Adrenal disorders pt II Flashcards
autosomal recessive disorder involving an steroidogenic enzymatic block (defective or absent enzyme) = deficiency in cortisol
Congenital Adrenal Hyperplasia (CAH)
for CAH depending on the exact enzymatic block there will be ____ or ______
either excessive
or
deficient aldosterone and/or androgen
MC cause of Congenital Adrenal Hyperplasia (CAH)
21-hydroxylase (CYP21A)
what are the 3 pathophys presentations of CAH
- salt wasting CAH (aldosterone def.)
- virilizing CAH (androgen excess)
- nonclassic CAH - less severe
(1&2 more severe)
s/s of CAH are related to what? (focusing on 21-hydroxylase deficiency)
- deficiency in mineralocorticoid and glucocorticoids
- excess of adrenal androgen
what are the 3 presentations of CAH in females? (21-hydroxylase deficiency)
-
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
what are the 3 CAH Clinical Presentation in males? (21-hydroxylase deficiency)
-
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
what are the enzymes affected in ambiguous genitalia or female genitalia (males)?
complete androgenic enzymatic block
1. steroidogenic acute regulatory (StAR) protein
2. classic 3-beta-hydroxysteroid dehydrogenase deficiency (HSD3B2)
3. 17-hydroxylase deficiency (CYP17A1)
work up for CAH
- 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
If you are r/o other disorders for CAH, what are you imaging?
-
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
what is the tx goal for CAH
- provide the smallest dose of gluco- and mineralocorticoid that will adequately suppress excess androgen precursors
- produce normalization of growth velocity and skeletal maturation
tx for CAH
-
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
with CAH pts who might you have to refer/consult?
- Pediatric endocrinologist
- Pediatric urologist or gynecologist
- specializing in genital reconstruction if ambiguous genitalia - Geneticist
- Mental health professional
inadequate control of CAH can lead to:
- precocious puberty (males) and masculinity (females)
- rapid skeletal maturation
- tall children → short adults - adrenal crisis
- psychosocial disturbances
A condition resulting from hypersecretion of aldosterone that doesn’t suppress with sodium loading
Primary Hyperaldosteronism
causes of Primary Hyperaldosteronism
- bilateral idiopathic adrenal hyperplasia - 60-70%
- unilateral aldosterone-producing tumor - 30-40%
- benign adenoma - aka Conn Syndrome
- malignant carcinoma
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?
Primary Hyperaldosteronism
- often onset at young age without other risk factors
- symptoms of hypokalemia - inconsistent finding
someone with primary hyperaldosteronism has increased CO2, what does this mean?
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
for initial lab findings of primary hyperaldosteronism, what happens with Plasma Renin Activity (PRA) and Aldosterone Concentration (PAC)
- 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)
what are the PAC/PRA Ratio Limitations
-
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
what is the confirmatory testing for primary hyperaldosteronism
-
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
if you’re doing a salt loading and their 24 hr urine collection comes back normal urine creatinine, what does that ensure?
adequate urine sample
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?
adequate sodium loading
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?
Conn syndrome
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
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
tx/medical management for Primary Hyperaldosteronism
- Low sodium diet
- K+ sparing diuretics
- spironolactone (DOC) - mineralocorticoid receptor blockade preventing aldosterone secretion
— alternative: eplerenone (Inspra) - if unable to tolerate SE of spironolactone - Additional BP meds
- ACE inhibitor, HCTZ
- Second-line K+ sparing diuretics: amiloride, triamterene
who might you have to refer to for a pt with Primary Hyperaldosteronism
- Endocrinologist
- once screening indicates hyperaldosteronism - Cardiologist
- in the presence of long-standing HTN as cardiovascular complications are common
a pt with Primary Hyperaldosteronism
what must you monitor?
close monitoring of BP and K+
Adrenal tumors are categorized as follows:
- functional (hormone-secreting) or silent
- benign or malignant
- incidentaloma¹
CT findings indicative of adrenal malignancy:
- > 4 cm (40mm)
- nodule growth (comparison required)
- density > 10 HU
a highly vascular tumor of the sympathetic paraganglia that arises most frequently from the adrenal medulla, that secretes epinephrine and norepinephrine
Pheochromocytoma
what are known as catecholamines
epinephrine and norepinephrine
Pheochromocytoma is MC in what location?
adrenal medulla (90%)
avg age of onset for Pheochromocytoma
40
can occur in early childhood and late adulthood
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
what is the classic triad of Pheochromocytoma
- Episodic palpitations
- HA
- profuse diaphoresis
- associated with anxiety, pallor, presyncope/syncope, tachycardia
- paroxysms last < 1 hour
- Classic triad plus HTN is highly suggestive
what can cause the classic triad of Pheochromocytoma
- emotions/physical stressors
- change in position
- urination (“bladder pheo”)
- various medications
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
what is the lab work up for Pheochromocytoma
-
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
work up - imaging for Pheochromocytoma
- CT/MRI w/ contrast chest/abdomen/pelvis
- MRI preferred in children and pregnant women - PET scan - utilized to rule out malignancy
management of Pheochromocytoma
- Complete resection of tumor is recommended
-
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 - Post-surgery assess ACTH level
- risk of post-surgical adrenal insufficiency
while waiting for surgery what is given to pts to manage their Pheochromocytoma
-
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 - Diet - high salt and increased water intake
- start 3 days after alpha adrenergic blockade due to risk of orthostasis
complications of Pheochromocytoma
hypertensive crisis
cardiac arrhythmias
cerebral vascular accident
myocardial infarction
benign neoplasm of adrenocortical cells that does not secrete steroids is what disease?
Nonfunctioning adrenal adenoma
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
presentation of adrenal adenoma
asx
presentation of functional adrenal adenoma
related to respective cellular involvement
- zona glomerulosa - hyperaldosteronism
- zona fasciculata - Cushing’s Disease
- zona reticularis - hyperandrogenism
- adrenal medulla - pheochromocytoma
work up for adrenal adenoma
- Detailed H&P to determine presence hormone excess
- Labs ordered based upon suspected adrenal zone affected by mass
- Imaging - CT abdomen
management for adrenal adenoma
refer to experienced surgeon
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
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%)
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
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
work up of adrenal carcinoma
-
hormonal evaluation
- pheochromocytoma
- hyperaldosteronism
- hypercortisolism
- hyperandrogenism
— FSH, LH, DHEAS, prolactin, 17-OHP, and total and free testosterone -
Image
- CT abdomen/pelvis with contrast
- PET - increased uptake leads to a higher index of suspicion -
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
management of adrenal carcinoma
- Staging of the malignancy
- TNM Staging - Refer to surgeon for complete resection
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
indication of glucocorticoids
inflammatory conditions - lungs, skin, GI tract, neurologic eye, kidney, musculoskeletal; allergic reactions; autoimmune disorders, endocrine disorders
caution with glucocorticoids in ?
PUD, CVD or HTN with CHF, varicella, TB, acute psychosis, DM, osteoporosis, glaucoma
CI of glucocorticoids
hypersensitivity, coadministration with live vaccines, systemic fungal infections
dosing for glucocorticoids
Dosing titration indicated if >7-10 days of therapy
DDI of glucocorticoids
live vaccine, inactivated vaccine, other immunosuppressants (oral/topical)
monitoring for glucocorticoids
elevated glucose, Na retention, K+ loss
pt ed for glucocorticoids
take with meals - avoid GI upset
SE of glucocorticoids
-
Endocrine and metabolic
- Suppression of HPA axis
- Growth failure in children
- Hyperinsulinemia/insulin resistance
- Abnormal glucose tolerance test result/DM -
GI
- Gastric irritation, peptic ulcer
- Acute pancreatitis
- Fatty infiltration of liver -
CV
- HTN
- Congestive heart failure in predisposed patients -
Hemopoietic
- Leukocytosis
- Neutrophilia
- Lymphopenia
- Eosinopenia
- Monocytopenia -
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 -
MSK
- Osteoporosis, spontaneous fractures
- Avascular necrosis of femoral and humeral heads and other bones
- Myopathy (particularly of the proximal muscles) -
Ophthalmic
- Posterior subcapsular cataracts
- Elevated intraocular pressure/glaucoma -
CNS
- Sleep disturbances, insomnia
- Euphoria, depression, mania, psychosis
- Obsessive behaviors
- Pseudotumor cerebri -
Other cushingoid features
- Hypokalemia
