Endocrine Flashcards
what hormones are produced by the pituitary gland?
Anterior pituitary: -prolactin -TSH -ACTH -GH -FSH -LH posterior pituitary: -oxytocin -vasopressin (ADH)
connected to the hypothalamus via the pituitary stalk
what are the types of hypothyroidism?
-primary hypothyroidism- problem with thyroid gland itself
secondary hypothyroidism- usually disorder of the pituitary gland e.g. pituitary apoplexy
congenital hypothyroidism- problem of thyroid dysgenensis or thyroid dyshormogenesis
causes of hypothyroidism?
- hashimoto’s thyroiditis- autoimmune disease associated with T1DM, Addison’s, pernicious anaemia, anti-TPO
- Subacute thyroiditis (de Quervain’s)- painful goitre and raised ESR
- Post-partum thyroiditis
- Riedel thyroiditis
- Drugs- lithium, amiodarone
- Iron deficiency- most common in developing world
causes of thyrotoxicosis?
- Grave’s disease- associated thyroid eye disease, pretibial myxoedema
- Toxic multinodular goitre- nodules secrete excess thyroid hormones
- Drugs- amiodarone
features of hyperthyroidism?
weight loss manic heat intolerance palpitations sweating pretibial myxoedema (lateral malleolus) clubbing diarrhoea oligomenorrhagia anxiety tremor
features of hypothyroidism?
weight gain lethargy cold intolerance dry non-pitting oedema coarse scalp hair constipation menorrhagia carpal tunnel syndrome decreased deep tendon reflexes
what is subclinical hypothyroidism?
high TSH, normal T4 (on the way to developing hypothyroidism)
what are the TSH and T4 for poor compliance with thyroxine?
high TSH, normal T4
TSH is more representative of long-term thyroid control
name some thyroid auto-antibodies?
anti-TPO (generally seen in hashimotos thyroiditis)
TSH receptor antibody (seen in grave’s disease)
thyroglobulin antibody
tx of hypothyroidism?
levothyroxine
SEs- hyperthyroidism, reduced BMD, AF, worsening of angina
mx of thyrotoxicosis?
propranolol- controls symptoms
carbimazole- reduces thyroid hormone production
radioiodine treatment
how does PTH work?
bone- increases osteoclast activity= more calcium in bloodstream
kidney- increases vit D activation and calcium resorption from the distal convoluted tubule and increase phosphate excretion
how does primary hyperparathyroidism work?
seen in elderly females with an unquenchable thirst and raised PTH
most commonly due to a solitary adenoma (80%)
symptoms of hypercalcaemia
hormone profile for primary hyperparathyroidism?
high PTH
high Ca
low phosphate
urine calcium: creatinine ratio >0.01
what is seen on XR of primary hyperparathyroidism?
pepperpot skull
tx of primary hyperparathyroidism?
parathyroidectomy if elevated serum calcium >1mg/dL above normal, hypercalciuria, <50 years, neuromuscular symptoms, osteoporosis
what is secondary hyperparathyroidism?
parathyroid gland hyperplasia occurs as a result of low calcium, almost always due to chronic renal failure
few symptoms or bone disease and soft tissue calcifications
Ix of secondary hyperparathyroidism?
high PTH, Ca low or normal, high phosphate, low Vit D
tx of secondary hyperparathyroidism?
medical therapy usually
surgery if bone pain, pruritic, soft tissue calcifications
what is tertiary hyperparathyroidism?
ongoing hyperplasia after correction of underlying renal disorder
features of tertiary hyperparathyroidism?
metastatic calcification
bone pain and/or fracture
nephrolithiasis
pancreatitis
ix of tertiary hyperparathyroidism?
Can (normal or high), high PTH, phosphate low or normal, vit D normal or low, alk phos high
tx of tertiary hyperparathyroidism?
allow 12 months to elapse following treatment as many cases will resolve
may need surgery
cause of primary hypoparathyroidism?
decreased PTH secretion
e.g. secondary to thyroid disease
Ix of primary hypoparathyroidism?
low calcium, high phosphate
features of primary hypoparathyroidism?
hypocalcaemia->
- periorbital paraesthesia
- trousseau’s sign- carpal spasm after BP cuff
- chovstek’s sign- tapping over parotid gland causes facial muscles to twitch
if chronic- depression, cataracts
ECH- prolonged QT interval
tx of primary hypoparathyroidism?
alfacalcidol
pseudohypoparathyroidism causes?
target cells are insensitive to PTH
due to abnormality in a G protein
features of pseudohypoparathyroidism?
low IQ, short stature, shortened 4th and 5th metacarpals
Ix of pseudohypoparathyroidism?
low calcium, high phosphate, high PTH
diagnosis- urinary cAMP and phosphate levels -following an infusion of PTH = pseudo= no rise in either
hypo= both rise
what is pseudopseudohypoparathyroidism?
pseudohypoparathyroidism with normal biochemistry
what acid-base balance is caused by hyperkalaemia?
metabolic acidosis
as K+ rises, fewer H+ ions leave bloodstream
They compete with each other for exchange with Na across cell membranes in distal tubule
ECG changes of hyperkalaemia?
tall-tended T waves
small p waves
widened QRS leading to a sinusoidal pattern and asystole
causes of hyperkalaemia?
AKI metabolic acidosis addison's disease rhabdomyolysis massive blood transfusion drugs- ACEi, spironolactone, ARBs, ciclosporin, heparin (due to inhibition of aldosterone secretion)
foods that are high in potassium?
salt substitutes, bananas, oranges, kiwi, avocado
mx of hyperkalaemia?
potassium >7 or ECG changes= URGENT
complication= life-threatening arrhythmias
1. stop precipitating drugs
2. stabilisation of the cardiac membrane- IV calcium gluconate
3. short-term shift in potassium from extracellular to intracellular fluid compartment- combined insulin/dextrose infusion, nebulised salbutamol
4. remove potassium from the body- calcium resonium, loop diuretics, dialysis
pathophysiology of hypokalaemia?
low K+ in ECF-> water concentration gradient out of cell -> hyperpolarisation of myocyte membrane -> myocyte excitability
causes of hypokalaemia?
with hypertension:
-cushings, conns, liddle’s syndrome
without hypertension:
-diuretics, GI loss e.g. D&V, renal tubular acidosis, bartter’s syndrome, gitelman syndrome
features of hypokalaemia?
muscle weakness, hypotonia, predisposition to digoxin toxicity
ECG features of hypokalaemia?
U waves
small or absent P waves
long QT
long PR
tx of hypokalaemia?
if severe- IV K+ - transfer to high care area with cardiac monitoring, 3x 1L bags of 0.9% saline with 40mmol KCl per bag over 24 hours
causes of hypocalcaemia?
HAVOC Hypoparathyrodism Acute pancreatitis Vitamin D deficiency Osteomalacia CKD
signs and symptoms of hypocalcaemia?
SPASMS Spasms Peripheral paraesthesia Anxious Seizures Muscle tone increase
ix of hypocalcaemia?
ECG- long QT interval
tx of hypocalcaemia?
mild- Adcal
Severe- calcium gluconate
causes of primary hyperaldosteronism?
bilateral idiopathic adrenal hyperplasia
adrenal adenoma- Conn’s
Adrenal carcinoma- rare
features of primary hyperaldosteronism?
hypertension
hypokalaemia e.g. muscle weakness
metabolic alkalosis
Ix of primary hyperaldosteronism?
1st line- plasma aldosterone:renin ratio (high aldosterone and low renin. Negative feedback due to sodium from aldosterone)
high resolution CT abdomen and adrenal vein sampling
mx of primary hyperaldosteronism?
bilateral adrenocortical hyperplasia: spironolactone (aldosterone antagonist)
adrenal adenoma: surgery
what is the hypothalamic-pituitary-adrenal axis?
stress-> hypothalamus -> CRH -> pituitary -> ACTH -> adrenal cortex -> cortisol -> mineralocorticoid effects, anti-inflammatory, protein synthesis, lipolysis
what is cushing’s syndrome?
excess cortisol and loss of HPA axis feedback and loss of circadian rhythm
what is cushing’s disease?
above caused by a pituitary adenoma
causes of cushing’s syndrome?
ACTH dependent causes-
- cushing’s disease- tumour secreted ACTH
- ectopic ACTH production e.g. SCLC
ACTH independent causes-
- iatrogenic- steroids
- adrenal adenoma
- adrenal carcinoma
- carney complex: syndrome including cardiac myoxma
- micronodular adrenal dysplasia
what is pseudo-cushings?
mimics cushings but due to alcohol excess or severe depression
causes first positive dexamethasone suppression test or 24 hour urinary free cortisol
insulin stress test may be used to differentiate
symptoms of cushing’s disease?
personality changes, CNS irritability, hyperglycaemia, moon face oedema, purple striae gynaecomastia increased susceptibility to infections thin extremities, thin skin fat deposits on face and back of shoulders OP amenorrhora, hirsutism
Ix of cushing’s syndrome?
- overnight dexamethasone suppression test
- 24 hr urinary free cortisol
FBC, U&E
MRI brain if adenoma suspected
CT
how does a dexamethasone suppression test work?
the patient has a dose of dexamethasone (a synthetic glucocorticoid steroid) at night (i.e. 10pm) and their cortisol and ACTH is measured in the morning (i.e. 9am). The intention is the find out whether the dexamethasone suppresses their normal morning spike of cortisol.
if cortisol remains high after low-dose= cushing’s syndrome not due to primary cause e.g. secondary to steroids
if cortisol remains high after low dose but not high dose= cushing’s disease
if cortisol not suppressed by either= ectopic ACTH e.g. lung cancer or adrenal adenoma producing cortisol
tx of cushing’s syndrome?
if iatrogenic- stop steroids
cushing’s disease- remove pituitary adenoma
remove adrenal adenoma
ectopic ACTH- remove tumour
hormone production of adrenal gland?
- medulla- produces catecholamines and adrenaline
- cortex-
- glucocorticoids- cortisol
- mineralocorticoids- aldosterone
- gonadocorticoids- androgens
what is addison’s disease?
autoimmune destruction of adrenal glands
other causes of destruction of adrenal glands?
TB, mets, HIV, antiphospholipid syndrome, pituitary disorders, exogenous glucocorticoid therapy
features of addison’s disease?
lethargy weakness anorexia N&V weight loss salt-craving hyperpigmentation- esp palmar creases, vitiligo, hypotension, hypoglycaemia
electrolyte abnormalities of addisons?
low Na and high K
features of addisons crisis?
collapse, shock, pyrexia
Ix of addison’s disease?
-ACTH stimulation test (short synacthen test)
plasma cortisol measured-> given IM synacthen 250ug -> cortisol measured 30 mins after
-in primary care, do 9am cortisol
100-500= prompts ACTH stimulation test
tx of addison’s diaease?
replace glucocorticoids- hydrocortisone
replace mineralocorticoids- fludrocortisone (isn’t required in an Addisonian crisis)
what is acromegaly?
excess growth hormone secretion
causes of acromegaly?
pituitary adenoma
ectopic GHRH
GH production by tumours e.g. pancreatic
features of acromegaly?
coarse facial appearance, spade-like hands, increased feet size
large tongue, prognathism, interdental spaces
sweat gland hypertrophy- excessive sweating and oily skin
features of pituitary tumour- hypopituitarism, headaches, bitemporal hemianopia
raised prolactin in 1/3 of cases-> galactorrhoea
6% have MEN 1
complications of acromegaly?
hypertension
diabetes
cardiomyopathy
colorectal cancer
Ix of acromegaly?
GH levels not reliable on their own
IGF-1 levels
oral glucose load-> lack of suppression of GH to <1ug/L
pituitary MRI-> pituitary adenoma
tx of acromegaly?
trans-sphenoidal surgery- remove adenoma
DA agonists- bromocriptine
Somatostatin analogue- directly inhibit the release of GH e.g. octreotide
GH receptor antagonist e.g. pegvisomant
what is diabetes insipidus?
a condition characterised by either a deficiency of anti-diuretic hormone, ADH (cranial DI) OR an insensitivity to ADH (nephrogenic DI)
causes of cranial DI?
Idiopathic post-head injury pituitary surgery craniopharyngiomas DIDMOAD haemochromatosis
causes of nephrogenic DI?
Genetics- affects vasopressin receptor
hypercalcaemia, hypokalaemia
demeclocycline, lithium
tubulo-interstitial disease: obstruction, sickle-cell, pyelonephritis
features of DI?
polyuria, polydipsia
Ix of DI?
High plasma osmolality
low urine osmolality- >700 excludes DI
water deprivation test
mx of DI?
Nephrogenic- thiazides, low salt/protein diet
Central- desmopressin
how does vasopressin (ADH) work?
V1- blood vessels (constriction)- increases arterial pressure
V2- kidneys (fluid reabsorption)- increases arterial pressue
what causes T2DM?
A relative deficiency of insulin due to an excess in adipose tissue
symptoms of T1DM and T2DM?
T1DM- weight loss, polydispia, polyuria, DKA- vomiting, abdo pain, reduced consciousness level
T2DM- often picked up incidentally on routine bloods cells, polyuria, polydipsia
diagnosis of diabetes?
if the patient is symptomatic only one of the following, if asymptomatic must be demonstrated twice-
- fasting glucose >7mmol/L
- random glucose >11.1mmol/L
HbA1C- glycosylated Hb
>6.5% (48mmol/mol)= diagnostic
false positives for increased red cell turnover e.g. haemolytic anaemia, HIV
what is pre-diabetes?
HbA1C 42-47
or fasting glucose 6.1-6.9
also called impaired fasting glucose
what is impaired glucose tolerance?
fasting glucose <7 and OGTT 2-hour value >7.8mmol/L but less than 11.1mmol/L
mx of T1DM?
HbA1c monitored every 3-6 months target of <48
blood glucose
insulin- long-acting e.g. insulin detemir
self-testing at least 4 times a day, more frequent monitoring during periods of illness, before,during and after sport
metformin- add if BMI >25
mx of T2DM?
1st line= metformin if HbA1c >58mmol/mol, add 1 of: -gliptin -sulphonylurea -pioglitazone -SGLT-2 inhibitor
if HbA1c continues to remain >58-
- insulin or
- metformin and sulphonylurea and 1 of:
- gliptin
- pioglitazone
- SGLT-2 inhibitor
if triple therapy not tolerated, CI’d or not effective AND BMI >35-> metformin, sulphonylurea and GLP-1 mimetic
lifestyle advice for T2DM?
diet and exercise
BP target <140/80
statin if QRISK2 >10%
what to give if metformin CI’d for T2DM?
gliptin OR
sulphonylurea OR
pioglitazone
meds for diabetic neuropathy and N&V?
neuropathy- amitriptyline, duloxetine
N&V- metoclopramide
SEs of insulin?
hypoglycaemia
weight gain
lipodystrophy
how does metformin work?
SEs, CIs and positives?
increases insulin sensitivity and decreases hepatic gluconeogenesis
SE- GI upset, lactic acidosis, CI- eGFR <30ml/min
positives- can cause weight loss
examples, mechanism, SEs and CI of sulphonylureas?
e.g. gliclazide
stimulates pancreatic beta cells to secrete insulin
SE- hypoglycaemia, weight gain, hyponatraemia
CI- pregnancy and breastfeeding- causes neonatal hypoglycaemia
examples, mechanism, SE and CI of glitazones?
pioglitazone
activates PPAR-gamma receptor in adipocytes to promote adipogenesis andfatty acid uptake
SE- weight gain, fluid retention, fractures
CI- heart failure
examples, SE and positives of DPP4 inhibitors?
e.g. gliptins increases incretin levels which inhibits glucagon secretion SE- pancreatitis positive- no weight changes
example, SE and positive of SGLT-2 inhibitors?
e.g. glifozins
inhibits resorption of glucose in the kidney
SE- UTI, DKA
positives- typically results in weight loss
pathophysiology of DKA?
caused by uncontrolled liplysis which results in an excess of free fatty acids that are ultimately converted to ketone bodies
precipitating features of DKA?
Infection
MI
missed insulin doses
features of DKA?
abdo pain
polyuria, polydipsia, dehydration
Kussmaul respiration (deep hyperventilation)
Acetone-smelling breath (‘pear drop’ breath)
diagnostic criteria for DKA?
Glucose >11mmol/L or known DM
pH <7.3
BICARB <15
ketones >3 or urine ketones ++ on dipstick
mx of DKA?
- Fluid replacement- 0.9% saline 1L in first hour then 0.9% saline and KCl over 2 hours and continued with increased time intervals
(slower in 15-25y/o due to risk of cerebral oedema) - Insulin- IV .1 unit/kg/hour
- Once BG is <15mmol/l start 5% dextrose infusion
- Correction of hypokalaemia if 3.5-5.5 (senior review if lower)
- Continue with long-acting insulin
complication of DKA?
gastric stasis VTE arrhythmias cerebral oedema ARDs AKI
what is hyperosmolar hyperglycaemic state?
hyperglycaemia in T2DM-> resulting in osmotic diuresis, severe dehydration and electrolyte deficiencies
-typically presents in the elderly
clinical features of hyperosmolar hyperglycaemic state?
onset in slower than T2DM (over days) and therefore dehydration and metabolic disturbances are worse
fatigue- lethargy, N&V
neuro- decreased consciousness, headaches, papilloedema, weakness
haem- hyperviscosity- increased risk of VTE, stroke
CV- dehydration, hypotension, tachycardia
diagnosis of hyperosmolar hyperglycaemic state?
- hypovolaemia
- marked hyperglycaemia (>30mmol/L) without sigf ketonuria or acidosis
- Significantly raised serum osmolarity (>320mosmol/kg)
- 2Na + glucose + urea
mx of hyperosmolar hyperglycaemic state?
- normalise the osmolality
- replace fluid and electrolyte imbalance
- normalise blood glucose
most common type of pituitary adenoma?
prolactinomas
symptoms of pituitary adenoma?
excess hormone e.g. cushings
depletion of hormone
stretching of dura around pituitary fossa -> headache
compression of optic chiasm -> bitemporal hemianopia
Ix of pituitary adenoma?
pituitary bloods- GH, prolactin, ACTH, TFT, FSH/LH
visual field testing
MRI
mx of pituitary adenoma?
hormonal therapy (e.g. bromocriptine for prolactinomas), surgery
what is MEN type 1?
- parathyroid (95%)- hyperparathyroidism due to parathyroid hyperplasia
- pituitary (70%)
- pancreas (50%) e.g. insulinoma, gastrinoma (leading to recurrent peptic ulceration)
what is MEN type 2?
medullary thyroid cancer e.g. phaeochromocytoma
what is the most common drug cause of gynaecomastia?
spirinolactone
symptoms of addisonian crisis?
hypovolaemia
hyponatraemia
hyperkalaemia
causes of addisonian crisis?
sepsis or surgery causing an acute exacerbation of chronic insufficiency (Addison’s, Hypopituitarism)
adrenal haemorrhage eg Waterhouse-Friderichsen syndrome (fulminant meningococcemia)
steroid withdrawal
mx of addisonian crisis?
hydrocortisone 100 mg im or iv
1 litre normal saline infused over 30-60 mins or with dextrose if hypoglycaemic
continue hydrocortisone 6 hourly until the patient is stable. No fludrocortisone is required because high cortisol exerts weak mineralocorticoid action
oral replacement may begin after 24 hours and be reduced to maintenance over 3-4 days
what is the most common presentation for MEN 1?
Hypercalcaemia
2 tests to confirm cushing’s syndrome?
overnight dexamethasone suppression test (most sensitive)
24 hr urinary free cortisol
what to do in a hypoglycaemic attack with impaired GCS?
give IV glucose if there is IV access
if GCS not impaired, give quick-acting carbohydrate such as GlucoGel®
causes of raised prolactin?
prolactinoma pregnancy oestrogens physiological: stress, exercise, sleep acromegaly: 1/3 of patients polycystic ovarian syndrome primary hypothyroidism
rules of radioactive iodine?
Involves drinking a single dose of radioactive iodine
This is taken up by the thyroid, and the emitted radiation destroys a portion of the thyroid cells
Patients can be left hypothyroid afterwards and require levothyroxine replacement
There are rules regarding:
Not pregnant or allowed to get pregnant within 6 months
Avoiding contact with children and pregnant women
Limiting contact with others for several days after receiving the dose
What cells secrete PTH?
chief cells
how to investigate pheochromocytoma?
adrenal tumour
plasma metanephrines or 24 hour urine catecholamines (both breakdown products of adrenalin).
mx of acromegaly?
Both somatostatin analogues (e.g. ocreotide) and dopamine agonists (e.g. bromocriptine)
causes of SIADH?
Post-operative from major surgery
Infection, particularly atypical pneumonia and lung abscesses
Head injury
Medications (thiazide diuretics, carbamazepine, vincristine, cyclophosphamide, antipsychotics, SSRIs, NSAIDSs,)
Malignancy, particularly small cell lung cancer
Meningitis
electrolyte abnormality of SIADH?
hyponatraemia (dilutional)
Clinical examination will show euvolaemia
mx of SIADH?
Fluid restriction
vaptans (ADH receptor blockers such as tolvaptan).
risk of rapid correction of hyponatraemia?
A rise in sodium that is too fast gives a risk of central pontine myelinolysis (a neurological condition).
antibodies in thyroid disease?
anti-TPO- Grave’s Disease and Hashimoto’s Thyroiditis
Antithyroglobulin Antibodies- Grave’s Disease, Hashimoto’s Thyroiditis and thyroid cancer.
TSH Receptor Antibodies- graves
what is levothyroxine?
synthetic T4 and metabolises to T3 in the body.
what causes pretibial myxoedema?
a reaction to the TSH receptor antibodies- there are deposits of mucin under the skin on the anterior aspect of the leg
what is De Quervain’s Thyroiditis?
De Quervain’s Thyroiditis describes the presentation of a viral infection with fever, neck pain and tenderness, dysphagia and features of hyperthyroidism. There is a hyperthyroid phase followed by hypothyroid phase as the TSH level falls due to negative feedback.
