Adrenal disorders pt II Flashcards
(65 cards)
1
Q
autosomal recessive disorder involving an steroidogenic enzymatic block (defective or absent enzyme) = deficiency in cortisol
A
Congenital Adrenal Hyperplasia (CAH)
2
Q
for CAH depending on the exact enzymatic block there will be ____ or ______
A
either excessive
or
deficient aldosterone and/or androgen
3
Q
MC cause of Congenital Adrenal Hyperplasia (CAH)
A
21-hydroxylase (CYP21A)
4
Q
what are the 3 pathophys presentations of CAH
A
- salt wasting CAH (aldosterone def.)
- virilizing CAH (androgen excess)
- nonclassic CAH - less severe
(1&2 more severe)
5
Q
s/s of CAH are related to what? (focusing on 21-hydroxylase deficiency)
A
- deficiency in mineralocorticoid and glucocorticoids
- excess of adrenal androgen
6
Q
what are the 3 presentations of CAH in females? (21-hydroxylase deficiency)
A
-
Classic virilizing adrenal hyperplasia
- genital atypia - clitoral enlargement, labial fusion, and formation of a urogenital sinus
- signs of adrenal (aldosterone) insufficiency within 1-4 wks if not treated
— recurrent vomiting, dehydration, hyponatremia, hyperkalemia, hypotensive shock -
Simple virilizing adrenal hyperplasia
- milder genital atypia
- variable signs of adrenal insufficiency within 1-4 weeks if not treated
- precocious puberty - accelerated growth and early skeletal maturation -
Nonclassic adrenal hyperplasia
- noticed during adolescent/early adulthood - oligomenorrhea, hirsutism, and/or infertility
7
Q
what are the 3 CAH Clinical Presentation in males? (21-hydroxylase deficiency)
A
-
Classic salt-wasting adrenal hyperplasia
- grossly normal appearing genitalia with hyperpigmented scrotum, enlarged phallus
- 1-4 wks - “failure to thrive”
— recurrent vomiting, dehydration, hyponatremia, hyperkalemia, hypotensive shock -
Simple virilizing adrenal hyperplasia
- 2-4 y/o with precocious puberty - pubic hair, adult body odor, accelerated linear growth and skeletal maturation -
ambiguous genitalia or female genitalia
- inadequate testosterone production in the 1st trimester of pregnancy due to complete androgenic enzymatic block
8
Q
what are the enzymes affected in ambiguous genitalia or female genitalia (males)?
A
complete androgenic enzymatic block
1. steroidogenic acute regulatory (StAR) protein
2. classic 3-beta-hydroxysteroid dehydrogenase deficiency (HSD3B2)
3. 17-hydroxylase deficiency (CYP17A1)
9
Q
work up for CAH
A
- Newborn Screening
- 21-hydroxylase deficiency (CYP21A2) - Ambiguous genitalia
- immediate hormonal, genetic and chromosomal testing - Hormonal workup
- steroidogenic enzymes metabolites
— serum 17-hydroxyprogesterone (CYP17) - increased in 21-hydroxylase deficiency
— other enzyme metabolites measured if less common deficiencies are suspected
- Serum DHEA (dehydroepiandrosterone) - increased (CYP21A1 def.) - Chemistry
- assess for electrolyte abnormalities associated with aldosterone deficiency - Imaging - not necessary for diagnosis
- unless r/o or assessing other disorders
10
Q
If you are r/o other disorders for CAH, what are you imaging?
A
-
CT abd - r/o bilat adrenal hemorrhage
- used only in patients without ambiguous genitalia -
Pelvic US - assessing organic anomalies associated with ambiguous genitalia
- look for renal anomalies, female sex organ abnormalities
11
Q
what is the tx goal for CAH
A
- provide the smallest dose of gluco- and mineralocorticoid that will adequately suppress excess androgen precursors
- produce normalization of growth velocity and skeletal maturation
12
Q
tx for CAH
A
-
Hydrocortisone
- Initial supraphysiologic doses (1-2 mg/kg/d) divided TID
— monitor for normalization of serum 17-hydroxyprogesterone
- Maintenance dose (0.3–0.5 mg/kg/d) divided TID
— adjust dose to maintain normal growth rate and skeletal maturation -
Fludrocortisone 0.05 - 0.15 mg daily
- monitor BP and plasma renin activity
13
Q
with CAH pts who might you have to refer/consult?
A
- Pediatric endocrinologist
- Pediatric urologist or gynecologist
- specializing in genital reconstruction if ambiguous genitalia - Geneticist
- Mental health professional
14
Q
inadequate control of CAH can lead to:
A
- precocious puberty (males) and masculinity (females)
- rapid skeletal maturation
- tall children → short adults - adrenal crisis
- psychosocial disturbances
15
Q
A condition resulting from hypersecretion of aldosterone that doesn’t suppress with sodium loading
A
Primary Hyperaldosteronism
16
Q
causes of Primary Hyperaldosteronism
A
- bilateral idiopathic adrenal hyperplasia - 60-70%
- unilateral aldosterone-producing tumor - 30-40%
- benign adenoma - aka Conn Syndrome
- malignant carcinoma
17
Q
28 y/o pt comes in with
refractory hypertension
HA
muscle weakness, fatigue, polyuria, polydipsia, paresthesias, tetany
BMP reveals serum sodium of 400 mmol/L (normal: 145 mmol/L
no other risk factors for their HTN
what could they possibly have?
A
Primary Hyperaldosteronism
- often onset at young age without other risk factors
- symptoms of hypokalemia - inconsistent finding
18
Q
someone with primary hyperaldosteronism has increased CO2, what does this mean?
A
metabolic alkalosis (increase bicarbonate)
- results from increased urinary H-/Na+ exchange and shifting of hydrogen ions into the cell due to hypokalemia
- asx or if severe muscle twitching, cramps, tingling in fingers/toes
19
Q
for initial lab findings of primary hyperaldosteronism, what happens with Plasma Renin Activity (PRA) and Aldosterone Concentration (PAC)
A
- obtained in AM in a seated position
- PRA - low
- PAC - elevated
- Plasma aldosterone/renin ratio¹
— normal is < 10
— ratio > 20-25 (95% sensitivity and 75% specificity for primary aldosteronism)
20
Q
what are the PAC/PRA Ratio Limitations
A
-
circadian rhythm of aldosterone secretion
- Recommended for lab draw:
— out of bed for 2 hrs
— seated for 15-60 min before blood draw (between 8-10 AM) -
Medications altering lab results
- Avoid mineralocorticoid receptor antagonist (spironolactone and eplerenone), ACE inhibitors, ARBs, direct renin inhibitors
- Safe BP meds - slow-release verapamil, hydralazine, terazosin, and doxazosin
21
Q
what is the confirmatory testing for primary hyperaldosteronism
A
-
Salt loading - oral or IV
- Oral - 3 d unrestricted salt (> 5g/d)
— serum K+ assessed every day due to increased risk of low K+
— day 3 assess serum electrolytes and begin 24 h urine collection for aldosterone, sodium and creatinine
——– urine aldosterone > 12 mcg/24h - confirms - IV - 2L NS / 4 hr while seated
- plasma aldosterone concentration > 10 ng/dL - consistent with dx
22
Q
if you’re doing a salt loading and their 24 hr urine collection comes back normal urine creatinine, what does that ensure?
A
adequate urine sample
23
Q
if you’re doing a salt loading and their 24 hr urine collection comes back as urine Na > 250 mEq/L, what does that ensure?
A
adequate sodium loading
24
Q
you suspect primary hyperaldosteronism and order a CT scan of the abdomen as part of your work up. You find a unilateral adrenal mass <4cm. What does that indicate?
A
Conn syndrome
25
you suspect primary hyperaldosteronism and order a CT scan of the abdomen as part of your work up. You find a unilateral adrenal mass >4cm. What does that indicate?
consider carcinoma
26
you suspect primary hyperaldosteronism and order a CT scan of the abdomen as part of your work up. Nothing was found, what is the next step?
**adrenal vein sampling**
1. assessing aldosterone levels in blood from adrenal vein
- _experienced_ interventional radiologist
- _last resort testing_ - invasive, expensive and often unsuccessful
- _recommended *only* if **severely uncontrolled HTN** *AND* **adrenalectomy** is being considered for tx_ in order to determine which gland is hyperactive
27
tx/medical management for Primary Hyperaldosteronism
1. Low sodium diet
2. K+ sparing diuretics
- **spironolactone (DOC)** - mineralocorticoid receptor blockade preventing aldosterone secretion
--- alternative: **eplerenone** (Inspra) - if unable to tolerate SE of spironolactone
3. Additional BP meds
- **ACE inhibitor, HCTZ**
- _Second-line_ K+ sparing diuretics: **amiloride, triamterene**
28
who might you have to refer to for a pt with Primary Hyperaldosteronism
1. Endocrinologist
- once screening indicates hyperaldosteronism
2. Cardiologist
- in the presence of long-standing HTN as cardiovascular complications are common
29
a pt with Primary Hyperaldosteronism
what must you monitor?
close monitoring of **BP** and **K+**
30
Adrenal tumors are categorized as follows:
1. functional (hormone-secreting) or silent
2. benign or malignant
3. incidentaloma¹
31
CT findings indicative of adrenal malignancy:
1. > 4 cm (40mm)
2. nodule growth (_comparison required_)
3. density > 10 HU
32
a highly vascular tumor of the sympathetic paraganglia that arises most frequently from the adrenal medulla, that secretes epinephrine and norepinephrine
Pheochromocytoma
33
what are known as catecholamines
epinephrine and norepinephrine
34
Pheochromocytoma is MC in what location?
adrenal medulla (90%)
35
avg age of onset for Pheochromocytoma
**40**
can occur in early childhood and late adulthood
36
what is the Rules of 10's for Pheochromocytoma
10% are bilateral
10% are extra-adrenal
10% are malignant
MOST are _unilateral, on the adrenal medulla, and benign_
37
what is the classic triad of Pheochromocytoma
1. Episodic palpitations
2. HA
3. profuse diaphoresis
- associated with anxiety, pallor, presyncope/syncope, tachycardia
- paroxysms last < 1 hour
- **Classic triad _plus_ HTN is highly suggestive**
38
what can cause the classic triad of Pheochromocytoma
1. emotions/physical stressors
2. change in position
3. urination (“bladder pheo”)
4. various medications
39
what is the most sensitive test for Pheochromocytoma
describe this test
**_Plasma free metanephrines_**
1. _collection technique is **key**_
- sitting for 15 minutes before collection;
--- *_if elevated_* - repeat in _supine_ after lying down x 30 min
- check with lab
2. _interpretation_
- normal results = r/o pheochromocytoma
- **elevated - assess urine metanephrines**
3. _interfering factors_ - false elevation
- any stressor, sleep apnea, certain drugs
40
what is the lab work up for Pheochromocytoma
1. **_Urine fractionated metanephrines and creatinine_**
- _collection options_:
--- 24 h collection (preferred)
--- overnight collection
--- shorter collection time frames
------- check with lab on normal ranges
- _interpretation:_
- Normal: total urinary metanephrine levels < 1300 mcg/24 hours
_Both_ plasma and urine metanephrine evaluation both need to be **> 3x upper limit of normal to be _diagnostic_**
41
work up - imaging for Pheochromocytoma
1. CT/MRI w/ contrast chest/abdomen/pelvis
- MRI preferred in children and pregnant women
2. PET scan - utilized to rule out malignancy
42
management of Pheochromocytoma
1. **Complete resection of tumor** is recommended
2. _Refer to a surgeon who is experienced in resection of pheochromocytomas_
- BP extremely labile during surgery
- anesthesiology needs to also be experienced in managing pheo surgical patients
3. Post-surgery assess ACTH level
- **risk of post-surgical adrenal insufficiency**
43
while waiting for surgery what is given to pts to manage their Pheochromocytoma
1. _BP needs to be consistently < 160/90 prior to surgery_
- **alpha-adrenergic blockers** - at least 14 d prior to surgery
--- doxazosin (Cardura)
--- prazosin (Minipress)
--- terazosin (Hytrin)
- **additional BP agents if needed** - BB’s, CCB’s, ACEI
2. Diet - **high salt and increased water intake**
- start 3 days after alpha adrenergic blockade due to risk of orthostasis
44
complications of Pheochromocytoma
hypertensive crisis
cardiac arrhythmias
cerebral vascular accident
myocardial infarction
45
benign neoplasm of adrenocortical cells that does not secrete steroids is what disease?
Nonfunctioning adrenal adenoma
46
_benign neoplasm_ >1 cm arising from the adrenal cortex that _secrete steroids independently from ACTH or the RAA system_
is what disease?
Functional adrenal adenoma
- cells of the zona glomerulosa - Primary Aldosteronism
- cell of the zona fasciculata - Cushing’s Disease
- cells of the zona reticularis - hyperandrogenism (rare)
- adrenal medulla - pheochromocytoma
47
presentation of adrenal adenoma
asx
48
presentation of functional adrenal adenoma
related to respective cellular involvement
- zona glomerulosa - hyperaldosteronism
- zona fasciculata - Cushing’s Disease
- zona reticularis - hyperandrogenism
- adrenal medulla - pheochromocytoma
49
work up for adrenal adenoma
1. Detailed H&P to determine presence hormone excess
2. Labs ordered based upon suspected adrenal zone affected by mass
3. Imaging - CT abdomen
50
management for adrenal adenoma
refer to experienced surgeon
51
etiology and risk factors of adrenal carcinoma
most are sporadic
some hereditary cancer syndromes
risk factors:
children living in southern Brazil (environmental and genetic)
adrenal hyperplasia
52
adrenal carcinoma MC happens when?
_2 peaks_
- birth -10 years - functional tumors more common
- 30-40 y/o - nonfunctional tumors are more common
functional (60%)
nonfunctional (40%)
53
presentation of functional adrenal carcinoma
will present with symptoms respective of adrenocortical cells involved
1. _virilization, cushinoid symptoms, hyperaldosteronism_
2. _feminization_ - rare
- gynecomastia in males
- precocious sexual development in young females
54
presentation of nonfunctional adrenal carcinoma
presents with **sx related to malignancy and/or metastasis**
1. most present with advanced disease and multiple metastatic sites
2. _Hx_: Fever, wt loss, abd pain/tenderness/fullness, back pain
3. PE - _palpable, firm, adherent mass of the abdomen_
55
work up of adrenal carcinoma
1. _hormonal evaluation_
- pheochromocytoma
- hyperaldosteronism
- hypercortisolism
- hyperandrogenism
--- FSH, LH, DHEAS, prolactin, 17-OHP, and total and free testosterone
2. _Image_
- CT abdomen/pelvis with contrast
- PET - increased uptake leads to a higher index of suspicion
3. _Fine Needle Aspiration_
- ***only*** to _r/o metastasis_ in _known malignancy_
--- _must r/o pheochromocytoma prior to FNA_
- not recommended to simply differentiate between adenoma and carcinoma
--- unreliable with **risk of tumor seeding** into the retroperitoneum
56
management of adrenal carcinoma
1. Staging of the malignancy
- TNM Staging
2. Refer to surgeon for complete resection
57
MOA of glucocorticoids
_Mimic physiologic steroids_
1. **Inhibit the inflammatory response**
2. **Decrease** chemotaxis of **inflammatory cells**
3. **Depress migration of polymorphonuclear (PMN) leukocytes**
4. **Lympholysis** (lysis of lymphocytes) → Decreased # of circulating lymphocytes
5. Reverse capillary permeability
6. **Reduce phagocytic and killing ability of neutrophils & macrophages**
58
indication of glucocorticoids
**_inflammatory conditions_** - lungs, skin, GI tract, neurologic eye, kidney, musculoskeletal; allergic reactions; autoimmune disorders, endocrine disorders
59
caution with glucocorticoids in ?
PUD, CVD or HTN with CHF, varicella, TB, acute psychosis, DM, osteoporosis, glaucoma
60
CI of glucocorticoids
hypersensitivity, coadministration with **live vaccines**, systemic fungal infections
61
dosing for glucocorticoids
Dosing titration indicated if >7-10 days of therapy
62
DDI of glucocorticoids
**live vaccine, inactivated vaccine**, other immunosuppressants (oral/topical)
63
monitoring for glucocorticoids
elevated glucose, Na retention, K+ loss
64
pt ed for glucocorticoids
take with meals - avoid GI upset
65
SE of glucocorticoids
1. **_Endocrine and metabolic_**
- _Suppression of HPA axis_
- Growth failure in children
- Hyperinsulinemia/insulin resistance
- Abnormal glucose tolerance test result/_DM_
2. **_GI_**
- _Gastric irritation, peptic ulcer_
- Acute pancreatitis
- Fatty infiltration of liver
3. **_CV_**
- _HTN_
- _Congestive heart failure_ in predisposed patients
4. **_Hemopoietic_**
- Leukocytosis
- Neutrophilia
- Lymphopenia
- Eosinopenia
- Monocytopenia
5. **_immune_**
- Suppression of delayed (type IV) hypersensitivity (important with Mantoux testing for tuberculosis)
- Inhibition of leukocyte and tissue macrophage migration
- Inhibition of cytokine secretion/action
- Suppression of the primary antigen response
6. **_MSK_**
- _Osteoporosis_, spontaneous fractures
- Avascular necrosis of femoral and humeral heads and other bones
- Myopathy (particularly of the proximal muscles)
7. **_Ophthalmic_**
- Posterior subcapsular cataracts
- _Elevated intraocular pressure/glaucoma_
8. **_CNS_**
- _Sleep disturbances_, insomnia
- _Euphoria, depression, mania, psychosis_
- Obsessive behaviors
- Pseudotumor cerebri
9. **_Other cushingoid features_**
- _Hypokalemia_
