Endocrinology Flashcards
What is Cushing’s DISEASE?
Pituitary adenoma which secretes excess ACTH
What are the causes of Cushing’s syndrome?
Pituitary adenoma
Adrenal adenoma
Paraneoplastic ACTH secretion - in SCLC associated with very low K+
Exogenous steroid use: prescription or non-prescription
What are the features of Cushing’s syndrome?
Central obesity with proximal muscle wasting Round face / C-spine hump Striae and skin thinning, easy bruising Fatigue, depression, insomnia Hypertension and hyperglycaemia Osteoporosis
Hypokalaemic metabolic alkalosis
How do you diagnose Cushing’s syndrome?
Dexamethasone suppression test:
Low dose: if suppression of cortisol production, normal
1mg if no suppression of cortisol, Cushing’s syndrome present
High dose: if suppression of cortisol production, Cushing’s DISEASE (pituitary adenoma)
8mg if no suppression of cortisol, peripheral cause of disease
if ACTH suppressed = adrenal adenoma, if not = ectopic production
MRI brain can look for pituitary adenoma
CT TAP- look for SCLC, adrenal adenoma
How do you manage Cushing’s syndrome?
In pituitary adenoma: trans-sphenoidal surgery
In adrenal adenoma: surgical removal
Removal of adrenal glands and lifelong replacement
Medical management: metyrapone inhibits cortisol production, ketoconazole
What are the types of adrenal insufficiency?
Primary: Addison’s disease= autoimmune condition whereby there is reduced secretion of cortisol and aldosterone
Secondary: Inadequate ACTH production - Damage to pituitary gland / hypoperfusion e.g. Sheehan’s
Tertiary: inadequate hypothalamic production of CRH (usually after cessation of long-term steroids)
What are the symptoms/signs of adrenal insufficiency?
Fatigue
Reduced libido
Weight loss
Nausea, cramps, abdominal pain
Signs:
Bronze colouration of the skin- esp palmar creases
Vitiligo
Hypotension, hypoglycaemia
What U&Es would you expect in Addison’s disease?
Low sodium and High potassium
May also have low glucose and a metabolic acidosis
How is Addison’s disease diagnosed?
Short synacthen test: failure of cortisol to rise = primary insufficiency
ACTH stimulation testing can be used to diagnose secondary causes
Antibody testing: adrenal cortex ab, 21-hydroxylase ab
How can different types of adrenal insufficiency be differentiated?
ACTH level: high in primary failure, low in secondary and tertiary
How do you manage adrenal insufficiency?
Fludrocortisone to replace aldosterone
Hydrocortisone to replace cortisol
Steroid cards should be carried at all times
Double dose of hydrocortisone in illness, fludrocortisone should stay the same
Should be treated with IM hydrocortisone injections to treat adrenal crisis
What are the symptoms of Addisonian crisis?
Reduced consciousness Pyrexia Hypotension Hypoglycaemia Hyponatraemia HYPERKALAEMIA
How would you manage Addisonian crisis?
IV hydrocortisone 100mg STAT and 6 hourly
IV fluids
Correct hypoglycaemia
Manage hyperkalaemia
Close monitoring of fluid balance and electrolytes
What are the types of hyperaldosteronism?
Primary: Conn’s syndrome (adrenal adenoma, adrenal hyperplasia, adrenal carcinoma, familial hyperaldosteronism)
Secondary: renal artery stenosis, renal artery obstruction, heart failure causing INCREASED renin production which stimulates aldosterone production
What are the features of hyperaldosteronism?
Nocturia, polyuria, thirst
Fatigue
Mood changes, inability to concentrate
Hypertension
Hypokalaemia
Alkalosis on ABG
How would you investigate hyperaldosteronism?
Renin: Aldosterone ratio: low renin, high aldosterone = primary, both raised in secondary
CT/MRI adrenal glands
How is hyperaldosteronism managed?
Aldosterone antagonists: epleronone, spironolactone
Treat cause: surgical removal of adenoma, percutaneous renal artery angioplasty
What is the action of ADH?
Stimulates water reabsorption in the collecting ducts of the kidney.
What are the causes of SIADH?
Post-operative Atypical pneumonia / lung abscess Head injury Malignancy Medication: Thiazides, NSAIDs, chemo, antipsychotics, SSRIs
What are the symptoms of SIADH?
Headache, fatigue, confusion
Muscle aches and cramps
May have nausea and vomiting but are generally EUVOLEMIC
Severe hyponatraemia can cause seizures and reduced consciousness
What would you find on investigation for SIADH?
Euvolemic on hydration status
U&E: hyponatraemia
Urinary sodium + osmolality raised
Serum sodium and osmolality low
How is SIADH managed?
Identify cause + treat e.g. stop causative medication
Slow sodium replacement with hypertonic saline (max 10mmol/L/24hr increase)
Fluid restriction to 500-1000ml per day
Tolvaptan can be used as a ADH receptor antagonist
What complication do you need to be careful of when replacing sodium in SIADH?
Central Pontine Myelinolysis
What is central pontine myelinolysis?
Osmotic demyelination syndrome
Water moves by osmosis across the BBB when there is low low sodium in the blood, the brain adapts to this and lowers solutes to prevent oedema. If hyponatraemia fixed too quickly, water will move back across too quickly and cause demyelination.
What are the symptoms of central pontine myelinolysis?
- Due to electrolyte imbalance:
Encephalopathy, confusion, headache, nausea, vomiting - Due to neurone demyelination
Spastic quadraparesis, pseudobulbar palsy, cognitive and behavioural change, risk of death
What is diabetes insipidus?
Either reduced production or reduced sensitivity to ADH, preventing the kidneys from being able to concentrate urine
Two types: nephrogenic and cranial
What are the symptoms of diabetes insipidus?
Polydipsia and polyuria
Hypovolemia/dehydration
Postural hypotension
HYPERNATRAEMIA - may cause weakness, restlessness, lethargy, confusion, seizures
What are the symptoms of diabetes insipidus?
Polydipsia and polyuria
Hypovolemia/dehydration
Postural hypotension
HYPERNATRAEMIA - may cause weakness, restlessness, lethargy, confusion, seizures
What are the causes of diabetes insipidus?
Nephrogenic: Kidney does not respond to ADH
Medication especially LITHIUM, renal disease, hypercalcaemia/hypokalaemia, ADH receptor mutation
Cranial: Reduced ADH production
brain tumour, head injury, brain malformation/infection, surgery/radiotherapy
What are the investigations for diabetes insipidus?
Urine osmolality: low
Urine sodium: low
Serum osmolality: high
Serum sodium: high
Water deprivation test + desmopressin suppression test = gold standard
Water deprivation- no change in osmolality rules out psychogenic polydipsia
If desmopressin causes suppression: cranial DI, if no suppression: nephrogenic DI
What is the diagnostic test for DI?
Water deprivation + desmopressin suppression test
What is the management for diabetes insipidus?
Desmopressin - in nephrogenic, need much higher doses and close monitoring
Prevent dehydration + electrolyte imbalances
What is phaeochromocytoma?
Tumour of adrenal chromaffin cells -> catecholamine secretion
25% familial
Associated with MEN2
10% rules: 10% bilateral, 10% malignant, 10% located outside adrenal glands
What are symptoms of phaeochromocytoma ?
Often secrete in bursts, leading to periods of symptoms of worsening and settling
Anxiety, sweating, headache
Hypertension, tachycardia, palpitations
Paroxysmal AF
How is phaeochromocytoma diagnosed?
24 hourly urine catecholamines
Plasma free metanephrines
Genetic testing
How is phaeochromocytoma managed?
a-blockers: phenoxybenzamine
B-blockers once established on a-blockers
Adrenalectomy - symptoms should be medically managed before surgery
What is acromegaly?
Excessive growth hormone production.
Most commonly caused by pituitary adenoma (95%)
Can also be due to cancer secreting GHRH or GH, usually SCLC or pancreatic cancer.
What symptoms are associated with acromegaly?
May have headache and bitemporal hemianopia associated with pituitary adenoma.
Tissue overgrowth: prominent forehead and brow, large nose, large tongue, large hands and feet, large protruding jaw, arthritis
Organ dysfunction: heart hypertrophy, HTN, T2DM, colorectal Ca
Raised GH: skin tags, profuse sweating and oily skin. 30% also present with ^ prolactin and galactorrhoea
What complications are associated with acromegaly?
Hypertension
Diabetes
Cardiomyopathy
Colorectal cancer
What investigations should be done in acromegaly?
IGF-1 = first line screening test
OGTT while measuring GH= usually high glucose and low GH, used to confirm
MRI brain
Visual field testing
How is acromegaly managed?
Trans-sphenoidal surgery = 1st line
Management of ectopic hormone-producing cancers
Medical GH blockers: somatostatin analogues, dopamine agonists, GH receptor blockers
What are causes of hypothyroidism?
Hashimoto’s thyroiditis : Anti-TPO antibodies
Iodine deficiency
Hyperthyroidism treatment
Medication: lithium, amiodarone
Central causes: hypopituitarism, tumours, infection, vascular, radiation
What are symptoms of hypothyroidism?
Fatigue, lethargy, weight gain Intolerance of the cold Dry skin, coarse hair, brittle nails Hair loss Menorrhagia Constipation
What are signs of hypothyroidism on examination?
Weight gain Fatigue Cold Bradicardia Cerebellar ataxia Ascites/oedema Round face/obesity Ileus Goitre Hyporeflexia
What is the management of hypothyroidism?
Levothyroxine: review after 4 weeks and adjust 4-6weekly as needed
In pregnancy, dose needs to be increased 25-30% in T1
Caution should be taken in the elderly and those with ischaemic heart disease
What are the causes of hyperthyroidism?
Grave’s disease: TSH receptor-stimulating antibodies
Solitary toxic nodule
Toxic multinodular goitre
Thyroiditis: drug-induced, post-partum, De Quervain’s
What symptoms are specific to Grave’s disease?
Thyroid eye disease: exophthalmus, lid lag, ophthalmoplegia
Proximal myopathy
Pretibial myxoedema
Diffuse goitre
What is De Quervain’s thyroiditis?
Hyperthyroidism triggered by infection
Fever + neck tenderness/pain + dysphagia + hyperthyroidism
Often followed by hypothyroid phase
Self limiting, supportive treatment with NSAIDs
What are symptoms of thyroid eye disease?
Grittiness, discomfort Photophobia Excessive lacrimation Diplopia, reduced visual acuity Pupil defects
Exophthalmus, proptosis, ophthalmoplegia, papilloedema
How do you test for thyroid eye disease?
H-test
Lid lag
Fundoscopy
What is the management for hyperthyroidism?
1st line = carbimazole, takes 4-8 weeks to work, often can stop after 18m
2nd line = PTU due to risk of severe hepatic reaction
B-blockers for symptomatic treatment
Radioactive iodine: can’t get pregnant for 6m, avoid contact with children and pregnant women for 3w
Surgical removal of thyroid + replacement
What is the key side effect to look out for with carbimazole treatment?
Agranulocytosis
Which drug is preferred in pregnancy for hyperthyroidism?
Propylthiouracil
What are the symptoms of thyroid storm?
Agitation, confusion Tachycardia, hyperthermia AF, palpitations, symptoms of heart failure D&V Thyroid bruit Coma
How do you manage somebody in thyroid storm?
IV access + fluids NG tube if vomiting Cardiac and BP monitoring Bloods: TFTs Propranolol +/- digoxin Antithyroid medication Steroids to prevent peripheral conversion of T4 to T3
What is the most common thyroid cancer?
Papillary (60%)
What are the symptoms as hyperparathyroidism?
Renal stones
Painful bones
Abdominal groans : constipation, N&V
Psychiatric moans: fatigue, depression, psychosis
What is the function of parathyroid hormone?
To increase calcium levels in the blood by:
Increasing osteoclast activity
Increasing intestinal absorption + renal reabsorption
Increasing vitamin D activity, which further increases calcium absorption
What are the causes of different types of hyperparathyroidism?
Primary: parathyroid tumour
Secondary: renal disease/vitamin D deficiency, causes low calcium and PT glands compensate -> hyperplasia
Tertiary: Secondary HPT causes gland hyperplasia which causes higher baseline level of PTH
What bloods would you expect in primary hyperparathyroidism?
Raised calcium, PTH and vitamin D, low phosphate
What bloods would you expect in secondary hyperparathyroidism?
High PTH, high or normal calcium, low vitamin D
What bloods would you expect in tertiary hyperparathyroidism?
High PTH, high calcium, high phosphate, low vitamin D
How is primary hyperparathyroidism managed?
Surgical management of the tumour
How is secondary hyperparathyroidism managed?
Calcium and vitamin D supplements
Renal transplant
How is tertiary hyperparathyroidism managed?
Surgical removal of SOME of the parathyroid tissue
What are the blood parameters for diagnosing diabetes?
Random/OGTT > 11 and fasting >7 mmol/L on 2 occasions
HbA1c over 48 mmol/mol
What is the management for DKA?
FIGPICK
Fluids: 1L NaCl STAT, 4L + K+ over 12 hours
Insulin: actrapid 0.1unit/kg/hr
Glucose: add dextrose once gluc <14mmol/L
Potassium: monitor 4hrly and correct
Infection: treat underlying triggers
Chart fluid balance
Ketones- monitor
What is the management of HHS?
Slow rehydration to prevent cerebral oedema
LMWH prophylaxis of VTE
Replace K+
Maintain blood glucose 10-15 for first 24 hours to prevent cerebral oedema
What are the key side effects of metformin?
GI side effects
Lactic acidosis - not suitable in severe renal impairment
In which populations are pioglitazone contraindicated?
Heart failure
Current or previous bladder cancer
What are side effects of pioglitazone?
Weight gain, visual disturbance, bone fracture
What are side effects of sulphonylureas e.g. gliclazide?
Weight gain
Hypoglycaemia
Nausea and diarrhoea
Increased risk CVD and MI
Which diabetes medication increases risk of pancreatitis?
DPP4-inhibitors such as sitagliptin
What are potential side effects of SGLT2 inhibitiors?
Hypoglycaemia Thrush, UTI Genital necrotising fasciitis Weight loss DKA
What is congenital adrenal hyperplasia?
Group of autosomal recessive disorders which affect steroid synthesis.
In response to loww steroid production, the anterior pituitary secretes a lot of ACTH which stimulates adrenal androgen production and causes hyperplasia
Can cause females to develop secondary male sexual characteristics
What are features of congenital adrenal hyperplasia?
Virilisation of female genitalia
Precocious puberty in males
Hypertension
Salt losing crises
What are the causes of pseudo-cushings?
Alcohol excess
Severe depression
Which antibodies are associated with T1DM?
Antibodies to glutamic acid decarboxylase (anti-GAD)
Islet cell antibodies
Insulin autoantibodies (very common in young children with T1DM)
What are examples of GLP-1 mimetics?
Liraglutide, Exenatide
Liraglutide often preferred as only needs to be administered once daily
What are examples of DPP-4 inhibitors?
Sitagliptin, vildagliptin
At what HBa1c should a second drug be added to metformin treatment?
58 mmol/mol
Which diabetes medication is best for those taking part in ramadan?
Pioglitazone
What is androgen insensitivity syndrome?
X-linked recessive condition.
Defect in androgen receptor results in resistance to testosterone & genotypically male children (46XY) to have a female phenotype.
Rudimentary vagina and testes present but no uterus.
Testosterone, oestrogen and LH levels are elevated
What is 5-a reductase deficiency?
Autosomal recessive condition. 46 XY
Results in the inability of males to convert testosterone to dihydrotestosterone (DHT).
Individuals have ambiguous genitalia in the newborn period.
Hypospadias is common.
Virilization at puberty.
What are the conditions for being able to drive with diabetes?
Awareness of hypos
No more than 1 hypo requiring help of another person within past 12 months
No visual impairment as a result
Neurological/physical ability to stop
What is Kallmann’s Syndrome?
X-linked recessive condition which causes delayed puberty in men secondary to hypogonadotropic hypogonadism.
Typically: anosmia in a boy with delayed puberty.
Low levels of LH and FSH, usually normal or above average height
What is Klinefelter’s syndrome?
47 XXY
Often taller than average with small, firm testes Lack of secondary sexual characteristics Infertile Gynaecomastia Elevated FSH/LH but low testosterone
Which malignancies are associated with MEN 1?
3Ps:
Parathyroid
Pancreas
Pituitary
Most common presentation = hypercalcaemia
Which malignancies are associated with MEN2?
Medullary thyroid cancer
Parathyroid
Phaeochromocytoma
Neuromas
How does myxoedema coma usually present?
Hypothermia and confusion
What is first line treatment for prolactinoma?
Bromocriptine
