Adrenal Disorders

Question 1

Primary Adrenal Insufficiency: General info, S/sxs, & PE

Answer 1

Aka Addison’s Disease

• Definition: Problem with the adrenal gland → lack of cortisol & aldosterone
  
  • MCC:autoimmune destruction and adrenal metastases
  • Worldwide: TB, secondary infx
• S/sxs:
  
  • hyperpigmentation: d/t increased POMC (proopiomelanocortin) → melanocytes
  • Salt craving b/c body is unable to retain salt
  • hypotension, fatigue
  • Myalgias
  • GI complaints, weight loss
    *

Question 2

Primary Adrenal Insufficiency: Dx & Tx

Answer 2

Aka Addison’s disease: Problem with the adrenal gland → lack of cortisol & aldosterone

• Dx:
  
  • High dose cosyntropin (synthetic ACTH) stimulation test→ cortisol < 18 at 30 AND 60 minutes = PAI
  • 21-OH antibody: autoimmune
  • 17-OH-Progesterone: congenital adrenal hyperplasia
  • Low 8am cortisol (<5 miccrogram/dL), high ACTH (>2x UNL) and no increase in cortisol level after the ACTH stimulation test
  • High potassium
  • Low sodium
  • Glucose: low
• Tx:
  
  • *Will need life-long maintenance therapy*
  • Hydrocortisone PO daily 10-25mg AM, 5-10mg PM or prednisone 5 mg AM, 2.5mg PM
  • Medical Alert Bracelet/ necklace/road ID
  • Stress Dosing:
    
    • minor stress = 2-3x normal dose
    • severe stress = 5-6x normal dose
  • Stress Dose for Illness:
    
    • sick day rules for home (2-3x dose) & hospital
    • emergency injectable: for shock, significant blood loss

Question 3

Adrenal (Addisonian) Crisis

Answer 3

• Definition:
  
  • sudden worsening of symptoms in chronic adrenal insufficiency due to acute lack of cortisol precipitated by a stressful event
    
    • (infx, trauma, surgery, dehydration, salt deprivation, vomiting, diarrhea, sepsis)
• Pathophys:
  
  • normal response to stress = 3x increase in cortisol, but these patients are unable to increase cortisol to meet the demand
• S/sxs:
  
  • Hypotension, Shock & AMS
  • fever
  • Dehydration
  • N/v, anorexia
  • weakness, apathy
  • hypoglycemia, seizure
• Dx:
  
  • hyponatremia, hyperkalemia, hypoglycemia
  • *DO NOT delay tx while diagnostic testing is performed
• Tx:
  
  • Endocrine Emergency → will die if no tx
  • Emergent IV Isotonic Saline 100mL or 5% glucose in isotonic saline
  • Hydrocortisone 100mg IV then same dose q6h x 24 hours or continuous infusion → once stable 50 mg IV

Question 4

Secondary Adrenal Insufficiency

Answer 4

• Definition:
  
  • Insufficient pituitary ACTH production →Lack of cortisol
    
    • aldosterone intact due to renin angiotensin aldosterone system
• MCC: pituitary macroadenoma or a central nervous system tumor
  
  • can be identified on MRI and removed through transphenoidal resection
• S/sxs:
  
  • weakness, fatigue
  • anorexia, weightloss
  • salt craving
  • GI disturbance: N/V/D, abd pain
• Dx:
  
  • Low cortisol, low ACTH, and increase in cortisol after ACTH administration, but no aldosterone deficiency
  • No increase in ACTH after a CRH injection
  • Glucose: low
  • Sodium: low
  • Potassium = normal (no problem in adrenal gland so it can make aldosterone)

Question 5

Tertiary Adrenal Insufficiency

Answer 5

• Definition:
  
  • Insufficient CRH production → decreased cortisol and normal aldosterone
  • MCC: sudden withdrawal of glucocorticoid therapy or after the cure of Cushing disease
• Dx:
  
  • Low cortisol, low ACTH, increase in cortisol after ACTH administration, but no aldosterone deficiency
  • ACTH levels increase after CRH injection

Question 6

Cushing Syndrome

Answer 6

• Etiology:
  
  • exogenous: high-dose glucocorticoid administration (MCC of hypercortisolism
  • endogenous:
    
    • Cushing’s Disease (85% of endogenous cases
    • ectopic ACTH-producing tumor, adrenal neoplasm, pituitary adenoma (corticotroph) → excess secretion of ACTH
• S/sxs;
  
  • HTN
  • Fat redistribution: truncal obesity, “moon face” round shaped face, buffalo hump, supraclavicular fat pad, thin extremities
  • Skin changes:
    
    • facial plethora (redness), thin skin, striae (purple or violaceous), easy bruising, acanthosis nigricans
  • Androgen excess: Hirsutism, oily skin, acne
  • psych disorders
  • cataracts

Question 7

Cushing Disease

Answer 7

• S/sxs:
  
  • HTN
  • Fat redistribution: truncal obesity, “moon face” round shaped face, buffalo hump, supraclavicular fat pad, thin extremities
  • Skin changes:
    
    • facial plethora (redness), thin skin, striae (purple or violaceous), easy bruising, acanthosis nigricans
  • Androgen excess: Hirsutism, oily skin, acne
  • psych disorders
  • cataracts
• Dx:
  
  • ** loss of diurnal variation of cortisol (high throughout the day) → ideal to test at 12 am (low in normal pts) **
  • 24 hour urinary free cortisol (UFC)x2: not for CKD4-5
  • Overnight 1mg dexamethasone suppression test (DSP): measure an AM cortisol level with a dexamethasone level, positive if cortisol level > 1.8 (for cushing syndrome- ACTH independent b/c ACTH is suppressed by dexamethasone → NOT for cushing disease), not for patients taking OCP or estradiol
  • Late-Night Salivary Cortisol x2: not for night shift workers
  • *start with one of these exams & if abnormal, do another one
  • AM ACTH: determine if ACTH-dependent vs independent
  • AM DHEA-S: often low in hypercortisolism
• Tx:
  
  • Perform screening (see dx) and refer to endo
  • *tx depends on source:
    
    • pituitary: surgery, radiation, meds
    • adrenal: surgery, meds
    • ectopic: surgery, chemo

Question 8

Pheochromocytoma

Answer 8

• definition:
  
  • catecholamine secreting adrenal tumor which secretes norepi & epi autonomously and intermittently
  • 90% = benign, 10% = malignant
  • Associated with neurofibromatosis type 1, MEN 2A/2B, and Von Hippel-Lindau Disease
• etiology:
  
  • women = men, but women have more symptoms
• S/sxs:
  
  • Episodic: 5Ps →
    
    • 1.Pressure (HTN)
    • 2.Pain (headache)
    • 3.Perspiration
    • 4.Palpitations (tachycardia)
    • 5.Pallor
  • TRIAD: HA, diaphoresis, tachycardia
• Dx:
  
  • 24-hour catecholamines (in urine) including metabolites (metanephrine and vanillylmandelic acid)
  • MRI or CT of abdomen to visualize catecholamine secreting adrenal tumor
• Tx:
  
  • complete adrenalectomy
  • Preoperative non-selective alpha-blockade: phenoxybenzamine or phentolamine x 7-14 days followed by beta blockers to control HTN
  • ** Refer to Endo **
  • DO NOT initiate therapy with beta blockade to prevent unopposed alpha constriction during catecholamine release triggered by surgery, which could lead to life-threatening HTN

Question 9

When to consider Pheochromocytoma

Answer 9

• young pts with HTN
• family hx of pheochromocytoma
• radiologic incidentalomas
• shock after anesthesia, surgery, invasive procedure
• other: cardiomyopathy

Question 10

Hyperaldosteronism

Answer 10

• Primary:
  
  • etiology:
    
    • aldosterone-producing adenoma: 35%
    • bilateral idiopathic hyperplasia: 60%
    • unilateral idiopathic hyperplasia: 2%
  • Most common cause of endocrine HTN!!!!!!!!!!!! Prevalence: 5-10%
• Secondary:
  
  • Pathophys: increased renin → increased aldosterone via RAAS
  • etiology:
    
    • renal artery stenosis, renal artery hypoperfusion
• S/sxs:
  
  • HTN: HA or facial flushing
• When to consider testing for Primary Hyperaldosteronism:
  
  • HTN & hypokalemia
  • Resistant HTN (3+ drugs)
  • Adrenal incidentaloma + HTN
  • onset of HTN at young age <30
  • severe HTN (160/100)
  • any consideration of secondary HTN
• Dx of primary:
  
  • plasma aldosterone concentration (PAC): high (>15)
  • plasma renin activity (PRA): low (<1)
  • PAC-PRA ratio: > 20ng/dL
  • Potassium: usually normal, may be hypokalemic (but indicates very far along)
• Tx:
  
  • refer to endo for further testing & eval →
    
    • oral salt loading test or IV saline infusion test
      
      • if hyperaldosteronism is established then adrenal CT or MRI may be done
  • Spironolactone: blocks aldosterone from binding to mineralocorticoid receptors in the renal CD (increases aldosterone level since it is completing with spironolactone for the receptor, but lower BP since it blocks the effect of aldosterone)
  • Unilateral Adrenalectomy: if adrenal vein sampling lateralizes site of overproduction

Question 11

Process of Diagnosing an Adrenal Incidentaloma

Answer 11

1. CT imaging without intravenous contrast = best initial study
2. if adrenal mass is < 10 Hounsfield Units = dx of adrenal adenoma (lipid-rich adenoma)
   
   1. >40 HU = Malignant!
3. If adrenal mass is > 10 HU then do CT with IV contrast
   
   1. speed of & % washout of IV contrast from an adrenal nodule can be quantified
      
      1. benign lesions generally have > 50% washout of IV contrast
      2. adenomas washout IV contrast rapidly (<15min)
      3. Equivocal CT → MRI = next step

Question 12

Define Hirsutism

Answer 12

Excess body hair often due to excess androgens

seen in Cushing’s Disease