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Delta Med - Endocrinology > Endocrinology 4 - Adrenology > Flashcards

Endocrinology 4 - Adrenology Flashcards

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1
Q

What are the zones of the adrenal cortex, and what do they produce?

A 
Glomerulosa - Mineralocorticoids
 - aldosterone and precursors
 - in response to ATII, K and ACTH
Fasciculata - Glucocorticoids
 - Cortisol
 - Cortocosterone
 - in response to ACTH (Il-1, Il-6, TNF and neuropeptides)
Reticularis
 - Adrenal androgens - DHEA/S, androstenedione
 - in response to ACTH
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2
Q

What is produced in the adrenal medulla?

A

Catecholamines

  • Adrenaline (metanephrine)
  • Noradrenaline (normetanephrine)
  • Dopamine
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3
Q

What are clinical features of ‘non-classical’ CAH?

A

Prevalence 1:500
Females with precocious puberty
Androgen excess (hirsuit, oligmenorrhoea, acne, infertility)
Random 17-OH progesterone may be normal
17-OH-P >45nmol/L post synacthen - Diagnostic
Rx often not needed - antiandrogens for troublesome hisruitism, glucocorticoid/stress not required, ovulation induction.

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4
Q

What are characteristics of cortisol, and what does this mean for screening excess/deficiency?

A

Highest at 8am - check here for adrenal failure

Lowest at 0000 - check here for cushing’s

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5
Q

What is cortisol bound to, and what influences this?

A

90-95% bound to plasma proteins

  • 80% corticosteroid binding globulin (CBG)
  • 10-15% serum albumin

Pregnancy, oestrogen, hyperthyroidism, inflammation increase CBG

Hypothyroidism, protein deficiency, diminished synthetic capacity (genetics)

CBG inversely proportional to insulin

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6
Q

What are clinical Symptoms of Addison’s Disease?

A 
Weakness, fatigue
Anorexia
NV abdo pain
salt craving
postural drop
arthralgia
myalgia
low-libido (women)
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7
Q

What are signs of Addison’s Disease

A 
Hypotension, dehydration (disproportionate)
Anorexia/weight loss
Hyperpigmentation
loss of axillary and pubic hair (F)
Autoimmune vitiligo
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8
Q

What are Lab findings in addison’s disease?

A 
Hyponatraemia
Hyperkalaemia
Raised urea
Metabolic acidosis
NN anaemia
eosinophilia
lymphocytosis
T4 low, elevated TSH
Hypercalcaemia
Hypoglycaemia
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9
Q

What happens to cortisol and aldosterone in addison’s?

A

Decreased cortisol

  • increased ACTH - pigmentation
  • hypoglycaemia
  • weight loss from anorexia

Decreased aldosterone

  • increased renin
  • hyponatraemia
  • hypoerkalaemia
  • hyperchloraemic acidosis
  • decreased H20 retention, weight and BP
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10
Q

What are causes of primary adrenal insufficiency?

A 
Acute - haemorrhage or infarction of adrenals
Slow onset
- Autoimmune disease adrenalitis
- Infection -TB, AIDS
- Cancer - lymphoma, metastases
- Drugs - ketoconazole, etomidate
- Other - congenital adrenal hyperplasia
- Adrenoleukodystrophy (Males)
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11
Q

What are causes of secondary adrenal insufficiency?

A 
Acute onset
- pituitary apoplexy
- pituitary/hypothalamic surgery
- TBI
Slow onset
- autoimmune disease - lymphocytic hypophysitis
- infectious disease - TB
- Cancer - pit/hypothalamic tumours/lymphoma
- Trauma - TBI, SAH, Radiation
- Drugs - megestrol acetate
Other
- discontinuation of exogenous steroids
- sarcoidosis
- empty sella syndrome
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12
Q

What is associated with HITTS?

A

bilateral adrenal haemorrhage

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13
Q

What is the first test in excluding adrenal insufficiency?

A

Early morning cortisol - if >550, reasonably exludes if patient not on glucocorticoids. 250-500 is probably sufficienct.

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14
Q

What is the role of the short synacthen test in adrenal insufficiency?

A

If cortisol is >550 at 30 or 60 minutes, reflects normal adrenal function in a well patient.

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15
Q

What is the role of the insulin tolerance test in adrenal insuffciency?

A

Gold standard test for ACTH/GH reserve.

only interpretable if hypoglycaemia induced 500, GH >20.

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16
Q

What is the significance of high ACTH and renin?

A

Indicates primary adrenal insufficiency (loss of aldosterone secretion)

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17
Q

When is imaging not indicated in adrenal disease?

A

IF there is associated autoimmune disease, adrenal autoantibodies.

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18
Q

What is the significance of autoimmune polyglandular syndrome?

A

If a diagnosis of primary hypothyroidism is made, but miss coexisting adrenal insufficiency, commencing thyroid replacement therapy can precipiate an adrenal crisis - given thyoroxine accelerates the metabolic clearance of cortisol.

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19
Q

What are features of Autoimmune polyendocrine syndrome type I?

A

Addison’s disease
Hypoparathyroidism
Mucocutaneous candidosis

Due to AIRE defect.

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20
Q

What are principal features of Autoimmune polyendocrine syndrome type II?

A

Addison’s disease
Diabetes mellitus type 1
Hypothyroidism

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21
Q

What is the mechanism of Autoimmune polyendocrine syndrome?

A

failure of normal thymic negative selection with autoreactive T-cells escaping to the periphery.

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22
Q

What are features of adrenoleukodystrophy?

A

X-linked recessive disorder

  • Cerebral ALD
    • childhood presentation
    • dementia, blindness, quadriplegia

Elevated very long chain fatty acids

Screen in any young man with adrenal insufficiency

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23
Q

What are features of adrenomyeloneuropathy?

A

X-linked recessive disorder

  • spasticity, distalpolyneuropathy
  • young men

Diagnosis - elevated very long chain fatty acids

Screen in any young man with adrenal insufficiency

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24
Q

What duration and dose of prednisone is required to cause HPA suppression?

A

> 5mg/day of pred for >4 weeks

Morning admin less likely to suppress vs nighttime admin.

Full recovery can take 12 months. HPA 2-5months, full adrenal function 9-12months

SST most commonly used method to test adrenal/HPA suppression.

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25
What is the effect of glucocorticoids on the liver?
hyperglycaemia - gluconeogenesis - glucose production from protein - increased pancreatic insulin pdn
26
What is the effect of glucocorticoids on muscle?
muscle catabolism - mobilisation of AA - inhibition of glucose uptake
27
What is the effect of glucocorticoids on fat tissue?
adipose tissue - inhibition of fat uptake promoting lipolysis - counteracted by increased insulin stimulating lipogenesis
28
What is the effect of glucocorticoids on the immune system?
anti-inflammatory: | - increased Neutrophils, decreased T/B lymphocytes, basophils, eosinophils
29
What is the effect of glucocorticoids on bone?
bone catabolism - decreased bone formation by direct inhibition of osteoblasts - stimulation of bone resorption
30
What is the effect of glucocorticoids on vascular/fluid balance?
hypertension - increased sensitivity to vasoconstrictors - mineralocorticoid like effect - increased free water excretion (ADH antagonism and ADH independent effects)
31
What clinical features are most discriminatory for cushing's syndrome?
``` easy bruising facial plethora proximal myopathy striae (esp if purple, >1cm) weight gain with decreasing growth velocity in children ```
32
What are the best screening tests for cushing's syndrome?
1. 24hr free urinary cortisol 2. 1mg overnight dexamethasone suppression 3. midnight salivary cortisol
33
What is the rationale of diagnosing cushing's syndrome?
1st exclude endogenous glucocorticoids perform 24hrFUC, 1mg ODS, Midnight SC exclude physiologic causes of hypercortisolism repeat one of above tests or consider Dex-CRH
34
What are recommended tests for cushing's in certain populations?
pregnancy - recommend using UFC instead of dex epilepsy - do not use dex testing as interaction with AEDs - recommend nonsuppressed midnight cortisol renal failure - 1mg overnight DST instead of UFC cyclic cushing syndrome - recommend UFC adrenal incidentaloma - recommend use of 1mg DST or late night cortisol, vs UFC
35
What conditions are associated with hypercortisolism in absence of cushing's syndrome?
``` Some clinical features present: Pregnancy Depression Alcohol dependence Glucocorticoid resistance Morbid obesity Poorly controlled DM ``` ``` Unlikely to have clinical features Physical stress Malnutrition, AN Intense chronic exercise Hypothalamic amenorrhoea CBG excess (increased serum, but not urine cortisol) ```
36
What is the next step following confirmation of cushing's syndrome?
Measurement of serum ACTH: - 20 - ACTH dependent - pituitary vs ectopic source 10-20 - usually ACTH dependent
37
What are features of pituitary cushings vs ectopic ACTH?
better responsiveness to dynamic testing, but substantial overlap. MRI pituitary not reliable (basically useless) BIPPS often necessary, unless MRI shows >6mm adenoma AND suppression with HDDST/increase in CRH. 10% ectopics are suppressed by HDDST ACTH/Cortisol >30% in CD, but not in ectopics on CRH test.
38
What is the most likely cause of ectopic ACTH secretion?
bronchial carcinoid (40%)
39
What conditions produce low renin and high aldosterone?
Primary hyperaldosteronism - bilateral adrenal hyperplasia - aldosterone producing adenoma (Conn) - Familial hyperaldosteronism - Pure aldo-producing carcinoma
40
What conditions produce high renin and alsoterone?
Secondary hyperaldosteronism - renal artery stenosis - diuretics (?surreptitious) - renin secreting tumour
41
What conditions produce low renin and low aldosterone?
Apparent mineralocorticoid excess - Exogenous mineralocorticoid - cushing's syndrome (production of mineralocorticoid compounds) - licorice (inhibits 11b-HSD2) - CAH/11bHSD2 deficiency - Liddle's syndrome (activating mutation of collecting tubule sodium channel)
42
What excess is associated with fluticasone and ritonavir?
high glucocorticoid but normal cortisol
43
What are clinical findings in primarly aldosteronism?
``` Hypertension >95% CV/CVD 4-12% Hypokalemia +/- alkalosis (40%) Hypokalemic Sx (fatigue, HA, arrhythmias, muscle weakness or cramping, paraesthesias, polyuria, impaired IGT) - 20% mild hypernatremia ```
44
What is the prevalence of various causes of primary aldosteronism?
bilateral idiopathic hyperplasia 60% aldosterone producing adenoma 35% Primary adrenal hyperplasia (unilat) 2% Pure aldo producing adrenocortical carcinoma (
45
When should testing for primary aldosteronism be considered?
``` HTN and hypokalemia resistant hypertension adrenal incidentaloma and hypertension onset of HTN160/100 whenever considering secondary hypertension ```
46
What should be initially tested in w/u of primary aldosteronism?
Plasma aldosterone concentration and plasma renin activity Increased PAC and Decreased PRA or PRC AND PAC/PRA ratio >=555 or >=20 Investigate for primary aldosteronism
47
What antihypertensives have minimal effects on ARR testing?
``` verapamil SR hydralazine prazosin doxazosin terazosin ```
48
What medications should be avoided in ARR testing?
``` B-blockers a2 agnoists (central) NSAIDs K+ wasting diruetics K+ sparing diuretics ACEi ARBs CCBs (dihydropyridine) Renin inhibitors ```
49
What are the most frequent Sx in phaeochromocytoma?
Headache 60-90% Sweating 55-75% Sustained HTN 50-60% Palpitations 50-70%
50
What precipitates phaeo crises?
anaesthesia surgery drugs (B-blockers, opiods, TCAs)
51
When is genetic testing indicated in phaeo?
young, 50% have genetic cause
52
What genes should be tested in phaeo?
Extra-adrenal - SDHB Adrenal - RET, VHL Multiple - SDHD, VHL Malignant - SDHB
53
What are features of tests for phaeo?
Plasma free metanephrines - Sn >95%, Sp 80-95% Urinary fraction metanephrines - Sn >90%, Sp 80-95% Urinary catecholamines - Sn 70-90%, Sp 70-95%
54
What are imaging featuers of phaeo?
often heterogenous, large HU>30
55
What are features of adrenal incidentalomas?
Common - up to 9% at autopsy, 4% of CT scans 25% increase in size on FU 40% of patients have mets to adrenals if cancer Hx Malignant
56
What are frequencies of adrenal mass aetiologies?
``` Nonfunctional adrenal adenoma 70% Subclinical cushing syndrome 5-10% Phaeochromactyoma 5% Adrenocortical carcinoma 4.5% Met 2.5% ```
57
What are features of adrenocortical adenomas?
Small, =50% washout of contrast at 10 minutes | Isointense on T2wI
58
what are indications for surgery in an incidental adrenal mass?
Size >6cm or imaging sugg of malgnancy Increase in Size Functioning tumour Phaeochromocytoma - for surgery Primary hyperaldosteronism - surgery if unilateral disease confirmed Autonomous cortisol secretion - consider if comobidities present, or in case of clearly abnormal endocrine tests.
59
What are S+Sx suggestive of androgen deficiency in men?
``` Incomplete sexual development, eunchoidism, aspermia Reduced sexual desire (libido), activity Decreased spontaneous erections Breast discomfort, gynaecomastia Loss of body hair, less shaving Very small/shrinking testis ( ```
60
What conditions are associated with decreased SHBG?
``` Moderate obesity nephrotic syndrome hypothyroidism GC/progestins/androgenic steroids Acromegaly Diabetes Mellitus ```
61
What conditions are associated with increased SHBG?
``` Aging hepatic cirrhosis and hepatitis hyperthyroidism use of anticonvulsants use of estrogens HIV disease ```
62
What are causes of primary androgen deficiency?
``` (elevated LH/FSH) Acquired: - testicular damage: trauma, orchitis, CTX/RTX/Toxins, spironolactone, ketoconazole Congenital: - klinefelter - cryptorchidism - mut in androgen bioenzyme synthesis - LH/FSH receptor mutations - myotonic dystrophy ```
63
What are causes of secondary androgen deficiency?
LH/FSH normal structural - pituitary/hypopit tumour, surgery, rad, trauma, infitration (fe, sarcoid, histiocytosis) genetic - kallman, idiopathic HH, LH/FSH beta subunit mutations functiona - hyperprolactinaemia, morbid obesity, curshing's syndrome partial/transient - acute illness, chronic disease (ESRD, COPD, HIV, T2DM) - drugs - GC, Opiods, GnRH agonist, anabolic steroids
64
What are the effects of adiposity on testosterone?
moderate adiposity: - increased visceral fat - increased insulin resistance - decrease SHBG - decreased total testosterone severe obesity (BMI >35) - massive increase in fat mass - increased aromatase - increased oestradiol - decreased LH - decreased free and total T
65
What are causes of hypogonadotropic hypogonadism?
Macroadenoma = mass effect | Micro-prolactinoma - PRL inhibits gonadotrophins
66
What is the relevance of prolactin in hypogonadotropic hypogonadism?
if >5-10x ULN, almost always due to prolactinoma
67
What should be monitored in patients on testosterone replacement therapy?
``` testosterone levels liver function PSA DRE lipids hct BMD if prev # ```

Delta Med - Endocrinology (4 decks)

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