adrenal disorders Flashcards
Causes of primary adrenal insufficiency
- Autoimmune destruction of adrenal gland: Addison’s Dz. 2. Infectious: TB, Fungi, HIV. 3. Infiltrative: Amyloid. 4. Hemorrhage. 5. Metastatic. 6. Metabolic*. 7. Surgery
causes of secondary adrenal insufficiency
Exogenous glucocorticoid withdrawal (common), cure of Cushings syndrome (less common), opioids, radiation, infectious, hypothalamic/pituitary lesions (uncommon)
Hormone levels in primary vs secondary adrenal insufficiency
primary: Cortisol, aldosterone and adrenal androgens are low, but ACTH and CRF are high. Secondary: cortisol, adrenal androgens, ACTH and CRF are all low, and aldosterone is nl
Signs/symptoms of adrenal insufficiency
Chronic: fatigue, weakness, myalgias, arthralgias, nausea, weight loss, salt craving, hypotension, tachycardia. Acute: above plus fever, hypotension, confusion
labs of adrenal insufficiency
hyponatremia, hypoglycemia, azotemia, anemia (hemodilution), eosinophilia (cortisol lowers eosinophils)
What are signs/sx/labs that show up in primary adrenal insufficiency only
Vitiligo, pigmentation, hyperkalemia
What causes hyponatremia in AI
Decreased cortisol causes decreased cardiac output and decreased vascular tone. This creates a relative hypovolemia which causes stimulation of ADH, increased free water reabsorption and hyponatremia
What causes hyperkalemia in primary AI
The adrenal cortex is damaged, so patients lack aldosterone which leads to decreased sodium reabsorption and decreased potassium excretion by the kidney.
What causes hyperpigmentation in primary AI
Increased production of POMC (an ACTH precursor in the pituitary). POMC is also used as a precursor for melanocyte stimulating hormone so elevated levels lead to hyperpigmentation. In secondary AI, this does not occur b/c ACTH levels and POMC levels are low.
What is polyglandular autoimmune syndrome (type 2)
Clustering of autoimmune adrenal insufficiency with the following: hypothyroid, and type 1 diabetes. HLA asssociated
What is polyglandular autoimmune syndrome (type 1)
Autoimmune insufficiency plus hypoparathyroidism, type 1 diabetes and mucocutaneous candidiasis. Associated with an autoimmune regulator gene
Proposed mechanism of polyglandular autoimmune syndrome (type 2)
- endocrine cell undergoes non-specific cellular damage (viral, toxin). 2. non-susceptible individual does not recognize the autoantigen or develops tolerance and the gland recovers. 3. a susceptible individual recognizes autoantigen as foreign leading to immune attack on the gland, with subsequent hypofunction
Best imaging tool for adrenal glands
CT
Compare normal vs abnormal adrenal glands on imaging
normal body size is 5-8mm, limb size is 2-3mm and total width is 2-3cm. Abnormal gland may be small atrophic +/- calcifications (autoimmune or metabolic) OR enlarged with hemorrhage or necrosis (infctious, hemorrhage or mets)
risk facors for adrenal insufficiency
other autoimmune diseases, coagulopathy/sepsis /trauma (adrenal hemorrhage), HIV/AIDS, known malignancy, recent glucocorticoid treatment/ withdrawal, recent complicated delivery (pituitary infarct), or head trauma (pituitary infarct).
Primary adrenal insufficiency diagnosis
- serum cortisol: 100pg/ml. 3. Adrenal CT scan: small adrenal gland if autoimmune or metabolic. Large if other causes
caveat to cosyntropin testing
If pituitary/hypothalamus injury is recent (2 weeks to 6 months), the adrenal gland may still respond to cosyntropin stimulation
Stages of primary adrenal insufficiency
stage 1: increased plasma renin activity and decreased or nl plasma aldosterone. Stage 2: stage 1 plus decreased cortisol response to ACTH. Stage 3: stage 2 plus increased plasma ACTH. Stage 4: clinically overt AI
Diagnosis of secondary adrenal insufficiency
- serum cortisol: <20ug/dl after 10-60 minutes following cosyntropin (synthetic ACTH). 2. Plasma ACTH nl or low. 3. Pituitary MRI shows pathology
Adrenal insufficiency treatment
Primary only: mineralocorticoid replacement with Fludrocortisone. Primary + Secondary: glucocorticoid replacement with hydrocortisone, prednisone and/or dexamethasone
Sx of primary aldosteronism
hypertension, hypokalemia and metabolic alkalosis due to elevated aldosterone secretion
prevalence of primary aldosteronism in hypertensive pts
0.10
Levels of renin and angiotensin II in primary aldosteronism
Both are low due to negative feedback by aldosterone
Types of primary aldosteronism
- aldosterone producing adenoma (34%). 2. idiopathic hyperaldosteronism aka bilateral adrenal hyperplasia (66%). 3. glucocorticoid-remediable hyperaldosteronism (rare). 4. aldosterone producing carcinoma (rare)
What causes glucocorticoid-remediable hyperaldosteronism
a mutation which fuses the promoter of 11-B hydroxylase (involved in cortisol synthesis) with aldosterone synthase creating a hybrid glomerulosa/fasciculata layer which produces aldosterone under the positive control of ACTH. Autosomal dominant. glucocorticoid treatment will inhibit ACTH, thus decreasing aldosterone release
Who should be screened for primary aldosteronism
hypertensive pts with hypokalemia (spontaneous or provoked by diuretics), severe HTN (>160/100), resistant HTN (>2 drugs), HTN earlier than 40 yrs, adrenal incidental adenoma, first degree relative with primary hyperaldosteronism
Diagnosis of primary aldosteronism
Morning samples: Plasma aldosterone >15ng/dl AND Plasma aldosterone/ plasma renin activity ratio >20. Restrict spironolacton usage. Plasma renin activity = direct renin/8
Primary aldosteronism confirmation tests
Sodium suppression testing: 1. Oral salt load -high NaCl diet for 3 days followed by a 24 hr urine aldosterone >12ug confirms diagnosis. 2. IV saline infusion- 2L NS over 4 hrs followed by plasma aldosterone >10ng/dl confirms diagnosis
How do you determine whether primary aldosteronism is due to adenoma or hyperplasia
adenoma is likely if age >40, severe HTN, hypokalemia, plasma aldosterone > 25ng/dl, urine aldosterone >30ug/24hrs. 1. CT abdomen. 2. adrenal vein sampling: lateralization indicates adenoma, no lateralization indicates hyperplasia.
Imaging of adrenal hyperplasia and adenomas
Anatomic: CT is best, MRI. Functional: PET, adrenocortical scintigraphy. Interventional: adrenal venous sampling
compare imaging of adrenal hyperplasia vs adenoma
Hyperplasia: enlarged limbs of one or both glands, normal shape, can be multinodular. Adenoma: round/oval mass, CT shows homogenous low density
What is adrenocortical scintigraphy
NP-59 is a cholesterol analog which binds to adrenal LDL receptors.
Treatment of primary aldosteronism
If aldosterone producing adenoma: pre-operative aldosterone antagonists then unilateral adrenalectomy. If idiopathic hyperaldosteronism: medical management with spironolactone or eplerenone plus BP meds (Ca channel blocker, ACEI, ARB)
What is a pheochromocytoma
tumor of the chromaffin cells in the adrenal medulla leading to excess NE and epi. Can also arise from extra-adrenal chromaffin tissue anywhere along the sympathetic chain in which case they are referred to as paragangliomas.
Pheochromocytoma Sx
HTN, headaches, sweating, palpitations
pheochromocytoma rul of 10s
10% are Malignant, 10% are Familial, 10% are Bilateral, 10% are Extra-Adrenal
List familial syndromes associated with pheochromocytoma
MEN type 2A/2B (mutation of ret receptor causes constitutive activation of neuroendocrine cells), von Hipppel Lindau syndrome, Neurofibromatosis type 1, familial paragangliomas (SDH mutations)
Who to screen for pheochromocytoma
hypertensive pts with spells of headaches, sweating and/or palpitations, severe HTN (>160/100), resistant HTN (>2 drugs), adrenal incidental adenoma, familial syndrome
Pheochromocytoma screening tests
- urine metanephrines. 2. Urine catecholamines. 3. Plasma metanephrines. Urine tests are best screening tests but plasma metanephrines is best for high risk patients
Pheochromocytoma false positives
levodopa, ethanol, TCA, anti-psychotics, acetaminophen, amphetamines, renal failure, sleep apnea, physical stress
Endocrine principle of pheochromocytomas
a biochemical diagnosis must be established prior to the anatomic localization. This is especially true for many adrenal disorders since 5-10% of people will have an adrenal mass on CT scan, and a majority of these masses are non-functioning.
Pheochromocytoma localization tests
Abd MRI (hyperintense on T2, heterogenous) or CT, PET scans, MIBG (localization for ectopic, recurrent and metastatic tumors). Not hard to find.
Pheochromocytoma treatment
Preoperative: First alpha blockers (phenoxybenzamine, prazosin, terazosin, doxazosin), then beta blockers, OR calcium channel blockers alone. Adrenalectomy
Causes of Cushings Syndrome
- 80% are endogenous- ACTH secreting pituitary tumor causes elevated cortisol and adrenal androgens. 2. 10% are ectopic ACTH secreting tumors causing elevated cortisol and adrenal androgens. 3. 10% are cortisol secreting adrenal tumors resulting in decreased ACTH, elevated cortisol and nl adrenal androgens
Cushings Syndrome clinical features
Fatigue, weakness, weight gain, facial plethora, easy bruising, HTN, central obesity, purple stretch marks, muscle weakness, thin skin, hirsutism, hyperglycemia, hyperlipidemia
Cushings syndrome screening
- elevated 24 hr urine cortisol. 2. Elevated bedtime salivary cortisol. 3. Following 1mg dexamethasone suppression test, cortisol is >1.8ug/dl
Compare the results of a dexamethasone suppression test for the three different causes of Cushings syndrome
- If pituitary ACTH secreting tumor, DST results in suppression of ACTH and cortisol. 2. If ectopic ACTH secretic tumor, DST does not suppress ACTH/ cortisol. 3. If adrenal cortisol secreting tumor, DST does not suppress ACTH/cortisol
Name conditions with hypercortisolism that is not Cushings
Pregnancy, depression, alcoholism, morbid obesity, diabetes (poorly controlled)
Cushings syndrome localization
Pituitary MRI, chest CT, Abdominal CT, inferior petrosal sinus sampling
Cushings syndrome treatment
- surgery. 2. ACTH secretion inhibitors- Cabergoline, pasireotide. 3. Cortisol synthesis inhibitors- ketoconazole, metyrapone, etomidate. 4. adrenolytic agents- mitotane. 5. cortisol receptor blockers- mefispristone
What is an adrenal incidentaloma
Benign finding on abd imaging. Usually non functioning- most common hormone abnormality is cortisol secretion
Adrenal incidentaloma imaging
- CT: if high lipid content/low HU it is benign. If low lipid content/high HU it is malignant. 2. PET: measure FDG uptake. If high it is malignant, if low it is benign
Adrenal incidentaloma surgery
remove if >4.5cm, progressive growth or hormone secretion.
