Adrenals Flashcards
Adrenal cortex physiology
CRF from hypothalamus stimulates ACTH from anterior pituitary
ACTH stimulates steroid production in adrenals
Zona fasiculata produces glucocorticoids
Zona glomerulosa produces mineralocorticoids
Zona reticularis produces androgens
What is Cushing’s syndrome
Chronic glucocorticoid excess + loss of normal feedback + loss of cortisol circadian rhythm
Cushing’s causes (inc ACTH)
Cushing’s disease (bilateral adrenal hyperplasia)
Ectopic ACTH production (small cell lung cancer, carcinoid tumours)
Ectopic CRF production (very rare, some thyroid medullary and prostate cancers)
Ectopic ACTH specific features
Hyperpigmentation
Hyperglycaemia
Hypokalaemic metabolic alkalosis
Weight loss
Cushing’s causes (low ACTH due to -ve feedback)
Steroids
Adrenal adenoma/ cancer
Adrenal nodular hyperplasia
(Rare) Genetic syndromes Carney complex/ McCune-Albright
Cushing’s presentation
Weight gain (central obesity, moon face, buffalo hump) Mood change (lethargy, depression) Acne
Proximal weakness
Recurrent Achilles tendon rupture
Osteoporosis
Raised BP + glucose
Cushing’s treatment for iatrogenic cause
Iatrogenic - stop medications
Treatment for Cushing’s disease
Cushing’s disease - trans-sphenoidal adenoma removal, bilateral adrenalectomy if can’t find source
Cushing’s treatment for adrenal adenoma/carcinoma
Adrenal adenoma - adrenalectomy (radiotherapy and mitotane follow if carcinoma)
Cushing’s treatment for ectopic ACTH
Ectopic ACTH - Surgery if tumour found and not spread
Metyrapone, ketoconazole + fluconazole decrease pre-op cortisol secretion
Intubation + mifepristone (cortisol competitive inhibitor) + etomidate (blocks cortisol synthesis) in severe ACTH psychosis
Cushing’s prognosis
Untreated - inc vascular mortality
Treated then good prognosis but DM, osteoporosis, HT often stay
Cushing’s investigations
Confirm raise cortisol
1st line - overnight dexamethasone suppression test + 24h urinary free cortisol
2nd line - 48h dex suppression test, 48h high-dose dex suppression test, midnight cortisol
Localisation tests
Overnight dexamethasone suppression test and interpreting results
Outpatient test
Dex 1mg PO at midnight, check serum cortisol at 8am
Normally cortisol ≤50nmol/L but no suppression in Cushing’s
False +ves seen in seen in depression, obesity, alcohol excess, inducers of liver enzymes, rifampicin
24h urinary free cortisol test results
Normal <280nmol/24h
48h dexamethasone suppression test and interpreting results
Dex 0.5mg/6h PO for 2d
Measure cortisol at 0 and 48h (last test 6h after last dose)
Failure to suppress in Cushing’s syndrome
48h high dose dexamethasone suppression test and interpreting results
Dex 2mg/6h
May distinguish pituitary (suppressed) from other causes (no/part suppression)
Midnight cortisol and interpreting results
Admit (unless salivary cortisol used)
Normal circadian rhythm (lowest at midnight, highest early morning) lost in Cushing’s so inc cortisol
Cushing’s localisation tests
If 1st + 2nd line +ve:
Plasma ACTH
If undetectable then adrenal tumour likely -> CT/MRI adrenal glands, if no mass then adrenal vein sampling
If ACTH detectable distinguish pituitary from ectopic with high-dose suppression test or CRH test
CRH test
100mcg ovine or human CRH IV, measure cortisol at 120mins
Cortisol rises with pituitary disease, doesn’t with ectopic ACTH production
Cushing’s investigations following cortisol studies
If cortisol responding to manipulation, Cushing’s disease likely so MRI pituitary + consider bilateral inferior petrosal sinus blood sampling
If cortisol not responding find ectopic ACTH: IV contrast CT of chest abdo pelvis ± MRI of neck thorax abdo
What is 1˚ adrenocortical insufficiency
Addison’s disease
Destruction of adrenal cortex leads to glucocorticoid + mineralocorticoid deficiency
Addison’s causes
80% due to autoimmunity
TB (commonest cause worldwide)
Congenital
Adrenal metastases
Adrenal haemorrhage
Lymphoma
HIV opportunistic infections
2˚ adrenal insufficiency cause
Iatrogenic due to long-term steroid use causing suppression of pituitary adrenal axis
Hypothalamic-pituitary disease leading to decreased ACTH production
Addison’s signs/symptoms
Lean, tanned, tired, tearful
Anorexia, dizzy, faints
Consider Addison’s in unexplained abdo pain/ vomiting
Pigmented palmar creases + buccal mucosa as ACTH cross reacts with melanin receptors, vitiligo
Postural hypotension
Shock, fever, coma in critical deterioration
Addison’s blood test results
Dec Na and inc K
Inc Ca
Dec glucose
Eosinophilia
Anaemia
Uraemia
Addison’s investigations
Short ACTH stimulation test 9am ACTH >300ng/L (low in 2˚ causes) 21-hydroxylase adrenal autoAbs +ve in autoimmune disease in >80% Plama renin + aldosterone AXR/CXR for TB
Short ACTH stimulation (Synthacten) test
Plasma cortisol and 1/2h after tetracosactide (Synthacten) 250mcg IM
If 30min cortisol >550nmol/L then Addison’s excluded
Beware in pregnancy and contraceptive pill as cortisol falsely inc due to inc cortisol binding globulin
Addison’s treatment
Replace steroids ~15-25mg hydrocortisone daily in 2-3 doses (avoid giving late as may cause insomnia)
Mineralocorticoids to correct postural hypotension (fludrocortisone PO 50-200mcg daily)
Steroid use considerations
Advise wearing bracelet declaring steroid use
Add 5-10mg hydrocortisone to daily intake before strenuous activity/exercise
Double cortisol steroids in febrile illness, injury or stress
Show how to inject 100mg IM hydrocortisone if vomiting prevents oral intake
Don’t stop suddenly
Addison’s follow up
Yearly BP, U+Es
Watch for autoimmune disease
What is 1˚ hyperaldosteronism
Excess aldosterone production independent of RAS
1˚ hyperaldosteronism presentation
Hypertension Hypokalaemia/alkalosis and not on diuretics Weakness Cramps Polyuria/polydipsia
1˚ hyperaldosteronism causes
~2/3 due to solitary aldosterone-producing adenoma (linked to mutations in K+ channels) - Conn’s syndrome
~1/3 due to bilateral adrenocortical hyperplasia
Rarely adrenal carcinoma or glucocorticoid-remediable aldosteronism (ACTH regulatory region of 11beta-hydroxylase gene fuses with aldosterone synthase gene so aldosterone production increased driven by ACTH)
1˚ hyperaldosteronism tests
Renin and aldosterone
Adrenal vein sampling
U+Es but beware >20% normokalaemic
Genetic testing for GRA
1˚ hyperaldosteronism treatment
Hyperplasia - treat medically with spironolactone/ amiloride
Adrenal carcinoma: surgery ± post-op adrenolytic mitotane therapy, poor prognosis
Conn’s - laparoscopic adrenalectomy, spironolactone 25-100mg/24h PO for 4wks pre-op controls BP + K+
GRA: dexamethasone 1mg/24h PO for 4wks, if BP still inc alternate to spironolactone
2˚ hyperaldosteronism causes
High renin from dec renal perfusion e.g. in renal artery stenosis, accelerated HT, diuretics, CCF, hepatic failure
What is Bartter’s syndrome
Congenital (autosomal recessive) salt wasting due to Na/Cl leak in loop of Henle via mutations in transporters
Different types for diff transporters affected
Bartter’s syndrome presentation
Presents in childhood with normal BP, polydipsia, polyuria, failure to thrive
Hypokalaemia + metabolic alkalosis
Bartter’s syndrome treatment
K+ replacement
NSAIDs to inhibit prostaglandins
ACE-i
What is phaeochromocytoma
Catecholamine producing tumours arising from sympathetic paraganglia
Phaeochromocytoma 10% rule
10% malignant
10% extra-adrenal
10% bilateral
10% familial
Phaeochromocytoma presentation
Triad:
Episodic headache
Sweating
Tachycardia
Phaeochromocytoma tests
24h urine for metanephrines/metadrenaline
Inc WCC
Localisation with abdo CT/MRI or meta-iodobenzylguanidine (MIBG, chromaffin-seeking isotope) to find extra-adrenal tumours
Phaeochromocytoma treatment
Surgery with heavy alpha-blockade (phenoxybenzamine) and beta-blockade if heart disease/tachycardic
Post-op monitor BP for fall and 24h urine metanephrine for 2wks
If malignant, chemo/ therapeutic MIBG used
Lifelong follow up + genetic screening
When to suspect Conn’s
HT with hypokalaemia
Refractory HT despite ≥3 anti-HT drugs
HT <40yrs old
What is hirsutism
Male pattern hair growth in women
Hirsutism causes
Familial
Idiopathic
Increased androgen secretion by ovary (PCOS, cancer), adrenal (late-onset congenital adrenal hyperplasia, Cushing’s, cancer) or steroids
PCOS presentation
Secondary oligo/amenorrhoea Infertility Obesity Acne Hirsutism
PCOS diagnosis
US, bilateral polycystic ovaries
Inc testosterone
Dec sex-hormone binding globulin
Hirsutism managment
Self-care e.g. optimise weight, hair removal, healthy diet
Oestrogens (combined contraceptive as drospirenone is an antimineralocorticoid, co-cyprindiol until 3mths after resolution unless HT/breast cancer)
Metformin/spironolactone sometimes tried
Clomifene used for infertility, specialist needed
What is virilism
Onset of amenorrhoea, cliteromegaly, deep voice, temporal hair recession + hirsutism
Virilism causes
Androgen-secreting adrenal or ovarian tumour
What is gynaecomastia
Abnormal amount of breast tissue in men, oestrogen:androgen ratio increased
Gynaecomastia causes
Hypogonadism
Liver cirrhosis (inc oestrogens)
Oestrogen/HCG producing tumours (testicular, adrenal, bronchial)
Drugs (spironolactone, oestrogens, digoxin, testosterone, marijuana)
Gynaecomastia treatments
If can’t treat cause, testosterone ± anti-oestrogen e.g. tamoxifen
Impotence causes
Psychological
Smoking, alcohol, diabetes
Atheroma
Renal/hepatic failure
Endocrine: hypogonadism hyperthyroidism, inc prolactin
Neuro: Cord lesions, MS, autonomic neuropathy
Pelvic surgery
Drugs: digoxin, beta-blockers, diuretics, antipsychotics, antidepressants, oestrogens, narcotics, finasteride
Impotence tests
Full sexual + psych history
U+Es, LFTs, glucose, TFTs, LH/FSH/testosterone/prolactin
Doppler for penile arterial pressure inflow
Check penile sensation
Impotence treatment
Treat causes
Counselling
PDE5 inhibitors (sildenafil 25-100mg short acting, tadalafil 10-20mg long t1/2, vardenafil 5-20mg)
Vacuum aids
PDE5 inhibitor CI
Concurrent nitrate use BP high or systolic <90 with arrythmia Degenerative retinal disorder Unstable angina/stroke <6mths prior MI <90d prior
What is male hypogonadism
Failure of testes to produce testosterone, sperm or both
Male hypogonadism features
Small testes Dec libido Erectile dysfunction Loss of pubic hair, muscle bulk + inc fat Gynaecomastia, osteoporosis
Male 1˚ hypogonadism causes
Testicular failure from:
Local trauma/chemo/radiotherapy
Post-orchitis (mumps/HIV/brucellosis/leprosy)
Renal failure/liver cirrhosis
Alcohol excess
Chromosomal abnormalities e.g. Kleinfelter’s
2˚ hypogonadism causes
Decreased gonadotropins (FH/LSH) from: Hypopituitarism Prolactinoma Kallman's syndrome (GnRH deficiency) Systemic illness Laurence-Moon-Biedl and Prader-Willi Age
Male hypogonadism treatment
Total testosterone ≤8nmol/L on 2 mornings then testosterone (e.g. 1% dermal gel) may help
Testosterone hypogonadism treatment CI
Inc Ca
Nephrosis
Polycythaemia
Prostate, male breast or liver cancer
What is Nelson’s syndrome
ACTH secreting tumour following bilateral adrenalectomy for Cushing’s disease
