What is the pathology behind Congenital adrenal hyperplasia ?
Autosomal recessive disorder
Reduced corticoids due to deficiency in 21-hydroxylase. Causes increase in ACTH to increase in androgens. Salt losing crisis causes hyperkalaemia + hyponatraemia
Why do you get hypovolaemic hyponatraemia?
mild dehydration
S+S Addisons
Fatigue Weakness N+V Weight loss Abdo pain Diarrhoea/ constipation Muscle cramps Hyperpigmentation Cravings for salt Hypotension Crisis brought on by infection of stress
Primary + secondary Addisons
Primary = inability to produce enough steroids in adrenal glands Secondary = inadequate stimulation by pituitary glands
Blood results for Addisons
Hyponatraemia Hyperkalaemia Hypercalcaemia Raised LFTs Reduced cortisol ACTH = high in primary, low in secondary
Management of addisons
Glucocorticoids (hydrocortisone) + mineralcorticoids (fludracortisone)
Steroids + chickenpox
At risk of severe chicken pox when on steroids
Cause pneumonia, hepatitis + shingles
When should addisons be suspected in hypothyroidism + diabetes?
Hypothyroidism = when symptoms worsen with thyroxine T1DM = unexplained hypos
How is Addisons diagnosed?
Adrenocorticotrophic hormone stimulation test
Management of adrenal crisis
IM or IV hydrocortisone
Mechanism of familial hypercholesterolaemia
Inherited defected gene
What blood results indicate FH may be present?
<30 y/o with total cholesterol >7.5
>30 y/o with total cholesterol >9
What is the primary care management of FH?
Lifestyle advice
High intensity statin or ezetimibe
Anti HTN drugs
Aspirin as primary prevention of CVD
What is the pathology of Cushings?
Prolonged exposure to high levels of steroids
What are the causes of Cushings?
ACTH dependant:
Cushings disease, ACTH producing tumours or excess ACTH meds
Non-ACTH dependant:
excess steroids, adrenal adenoma or carcinoma
What is Cushings disease?
Excessive ACTH from pituitary (pituitary adenoma)
RF for Cushings
Females
25-40
S+S of Cushings
Truncal obesity, buffalo hump, supraclavicular fat pads Facial fullness/ moon face Proximal muscle wasting + weakness Diabetes Gonadal dysfunction HTN Skin atrophy, easy bruising, hirsuitism, acne Depression Osteoporosis Thirst, polyuria/dipsia
Investigations for ?Cushings
24hr urine cortisol Overnight dexamethasone suppression test Late night salivary cortisol RBC - raised WCC Hypokalaemia, metabolic alkalosis Plasma ACTH (high + elevated cortisol = ACTH dependant Cushings)
What is inferior petrosal sinus sampling?
Performed with CRH stimulation to aid in diagnosing source of excess ACTH
Management of Cushings
Surgery or RT
Metyrapone, ketoconazole, and mitotane can all be used to lower cortisol
Complications of Cushings
Metabolic syndrome HTN Diabetes Obesity Hyperlipidemia Osteoporosis Thrombophilia Nelson's syndrome Primary pituitary tumour
Presentation of congenital adrenal hyperplasia
Females = ambiguous genitalia
Boys with classic form = no signs at birth, possible penis enlargement. Early virilisation at 2-4 y/o
Boys with salt-losing form = present at 7-14 days with vomiting, weight loss, lethargy, dehydration
Non classic = hyperandrogenism in later childhood (early puberty, infertility, hirsutism, acne, PCOS)
Investigations for ?congenital adrenal hyperplasia
Hyponatraemia Hyperkalaemia Hypoglycaemia High serum 17-hydroxyprogesterone Corticotropin stimulation test Pelvic US for ambiguous genitalia
Management of classic congenital adrenal hyperplasia
Hydrocortisone (kids) + prednisolone (adults)
Fludrocortisone
Additional salt intake in hot weather + exercise
Management of non-classic congenital adrenal hyperplasia
Treatment only for symptomatic
Hydrocortisone + hormones (female)
Complications of congenital adrenal hyperplasia
Poor growth Obesity Insulin resistance HTN CVD Central precocious puberty Infertility PCOS Testicular adrenal rest tumours
What is hyperaldosteronism?
Excess levels of aldosterone due to high renin levels (secondary) or independant of renin-angiotensin axis (primary)
What does excess aldosterone do in the kidneys?
Acts at distal renal tubule, promoting sodium retention
causes water retention + HTN
Excretion of potassium
Causes of primary hyperaldosteronism
Adrenal adenoma (Conn’s syndrome)
Adrenal hyperplasia
Familial hyperaldosteronism
Adrenal carcinoma
S+S of hyperaldosteronism
HTN
Polyuria/ dipsia
Weakness
Headaches + lethargy
Blood results for hyperaldosteronism
Hypokalaemia
Metabolic alkalosis
Hypernatraemia
Spot renin + aldosterone levels (low renin + high aldosterone for primary)
Diagnosis of hyperaldosteronism
Selective adrenal venous sampling
CT/ MRI
Salt loading test
What is the key differential of hyperaldosteronism + how is it different?
Renal artery stenosis due to HTN + hypokalaemia
Renal arteriogram
Management of Conn’s syndrome + hyperaldosteronism
Aldosterone antagonists (spironolactone or amiloride) Surgery - adrenalectomy
Causes of secondary hyperaldosteronism
Diuretics, HF, hepatic failure, nephrotic syndrome, RAS, malignant HTN
Investigation results for hypoaldosteronism
Hyperkalaemia
Metabolic acidosis
What is hypoaldosteronism also known as?
Type 4 renal tubular acidosis
Causes of hypoaldosteronism
Reduced aldosterone: hyporeninemic hypoaldosteronism, pharmacologic inhibition of renin or angiotensin II, heparin therapy, and primary adrenal insufficiency
Aldosterone resistance: pharmacologic inhibition of the epithelial sodium channel in the collecting tubule, due either to potassium-sparing diuretics or antibiotics
Management of hypoaldosteronism
Fludrocortisone
Pathology of SIADH
Ingestion of water does not suppress ADH
Concentrated urine leads to water retention
This lowers plasma sodium by dilution
High total body water triggers increased urinary sodium excretion
Causes of SIADH
CNS disorders (stroke, hemorrhage, infection, trauma)
SCC of lung producing ADH
Some drugs increase ADH release
Surgery
Pulmonary disease eg pneumonia, asthma, acute resp failure
Management of SIADH
Fluid restriction
NaCl (oral or IV)