Endocrinology Flashcards
Adrenal insufficiency/Addison’s definition
Adrenal glands do not produce enough steroid hormones (cortisol & aldosterone)
Addison’s disease = primary adrenal insuff. caused by autoimmunity
Primary adrenal insufficiency definition
Adrenal glands damaged, resulting in low cortisol and aldosterone secretion (inc. Addison’s; specifically autoimmune)
Secondary adrenal insufficiency definition
Inadequate ACTH resulting in a lack of stimulation of adrenal glands
Result of loss of/damage to pituitary from pituitary adenoma, surgery, radiotherapy or trauma
Tertiary adrenal insufficiency definition
Insufficient CRH release from hypothalamus
Usually from patients on long-term (>3 weeks) steroids not tapering doses correctly
Adrenal insufficiency presentation
Fatigue
Muscle weakness
Muscle cramps
Dizziness and fainting
Thirst and craving salt
Weight loss
Abdominal pain
Depression
Reduced libido
Bronze hyperpigmentation of the skin, particularly in creases (ACTH stimulates melanocytes to produce melanin)
Hypotension (particularly postural hypotension – with a drop of more than 20 mmHg on standing)
Adrenal insufficiency investigations
Hyperkalaemia (high potassium)
Hypoglycaemia (low glucose)
Raised creatinine and urea due to dehydration
Hypercalcaemia (high calcium)
Early morning cortisol often falsely low
ACTH measured directly may be high or low depending on primary/secondary/tertiary
Adrenal cortex or 21-hydroxylase antibodies may be present in Addison’s
CT or MRI of adrenal glands or MRI of pituitary may be helpful
Test for adrenal insufficiency
Short synacthen test
Synthetic ACTH given & cortisol checked after 30 and 60 minutes
Should double cortisol levels
If failure to double, either primary adrenal insufficiency or significant adrenal atrophy from prolonged secondary adrenal insufficiency
Management of adrenal insufficiency
Hydrocortisone to replace cortisol
Fludrocortisone to replace aldosterone if needed
When ill, double hydrocortisone dose to mimic body’s response to stressors, and attend A&E if vomiting
Will have medical ID bracelet and steroid card, and should carry emergency hydrocortisone injection
Adrenal crisis definition, presentation & management
Acute presentation of severe adrenal insufficiency
Present with:
Reduced consciousness
Hypotension
Hypoglycaemia
Hyponatraemia and hyperkalaemia
Manage with IV hydrocortisone, IV fluids, IV dextrose
ABCDE approach to management
Hyperthyroidism definition
Over-production of thyroid hormones, T3 & T4 by thyroid gland
Thyrotoxicosis definition
Effects of an abnormal/excessive amount of thyroid hormones on the body
Primary hyperthyroidism definition
Dysfunction of the thyroid gland itself, producing excessive thyroid hormone e.g. Grave’s disease, in which autoantibodies stimulate TSH receptors
Secondary hyperthyroidism definition
Dysfunction of the pituitary or hypothalamus and over-production of TSH e.g. from a pituitary adenoma
Sub-clinical hyperthyroidism definition
Thyroid hormones (T3/T4) are normal but TSH is suppressed/low
(May have mild or absent symptoms)
Grave’s disease definition
Form of primary hyperthyroidism in which anti-TSH receptor antibodies bind to the receptors on the thyroid and stimulate excessive thyroid hormone secretion
Plummer’s disease definition
Form of primary hyperthyroidism in which nodules develop on the thyroid gland which are unregulated by the thyroid axis and continually secrete thyroid hormones
(Most common in patients >50 years old)
Grave’s disease presentation
In addition to the universal symptoms of hyperthyroidism
Also present with Grave’s eye disease, which is evident via lid lag and exophthamos
Pretibial myxoedema (gives skin a discoloured, waxy, oedematous appearance)
Goitre
Hyperthyroidism presentation
Anxiety and irritability
Sweating and heat intolerance
Tachycardia
Weight loss
Fatigue
Insomnia
Frequent loose stools
Sexual dysfunction
Brisk reflexes on examination
Thyroid storm presentation and management
Acute presentation of hyperthyroidism
Presents with fever, tachycardia and delirium
symptomatic treatment e.g. paracetamol
treatment of underlying precipitating event
beta-blockers: typically IV propranolol
anti-thyroid drugs: e.g. methimazole or propylthiouracil
Lugol’s iodine
dexamethasone/hydrocortisone - blocks the conversion of T4 to T3
Hyperthyroidism management & drug contraindications
Carbimazole = first line drug
Propylthiuracil = second line drug
(Both can cause agranulocytosis, if suffering sore throat stop taking and see a doctor ASAP
Carbimazole is contraindicated in pregnancy)
Propranolol for symptomatic relief
Radioactive iodine can be used as a definitive treatment
Hyperparathyroidism definition
Overactivity of the 4 parathyroid glands, resulting in excessive secretion of PTH
Hyperparathyroidism presentation
Bones, moans, stones & groans
(bone pain, depression, delirium, kidney stones, abdominal moans [vomiting, nausea and constipation])
Categorised by hypercalcaemia
Primary hyperparathyroidism definition, biochem presentation and management
Uncontrolled PTH release from the parathyroid glands e.g. from a tumour
Presents with elevated PTH and calcium
Manage surgically
Secondary hyperparathyroidism definition, biochem presentation and management
Insufficient vitamin D or chronic kidney disease reduces calcium absorption, leading to hypocalcaemia
Presents with elevated PTH but low/normal calcium
Treat by correcting underlying condition
Tertiary hyperparathyroidism definition, biochem presentation and management
Caused by hyperplasia of the parathyroid gland due to prolonged secondary hyperparathyroidism post-resolution
Presents with high PTH and high calcium
Treat by surgically removing part of parathyroid tissue
Hypothyroidism definition
Insufficient thyroid hormones, T3 & T4
Primary hypothyroidism definition & biochem
Thyroid behaves abnormally and produces inadequate thyroid hormones e.g. iodine deficiency
Loss of negative feedback, hence presents with elevated TSH
Secondary hypothyroidism definition & biochem
Secondary hypothyroidism is often associated with a lack of other pituitary hormones, such as ACTH, referred to as hypopituitarism. This is rarer than primary hypothyroidism, and may be caused by:
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
Low TSH, Low T3/4
Hashimoto’s thyroiditis definition
Autoimmune condition associated with anti-TPO and anti-Tg
Causes goitre followed by wasting/atrophy of thyroid gland
Hypothyroidism management
Oral levothyroxine = first-line treatment (synthetic T4)
Liothyronine sodium = rarely used under specialist care (synthetic T3)
Hypothyroidism presentation
Weight gain
Fatigue
Dry skin
Coarse hair and hair loss
Fluid retention (including oedema, pleural effusions and ascites)
Heavy or irregular periods
Constipation
Goitre for iodine deficiency
Cushing’s syndrome & disease definition
Refers to prolonged high levels of glucocorticoids in the body (primarily cortisol)
Cushing’s disease refers specifically to high levels from a pituitary adenoma secreting excessive ACTH
Cushing’s syndrome presentation
Round face (known as a “moon face”)
Central obesity
Abdominal striae (stretch marks)
Enlarged fat pad on the upper back (known as a “buffalo hump”)
Proximal limb muscle wasting (with difficulty standing from a sitting position without using their arms)
Male pattern facial hair in women (hirsutism)
Easy bruising and poor skin healing
Hyperpigmentation of the skin in patients with Cushing’s disease
Causes of Cushing’s mnemonic
CAPE
Cushing’s disease
Adrenal adenoma
Paraneoplastic syndrome (ACTH from tumour somewhere other than pituitary)
Exogenous steroids
Cushing’s syndrome diagnostic test
Dexamethasone suppression test
First line = low dose overnight test, give dexamethasone at 11pm and check cortisol at 9am - suppressed normally
For the low-dose 48-hour test, dexamethasone (0.5mg) is taken every 6 hours for 8 doses, starting at 9 am on the first day. Cortisol is checked at 9 am on day 1 (before the first dose) and 9 am on day 3 (after the last dose). A normal result is that the cortisol level on day 3 is suppressed. Failure of the dexamethasone to suppress the day 3 cortisol could indicate Cushing’s syndrome, and further assessment is required.
The high-dose 48-hour test is carried out the same way as the low-dose test, other than using 2mg per dose (rather than 0.5mg). This higher dose is enough to suppress the cortisol in Cushing’s syndrome caused by a pituitary adenoma (Cushing’s disease), but not when it is caused by an adrenal adenoma or ectopic ACTH.
Cushing’s syndrome management
Trans-sphenoidal (through the nose) removal of pituitary adenoma
Surgical removal of adrenal tumour
Surgical removal of the tumour producing ectopic ACTH (e.g., small cell lung cancer), if possible
Hyperaldosteronism/Conn’s syndrome definition
Refers to high levels of aldosterone
Conn’s specifically refers to an adrenal adenoma producing too much aldosterone
May be present in 5-10% patients with hypertension
Primary hyperaldosteronism definition and causes
Adrenal glands directly responsible for producing too much aldosterone
Serum renin will be low due to negative feedback
May be due to a bilateral adrenal hyperplasia, adrenal adenoma (aka Conn’s) or familial
Secondary hyperaldosteronism definition and causes
Caused by excessive renin stimulating the release of excessive aldosterone
Usually due to disproportionately lower blood pressure in the kidneys e.g. renal artery stenosis, liver cirrhosis, heart failure
Hyperaldosteronism biochem & investigatons
High aldosterone
Low renin (primary) or high renin (secondary)
Hypertension
Hypokalaemia
Alkalosis
Adrenal vein sampling
CT/MRI
Hyperaldosteronism management
Aldosterone antagonists - eplerenone & spironolactone
Treating underlying cause e.g. surgical removal of tumour
Acromegaly definition
Result of excessive growth hormone
Usually from pituitary adenoma
Also linked to carpal tunnel syndrome
Acromegaly presentation
Headaches
Bitemporal hemianopia
Prominent forehead and brow (frontal bossing)
Coarse, sweaty skin
Large nose
Large tongue (macroglossia)
Large hands and feet
Large protruding jaw (prognathism)
Acromegaly investigations
Insulin-like growth factor-1 can be tested on a blood sample
Also glucose tolerance test
Pituitary MRI
Acromegaly management
Trans-sphenoidal surgery
Pegvisomant (growth hormone receptor antagonist given daily by a subcutaneous injection)
Somatostatin analogues (e.g., octreotide) block growth hormone release
Dopamine agonists (e.g., bromocriptine) block growth hormone release
Phaeochromocytoma definition
Tumour of the adrenal glands secreting unregulated and excessive amounts of catecholamines i.e. adrenaline
10% rule of phaeochromocytoma
10% bilateral
10% cancerous
10% outside adrenal gland
Phaeochromocytoma presentation
Anxiety
Sweating
Headache
Tremor
Palpitations
Hypertension
Tachycardia
Phaeochromocytoma diagnosis
Tests include plasma free metanephrines (breakdown products of catecholamines) & 24 hour urine catecholamines
Phaeochromocytoma management
Alpha blockers e.g. henoxybenzamine or doxazosin
Beta blockers, only when established on alpha blockers
Surgical removal of the tumour
Diabetes insipidus definition
Rare disease in which the body makes too much urine
Can be cranial DI (lack of ADH) or nephrogenic DI (lack of response to ADH)
ADH function
Produced in hypothalamus & secreted by posterior pituitary gland
Stimulates water reabsorption from the collecting ducts in the kidneys
Lack of ADH results in polyuria and polydipsia
Primary polydipsia definition
Primary polydipsia is when the patient has a normally functioning ADH system but drinks excessive amounts of water, leading to excessive urine production (polyuria) - this is not diabetes insipidus
Nephrogenic diabetes insipidus definition and causes
Collecting ducts of the kidneys do not respond to ADH
Idiopathic
Medications e.g. lithium
Familial (X-linked recessive inheritance for ADH rec gene)
Hypercalcaemia
Hypokalaemia
Kidney diseases
Cranial diabetes insipidus definition and causes
Hypothalamus does not produce ADH for the pituitary gland to secrete
Idiopathic
Brain tumours
Brain injury
Brain surgery
Brain infection
Familial (ADH gene autosomal dominant inheritance)
Wolfram syndrome
Diabetes insipidus presentation
Polyuria
Polydipsia
Dehydration
Postural hypotension
Diabetes insipidus investigations results
Low urine osmolarity
High/normal serum osmolarity
>3l on 24-hr urine collection
Diabetes insipidus test
Water deprivation test/desmopressin stimulation test
Patient avoids fluids for ~8hrs before test
After water deprivation, urine osmolarity is measured. If low, synthetic ADH (desmopressin) is given, then urine osmolarity is measured over 2-4 hours after
If high urine osmolarity after water deprivation - likely to be primary polydipsia & no ADH is given
Cranial diabetes insipidus - patient lacks ADH, therefore after synthetic ADH given their osmolarity should increase and be high
Nephrogenic diabetes insipidus - ADH will not have an effect therefore osmolarity will still be low
Diabetes insipidus management
Treat underlying cause
Desmopressin for cranial DI, but monitor sodium for hyponatraemia
Nephrogenic DI can be treated with thiazide diuretics, high dose desmopressin, NSAIDs and good access to water
Type 1 diabetes
Pancreas no longer able to produce adequate insulin, resulting in a loss of ability to absorb glucose from the blood
Type 1 diabetes presentation
Polyuria
Polydipsia
Weight loss
(DKA)
DKA definition
Diabetic ketoacidosis is a consequence of inadequate insulin
When body recognises low glucose due to lack of insulin signalling, ketogenesis occurs, producing ketones. Usually buffered by the kidneys to prevent ketone acids causing acidosis. But when diabetes causes excess ketones, causes life-threatening metabolic acidosis = DKA
DKA presentation & usual patients
The initial presentation of type 1 diabetes
An existing type 1 diabetic who is unwell for another reason, often with an infection
An existing type 1 diabetic who is not adhering to their insulin regime
Ketoacidosis
Dehydration
Potassium imbalance
Metabolic acidosis w low bicarb
Hyperglycaemia
Sweet smelling breath
Hypotension
Altered consciousness
DKA management
FIG-PICK
Fluids - normal saline, 1L in first hr then 1L per 2hrs
Insulin - fixed rate infusion
Glucose - if blood glucose <14mmol/L
Potassium
Infection - treat underlying infection if applicable
Chart fluid balance
Ketones - monitor
Key complications from DKA treatment
Hypoglycaemia (low blood sugar)
Hypokalaemia (low potassium)
Cerebral oedema, particularly in children
Pulmonary oedema secondary to fluid overload or acute respiratory distress syndrome
Autoantibodies in T1D
Anti-islet cell antibodies
Anti-GAD antibodies
Anti-insulin antibodies
Serum C-peptide can give a measure of insulin
Long term T1D management
Subcutaneous insulin (rotate injection sites to avoid lipodystrophy)
Monitor carb intake
Monitor blood sugar
Monitor for complications
T1D basal-bolus regime
Combination of background long-acting insulin injected once a day & short actin insulin injected 30 mins before carb intake
Insulin pump definition, pros & cons
Small device continuously infusing insulin at different rates to control blood sugar levels
Cannula replaced every 2-3 days and insertion site rotated
Pros:
Better blood sugar control
More flexibility with eating
Fewer injections
Cons:
Difficulties learning to use the pump
Having it attached at all times
Blockages in the infusion set
A small risk of infection
T2D risk factors
Non-modifiable:
Older age
Ethnicity (Black African/Caribbean & South Asian)
Family history
Modifiable:
Obesity
Sedentary lifestyle
High carb diet
T2D presentation
Tiredness
Polyuria
Polydipsia
Unintentional weight loss
Opportunistic infection
Slow wound healing
Glycosuria
Acanthosis nigricans
HbA1c >48mmol/mol indicates T2D, repeated 1 month apart to confirm
Pre-diabetes definition & criteria
Pre-diabetes is an indication that the patient is heading towards diabetes. They do not fit the full diagnostic criteria but should be educated about the risk of diabetes and lifestyle changes
An HbA1c of 42 – 47 mmol/L indicates pre-diabetes
T2D management
Education
Low-glycaemic index, high fibre diet
Exercise
Weight loss
Anti-diabetic drugs
Monitor/manage complications
T2D treatment targets
HbA1c
48 mmol/mol for new type 2 diabetics
53 mmol/mol for patients requiring more than one antidiabetic medication
T2D medical management
First line = metformin
Add SGLT-2 inhibitor if patient has CVD or heart failure or with QRISK >10% (side effect to be aware of = DKA)
Second-line is to add a sulfonylurea, pioglitazone, DPP-4 inhibitor or SGLT-2 inhibitor.
Third-line options are:
Triple therapy with metformin and two of the second-line drugs
Insulin therapy (initiated by the specialist diabetic nurses)
Metformin mechanism of action & side effects
Increases insulin sensitivity & decreases glucose production by liver
GI symptoms, including pain, nausea, diarrhoea
Lactic acidosis
Try modified-release metformin if bad GI effects
SGLT-2 inhibitors mechanism of action & side effects
End with suffix -gliflozin
Inhibits sodium-glucose co-transporter 2 protein, preventing reabsorption of glucose from urine
Glycosuria
Increased urine frequency and output
Genital and urinary tract infections (e.g. thrush)
Weight loss
DKA (with moderately raised glucose)
Fournier’s gangrene (rare, severe infection of genitals or perineum)
Pioglitazone mechanism of action & side effects
Increases insulin sensitivity and decreases liver production of glucose
Weight gain
heart failure
Small increased risk of bladder cancer
Increased risk of bone fractures
T2D complications
Infections
Diabetic retinopathy
Peripheral neuropathy
Autonomic neuropathy
Chronic kidney disease
Diabetic foot
Gastroparesis
Hyperosmolar hyperglycaemic state
T2D neuropathic pain management
Amitriptyline – a tricyclic antidepressant
Duloxetine – an SNRI antidepressant
Gabapentin – an anticonvulsant
Pregabalin – an anticonvulsant
Hyperosmolar hyperglycaemic state definition, presentation & management
Characterised by hyperosmolality (water loss leads to very concentrated blood), hyperglycaemia and the absence of ketones, distinguishing it from ketoacidosis
Presents with polyuria, polydipsia, weight loss, dehydration, tachycardia, hypotension and confusion
Manage with IV fluids and careful monitoring (involve seniors)
Hypoglycaemia definition
Blood glucose below 3.5 mmol/L
Hypoglycaemia presentation
Trembling
Sweating
Palpitations
Hunger
Headache
Double vision
Difficulty concentrating
Slurred speech
Confusion
Coma
Hypoglycaemia causes
Drugs (insulin, sulphonylureas, GLP-1 analogues, DPP-4 inhibitors, beta blockers)
Alcohol
Acute liver failure
Sepsis
Adrenal insufficiency
Insulinoma
Glycogen storage disease
Mild hypoglycaemia management
ABCDE approach
15-20g of fast-acting carbohydrate
Follow with slow-acting carbohydrate
Severe hypoglycaemia management
ABCDE approach
200ml 10% dextrose IV
1mg glucagon IM if no IV access (won’t work if alcohol ingestion is cause)
Manage seizures
Hypoglycaemia investigations
Whipple’s triad:
Plasma hypoglycaemia
Symptoms attributable to a low blood sugar
Resolution of symptoms when correcting blood sugar
Measure insulin, C-peptide and proinsulin levels to differentiate between exogenous and endogenous insulin sources
High C-peptide/proinsulin = endogenous
Low C-peptide/proinsulin = exogenous
Review medication history for drugs that may cause issue
Diabetic neuropathy definition
Refers to a variety of peripheral nerve disorders as a result of diabetes
Primary causative factor is chronic hyperglycaemia
Develops from both type 1 & type 2 DM
Diabetic neuropathy types and presentation
Distal Symmetrical Sensory Neuropathy
Most common form
Resulting from loss of large sensory fibres
Sensory loss in a ‘glove and stocking’ distribution, typically affecting touch, vibration and proprioception
Small-fibre Predominant Neuropathy
Due to loss of small sensory fibres
Deficits in pain and temperature sensation in a ‘glove and stocking’ distribution, with episodes of burning pain
Diabetic Amyotrophy
Originates from inflammation of the lumbosacral plexus or cervical plexus
Severe pain around the thighs and hips, along with proximal weakness.
Mononeuritis Multiplex
Typically painful
Defined as neuropathies involving two or more distinct peripheral nerves
Autonomic Neuropathy
Postural hypotension
Gastroparesis
Constipation
Urinary retention
Arrhythmias
Erectile dysfunction
Diabetic neuropathy investigations
Neuro exam
Nerve conduction studies
Bloods - glucose levels, HbA1c, B12, thyroid function, liver function
Diabetic neuropathy management
Control blood glucose
Pain control
Manage complications
Chvostek’s sign
Facial twitch obtained by tapping the distribution of the facial nerve in front of the tragus
Caused by mechanical irritability of peripheral nerves
Indicative of hypocalcemia and is the most reliable test for hypocalcemia
Hyperprolactinaemia definition and levels
Elevated serum prolactin
Mildly increased levels (400-600mu/L) may be physiological and asymptomatic, higher levels usually pathological
Very elevated levels (>5,000 mu/L) usually imply a prolactin-secreting pituitary tumour
Hyperprolactinaemia presentation
Amenorrhoea, oligomenorrhoea or anovulatory cycles
Galactorrhoea
Breast pain & enlargement
Infertility
Loss of libido
Hirsutism
For men:
Impotence
Loss of libido
Decreased seminal volume
Galactorrhoea
Gynaecomastia
Hyperprolactinaemia investigations
MRI/CT
Formal assessment of visual fields
Hypercalcaemia secondary to malignancy presentation
Hypercalcaemia
Low PTH
Low phosphate
High PTHrP
Changes to hypothyroidism medication during pregnancy
increase dose by up to 50% in first 4-6 weeks of pregnancy
DM1 sick day rules
If on insulin, they must not stop it due to the risk of diabetic ketoacidosis
Check blood glucose more frequently, for example, every 1–2 hours including through the night
Consider checking blood or urine ketone levels regularly
Maintain normal meal pattern if possible
If appetite is reduced meals could be replaced with carbohydrate-containing drinks (such as milk, milkshakes, fruit juices, and sugary drinks)
Aim to drink at least 3 L of fluid (5 pints) a day to prevent dehydration
DM2 sick day rules
Advise the patient to temporarily stop some oral hypoglycaemics during an acute illness
Medication may be restarted once the person is feeling better and eating and drinking for 24-48 hours
Metformin: stop treatment if there is a risk of dehydration, to reduce the risk of lactic acidosis
Sulfonylureas: may increase the risk of hypoglycaemia
SGLT-2 inhibitors: check for ketones and stop treatment if acutely unwell and/or at risk of dehydration, due to the risk of euglycaemic DKA
GLP-1 receptor agonists: stop treatment if there is a risk of dehydration, to reduce the risk of AKI
if on insulin therapy, do not stop treatment, as above
monitor blood glucose more frequently as necessary
De Quervain’s thyroiditis
Also known as subacute thyroiditis
Hyperthyroid period followed by hypothyroidism, before returning to euthyroid
Can present with antibodies
Results in decreased isotope uptake
Goitre is usually painful
Addison’s steroid dosing/regime
the hydrocortisone dose is split with the majority given in the first half of the day
How many times a day should a type 1 diabetic check blood sugars?
At least 4 times a day, including before meals and before bed
