Block 6: Addison's, Acromegaly, Cushing's Flashcards
1
Q
Hyperaldosteronism
A
Primary: Bilateral adrenal hyperplasia (most common)
Adrenal adenoma: Conns
2
Q
Primary hyperaldosteronism features
A
- Hypertension
- Hypernatraemia, polydipsia, polyuria
- Hypokalaemia i.e. muscle weakness
- Dizziness
- Headache, visual changes
3
Q
Investigating primary hyperaldosteronism
A
Bedside: ECG
Bloods:
- Repeat U&Es (to monitor)
- plasma aldosterone:renin ratio (high aldosterone and low renin = suggestive of primary hyperaldosteronism (not driven by hyperreninism).
- Blood gas may show alkalosis due to aldosterone causing H+ loss
Imaging: MRI/CT for adrenal tumour
4
Q
Management of primary hyperaldosteronism
A
Conservative:
- Risk assessment – driving, job, children. Review other medications (COCP).
- Put in touch with support group/specialist nurses.
Medical: Aldosterone antagonists: Eplenerone/Spironolactone (K+ and hypertension).
Surgical: Following imaging for cause: if adenoma then surgical removal.
- Don’t usually need surgery for bilateral adrenal hyperplasia
5
Q
Addison’s disease
A
Primary adrenal insufficiency caused by the destruction of the adrenal cortex. Causes lack of glucocorticoids (cortisol) and mineralocorticoids (aldosterone). Increased CRH and ACTH, decreased adrenal steroids
6
Q
Different part of the adrenal gland
A
- Medulla: Catecholamines
- Cortex- Zona glomerulosa: Mineralocorticoids
- Cortex- Zona fasciculata: Glucocorticoids
- Cortex- Zona reticularis: androgens
7
Q
Addisons- causes
A
- Autoimmune –most common cause in developed world. Can be part of autoimmune polyglandular syndromes (APS) type 1 or 2.
- Tuberculosis-most common cause worldwide
- Adrenal metastasis
- Adrenal haemorrhage
- Infections: histoplasmosis, cryptococcosis, CMV, HIV
- Amyloidosis and haemochromatosis
- Congenital adrenal hyperplasia
- Bilateral adrenalectomy
- Congenital or neonatal primary adrenal insufficiency
- Other genetic causes: Mutations in genes like CYP21A2 (congenital adrenal hyperplasia) and AIRE (APS-1)
8
Q
Addison’s disease: pathophysiology
A
- Cortisol deficiency:needed for maintaining glucose homeostasis, immune function, and stress response. Reduced cortisol production results in hypoglycemia, increased susceptibility to infection.
- Aldosterone deficiency:Aldosterone is responsible for regulating sodium and potassium balance. Insufficient aldosterone production leads to hyponatremia, hyperkalemia, and volume depletion, causing orthostatichypotensionand impaired renal function.
- Adrenal androgens deficiency:adrenal androgens (dehydroepiandrosterone [DHEA] and androstenedione) are involved in secondary sexual characteristics and libido. A deficiency may result in reduced body hair and decreased libido.
9
Q
Addison’s disease: Epidemiology
A
- Rare
- Common between 30-50 year olds
- More prevalent in women than men
- Fatal if not treated, must be treated lifelong. Even with treatment increased risk of premature death
10
Q
Addison’s clinical features
A
- Weight loss, malaise, weakness
- Low libido, amenorrhea
- N+V, diarrhoea, confusion
- Abdominal pain, constipation
- Myalgia, joint or back pain
- Pigmentation especially of new scars and palmar creases
- Postural hypotension: dehydration, salt craving
- Buccal pigmentation, hyperpigmentation, loss of body hair
11
Q
Addison’s disease: diagnosis
A
- Morning cortisol (8-9am): if <100 nmol/l it 100-400 nmol/L do a ACTH stimulation (synathen) test
- Short Synacthen test (SST)- ACTH stimulation test: Cortisol at 0 minutes, administer ACTH (250mcg IV or IM). Measure cortisol at 30 and 60 mins. If doubles from baseline probably normal. If cortisol < 500 nmol/l at 30 or 60 mins indicate AI. Perform 18-24h after last steroid dose
- ACTH: elevated
- Na: normal or low
- Hyperkalaemia, hypoglycaemia, metabolic acidosis
- Adrenal antibodies (positive 80%)
- CT abdomen
12
Q
Addison’s disease: treatment
A
- Glucocorticoid replacement: Hydrocortisone 15-30 mg daily in divided doses. Following circadian rhythm (breakfast, lunch, dinner: 10-5-5). Prednisone and dexamethasone can also be used. Sick rules: double the dose while unwell or IM hydrocortisone if diarrhoea or vomiting
- Mineralocorticoid replacement: Fludrocortisone 50-300 mcg daily
- Androgen replacement: (not licensed in UK): Dehydroepiandrosterone (DHEA)
- MedicAlert bracelet and steroid cards
- Emphasise importance of not missing doses
13
Q
Adrenal crisis
A
A life threatening endocrine emergency, requires urgent treatment. When steroid requirements is higher then steroids being administered
14
Q
Adrenal crisis: clinical features
A
- Fatigue, lack of energy, weight loss
- Low blood pressure, postural hypotension dizziness, collapse, in severe cases hypovolaemic shock
- Abdominal pain, tenderness and guarding, nausea, vomiting
- Fever
- Confusion, somnolence, in severe cases delirium or coma
- Back and leg cramps/spasms
- Low blood pressure and abdominal pain think adrenal crisis
15
Q
Adrenal crisis: lab findings
A
- Hyponatraemia
- Hyperkalaemia
- Pre-renal failure (increased serum creatinine due to hypovolaemia)
- Hypoglycaemia
16
Q
Adrenal crisis investigations
A
- Adrenal insufficiency should be ruled out in any acutely ill patient
- Assess blood pressure and fluid balance status; measure blood pressure from supine to standing to check for postural drop
- Take drug history (glucocorticoids?)
- Bloods: FBC, U&E, TFT, cortisol and ACTH
- Diagnostic measures should never delay treatment. No adverse effects for initiating hydrocortisone
17
Q
Adrenal crisis treatment
A
- Hydrocortisone: (immediate bolus injection of 100mg hydrocortisone i.v. or i.m) followed by continuous intravenous infusion of 200mg hydrocortisone per 24h (alternatively 50mg hydrocortisone per i.v. or i.m. Injection every 6h)
- Rehydration: with rapid intravenous infusion of 1000mL of isotonic saline infusion within the first hour, followed by further intravenous rehydration as required (usually 4–6L in 24h)
- Contact an endocrinologist for urgent review
18
Q
Complications of Addison’s disease
A
- Adrenal crisis: severe hypotension, hypoglycaemia and altered mental state
- Chronic complications: inadequate hormone replacement can cause persistent fatigue, weight loss and electrolyte imbalance
- Osteoporosis: due to long term glucocorticoid therapy
- Infections: increased susceptibility
19
Q
Acromegaly definition
A
Long term endocrine condition due to hyper-secretion of growth hormone, normally due to a pituitary adenoma. Causes enlargement of extremities (fingers, toes). A minority of cases are caused by ectopic GHRH or GH production by tumours e.g. pancreatic.
20
Q
Acromegaly initial presentation
A
- Diagnosed in 5th to 7th decade
- Present with Type 2 Diabetes, Blood pressure
- Change in glove size, shoe size, spade like hands
- Large fingers, toes
- Visual field defect: bitemporal hemianopia
21
Q
Acromegaly: clinical presentation
A
- Coarse facial features: jaw protruding, large lips and tongue
- Increase in inter-dental spacing: teeth separated
- Growth in soft tissue, cartilages, membranous bones
- Sweating, headache
- Carpal tunnel syndrome
- Obstructive sleep apnoea
- Cardiovascular disease, Osteoporosis
- Long term association with cancer
- Can have galactorrhoea and 6% have MEN-1
22
Q
Acromegaly Diagnosis
A
- High IGF-1: if moderate to oral glucose tolerance
- Oral Glucose Tolerance Test: Failure of suppression of GH to <2 mu/L
- Pituitary MRI
23
Q
Acromegaly monitoringand screening
A
- Screening for cancer: Colonoscopy
- Monitor for end organ problems: Echo, DEXA Scan
- Monitor IGF-1 Level for recurrence
24
Q
Cushing’s syndrome: definition
A
Due to chronic exposure to excess glucocorticoids. Important endocrine cause of obesity
25
Q
Steroid biosynthesis
A
- All made from cholesterol.
- Mineralocorticoid pathway results in Aldosterone.
- Glucocorticoid pathway results in cortisol. Made in Zona fascicular of adrenal cortex
- Androgenic pathway results in Testosterone and oestrogen
26
Q
Cushing’s syndrome: pathophysiology
A
- Anti-inflammatory and immunosuppressive
- Increases hepatic gluconeogenesis decreases peripheral glucose uptake: elevated blood glucose
- Bone metabolism: osteoporosis
- Protein catabolism: muscle wasting
27
Q
Cushing’s syndrome: signs and symptoms
A
- Decreased libido, menstrual changes
- Red cheeks, extensive striae, skin bruising
- Central Obesity, round face (moon face), thin arms and legs, large stomach, nuchal fat pads
- Thin skin, Hirsuitism
- Hypertension
- Ecchymoses: red marks
- Lethargy, depression
- Abnormal glucose tolerance
28
Q
Cushing’s investigations: confirm cortisol use
A
- Elevated 24-hour urinary free cortisol (UFC) excretion= calculate cortisol:creatinine ratio. Two measurements are required
- Bedtime salivary cortisol: two measurements are required
- Overnight 1 mgDexamethasone suppression test (DST): Give at 11 PM. Cortisol checked at 9 AM. Cushing’s syndrome suspected if no suppression and >/= to 50 nmol/L
29
Q
Cushings: Tumour location
A
- Pituitary tumours are ACTH dependent: 70%
- Ectopic ACTH secretion secondary to malignancy is also ACTH dependent
- Adrenal adenoma are cortisol dependent
30
Q
Cushings: general findings
A
- Hypokalaemic metabolic alkalosis
- Impaired glucose tolerance
- Ectopic ACTH secretion: very low potassium
31
Q
Cushings investigations: localise the site (pituitary or adrenal)
A
- Undetectable ACTH suggests adrenal pathology: Proceed to adrenal imaging (CT scan)
- Detectable ACTH (suspect pituitary) – proceed to 48 hr High dose Dexamethasone suppression test= 2 mg ofdexamethasoneorally every six hours at 8 AM, 2 PM, 8 PM, and 2 AM. If 48 hour 9 AM cortisol is <50% of the basal value after 48 hours of last dose then suppressed.
- Suppression with high dose dexamethasone is seen in pituitary Cushing’s disease but not ectopic ACTH production or adrenal tumours → Proceed to Pituitary MRI
32
Q
Cushings: interpreting high dose dexamethasone suppression test
A
- Adrenal adenoma: Cortisol not suppressed, ACTH suppressed
- Pituitary adenoma: Cortisol suppressed, ACTH suppressed
- Ectopic ACTH syndrome: Cortisol not suppressed, ACTH not suppressed
33
Q
Cushing’s: other tests
A
- CRH stimulation: if pituitary source then cortisol rises. If ectopic/adrenal then no change in cortisol
- Petrosal sinus sampling of ACTH may be needed to differentiate between pituitary and ectopic ACTH secretion.
- An insulin stress test is used to differentiate between true Cushing’s and pseudo-Cushing’s.
34
Q
Cushing’s medical management
A
- Metyrapone, Ketocanazole
- Use pre-operatively or conservatively if not fit for surgery
35
Q
Cushing’s surgical management- pituitary tumours
A
- Trans-sphenoidal surgery: Pituitary radiotherapy as adjunctive treatment if surgical cure not achieved
- Laparoscopic or open adrenalectomy for adrenal tumours
- Surgery is definitive treatment
36
Q
Cushings complications
A
Venous thromboembolism, stroke and myocardial infarction. Good survival patients live >40 years post cure
37
Q
Hypernatraemia
A
- > 145mmol
- Two variables: can have hypernatremia due to high sodium or low water. Normally due to too little water
- Risk factors: hospital admission, inability to drink water/access water, infancy, old age, Nursing home residents
- Dehydration: the elderly, terminal illness, water loss>water intake
- Excess Na+ in IV therapy: saline
38
Q
Clinical features of DI
A
- Urinary frequency, nocturia
- Pale urine
- Hypernatremia, normal glucose, high plasma osmolarity
- Dehydration: fatigue, dizziness, weakness
- Space occupying lesion causing DI: headache, visual changes, seizure
39
Q
ADH
A
- Osmoreceptors detect increased osmotic pressure
- Baroreceptors (carotid sinus, aortic arch) detect decreased blood pressure
- Posterior pituitary releases ADH
- Causes blood vessel vasoconstriction and increased reabsorption of water in the kidneys
- Leads to increased blood volume and pressure
40
Q
Diagnosis of diabetes insipidus
A
- Water deprivation test: deprive patient of fluids to allow serum osmolality to rise and assess whether urine concentrates (i.e. urine osmolality increases)
- Patient usually fasted overnight though is allowed to have fluids
- Weight, Serum and urine osmolality measured regularly
- Test stopped early if >3% body weight lost
- Diabetes Insipidus: Continued production of dilute urine despite fluid deprivation, when the kidneys should usually conserve water. High plasma sodium and increased plasma osmolality with inappropriately low urine osmolality
41
Q
Water deprivation test: results
A
- Cranial DI: urine osmolality <300, Urine osmolality after vasopressin administration: >800
- Nephrogenic DI: urine osmolality <300, Urine osmolality after vasopressin administration <300
- Primary polydipsia (patient drinking too much water): urine osmolality >800, urine osmolality after vasopressin administration >800
- Vasopressin is given after water deprivation test
- Cranial DI: issues with ADH release from posterior pituitary
- Nephrogenic DI: issues with ADH site of action in CD
42
Q
Causes of DI
A
- Cranial Acquired: Trauma, surgery (pituitary), tumours (germ cell) (craniopharyngiomas), sarcoid, TB, infections (meningitis), idiopathic. Commonly due to destruction of magnocellular cells
- Cranial familial: DIDMOAD ( syndrome with following conditions= D.I, diabetes mellitus, optic atrophy, deafness- Wolfram syndrome)
- Nephrogenic Acquired: Drugs (lithium), chronic renal disease, post obstructive uropathy, metabolic (hypercalcaemia, hypokalaemia)
- Nephrogenic familial: (X linked recessive (mutations in vasopressin-2-receptor) and autosomal recessive(mutations in aquaporin 2 gene)).
- Gestational DI
- Dipsogenic DI: impairement of thirst mechanism- chronic meningitis, MS
43
Q
DI investigations
A
- 24 hour urine volume measurement (> 3 litres/day)
- Exclude diabetes mellitus, renal failure i.e. OGGT, U&E, calcium
- Check electrolytes (calcium and potassium)
- Urine and serum osmolality to calculate the urine to plasma (U:P) osmolality ratio= If U:P ratio is <2:1 DI likely
- Water deprivation test
- MRI brain: tumours
- Serum ACE: sarcoidosis
- Serum copeptin: precursor of ADH, high in nephrogenic DI
44
Q
DI treatment
A
- Desmopressin: ADH analogue with longer half life. Oral and nasal administration. Monitoring of serum sodium and osmolality. Acts on kidneys, little effect on blood vessels. For cranial DI
- Due to treatment cranial DI has fewer symptoms then nephrogenic
45
Q
Nephrogenic DI treatment
A
- Correction of the underlying cause
- High doses of desmopressin can be trialled
- High fluid intake
- Thiazides diuretics and some NSAID’s can be helpful: inhibit local prostaglandins
46
Q
Types of hormones
A
- Endocrine – enters circulation and has an effect on a target cell/organ
- Paracrine – has an effect on a local cell but does not enter circulation
- Autocrine – affects cell type that secreted it
- Intracrine – acts intracellularly
- All secreted internally
47
Q
Three main classes of hormones
A
- Protein (peptides e.g insulin) or amino acid (usually tyrosine e.g.thyroxine) derivatives
- Steroids
- Eicosanoids e.g.prostaglandins: tend to be paracrine or autocrine
48
Q
Anatomy of hormone signalling
A
- Three tiers: Tertiary (hypothalamus), Secondary (Pituitary), Primary (secretory gland)
- Vascular signalling- anterior pituitary. Blood flows from the hypothalamus into the anterior pituitary and the rest of the body, its a porto-venous system
- Neural signalling- posterior pituitary
49
Q
Hormones released from anterior pituitary
A
- TSH → Thyroid gland
- ACTH → Adrenal cortex
- FSH → testes/ovaries
- LH → testes/ovary
- Prolactin → breast
- Growth hormone → Liver (affects bone and muscle growth)
50
Q
Pituitary tumours
A
Affects the internal carotid artery, cranial nerves and the optic chiasm
51
Q
Addisons bloods
A
- Hyperkalaemia
- Hypoglycaemia
- Raised creatinine and urea
- Hypercalcaemia
