Adrenal Flashcards
Does abnormal renal development change adrenals?
Adrenal gland development occurs normally in the absence of the ipsilateral renal unit development, malrotation, or malascent.
What percentage of neonates have adrenal rests? What percentage of adults?
50% of neonates
1% of adults (it atrophies)
What happens to adrenal rests in CAH?
In congenital adrenal hyperplasia, adrenal rests within the testis may become hyperplastic and present as a testicular mass
What do the zona glomerulosa, fasciculata, and reticularis do?
zona glomerulosa: mineralocorticoid (100-50 mcg/day)–salt
zona fasciculata: glucocorticoid (10-20 mg/day)–sugar
zona reticularis: androgens (>20 mg/day)–sex
Up to 50% of patients with Cushing’s syndrome will get THIS common urologic issue
Nephrolithiasis
(NB: It is also relatively common to see Cushing’s syndrome cause hypogonadotropic hypogonadism)
Hyper-Aldosterone Testing
IV saline infusion test - 2L of 0.9% NaCl IV over 4 hours
Performed in the morning after a overnight fast, while the patient is recumbent
Draw aldosterone, >5 ng/dL is diagnostic of primary hyperaldosterone and >10 ng/dL suggestive of aldosterone-producing adenomas
Only do captopril suppression test for patients with cardiac and renal disease, which prohibits sodium loading - give 25-50 mg ACE inhibitor followed by measurement of aldosterone (again recumbent) - positive test if >15 ng/dL
Adrenal mass with HTN workup?
Morning aldosterone to renin radio (ARR) and aldosterone level
-Stop potassium sparing diuretics for 6 weeks, consider stopping beta blockers
IF result abnormal, consider confirmatory testing with endocrinology and possible adrenal vein sampling
What percentage of aldosterone producing tumors will be less than 1 cm in size?
20%!!
CT is good, MRI does not usually offer an advantage in delineating primary aldosteronism subtypes
Adrenal vein sampling for aldosterone
The value of adrenal vein sampling in evaluating the presence of lateralized aldosterone secretion
-22% of patients would have been incorrectly excluded from adrenalectomy and 25% would have been inappropriately recommended to undergo adrenalectomy based on CT findings instead of adrenal vein sampling
Make sure to do in the morning
Correct hypokalemia first
Withdraw contraindicated medicines (K sparing diuretics and beta blockers)
Make sure to evaluate cortisol ratio first, then aldosterone ratio (cortisol in the IVC should be less than the samples from the renal veins - confirms you actually got renal vein samples from the veins)
Antihypertensive of choice in patients with primary aldosteronism?
Spironolactone and epleronone
-Androgen receptor antagonists
List side effects of aldosterone receptor antagonists?
Spironolactone and Epleronone (more favorable)
gynecomastia
impotence
menstrual disturbances
hyperkalemic
What conditions are associated with pheochromocytomas?
Rearranged Transfection Protooncogene (RET) - MEN2A and MEN2B - 50% risk of pheo
-Remember MEN2A - Medullary thyroid cancer, hyperparathyroidism, and pheo
-Men2B - Medullary thyroid cancer, neuromas, marfanoid habitus, pheo
von Hippel-Lindau (VHL) - 20% risk of pheo
Neurofibromatosis type 1 (NF1)
Mitochondrial succinate dehydrogenase subtype D and B genes (SDHD, SDHB)
VHL is the most relevant syndrome (10-20% risk) as these patients are already being screened for RCC
Why do we measure plasma metanephrines? For pheos
The conversion of catecholamines to metanephrines is an uninterrupted process within pheochromocytomas, measurement of plasma metanephrines is a much more sensitive means of tumor detection than catecholamines, which may be paroxysmal.
-Measure in plasma or urine
Stop acetaminophen 5 days prior
Draw in supine position
Functional evaluation of adrenal tumors with suspicion for adrenal cortical carcinomas
Glucocorticoid excess:
-Low dose dexamethasone suppression test or late night salivary or 24 hour urine cortisol
Sexual steroids and steroid precursors:
- DHEA
- 17-OH-Progesterone
- Androstenedione
- Testosterone
- 17Beta-estradiol (only in men and post menopausal women)
Catecholamine excess:
-Serum or urinary metanephrines
Mineralocorticoid excess:
-Aldosterone to renin ratio (only in patients with HTN or hypokalemia)
Adrenal Adenoma:
Imaging, appearance on imaging, and workup
Non-contrast CT
<10 HU
7% of adrenal adenomas exhibit metabolic hyperactivity
<2% gain function
Evaluate for excess cortisol (low dose dexamethasone suppression) and catecholamine secretion (urine or plasma metanephrines)
In patients with hypertension, test for hyperaldosteronism
Campbells says resect all adrenal masses >6 cm, others argue 4 cm
Reimage at 6, 12, and potentially 24 months
Which adrenal masses do you test?
The NIH consensus statement recommends metabolic testing for all adrenal incidentalomas
Test all new adrenal masses for cortisol and catecholamine hypersecretion
In a patient with hypertension, test for aldosterone hypersecretion
What medication can mess with a dexamethasome suppression test?
Oral contraceptives!
50% false positive rate because it increases total but not bioavailable cortisol levels by raising the patient’s cortisol binding globulin concentration
What medication can mess with a dexamethasome suppression test?
Oral contraceptives!
50% false positive rate because it increases total but not bioavailable cortisol levels by raising the patient’s cortisol binding globulin concentration
What medicine can interfere with catecholamine testing?
Acetaminophen (false positive result)
- Cross reactivity with plasma free metanephrines or 24 hour urinary fractionated metanephrines
Watch out for tricyclic antidepressants and phenoxybenzamine
Take off beta blockers
Surgical Indication for Adrenalectomy
Functional adrenal mass (cortisol hypersecretion, pheochromocytoma, aldosterone hypersecretion)
Mass >4 cm with the exception of myelolipoma
Mass with imaging findings suggestive of malignancy (lipid poor, heterogenous, irregular borders, infiltrates surrounding structures)
Adrenal incidentaloma with >1 cm growth on follow up
Extremely large or symptomatic myelolipomas
Isolated adrenal metastases
During radical nephrectomy if:
-Adrenal abnormal or not seen on imaging with large tumor size
-Large >7 cm upper pole mass
-Vein thrombus to the level of the adrenal vein
Failed neurosurgical treatment of Cushing’s disease, requiring bilateral adrenalectomy
Select patients with ectopic ACTH syndrome, requiring bilateral adrenalectomy
ACTH independent macronodular adrenal hyperplasia
Primary pigmented nodular adrenocortical disease
Once more:
Adrenal mass with benign features and mass <4 cm
Workup?
- Low dose dexamethasone suppression test or late night salivary cortisol or 24 hour urinary cortisol
- 24 hour urinary fractionated metanephrines or plasma free metanephrines
- If patient hypertensive, morning plasma aldosterone to renin radio and morning plasma aldosterone level
Adrenal mass with benign features <4 cm - follow up
- Repeat imaging at 6, 12, and 24 months
- Repeat functional workup annually for 4 years (per Campbells)
CAH: 21 Hydroxylase Deficiency
95% of CAH - elevated 17hydroxyprogesterone and progesterone (and androstendione according to the other book but not campbells)
A pelvic ultrasound demonstrating the presence of mullerian tissues is confirmatory (if female and virilized)
75% with salt wasting (hypotension) - failure to regain birth weight, progressive weight loss, dehydration
-Adrenal crisis within 10-21 days in severe forms
25% simple virilization
11 Beta Hydroxylase Deficiency
5% of CAH
High amount of deoxycorticosterone (DOC) causes high blood pressure EVEN THOUGH you don’t get all the way to cortisol on the chart of enzymes
Test 11 deoxycorisol and 11 DOC
Hypertension and virilization
3 Beta hydroxysteroid dehydrogenase deficiency
Increased 17-hydroxypregnenelone and hydroepiandrosterone (DHEA)
Can you do prenatal testing for CAH? What do you do if you find something?
YES
Measure amniotic fluid for 17 hydroxyprogesterone (or during chorionic villus sampling)
Treat mother with dexamethasone, which suppresses fetal production of ACTH, which prevents virilization of the genitalia
Complete Androgen Insensitivity
46XY
Bilateral testes
Female appearing genitalia
Absence of mullerian derivates
5 Alpha Reductase Deficiency
Male undervirilization
46XY
Penoscrotal hypospadias or markedly ambiguous genitalia
Elevated testosterone, low DHT
Test for Cushing’s
Overnight low-dose (1-mg) dexamethasone suppression test (OST)
Late-night salivary cortisol test (SCT)
24-hour urinary-free cortisol evaluation (UFC)
To perform the OST, a dose of 1 mg dexamethasone is given at 23:00 hours followed by measurement of serum cortisol and dexamethasone the following morning at 08:00.
A putative diagnosis of Cushing Syndrome is made if the serum cortisol level is > 5 micrograms/dL following an OST.
An ACTH level can be checked to ascertain whether it is ACTH-independent or -dependent.
A low/suppressed ACTH or DHEA-sulfate support an adrenal source.
Who to screen for hyperaldosteronism? (Conn’s syndrome)
Any patient with sustained blood pressure above 150/100 on three separate measurements taken on different days
Hypertension resistant to 3 antihypertensives
Hypertension controlled with four or more medications
Hypertension and low potassium
Hypertension and a newly diagnosed adrenal incidentaloma
Hypertension and concomitant sleep apnea
Hypertension and a family history of early onset hypertension or stroke before age 40
All first-degree relatives of patients with a diagnosis of primary aldosteronism
What do you do if you have elevated aldosterone or an elevated aldosterone renin ratio to confirm hyperaldosteronism?
A positive ARR screen should prompt a confirmatory 24-hour urine study with salt loading to assess for primary aldosteronism.
It is also important to note that positive testing for aldosterone hypersecretion does not guarantee a unilateral source, and therefore, adrenal venous sampling is recommended prior to surgical intervention.
For those patients with pheochromocytoma and age < 50, family history, or extra-adrenal pheochromocytoma….
Investigation for familial syndromes with genetic testing is warranted, with emphasis on mutation of the RET proto-oncogene (multiple endocrine neoplasia type 2), VHL (von Hippel-Lindau disease), or succinate dehydrogenase genes
What is an adrenal protocol CT?
An adrenal protocol CT scan is a triphasic study. The first phase of the study is without contrast. This is followed by imaging immediately after intravenous administration of contrast. The final phase is imaging after 10 to 15 minutes. Adrenal washout can be presented as absolute percentage contrast-washout ((enhanced HU – 15-min delayed HU)/(enhanced HU – unenhanced HU) x 100%) or as relative percentage contrast washout ((enhanced HU – 15-min delayed HU)/enhanced HU x 100%).
The 2017 ACR guidelines denote thresholds of
> 60% absolute percentage washout or
> 40% relative percentage washout as characteristic of benign incidentalomas.
Pheochromocytoma Imaging
Pheochromocytomas measure greater than 10 HU on unenhanced CT scans and will enhance to more than 100 HU on contrast studies, often exhibiting a well-circumscribed appearance with or without necrotic or cystic elements.
Recent data suggest that if HU are <10 then biochemical testing for pheochromocytoma is not necessary.
The classic “light bulb” signal on T2-weighted MRI may be helpful, but recent studies suggest that this sign is less sensitive and specific than previously thought.
Additional imaging, such as meta-iodobenzylguanidine (MIBG) scanning may also be warranted in this setting, especially if assessing for an extra-adrenal, metastatic, or recurrent pheochromocytoma.
Adrenocortical carcinomas on imaging
Adrenocortical carcinomas typically are larger than 4 cm and exhibit a heterogeneous appearance on CT, with calcifications and necrosis often present.
HU measurement on non-contrast CT are typically >25 HU with <50% washout demonstrated at 10 minutes post-contrast imaging.
Adrenal metastasis may also have a similar appearance, which belies the importance of clinical history in this setting.
Lipid-poor adenomas may have attenuation values of 20-40 HU, but a washout of >50% is believed to distinguish these lesions from adrenal carcinomas.
How do you distinguish lipid-poor adenomas from adrenal carcinomas?
Lipid-poor adenomas may have attenuation values of 20-40 HU, but a washout of >50% is believed to distinguish these lesions from adrenal carcinomas.
If an adrenal is _____ (size), it should be removed regardless of function.
There is some controversy over the management of masses between 4-6 cm.
The American Association of Clinical Endocrinologists/American Association of Endocrine Surgeons (AACE/AAES) guidelines recommend removal of all masses over 4 cm regardless of functional status or imaging characteristics, unless it is clearly a myelolipoma.
Algorithm for Workup and Management of Adrenal Incidentalomas
Biochemical Testing for Functional Adrenal Adenomas:
Adrenal Pathology and Associated Characteristics
Preoperative meds for pheochromocytoma
ALSO aggressive peri-operative hydration
