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Adrenals Flashcards

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1
Q

Adrenal cortex physiology

A

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

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2
Q

What is Cushing’s syndrome

A

Chronic glucocorticoid excess + loss of normal feedback + loss of cortisol circadian rhythm

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3
Q

Cushing’s causes (inc ACTH)

A

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)

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4
Q

Ectopic ACTH specific features

A

Hyperpigmentation
Hyperglycaemia
Hypokalaemic metabolic alkalosis
Weight loss

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5
Q

Cushing’s causes (low ACTH due to -ve feedback)

A

Steroids
Adrenal adenoma/ cancer
Adrenal nodular hyperplasia
(Rare) Genetic syndromes Carney complex/ McCune-Albright

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6
Q

Cushing’s presentation

A 
Weight gain (central obesity, moon face, buffalo hump)
Mood change (lethargy, depression)
Acne

Proximal weakness
Recurrent Achilles tendon rupture
Osteoporosis

Raised BP + glucose

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7
Q

Cushing’s treatment for iatrogenic cause

A

Iatrogenic - stop medications

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8
Q

Treatment for Cushing’s disease

A

Cushing’s disease - trans-sphenoidal adenoma removal, bilateral adrenalectomy if can’t find source

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9
Q

Cushing’s treatment for adrenal adenoma/carcinoma

A

Adrenal adenoma - adrenalectomy (radiotherapy and mitotane follow if carcinoma)

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10
Q

Cushing’s treatment for ectopic ACTH

A

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

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11
Q

Cushing’s prognosis

A

Untreated - inc vascular mortality

Treated then good prognosis but DM, osteoporosis, HT often stay

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12
Q

Cushing’s investigations

A

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

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13
Q

Overnight dexamethasone suppression test and interpreting results

A

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

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14
Q

24h urinary free cortisol test results

A

Normal <280nmol/24h

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15
Q

48h dexamethasone suppression test and interpreting results

A

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

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16
Q

48h high dose dexamethasone suppression test and interpreting results

A

Dex 2mg/6h

May distinguish pituitary (suppressed) from other causes (no/part suppression)

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17
Q

Midnight cortisol and interpreting results

A

Admit (unless salivary cortisol used)

Normal circadian rhythm (lowest at midnight, highest early morning) lost in Cushing’s so inc cortisol

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18
Q

Cushing’s localisation tests

A

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

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19
Q

CRH test

A

100mcg ovine or human CRH IV, measure cortisol at 120mins

Cortisol rises with pituitary disease, doesn’t with ectopic ACTH production

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20
Q

Cushing’s investigations following cortisol studies

A

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

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21
Q

What is 1˚ adrenocortical insufficiency

A

Addison’s disease

Destruction of adrenal cortex leads to glucocorticoid + mineralocorticoid deficiency

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22
Q

Addison’s causes

A

80% due to autoimmunity
TB (commonest cause worldwide)
Congenital

Adrenal metastases
Adrenal haemorrhage

Lymphoma
HIV opportunistic infections

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23
Q

2˚ adrenal insufficiency cause

A

Iatrogenic due to long-term steroid use causing suppression of pituitary adrenal axis
Hypothalamic-pituitary disease leading to decreased ACTH production

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24
Q

Addison’s signs/symptoms

A

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

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25
Addison's blood test results
Dec Na and inc K Inc Ca Dec glucose Eosinophilia Anaemia Uraemia
26
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 ```
27
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
28
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)
29
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
30
Addison's follow up
Yearly BP, U+Es | Watch for autoimmune disease
31
What is 1˚ hyperaldosteronism
Excess aldosterone production independent of RAS
32
1˚ hyperaldosteronism presentation
``` Hypertension Hypokalaemia/alkalosis and not on diuretics Weakness Cramps Polyuria/polydipsia ```
33
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)
34
1˚ hyperaldosteronism tests
Renin and aldosterone Adrenal vein sampling U+Es but beware >20% normokalaemic Genetic testing for GRA
35
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
36
2˚ hyperaldosteronism causes
High renin from dec renal perfusion e.g. in renal artery stenosis, accelerated HT, diuretics, CCF, hepatic failure
37
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
38
Bartter's syndrome presentation
Presents in childhood with normal BP, polydipsia, polyuria, failure to thrive Hypokalaemia + metabolic alkalosis
39
Bartter's syndrome treatment
K+ replacement NSAIDs to inhibit prostaglandins ACE-i
40
What is phaeochromocytoma
Catecholamine producing tumours arising from sympathetic paraganglia
41
Phaeochromocytoma 10% rule
10% malignant 10% extra-adrenal 10% bilateral 10% familial
42
Phaeochromocytoma presentation
Triad: Episodic headache Sweating Tachycardia
43
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
44
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
45
When to suspect Conn's
HT with hypokalaemia Refractory HT despite ≥3 anti-HT drugs HT <40yrs old
46
What is hirsutism
Male pattern hair growth in women
47
Hirsutism causes
Familial Idiopathic Increased androgen secretion by ovary (PCOS, cancer), adrenal (late-onset congenital adrenal hyperplasia, Cushing's, cancer) or steroids
48
PCOS presentation
``` Secondary oligo/amenorrhoea Infertility Obesity Acne Hirsutism ```
49
PCOS diagnosis
US, bilateral polycystic ovaries Inc testosterone Dec sex-hormone binding globulin
50
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
51
What is virilism
Onset of amenorrhoea, cliteromegaly, deep voice, temporal hair recession + hirsutism
52
Virilism causes
Androgen-secreting adrenal or ovarian tumour
53
What is gynaecomastia
Abnormal amount of breast tissue in men, oestrogen:androgen ratio increased
54
Gynaecomastia causes
Hypogonadism Liver cirrhosis (inc oestrogens) Oestrogen/HCG producing tumours (testicular, adrenal, bronchial) Drugs (spironolactone, oestrogens, digoxin, testosterone, marijuana)
55
Gynaecomastia treatments
If can't treat cause, testosterone ± anti-oestrogen e.g. tamoxifen
56
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
57
Impotence tests
Full sexual + psych history U+Es, LFTs, glucose, TFTs, LH/FSH/testosterone/prolactin Doppler for penile arterial pressure inflow Check penile sensation
58
Impotence treatment
Treat causes Counselling PDE5 inhibitors (sildenafil 25-100mg short acting, tadalafil 10-20mg long t1/2, vardenafil 5-20mg) Vacuum aids
59
PDE5 inhibitor CI
``` Concurrent nitrate use BP high or systolic <90 with arrythmia Degenerative retinal disorder Unstable angina/stroke <6mths prior MI <90d prior ```
60
What is male hypogonadism
Failure of testes to produce testosterone, sperm or both
61
Male hypogonadism features
``` Small testes Dec libido Erectile dysfunction Loss of pubic hair, muscle bulk + inc fat Gynaecomastia, osteoporosis ```
62
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
63
2˚ hypogonadism causes
``` Decreased gonadotropins (FH/LSH) from: Hypopituitarism Prolactinoma Kallman's syndrome (GnRH deficiency) Systemic illness Laurence-Moon-Biedl and Prader-Willi Age ```
64
Male hypogonadism treatment
Total testosterone ≤8nmol/L on 2 mornings then testosterone (e.g. 1% dermal gel) may help
65
Testosterone hypogonadism treatment CI
Inc Ca Nephrosis Polycythaemia Prostate, male breast or liver cancer
66
What is Nelson's syndrome
ACTH secreting tumour following bilateral adrenalectomy for Cushing's disease

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