Endocrinology Flashcards
What hormones are released by the anterior pituitary gland?
TSH
FSH/LH
Prolactin
GH
ACTH
What hormones are released by the posterior pituitary?
Oxytocin
ADH
Describe the thyroid axis
Hypothalamus releases thyrotropin releasing hormone (TRH) -> Anterior pituitary releases TSH -> Thyroid gland releases T3 and T4
T3 and T4 have negative feedback on both anterior pituitary and hypothalamus
Describe the adrenal axis
Hypothalamus releases corticotrophin-releasing hormone (CRH) -> anterior pituitary releases ACTH -> Adrenal glands release cortisol (negative feedback)
What is the role of cortisol?
Increase alertness
Inhibit immune system
Inhibit bone formation
Raise blood glucose
Increase metabolism
Describe the parathyroid axis
Parathyroid hormone (PTH) released from parathyroid glands in response to low calcium
PTH increases activity and number of osteoclasts in bone, increases calcium reabsorption in the kidney and stimulated kidney to convert D3 to calcitriol to increase intestinal absorption
Describe the growth hormone axis
Hypothalamus releases GHRH -> anterior pituitary releases GH which stimulates release of IGF-1 from liver
Describe the Renin-Angiotensin-Aldosterone system
Renin secreted by Juxtaglomerular cells in afferent arterioles -> sense blood pressure and secrete more renin if BP low
Renin converts angiotensinogen-> angiotensin I -> angiotensin II in lungs with the help of ACE
Angiotensin II causes vasoconstriction and stimulates aldosterone
aldosterone causes cardiac remodelling, increases Na reabsorption, increase K secretion and hydrogen secretion
What are 4 causes of primary hyperthyroidism
Graves disease
Inflammation (thyroiditis)
Solitary toxic thyroid nodule
Toxic multinodular goitre
What are 3 causes of primary hypothyroidism
Hashimoto’s thyroiditis
Iodine deficiency
Treatment for hyperthyroidism
What can radioisotope scans be used for and what would they show
- Diffuse high uptake in Grave’s disease
- Focal high uptake in toxic multinodular goitre and adenomas
- Cold areas in thyroid cancer
What are the TSH, T3 and T4 levels in primary hyperthyroidism
TSH = low
T3 + T4 = high
What are the TSH, T3 and T4 levels in secondary hyperthyroidism
TSH = high
T3 and T4 = high
What are the TSH, T3 and T4 levels in primary hypothyroidism
TSH = high
T3 + 4 = low
What are the TSH, T3 and T4 levels in secondary hypothyroidism
TSH = low
T3 + 4 = low
what causes secondary hyperthyroidism
pathology in hypothalamus or pituitary
What is subclinical hyperthyroidism
Thyroid hormones (T3 and T4) are normal and thyroid-stimulating hormone (TSH) is suppressed (low). There may be absent or mild symptoms.
What is the pathophysiology of Grave’s disease
autoimmune, TSH receptor antibodies stimulate TSH receptors on the thyroid causing primary hyperthyroidism
What is a toxic multinodular goitre? (Plummer’s disease)
nodules develop on the thyroid gland, which are unregulated by the thyroid axis and continuously produce excessive thyroid hormones. It is most common in patients over 50 years.
What are 4 types of thyroiditis
De Quervain’s thyroiditis
Hashimoto’s thyroiditis
Postpartum thyroiditis
Drug-induced thyroiditis
How can hyperthyroidism present
- anxiety and irritability
- sweating and heat intolerance
- tachycardia
- weight loss
- fatigue
- insomnia
- frequent loose stools
- sexual dysfunction
- brisk reflexes
What are some specific features of Graves relating to presence of TSH receptor antibodies
- Diffuse goitre
- Graves’ eye disease (incl. exophthalmos)
- Pretibial myxoedema
- thyroid acropachy (hand swelling and finger clubbing)
What are the 3 phases of De Quervain’s thyroiditis?
- Thyrotoxicosis
- Hypothyroidism
- return to normal
What are some features of thyrotoxicosis
Excessive thyroid hormones
Thyroid swelling and tenderness
Flu-like illness
Raised inflammatory markers
What is the treatment for De Quervain’s thyroiditis
supportive
- NSAIDS (pain and inflammation)
- Beta blockers (symptoms of hyperthyroidism)
- Levothyroxine (symptoms of hypothyroidism)
Features of a thyroid storm (thyrotoxic crisis)
Fever, tachycardia, delirium
Management of thyroid storm
admission and monitoring
may need fluid resuscitation, anti-arrhythmic medications, beta blockers
What is the 1st line drug for hyperthyroidism
Carbimazole
What is the 2nd line drug for hyperthyroidism
Propylthiouracil
What are some cautions for radioactive iodine therapy
- pregnant or breast feeding women, women must not get pregnant within 6m of treatment
- men must not father children within 4m of treatment
- limit contact with people after dose (esp children and pregnant women)
What is the first choice medication for the adrenalin-related symptoms of hyperthyroidism
Propranolol
What are 4 causes of primary hypothyroidism
Hashimoto’s thyroiditis
Iodine deficiency
Treatments for hyperthyroidism e.g. Carbimazole
Medications e.g. lithium, amiodarone
What is the most common cause of hypothyroidism in the developed world
Hashimoto’s thyroiditis
What is the most common cause of hypothyroidism in the developing world?
Iodine deficiency
Name 2 antibodies associated with Hashimoto’s thyroiditis
anti-thyroid peroxidase (anti-TPO)
anti-thyroglobulin (anti-Tg)
What are some causes of secondary hypothyroidism
Tumours (pituitary adenomas)
Surgery to the pituitary
Radiotherapy
Sheehan’s syndrome
Trauma
what are some features of hypothyroidism
Weight gain
Fatigue
Dry skin
Coarse hair and hair loss
Fluid retention (incl. oedema, pleural effusions and ascites)
Heavy or irregular periods
Constipation
What types of hypothyroidism cause a goitre
Iodine deficiency
Hashimoto’s can initially cause a goitre after which there is atrophy of the thyroid gland
What is the management of hypothyroidism
Oral Levothyroxine
What is Cushing’s syndrome
prolonged high levels of glucocorticoids e.g. cortisol
What causes Cushing’s disease
pituitary adenoma secreting excessive adrenocorticotrophic hormone (ACTH) stimulating excess cortisol release from the adrenal glands
What are some features of Cushing’s syndrome
round face
central obesity
abdominal striae
enlarged fat pad on upper back (buffalo hump)
proximal limb muscle wasting
hirsutism
easy bruising and poor skin healing
hyperpigmentation (in Cushing’s disease due to high ACTH)
What are some metabolic effects of Cushing’s syndrome
Hypertension
Cardiac hypertrophy
Type 2 diabetes
Dyslipidaemia
Osteoporosis
What are some mental health effects of Cushing’s syndrome
Anxiety
Depression
Insomnia
Psychosis
What are the causes of Cushing’s syndrome
Cushing’s disease - pituitary adenoma releases excessive ACTH
Adrenal adenoma - adrenal tumour secreting excess cortisol
Paraneoplastic syndrome
Exogenous steroids
What investigations are used to diagnose Cushing’s syndrome
dexamethasone suppression tests
What would dexamethasone suppression tests show for a patient with an adrenal adenoma
low dose test cortisol = not suppressed
high dose = not suppressed
ACTH = low
What would dexamethasone suppression tests show for a patient with a pituitary adenoma
low dose test cortisol = not suppressed
high dose = low
ACTH = high
What would dexamethasone suppression tests show for a patient with an ectopic ACTH e.g. small cell lung cancer
Low dose test cortisol = not suppressed
high dose = not suppressed
ACTH = high
What is an alternative test to dexamethasone suppression test for Cushing’s syndrome
24-hour urinary free cortisol
What is the treatment of Cushing’s disease
Trans-sphenoidal removal of pituitary adenoma
What is Nelson’s syndrome
the development of an ACTH-producing pituitary tumour after the surgical removal of both adrenal glands due to a lack of cortisol and negative feedback. It causes skin pigmentation (high ACTH), bitemporal hemianopia and a lack of other pituitary hormones.
What is Conn’s syndrome
an adrenal adenoma producing too much aldosterone
what is primary hyperaldosteronism
adrenal glands are directly responsible for producing too much aldosterone
What are some causes of primary hyperaldosteronism
bilateral adrenal hyperplasia (most common)
adrenal adenoma (Conn’s)
familial hyperaldosteronism
What is secondary hyperaldosteronism
caused by excessive renin stimulating the release of excessive aldosterone. Excessive renin is released due to disproportionately lower blood pressure in the kidneys
What are 3 causes of secondary hyperaldosteronism
renal artery stenosis
heart failure
liver cirrhosis and ascites
What are some symptoms of hyperaldosteronism
HYPERTENSION
headaches, muscle weakness, fatigue
what investigation is used to screen for hyperaldosteronism
aldosterone-to-renin ratio
What would the aldosterone-to-renin ratio be in primary hyperaldosteronism
high aldosterone
low renin
What would the aldosterone-to-renin ration be in secondary hyperaldosteronism
high aldosterone
high renin
What electrolyte would be low in hyperaldosteronism
low potassium
What is the medical management of hyperaldosteronism
aldosterone antagonists e.g. Eplerenone, spironolactone
What investigations can be done to find the underlying cause of hyperaldosteronism
CT/MRI for adrenal tumour or adrenal hyperplasia
Renal artery imaging e.g. doppler for renal artery stenosis
Adrenal vein sampling
What is the most common cause of secondary hypertension
hyperaldosteronism
What is Addison’s disease
damage to adrenal glands resulting in reduced cortisol and aldosterone secretion
What is secondary adrenal insufficiency + causes
inadequate ACTH leading to low cortisol as a result of damage to pituitary gland
causes: tumours, surgery, radiotherapy, Sheehan’s, trauma
What is tertiary adrenal insufficiency
inadequate CRH released by hypothalamus - suddenly stopping exogenous steroids
What are some symptoms of adrenal insufficiency
fatigue
muscle weakness + cramps
dizziness and fainting
thirst and salt craving
weight loss
abdominal pain
depression
reduced libido
what are some signs of adrenal insufficiency
bronze hyperpigmentation (particularly in skin creases)
hypotension
what is a key biochemical finding in adrenal insufficiency
hyponatraemia
What tests is used to diagnose adrenal insufficiency
short Synacthen test
What are the ACTH levels in primary vs secondary adrenal insufficiency
primary = high
secondary = low
What is the management of adrenal insufficiency
hydrocortisone (to replace cortisol)
Fludrocortisone (to replace aldosterone)
How would an adrenal crisis present
reduced consciousness
hypotension
hypoglycaemia
hyponatraemia and hyperkalaemia
What is the management of an adrenal crisis
ABCD
IM or IV hydrocortisone(100mg followed by an infusion or 6hrly doses)
IV fluids
Correct hypoglycaemia e.g. IV dextrose
monitor electrolytes and fluid balance
What is the classic triad of symptoms of hyperglycaemia seen in type 1 diabetes ?
Polyuria
Polydipsia
Weight loss
What are some presenting features of diabetic ketoacidosis
Hyperglycaemia
Dehydration
Ketosis
Metabolic acidosis (with low bicarbonate)
Potassium imbalance
Polyuria
Polydipsia
N+V
Hypotension
Altered consciousness
What are the 3 diagnostic features of DKA
Hyperglycaemia (e.g., blood glucose above 11 mmol/L)
Ketosis (e.g., blood ketones above 3 mmol/L)
Acidosis (e.g., pH below 7.3)
How do you manage a patient in diabetic ketoacidosis?
‘FIG-PICK’
Fluids (IV saline)
Insulin (fixed rate insulin infusion e.g. Actrapid)
Glucose (closely monitor blood glucose and add glucose infusion when less than 14mmol/L)
Potassium (add K to IV fluids and monitor closely)
Infection (treat any underlying infection)
Ketones (monitor blood ketones, pH and bicarbonate)
What are some key complications in the treatment of DKA
hypoglycaemia
hypokalaemia
cerebral oedema (particularly in children)
pulmonary oedema
What autoantibodies are present in type 1 diabetes?
Anti-islet cell antibodies
Anti-GAD antibodies
Anti-insulin antibodies
What does the Basal-Bolus Regime consist of?
combination of:
Background, long-acting insulin injected once a day
Short-acting insulin injected 30 minutes before consuming carbohydrates (e.g., at meals)
Why should patients rotate their injection sites?
risk of lipodystrophy
What are some macrovascular complications of diabetes
Coronary artery disease
Peripheral ischaemia
Stroke
Hypertension
What are some microvascular complications of diabetes
Peripheral neuropathy
Retinopathy
Kidney disease
What are some non-modifiable risk factors for type 2 diabetes
Older age
Ethnicity (black African or Caribbean and South Asian
Family history
What are some modifiable risk factors of type 2 diabetes
Obesity
Sedentary lifestyle
High carbohydrate diet
What are some presenting features of type 2 diabetes
Tiredness
Polyuria + polydipsia
unintentional weight loss
opportunistic infections
slow wound healing
glucose in urine
What HbA1c indicates pre-diabetes
42-47 mmol/mol
What HbA1c is diagnostic for type 2 diabetes
> 48 mmol/mol, sample is repeated after 1 month to confirm diagnosis
how should type 2 diabetes be managed?
A structured education program
Low-glycaemic-index, high-fibre diet
Exercise
Weight loss (if overweight)
Antidiabetic drugs
Monitoring and managing complications
what are the treatment targets for type 2 diabetes
48 mmol/mol for new type 2 diabetics
53 mmol/mol for patients requiring more than one antidiabetic medication
What are the medical management options for type 2 diabetes
1st: Metformin
+ SGLT-2 inhibitor e,g, dapagliflozin if CVD
2nd: + sulfonylurea, pioglitazone, DPP-4 inhibitor or SGLT-2 inhibitor
3rd: Triple therapy, insulin therapy
What are some side effects of metformin
GI symptoms
Lactic acidosis
What are some side effects of SGLT-2 inhibitors?
Glycosuria
Increased urine output + frequency
Genital and urinary tract infections
Weight loss
DKA
lower limb amputations
Fournier’s gangrene
What are some side effects of pioglitazone?
Weight gain
Heart failure
Increased risk of bone fractures
Small increase in risk of bladder cancer
What are some side effects of sulfonylureas
weight gain
hypoglycaemia
What are some side effects of DPP-4 inhibitor e.g. sitagliptin
headaches
low risk of acute pancreatitis
What are some side effects of GLP-1 mimetics?
Reduced appetite
Weight loss
GI
What are some complications of type 2 diabetes
Infections (e.g., periodontitis, thrush and infected ulcers)
Diabetic retinopathy
Peripheral neuropathy
Autonomic neuropathy
Chronic kidney disease
Diabetic foot
Gastroparesis (slow emptying of the stomach)
Hyperosmolar hyperglycemic state
how does hyperosmolar hyperglycemic state present
polyuria
polydipsia
weight loss
dehydration
tachycardia
hypotension
confusion
how is hyperosmolar hyperglycemic state managed
IV fluids
careful monitoring
What causes Acromegaly?
excessive growth hormone most commonly caused by a pituitary adenoma
What visual disturbance can be present in acromegaly and why?
bitemporal hemianopia due to a pituitary tumour pressing on the optic chiasm
What are some features of Acromegaly?
Prominent forehead and brow (frontal bossing)
Coarse, sweaty skin
Large nose
Large tongue (macroglossia)
Large hands and feet
Large protruding jaw (prognathism)
What are some systematic symptoms of Acromegaly?
Hypertrophic heart
Hypertension
Type 2 diabetes
Carpal tunnel syndrome
Arthritis
Colorectal cancer
How is Acromegaly investigated?
Insulin-like growth factor-1 (IGF-1)
growth hormone suppression test
MRI of pituitary
What is the treatment of Acromegaly?
1st: Trans-sphenoidal surgery to remove pituitary adenoma
2nd: radiotherapy, medical (Growth hormone receptor antagonist e.g. Pegvisomant, somatostatin analogues, dopamine agonists)
What are some symptoms of hypercalcaemia?
Kidney stones
Painful bones
Abdominal groans (constipation, nausea and vomiting)
Psychiatric moans (fatigue, depression and psychosis)
What causes primary hyperparathyroidism and how is it treated?
caused by uncontrolled parathyroid hormone production by a tumour of the parathyroid glands. This leads to a raised blood calcium (hypercalcaemia). Treatment is to remove the tumour surgically.
What causes secondary hyperparathyroidism and how is it treated?
insufficient vitamin D or chronic kidney disease reduces calcium absorption from the intestines, kidneys and bones. This result in low blood calcium (hypocalcaemia). The parathyroid glands react to the low serum calcium by excreting more parathyroid hormone. Treatment is to correct the underlying vitamin D deficiency or chronic kidney disease (e.g., renal transplant).
What causes tertiary hyperparathyroidism and how is it treated?
secondary hyperparathyroidism continues for an extended period, after which the underlying cause is treated. Hyperplasia (growth) of the parathyroid glands occurs as they adapt to producing a higher baseline level of parathyroid hormone. In the absence of the previous pathology, this high parathyroid hormone level leads to the inappropriately high absorption of calcium in the intestines, kidneys and bones, causing hypercalcaemia. Treatment is surgically removing part of the parathyroid tissue to return the parathyroid hormone to an appropriate level.
What is the PTH and calcium level in primary hyperparathyroidism?
PTH = high
Calcium = high
What is the PTH and calcium level in secondary hyperparathyroidism?
PTH = high
calcium = low/normal
What is the PTH and calcium level in tertiary hyperparathyroidism?
PTH = high
Calcium = high
What is the pathophysiology of inappropriate anti-diuretic hormone?
Increased release of antidiuretic hormone (ADH) from the posterior pituitary which increases water reabsorption from the urine, diluting the blood and leading to hyponatraemia
How does SIADH present?
hyponatraemia
headache
Muscle aches and cramps
confusion
severe = seizures and reduced consciousness
What are some causes of SIADH?
Post-operative after major surgery
Lung infection, particularly atypical pneumonia and lung abscesses
Brain pathologies, such as a head injury, stroke, intracranial haemorrhage or meningitis
Medications (e.g., SSRIs and carbamazepine)
Malignancy, particularly small cell lung cancer
Human immunodeficiency virus (HIV)
What clinical features are useful in the diagnosis of SIADH?
Euvolaemia
Hyponatraemia
Low serum osmolality
High urine sodium
High urine osmolality
How is primary polydipsia differentiated from SIADH?
primary polydipsia has low urine sodium and urine osmolality
How is SIADH managed?
Admission if symptomatic or severe (e.g., sodium under 125 mmol/L)
Treating the underlying cause (e.g., stopping causative medications or treating the infection)
Fluid restriction
Vasopressin receptor antagonists (e.g., tolvaptan)
What is Osmotic Demyelination Syndrome?
also known as central pontine myelinolysis (CPM). It is usually a complication of long-term severe hyponatraemia being treated too quickly. Patient presents encephalopathic and confused then demyelination occurs
What are the 2 types of diabetes insipidus and what causes them?
A lack of antidiuretic hormone (cranial diabetes insipidus)
A lack of response to antidiuretic hormone (nephrogenic diabetes insipidus)
What can cause nephrogenic diabetes insipidus?
Medications, particularly lithium (used in bipolar affective disorder)
Genetic mutations in the ADH receptor gene (X-linked recessive inheritance)
Hypercalcaemia (high calcium)
Hypokalaemia (low potassium)
Kidney diseases (e.g., polycystic kidney disease)
What are some causes of cranial diabetes insipidus?
Brain tumours
Brain injury
Brain surgery
Brain infections (e.g., meningitis or encephalitis)
Genetic mutations in the ADH gene (autosomal dominant inheritance)
Wolfram syndrome (a genetic condition also causing optic atrophy, deafness and diabetes mellitus)
How does diabetes insipidus present?
Polyuria (producing more than 3 litres of urine per day)
Polydipsia (excessive thirst)
Dehydration
Postural hypotension
How is diabetes insipidus diagnosed?
Water deprivation test (desmopressin stimulation test)
What will a water deprivation test show in cranial diabetes insipidus?
urine osmolality after water deprivation = low
after desmopressin = high
What will a water deprivation test show in nephrogenic diabetes insipidus?
urine osmolality after water deprivation = low
after desmopressin = low
How is diabetes insipidus managed?
Treat underlying cause
Desmopressin in cranial
nephrogenic = water, high-dose desmopressin, thiazide diuretics, NSAIDs
What is a phaeochromocytoma?
tumour of the adrenal glands that secretes unregulated and excessive amounts of catecholamines (adrenaline).
What genetic disorders increase the risk of phaeochromocytoma
Multiple endocrine neoplasia type 2 (MEN 2)
Neurofibromatosis type 1
Von Hippel-Lindau disease
How does a phaeochromocytoma present?
Signs and symptoms tend to fluctuate
Anxiety
Sweating
Headache
Tremor
Palpitations
Hypertension
Tachycardia
How are phaeochromocytoma’s diagnosed?
Plasma free metanephrines
24-hour urine catecholamines
CT/MRI to look for tumour
How are phaeochromocytoma’s managed?
Alpha blockers (e.g., phenoxybenzamine or doxazosin)
Beta blockers, only when established on alpha blockers
Surgical removal of the tumour
