Block 6: Addison's, Acromegaly, Cushing's Flashcards
Hyperaldosteronism
Primary: Bilateral adrenal hyperplasia (most common)
Adrenal adenoma: Conns
Primary hyperaldosteronism features
- Hypertension
- Hypernatraemia, polydipsia, polyuria
- Hypokalaemia i.e. muscle weakness
- Dizziness
- Headache, visual changes
Investigating primary hyperaldosteronism
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
Management of primary hyperaldosteronism
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
Addison’s disease
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
Different part of the adrenal gland
- Medulla: Catecholamines
- Cortex- Zona glomerulosa: Mineralocorticoids
- Cortex- Zona fasciculata: Glucocorticoids
- Cortex- Zona reticularis: androgens
Addisons- causes
- 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)
Addison’s disease: pathophysiology
- 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.
Addison’s disease: Epidemiology
- 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
Addison’s clinical features
- 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
Addison’s disease: diagnosis
- 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
Addison’s disease: treatment
- 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
Adrenal crisis
A life threatening endocrine emergency, requires urgent treatment. When steroid requirements is higher then steroids being administered
Adrenal crisis: clinical features
- 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
Adrenal crisis: lab findings
- Hyponatraemia
- Hyperkalaemia
- Pre-renal failure (increased serum creatinine due to hypovolaemia)
- Hypoglycaemia
Adrenal crisis investigations
- 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
Adrenal crisis treatment
- 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
Complications of Addison’s disease
- 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
Acromegaly definition
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.
Acromegaly initial presentation
- 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
