxine regardless of symptom status if \< 70 years
* In 70+ consider conservative management and repeating TFTs
142
causes of hyperthyroidism
* **primary**
* Graves, thyrotoxicosis, toxic adenoma, thyroiditis
* amiodarone, lithium, exogenous iodine, levo overtreatment
* **secondary**
* TSH pit. adenoma, hCG secreting tumour (e.g. molar), gestational thyrotoxicosis
143
what is the management of hyperthyroidism?
* **Sx** - beta blocker
* **anti-thyroid**
* carbimazole or prophythiouracil
* 2-3 weeks
* block and replace or dose titration
* assess if remission 18-24 months
* **radioiodine**
* takes 3-4 months
* CI: pregnancy, no conception within 6 months
* indicated: relapse, poor compliance, toxic nodular
* **surgery**
* if compression, failure of medical treatment
* subtotal/total 98% cure rate
* SE: haemorrhage, hypoparathyroidism, vocal cord paralysis, hypothyroidism (long-term)
144
what are the classes of obesity?
* BMI 25-29.9 - overweight
* BMI 30-34.9 - obese (grade I)
* BMI 35-39.9 - obese (grade II)
* BMI _\>_ 40 - morbidly obese (grade III)
145
medical management of obesity
* **Orlistat** - pancreatic lipase inhibitor
* Indicated: BMI \> 28 with RF, BMI \> 30, continued weight loss e.g. 5% in 3 months
* SE: faecal urgency, incontinence, flatulence
* **Liraglutide** - GLP1 receptor antagonist
* Indicated: BMI \> 30, BMI 27-30 with other weight related issues
* Stop treatment after 12 weeks if weight loss \< 5%
* Consider vitamin and mineral supplements - esp. for elderly or growing adolescents
146
definition of osteomalacia and causes:
*Osteomalacia* is a disorder of bone matrix mineralisation characterised by incomplete mineralisation of mature bone matrix following growth plate closure in adults
* Dietary deficiency
* Poor sunlight exposure
* Malabsorption
147
Ix of osteomalacia
* **Bloods**
* ABG - acutely unwell, exclude renal tubular acidosis
* calcium (low or normal), phosphate (low), ALP (high) - bone profile
* 25-hydroxy vitamin D
* ↑ risk to bone health if \< 25 nmol/L
* Inadequate if 25-50nmol/L
* \> 50 is usually sufficient for most
* PTH (high-secondary)
* U&Es - assessment for CKD
* **Imaging**
* Limb x-ray - may be normal or may show osteopaenia.
* *Looser’s zone* – wide, transverse lucencies traversing part way through a bone (usually at right angles)
148
management of osteomalacia
* Lifestyle
* Advise about dietary source + safe sunlight exposure
* Vitamin D and calcium replacement
* Rapid correction - vitamin D
* Indication: symptomatic, need correction prior to anti-resorptive treatment
* consider combined calcium-vit D
* Non-urgent correction vitamin D
* 800-2000 IU daily, no requirement for loading
* Monitor with serum calcium, phosphate, ALP, PTH - 1/12
* no need to repeat vit D routinely
* Treat any underlying cause.
149
what causes osteoporosis?
* **primary**
* idiopathic, post-menopausal, age related
* **secondary**
* malignancy - myeloma, mets
* Cushing's, thyrotoxicosis, 1 hyperparathyroidism, hypogonadism
* drugs - corticosteroid, heparin, PPI, SSRI, anti-epileptics, aromatase inhibitors
* malabsorption syndromes
* anorexia nervosa
* ETOH, smoking
150
what are the RF for osteoporosis?
**Osteoporosis RF (secondary) SHATTERED**
* **S**teroid use \>5mg/day of prednisolone
* **H**yperthyroidism, hyperparathyroidism, hypercacliuria
* **A**lcohol and tabacco use
* **T**hin \< 22
* **T**estosterone low
* **E**arly menopause
* **R**enal or liver failure
* **E**rosive/Inflammatory bone disease
* **D**ietary low calcium or malabsorption, DM1
151
what are the Ix for osteoporosis
* Urinary bence-jones protein
* **Bloods**
* calcium, phosphate, Alk Phos, vitamin D (**normal** in primary osteoporosis)
* TFTs
* Testosterone
* **Imaging**
* **X-ray**
* **DEXA scan (gold standard):** hip and lumbar spine usually
* MRI spine - assess for vertebral #
* **Specialist or scoring**
* **FRAX score** - assess fracture risk
* Used for those 40-90, with or without BMD values
* **Qfracture** - 10 year predicted absolute fracture risk
* Used for those 30-84, BMD cannot be incorporated
152
how is FRAX score interpreted?
* **FRAX score** - assess fracture risk
* Used for those 40-90, with or without BMD values
* Age, sex, secondary osteoporosis, alcohol intact, weight, height, previous fracture, parent hip #, smoking, glucocorticoid, RA, BMD
* Results interpretation
* Without BMD
* Low risk - reassure
* Intermediate - offer DEXA
* High - offer bone protective treatment
* With BMD
* Low risk - reassure
* Intermediate - consider treatment
* High - strongly recommend treatment
153
who should have a fracture risk score calculated?
1. All men \> 75
2. All women \> 75
3. All men and women \> 50 if they have:
* FHx of hip #, falls Hx, previous fragility #, low BMI, ETOH \> 4 units/day, are/were on steroids, disease associated with osteoporosis (coeliac, IBD, hyperparathyroidism)
154
describe anti-resorptive medications available
* ***Bisphosphonates*** - oral, alendronic acid, ibandronic acid, risedronate sodium
* Indicated: 10 year # risk \> 1%
* Usually given weekly
* MOA - incorporated into osteoclast cells and cause dysfunctional cell processes → non-functional + undergo apoptosis
* ***Denosumab** -* Mab, RANK-L → prevents maturation and formation of osteoblasts
* 6/12 SC injection
* CI - low serum calcium
* SE: joint and muscle pain in limbs
* on stopping rapid ↓ BMD (prefer bisphos.)
* ***Raloxifene*** - SERM → preserve BMD
* For post-menopausal
* Can worse menopausal Sx
* ↓ risk of vertebral fractures and show to improve BMD
* ***HRT*** - utilised in young women who have undergone premature ovarian insufficiency
* ***Teriparatide*** - synthetic PTH, stimulates bone growth
155
what is primary prevention of post-menopausal women for osteoporosis?
1. Bisphosphonates
* 10mg OD or 70mg once weekly
2. Denosumab
* SC injection once every 6/12
3. Consider vitamin D and calcium supplement as required (AdCal)
156
conservative management of osteoporosis
* ↓ RF - stop smoking, ↑ diabetic control, ↓ ETOH
* Diet - adequate vitamin D, calcium and protein intake
* Regular weight bearing exercise
* More information from National Osteoporosis society
* Falls risk assessment
* Hip protectors for elderly in care homes
157
osteoporosis secondary prevention in post-menopausal women
1. Bisphosphonates
2. Raloxifen and teriparatide
* Indicated - unable to comply with bisphosphonate, CI to bisphosphonate, combination of low T score + independent clinical RF for fracture
3. Consider vitamin D and calcium supplements as required (AdCal)
158
What is Paget's disease
Condition characterised by increased bone turnover in focal bone regions resulting in abnormal bone structure and increased risk of fracture
* controlled bone turnover
* high osteoclast + osteoblast activity so disorganised bone breakdown and formation
159
Paget's complications
* Disruption of anatomy
* Pain
* Deformity + #
* Hearing loss - vestibulocochlear nerve compression or ossicle ossification
* Spinal stenosis
* Osteoarthritis
* Nerve compression
* Effects of abnormal metabolism
* Osteosarcoma (\<1%)
* High output heart failure
160
management of Paget's disease
1. **Analgesia**
2. **Supportive -** orthotics, physiotherapy, hearing aids
3. **Bisphosphonates** - alendronic acid, pamidronic acid _+_ calcium and vitamin D as required
4. Monitor every 6-12 for recurrence, ALP = marker
* Indefinite due to risk of osteosarcoma
161
define phaeochromocytoma and causes
Refers to a catecholamine producing tumour, usually originating from chromaffin cells in the adrenal medulla
causes
* adrenal medullary tumour
* sporadic (most)
* familial - MEN2 (bilat), VHL, NF1, Paraganglioma syndromes
162
rule of 10s for phaes
* 10% bilateral
* 10% malignant
* 10% extra-adrenal
163
investigations for phaechromocytomas
* **Bedside**
* BP + fundoscopy - HTN CoD
* **Bloods**
* **Serum plasma free metanephrines, catecholamines and VMA**
* Glucose (often ↑), calcium (may be ↑), FBC (Hb may be ↑)
* **Imaging**
* CT CAP scan - assess for tumour
* MIBG scan - if biochem +ve but CT -ve ,uses MIBG labelled with iodine
* **Specialist or scoring**
* **Urinary metanephrines****, catecholamines and VMA** (vanillylmandelic acid)
* Genetic testing
164
management of phaeochromocytoma
1. **Alpha blockage** - short acting → long-acting
2. **Beta blockage** - propranolol
3. **Surgery** - only once BP is controlled, usually 4-6 weeks after alpha-block to ensure full block
* Resection
* Repeat 24 hr urinary collection 2/52 to assess success
4. **_+_ chemo/radiotherapy** - indicated if on histology mass is malignant
165
what is the diagnostic criteria of PCOS?
1. Oligomenorrhea/irregular menses for 6 months
2. Hyperandrogenism
* Clinical evidence - hirsutism, male pattern alopecia
* Biochemical - raised free testosterone
3. Polycystic ovaries on USS
166
investigations in PCOS?
* **USS of ovaries** (TVUSS) - polycystic morphology defined as \> 12 follicles 2-9mm or ovarian volume \> 10mL (NICE)
* **LH and FSH** - raised LH, ↑ LH:FSH ratio
* **Steroid hormone panel** - raised androgens (↑ testosterone, ↑ androstenedione, ↓ SHBG)
* **Hormone levels** to exclude other endocrine conditions
* TFTs
* prolactin,
* 7-hydroxyprogesterone (CAH), 24-hr
* urinary cortisol (Cushing's)
* DHEA-S and free androgen index (androgen secreting tumours)
* **Glucose tolerance test**
* **Fasting lipid panel**
167
conservative management of PCOS
* **Reduce weight** (5% loss can resume ovulation)
* May reduce high insulin and androgen levels, ↓ DM and CVD risk, result in menstrual regularity and improve chances of falling pregnant
* **Dietary modification and exercise**
* **Screening** - for DM2 and CVD, at higher risk of developing
* **Advice**
* Inform them of ↑ risk of T2DM + GDM if they become pregnant, CVD and OSA
* Smoking cessation
168
management for PCOS patients who are fertility desiring
* **Clomiphene**
* Clomiphene (NICE)- antioestrogen (so ↑ FSH and LH
* Given days 2-6 for follicle maturation
* step wise 50mg → 100mg → 150mg
* ***Letrozole*** (NICE) - recent medication, thought to be more effective in those with BMI \< 30-35
* _Metformin_ - Add as adjunct if 3 cycles of clomiphene have failed
* **Gonadotrophins**
* For clomiphene resistant, daily SC FSH + LH
* Start with a low dose, ↑ dose every 5-7 days until ovaries response, USS monitor
* **Laparoscopic ovarian diathermy** (ovarian drilling)
* Destroys some ovarian stroma, can induce more regular ovulation which may continue for years
* **IVF**
169
management of PCOS not desiring fertility
* **Oral contraceptive pill**
* **Metformin** - for subset with hyper-insulinaemia and CVS risk factors
* off license use
* **Mechanical hair removal or topical treatments**
* Eflornithine topical → Slows hair growth
* minoxidil topical → tx androgenic alopecia
* **Anti-androgen**
* For those with severe hirsutism or CI to hormonal contraception
* 1st line - **Spironolactone** (block AR)
* 2nd line - finasteride (5-alpha reductase inhibitor)
170
causes of hyperaldosteronism
* Adrenal adenoma → **Conn's syndrome**, majority (70%)
* Bilateral adrenal hyperplasia (2nd most common)
* Familial hyperaldosteronism
* Adrenal carcinoma (rare)
171
Ix for hyperaldosteronism?
* **Bedside -** BP, ECG
* **Bloods**
* VBG - alkalosis
* U&Es - hypokalaemia, normal sodium usually
* Aldosterone: renin ratio - ↑ ratio (↑ aldosterone, ↓ renin)
* LFT, FBC, ESR, bone profile
* **Imaging**
* CXR
* **Adrenal CT** with contrast - localise adrenal lesion
* **Specialist or scoring**
* _Selective adrenal venous sampling_ - *gold standard*, helps to identify if the source of excess aldosterone is from one isolated adrenal (Conn's) or from both (hyperplasia)
* Saline suppression test
* Failure of aldosterone levels to suppress after salt loading - confirms dx
172
management of hyperaldosteronism - unilateral disease
* Surgical → laparoscopic adrenalectomy - removal of affected adrenal gland
* Spironolactone post-operatively for 4 weeks to control BP and K+
173
management of bilateral hyperaldosteronism
* Optimise HTN with anti-hypertensives
* Potassium sparing diuretics - amiloride, **_spironolactone_**, eplerenone
* Can help lower BP while promoting potassium retention
174
causes of a high prolactin
* Excess pituitary production
* Pregnancy, breastfeeding
* Hypothyroidism (↑ TRH, stimulates prolactin)
* Prolactinoma
* Compression of pituitary stalk (prevents DA inhibition)
* Pituitary adenoma
* Craniopharyngioma
* Dopamine antagonists (most common cause of ↑ prolactin)
* Anti-emetics - metoclopramide
* Anti-psychotics - risperidone, haloperidol
175
investigations for high prolactin?
* **Bedside**
* Visual field testing
* Pregnancy test - exclude
* **Bloods**
* Prolactin - massively raised, \> 6000
* Hormones - GH/IGF-1, ACTH, FH + LSH (gonadotrophins)
* TFTs - assess for hypothyroidism
* **Imaging**
* **MRI brain w/ contrast**
176
management of prolactinoma
**Medical**
* *Dopamine agonist* → _1st line_, cabergoline, bromocriptine
* Tx usually long term
* *Hormone replacement therapy* → e.g. oestrogen
* During period of hypogonadism, if fertility not issue
**Surgery**
* Trans-sphenoidal hypophysectomy→ _2nd line_
* Indicated: significant SOL symptoms, failure of medical treatment
**Radiotherapy** - 2nd line, alternative to surgical management
177
key biochemical features of SIADH
**High urine osmolality (\>100) + low serum osmolality + high renal sodium (\>20mmol/L) + normal 9am cortisol and TFTs**
178
what must be excluded before SIADH is diagnosed?
_Diagnosis of exclusion_ - must rule out Addison's and abnormal thyroid function
* 9am cortisol + TFTs
179
management of SIADH
1. Stabilisation - resuscitation if Sx + severe hyponatraemia (\<125 mmol/L)
* IV hypertonic saline - slow rate, monitor for neurological change
2. Fluid restriction
3. Treat underlying cause
4. Demecycline, tolvaptan (vasopressin receptor antagonists) → induced DI state, but very expensive
180
types of thyroiditis
* **Hashimoto's thyroiditis**
* Autoimmune thyroiditis
* Destruction of thyroid cells by auto-antibodies
* De Quervain’s thyroiditis
* Subacute granulomatous thyroiditis.
* Thought to have a viral origin.
* Associated with coxsackie
* Post-partum thyroiditis
* Affects 5% women giving birth every year.
* 1 in 5 of those need long-term levo
* Drug-induced thyroiditis
* Damage from drugs
* _Common_: interferons, amiodarone, lithium
* Acute or infectious thyroiditis
* Suppurative thyroiditis.
* Infection by bacteria
* e.g. S. aureus, S. pyogenes, S. pneumoniae, Klebsiella, H. Influenza
* Riedel’s thyroiditis
* Chronic form of thyroiditis, AI
* Characterised by fibrosis and infiltration of IgG4 secreting plasma cells.
181
-gliflozins Drug class
SGLT2 inhibitors
182
- glitazones
Thalizodinediones
183
- gliptin Drug class
DDP4 inhibitor Inhibit DDP4i which increases incretins like GLP-1 level (not metaglised ny DDP4) Causes rise in insulin secretion + inhibition of glucagon
184
- tide Drug class
GLP 1 agonists
185
what are the pre-diabetes ranges - fasting glucose?
fasting 6.1-6.9
186
what are the pre-diabetes ranges OGTT and random glucose?
7.8-11.1
187
how to calculate the amount 1 unit of insulin will reduce someone's blood sugar
correction factor = 100/total number daily units
correction factor is how much 1 unit of rapid acting insulin will lower BS
188
alpha blocker used in phaeo
phenoxybenzamine
