Endo Flashcards
Antibodies in thyroid glands
- Anti-thyroid peroxidase Abs: autoimmune so Hashimito’s and Graves
- Anti-thyroglobulin Abs: Graves, Hashimoto, cancer
- TSH receptor Abs: bind to TSH and stimulate so Graves
Radioisotope findings in thyroid
- diffuse: Graves
- focal area: toxic multinodular goitre and adenomas
- cold area: cancer
difference between primary and secondary hyperT
- 1: thyroid gland behaving abnormally
- 2: hypothal/pit behaving abnormally
most common cause of hyperthyroidism.
Graves
Toxic multinodular goitre
- aka Plummer’s disease
- nodules develop on the thyroid gland, which are unregulated by the thyroid axis and produce excessive thyroid hormones
- most common in over 50 y/os
Reason for exopthalmos in Graves
- TSH receptors behind the eye
- Inflammation, swelling and hypertrophy of the tissue behind the eyeballs forces them forward
What is pretibial myxoedema
- caused by deposits of glycosaminoglycans under the skin on the anterior aspect of the leg (the pre-tibial area).
- Gives the skin a discoloured, waxy, oedematous appearance over this area
- Specific to Grave’s: reaction to TSHR abs
causes of hyperthyroidism
GIST
- Graves
- Inflammation (thyroiditis)
- Solitary toxic thyroid nodule
- Toxic multinodular goitre
Causes of hypothyroidism
- Hashimoto’s (developed)
- Iodine deficiency (developing)
Causes of thyroiditis (hyperT then hypoT)
- De Quervain’s thyroiditis
- Hashimoto’s thyroiditis
- Postpartum thyroiditis
- Drug-induced thyroiditis
Features of hyperthyroidism
- anxiety and tachycardia
- sweating and heat intolerance
- weight loss
- Fatigue
- Insomnia
- Frequent loose stools
- Sexual dysfunction
- Brisk reflexes on examination
Graves’ disease specific features relating to the presence of TSH receptor antibodies
- Diffuse goitre (without nodules), not painful
- Eye disease, inc exophthalmos
- Pretibial myxoedema
- Thyroid acropachy (hand swelling and finger clubbing)
what is a Solitary Toxic Thyroid Nodule
usually benign adenoma
Mx- remove surgically
Phases of De Quervain’s thyroiditis
- Thyrotoxicosis (flu like sx)
- Hypothyroidism
- Return to normal
painful goitre
Mx of De Quervain’s thyroiditis
- NSAIDs for symptoms of pain and inflammation
- Beta blockers for hyperthyroidism
- Levothyroxine for hypothyroidism
what is a thyroid storm
- rare presentation of hyperthyroidism aka thyrotoxic crisis
- fever, tachycardia and delirium
- can be life-threatening
Mx of thyroid storm
- admission for monitoring
- symptomatic treatment e.g. paracetamol
- treatment underlying event
- typically IV propranolol
- anti-thyroid drugs: e.g. methimazole or propylthiouracil
- Lugol’s iodine
- dexamethasone - blocks conversion of T4 to T3
Mx of hyperthyroidism
- Carbimazole (1st line)
- Propylthiouracil
- Radioactive iodine
- Beta blockers
- Surgery
How does carbimazole work
- take for 12 to 18 months then continue on maintenance dose and either:
- The carbimazole dose is titrated to maintain normal levels
- A higher dose blocks all production, and levothyroxine is added
Risk of taking carbimazole
acute pancreatitis
How does propylthiouracil work
- preferred if pt is pregnant
- second-line drug
- Used in a similarly to carbimazole
- Small risk of severe liver reactions, including death
Potential side effect of carbimazole and PTU
agranulocytosis
How does radioactive iodine work
- drink a single dose of radioactive iodine
- emitted radiation destroys a proportion of the thyroid cells
- Remission can take 6 months, after which the thyroid is often underactive, requiring long-term levothyroxine
- Women must not be pregnant, breastfeeding and must not get pregnant within 6 months of tx
- Men must not father children within 4 months of treatment
- Limit contact with people after dose, particularly children and pregnant
How do BBs work in hyperthyroidism
- block the adrenalin-related symptoms of hyperthyroidism.
- Propranolol
- control the symptoms e.g. palpatations
Surgical mx of hyperthyroidism
- thyroidectomy
- need levothyroxine
Complications of thyroid surgery
damage to parathyroid glands can result in hypocalcaemia –> QTc elongation on ECG
drug that can cause goitre and hypothyroidism
lithium
drug that can cause hypothyroidism and thyrotoxicosis
amiodarone
causes of secondary hypothyroidism
rarer
- Tumours (e.g., pituitary adenomas)
- Surgery to the pituitary
- Radiotherapy
- Sheehan’s syndrome (where major post-partum haemorrhage causes avascular necrosis of the pituitary gland)
- Trauma
presentation of hypothyroidism
- Weight gain and fatigue
- Dry skin, coarse hair and hair loss
- Fluid retention
- Heavy or irregular periods
- Constipation
Mx of hypothyroidism
levothyroxine
What is myxoedema coma
- Hypothermia and confusion
- due to hypothyroidism
Mx of myxoedema coma
- IV thyroxine
- hydrocortisone
what is cushing’s syndrome
- prolonged high levels of glucocorticoids in the body (cortisol)
- hypokalaemic metabolic alkalosis
What is cushing’s disease
pituitary adenoma secreting excessive ACTH, which stimulates excessive cortisol release from the adrenal glands.
Not the only cause of Cushing’s syndrome
Causes of Cushing’s syndrome
CAPE
- Cushing’s disease
- Adrenal adenoma
- Paraneoplastic (ACTH released from a tumour outside of pituitary e.g. SCLC, carcinoid tumour)
- Exogenous steroids (dex, pred)
Features of Cushing’s
- moon face
- buffalo hump
- abdominal striae
- central obesity
- proximal limb muscle wasting
- easy bruising
- hirsutism
- hyperpigmentation (due to ACTH)
Conditions caused by Cushing’s
- Hypertension
- Cardiac hypertrophy
- Type 2 diabetes
- Dyslipidaemia
- Osteoporosis
- Adverse mental health
how does ACTH cause skin bronzing
stimulates melanocytes to produce melanin
how can you differentiate the cause of excess cortisol
Cushing’s disease and ectopic ACTH have excess ACTH so bronzing
Adrenal adenoma and exogenous don’t have it
Ix for Cushing’s
- Overnight dexamethasone suppression test: should reduce cortisol, -veFB on CRH
- 24hr urinary free cortisol
- inferior pituitary
petrosal sinus
sampling - CT/PET to find ectopic source
Mx of Cushing’s syndrome
- trans-sphenoidal surgery to remove pituitary adenoma
- surgical removal of adrenal tumour
- surgical removal of tumour producing ectopic ATC e.g. SCLC
- bilateral adrenalectomy and then lifelong steroid replacement
key presenting feature of hyperaldosteronism
hypertension
where is renin produced
JG cell in afferent arterioles in kidney
where is ACE made
lungs
what is the effect of angiotensin II
- stimulates release of aldosterone from adrenals
- vasconstriction increasing BP
what is aldosterone and its effects
mineralocorticooid steroid acts on nephron to:
- increase sodium reabsorption
- increase potassium and hydrogen secretion
What is Primary hyperaldosteronism
- adrenal glands produce too much aldosterone
- renin low because of high BP
causes of primary hperaldosteronism
- Bilateral adrenal hyperplasia (most common)
- An adrenal adenoma secreting aldosterone (known as Conn’s syndrome)
- Familial hyperaldosteronism (rare)
What is secondary hyperaldosteronism
- excess renin stimulating excess aldosterone
causes of secondary hyperaldosteronism
renin is released due to disproportionately lower blood pressure in the kidneys, usually due to:
- Renal artery stenosis
- Heart failure
- Liver cirrhosis and ascites
Ix for hyperaldosteronism
aldosterone: renin
high aldosterone and low renin= primary (conn’s)
high aldosterone and high renin = secondary
effects of aldosterone
- Raised blood pressure (hypertension)
- Low potassium (hypokalaemia)
- Blood gas analysis (alkalosis)
Mx of hyperaldosteronism
- eplerenone
- spironolactone
- > 4cm surgical removal of adrenal adenoma
electrolyte imbalance in hyperaldosteronism (conn’s)
high Na
low K
what is adrenal insufficiency
adrenal glands do not produce enough steroid hormones, particularly cortisol and aldosterone
Addison’s disease
- adrenal glands have been damaged
- reduced cortisol and aldosterone
- primary adrenal insufficiency
- MC cause if autoimmune
electrolyte imbalance in adrenal insufficiency
because low cortisol and aldosterone
- low Na
- high K
- low glucose
what is secondary adrenal insufficiency
inadequate adrenocorticotropic hormone (ACTH) and a lack of stimulation of the adrenal glands, leading to low cortisol.
loss or damage to pituitary
causes of secondary adrenal insufficiency
- Tumours (e.g., pituitary adenomas)
- Surgery to the pituitary
- Radiotherapy
- Sheehan’s syndrome (where major post-partum haemorrhage causes avascular necrosis of the pituitary gland)
- Trauma
What is tertiary adrenal insufficiency
- Inadequate corticotropin-releasing hormone (CRH) release by the hypothalamus
- usually due to long term steroids
Presentation of adrenal insufficiency
- fatigue
- Muscle weakness
- Muscle cramps
- Dizziness and fainting
- Thirst and craving salt
- Weight loss
- Abdominal pain
- Depression
- Reduced libido
Signs of adrenal insufficiency
- bronze hyperpigmentation (low cortisol so ACTH stimulated, which stimulated melanocytes to produce melanin)
- hypotension (postural)
Ix for adrenal insufficiency
- hyponatraemia
- short SynACTHen test: ACTH can be measured directly. High in primary, low in secondary
Mx of adrenal insufficiency
- replace steroids with hydrocortisone for cortisol and fludrocortisone for aldosterone
- medical alert tag
- double dose during illness
What is Addisonian crisis
- severe adrenal insufficiency
- Reduced consciousness
- Hypotension
- Hypoglycaemia
- Hyponatraemia and hyperkalaemia
- Can be triggered by infection etc.
Mx of Addisonian crisis
- IM or IV 100mg hydrocortisone
- IV fluids
- IV dextrose
Ideal body glucose conc
4.4-6.1
how to diagnose DKA
- Hyperglycaemia >11
- Ketonsis >3
- Acidosis <7.3
Mx of DKA
- IV fluids over 48hrs
- Insulin fixed rate infusion started after 1hr + 40mmol potassium as insulin drives it into cells
- dextrose when glucose <14
can stop IV insulin and glucose when on subcut and no more ketones or acidosis and more alert and wanting to eat food
complications during DKA mx
- hypoglycaemia
- cerebral oedema
- hypokalaemia
- pulmonary oedema
autoantibodes in T1DM
- Anti-islet cell antibodies
- Anti-GAD antibodies
- Anti-insulin antibodies
long term complications of T1DM
Macrovascular
- CAD
- peripheral ischaemia
- stroke and hypertension
Microvascular
- peripheral neuropathy
- retinopathy
- kidney disease (nephropathy)
- UTI, candidiasis, pneumonia
HbA1c targets in T2DM
- 48 for new T2
- 48 for Lifestyle + metformin
- 53mmol/mol for any drug that may cause hypoglycaemia (sulfonylurea)
- 53 for pt requiring more than one antidiabetic medication
Mx of T2DM flowchart
- metformin ( and add SGLT2 if CVD risk)
- sulfonylurea, pioglitazone, DPP-4 inhibitor or SGLT-2 inhibitor
- triple therapy or insulin therapy
- switch one of triple therapy to GLP1 (BMI >35)
example of SGLT2 inihibitor
flozins (dapaglaflozin)
wee out sugar
example of DPP4 inhibitor
gliptins (sitagliptin)
cause headaches
example of sulfonylureas
amides/ides (gliclazide)
can cause weight gain
when is pioglitazone contradindicated
in heart failure
side effects of metformin
- GI sx (try modified release)
- lactic acidosis secondary to AKI
what is Hyperosmolar Hyperglycemic State
- rare but potentially fatal complication of T2DM
- hyperosmolality (water loss leads to very concentrated blood)
- high sugar levels (hyperglycaemia)
- absence of ketones
presentation of HHS
- polyuria
- polydipsia
- weight loss
- dehydration
- tachycardia
- hypotension
- confusion
Mx of HHS
IV fluids
senior escalation
careful monitoring
options for mx of diabetic neuropathy
- Amitriptyline – TCA
- Duloxetine – SNRI (don’t use if eGFR<30)
- Gabapentin –anticonvulsant
- Pregabalin – anticonvulsant
what is acromegaly
excess growth hormone from pituitary
presentation of acromegaly
SOL in pituitary- headache and bitemporal hemianopia
- frontal bossing
- coarse sweaty skin
- large nose, hands, feet, jaw
- macroglossia
- Hypertension, T2DM, hypertrophic heart, arthritis
- bilateral carpal tunnel syndrome
Ix for Acromegaly
- OGTT (glucose should suppress GH normally)
- Insulin like growth factor (first line)
- MRI pituitary
Findings in acromegaly
- high glucose, calcium, phosphate
- high GH and prolactin
Mx of acromegaly
- trans-sphenoidal surgery
- pituitary radiotherapy
- Pegvisomant: GH antagonist
- Octreotide: stop GH release
- Dopamine agonists (cabergoline, bromocriptine)
- somatostatin
role of PTH
raise blood calcium by:
- increase osteoclast activity
- increase calcium reabsorption in kidneys
- activate vit D, increasing Ca absorption in intestines
Sx of hypercalcaemia
stones, bones, groans and moans
- kidney stones
- painful bones
- abdo groans
- psych moans
what is primary hyperparathyroidism
- uncontrolled PTH by tumour in PT gland
- Depression, nausea, constipation, bone pain due to high Ca2+
- raised ca, low phosphate
- pepperpot skull on XR
Mx- remove tumour or cinacalcet if co-morbidities
what is secondary hyperparathyroidism
- insufficient vit D or CKD reduces Ca absorption in intestines.
- So PT glands excrete more PTH
- Ca is low or normal, PTH is high
Mx: correct vit D deficiency or renal transplant
What is tertiary hyperparathyroidism
- when secondary happens for too long causing unregulated PTH.
- Pt glands hyperplasia causes increase PTH
- so high Ca
What is SIADH
- increased release of ADH from posterior pituitary
- increases water reabsorption –>dilute blood–>hyponatraemia
- euovolaemic hyponatraemia
- high urine osmolality and high urine sodium
presentation of SIADH
- headache
- fatigue
- muscle ache and cramps
- confusion
- severe hypoNa= seizure and reduced GCS
causes of SIADH
- Post-operative after major surgery (1)
- Lung infection, particularly atypical pneumonia and lung abscesses
- Brain pathologies, e.g. head injury, stroke, intracranial haemorrhage or meningitis
- Medications (SSRIs (2) and carbamazepine)
- Malignancy, particularly small cell lung cancer (3)
- HIV
how to diagnose SIADH
- exclude other causes
- very high urine osmo and low serum osmo
Mx of SIADH
- admit if symptomatic or severe
- treat underlying cause
- fluid restrict
- Vasopressin receptor antagonist (tolvaptan)
What is osmotic demyelination syndrome
- AKA central pontine myelinolysis
- correcting severe hypoNa too quickly
What is diabetes insipidus
- lack of ADH (cranial)
- lack of response to ADH (nephrogrenic)
kidneys unable to reabsorb water and concentrate urine
What is primary polydipsia
normally functioning ADH system but drinks excessive amounts of water, leading to excessive urine production (polyuria). This is not diabetes insipidus.
Nephrogenic DI
- kidneys do not respond too ADH
Causes - idiopathic
- Medications, particularly lithium
- Genetic mutations in the ADH receptor gene
- Hypercalcaemia
- Hypokalaemia
- Kidney diseases (e.g PCKD)
What is cranial DI
- hypothalamus does not produce ADH for the pituitary gland to secrete
Causes
- idiopathic
- brain tumours, injury or surgery
- meningitis or encephalitis
- Genetic mutations in the ADH gene
- Wolfram syndrome (a genetic condition also causing optic atrophy, deafness and diabetes mellitus)
Presentation of diabetes insipidus
- Polyuria (> 3L urine per day)
- Polydipsia
- Dehydration
- Postural hypotension
Ix of diabetes insipidus
- Serum glucose (to exclude diabetes mellitus)
- Serum K+ (exclude hypokalaemia)
- Serum Ca (exclude hypercalcaemia)
- Plasma and urine osmolality
- (diagnostic): 8-hour water deprivation test
Water deprivation test findings
measure urine osmolality post deprivation.
Give desmopressin (synthetic ADH)
- primary polydipsia: deprivation increases urine osmolality- no desmopressin needed
- Cranial DI, osmolality high after giving desmopressin as kidneys can respond to ADH
- Nephrogenic DI: urine osmolality before and after desmopressin
Mx of Diabetes insipidus
- treat underlying cause (e.g. lithium)
- desmopressin for cranial DI
Nephrogenic
- access to plenty of water
- high dose desmopressin
- thiazide diuretics
- NSAIDs
what is a phaeochromacytoma
tumour of the adrenal glands that secretes unregulated and excessive amounts of catecholamines (adrenaline)
where is adrenalin produced
chromaffin cells in the medulla of the adrenal glands
genetic disorders associated with phaeochromacytoma
- Multiple endocrine neoplasia type 2 (MEN 2)
- Neurofibromatosis type 1
- Von Hippel-Lindau disease
Presentation of phaeochromacytoma
fluctuating sx due to adrenaline production
- anxiety, sweating
- headache, palpitations
- tremor
- hypertension
- tachycardia
Ix for phaeochromacytoma
- Plasma free metanephrines
- 24-hour urine catecholamines
- 24hr urine metanephrines 1st line
Mx of Phaeochromacytoma
- Alpha blockade (phenoxybenzamine or doxazosin)
- Beta blockade
- Cut out- surgery when BP is well controlled
Type of multiple endocrine Neoplasia
Men 1
Men 2a
Men 2b
MEN1
3P’s
- pituitary
- pancreatic (insulinoma)
- parathyroid (hyperparathyroidism)
MEN2a
2P’s 1M
- parathyroid
- phaeochromacytoma
- medullary thyroid
MEN 2b
1P 2M’s
- phaeochromacytoma
- Medullary thyroid,
-Mucocutaneous neuromas
(& Marfanoid)
serum osmolality formula
serum osmolality = (2 x Na+) + glucose + urea.
side effects of steroids
proximal myopathy
what can interfere with levothyroxine absorption
iron and calcium carbonate, take 4hrs apart
MODY features
Many types
onset by 25
if HNF1A subtype- give low dose sulfonylureas
When is metformin contraindicated
when GFR <30
sign of insulinoma
Whipple’s triad
1. Hypoglycaemia with fasting or exercise
2. reversal of symptoms with glucose
3. recorded low BMs at the time of sx
what is Hashimoto’s associated with the development of
MALT lymphoma
most common complication of thyroid eye disease
exposure keratopathy
other complications of thyroid eye disease
- optic neuropathy: emergency
- Strabismus and diplopia
Features of thyroid eye disease
- exophthalmos
- conjunctival oedema
- optic disc swelling
- ophthalmoplegia
- inability to close the eyelids may lead to sore, dry eyes. If severe and untreated patients can be at risk of exposure keratopathy
Mx of thyroid eye disease
- smoking cessation
- topical lubricants may be needed to help prevent corneal inflammation caused by exposure
- steroids
- radiotherapy
- surgery
Over-replacement with thyroxine increases the risk of
osteoporosis
hyperthyroidism: due to over treatment
worsening of angina
atrial fibrillation
MODY inheritance pattern
AD
Types of thyroid cancer
- papillary 70% excellent prognosis
- follicular 20%
- medullary 5% Cancer of parafollicular (C) cells, secrete calcitonin, part of MEN-2
- anaplastic 1% Not responsive to treatment, can cause pressure symptoms
- lymphoma rare Associated with Hashimoto’s thyroiditis
What is congenital adrenal hyperplasia
group of autosomal recessive disorders that impair adrenal steroid biosynthesis
- 21-hydroxylase deficiency (90%)
leading to cortisol deficiency and excess androgen production
- 11-beta hydroxylase deficiency (5%)
results in hypertension due to excess deoxycorticosterone
- 17-hydroxylase deficiency (very rare)
leads to mineralocorticoid excess with low androgen and estrogen levels
side effects of SGLT-2 inhibitors
- UTIs
- genital infection (secondary to glycosuria). Fournier’s gangrene has also been reported
- normoglycaemic ketoacidosis
- risk of lower-limb amputation
Klinefelters
- high LH and FSH
- low testosterone
- 47 XXY
- taller than average
- lack of secondary sexual characteristics
- small, firm testes
- infertile
- gynaecomastia
Impaired fasting glucose
6.1-6.9
Kallman’s syndrome
- LH & FSH low-normal and testosterone is low
- anosmia
- ‘delayed puberty’
- hypogonadism, cryptorchidism
PTH and PTHrP in malignancy
In hypercalcaemia secondary to malignancy, PTH is low, although PTHrP may be raised
Mx of gastrperesis due to diabetes
metoclopramide
how do steroids affect neutrophils
neutrophilia
Diabetic med associated with an increased risk of bladder cancer
Thiazolidinediones (pioglitazones)
what med needs to be stopped in a diabetic patient w renal impairment before CT
metformin, can induce contrast nephropathy (treat with lots of IV fluids prior)x
diabetic medications that can be taken on day of surgery
- DPP4i gliptins
- GLP 1 tides
