Endocrinology - Clinical Flashcards
What syndrome results from hyperfunction of the adrenal gland?
Cushing syndrome
What causes Cushing syndrome?
Prolonged exposure to elevated levels of cortisol or exogenous glucocorticoid drugs
What other general features can be caused by excess cortisol?
1) Osteoporosis
2) Negative nitrogen balance
3) Increase appetite
4) Obesity
5) Increased susceptibility to infection
What is Cushing disease caused by?
A pituitary tumour producing excess ACTH
What are clinical features of Cushing?
- Obesity
- Hypertension
- Hirsutism
- Purple/red striae
- Acne
- Bruising due to thin skin
- Neuropsychiatric defects
- Menstrual disorders
- Impotence
- Glucose intolerance
- (Worsening) diabetes
- Fatigue
- Low mood
- Thin arms and legs (myopathy)
- Red cheeks
- Moon face
- Poor wound healing
- Distended abdomen
- Fat pads (buffalo hump)
What are possible causes of adrenal hyperfunction?
1) ACTH dependent - pituitary (Cushing’s)
2) ACTH independent - adrenal adenoma/carcinoma
3) Exogenous steroids
Why is Cushing’s syndrome hard to confirm?
Because it can’t be confirmed by one blood test - need 2 or 3 positives
Describe 3 tests used to confirm Cushing’s
1) Low dose dexamethasone suppression test - unsuppressed cortisol next morning → overproduction
2) 24h urinary cortisol
3) Loss of diurnal rhythm (mid night cortisol) - insert cannula before sleep and take sample when asleep → lack of change indicates under regulated production
What is an intervention treatment used to treat Cushing’s and describe it ?
Laparoscopic adrenalectomy
- Give replacement glucocorticoids (hydrocortisone) to prevent feeling like they have adrenal under function
- Many of the features improve → BP, diabetes but psychological disturbances may continue
What are the different modes of action for drug treatment for Cushing’s?
1) Inhibit steroid biosynthesis
2) Inhibit ACTH release
3) Inhibit glucocorticoid receptor
What medication is used to inhibit steroid biosynthesis to treat Cushing’s?
1) Metyrapone - 11β-hydroxylase inhibitor
2) Ketoconazone - 17α-hydroxylase and 11β-hydroxylase inhibitor
What medication is used to inhibit ACTH release to treat Cushing’s?
1) Pasireotide - SSTR5 (somatostatin analogue) agonist
2) Cabergoline - dopamine D2 agonist
What medication is used to inhibit the glucocorticoid receptor to treat Cushing’s?
Mifeprestone - also a progestogen receptor antagonist
What is pheochromocytoma?
Tumour of the adrenal medulla which secretes noradrenaline or adrenaline
Describe the presentation of pheochromocytoma
1) Headaches
2) Palpitations, heart racing
3) Sense of doom
4) Chest pain
5) Sweating
6) Weight loss
7) Episode of collapse
How do you diagnose pheochromocytoma?
24h urine catecholamines
How do you treat pheochromocytoma?
Surgical removal after pre-treatment with alpha and B blockade e.g. doxazosin
What are the signs and symptoms of hyperaldosteronism?
1) Resistant hypertension
2) Low K
3) Low renin
4) Elevated aldosterone
Describe primary hyperaldosteronism
1) Autonomous hypersecretion of aldosterone
2) Independent of RAS
3) Low/suppressed renin
What is an example of a primary hyperaldosteronism syndrome?
Conn’s syndrome - hypertension, hypokalaemia, alkalosis, unilateral adenoma
How do you confirm primary hyperaldosteronism?
1) Measurement of PRA (suppressed) and aldosteorne (high) in salt-replete individuals
2) Selective venous sampling
How do you treat Conn’s syndrome?
1) Remove the adenoma - laparoscopic
2) Drug treatment - spironolactone (aldosterone agonist, used as K sparing diuretic) or eplerenone
What disease is caused by hypofunction of the adrenal gland?
Addison’s disease
What is primary adrenal insufficiency due to?
Destruction of the adrenal cortex - all hormones affected
What is secondary adrenal insufficiency due to?
Lack of ACTH
How do you treat adrenal insufficiency?
Replacement therapy with fludrocortisone
What are the clinical features of Addison’s disease?
1) Weakness
2) Fatigue
3) Anorexia
4) Weight (and hair) loss
5) Hyperpigmentation esp. in oral mucosa, palmar creases and knuckles - uncalled for tan, new scars
6) Hypotension (syncope)
7) Gastrointestinal disturbances - diarrhoea, nausea, vomiting
8) Salt craving
9) Postural symptoms (hypotension) - systolic drop of >20mmHg and diastolic of 10mmHg
10) Muscle pain (myalgia)
11) Malaise
12) Dehydration
What are causes of primary hypoadrenalism?
1) Abrupt discontinuation of steroids
2) Addison’s
3) TB
4) Surgery
5) Haemorrhage/infarction - meningococcal septicaemia
6) Infiltration - malignancy, amyloid
What are investigations used to diagnose hypoadrenalism?
1) Random cortisol
2) Short synacthen test - dynamic test, synthetic ACTH, fail to see cortisol rise over 420nm/l
3) Plasma ACTH
4) Urea, electrolytes and glucose
5) Adrenal antibodies (autoimmune)
Describe the treatment for adrenal failure
1) Emergency, life-threatening adrenal crisis - ICU care, fluids, sodium , IV hydrocortisone at high dose
2) Maintenance treatment - glucocorticoid (hydrocortisone), mineralocorticoid (fludrocortisone) and maybe DHEA
What results from adrenal hypofunction?
Addison’s disease
What results from adrenal hyperfunction?
Cushing’s, pheochromocytoma, Conn’s/hyperaldosteronism
What are effects of hyperprolactinaemia?
1) Galactorrhea (milk secretion from breast when not pregnant)
2) Gynaecomastia (excess breast growth in females and males)
3) Infertility in males and females
What is used to treat hyperprolactinaemia?
D2 agonists bromocriptine and cabergoline as dopamine inhibits prolactin secretion via D2 receptors
What clinical conditions are caused by hypersecretion of GH?
1) Gigantism - before fusion of epiphyses (closure of long bone)
2) Acromegaly - after fusion of epiphyses, often caused by pituitary tumour
What clinical conditions are caused by hyposecretion of GH?
1) Short stature - before fusion of epiphyses
2) Adult GH deficiency - after fusion of epiphyses
What happens in acromegaly to GH release?
You lose the pulsatile release during sleep - more constant
What are treatment options for acromegaly?
1) Trans-sphenoidal surgery
2) Bromocriptine/cabergoline - tumour tends to produce D2 receptors, so can control GH release using D2 agonists
3) Octreotride/Lanreotide - long acting somatostatin (SST) analogues, SST2 > SST5
4) Pasireotide - SST analogue, SST5 > SST2
- SST2+5 inhibit GH release, SST5 inhibits ACTH and insulin release
What are treatment options for short stature?
1) Recombinant humanGH (somatropin)
2) Recombinant hIGF-1 (mecasermin)
Why does a sellar pituitary mass also extend into the suprasellar space?
Bc it is easier to grow upwards than down into the bony space
How does a (supra)sellar pituitary mass cause visual defects?
1) The mass compresses the optic chiasm
2) The nerve fibres within the optic fibres are no longer signalling
3) The lesion at the chiasm causes bitemporal hemianopia - cannot see images in temporal lobe (nasal retina)
What are symptoms of a pituitary mass?
1) Reduced hair growth
2) Decreased libido
3) Reduced energy
4) Weight gain
5) Headache
6) Diplopia (double vision)
What do you need to evaluate for hypopituitarism (deficiency of pituitary hormones)?
1) Fatigue, lethargy
2) Weight (and where)
3) Libido
4) Menses
5) Hair
6) Skin
7) Vision (more for mass lesion)
What do you need to examine for hypopituitarism?
1) Mood
2) Affect and behaviour
3) Skin
4) Colour
5) Neurophthalmic (incl. acuity, visual field defects, III-VI, eye movement)
6) Fat distribution
7) Proximal muscles
8) Body hair
9) Testicular volume
Why does a pituitary tumour result in hypopituitarism?
As the tumour grows, it begins to interfere with communication between the hypothalamus and anterior pituitary
Describe the features of almost complete anterior pituitary failure (caused by a tumour?)
- Slightly increased prolactin
- Decreased GH and cortisol response to hypoglycaemia
- Decreased testosterone
- Normal thyroxine
- Normal overnight urinary concentration
How do you test for pituitary hypofunction?
Measure the pituitary (trophic) hormone and the target hormone
How would you test for pituitary hypofunction by testing for each hormone?
1) PRL - lactation
2) TSH - T4, T3
3) LH - testosterone/oestrogen
4) FSH - spermatogenesis / folliculogenesis
5) GH - IGF-1, insulin tolerance test (ITT)
6) ACTH - cortisol, synacthen test for cortisol, ITT
What are the two possible causes and indications of hypothyroidism?
1) Primary hypothyroid - low T4, high TSH
2) Hypopituitary - low T4, low TSH (normal thyroid gland)
What are the 2 sizes of a pituitary tumour?
1) Microadenoma < 10mm of average size
2) Macroadenoma > 10mm of average size
What are the 2 types of pituitary tumour?
1) Non-functioning
2) Functioning → endocrine syndromes as some secrete excess hormones
Depending on what hormone the macroadenoma secretes, what syndromes can it cause?
1) GH → acromegaly
2) ACTH → Cushing’s
3) PRL → galactorrhoea and amenorrhoea
4) TSH → thyrotoxicosis
What are the 5 different ways a pituitary tumour can present?
1) Mass effect e.g. visual field defect
2) Hypopituitarism
3) Incidental
4) Hyperfunction (functioning tumour) - most common is PRL production
5) Pituitary apoplexy/haemorrhage (acute)
What are the 4 different ways to treat a pituitary tumour?
1) Conservative/surveillance → microadenoma
2) Surgery → macroadenoma
3) Medical → for PRL secreting tumours, administering dopamine agonist
4) Radiotherapy → as second line treatment, can prevent regrowth
What are the principles of hormone replacement for hypopituitarism?
1) The goal of treating hypopituitarism is to replace the hormones that nature would have intended
2) Replacement needs to recognise diurnal variation and the ‘natural’ evolution of hormone levels over time
What hormones would be replaced in hypopituitarism?
Cortisol (hydrocortisone), testosterone/oestrogen, GH
Why do you need to take hydrocortisone several times a day for hormone replacement?
To mimic the natural pattern
What is an insulin stress test?
When you make the patient hypoglycaemic to test if the necessary hormones are released
