Adrenal disorders pt I Flashcards
(83 cards)
1
Q
what are the 2 distinct tissues of the adrenal glands
A
- cortex
- medula
2
Q
the adrenal gland is enclosed by connective tissue known as the ___
A
capsule
3
Q
what are the 3 zones of the cortex
A
zona …
1. glomerulosa
2. fasciculata
3. reticularis
(GFR)
4
Q
which zone of the cortex secrets mineralocorticoids, primarily aldosterone
A
glomerulosa (outer)
GMA - Glomerulosa, Mineralocorticoids, Aldosterone
5
Q
what hormone regulates bp and electrolyte balance by the RAAS
A
aldosterone
sodium retention
water retention
potassium excretion
increases bp and blood volume
6
Q
if there is excess aldosterone, what happens to the renin?
A
decreases
7
Q
if there is an aldosterone deficiency, what happens to the renin
A
increases
8
Q
which zone of the adrenal cortex secretes glucocorticoids, primarily cortisol?
A
zona fasciculata (middle)
FGC - Fasciculata, Glucocorticoids, Cortisol
9
Q
increased cortisol release during stress via ?
A
ACTH stimulation (from the pituitary)
10
Q
functions of the zona fasciculata (middle)
A
- gluconeogenesis in liver
- utilizes (decreases) protein stores - immune system suppression
- ↓ eosinophil, lymphocytes and lymph tissue - decreases inflammation
11
Q
functions of the HPA axis
A
- controls glucocorticoid release
- Release occurs in a circadian rhythm, after meals and in response to endogenous and exogenous stressors
- Cortisol provides a negative feedback
12
Q
describe the steps of the HPA axis
A
- hypothalamus releases corticotropin-releasing hormone (CRH).
- CRH binds to the anterior pituitary gland = adrenocorticotropic hormone (ACTH) releases
- ACTH binds to receptors on the adrenal cortex and stimulates adrenal release of cortisol
- Cortisol exerts negative feedback to the hypothalamic release of CRH and the pituitary release of ACTH (negative feedback).
13
Q
Cortisol levels are highest during when (time) of the circadian rhythm cycle?
A
morning
lowest - PM
14
Q
which zone of the adrenal cortex secretes gonadocorticoids, primarily dehydroepiandrosterone (DHEA)
A
zona reticularis (inner)
15
Q
what hormone converts sex steroids in gonads
stimulates, controls, and maintains the development of sex characterstics
A
DHEA
RGD - Reticularis, Gonadocorticoids, DHEA
16
Q
what part of the adrenal gland is composed of chromaffin cells
secretes epinephrine and norepinephrine aka our fight-or-flight response?
A
medulla
17
Q
how would a destruction of the adrenal glands affect ACTH and CRH levels?
A
chronic increase
18
Q
what hormone stimulates adrenal cells to begin steroid synthesis
A
ACTH
19
Q
what does the adrenal cells require in order to synthesize steroid hormones?
A
cholesterol
20
Q
what hormone is an important source of estrogen in the body
A
DHEA
21
Q
what are the 2 adrenal disorders
A
cushing’s
adrenal insufficiency
22
Q
if there is an adrenal gland dysfunction:
what happens to the hormones released?
what type of adrenal insufficiency is it?
A
↓cortisol/aldosterone
primary
23
Q
if there is pituitary gland dysfunction:
what happens to the hormones released?
what type of adrenal insufficiency
A
↓ ACTH, ↓ cortisol
secondary
24
Q
if there is a hypothalamic dysfunction:
what happens to the hormones released?
what type of adrenal insufficiency
A
↓ CRH
↓ ACTH
↓ cortisol
Tertiary
25
a destruction/dysfunction of the adrenal cortex resulting in insufficient production of glucocorticoids and mineralocorticoids.
what disease?
Addison's Disease
26
Addison's disease is MC cause by ?
autoimmune (80% in US)
- _CYP21A2 (21-hydroxylase) - MC_
- CYP11A1 (side-chain cleavage enzyme)
- CYP17 (17-alpha-hydroxylase)
27
describe the etiology of autoimmune Addison's disease?
- **adrenal function decreases over several years** as it progresses to overt adrenal insufficiency
- presents between 2nd and 5th decade (10-40 y/o)
autoimmune = MC!
28
genetic disorder resulting in _accumulation of very long-chain fatty acids_ in the adrenal cortex _inhibiting the effects of ACTH_ on the adrenocortical cells
Adrenoleukodystrophy
29
genetic mutation or absence of adrenal cortex
Congenital adrenal insufficiency/hyperplasia
30
Causes of Addison's disease
1. autoimmune
2. Adrenoleukodystrophy
3. Congenital adrenal insufficiency/hyperplasia
4. Infection - rare etiology
- MC - TB
5. Drugs
6. Adrenal hemorrhage
7. Adrenal “addisonian” Crisis
31
what drug is known to inhibit cortisol biosynthesis
ketoconazole - inhibits adrenal cytochrome P450
32
what drugs accelerate the metabolism of cortisol
phenytoin, barbiturates, rifampin
33
what adrenocorticolytic drug diminishes cortisol synthesis
mitotane - blocks steroid biosynthesis - used to treat adrenocortical carcinoma
34
what type of drug suppresses the CRH or ACTH production
glucocorticoids
35
what can cause adrenal hemorrhage
results from sepsis, heparin-induced thrombocytopenia, anticoagulation, antiphospholipid antibody syndrome, trauma, surgery
36
emergent condition resulting from _insufficient cortisol_
caused by a _physical or emotional stressor_ in an Addison’s disease patient
Ex: infection, trauma, surgery, emotional turmoil
Adrenal “addisonian” Crisis
37
what is often the first and only symptom for years in Addison's disease?
_Skin and mucosal hyperpigmentation_
prominent on:
- sun-exposed skin
- extensor surfaces
- palmar creases, nail beds
- mucosal membranes
38
what is the chronic presentation of Addison's that results with patchy hypopigmentation
vitiligo
result of autoimmune destruction of dermal melanocytes
39
Chronic presentation of Addison's
1. First symptoms: _anorexia, wt loss, fatigue, ↓ stamina_
2. Hypotension, dehydration, orthostatic lightheadedness
3. Hypoglycemia, weakness
4. Fevers, lymphoid tissue hyperplasia
5. Abd pain, N/V/D
6. Change in axillary, pubic and body hair
7. generalized pain
- muscles, joints, chest, abdomen, back, legs, headache
8. psychiatric
- anxiety, irritability, depression
9. neurologic
- gait disturbance, cognitive dysfunction → coma
10. amenorrhea
40
if a pt comes in with a sudden onset of:
- 105℉
- severe abdominal pain, N/V
confusion
- hypotensive shock
what are they experiencing?
adrenal crisis
41
how is adrenal hemorrhage presented differently than adrenal crisis?
w/o fever
42
work up for Addison's disease
1. CBC
- eosinophilia, lymphocytosis
2. CMP
- hyponatremia, hyperkalemia
- ↑ BUN/Cr - results from dehydration
- hypoglycemia if fasting or may occur spontaneously
3. Cx - blood, sputum, urine
4. Plasma Cortisol
- 8 AM: _< 3 mcg/dL = diagnostic if accompanied by elevated ACTH_
- Random cortisol _> 25 mcg/dL = rules *out* Addison’s_
5. Plasma ACTH
> 200 pg/mL (7-63 pg/mL - normal value 7-10 AM)
6. Rapid ACTH stimulation Test
- _Utilized when serum cortisol and serum ACTH are non-diagnostic_
7. Plasma renin
- multiple interfering factors tho
8. CXR
- if suspecting signs of TB (etiology) or pneumonia (precipitating crisis etiology)
CT abdomen - adrenal findings vary.
- vomiting/diarrhea may mask hyperkalemia
- use random cortisol in emergency setting
43
during rapid ACTH stimulation test, what serum lvl would be indicative of Addison's
**rise in serum cortisol < 20 mcg/dL**
Normal = rise in serum cortisol ≥ 20 mcg/dL
- a rise could also indicated a secondary/tertiary etiology
44
factors to consider for Rapid ACTH stimulation test
1. Hold hydrocortisone for 24 hours prior to test
- LA glucocorticoid (dexamethasone) - switch to SA (hydrocortisone) days prior to testing
2. Cost: must be performed in hospital setting
3. ***Utilized when serum cortisol and serum ACTH are non-diagnostic***
4. SE: nausea, HA, dizziness, dyspnea, palpitations, flushing edema, local site reaction
45
what are the steps of administering the rapid ACTH stimulation test
Step 1: Measure serum cortisol
Step 2: Administer Cosyntropin (synthetic ACTH) 0.25 mg given IM
Step 3: Measure serum cortisol 45 minutes post injection
46
what happens to plasma renin [PRA] levels in Addison's
increased due to diminished aldosterone resulting depleted intravascular volume
***indicates need for mineralocorticoid replacement***
47
during CT of abdomen you see small w/o calcifications, what is the etiology of Addison's
autoimmune
48
during a CT of the abdomen it shows its enlarged, what is the etiology of Addison's?
TB, fungal, adrenal hemorrhage, metastatic
49
during a CT of the abdomen it shows calcifications, what is the etiology of Addison's?
TB, fungal, adrenal hemorrhage, pheochromocytoma, melanoma
50
baseline therapy for addison's
_Oral Glucocorticoids_
1. **_Hydrocortisone 15-30 mg daily_**
- has both glucocorticoid and mineralocorticoid (at higher doses) effects
- ⅔ dose in morning and ⅓ dose in late afternoon/early evening
2. _Alternatives_
- **Prednisone or methylprednisolone**
- ⅔ am and ⅓ pm
51
what is the tx for chronic addison's
**_Glucocorticoid Stress therapy_**
1. increase dose of steroid by _up to 50%_
2. _Stressors_: infection, surgery, trauma, pregnancy (3rd trimester), labor, stressful diagnostic procedures, severe emotional stress
3. Increase dosage based on severity of stress and symptoms
4. Return dose to baseline upon resolution of stressor
**_Mineralocorticoid therapy_**
1. Higher “stress” doses of glucocorticoids (> 100 mg/d of hydrocortisone) will supply sufficient mineralocorticoid activity
2. Lower maintenance glucocorticoid doses require mineralocorticoid supplementation
- **Fludrocortisone 0.05 - 0.3 mg daily or every other day**
--- higher doses needed for orthostatic hypotension, hyponatremia, hyperkalemia
--- _monitor with PRA_
+ oral Glucocorticoids
52
if a pt is taking fludrocortisone and their PRA is increased, what is the next step?
increase dosage
53
tx for acute adrenal crisis
1. no previous dx = order serum **cortisol** and **ACTH**, start treatment anyways
2. Hydrocortisone
- Step 1: _Loading dose - IV hydrocortisone 100-300 mg in NS_
- Step 2: _IV hydrocortisone 50-100 mg q6h x 24 hours then tapered_ based upon patient condition
- Step 3: _switch to oral hydrocortisone once pt can tolerate PO_
--- oral dose 10-20 mg q6h then reduce to maintenance levels
3. broad-spectrum abx
- adjust accordingly based upon cultures
4. treat all electrolyte/glucose/volume abnormalities
54
monitoring/management for addison's
1. Symptom resolution w/o development of Cushing syndrome
2. WBC diff, electrolytes and renal function should return to normal
3. DEXA scan: screen for osteoporosis
- increased risk due to chronic steroid use
4. Referral
- Endocrinologist should be involved in *both* acute and chronic disease management
55
pt education for addison's
1. Medical alert bracelet
- “Adrenal insufficiency - takes hydrocortisone”
2. _All infections must be treated immediately_
3. Consider providing patient with _injectable hydrocortisone_
56
a condition that results from an excessive amount of systemic cortisol
Cushing’s Syndrome/Disease
57
difference between cushing's syndrome and disease
syndrome
- manifestations of excessive corticosteroids
- other spontaneous production of corticosteroids by the adrenal gland
disease - manifestations of excessive corticosteroids due to hypersecretion of ACTH
58
MC cause of cushing's disease is ?
benign anterior pituitary adenoma
females > male
59
causes of ACTH independent (aka Cushing Syndrome)
1. Iatrogenic or factitious Cushing's syndrome
- MC - exogenous steroids
2. Adrenocortical adenomas and carcinomas
60
etiology of ACTH Dependent (aka Cushing Disease)
_manifestations of excessive corticosteroids due to hypersecretion of ACTH_
1. _Cushing's disease_
- pituitary hypersecretion of ACTH
2. _Ectopic secretion of ACTH_
- non-pituitary tumor - MC locations lungs, thymus, pancreas
3. _Ectopic secretion of CRH_
- non-hypothalamic tumors causing pituitary hypersecretion of ACTH - rare < 1 %
4. _Iatrogenic/factitious Cushing's syndrome_
- due to administration of exogenous ACTH – rare <1%
61
presentation of cushing's
1. fatigue, reduced physical endurance
- often first & long lasting symptom
2. Weight gain
- central obesity with thin extremities
- plethoric “moon face”
- supraclavicular fat pads
- “buffalo hump”
3. skin atrophy with large purple striae
4. easy bruisability
5. proximal muscle weakness
6. immune system suppression
7. frequent infections
8. menstrual irregularities
9. Additional s/s associated with increased ACTH
- hyperpigmentation
- elevated BP
- hirsutism, male pattern hair loss
62
work up for cushing's syndrome/disease
1. CBC
- _leukocytosis_ - neutrophilia, lymphocytopenia, ↓ eosinophils
2. CMP
- _↑ glucose_
- _+/- hypernatremia, hypokalemia_
3. Establish presence of hypercortisolism
- 3 first line testing options - **_2 positive tests = diagnosis_**
--- Dexamethasone Suppression Test
--- 24 Urine Free Cortisol (2 measurements)
--- Late night salivary cortisol (2 measurements)
63
what are the diagnostic workup goals for cushing's syndrome/disease
1. Determine exogenous vs endogenous etiology
2. Establish presence of hypercortisolism
3. Determining cause for hypercortisolism
64
what is the Low-dose Dexamethasone Suppression Test
1. dexamethasone 1 mg PO at 11 PM
2. serum cortisol next morning at 8 AM
3. Results - _< 5 mcg/dL likely *excludes* Cushing’s syndrome_
- 3% false-negative rate
--- 8% Cushing disease have normal suppression of cortisol
antiseizure drugs, rifampin and estrogens diminish suppressibility
- 20-30% false-positive rate
--- psychiatric disorders, emotional/physical stress
65
what is the 24 Hour Urine Free Cortisol test
1. begin collection AFTER first morning void
2. document time
3. collect ALL urine thereafter until 24 hours is reached, include first morning void of the next day (end of 24 hours)
**Positive test** - _elevated urine cortisol 3x upper limit of normal on *both* occasions_
- normal values vary based upon age and sex
66
what is the Late night salivary cortisol (Salivette)
1. collected by patient between 11 pm and midnight
- specimen stable at room temp for days
- _Interfering factors_: steroid use, brushed teeth, oral intake, inadequate collection
2. Normal at 11 p.m.-midnight: <100 ng/dL
- factors that elevate levels: erratic sleep schedules or shift work, pregnancy, exogenous steroid/estrogen use, anticonvulsants, mental illness,
chronic alcohol use, acute stress (hospitalization/surgery)
3. perform on 2 separate occasions
- **both tests must yield an abnormal result (_elevated cortisol_) = _positive test_**
67
what is the diagnostic testing interpretation for cushing's syndrome/disease?
1. **2 first line test with negative results**
- low suspicion = _monitor_
- high suspicion = _refer to endocrinologist_
2. **1 out of the 2 tests are positive**
- if saliva or 24-UFC is not confirmatory = _repeat test at random intervals_
- consider cyclic Cushing Disease as dx
--- MC etiology - ACTH-secreting pituitary adenoma
- _refer to endocrinologist_
3. **both test are positive**
- _refer to endocrinologist_ for evaluation of underlying etiology
68
determining the cause for hypercortisolism
1. **Serum ACTH**
- differentiate ACTH-dependent vs. ACTH-independent etiology
- ensure proper collection
--- preferred collection between 6-9 AM
--- collected in EDTA tube - on ice, spun soon after collection, and stored at -20°C (-4°F) until assay
- interpretation
--- _< 20 pg/dL_ order _adrenal CT_
--- _> 20 pg/dL order pituitary MRI_
69
red flags for malignant carcinoma of adrenal gland?
1. > 4 cm (40 mm)
2. growth of nodule (requires previous CT for comparison)
3. density of lesion is > 10 Hounsfield units (HU)
- Hounsfield unit is a quantitative scale for describing radiodensity of an object.
- Air has a hounsfield unit of -1000; water has a hounsfield unit of 0.
70
imaging for cushing's what are you looking at?
1. _CT - adrenal gland_ - benign vs malignant etiology
2. _MRI w/ contrast_ - pituitary gland
3. Search for ectopic source if indicated
- _CT scan of chest/abdomen_, if negative perform whole body PET scan
71
From the pituitary gland a sample of the inferior petrosal sinus was taken showing _elevated ACTH lvls_, what does this indicate?
pituitary Cushing's disease
72
from the pituitary gland a sample of the inferior petrosal sinus was taken showing _normal ACTH lvls_, what is the next step?
look for ectopic source of ACTH
73
during the MRI w/ contrast of the pituitary gland you find no lesions, what is the next step?
need inferior petrosal sinus sampling
(_no lesions or lesion < 5mm_)
74
what type of interpretation is needed to begin tx from a MRI w/ contrast of the pituitary gland?
a lesion >5 mm
75
management for Cushing's syndrome (exogenous)
1. **Slowly titrate down glucocorticoid/ACTH therapy**
2. _Adrenal adenoma/carcinoma, pituitary adenoma, ectopic ACTH-secreting tumor_
- **surgical removal** - post surgical adrenal insufficiency will require lifelong glucocorticoid replacement
- **pituitary radiation**
76
prolonged therapy can suppress the HPA axis; rapid withdrawal can result in ?
**acute adrenal insufficiency**
HPA axis is usually fully recovered within 6-12 months
77
what is the drug of choice to help with recovery of HPA axis
hydrocortisone - short acting glucocorticoid
78
indications for medical management for cushing's syndrome/disease
surgical decline/contraindication or awaiting surgery
79
what medications are used for hypercortisolism during medical management for cushing's syndrome/disease
1. _11β-hydroxylase inhibitors_ - blocking cortisol steroidogenesis
- Rx: **metyrapone** and **osilodrostat**
2. **ketoconazole** - inhibits the early steps of steroidogenesis
80
what medication is used for a pituitary ACTH tumor
**pasireotide (Signifor)**
- somatostatin analog
- inhibits ACTH secretion
81
what is the DOC for Mineralocorticoid HTN
1. Mineralocorticoid receptor antagonist (aka K+ sparing diuretic)
- **spironolactone, eplerenone**
2. **ACEI** (second line)
82
what is the DOC for Hyperandrogenism seen in women?
**flutamide**
- antiandrogen agent
- inhibits androgen uptake and/or inhibits binding of androgen in target tissues
83
cortisol related complications from cushing's
1. osteoporosis
2. cardiovascular disease
3. psychiatric disorders
- insomnia, depression, and memory loss
4. diabetes mellitus
5. hypokalemia
6. muscle weakness
7. infections
8. sleep apnea
