CAM 2013: Exam One

partial/complete destruction of adrenal gland (primary adrenal insufficinecy)

• Can be precipitated by (Keto, Phen, Pheno, Rif)
•      Ketoconazole
•      Phenytoin
•      Phenobarbital
•      Rifampin

• S/S
•      increased ACTH causes increased pigmentation
•      weight loss, fatigue/weakness, hair loss, depression, ab pain

• Labs
•      hypnatremic
•      hyperkalemia
•      elevated BUN & sCr
•      metabolic acidosis
•      increased ACTH; decreased aldosterone

• Glucocorticoid therapy:  cortison/hydrocortisone
•      SE:  wt gain, edema, HTN, hypokalemia, insomnia, DM, electrolyte imbalance, GI upset
•      Monitor sxs q 6-8 wks
•      ADE w/ prolonged use:  iatrogenic Cushing's (weight gain, moon face, buffalo hump), increased infection risk, edema, electrolyte imbalance

• Mineralcorticoid therapy:  fludrocortisone
•      SE:  same as glucorticoids + excitability
•      Monitor sxs, electrolytes, BP

• Supplement:  DHEA
•      positive effects on wellbeing & mood
•      reserved for patients in which G and M are not working; limited efficacy
•      Monitor:  lipids, breast & prostate cancers

cause:  exogenous steroid use/hypothalamic-pituitary tumor

Presentation:  normal to low ACTH causing hypopigmentation; ALD secretion preserved

Tx:  G/M therapy

Presentation:  weakness, dizziness, weight loss, ab pain, myalgia, tachycardia

Labs:  hyperkalemia, hypoglycemia, hyponatremia, hypotension leading to shock

Causes (CISTS):  chronic exogenous CS use, infection, stress, trauma, surgery

• hydrocortisone via rapid infusion, then PO taper
• fluid replacement
• supportive therapy

usually part of a larger insufficency such as Addison's

Presentation/Labs:  hyponatremia, hyperkalemia, hypercholremic metabolic acidosis

Fludrocortisone

excessive secretion of androgens from adrenal gland via an androgen secreting tumor

Sxs:  hirsutism, voice deepening, acne, increase muscle mass, menstrual abnormality, lose female figure, hair recession

Glucocorticoids to suppress HPA-axis

Etiology can be genetic, med related, adrenal/ovary overproduction

Tx:  cosmetic approaches, eflonithine HCl cream, glucocorticoid suppression therapy

Monitor:  glucose, electrolytes, growth and development

Counseling:  don't stop abruptly; increase dose during stress; take second dose 6-8 hours after first dose which is taken in the AM

• HPA-axis suppression problem:  use shortest duration, taper slowly, QOD therapy
• Osteoporosis:  consider Ca²⁺ or BPh; NOT QOD therapy
• Weight gain:  monitor and use shortest possible duration

adrenal cortex abnormality

• 65% of cases is bilateral adrenal hyperplasia (BAH)
• 30% are aldosterone-producing adenoma (APA, Conn's Syndrome

Clinical presentation:  hypernatremia (HTN), hypokalemia (muscle weakness/fatigue/arrythmias), low plasma renin, increased ALD, polydipsia, polyuria, metabolic alkalosis

First line = meds

• Spironolactone
•      MOA:  ALD receptor antagonist
•      salicyclates increase elimination of active metabolite
•      SE:  gynecomastia, menstrual irregularites, GI discomfort, impotence

Eplerenone

Amiloride

Surgery is last line

First line = surgery:  laparoscopic resection of adenoma

Last line is meds

Causes:  extra-adrenal factor, RAAS, excessive potassium, OC use, pregnancy

Tx Goal:  correct extra-adrenal issue, but use spironolactone unitl etiology found

most common cause is exogenous adminstration of cortisol

• endogenous overproduction
•      90% ACTH-dependent hypercortisolism via ACTH- secreting pituitary tumor (Cushing's) or ectopic ACTH secretion

Presentation:  wt gain, central obestiy, moon face, buffalo hump, brusing, stretch marks, hirsutism, osteoporosis, muscle weakness, HTN, hypokalemia, edema, DM, depression, decreased WBC

Establish presence of hypercortisolism by 24-hour urinary free cortisol secretion and dexamethasone overnight test  (Normal cortisol:  10-100 mcg)

• Establish cause and location of problem
•      low ACTH --> ACTH-independent adrenal tumor
•      normal/high ACTH --> ACTH dependent

• obestiy
• alcoholism
• depression
• acute illness

selective removal of pituitary corticotrope tumor

• Other options:
•      Bilateral adrenalectomy - take out adrenal gland
•      Adrenal adenoma resection - take out portion of adrenal gland that's not working

• Metyrapone
• Aminoglutethimide
• Ketoconazole
• Etomidate 
• Mifepristone
• Mitotane 
• Cyproheptadine
• Pasiretoide

• MOA:  inhibits cortisol production     
• SE:  hypotension, hair growth, voice deepening

• MOA:  suppresses adrenal cortex     
• Should NOT use alone --> use metryapone to allow for lower doses     
• SE:  severe sedation

• inhibits adrenal & gonadal steroidogenesis  
• potent inhibitor of 17, 20 desmolase and 17α-hydroxylase     
• at high doses, inhibitor of CE --> pregnenolone (aminoglutethimide) and DHEA --> androsternedione (3β-dehydrogenase)    
• SE:  low cortisol & hepatoxicity

• MOA unknown; parenteral use only     
• SE:  myoclonus (muscle twitching)

• MOA:  competitve antagonist of cortisol effects on GLU metabolism and increases circulating cortisol concentration     
• SE:  edema, HTN, fatigue, HA, hypokalemia, N/V

• MOA:  decreases production of cortisol & alters steroid metabolism
• CNS side effects

• MOA:  decreases ACTH secretion     
• SE:  sedation, increased appetite

GHIH (somatostatin) analog that inhibits ACTH secretion and decreases cortisol

SE (HAD No CHF):  HA, ab pain, diarrhea, nausea, cholethiasis, hyperglycemia, fatigue

• Classic Triad:  HA, sweating, palpitations
• persistent HTN
• Sxs:  anxiety, chest pain, polyuria, polydypsia, heat intolerance

Genetic Causes:  autosomal dominant multiple endocrine neoplasia (MEN) syndrome, Von Hippel-Lindaw (VHL) disease, family history

Med Causes:  glucagon, histamine, contrast dyes, metoclopramide, TCAs BB, opiates

• chromogranin A
• neuropeptide Y
• biogenic amines - Epi, Norepi, dopamine

TOC:  complete tumor removal

Preoperative tx:  phenoxybenzamine - alpha blocker to maintain BP of 160/90; may add another BB for tachycardia (propanolol, which shouldn't be used alone)

Postop tx:  maintain BP

Malignant Pheochromocytoma:  tumor mass reduction +/- alpha blockers +/- chemo +/- radiation

Monitor:  BP, catecholamines q 6-12 mos, sxs of excess catecholamines