Endocrinology Flashcards
Antibodies associated with T1DM?
Anti-islet and anti-GAD
Diagnosis for diabetes on blood sugars?
Fasting > 7 / HbA1c >48mmol/L (6.5%)
2-hours post OGTT / Random glucose > 11.1mmol/L
What is the definition of impaired fasting glucose?
6.1 - 7.0
Offer these OGTT, If this is 7.8 - 11.1 = IMPAIRED GLUCOSE TOLERANCE
Conservative management of diabetes?
MDT
The 4 C’s? = Control, compilations, competency and coping
Diabetes conservative management - Control?
Record of complications e.g. DKA, HONK and hypo’s
CBG - target of 5-7 on waking and 4-7 pre-meal
HbA1c <6.5% or 48mmol/L
Check every 3-6 months then 6-monthly when stable
Control HTN - <140/80 if no end organ damage
<130/80 if end organ damage
What are BP targets for diabetics?
Control HTN - <140/80 if no end organ damage
<130/80 if end organ damage
Conservative management of diabetes - Complications?
Macro = Pulses, BP, cardiac
Micro = Fundoscopy, U&E’s and sensory testing
Conservative management of diabetes - Competency?
With insulin injections, checking injection sites and BM monitoring
Conservative management of diabetes - coping?
Psychological, occupational and domestic
Sick day rules for diabetes?
Increase frequency of blood sugars
Aim for at least 3 litres of fluid a day
Access to mobile and emergency food supplies
Continue all medication
Medical management of T1DM?
Always need insulin
Biphasic = first line = Twice daily insulin detemir
Management of type 2 diabetes - metformin tolerated?
If metformin tolerated it is 1st line
2nd line once HbA1c > 58mmol/L (7.5%) =
Add in gliptin / sulfonylurea / pioglitazone / SGLT-2 inhibitor
3rd line once HbA1c > 58mmol/L (7.5%) = metformin plus:
Sulfonylurea + gliptin
Sulfonylurea + pioglitazone
Sulfonylurea + SGLT-2 inhibitor
Pioglitazone + SGLT-2 inhibitor
3rd line = insulin
OR
Metformin + sulfonylurea + GLP-1 mimetic
When should you not use metformin?
End stage renal disease
Management of type 2 diabetes - metformin not tolerated?
1st line = gliptin or sulfonylurea or pioglitazone
2nd line once HbA1c >58mmol/L (7.5%):
Gliptin + pioglitazone
Gliptin + sulfonylurea
Pioglitazone + sulfonylurea
3rd line = insulin
When HbA1c hits what level do you move onto the next treatment in T2DM?
58 mmol/L or 7.5%
When can you use metformin + sulfonylurea + GLP-1 mimetic?
When normal triple therapy not effective (3rd line), then use this if BMI >35, or BMI<35 but weight loss or using insulin would have a big impact
Metformin - MOA, SE’s and CI’s?
Increases insulin sensitivity + decreases hepatic neogenesis
Nausea, diarrhoea, abdominal pain, lactic acidosis
Cannot use if eGFR <30ml/minute
Sulfonylureas - Examples, MOA, SE’s?
Gliclazide or Glimepiride
Stimulate pancreatic beta cells to stimulate insulin
SE’s = hypoglycaemia, WEIGHT GAIN, hyponatraemia
Thiazolidinediones - Example, MOA, SE’s?
Pioglitazone (contraindicated in blander cancer and heart failure)
Activate PPAR-gamma receptor in adipocytes to promote adipogenesis and fatty acid reuptake, reducing peripheral insulin resistance
SE’s = Weight gain and fluid retention
DPP-4 inhibitors / Gliptins - examples, MOA and SE’s?
Vildagliptin and sitagliptin
Increases incretin levels which inhibit glucagon secretion
SE = increased risk of pancreatitis
SGLT-2 inhibitors - MOA, SE’s?
-Gliflozins
Inhibit resorption of glucose in the kidneys - typically results in WEIGHT LOSS
SE’s = UTI as more glucose in the urine
GLP-1 agonists - How do you take it, MOA and SE’s?
Exanitide
Subcut
Incretin mimetic which inhibits glucagon secretion - typically results in WEIGHT LOSS
SE’s = N&V, pancreatitis
Macrovascular complications of diabetes?
MI/CVA
Microvascular complications of diabetes?
Diabetic foot
Nephropathy
Retinopathy
Neuropathy
Microvascular complications of diabetes - diabetic foot?
ISCHAEMIA = hyperglycaemia damages blood vessels = critical toes, absent pulses and painful punched out ulcers
NEUROPATHY = hyperglycaemia can cause damage to nerves = loss of protective sensation = CHARCOTS FOOT = painless ulcers
Management of diabetic foot?
Conservative = regular inspection, comfortable therapeutic footwear. Regular chiropody
Medical = treat any infections and pain management e.g. amitriptyline
Surgical = abscesses, cellulitis or gangrene
Microvascular complications - nephropathy?
Hyperglycaemia = nephron loss and glomerulosclerosis
Clinical features = Microalbuminaemia - urine albumin:creatinine ratio > 30
Management = ACEI’s and ARBS
Microvascular complications - Retinopathy?
Leading cause of blindness <60
Due to small vessel damage = ischaemia = VEGF = neovascularisation
Classification of diabetic retinopathy
Mild NPDR = 1 or more microaneurysm
Moderate NPDR: Microaneurysms Blot haemorrhages Hard exudate Cotton wool spots, venous bleeding
Severe NPDR:
Blot haemorrhages and micro aneurysms in all quadrants
Venous bleeding in two quadrants
PROLIFERATIVE = neovascularisation
Microvascular complications of diabetes - neuropathy
Nerve damage due to hyperglycaemia
Symmetrical sensory loss = polyneuropathy
Mononeuropathy = CN3 and 6 palsies
Autonomic neuropathy = postural hypotension, diarrhoea, urinary retention
Physiology of DKA?
Reduced insulin means cannot utilise glucose = B-oxidation of fats = Ketones
Dehydration due severe hyperglycaemia causing osmotic diuresis. Also ketones cause vomiting
Diagnostic criteria of ketoacidosis?
Glucose >11mmol or known diabetic
pH <7.3
Bicarbonate <15mmol/L
Ketones >3mmol/L or urine ketones ++ on dipstick
Management of DKA?
ABC Fluids until systolic >90 then: 1L over 2 hours 1L over 2 hours 1L over 4 hours 1L over 4 hours 1L over 6 hours
Start potassium in the second bag of fluids:
>5.5 = none needed
3.5-5.5 = 40mmol/L
<3.5 = consult senior
Insulin act rapid 0.1unit / kg / hour. Once glucose >15 start 5% dextrose infusion
LMWH
At what rate do we want to improve in DKA, and when is resolution?
Continuous monitoring aiming to reduce ketones by >0.5 per hour, or increase bicarb by >3 per hour
Ketones <0.3mmol/L venous pH >7.3, or bicarb >15
What are the criteria for HHS?
Profound hyperglycaemia > 33
Hyperosmolarity = serum osm > 320
Dehydration in the absence ketoacidosis = pH >7.3 and ketones <0.3mmol/L
Management of HSS?
Rehydrate the same as DKA
Wait 1 hour prior to starting insulin as many may not need it
What are the causes of thyrotoxicosis?
Most common = graves
Toxic nodular goitre (Hot nodules)
Acute phase of hashimotos / de Quervains (decreased iodine uptake)
Graves specific signs ?
Diffuse goitre and increased uptake
Ophthalmopathy = Exophthalmos and ophthalmoplegia
Pre-tibial myxoedema
Thyroid acropachy
Management of thyrotoxicosis?
Anti-thyroid drugs = Carbimazole 40mg
SE = agranulocytosis
Symptomatic = propranolol to ameliorate the adrenergic symptoms
Refractory = radioiodine
Clinical features of a thyroid storm?
Raised temperature
Tachycardia and AF
Acute abdomen / heart failure
Agitated and confused
Management of thyroid storm?
Fluids and NGT
Propranolol
Carbimzaole and lugs iodine
Hydrocortisone
Causes of hypothyroid?
Hashimotos thyroiditis commonest in UK = anti-TPO and anti-Tg
Atrophic thyroiditis = similar to hashimotos but antibodies vs TSH and TPO
Post-partum
De Quervains
Management of hypothyroid?
Levothyroxine:
Start dose low in elderly / IHD
Normal dose 50-100ug OD
Therapeutic goal is TSH 0.5-2.5
SE’s:
Hyperthyroid, reduced BM density, worsening of angina
What reduces levothyroxine absorption?
When taken with iron
What is simple colloid goitre?
A benign diffuse multinodular goitre
Mass effect = Dysphagia, stridor and SVC obstruction
What is hashimotos?
Autoimmune disease vs anti-TPO
Clinical features = Middle aged women, diffuse NON-TENDER goitre
Management of hashimotos?
Levothyroxine
Most common cause of hypothyroid in developing world?
Iodine deficiency
= diffuse massive thyroid enlargement
What is subacute thyroiditis?
Often following viral infection, typically presents with:
- 4 weeks of hyperthyroidism + PAINFUL goitre
- 2 weeks of euthyroid
- Months of hypothyroid
What is the scan uptake for subacute thyroiditis?
Globally reduced uptake on iodine scan
Management of subacute thyroiditis?
Usually self-limiting
More severe may need steroids
What is Riedels thyroiditis?
Rare cause of hypothyroidism where dense fibrous tissue replaces the normal thyroid parenchyma
Clinical features of Riedels thyroiditis?
Hard, fixed painless goitre
Associated with retroperitoneal fibrosis
Management of Riedels thyroiditis?
Corticosteroids
What is graves disease?
Autoantibodies to TSH receptor antibodies and TPO antibodies
What is toxic multi nodular goitre / Plummer’s?
Gland contains a number of autonomously functioning thyroid nodules
what is the uptake in Plummer’s?
Patchy uptake on the iodine scan
Management of plumbers?
Radioiodine
What is the commonest thyroid malignancy?
Papillary carcinoma
Branching papillary structure with fibrous stroma and psammoma bodies
Clinical features of thyroid papillary carcinoma?
20-40 years
Slow growing solitary thyroid nodule
Commonly enlarged cervical LN’s
Euthyroid
Scanning shows NO UPTAKE
Management of thyroid papillary carcinoma?
Thyroidectomy
- remove any palpable cervical LN’s at the same time
Total thyroidectomy has slightly increased risk of post-op hyperparathyroidism but means any recurrence can be treated with radioiodine
Give levothyroxine too……
Tumour / mets need high TSH, which only occurs if normal tissue left - so give levothyroxine to keep TSH low
How do you check for recurrence of papillary carcinoma?
Thyroglobulin levels
Histology of follicular carcinoma?
Well developed follicular pattern
Management of follicular carcinoma?
RARE, 40-50 years
Subtotal / total thyroidectomy
May opt for a total as allows for better uptake of radioiodine for mets
Endocrine features of medullary carcinoma?
Arises from parafollicular / C-cells = excess calcitonin
May also secrete serotonin and ACTH
Clinical features of medullary carcinoma?
RARE
Stony hard tumour
Secondaries in cervical nodes and poor prognosis
Management of medullary carcinoma?
Need aggressive surgery, won’t take up radioiodine
What is anaplastic thyroid carcinoma?
Extremely aggressive tumour, appalling prognosis
Histology = sheets of differentiated cells
Will rapidly invade local structures = Recurrent laryngeal, early mets, oesophageal obstruction
Complications of thyroid surgery?
Laryngeal oedema
Recurrent laryngeal nerve damage = right sided more common due to oblique ascent
Hypocalcaemia = due to parathyroid dysfunction PC: - Tingling lips and fingers - Wheeze and stridor - Chvosteks and trousseaus
Thyroid storm
Mechanism of PTH?
Secreted in response to low calcium
Causes osteoclast activity up and increased calcium reabsorption
Causes of primary hyperparathyroidism?
Biochem?
80% = solitary adenoma 20% = hyperplasia
Raised calcium and PTH, low phosphate
Management of primary hyperPTH?
Increased fluid intake
Avoid dietary calcium and thiazides
Surgical excision if hypercalcaemia, <50 years, low T-score
Causes of secondary hyperparathyroidism?
Biochem?
Vitamin D deficiency
Chronic renal failure
Malabsorption e.g. Coeliacs
Calcium low, PTH and phosphate raised
Management of secondary hyperparathyroidism?
Correct causes
Medical = phosphate binders e.g. calcichew
Vitamin D supplementation
Surgical for renal if:
- Bone pain
- Persistent pruritus
- Soft tissue calcifications
Causes of tertiary hyperparathyroidism?
biochem?
Prolonged secondary, leads to autonomous PTH secretion
Calcium and PTH raised, low phosphate
Features of low calcium?
SCAPS:
Spasma = Trousseaus and Chvosteks Confused Anxious and irritable Prolonged QT Seizures
Causes of hypoparathyroidism?
Autoimmune
Congenital = Di George: Cardiac abnormality Abnormal facies Thymic aplasia Cleft palate Hypocalcaemia Chr22
Iatrogenic = surgery or radiation
management of hypoparathyroidism?
Calcium supplementation
What is pseudohypoparathyroidism?
Biochem?
Failure of the target organ to respond to PTH = abnormality in G protein
Low calcium, raised PTH and phosphate
How to diagnose pseudohypoparathyroidism?
Measure urinary cAMP and phosphate levels following PTH infusion.
If type 1 neither will rise
Type two only cAMP will rise
What is Cushing’s syndrome?
Clinical state produced by excess glucocorticoid
Causes of Cushing syndrome?
ACTH dependant = High ACTH:
- Cushings disease 80% = Pituitary tumour secreting ACTH, causes adrenal hyperplasia
- Ectopic ACTH from small cell lung cancer or carcinoid tumour
ACTH independent = low ACTH:
- Adrenal adenoma 15%
- Iatrogenic steroids
- Carney complex = syndrome including cardiac myxoma
Pseudo cushings = Due to alcohol and stress
Clinical features of Cushing’s?
Catabolic state = Proximal myopathy, striae and bruising
Glucocorticoids = DM, obesity
MR affects = HTN and hypokalaemia
Investigations to confirm Cushings?
Overnight dexamethasone suppression test and urinary 24 hour cortisol
Then we need to localise:
1st line = 9am and midnight ACTH. if suppressed then non-ACTH cause
Next do a high dose dexamethasone suppression test - pituitary source (cushings disease) will be supressed, ectopic / adrenal will not
Management of Cushings?
Treat the cause:
Cushings disease = Trans=sphenoidal excision
- may also need bilateral adrenalectomy to control excess cortisol
Adrenal adenoma = adrenalectomy
Ectopic ACTH = tumour excision and metyrapone can inhibit cortisol synthesis
What is Nelson’s syndrome?
Rapid enlargement of a pituitary adenoma following bilateral adrenalectomy for Cushings syndrome
= Bitemporal hemianopia and hyper pigmentation
Primary causes of hyperaldosteronism?
Bilateral adrenal hyperplasia 70%
Adrenocortical adenoma (CONNS) 30%
Clinical features of hyperaldosteronism?
HYPOKALAEMIA = weakness, hypotonia, hyporeflexia and cramps
Paraesthesia
HTN
What does aldosterone do?
Absorbs sodium and water, excreting potassium by acting on the MR receptors in the collecting duct and DCT
Biochemistry and ECG changes in hyperaldosteronism?
Low potassium, high sodium
HYPOKALAEMIC ALKALOSIS
High serum aldosterone, low serum renin
Can do adrenal vein sampling
ECG = flat t-waves, depressed ST
Management of primary hyperaldosteronism?
Adrenal adenoma = surgery
Bilateral hyperplasia = Aldosterone antagonist = spironolactone
Secondary causes of hyperasldosteronism?
Due to increased renin from reduced renal perfusion:
Renal artery stenosis
Diuretics
CCF
Nephrotic syndrome
NORMAL ALDOSTERONE TO RENIN RATIO
What is barters syndrome?
Autosomal recessive condition associated with severe hypokalaemia
Defective chloride absorption at the Na K 2Cl co-transporter in ascending loop of Henle
Causes of adrenal insufficiency?
Primary = Addisons = destruction of there adrenal cortex so no glucocorticoids or mineralcorticoids:
- Autoimmune 80%
- TB commonest worldwide
- Metastases
- CAH
Secondary = hypothalamus or pituitary failure:
- Chronic steroid use
- Pituitary apoplexy / Sheehan’s
- Pituitary macroadenoma
clinical features of adrenal failure?
Weight loss N&V Hyperpigmentation Postural hypotension Vitiligo Hypoglycaemia
Which type of adrenal insufficiency will NOT give you hyper pigmentation?
Secondary as you still have normal mineralocorticoid production = low ACTH
Biochemistry for adrenal insufficiency?
Low sodium and high potassium
ACTH stimulation test:
- Plasma cortisol measured before and 30 minutes after giving 250ug IM Synacthen
- excludes Addison’s if raised cortisol
Management of adrenal insufficiency?
Hydrocortisone and fludrocortisone
Don’t stop steroids suddenly during illness, double dose!
What is addisonian crisis?
Shocked = tachycardia, postural BP, oliguria and confused
Management = Hydrocortisone
Fluids
Septic screen and treat underlying cause
What is a phaeochromocytoma?
Catecholamine producing tumour arising from sympathetic paraganglia, usually in the adtrenal medulla
Clinical features of phaeochromocytoma?
Classic triad = headaches, sweating and tachycardia
Investigations for phaeochromocytoma?
24 hour urinary metanephrines
Abdominal CT/MRI
Management of phaeochromocytoma?
Often volume depleted = fluids
Surgical adrenalectomy is definitive, but must stabilise first:
alpha blockers first = phenoxybenzamine 10mg PO BD
Beta blockers = propranolol
Phaeochromocytoma: Clinical presentation and management of hypertensive crisis?
PC = pallor, pulsating headache, feeling of impending doom and raised BP
Phentolamine 5mg IV of Sodium nitroprusside
Followed by elective surgery 4 weeks after alpha blockade
What is multiple endocrine neoplasia?
Functioning hormone tumours In multiple organs.
Autosomal dominant
What is MEN1?
Pituitary adenoma = prolactin or GH
Parathyroid adenoma
Pancreatic tumours = Gastrinoma or insulinoma
What is MEN2a?
Thyroid medullary cancer
Phaeo
Parathyroid
What is MEN2b?
Thyroid medullary cancer
Phaeo
Marfanoid habitus and neuromas
Genes associated with MEN1 vs MEN2?
MEN1 = MEN1
MEN2 = RET oncogene
Clinical features of MEN?
Positive FHx and young age
Kidney stones
MEN1 = Facial angiofibromas and collagenomas
MEN2 = Neuromas = bumpy lips, marfanoid, palpable thyroid nodules
Investigations for MEN?
PTH levels, calcium
MEN1 = fasting serum gastrin, IGF 1 levels, prolactin
MEN2 = Serum calcitonin and CEA = medullary thyroid, urinary metanephrines
management of MEN?
HyperPTH = fluids and bisphosphonates / Cincalet
Gastrinoma = PPI Prolactinoma = Bromocriptine
Phaeo = alpha and BB, adrenalectomy
What is Carney complex?
LAMES
Lentigenes = spotty pigmentation
Atrial Myxoma
Endocrine tumours = pituitary or adrenal hyperplasia
Schwannomas
What is peutz-Jeghers?
Autosomal dominant disease characterised by numerous hamartomatous polyps in the GI tract
Clinical features of Peutz Jeghers?
Mucocutaneous freckling on lips / mucosa / palms and soles
GI hamartomas = obstruction and bleeds
Pancreatic endocrine tumours
What is Von Hippel-Lindau?
Autosomal dominant condition with an abnormality in the VHL gene located on chromosome 3
clinical features of Von hippie-Lindau syndrome?
Renal cysts
Bilateral renal cell carcinoma
Haemangioblastomas - often in cerebellum = cerebellar signs
Phaeochromocytoma
Clinical features of NFT1?
Cafe au last spots >6, 15mm in diameter Axillary and groin freckling Iris hamartomas (lisch nodules) Peripheral neurofibromas Scoliosis Phaeo
clinical features of NFT2?
bilateral acoustic neuromas
Multiple schwannomas and meningiomas
What does the hypothalamus release, and what does this cause the pituitary to release?
TRH - TSH and prolactin
CRH - ACTH
GnRH - LH and FSH
GHRH - GH
What do the pituitary hormones act upon?
TSH acts on thyroid = thyroxine = HR, temperature and metabolism
ACTH acts upon the liver = cortisol = maintains blood sugar and BP
LH and FSH = testosterone or oestradiol = spermato/oo-genesis
GH acts on liver = IGF1
Prolactin acts upon the breast = MILK
What is released from the posterior pituitary?
ADH and oxytocin
Causes of hypopituitarism?
Neoplastic =
- Pituitary adenoma (upper fields first)
- Craniopharyngoma (lower fields first), originates from Rathkes pouch
Vascular = Pituitary apoplexy, or Sheehan’s
Infiltrative = Sarcoidosis or TB
Congenital = Kallmans - delayed puberty, anosmia, tall and hypogonadism
Investigations and management for hypopituitarism?
Test all the hormones e.g. low 9am cortisol, TFT’s, sex hormones low, prolactin can be raised if prolactinoma, IGF-1 low
Management = replace all the hormones e.g. Hydrocortisone, levothyroxine, gonadotrophin, recombinant human GH and desmopressim
Classification of pituitary tumours?
<1cm = Microadenoma
> 1cm = Macroadenoma
40% produce prolactin
Clinical features of pituitary tumours?
Mass effects = headaches, bitemporal hemianopia, CN3/4/5/6 palsies
Hormone effects:
Prolactin = galactorrhoea, low libido
GH = acromegaly
ACTH = cushings
Management of pituitary tumours?
If prolactin = Cabergoline 0.25mg PO twice weekly
GH = octreotide
ACTH = tran-sphenoidal excision
Cabergoline SE’s?
Nausea, postural hypotension and fibrosis
What is acromegaly?
Chronic progressive disease due to excessive secretion of growth hormone.
GH stimulates bone and soft tissue via IGF1
Causes of acromegaly?
99% = pituitary adenoma
Rarely hyperplasia from GHRH secreting carcinoid tumour
Clinical features of acromegaly?
Coarse facial appearance
Carpal tunnel
Large tongue and prognathism
Excess sweating and oily skin
features of pituitary tumour e.g. bitemporal hemianopia and headaches
Investigations in acromegaly?
Visual fields
OGTT with serial GH measurements - normal patient swill suppress to <2
Pituitary MRI
Management of acromegaly?
First line = aran-sphenoidal excision
2nd line = somatostatin analogues = octreotide 10mg IM ever month for three months
What is diabetes insidious?
Metabolic disorder characterised by the inability to concentrate urine
What causes DI?
either an absolute deficiency in ADH from the posterior pituitary, or an insensitivity to the receptors
Causes of cranial DI?
Idiopathic
Trauma
Post pituitary surgery
DIDMOAD / Wolframs
Cause sof nephrogenic DI?
Genetic
Electrolytes = Hypercalcaemia and hypokalaemia
Drugs e.g. democlocycline
Investigations for DI?
High plasma osm, low urine osm (if urine >700 excludes DI)
Water deprivation test = urine osmolality stays low
Desmopressin test = if nephrogenic still won’t respond
Management of DI?
Fluids
Cranial = desmopressin
Nephrogenic = treat underlying cause, give chlorothiazide
Causes of hirsutism?
Familial
Idiopathic
Raised androgens e.g. PCOS, Cushings
Clinical features of PCOS?
Investigations?
Management?
Subfertility / infertility
Oligo / amenorrhoea
Hirsutism / acne
Obesity
USS of ovaries
Raised LH:FSH ratio
Management = Metformin, COCP, clomiphene for infertility
Causes of gynaecomastia?
Cirrhosis Hypogonadism Hyperthyroid Oestrogen Drugs e.g. spironolactonme
What is orlistat?
weight loss drug, pancreatic lipase inhibitor
SE’s of orlistat?
Faecal urgency / incontinence and flatus
Indications for orlistat?
Part of overall weight loss plan
BMI >28 with RF’s
BMI > 30
Continued weight loss
