Endocrinology Flashcards
Primary hypothyroidism
Low levels of blood thyroid hormone due to destruction of the thyroid gland
Causes:
- Autoimmune – Hashimoto’s thyroiditis (thyroid peroxidase antibodies)
- Iodine deficiency
- Drugs – amiodarone, lithium
- Surgery, radiotherapy
Secondary hypothyroidism
Decreased activity of the thyroid caused by failure of the pituitary gland
Causes:
- Tumours
- Surgery
- Radiotherapy
- Sheehan’s syndrome – postpartum hypopituitarism caused by necrosis of the pituitary gland
- Trauma
Hypothyroidism symptoms and signs
Symptoms – weight gain, cold intolerance, fatigue, constipation, hoarse voice, low mood +/- depression, dry & thin hair, dry skin, menorrhagia
Signs – bradycardia, thickening of skin and puffiness around the eyes (myxoedema)
Hypothyroidism investigations
TFTs – low T3 and T4, elevated TSH
Thyroid antibodies – anti-TPO
USS of thyroid
Other – FBC, B12 and folate, serum lipids, HbA1c, coeliac serology
Hypothyroidism TFT results
Primary hypothyroidism – thyroid gland, high TSH, low T3 & T4
Secondary hypothyroidism – pituitary gland, low TSH, low T3 & T4
Hypothyroidism management
Levothyroxine (T4)
Hypothyroidism monitoring
TSH
- Elevated: under-replacement, poor compliance, malabsorption
- Suppressed: over-replacement (increased risk of AF and osteoporosis)
If symptomatic despite treatment, investigate for non-thyroid pathology
Hyperthyroidism causes
Autoimmune – grave’s disease
Nodular thyroid disease – solitary toxic thyroid nodule or toxic multinodular goitre
Thyroiditis – De Quervain’s thyroiditis, postpartum thyroiditis, drug-induced thyroiditis (amiodarone, lithium)
Follicular thyroid cancer
TSH-secreting pituitary adenoma
Exogenous – iodine excess, levothyroxine
Hyperthyroidism symptoms and signs (+ specific to Graves)
Symptoms – weight loss with increased appetite, insomnia, irritability, anxiety, heat intolerance, diarrhoea, amenorrhoea, reduced libido, hair loss
Signs – tachycardia, palpitations, tremor, palmar erythema
Graves – exophthalmos (proptosis), lid retraction and chemosis (eye irritation), goitre, pretibial myxoedema, thyroid acropachy (hand swelling and finger clubbing)
Hyperthyroidism investigations
TFTs – low TSH, high T3 & T4
Thyroid antibodies – TSH receptor antibodies
USS thyroid gland
Thyroid scintigraphy – radioactive iodine/technetium uptake can determine cause
- Overall increase in Graves
- Only in nodules for nodular causes
- Absent in thyroiditis
Hyperthyroidism TFT results
Hyperthyroidism (all other causes) – high T3 & T4 and low TSH
Pituitary adenoma – high T3 & T4 and high TSH
Hyperthyroidism management
Medical – carbimazole, propylthiouracil, reduce synthesis of T3 & T4, can take 4-6 weeks to feel effect
- Can causes agranulocytosis (severe form of neutropenia) -> if unexplained fever/sore throat request urgent blood for pancytopenia (deficiency of red cells, white cells and platelets)
Beta-blockers may also be used to control symptoms
Definitive treatment – radioactive iodine (single dose): contraindicated in pregnancy and commonly causes hypothyroidism, thyroidectomy: complications of bleeding, infection, recurrent laryngeal nerve damage, hypothyroidism
Parathyroid gland
Chief cells – secrete PTH
Oxyphil cells – purpose unknown, increase in number with age
PTH actions – increase calcium levels in the body
1) Increased bone resorption – PTH acts directly on bone, induce osteoclast activity
2) Increased reabsorption in the kidney – increases absorption of calcium from loop of Henle & distal tubules & increases rate of phosphate excretion to prevent calcium phosphate stones
3) Vitamin D synthesis – stimulates formation of vitamin D -> increases absorption of calcium from the gut
Hyperparathyroidism types
Primary – uncontrolled PTH production by a tumour of parathyroid glands (malignant and benign)/hyperplasia of glands
Secondary – insufficient vitamin D/CKD reduces calcium absorption from intestines, kidneys and bones -> compensatory to a prolonged hypocalcaemia
Tertiary – development of parathyroid hyperplasia after secondary hyperparathyroidism occurs for an extended period of time & underlying cause is left untreated
Malignant – some tumours produce PTHrP
Hyperparathyroidism symptoms and signs
Reflective of hypercalcaemia & raised PTH
Stones – renal calculi
Bones – fragility fractures, bone pain
Moans – mood disturbances, depression, fatigue, psychosis, confusion
Groans – abdominal pain, N&V, constipation, pancreatitis
Polyuria, polydipsia, fatigue, insomnia, dehydration, HTN
Hyperparathyroidism investigations
Bloods – ALP (raised), vitamin D (deficiency in secondary), U&Es (secondary), decreased phosphate (unless in renal failure) PTH (elevated in all causes except malignant), serum calcium (increased in all except secondary)
Imaging – DXA scan for osteopenic & osteoporotic changes, USS to identify abnormal parathyroid glands
Hyperparathyroidism management
Treat underlying cause
Primary: mild – monitor, increase fluids, vit D supplementation, if symptomatic or Ca2+ > 2.85mmol/L – parathyroidectomy, cinacalcet – calcimimetic (lowers serum calcium & PTH), consider bisphosphonates for bone protection
Secondary: vit D supplementation, UV exposure, calcium, CKD -> reduce phosphate intake & consider phosphate binders
Tertiary: cinacalcet & parathyroidectomy
Malignant: treatment of malignancy, bisphosphonates & cinacalcet
Parathyroidectomy complications
Hypoparathyroidism
Hypocalcaemia
Recurrence
Recurrent laryngeal nerve palsy
Hypoparathyroidism types
Primary – gland failure (autoimmune), congenital (Di George syndrome)
Secondary – radiation, surgery, hypomagnesaemia (Mg required for PTH secretion)
Pseudohypoparathyroidism – failure of target cells to respond to PTH, genetic cause, short stature, round face, calcified basal ganglia, short metacarpals (4th and 5th)
Pseudopseudohypoparathyroidism – same as pseudo but with normal biochemistry
Hypoparathyroidism investigations
Serum calcium decreased
PTH
- Decreased in primary and secondary
- Increased in pseudohypoparathyroidism
- Normal in pseudopseudohypoparathyroidism
ALP normal or increased
ECG - prolonged QT interval indicated severe, life-threatening hypocalcaemia
Bloods - magnesium, vitamin D, phosphate, creatinine
Hypoparathyroidism symptoms and signs
Hypocalcaemia - muscle weakness, hypotonia, hyporeflexia, cramps, tetany, palpitations, light-headedness, arrhythmias – tachycardias, constipation- ileus, rhabdomyolysis
Symptoms of underlying cause
Hypoparathyroidism management
Management – calcium supplementation & calcitriol (synthetic vitamin D)
If hypomagnesaemia – oral or IV magnesium
Central (cranial) diabetes insipidus
Lack of ADH
- Idiopathic (most common)
- Tumours - primary (hypothalamic), secondary (lung, leukaemia, lymphoma)
- Trauma to the head - temporary if distal to pituitary stalk
- Neurosurgery (hypophysectomy)
- Hypopituitarism
- Infection - meningitis, TB, abscess
- Infiltration - sarcoidosis, histiocytosis
Nephrogenic diabetes insipidus
Lack of response to ADH
- Inherited - defect in the gene for the ADH receptor
- Metabolic - hypokalaemia, hypercalcaemia
- Drugs - lithium
- Tubulo-interstitial disease - obstruction, pyelonephritis, chronic renal disease
Diabetes insipidus symptoms and signs
Polyuria - large volumes of dilute urine
Polydipsia
Nocturia
Dehydration
Symptoms of hypernatraemia
- Fatigue, weakness, irritability, nausea and vomiting, fever, thirst, confusion
Postural hypotension
Primary polydipsia
Patient has normally functioning ADH system
Drinks excessive amounts of water, leading to excessive urine production
Not diabetes insipidus
Diabetes insipidus investigations
Bloods - U&Es, Ca2+, glucose (+HbA1c)
Urine dipstick - exclude DM, evidence of renal disease
MRI head
Test pituitary function
Serum osmolality - high, >295 mOsmol/Kg
Urine osmolality - low, <300 mOsmol/Kg, excluded if >600 mOsmol/Kg or double serum osmolality
Urine volume >3L/24 hrs
Water deprivation test
Deprive patients of fluids for 8 hrs or until 3% loss of body weight
Measure serum osmolality, urine volume and osmolality hourly
If urine osmolality >600 mOsmol/Kg and serum osmolality <300 mOsmol/Kg, DI excluded as the condition causes inappropriately dilute urine
Patient is then given synthetic ADH (desmopressin) to differentiate between cranial and nephrogenic DI
Water deprivation results (urine osmolality)
Primary polydipsia – high after water deprivation
Cranial DI – low after water deprivation, high after desmopressin
Nephrogenic DI – low after water deprivation, low after desmopressin
Diabetes insipidus management
Cranial DI
- Give desmopressin intranasally, orally, sublingually or parenterally
- If acute - desmopressin first line and consider oral/IV fluids
- Monitor serum sodium levels as risk of hyponatraemia with desmopressin
Nephrogenic
- Treat the cause
- Drink according to thirst to manage water loss
- If persists, bendroflumethiazide
- NSAIDs - lower urine volume and plasma Na+ by inhibiting prostaglandin release
- Low salt, low protein diet
If hypernatraemic
- Oral/IV fluids, 5% dextrose infusion
SIADH causes
Malignancy
- SCLC, pancreas, prostate, thymus, lymphoma
CNS disorders
- Meningoencephalitis, abscess, stroke, subarachnoid or subdural haemorrhage, head injury, neurosurgery, vasculitis, SLE, Guillain-Barre
Chest disease
- TB, pneumonia, abscess, aspergillosis
Drugs
- Opiates, psychotropics, SSRIs, cytotoxics
Other
- Post-operative, porphyria, major abdominal or thoracic injury, HIV
SIADH symptoms and signs
May be asymptomatic or present with non-specific symptoms
Confusion
Nausea
Irritability
Later - seizures and coma
NO oedema
Symptoms of hyponatraemia
- Lethargy, anorexia, headache, weakness, reduced GCS, hyporeflexia
SIADH investigations
Diagnosis of exclusion
Urine osmolality - high, >100 mOsmol/Kg, urine Na+ - high, >20/30 mmol/L
Serum osmolality - low, <260 mOsmol/Kg, serum Na+ - low, <125 mmol/L
If no cause for SIADH is found, cross-sectional imaging or bowel investigation may be required to find any underlying malignancy
TFTs - hypothyroidism can cause increased ADH release
ACTH - hyponatraemia in Addison’s disease presents in the same way (cortisol deficiency causes increase in ADH activity)
SIADH management
Treatment of the underlying cause
Fluid restriction - 1-1.5L per day (poorly tolerated)
If intolerant to fluid restriction
- Sodium chloride tablets with furosemide - increase urine output and improve serum Na+ levels (monitoring of serum K+ levels)
Correction of hyponatraemia
- Slowly 8-10 mmol/L/day, prevent osmotic demyelination syndrome/cerebral pontine myelinolysis
Vasopressin receptor antagonists - tolvaptan (short period of time, not in patients with liver injury)
Demeclocycline - tetracycline Abx, causes an iatrogenic nephrogenic DI by inhibiting ADH
Adrenal insufficiency symptoms and signs
Fatigue, muscle weakness and cramping
Dizziness and fainting - postural hypotension
Thirst and craving salt
Weight loss, abdominal pain, N&V
Depression
Reduced libido
Hyperpigmentation of the skin creases (increased ACTH causes increased melanin)
Loss of pubic and axillary hair
Hypoglycaemia
Crisis – reduced consciousness, confusion, hypotension (shock), pyrexia, N&V
Adrenal insufficiency types
Primary – destruction/dysfunction of the adrenal cortex
- Addison’s disease
- Infection, infiltration (when antibody -ve)
Secondary – reduction in ACTH release
- Hypopituitarism, isolated deficiency (ACTH), following brain injury, stopping long term steroids
Tertiary – reduction in CRH
- Following chronic glucocorticoid steroid use
Adrenal insufficiency investigations
9am cortisol - low
ACTH concentration - high (low in secondary and tertiary)
ACTH stimulation/Synacthen test - when morning cortisol doesn’t give definitive result
- Synthetic ACTH given, cortisol measured before and 30 and 60 mins after the dose
- Cortisol level should at least double, failure indicates adrenal insufficiency
Hyponatraemia, hyperkalaemia, hypoglycaemia
Anaemia
Raised creatinine and urea
Imaging - CT, MRI of adrenals if suspecting structural pathology, MRI pituitary if underlying pituitary pathology
Adrenal antibodies
Elevated renin levels, low aldosterone levels
Adrenal insufficiency management
Lifelong glucocorticoid and mineralocorticoid steroid replacement
- Hydrocortisone - cortisol (sometimes low dose prednisolone is used)
- Fludrocortisone - aldosterone
Can offer androgen replacement to premenopausal women with low libido
Steroid sick day rules
Instruct patients to double their glucocorticoid doses in times of illness and to continue with this until the illness resolves
May need IV or IM doses during a surgery or cases of prolonged vomiting or diarrhoea
Patients should also carry a steroid emergency card and are encouraged to wear medical alert jewellery
Adrenal crisis management
IV fluids – dehydration & hypotension
IV hydrocortisone
IV dextrose infusion for hypoglycaemia
Cushing’s syndrome symptoms and signs
Round face (moon face), red face (plethora), central obesity, abdominal striae (purple), “Buffalo hump” - enlarged fat pad on the upper back
Proximal limb muscle wasting
Hirsutism
Easy bruising and poor skin healing, hyperpigmentation of the skin (ACTH dependent)
Depression, lethargy, irritability
Gonadal dysfunction - erectile dysfunction, irregular menses
Osteoporosis
If malignant cause - weight loss
Cushing’s syndrome causes
ACTH dependant (high ACTH)
- Cushing’s disease - pituitary adenoma secreting excessive ACTH
- Ectopic ACTH production - SCLC, carcinoid tumours
ACTH independent (low ACTH)
- Iatrogenic - exogenous steroids
- Adrenal adenoma/hyperplasia (+ carcinoma rarely) - secretes excess cortisol (no dexamethasone suppression)
Cushing’s syndrome investigations
Plasma ACTH
Dexamethasone suppression test
24 hr urinary free cortisol (elevated)
Late-night salivary cortisol (elevated)
CRH stimulation - pituitary source if cortisol rises
Pregnancy testing in women of reproductive age
Imaging - pituitary MRI, adrenal CT, CT chest, abdo, pelvis, MRI chest
Inferior petrosal sinus blood sampling - pituitary lesions
Adrenal adenoma investigations results (Cushing’s)
Low dose test – not suppressed
High dose test – not suppressed
ACTH – low
Pituitary adenoma investigations results (Cushing’s)
Low dose test - not suppressed
High dose test – low
ACTH – high
Ectopic ACTH investigations results (Cushing’s)
Low dose test – not suppressed
High dose test - not suppressed
ACTH – high
Cushing’s syndrome management
Iatrogenic - stop medications
Cushing’s disease - removal of pituitary adenoma (trans-sphenoidal), bilateral adrenalectomy if source not located or recurrence post-op, consider post-op PTH and/or cortisol replacement
Adrenal - adrenalectomy + permanent post surgical corticosteroid replacement therapy
Ectopic - treatment of tumour, resection if located and no spread, radiotherapy
Metyrapone, ketoconazole and fluconazole decrease cortisol
Hyperaldosteronism types
Primary hyperaldosteronism – cause is from adrenal gland directly
- Serum renin will be low as the hypertension suppresses it
- Causes: bilateral adrenal hyperplasia, adrenal adenoma secreting aldosterone (Conn’s syndrome), familial (rare)
Secondary hyperaldosteronism - caused by excessive renin stimulating release of aldosterone
- Usually due to disproportionately lower blood pressure in the kidneys
- Renal artery stenosis, heart failure, liver cirrhosis
Hyperaldosteronism investigations
Bloods - U&Es, aldosterone:renin ratio
- High aldosterone, low renin - primary
- High aldosterone, high renin - secondary
CT, MRI - adrenal tumour or hyperplasia
Renal artery doppler, CT angiogram, MR angiography - renal artery stenosis
Hyperaldosteronism management
Aldosterone antagonists - spironolactone, eplerenone
Treat underlying cause - surgical resection, renal artery angioplasty
Phaeochromocytoma
Tumour of the adrenal medulla (chromaffin cells) that secretes unregulated and excessive catecholamines (adrenaline)
Phaeochromocytoma symptoms and signs
Anxiety, sweating, headache, tremor, palpitations, hypertension, tachycardia
If untreated: hypertensive crisis, encephalopathy, hyperglycaemia, pulmonary oedema, cardiac arrhythmias
Phaeochromocytoma investigations
24 hr metanephrines (metabolites of catecholamines)
Plasma metanephrines
CT/MRI of adrenals to locate tumour
Phaeochromocytoma management
Surgical excision of the tumour
Alpha +/- beta blockers for hypertension control, make sure to give alpha blocker first (and beta blockers cover tachycardia)
High sodium diet due to volume loss
Hyperprolactinemia symptoms and signs
Amenorrhoea or oligomenorrhoea
Infertility
Galactorrhoea
Decreased libido
Weight gain
Dry vagina
Erectile dysfunction, decreased facial hair in males
Hyperprolactinaemia causes
Pregnancy, breastfeeding
PCOS
Pituitary tumours - prolactinomas
Drugs - metoclopramide, haloperidol, methyldopa, antipsychotics
Renal failure, primary hypothyroidism
Hyperprolactinaemia investigations and management
Prolactin levels, pregnancy test, TFTs, U&Es
MRI pituitary - lesions
Management
- Prolactinomas (benign tumour of pituitary gland) treated with dopamine agonists - cabergoline or bromocriptine
- If visual disturbances or raised ICP - may need surgical resection, though many decrease in size with dopamine antagonists
Acromegaly symptoms and signs
Increased size of hands and feet, coarse facial features - frontal bossing of the forehead, protrusion of the chin and widely spaced teeth
Soft tissue swelling - enlargement of the tongue and soft palate (snoring and sleep apnoea), puffiness of hands (carpal tunnel syndrome)
Acroparaesthesia (numbness in extremities), headaches, sweating, decreased libido
If pituitary tumour - bitemporal hemianopia may be present
Increased risks - cardiovascular disease, colorectal cancer, arthritis, T2DM, thyroid cancer
Acromegaly causes
GH secreting pituitary tumours
Ectopic GH secretion - lung or pancreatic tumours
Excess GHRH - hypothalamic tumours
Acromegaly investigations
IGF-1 - cannot test GH directly as fluctuates through the day and with physiological states
OGTT (oral glucose tolerance test) - serum GH measured before and after dose, in acromegaly, GH not suppressed
GHRH levels - hypothalamic cause
MRI brain - pituitary lesions
CT chest, abdo, pelvis - ectopic causes
Investigate for complications - ECG, echo, glucose etc.
Acromegaly management
Surgery - trans-sphenoidal removal of pituitary tumours, or other for other tumours
Medical
- Somatostatin analogues (octreotide)
- Dopamine agonists (bromocriptine)
- Growth hormone receptor antagonist
Radiotherapy
