Endocrinology / Metabolic disease Flashcards
Hypertriglyceridaemia treatment
1) Fibrates (fenofibrate, gemfibrozil)
2) Add statin OR ezetimibe
Omega 3 good for all (reduces CVD deaths)
Treatment (familial) hypercholesterolaemia
1) high dose statin
2) Add ezetimibe
Others:
- evolucumab - if LDL peristently >3.5
- fibrates… more for hypertriglyceridaemia
Hypothyroidism features
- main: tired, cold intolerance, bradycardia, weight gain
- skin: sweating, yellow tinge, brittle nails, coarse hair, myxoedema, co-exsistant alopecia / vitiligo
- eyes: periorbital oedema
- GI: constipation, decreased taste, co-existant pernicious anaemia, co-existant coeliac
- neuromuscular: thyroid myopathy, carpal tunnel / peripheral neuropathies, myxoedema coma, hashimoto encephalopathy
McArdle’s Disease
- autosomal recessive type V glycogen storage disease
- decreased muscle glycogenolysis
- muscle pain and stiffness following exercise w/ second wind phenomenon
- muscle cramps
- myoglobinuria
- low lactate levels during exercise
- avoidance of low carbohydrate diets
- low intensity aerobic exercise
Hypokalaemia
1) urinary K
- low? Alkalosis, insulin, extrarenal losses
- high? renal losses confirmed
2) blood pressure, renin, aldosterone, blood gas
- high blood pressure, high renin: malignant HTN, renovascular disease, renin secreting tumour
- high blood pressure, low renin, high aldosterone: hyperaldosteronism e.g. Conn’s / adrenal hyperplasia
- high blood pressure, low renin, low aldosterone: Liddle’s, apparent mineralocorticoid excess (congenital adrenal hyperplasia, liquorice ingestion), cushing’s, mineralocorticoid ingestion
- low/normal blood pressure, alkalosis: Bartter, Gietelman, diuretics, magnesium deficiency
- low/normal blood pressure, acidosis: RTA (1/2 - 4 is hyperK)
Criteria for atorvastatin 20mg ON in T1DM
aged > 40 OR
>10 years diagnosis OR
diabetic nephropathy OR
other CVD risk factors
Fabry Disease
X linked recessive lysosomal storage disease
Symptom onset in adolescence
Pain on exercise
Hypertension
Cardiomegaly
CKD
Thrombosis e.g. VTE / CVA
Angiokeratomas on skin (red macules / papules) typically peri-umbilical
Mx: alpha galactosidase A - enzyme replacement
Diagnosing sulfonylureas as cause of hypoglycaemia
- insulin / c-peptide measurement not helpful
- urinary sulfonylurea can be measured
Addisonian patients taking steroids during periods of illness should change their steroid dose by how much and for how long?
2-3 x dose for 3 days and review
Side effects of sulfonylureas
Hypogylcaemia, weight gain
Indications for GLP-1 drugs e.g. exenatide, liraglutide, dulaglutide
Add to metformin / sulfonylurea for BM control if
- BMI ≥35 and problems associated with high weight
- BMI <35 and insulin is unacceptable because of hypo risk OR weight loss would benefit co-morbidities (e.g. ischaemic heart disease)
DPP4 inhibitors e.g. sitagliptin
- do not cause weight gain
- no hypos
- HOWEVER, has a heart failure risk
SGLT2 inhibitors e.g. dapagliflozin
Benefits: weight loss, improvements in heart failure, no hypos
Indications: BM control in addition to metformin in heart failure patients
Risks: UTIs, DKA
Subacute (post viral) thyroiditis mx
1) NSAIDs
2) prednisolone
MEN-1
AD PaPaPi - parathyroid adenoma - pancreatic tumour (most typically gastrinoma -> zollinger-ellison syndrome) - pituitary gland tumours
MEN-2a
AD PaPhThy - parathyroid adenoma - phaeo - medullary thyroid cancer
MEN-2b
AD
PhThy + marfanoid and neurofibromas
Sick euthyroidism
- low T3 and T4
- normal / low TSH
- associated with severe illness
- do not treat!
Type 1 amiodarone thyroiditis
- goitre
- USS hypervascularity
- Mx: stop amiodarone, carbimazole
Type 2 amiodarone thyroiditis
- no goitre
- low radioiodine uptake
- Mx: stop amiodarone, start steroids
Type of diabetes caused by hereditary haemochromatosis
Type 2 DM
Papillary carcinoma
- most common
- hard nodules
- often young females
- good prognosis
- Mx: total thyroidectomy + radioiodine therapy
- yearly thyroglobulin to monitor recurrence
Folliculuar adenoma and carcinoma
- adenoma is without local capsular invasion
- solitary thyroid nodule
- Mx: total thyroidectomy + radioiodine therapy
- yearly thyroglobulin to monitor recurrence
Medullary carcinoma
- MEN-2 associated
- secretes calcitonin - marker of recurrence
- poor prognosis when nodes invovled
Anaplastic carcinoma
- elderly females
- local invasion common
- Mx: resection where possible. Consider palliative surgery + RT
Thyroid lymphoma
- rare
- associated with Hashimoto’s
Relevance of TSH in thyroid cancer
- high risk cancers should have TSH suppressed <0.1 with supplemental thyroxine post op
- if low risk aim TSH 0.1-0.5
Thyroid nodule ix
- USS: <1cm, age 20-60, no symptoms, not rapidly growing, no prev ca / irradiation -> no further ix
- otherwise FNA
Congenital adrenal hyperplasia phenotypes
- classical phenotype: presents early childhood with salt wasting and failure to make cortisol
- non-classical phenotype: androgen excess -> hirsuitism, primary amenorrhoea, acne, precocious puberty in males
Causes of CAH
- 95% 21 hydroxylase deficiency. 60-70% salt wasting crisis in early life
- 11 beta hydroxylase deficiency: apparent mineralocorticoid excess (low renin/aldosterone), androgen excess. Classically ambiguous genitalia
- 17-hydroxylase deficiency: non-virilising in females, inter-sex in boys, hypertension
Management of hyperthyroidism in pregnancy
- 1st trimester: propylthiouracil (risk hepatotoxicity)
- 2nd trimester: carbimazole (risk congenital defects)
- breast feeding: propylthiouracil
- keep free T4 in upper 1/3 of normal range to avoid foetal hypothyroidism
Management of hypothyroidism in pregnancy
- most require 50% increase in dose
- do this in steps of 25mcg and review every month
- thyroxine is safe with pregnancy and breastfeeding
Post partum thyroiditis
- hyperthyroidism in first few months after birth -> normal / low thereafter
- TPO and TSH -R abs may be +ve
Grave’s in pregnancy
- measure TSH-R abs and treat if +ve, even if euthyroid
as can cross placental barrier
Pseudohypoparathyroidism
- PTH insensitivity
- AD inheritance of receptor GPC-R defect
- low calcium, high phosphate, but HIGH PTH
- short 4-5th metacarpals, short stature, cognitive impairment, obesity
VIPoma
- pancreatic tumour with malignant potential
- watery diarrhoea, hypokalaemia, acidosis
- facial flushing
Klinefelter syndrome
- XXY Males
- tall
- cognitive impairment
- lack of secondary sexual characteristics
- infertile
- gynaecomastia
- raised FSH & LH
- low testosterone
Autoimmune polyglandular syndrome type 2
Triad
- primary adrenal insufficiency
- type 1 diabetes
- hypothyroidism
NB: sometimes primary gonadal failure is also present.
Assoc with vitiligo and pernicious anaemia
Autoimmune polyglandular syndrome type 1
2+
- hypoparathyroidism
- primary adrenal insufficiency
- chronic mucocutaneous candidiasis
- primary gonadal failure
- primary hypothyroidism
Thyrotoxicosis fictitia
- thyroxine OD
- high T4, low TSH
- THYROGLOBULIN LEVELS LOW
- low uptake of thyroid scintigraphy
- NO GOITRE
Hyperprolactinaemia causes
- pituitary adenoma -> pituitary stalk compression
- prolactinoma (macro >10000)
- acromegaly
- drugs: D-R antagonists, verapamil,
- hypothyroidism
- pregnancy
- oestrogens
- physiological: stress, sleep, exercise
- seizures
Features of hyperprolactinaemia
- men: impotence, loss of libido
- women: amenorrhoea
- both: galactorrhoea
Thyroid storm mx
- IV fluids
- electrolyte replacement
- carbimazole / propylthiouracil -> then lugol’s iodine
- hydrocortisone 100mg
- VTE prophylaxis
Myxoedema coma management
- IV fluids
- IV hydrocortisone (until adrenal insufficiency excluded)
- levothyroxine (T4) and liothyronine (T3) IV
- electrolyte replacement
Features of acquired GH deficiency (e.g. secondary to TBI)
- fatigue
- depression
- reduced muscle mass
- reduced libido
- increased fat mass
Acromegaly mx
1) Transphenoidal excision
2) Somatostatin analogues e.g. octreotide
Cushing’s ix
Initial test options
- 24 hour urinary cortisol
- midnight cortisol
1st proper test
- overnight dexamethasone suppression test -> failure to suppress indicates Cushing’s
Late night ACTH is used for localisation
- suppressed indicates adrenal adenoma / tumour
- non-suppressed suggests ACTH dependent cause e.g. pituitary OR ectopic ACTH
Other localisation tests
- MRI pituitary (>6mm significant)
- high dose dex suppression (pituitary adenoma will suppress)
- inferior petrosal sinus sampling (central -> peripheral ACTH gradient suggests central cause)
Type of diabetes insipidus caused by lithium
Nephrogenic diabetes insipidus
Mx nephrogenic diabetes insipidus
- Low salt diet
- Discontinue precipitating agent
2) Thiazide diuretics or amiloride
Mx hypertension in Conn’s
Spironolactone
Mx of Grave’s if neutropenia occurs during carbimazole
- stop carbimazole permanently
- not for propylthiouracil
- surgery or radioiodine instead
Mx macroprolactinoma
- dopamine agonist e.g. cabergoline
- transphenoidal excision only if medical mx fails
Ix insulinoma
- insulin, C-peptide and glucose during an episode
- no role for random bloods of the above
- exercise provocation after overnight fast +/- above bloods
Apparent mineralocorticoid excess
- low renin and aldosterone
- AR 11-hydroxysteroid dehydrogenase mutation
- excess liquorice can inhibit this enzyme too
Gestational diabetes diagnosis and management
Diagnosis
- fasting glucose ≥5.6
- 2 hour glucose ≥7.8
Fasting BM <7
- > trial diet/exercise and re-check in 1-2 weeks
- if BMs still raised but <7 -> metformin (OR glibenclamide)
- if BMs still raised, <7 but complications with baby -> insulin
BMs ≥ 7
- insulin
Thyroid eye disease
Aetiology
- 25-50% graves
- can have any thyroid status
- RFs: smoking, radioiodine
Features
- exopthalmos
- conjuntival oedema
- optic disc swelling
- loss of colour vision
- complex ophthalmoplegia
Mx
- topical lubricants
- steroids +/- decompressive surgery
Agents that reduce thyroxine absorption
- calcium
- iron
- PPIs
- antacids
- colestyramine
Effect of beta blockers on thyroxine
reduces conversion to more active t3
