Endocrinology Flashcards
What is diabetes mellitus?
Syndrome of chronic hyperglycaemia due to relative insulin deficiency or insulin resistance or both.
What is T1DM?
An autoimmune disorder where the islet of Langerhans cells in the pancreas are destroyed by the immune system. This causes a deficiency of insulin which results in raised glucose levels.
What is T2DM?
Caused by a relative deficiency of insulin due to an excess of adipose tissue, resulting in raised blood glucose.
How does diabetes present?
Polyuria Polydipsia Weight loss Fatigue DKA Sx Complications Sx
How can you check blood glucose?
- finger prick
- one off glucose
- HbA1c
- glucose tolerance test
What is the diagnostic criteria for diabetes?
> fasting plasma glucose >/7.0mmol/L
random plasma glucose >/11.1mmol/L
HbA1c >/48mmol/L (6.5%)
Symptomatic pt needs 1 abnormal value
Asymptomatic pt needs 2 abnormal values
How is T1DM managed?
Insulin
If BMI>25 add metformin
Monitor HbA1c levels
SE of insulin?
Hypoglycaemia
Weight gain
Lipodystrophy
How is T2DM managed?
Dietary changes Metformin Sulfonylurea Gliptin Piolitazone
What is DKA?
Diabetic ketoacidosis: metabolic emergency
- uncontrolled catabolism associated with insulin deficiency
What can cause DKA?
5 I’s:
- infection
- intoxication
- infarction
- inappropriate withdrawal of insulin
- intercurrent illness
How does DKA present?
Pear drop breath Kussmaul's breathing Profound dehydration Abdo pain Drowiness, vomiting Sunken eyes, decreased tissue turgor, dry tongue
How is DKA diagnosed?
Blood glucose >11.1mmol/L
Raised plasma ketones >3mmol/L
Acidaemia (blood pH <7.3)
Metabolic acidosis with bicarbonate <15mmol/L
Urine stick test: heavy glycosuria + ketonuria
High urea + creatitine
How is DKA treated?
0.9% saline
Restore electrolyte + fluid loss
Insulin + gluocse
What are some complications of DKA management?
Hypotension
Coma
Cerebral oedema
Hypothermia
Later: pneumonia, DVT
Definition of hypoglycaemia
Plasma glucose <3mmol/L
Causes of hypoglycaemia?
Diabetics: insulin/sulphonylurea treatment
Non-diabetics:
- Exogenous drugs
- Liver failure
- Addison’s disease
- Islets cell turnover + immune hypoglycaemia
- Non-pancreatic neoplasm
How does hypoglycaemia present?
Autonomic:
- sweating, anxiety, hunger, tremor, palpitations, dizziness
Neuroglycopenic:
- confusion, drowsiness, seizures, coma
How is hypoglycaemia diagnosed?
Fingerprick blood test during attack
Bloods: glucose, insulin levels etc
How is hypoglycaemia treated?
Oral sugar + long-acting starch (e.g. toast)
> IM glucagon, IV glucose
What is hyperosmolar hyperglycaemic state?
Life-threatening emergency characterised by marker hyperglycaemia, hyperosmolality and mild/no ketones
> metabolic emergency characteristic of uncontrolled T2DM
How does hyperosmolar hyperglycaemic state present?
Severe dehydration Decreased LOC Hyperglcyaemia Hyperosomolality No ketones in blood or urine Stupor or coma Bicarbonate normal
How is hyperosmolar hyperglycaemic state diagnosed?
Blood glucose >11mmol/L
Heavy glycosuria
Very high plasma osmolality
Total body K+ is low
How is hyperosmolar hyperglycaemic state treated?
Lower rate of infusion of insulin
0.9% saline fluid
LMWH (SC Enoxaparin)
Restore electrolyte loss
What is MODY?
Maturity-onset diabetes of the young
- diagnosed <25yrs old
- autosomal dominant
- absence of islet autoantibodies
What is hyperthyroidism and what causes it?
Overproduction of the thyroid hormone Causes: - Grave's disease - Toxic multi nodular goitre - De Quervain's thyroiditis
What is grave’s disease?
Autoimmune induced excess production of thyroid hormone.
Clinical presentation of hyperthyroidism?
Tremor, anxiety, palpitations, weight loss, diarrhoea, increased appetite, double vision, SOB, sweating, heat intolerance, Palma erythema, irritatibility
Clinical presentation of Grave’s disease?
How is it treated?
Grave's opthalmology: Exopthalmos Proptosis Diplopia Ophthalmoplegia
Grave’s dermopathy:
- pretibial myxoedema
- thyroid acropachy
Tx:
- IV methylprednisolone
- surgical decompression
- eyelid surgery
How is hyperthyroidism diagnosed?
Bloods to test thyroid function
- low TSH
- high T4
- high T3
USS thyroid
How is hyperthyroidism treated?
Oral carbimazole
Radioactive iodine
Total thyroidectomy
Beta-blockers
What is de quervain’s thyroiditis?
Transient hyperthyroidism sometimes results from acute inflammation of the thyroid gland, probably due to viral infection.
- tender goitre
- hyperthyroidism
- raised ESR
- globally reduced uptake on tectretium thyroid scan
Treat with aspirin.
What is the triad for grave’s treatment?
- propanolol
- propylthiouracil
- prednisolone
What drugs can induce hyperthyroidism?
Amiodarone
Iodine
Lithium
What are some complications of total thyroidectomy?
Tracheal compression (from post-op bleeding) Laryngeal nerve palsy (hoarse voice) Transient hypocalcaemia (removal of parathyroid gland)
What is a complication of hyperthyroidism?
Thyroid storm/crisis
What is hypothyroidism?
Under-activity of the thyroid gland, underproduction of the thyroid hormone.
What can cause hypothyroidism?
Primary
- Hashimoto’s thyroiditis
- iodine deficiency
- post-thyroidectomy
- post-partum
- drugs: carbimazole, lithium, amiodarone, interferon
Secondary
- hypopituitarism
What is the clinical presentation of hypothyroidism?
Bradycardia, constipation, cold intolerant, weight gain, menorrhagia, tired, weak, myxoede,a, ascites, dry thin hair and skin, ataxia
Investigations for hypothyroidism?
Primary: high TSH, low T4 + T3
Secondary: low TSH, low T4
Thyroid antibodies (e.g. TPO-Ab)
High serum aspartate transferase
High serum creatinine kinase
How is hypothyroidism treated?
Oral levothyroxine (T4)
Complications of hypothyroidism?
Myxoedema
- may present with confusion and coma
- medical emergency
Tx: give IV/oral T3 and glucose infusion
What are the different types of thyroid carcinoma?
Papillary (70%) Follicular (20%) Anaplastic Lymphoma Medullary cell
How do thyroid carcinomas present?
Thyroid nodules
Cervical lymphadenopathy
Dysphagia
Hoarse voice
O/E:
- thyroid gland: increase in size, hard + irregular
How do you diagnose thyroid carcinomas?
> Fine needle aspiration cytology biopsy
> Blood tests
- thyroglobulin
- TFTs
> US of thyroid
How are thyroid carcinomas treated?
Radioactive iodine
Levothyroxine
Thyroidectomy
External radiotherapy
What are the 3 presentation features of an anterior pituitary tumour?
- pressure on local structures
- optic chasm: bitemporal hemianopia - pressure on normal pituitary
- hypopituitarism - functioning tumour
- hyperpituitarism
What is Cushing’s syndrome?
Chronic excessive and inappropriate elevated levels of circulating cortisol whatever the cause.
What is Cushing’s disease?
Excess glucocorticoids resulting from inappropriate ACTH secretion from the pituitary due to tumour.
Where is cortisol released from?
Zona fasiculata of the adrenal cortex
What are the functions of cortisol?
- sodium retention
- increased renal potassium loss
- increased carbohydrate + protein catabolism
- increased deposition of fat + glycogen
Causes of high cortisol?
ACTH-dependent causes
- Cushing’s disease
- Ectopic ACTH production
- ACTH treatment
ACTH-independent causes
- adrenal adenoma
- iatrogenic
Clinical presentation of Cushing’s disease?
Obese: buffalo hump Moon face + plethoric complex Osteoporosis Hyperglycaeimia Mood changes Irregular period + ED Muscle atrophy Thin skin Purple stirae on abdo, breasts + thighs
How is Cushing’s disease diagnosed?
> Random plasma cortisol - if this is high continue with:
- Overnight dexamethasone suppression test
- Urine free cortisol over 24hrs
- 48hr dexamethasone suppression test
If above tests are positive:
> plasma ACTH
Undetectable: adrenal tumour likely
Detectable: do high dose dex suppression test or CRH test
- if cortisol responds to CRH: Cushing’s disease likely
- if cortisol does not respond to CRH: find ectopic source of ACTH
How can you find ectopic source of ACTH?
- IV contrast CT of chest, abdo, pelvis
- MRI of neck, thorax + abdo
- CXR lungs for SCLC
How do you treat cushings?
Trans-sphenoidal removal of pituitary adenoma Bilateral adrenalectomy Stop steroids Drugs that inhibit cortisone synthesis - metyrapone, ketoconazole, fluconazole
What is acromegaly?
Excess GH in adults
- 5% assoc with MEN1
What are some symptoms of acromegaly?
Insidious onset, many years between Sx + Dx Headaches Increased size of hands + feet Excessive sweating Visual deterioration Snoring Wonky bite Increased weight Decreased libido Amenorrhoea Arthralgia + back ache Acroparaesthesia
What are some signs of acromegaly?
Skin darkening Coarsening face with wide nose Prognathism Big supraorbital ridge Interdental separation Rings become tight Fatigue Deep voice Carpel tunnel syndrome (50%) Large tongue
What are some co-morbidities/complications of acromegaly?
Impaired glucose tolerance Diabetes mellitus Sleep apnoea HTN, ventricular hypertrophy, cardiomyopathy, arrhythmias, stroke Colon cancer Arthritis
How is acromegaly diagnosed?
> High glucose, calcium + phosphate > IGF-1 screening test > Plasma GH levels - exclude it if GH <0.4ng/ml + normal IGF-1 - if delectable ---> do GTT > Visual field examination > MRI of pituitary fossa
What causes an increase in GH?
GH secretion is pulsatile. Increases in:
- stress, sleep, puberty + pregnancy
How do you treat acromegaly?
- Trans-sphenoidal surgery (remove tumour)
- IM octreotide (inhibit GH release)
- SC pegvisomant (suppresses IGF-1)
- Oral cabergoline/bromocriptine
- Radiotherapy
What is a prolactinoma?
Lactotroph cell tumour of the pituitary
What is the effect of prolactinoma?
- menstrual irregularity/amennorhea
- infertility
- galactorhhoea
- low libido
- low testosterone in men
- headache
- visual field defect
- CSF leak
What is the visual field defect seen in prolactinoma?
Bitemporal hemianopia
What can cause prolactinoma?
Pituitary adenoma Anti-dopaminergic drugs Stress Drugs Pressure on pituitary stalk
How do you diagnose a prolactinoma?
How is it treated?
Serum prolactin
Tx: Dopamine agonists
- cabergoline
- bromocriptine
- quinagolide
What does the anterior pituitary produce?
FSH LH ACTH TSH Prolactin GH
What does the posterior pituitary produce?
Vasopressin (ADH)
Oxytocin
What is Conn’s syndrome?
Primary hyperaldosteronism - excess production of aldosterone, independent of RAAS. Resulting in increased sodium and water retention and decreased renin release.
What causes Conn’s syndrome?
2/3rds: adrenal adenoma that secretes aldosterone
1/3rd: bilateral adrenocortical hyperplasia
How does Conn’s syndrome present?
- hypertension
- hypokalaemia (weakness, cramps, polyuria)
How is Conn’s syndrome diagnose?
Plasma aldosterone:renin ration
- aldosterone is much higher
Fludrocortisone or 0.9% saline infusion unable to suppress plasma aldosterone.
ECG: hypokalaemia
CT/MRI adrenals to differentiate adenomas from hyperplasia
What is seen on a hypokalaemic ECG?
Flat T-waves
ST depression
Long QT
How is Conn’s syndrome treated?
Laparoscopic adrenalectomy Aldosterone antagonist (e.g. oral spironolactone)
What is Addison’s disease?
Primary hypoadrenalism - destruction of the entire adrenal cortex resulting in mineralocorticoid, glucocorticoid and sex steroid deficiency.
What causes Addison’s?
Autoimmune (80%) - destruction of adrenal cortex by organ-specific Ab TB Long term steroid use Adrenal haemorrhage
How does Addison’s present?
Tanned bronze skin Lethargy, depression, low mood and self esteem Anorexia + weight loss Postural hypotension Impotence/amenorrhoea Vitilgo N+V New scars + palmar creases Diarrhoea, constipation + abdo pain Dehydration
How is Addison’s diagnosed?
Unexplained abdo pain/vomiting Bloods - hyponatraemia + hyperkalaemia - hypoglycaemia - hypoaldosternoism - low cortisol
Short ACTH stimulation test
- measure plasma cortisol before and 30mins after IM Tetracosactide
Adrenal antibodies
- 21-hydroxylase antibody
9am ACTH levels
- inappropriately high
AXR/CXR
How is Addison’s treated?
Seriously ill:
- IV hydrocortisone
- IV 0.9% saline 1L
- Glucose infusion (if hypoglycaemic)
Replace steroids daily 3x a day (mimic circadian rhythm)
- oral hydrocortisone/prednisolone
- oral fludrocortisone
What is secondary hypoadrenalism?
Issue with pituitary, not adrenal glands. Reduction of release of ACTH = low glucocorticoid (cortisol.)
Mineralcorticoid production remains normal.
Tx: oral hydrocortisone
What is diabetes insidious?
Passage of large volumes of dilute urine due to impaired water reabsorption in the kidney, either because of:
- reduced ADH secretion (cranial DI)
- impaired response of kidney to ADH (nephrogenic DI)
How does DI present?
Polyuria Polydipsia No glycosuria Hypernatreaemia (lethargy, thirst, weakness, irritability) Dehydration
Ix: water deprivation test
How do you treat cranial DI?
How do you treat nephrogenic DI?
MRI head + ant pituitary
Oral desmopressin
Oral bendroflumethiazide
Ibuprofen
What is SIADH?
Continuous secretion of ADH despite the plasma being very dilute leading to retention of water and excess blood volume, thus hyponatraemia.
Clinical presentation of SIADH?
- anorexia, nausea, malaise, weakness, aches, confusion, drowsiness, fits
What is seen biochemically in blood/urine in SIADH?
BLOOD
- low sodium
- low osmolarity
URINE
- high sodium
- high osmolality
How is SIADH treated?
Restrict fluid intake Hypertonic saline Oral demeclocyline daily Oral tolvaptan Oral furosemide
What are the actions of PTH?
- increase osteoclastic resorption of bone
- increase intestinal absoption of calcium
- activation of 1,25-dihydroxyvitD in kidney
- increase renal tubular reabsorption of calcium
- increase excretion of phosphate
What is calcitrol?
What are its roles?
Active form of vitamin D
Roles:
- increase calcium + phosphate absorption in gut
- inhibit PTH release
- enhanced bone turnover by increased no. of osteoclasts
- increased calcium + phosphate reabsorption in kidneys
Clinical presentation of hypercalcaemia?
Stones (renal colic, biliary stones)
Bones (pains, fractures)
Moans (abdo pain, nausea, constipation)
Psychic groans (depression, anxiety, insomnia)
Difference between primary and secondary hyperparathyroidism?
Primary: usually caused by adenoma
- high PTH, high calcium
- low phosphate
Secondary: physiological compensatory hypertrophy of all parathyroids causes excess PTH due to low calcium e.g. CKD, vit D deficiency Sx: osteomalacia, joint pain - high PTH, low calcium - high phosphate
What is tertiary hyperparathyroidism?
Occurs many years after secondary, causing glands to act autonomously having undergone hyperplastic or adenomatous change
= XS PTh secretion that is unlimited by feedback control
e.g. chronic renal failure
- high PTH, high Ca
- high phosphate
How do you treat acute severe hypercalcaemia?
Medical emergency
- IV 0.9% saline fluids
- IV pamidronate
- glucocorticoid steroids
Causes of hypocalcaemia?
CKD
Severe vit D deficiency
Reduced PTH function
Drugs (e.g. bisphosphonates)
How does hypocalcaemia present?
Parathesia Cramps Tetany Increased excitability of muscles + nerves Chvostek + Trousseau's sign Diarrhoea Impetigo herpetiformis Dermatitis Confusion Papilloedma
Prolonged QT on ECG
What is Chvostek’s sign?
Tapping over the facial nerve in region of parotid gland causes twitching of the ipsilateral facial muscles.
What is Trousseau’s sign?
Carpopedal spasm induced by inflation of sphygmomanometer cuff to a level above systolic BP
How do you treat acute hypocalcemia?
eg. tetany
IV calcium gluconate
What is definition of hyperkalaemia?
Serum K+ > 5.5mmol/L
> 6.5mmol/L = medical emergency
Causes of hyperkalaemia?
Drugs Renal failure Endocrine (e.g. Addison's) Artefact (pseudo high K+) DKA
Clinical presentation of hyperkalaemia?
Asymptomatic until high enough to cause cardiac arrest
- fast, irregular pulse, chest pain, weakness, light headed, fatigue, Kussmaul’s respiration
What is seen on ECG in hyperkalaemia?
Tall tented T-waves
Small P waves
Wide QRS complez
How is hyperkalaemia treated?
URGENT
- IV 10ml 10% calcium gluconate
- IV actrapid
- IV/neb salbutamol
NON-URGENT
- underlyng cause
- dietary restriction
Definition of hypokalaemia?
Serum K+ <3.5mmol/L
<2.5mmol/L = urgent
Causes of hypokalaemia?
Increased renal excretion (e.g. diuretics)
Reduced dietary intake
Redistribution to cells (e.g. salbutamol)
GI losses (e.g. vomiting, diarrhoea)
Clinical presentation of hypokalaemia?
Muscle weakness, cramps, hypotonia, hyporefelxia, tetany, palpitations, light headed, constipation
What is seen on ECG in hypokalaemia?
Small of inverted T waves
Prominent U waves
Long PR interval
Depressed ST segments
How is hypokalaemia treated?
Oral K+ supplements if mild
IV K+ if severe
What is a carcinoid tumour?
Tumours that originate from the enterochromaffin cells and are capable of production serotonin.
What are the effects of serotonin?
Bowel function Mood Clotting Nausea Bone density Vasoconstriction Increased force of contraction and heart rate
What is carcinoid crisis?
When a tumour outgrows its blood supply or is handled too much during surgery (mediators flow out.)
- vasodilation
- hypotension
- tachycardia
- bronchoconstriction
- hyperglycaemia
Tx: octereotide
How do you diagnose carcinoid tumour?
US liver
CXR chest/pelvis
MRI/CT
Urine: high conc of 5-hydroxyindoleacetic acid
