Endocrinology Flashcards
At what eGFR is metformin contraindicated?
<30
What is phaeochromocytoma?
A rare catecholamine secreting tumour of the adrenal medulla
What are the two parts of the adrenal gland?
Outer cortex
Inner adrenal medulla
What does the adrenal cortex produce?
Mineralocorticoids - e.g. aldosterone
Glucocorticoids - mainly cortisol
Androgens - mainly dehydroepiandrosterone (DHEA) and testosterone
Where is ACTH made/secreted from?
Anterior pituitary gland
What does the adrenal medulla produce?
Catecholamines - e.g. adrenaline, noradrenaline and dopamine.
Describe the HPA axis
Hypothalamus produces CRH
CRH activates the anterior pituitary
Ant. pituitary releases ACTH which stimulates the cortex of the medulla
What is Cushing’s syndrome?
This is a disorder in which the body produces too much cortisol (glucocorticoid)
What is more common, exogenous or endogenous Cushing’s?
Exogenous is far more common
What is an exogenous cause of Cushing’s?
Steroid therapy e.g. for eczema, asthma, RA etc
How can we split endogenous causes of Cushing’s?
ACTH dependent
ACTH independent
What are some ACTH dependent causes of Cushing’s?
Cushing’s disease (80%) - pituitary tumour secreting ACTH resulting in adrenal hyperplasia
Ectopic ACTH production (5-10%) - e.g. small cell lung cancer
What are some ACTH independent causes of Cushing’s syndrome?
Adrenal adenoma
Adrenal carcinoma
Carney complex
Micronodular adrenal dysplasia
What are signs/symptoms of Cushing’s syndrome?
Central obesity (but thin arms/legs) Round moon-like face Fat deposition above collar bone, behind neck Thin skin Muscle weakness High BP High blood sugar Reduced libido/ED
What are some causes of pseudo-Cushing’s?
Alcohol excess
Severe depression
How can we differentiate pseudo-cushing’s from cushing’s?
Insulin stress test
What might you see on an ABG in Cushing’s?
A hypokalaemic metabolic alkalosis
What two tests do we commonly do to diagnose Cushing’s?
Overnight dexamethasone suppression test (most sensitive)
24 hr urinary free cortisol
Dexamethasone suppression results interpretation
Cortisol not suppressed by low dose - Cushing’s syndrome
Suppressed by high dose - Cushing’s disease (pituitary adenoma)
Not suppressed by low or high dose - ectopic ACTH syndrome likely
High dose suppresses ACTH but not cortisol - adrenal tumour
What is primary adrenal failure?
Atrophy/destruction of the adrenal gland
What is secondary adrenal failure?
Inadequate ACTH production
Most commonly from acute steroid withdrawal
Symptoms/features of primary adrenal failure?
Lethargy Weakness Anorexia Nausea + vomiting Weight loss Hyperpigmentation (particularly palmar creases) Loss of pubic hair Hypotension (hypovolaemic shock is commonly how acute adrenal insufficiency presents) Hypoglycaemia Hyponatraemia Hyperkalaemia
Is ACTH high or low in primary adrenal failure?
High
What is the common cause of primary adrenal failure?
Addison’s disease - autoimmune destruction of the adrenal glands
What is reduced in adrenal failure?
Cortisol (and aldosterone)
How can we temporarily lower cortisol before surgery/other curative treatment for cushing’s syndrome?
Metyrapone (inhib. cortisol synth.) or ketoconazole (p450 inhibition)
What is Addison’s disease associated with?
Vitiligo
Premature ovarian failure
Hypothyroidism
Female gender
What is the mechanism of pathology in secondary adrenal failure?
Chronic steroid use lowers ACTH levels
This causes adrenal cortex atrophy
If suddenly stopped can provoke adrenal failure
How do we investigate adrenal failure?
Short synacthen test (measure cortisol, give them ACTH and then measure cortisol again)
Can also measure adrenal autoantibidoies (e.g. anti-21-hydroxylase)
How do we manage adrenal failure?
Chronic
Hydrocortisone (20mg/day), double during infection
Can give fludrocortisone as well but only in primary adrenal failure (because then mineralocorticoids are affected as well)
Acute
Medical emergency - resus + hydrocortisone
Address precipitating factor (e.g. infection)
What is congenital adrenal hyperplasia?
A group of autosomal recessive disorders that affect adrenal steroid biosynthesis
Is ACTH high or low in congenital adrenal hyperplasia?
ACTH is high in response to low cortisol levels
What can high ACTH cause in female infants?
Adrenal androgens that may virilise them
What deficiencies cause congenital adrenal hyperplasia?
21-hydroxylase (90%)
11-beta hydroxylase (5%)
17-hydroxylase (v. rare)
Features of congenital adrenal hyperplasia?
Virilization of female genitalia
Precocious puberty in males
Salt losing crisis
Treatment of CAH?
Dexamethasone (I think)
What is Conn’s syndrome and what does it cause?
Benign adrenal adenoma causing primary hyperaldosteronism
Features of hyperaldosteronism
HTN
Hypokalaemia (muscle weakness)
Alkalosis
How to diagnose hyperaldosteronism?
Aldosterone/reniin ratio (should show high aldosterone levels alongside low renin levels - due to negative feedback from sodium retention by aldosterone)
CT
How do we treat hyperladosteronism?
Surgical removal Aldosterone antagonist (e.g. spironolactone)
What are features of phaeochromocytoma?
Usually episodic, brought on by exercise etc.) HTN (90%) Headaches Palpitations Sweating Anxiety
How do we test for phaeochromocytoma?
24 hour urinary collection of metanephrines (metabolites of catecholamines)
MRI
Treatment of phaeochromocytoma?
Initial:
Alpha blockade - phenoxybenzamine
Beta blockade - propanolol
Definitive:
Adrenalectomy
What is Addisonian crisis?
A severe adrenal insufficiency that is life threatening
What causes Addisonian crisis?
Sepsis/surgery exacerbating the chronic insufficiency from Addison’s/hypopituitarism
Adrenal haemorrhage (e.g. Waterhouse-Friderichsen syndrome)
Steroid withdrawal
How do we manage addisonian crisis?
Hydrocortisone (100mg im/iv), then continue 6 hourly till patient is stable
1 litre normal saline infused over 30-60 mins (or with dextrose)
Oral replacement after 24 hours, reduced to maintenance after 3 days
What are features of addisonian crisis?
Sudden penetrating pain in legs/lower back/abdomen Confusion/psychosis, slurred speech Severe lethargy Convulsions Fever Hyperkalaemia Hypercalcaemia Hypot./hypon./hypogly. Syncope
Control of thyroid hormone secretion
Hypothalamus produces thyrotropin-releasing hormone (TRH)
TRH stimulates the anterior pituitary to release thyroid-stimulating hormone (TSH)
TSH stimulates the thyroid to release thyroxine (T4) and triiodothyronine (T3)
What do T3/T4 do?
They act on a wide variety of tissues helping the regulation of energy sources, protein synthesis and also affects their sensitivity to other hormones
Which is active, T3 or T4?
T3. T4 is converted peripherally into T3 which is 4x more potent.
T3 is less tightly bound than T4 to plasma proteins
How do we classify hypothyroidism?
Primary - problem with the thyroid itself
Secondary - problem with the pituitary gland
Congenital
What are causes of primary hypothyroidism?
Hashimoto's thyroiditis (most common) Subacute thyroiditis (De Quervain's) Iodine deficiency Drug therapy (e.g. lithium, carbimazole, amiodarone)
What are causes of secondary hypothyroidism?
Pituitary failure
Down’s
Turner’s
Coeliac’s
What are features of hypothyroidism?
Weight gain Lethargy Cold intolerance Dry, cold skin Constipation Menorrhagia Decreased deep tendon reflexes
What is hashimoto’s thyroiditis?
Autoimmune disease causing hypothyroidism, it is the most common cause of hypothyroidism
Features of hashimoto’s thyroiditis
Associated with T1DM, Addison’s/pernicious anaemia
Can cause transient thyrotoxicosis in the acute phase
5-10 times more common in women
What is de Quervain’s thyroiditis?
Hypothyroidism that is usually triggered by a viral infection, it presents with a painful goitre/fever, and it causes a raised ESR
What is Riedel’s thyroiditis?
When fibrous tissue replaces the normal thyroid parenchyma
It causes a painless goitre
What are the TSH and free T4 levels in Hashimoto’s thyroiditis?
High TSH
Low T4
What is the TSH and T4 in secondary hypothyroidism?
Both are low
What would you see in TSH/T4 if compliance with thyroxine was bad?
High TSH
Normal T4
(Patient with poor compliance may just be taking thyroxine in the days before their blood test)
Which autoantibodies should be tested for in thyroid disorders?
Anti-thyroid peroxidase (anti-TPO)
TSH receptor antibodies
Thyroglobulin antibodies
TSH receptor antibodies are almost always present in Grave’s disease
Anti-TPO antibodies are almost always present in Hashimoto’s
What is subclinical hypothyroidism?
Where TSH is high and T4 is normal, basically they are on their way to developing hypothyroidism but still have normal thyroxine
What is the treatment for hypothyroidism?
Levothyroxine (25mcg if cardiac disease/over 50 as well, 50-100mcg otherwise)
Levothyroxine management of hypothyroid
Test thyroid function 8-12 weeks after levothyroxine change
Normal TSH of 0.5-2.5
If pregnant, levothyroxine should be increased by 25-50mcg
What are side effects of thyroxine?
Reduced bone mineral density
AF
Worsening of angina
Hyperthyroid
Symptoms of thyrotoxicosis?
Weight loss Heat intolerance Palpitations (tachycardia) Diarrhoea Oligomenorrhoea Anxiety Tremor
What are causes of thyrotoxicosis?
Graves’ disease
Toxic nodular goitre
Acute phase of de Quervain’s thyroiditis/Hashimoto’s
Amiodarone therapy
What do you see on investigation in thyrotoxicosis?
TSH down
T3/T4 up
What are features of graves’ disease not present in other causes of thyrotoxicosis?
Exophthalmos
Ophthalmoplegia
Pretibial myxoedema
Thyroid acropachy
What is myxoedema?
A dermatological change commonly seen in severe hypothyroidism. Mucopolysaccharides are deposited in the dermis resulting in swelling of the area
What is pretibial myxoedema?
Myxoedema of the lower limb, seen in Graves’ disease
What is the pathophysiology of thyroid eye disease?
Caused by an autoimmune response against an autoantigen (maybe TSH receptor?) causing retro-orbital inflammation
How can you prevent thyroid eye disease?
Smoking prevention
Radioiodine treatment can increase the inflammatory symptoms of thyroid eye disease
What is exophthalmos?
Bulging of the eye anteriorly (usually bilaterally in Graves’) due to abnormal connective tissue deposition in the orbit/extraocular muscles
How do we treat thyroid eye disease?
Topical lubricants
Steroids
Radiotherapy
Surgery
What is ophthalmoplegia?
Paralysis of the muscles within the eye/surrounding the eye
What are the features of thyroid eye disease?
Exophthalmos
Conjunctival oedema
Optic disc swelling
Ophthalmoplegia
What is the treatment of Graves’ disease?
Anti-thyroid drugs:
Carbimazole
Radioiodine treatment (can make thyroid eye disease worse)
What are the two ways you can give carbimazole in Graves’?
Anti-thyroid drug titration
Block and replace
What is the concerning side-effect of carbimazole therapy?
Agranulocytosis
What is thyroid storm?
A rare, life-threatening complication of thyrotoxicosis
What causes thyroid storm?
Usually has a precipitating event: Surgery Trauma Infection Acute iodine overload (e.g. from CT contrast)
Clinical features of thyroid storm?
Fever >38.5 Tachycardia Confusion/agitation Nausea and vomiting HTN Heart failure Abnormal liver function (jaundice?)
How do we manage thyroid storm?
Paracetamol
Treat precipitating event
Beta blockers (IV propanolol)
Propylthiouracil/methimazole (anti-thyroid drugs)
Dexamethasone (blocks T4 conversion to T3)
What are the parathyroid glands?
Four tiny glands located in the neck that control the body’s calcium levels
They do this via secretion of parathyroid hormone
How does PTH affect calcium?
3 ways:
Stimulates osteoblasts (and osteoclasts indirectly) to break down and release calcium
Stimulates GI calcium absorption by activating vitamin D
Promotes calcium conservation at the kidineys
What does PTH do to phosphate levels?
PTH is the major regulator of serum phosphate concentrations via the kidney. It inhibits its reabsorption and thus lowers the levels of phosphate
What are the features of hypercalcaemia?
‘bones, stones, abdominal groans and psychic moans’:
Polydipsia, polyuria Peptic ulceration/constipation/pancreatitis Renal stones Depression HTN
What are the findings in hyperparathyroidism investigations?
Raised calcium
Low phosphate
PTH may be raised
Pepperpot skull is characteristic on x-ray
Primary vs secondary hyperparathyroidism?
Primary:
Proliferation of chief cells in the parathyroid
Secondary:
Renal disease resulting in calcium loss/vit. D deficiency can result in compensation from the parathyroid (hypertrophy to synthesise more PTH)
Treatment of primary hyperparathyroidism?
Total parathyroidectomy
Medical: Cinacalcet
What is the main cause of primary hyperparathyroidism?
80% are caused by a parathyroid adenoma
What is an adenoma?
A benign proliferation of glandular tissue
Primary hypoparathyroidism
Decreased PTH secretion
Can be caused by things like thyroid surgery
You get a low calcium and high phosphate
What are the symptoms of hypoparathyroidism?
Symptoms of hypocalcaemia: Tetany (muscle twitching/cramping/spasm) Perioral paraesthesia Trousseau's sign (carpal spasm) Chvostek's sign (tapping over parotid causes facial muscles to twitch) ECG: prolonged QT interval Chronic: depression/cataracts
What is pseudohypoparathyroidism?
Where the target cells are insensitive to PTH
This is due to an abnormality in a G protein
You get low calcium, high phosphate and high PTH
How do we treat hypoparathyroidism?
Alfacalcidol
What does the anterior pituitary produce?
ACTH Growth hormone Luteinising hormone and FSH Prolactin TSH
What does the posterior pituitary store and release (originally produced in hypothalamus)?
ADH (vasopressin)
Oxytocin
What does the intermediate pituitary gland produce?
Melanocyte-stimulating hormone
What is acromegaly
A condition caused by an excess of growth hormone secondary to a pituitary adenoma in 95% of cases
What are the features of acromegaly
Coarse facial appearance Spade like hands Large shoe size Large tongue Prognathism (outward jaw) Excess sweating/oily skin Pituitary tumour features (headache, bitemporal hemianopia) Raised prolactin
What are complications of acromegaly
HTN
Diabetes
Cardiomyopathy
Colorectal cancer
How do we investigate acromegaly
Serum IGF-1 levels + OGTT
In normal patients growth hormone is suppressed to <2, there’s no suppression in acromegaly
How do we manage acromegaly?
Trans-sphenoidal surgery is first line
Dopamine agonists (bromocriptine)
Somatostatin analogue (directly inhibits growth hormone release) - octreotide
What is a prolactinoma?
A tumour of the pituitary gland which produces high levels of prolactin
Features of hyperprolactinaemia
Infertility
Decreased sex drive
Bone loss
Women:
Vaginal dryness
Irregular periods
Production of milk when not pregnant/nursing
Men:
ED
Breast enlargement
Decreased muscle mass/body hair
How to diagnose hyperprolactinaemia?
Blood test
Thyroid tests too (rule out hypothyroidism as cause)
Pregnancy test
MRI head for prolactinoma
Treatment for hyperprolactinaemia
Surgery for tumour
Bromocriptine and cabergoline reduce prolactin production
Radiation
Causes of high prolactin
Prolactinoma Hypothyroidism Chest wall injuries/shingles Chronic liver/kidney disease Drugs
What causes hypopituitarism?
Tumours in or near the pituitary gland Radiation treatment for a tumour Chemo Brain surgery Traumatic bain injury TB/meningitis
Symptoms of hypopituitarism?
Stomach pain, decreased appetite, nausea and vomiting, constipation Excessive thirst/urination Fatigue/weakness Anaemia Headache/dizziness
How do we treat hypopituitarism?
Replacement of the missing hormones
Surgery to remove the tumour
What type of adenoma causes hypopituitarism?
Macroadenomas
How do we classify pituitary tumours?
By size:
Microadenoma - <1cm in diameter
Macroadenoma >1cm in diameter
Hormone status:
e.g. prolactinoma
What type of hemianopia can we get in pituitary adenomas with mass effect?
Bitemporal hemianopia due to compression of the optic chiasm
How do you investigate pituitary tumours?
Pituitary blood profile (prolactin, TFTs, ACTH, GH and FSH/LH)
Visual field testing
MRI brain with contrast
What is diabetes insipidus?
A disorder characterised by lack of ADH/or insensitivity to ADH
What are causes of cranial DI?
Idiopathic
Head injury
Pituitary surgery
Haemochromatosis
What are causes of nephrogenic DI?
Genetic (vasopressin receptor affected - aquaporin 2 channel)
Tubulo-interstitial disease - obstruction/pyelonephritis, sickle-cell
What are features of DI?
Polyuria
Polydipsia
What is the difference between cranial and nephrogenic DI?
Deficiency to produce ADH (cranial)
Insensitivity to ADH (nephro)
What are investigation findings in DI?
Urine osmolality of >700 excludes DI
Water deprivation test
How do we treat DI?
Thiazides, low salt/protein diet (nephrogenic)
Desmopressin (cranial)
What is Nelson’s syndrome?
This is where, say you removed the adrenal gland, that you then get zero negative feedback to the pituitary. It keeps producing ACTH and hypertrophies.
Symptoms include discolouration of skin, visual disturbance, headache
