Adrenal disorders

Question 1

Addison’s disease - adrenocortical hypofunction, hypoadrenalism

Impaired secretory function of adrenal gland WITH intact hypothalamic and pituitary
Autoimmune adrenalitis
Infectious adrenalitis (TB, HIV, histoplasmosis, coccidiomycosis, CMV, toxoplasmosis)-develop
Bilateral adrenal infiltration (amyloidosis, sarcoidosis, hemochromatosis, lymphoma)
Bilateral adrenal metastasis (lung, breast, kidney, colon)
Surgery
Bilateral adrenal hemorrhage
Medications (azoles, etomidate, phenytoin, rifampin, heparin, warfarin)

Answer 1

primary chronic adrenal insufficiency

Question 2

which is more common: primary or secondary chronic adrenal insufficiency?

Answer 2

secondary

Question 3

ACTH deficiency, impaired stimulation of adrenal glands due to DISRUPTION of normal pituitary secretion or lack of responsiveness
Exogenous steroid use with abrupt cessation - patients unable to increase cortisol under stress
– hypopituitarism, mass lesions, pituitary irradiation, infiltration, congenital deficiency

Answer 3

secondary chronic adrenal insufficiency

Question 4

impaired stimulation due to disruption of normal hypothalamic secretion of CRH or vasopressin, or both, inhibiting secretion of ACTH
Exogenous use of high dose steroids
– space occupying lesion or trauma, infectious or infiltrative processes

Answer 4

tertiary chronic adrenal insufficiency

Question 5

Aldosterone falls → hyperkalemia and hyponatremia, low BV, metabolic acidosis

Salt craving, nausea, vomiting, abdominal pain, dizziness, low BP, HOTN, orthostatic HOTN

Increased ACTH → hyperpigmentation of skin in sun-exposed areas and joints (elbows, knees, knuckles)

In pregnancy = anovulation and reduced fertility with first trimester fatigue, N/V, abdominal pain, orthostasis, hyperpigmentation
Undiagnosed → fetal loss, shock

Type 1 D: hypoglycemia with onset, must lower dose of insulin

Answer 5

primary chronic adrenal insufficiency

Question 6

Cortisol falls → low BG in times of stress with weakness, fatigue, disorientation

Lack of energy

Women = loss of pubic and axillary hair, decreased sex drive, dry and itchy skin (men not affected!)

Answer 6

secondary chronic adrenal insufficiency

Question 7

How do you differentiate between acute and chronic adrenal insufficiency?

Answer 7

ACUTE: generally severe with HOTN, vomiting, abdominal pain, fever, and AMS

CHRONIC: more nonspecific with fatigue, anorexia, weight loss, weakness, abdominal pain, arthralgias

Question 8

primary adrenal insufficiency is more common in what age group?

Answer 8

30-50

Question 9

secondary adrenal insufficiency is more common in what age group?

Answer 9

50-60

Question 10

where is the most frequent insufficient location?

Answer 10

Hypothalamic-pituitary origin

Question 11

what are the diagnostic steps for adrenal insufficiency?

Answer 11

baseline cortisol low –> measure serum ACTH –> ACTH stimulation and further testing

Question 12

What is the screening test for adrenal insufficiency?

Answer 12

cortisol levels, post-ACTH stimulation test – if with stimulation cortisol is STILL low = insufficiency

Question 13

how do you differentiate between primary and secondary adrenal insufficiency?

Answer 13

measuring plasma ACTH:
Plasma ACTH >22 with high renin and low aldosterone, cortisol, hyponatremia, and hyperkalemia = primary

Plasma ACTH <12 with normal renin and aldosterone, low cortisol = secondary/tertiary

Question 14

What should you do next with a primary adrenal insufficiency?

Answer 14

CT scan, measuring autoantibodies

Enlarged = metastatic or granulomatous disease
Calcifications = hemorrhage, infection, pheochromocytoma, melanoma
Small, noncalcified adrenals = Addison’s

Question 15

What should you do next with secondary adrenal insufficiency?

Answer 15

MRI of pituitary to assess for lesions

Question 16

—- adrenal insufficiency includes prolonged, or exaggerated ACTH response

Answer 16

tertiary

Question 17

ACTH stimulation, CRH stimulation test, insulin tolerance test can be used for 2ndary, but not routinely used due to safety concerns are all –

Answer 17

options for further testing for adrenal insufficiency

Question 18

how do you treat primary adrenal insufficiency?

Answer 18

1= medical alert bracelet (I take hydrocortisone), provide dose escalation schedule (increased in illness, accidents, procedures, fludrocortisone for hot weather or prolonged exercise), automatic refills, routine antiemetic, self-injection in event of vomiting
Hydrocortisone daily divided in 2-3 doses
Based on symptoms NOT levels
Partial ACTH deficiency with morning cortisol >8mg = lower doses
Neutrophilia and lymphopenia = overtreatment
Fludrocortisone acetate
DHEA replacement for women with low libido, depressive symptoms, low energy levels
Seek ER if vomiting or severe illness
All infections treated immediately and vigorously

Question 19

How do you treat 2ndary and tertiary adrenal insufficiency?

Answer 19

hydrocortisone

Question 20

Magnified chronic adrenal insufficiency and have acute deterioration in health – acute GI symptoms, fever mimicking abdominal emergency, back pain, arthralgia, fatigue, delirium/coma, hypoglycemia, orthostatic dizziness/HOTN, cardiomyopathy and HF, shock unresponsive to fluids and vasopressors

Answer 20

acute adrenocortical insufficiency/crisis

Question 21

What can cause an adrenal crisis?

Answer 21

stress

Question 22

Emergency caused by insufficient cortisol causing threat to life, from severe stress, minor stress, hyperthyroidism or untreated adrenal insufficiency, nonadherence to steroids/abrupt withdrawal, bilateral adrenalectomy, destruction of pituitary gland, damage, IV etomidate
Addisonian crisis

Answer 22

adrenal crisis

Question 23

Identifying adrenal crisis is similar to

Answer 23

adrenal insufficiency

Question 24

Cultures, plasma ACTH, cortisol, glucose, BUN, Cr, electrolyte levels, UA – hyponatremia, hyperkalemia, hypoglycemia

Differentiate primary and secondary per usual

Answer 24

adrenal crisis

Question 25

How do you treat adrenal crisis?

Answer 25

Without waiting for results: treatment initiated immediately –hydrocortisone + IV fluids 2-3L bolus + fludrocortisone + broad-spectrum antibiotics

Question 26

Neisseria = petechial rash, large purpura over time, fever & chills due to sepsis, addisonian crisis (pain in low back, abdomen, legs, severe V/D, HOTN, syncope)

Answer 26

Waterhouse-Friderichsen syndrome

Question 27

What puts someone at risk for Watrehouse-Friderichsen syndrome?

Answer 27

adrenal crisis

Question 28

Blood vessels in adrenal gland rupture during a severe bacterial infection – adrenal glands turn into sacks of blood Neisseria meningitidis, pseudomonas aeruginosa, haemophilus influenzae – pressure increases -> rupture Can trigger DIC

Answer 28

Waterhouse-Friderichsen syndrome

Question 29

Waterhouse-Friderichsen syndrome dx:

Answer 29

ACTH stimulation test, blood culture, US or CT

Question 30

Waterhouse-Friderichsen syndrome tx:

Answer 30

Antibiotics + steroids + hormone supplementation

Question 31

Genetic defect in one of the adrenal enzymes responsible for glucocorticoid production → glucocorticoid insufficiency with or w/o changes in excess mineralocorticoid and/or adrenal sex steroid production Low levels of cortisol = more ACTH → proliferation – enlargement 21-hydroxylase deficiency (CYP21A2 def.) or 11-hydroxylase deficiency 17-hydroxylase deficiency

Answer 31

congenital adrenal hyperplasia

Question 32

21-hydroxylase deficiency – hypoglycemia, salt wasting (low sodium/water, increase in potassium), MORE androgens with masculinization of female genitals, early 2ndary sex characteristics 11-hydroxylase deficiency – HTN! 17-hydroxylase deficiency - poorly developed genitals and secondary sex characteristics in males, lack of sex characteristics in females w/ hypernatremia, hypokalemia, HTN, low aldosterone

Answer 32

congenital adrenal hyperplasia

Question 33

How do you treat congenital adrenal hyperplasia?

Answer 33

Hormonal therapy, early surgical correction of genitals

Question 34

HTN, central obesity, muscle/bone/skin breakdown, easy bruising, abdominal striae, fractures, hyperglycemia, poor wound healing “Moon face” “Buffalo hump”, truncal obesity, edema, amenorrhea Depression Fat trunk + thin extremities Cortisol levels are higher than normal, elevated BG - insulin resistance Polyuria → increased free water clearance (DM with glycosuria may worsen it) Leukocytosis with granulocytosis and relative lymphopenia, hypokalemia Hyperglycemia

Answer 34

Cushing syndrome

Question 35

Supraphysiologic doses of steroid drugs → excessive ACTH secretion, or autonomous cortisol production by adrenal cortex Either: 1) Cushing disease with elevated or normal ACTH levels (from benign ACTH adenoma) (ACTH-dependent) --------------<5mm adenoma in anterior pituitary, women, neoplasm 2) Cushing syndrome with normal or low ACTH levels (ACTH- independent) ---------------Unilateral adrenal tumor causing cortisol secretion

Answer 35

cushing syndrome

Question 36

What are the three initial tests when trying to diagnose cushing syndrome?

Answer 36

1 Lack of cortisol diurnal variation (night cortisol) 2 Reduced suppressibility of cortisol by dexamethasone (test) 3 Increased 24-hour urine free cortisol → At least ⅔ must be positive

Question 37

What would be the steps of cushing syndrome diagnosis

Answer 37

1. late night salivary cortisol, overnight dexamethasone suppression (low dose) (increased cortisol, failure to suppress) confirm with 24 hour urinary cortisol 2. plasma ACTH - <6 = independent, adrenal tumor>6 = dependent with pituitary or ectopic tumors 3. independent - CT, dependent - MRI

Question 38

With an ACTH independent Cushing syndrome, what is the diagnostic step?

Answer 38

CT of the adrenals to detect a mass - likely an adrenal tumor or carcinoma

Question 39

With an ACTH dependent Cushing syndrome, what is the diagnostic step?

Answer 39

MRI -- pituitary gland to demonstrate pituitary, CT scan of chest and abdomen (ectopic sources) + biopsy, whole body imaging (PET/CT) changes with CRH stimulation test confirms pituitary location

Question 40

How do you treat cushing syndrome?

Answer 40

Dependent on underlying cause - treat comorbidities, decrease drug causing this Pituitary cushing’s disease = transsphenoidal surgical resection unsuccessful/unable to do surgery: osilodrostat (may cause adrenal insufficiency, prolonged QT, hirsutism, acne) Spironolactone, eplerenone, dihydropyridine (HTN) Flutamide (hyperandrogenism in women) Cabergoline (hypercortisolemia) Pasireotide (pituitary tumors) Ketoconazole (steroidogenesis)

Question 41

Refractory HTN in youths + middle-aged adults - may be diastolic hypertension Edema (2), hypokalemia (muscle weakness, paresthesia with tetany, headache, polyuria, polydipsia Metabolic alkalosis, hypomagnesemia HTN (headache, flushing) + hypokalemia (proximal muscle weakness, polyuria) + metabolic alkalosis

Answer 41

hyperaldosteronism

Question 42

hyperaldosteronism can be a secondary disease from

Answer 42

HF, cirrhosis

Question 43

MCC = primary aldosteronism - renin-independent – from either bilateral adrenal cortical hyperplasia (men, 50-60), Conn syndrome (women, 30-50), familial Secondary = renin dependent, chronic low BP, high levels of renin with excess aldosterone Genetic testing recommended for patients with confirmed primary aldosteronism by age 20 and those with family history of primary aldosteronism or stroke at a young age <40

Answer 43

hyperaldosteronism

Question 44

Is primary or secondary hyperaldosteronism more common?

Answer 44

primary - renin-independent – from either bilateral adrenal cortical hyperplasia (men, 50-60), Conn syndrome (women, 30-50), familial

Question 45

What should you test for with any of these: Sustained HTN >150/100 x 3 d Resistant to 3 drugs On 4+ anti-HTN drugs Hypokalemia Family history of young onset First degree family hx Presence of adrenal mass Low PRA

Answer 45

hyperaldosteronism

Question 46

Testing – 2 weeks prior requires hypokalemia correction, high NaCl diet, withholding of certain medications (HTN, contraceptives, NSAIDs) For testing, out of bed for at least 2h and seated for 15-60m, proper technique, plasma K must be normal Primary aldosteronism = suppressed PRA, aldosterone >15 (lack of aldosterone suppression) Secondary = high renin and aldosterone 24 hour urine is used to confirm 18-hydroxycorticosterone assay >100 = adrenal aldosteronoma Posture stimulation test - >20 = unilateral, <20 but rises = bilateral

Answer 46

hyperaldosteronism

Question 47

how do you confirm hyperaldosteronism?

Answer 47

biochemical confirmation = thin-section CT scan screening Adrenal vein sampling only if surgery is contemplated to direct surgeon to correct adrenal gland and distinguish between adenoma and bilateral hyperplasia

Question 48

How do you treat hyperaldosteronism?

Answer 48

Unilateral adrenal adenoma = laparoscopic adrenalectomy (2nd tri) or long term medical therapy Bilateral adrenal hyperplasia --Spironolactone most effective --Eplerenone Other anti-HTN = amlodipine, ACE, ARBs finerenone

Question 49

Non-functioning: both glands (rare) → primary adrenal insufficiency with weight loss, fatigue, low BP, darkening of skin, can press on nearby structures with subsequent symptoms Aldosterone = Conn syndrome or primary aldosteronism, hypokalemia (muscular aches, weakness, spasms, numbness, heart palpitations), HTN (treatment-resistant) Cortisol = Cushing syndrome

Answer 49

adrenal tumors

Question 50

85% = non functioning - but others secrete cortisol (fasciculata) or aldosterone (glomerulosa) could also be below

Answer 50

adrenal tumors

Question 51

Aldosterone tumor: serum potassium (low), aldosterone (high), plasma renin (low), sodium (high) → confirm with abdominal CT or MRI Cortisol tumor: free 24 hour cortisol, blood/saliva test at midnight, ACTH plasma, dexamethasone test (unchanged) → confirm with abdominal CT or MRI Patients with adrenal mass >1 cm require diagnostic evaluation → screening for hormone excess, CT of adrenals Screen for pheochromocytoma with plasma fractionated free metanephrines

Answer 51

adrenal tumor

Question 52

How do you treat an adrenal tumor?

Answer 52

Aldosterone: surgery, if bilateral, spironolactone Surgery generally with confirmed hormone excess or suspected malignancy Surgical resection in adrenal incidentalomas >4cm Smaller = observed

Question 53

adrenocorticol carcinomas are rare, and seen in

Answer 53

somatic mutations in TP53, IGF2 overexpression

Question 54

What score is used for the adrenocorticotropic carcinoma?

Answer 54

Weiss score High nuclear grade Mitotic rate (>5/HPF) Atypical mitosis <25% clear cells Diffuse architecture Presence of necrosis, venous invasion, invasion of sinusoidal structures and tumor capsule Requires 3+ suggests ACC

Question 55

Where does adrenocorticotropic carcinomas metastasize to?

Answer 55

liver and lung

Question 56

how do you treat adrenocorticotropic carcinomas?

Answer 56

Complete surgical removal + mitotane, tumor staging, 18-FDG-PET imaging to detect metastasis or local recurrence Prognosis = Ki67 proliferation index

Question 57

Adrenal incidentaloma, HTN crisis + associated cerebrovascular or cardiac complications May be asymptomatic for years – triad of palpitations, headache, and profuse sweating (and HTN) Episodes = anxious, pale, tachycardia, palpitations that last <1 hour PHE - palpitations, headache + excessive sweating

Answer 57

pheochromocytoma

Question 58

pheochromocytoma episodes are precipitated by

Answer 58

surgery, position change, exercise, pregnancy, urination, meds

Question 59

Catecholamine-producing tumors arising from adrenal medulla and secrete epinephrine + norepinephrine – sporadic, inherited (MEN2, VHL disease, NF-1, familial paraganglioma syndromes)

Answer 59

pheochromocytoma

Question 60

What are the diagnostic steps of pheochromocytoma?

Answer 60

1 Biochemical testing – elevated plasma + urine levels of catecholamines and metanephrines are cornerstone of diagnosis ------Most sensitive = plasma fractionated free metanephrines -----------CONFIRM with pheochromocytomas detected by above 2 CT + MRI ----Noncontrast CT of abdomen (NO glucagon, no dye needed), MRI in pregnancy

Question 61

How do you treat a pheochromocytoma?

Answer 61

Lower BP - AVOID BB USE ALONE - firstly use alpha blocker (phenoxybenzamine, doxazosin) + CCBs (nifedipine) (good for longer term, can use both or just this) REMOVE!! But, BP should be maintained for a minimum of 4-7 days or until optimal status is established Always require lifelong follow up, recheck BP + plasma fractionated metanephrine levels, whole body scan 3 months post op