Endocrine Flashcards
hyperthyroidism definition
over-production of the thyroid hormones, triiodothyronine (T3) and thyroxine (T4), by the thyroid gland
thyrotoxicosis definition
refers to effects of an abnormal and excessive quantity of thyroid hormones in the body
primary hyperthyroidism
due to thyroid pathology
thyroid is behaving abnormally and producing excessive thyroid hormone
secondary hyperthyroidism
- pathology in the hypothalamus or pituitary
- pituitary gland produces too much thyroid-stimulating hormone, stimulating the thyroid gland to produce excessive thyroid hormones.
subclinical hyperthyroidism
- thyroid hormones (T3 and T4) are normal and thyroid-stimulating hormone (TSH) is suppressed (low)
what is grave’s disease?
- an autoimmune condition where TSH receptor antibodies cause primary hyperthyroidism
- These TSH receptor antibodies stimulate TSH receptors on the thyroid
- most common cause of hyperthyroidism
what is Toxic multinodular goitre?
- a condition where nodules develop on the thyroid gland, which are unregulated by the thyroid axis and continuously produce excessive thyroid hormones
- It is most common in patients over 50 years.
which hormones are released by anterior pituitary
FLAT PEG
- FSH
- LH
- Adrenocorticotropic hormone (ACTH)
- Thyroid-stimulating hormone (TSH)
- Prolactin
- Growth hormone (GH)
briefly outline the thyroid axis?
- hypothalamus releases thyrotropin-releasing hormone (TRH)
- TRH stimulates the anterior pituitary to release thyroid-stimulating hormone (TSH)
- TSH stimulates the thyroid gland to release triiodothyronine (T3) and thyroxine (T4)
NB hypothalamus and anterior pituitary respond to T3 and T4 by suppressing the release of TRH and TSH = negative feedback
which hormones are release by posterior pituitary?
Oxytocin
Antidiuretic hormone (ADH)
briefly summarise the growth hormone axis
- hypothalamus produces growth hormone-releasing hormone (GHRH)
- GHRH stimulates the anterior pituitary to release growth hormone (GH)
- Growth hormone stimulates the release of insulin-like growth factor 1 (IGF-1) from the liver
what hormone inhibits growth hormone release from anterior pituitary?
somatostatin
what does insulin-like growth factor do?
- stimulates fat breakdown
- releases glucose from liver
- cell division
- protein synthesis
- increased bone density
causes of hyperthyroidism?
G – Graves’ disease
I – Inflammation (thyroiditis)
S – Solitary toxic thyroid nodule - usually benign adenoma
T – Toxic multinodular goitre
causes of thyroiditis (gland inflammation that causes hyperthyroid then hypothyroid) ?
- DeQuervain’s - transient inflammation of thyroid after viral infection
- Hashimoto’s
- Post-partum
- Drug-induced - amiodarone, iodine, lithium
Hyperthyroidism Px
Anxiety and irritability
Sweating and heat intolerance
Tachycardia
Weight loss
Fatigue
Insomnia
Frequent loose stools
Sexual dysfunction
Brisk reflexes on examination
Graves specific Px ?
Diffuse goitre (without nodules)
Graves’ eye disease, including exophthalmos (eye bulging)
Pretibial myxoedema
Thyroid acropachy (hand swelling and finger clubbing)
Hyperthyroidism Ix
- TFTs - high T3/4, TSH low (high in 2ndary)
- Thyroid ABs - TSHR-Ab, TPO-Ab, TgAb
- CRP / ESR - thyroiditis
- baseline FBC, U/E
- US thyroid - if lump
- thyroid isotope scan
Hyperthyroidism Mx
1st line = carbimazole (start high, titrate down, block and replace by adding lego)
2nd line = propylthiouracil
- radioactive iodine
- subtotal / total thyroidectomy
beta blockers can be used for symptom control
What is a thyrotoxic crisis and how do you manage it?
- rapid T4 increase / release
- eg stress, infection, surgery, stopping anti-thyroid drugs
Px
- high temp, tachy, restless, delirium, coma, death
Mx
- IV fluids, corticosteroids, BBs, carbimazole / propylthiouracil
- potassium iodide
what is hypothyroidism? define primary and secondary?
Low TH - T3/4
Primary - thyroid gland disease - T3/4 low, TSH high
Secondary - disease of hypothalamus / pituitary - T3/4 low, TSH low
Causes of hypothyroidism
Primary:
1. Hashimoto’s - autoimmune inflammation
2. iodine deficiency
3. hyperthyroidism Tx
4. lithium
Secondary:
1. Tumours (e.g., pituitary adenomas)
2. Surgery to the pituitary
3. Radiotherapy
4. Sheehan’s syndrome (where major post-partum haemorrhage causes avascular necrosis of the pituitary gland)
5. Trauma
what antibodies are associated with Hashimoto’s?
- anti-thyroid peroxidase (anti-TPO) antibodies
- anti-thyroglobulin (anti-Tg) antibodies
what is Sheehan’s syndrome?
major post-partum haemorrhage causes avascular necrosis of the pituitary gland leading to hypopituitarism
Hypothyroidism Px
Weight gain
Fatigue
Dry skin
Coarse hair and hair loss
Fluid retention (including oedema, pleural effusions and ascites)
Heavy or irregular periods
Constipation
Hypothyroidism Ix
- TFTs
- thyroid ABs - anti-TPO, anti-Tg
- FBC - anaemia
Hypothyroidism Mx
- levothyroxine
Myoxedema coma
- severe hypothyroidism
Px
- confusion, coma, hypothermia, hypoglycaemia, hyponatraemia
Mx
- T3/4 replacement (T3 causes arrhythmias)
- IV glucose
- hydrocortisone if needed
- fluids / supportive care
What is cushing’s?
excess cortisol
Causes of cushing’s?
ACTH dependent (high)
- Cushing’s disease - ACTH-secreting pituitary adenoma + bl adrenal hyperplasia
- Ectopic ACTH - sg SCLC - paraneoplastic
ACTH independent (low)
- Exogenous steroids
- adrenal adenoma
Cushing’s Px
- round moon face, central obesity, proximal limb muscle wasting
- abdo striae, buffalo hump, hirsutism, acne, bruising, poor skin healing, osteoporosis
- hyperpigmentation - with high ACTH
- metabolic - HTN, T2DM, lipids,
- mental health - anxiety, depression, insomnia, psychosis rarely
What is pseudo-cushing’s?
- mimics cushings
- often from alcohol excess
- false positive on dex suppression test / 24hr urinary free cortisol
- insulin stress test to differentiate
Cushing’s Ix
- Bloods - hypokalaemic metabolic acidosis, impaired glucose tolerance
Dexamethasone suppression test
- high 9am cortisol after dex administration
- low dose test - high cortisol -> Cushing’s syndrome
- high dose test -> high cortisol - adrenal adenoma / ectopic ACTH
- ACTH levels
- 24hr urinary free cortisol
- midnight + waking salivary cortisol
- CT / MRI adrenals / pituitary / TAP
Cushing’s Mx
- stop steroids
- Cushing’s - transsphenoidal resection of adenoma
- Adrenal adenoma - adrenalectomy
- adrenal carcinoma - surgery / radio / mitotane
- ectopic ACTH - surgery / metyrapone / ketoconazole
Nelson’s syndrome
- increased skin pigmentation from high ACTH from enlarging pituitary tumour - after adrenalectomy - removes -ve feedback
Hyperaldosteronism
excess aldosterone
Primary
- excess aldosterone independent of RAAS, renin low
Secondary
- high renin levels -> high aldosterone
Causes of hyperaldosteronism
Primary
- Adrenal adenoma - Conn’s syndrome
- bl adrenocortical hyperplasia (more common)
Secondary
- reduced renal perfusion - eg RAS, HTN, diuretics, CCF, liver cirrhosis, ascites
Hyperaldosteronism Px
- asym
- HTN, headaches, flushing
- metabolic alkalosis - H secretion
- hypokalaemia - weakness, cramps, paraesthesia, polyuria, polydipsia, constipation, arrhythmias
Hyperaldosteronism Ix
- U/E - low K, high Na
- Aldosterone to renin ratio - high aldosterone, low renin in primary
- ECG
- CT / MRI adrenals
- renal artery imaging - eg doppler, angiography
- adrenal vein sampling - which adrenal gland is producing more aldosterone
Hyperaldosteronism Mx
- oral spironolactone
- laparoscopic adrenalectomy
Types of adrenal insufficiency?
Primary - low cortisol + aldosterone from adrenal cortex impairment
Secondary - low cortisol from low ACTH - pituitary / hypothalamus damage
Tertiary - lack of CRH from hypothalamus - suppression of HPA axis from exogenous steroids
Causes of adrenal insufficiency?
Primary
- worldwide - TB
- UK - Addison’s disease - autoimmune destruction
- mets, trauma
Secondary
- long-term steroid use
- hypothalamic / pituitary disease - tumour, trauma, surgery, sheehans…
Adrenal insufficiency presentation?
- tanned, toned, tired, tearful
- fatigue, muscle weakness, cramps, dizziness, fainting, thirst, wt loss, abdo pain, N+V, depression, reduced libido, vitiligo, bronze hyperpigmentation, postural hypotension
Adrenal insufficiency Ix
- bloods - low Na, high K, low glucose, high Ca, dehydration (raised urea / creatinine)
- short synacthen test - failure of cortisol to rise after synacthen
- ACTH levels
- adrenal ABs - adrenal cortex ABs, 21-hydroxylase ABs
- CT / MRI adrenals
- MRI pituitary
Adrenal insufficiency Mx
- hydrocortisone (double when ill)
- fludrocortisone
- steroid card, ID tag, IM hydrocortisone
Adrenal crisis
- acute severe adrenal insufficiency - eg infection, trauma
Px
- low GCS, hypotension, low BMs, low Na, high K
Mx
- IM/IV hydrocortisone, IV fluids, IV dextrose
Acromegaly
- excess GH in adults due to pituitary adenoma (most common) or ectopic production of hormones involved in growth hormone axis (GH/ GHRH) (usually cancer e.g. lung/pancreas)
what visual field defect might be seen with a pituitary tumour?
bitemporal hemianopia
Acromegaly Px
Excess growth hormone causes tissue growth:
- Prominent forehead and brow (frontal bossing)
- Coarse, sweaty skin
- Large nose
- Large tongue (macroglossia)
- Large hands and feet
- Large protruding jaw (prognathism)
Additional features include:
- headaches
- Hypertrophic heart
- Hypertension
- Type 2 diabetes
- Carpal tunnel syndrome
- Arthritis
- Colorectal cancer
Acromegaly Ix
- IGF-1 = raised
- growth hormone suppression test = 75g glucose drink with growth hormone tested at baseline and 2 hours following the drink.Glucose should suppress GH level. Failure to suppress GH suggest acromegaly.
- MRI pituitary
Acromegaly Mx
- surgical = transsphenoidal resection of adenoma
- medical = IM octreotide (somatostatin analogue)
- oral cabergoline, bromocriptine (dopamine agonist)
- SC pegvisomant (GH receptor antagonist)
growth hormone deficiency: Px, Ix and Mx
Px = small physical features, low energy levels, short stature
Ix = low IGF-1
Mx = daily injections of recombinant human growth hormone
T1DM
Autoimmune destruction of beta cells in pancreas leading to lack of insulin production
T1DM Px
- asym
- DKA
- polyuria
- polydipsia
- wt loss
T1DM Ix
- cap BMs
- urine dip - glucose, ketones
Serum blood glucose
- fasting >7, IGT 6.1-6.9
- random >11.1, IGT 7.8-11
- if asym - meet criteria on 2 separate occasions
HbA1c (not helpful in T1DM)
- >6.5% (48) - rpt if asym
- IGT (42-48)
OGTT
- >11.1 2hrs after 75g glucose - diagnostic
- consider c-peptide, auto-ABs
T1DM Mx
- monitor HbA1c every 3-6mo
- self-monitor BMs - before every meal / bed - 5-7 on waking, 4-7 before meals
S/C insulin
- basal-bolus regime
- insulin pumps
- pancreas transplant
- FreeStyle libre
- closed loop system
T1DM sick day rules
- Don’t stop insulin
- Check BMs more frequently
- Consider checking ketones
- Maintain normal meal pattern if possible - carb drinks if necessary
- Drink plenty fluids
T1DM complications
- insulin - hypos, lipohypertrophy, wt gain
Macrovascular
- atherosclerosis, stroke, IHD, PVD
Microvascular
- diabetic retinopathy, nephropathy, neuropathy, infections
Acute
- DKA, HHS, hypos
VRIII / sliding scale
- to control BMs
- actrapid infusion in one arm
- infusion 5% dextrose + KCl in other arm
- stop OHAs, short acting insulins, pre-mixed insulins
- continue long-acting insulins
Indications
- no oral intake
- vomiting
- NBM
- severe illness, eg sepsis
Prescribing insulin …
Who needs
- T1DM
- DKA
- OHAs not enough
Calculating TDD
- total no units over 24hrs on VRIII
- 0.5units/kg/24hrs
- start on small dose - 6-8 units long-acting / mixed, 4-6 units short acting with meals
How to split
- long acting only - extra boost
- mixed BD insulin - eg T2DM
- basal-bolus - eg T1DM
T2DM - pathophysiology and RFx
increased insulin resistance and decreased production, leading to persistent hyperglycaemia
RFs
- non-modifiable - older age, Black / South Asian, FHx
- modifiable - obesity, sedentary lifestyle, high sugar diet
T2DM Px
- asym
- fatigue
- polyuria, polydipsia
- wt loss
- opportunistic infections - eg oral thrush
- slow wound healing
- acanthosis nigricans
T2DM Ix
- cap BM, urine dip
Serum blood glucose
- fasting >7, IGT 6.1-6.9
- random >11.1, IGT 7.8-11
- if asym - meet criteria on 2 separate occasions
HbA1c
- >6.5% (48) - rpt if asym
- IGT 42-48)
- measure every 3-6mo, aim for 48 in new dx, or 52 if on 1+ med
OGTT
- >11.1 2hrs after 75g glucose - diagnostic
- bloods, FBC, U/E, LFTs etc
T2DM Mx
- diet (eg low glycaemic index), exercise, wt loss
- HTN - ramipril (if black - ARB)
- atorvastatin 20mg if QRISK >10%, 80mg if pre-existing disease
- oral hypoglycaemic agents
- insulin
OHAs
1st - metformin, add SGLT-2 if CVD / QRISK
2nd - add sulfonylurea / pioglitazone / DPP4 inhibitor / SGLT-2 inhibitor
3rd - triple therapy metformin + 2 second line drugs / insulin therapy / switch one drug to GLP-1 mimetic
T2DM Mx 1st line
- metformin - titrate up slowly, modified release if GI sx
- if CVD / HF / QRISK>10% - add SGLT-2 inhibitor (add at any point if these develop)
if metformin CI’d
- SGLT-2 (if CVD/HF/QRISK)
- or DPP4/pioglitazone/sulfonylurea
T2DM Mx 2nd line
- add 2nd drug if HbA1c rises to 58
- continue metformin
- add sulfonylurea / pioglitazone / DPP4 / SGLT-2 (criteria)
T2DM Mx 3rd line
Triple therapy
- Metformin + DPP4 + sulfonylurea
- Metformin + pioglitazone + sulfonylurea
- Metformin + pioglitazone/sulfonylurea/DPP4 + SGLT-2 (if criteria met)
Insulin therapy
- consider if HbA1c>58 after >3mo dual oral therapy - humulin 1, continue metformin
T2DM further Mx …
If triple therapy fails and BMI>35, or if BMI<35 and insulin not suitable:
- Switch one drug to GLP-1 mimetic - only continue if reduction of >11 (1%) in HbA1c and weight loss >3% in 6mo
- Only add to insulin under specialist care
T2DM sick day rules
- Some OHAs may be stopped, restart once feeling better
- Metformin - stop if risk of dehydration
- Sulfonylureas - increase hypo risk
- SGLT-2 - check ketones
- GLP-1 - stop if dehydrated
- Monitor BMs more
DVLA diabetes rules
Group 1
- insulin - can drive if has hypo awareness, <1 bad hypo in last 12mo, no visual impairment
- tablets - no need to notify DVLA
- diet controlled - no need to notify
Group 2 must meet
- no severe hypos <12mo
- control of condition, monitoring etc
- understand hypo risks
- no cx of DM
DM advice during Ramadan
- Try to eat meal with long-acting carbs prior to sunrise (Suhoor)
- Use BM monitor
- If taking metformin - 1/3 dose before sunrise, 2/3 after sunset (Iftar)
- Switch OD sulfonylureas to after sunset
- If taking BD gliclazide - take larger proportion of dose after sunset
- No adjustments for pioglitazone
Diabetic neuropathy?
- Glove + stocking sensory loss
- If painful - neuropathic pain meds, pain clinic
Also GI autonomic neuropathy
- Gastroparesis - erratic blood control, bloating, vomiting, Mx with metoclopramide, domperidone, erythromycin
- Chronic diarrhoea
- GORD
Diabetic foot
- from neuropathy / PAD
- loss of sensation, absent foot pulses, reduced ABPI
- calluses, ulcers, Charcot’s arthropathy, cellulitis, osteomyelitis,
- screen annually - palpate pulses, 10g monofilament
Biguanides - metformin
Mechanism and S/E
- reduce gluconeogenesis, increase insulin sensitivity
S/Es
- D+V
- lactic acidosis
When to stop
- not E+D
- AKI
- raised lactate
- before IV contrast
SGLT-2 inhibitors - cana/empa/dapa-gliflozin
Mechanism and S/E
- inhibit glucose resorption, increase urinary glucose loss
S/Es
- genital candidiasis, Fournier’s gangrene, UTIs
- increased UO, freq
- wt loss, DKA / EKA (stop on admission to hospital)
Thiazolidinediones / glitazones - pioglitazone, rosiglitazone
Mechanism and S/E
- increase insulin sensitivity, decrease liver glucose production
S/Es
- wt gain, fluid retention, HF, liver impairment
- bladder Ca risk
- fracture risk
Sulfonylureas - gliclazide, tolbutamide
Mechanism and s/e
- stimulate insulin secretion from pancreas
S/Es
- wt gain
- hypos
- SIADH, bone marrow suppression, hepatotoxicity
Meglitanides work the same
DPP4 inhibitors - sita/lina/saxa-gliptin
Mechanism and S/E
- enhance incretin effect (increased insulin response to oral glucose) - increase insulin, lower glucagon
S/Es
- nausea, headaches
- pancreatitis
GLP-1 agonists - exanatide, liraglutide
Mechanism and S/E
- injectable S/C - increase incretin effect
S/Es
- nausea, GI sx, reduced appetite
- pancreatitis, AKI, wt loss
