Digital PharmD

Informatics in Pharmacy

Endocrine Disorders

Thyroid Disorders: Hyperthyroid

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  • Graves Disorder, pituitary adenomas, toxic goiter, drug-induced (excess thyroid hormone, amiodarone)
    elevated free T4, suppressed TSH
  • Can use radioactive iodine update study to diagnose. Uptake is elevated if thyroid is excessively secreting T4 or T3: Graves disease, TSH-secreting adenoma, toxic adenoma, multinodular goiter
  • Clinical presentation: weight loss, lid lag, heat intolerance, goiter, fine hair, tachycardia, nervousness, menstrual disturbances, sweating, exophthalmos
  • Normal TSH: 0.4-4 (clinically significant if less than <2.5).

Treatment:

  • Ablation is the treatment of choice
  • Can use meds in patients waiting for ablation or those who are not surgical candidates
    • propylthiouracil 100 mg TID, max 400 mg TID, may reduce to 50 mg when euthyroid.
      • PTU may cause hepatotoxicity. Routine liver tests suggested.
    • methimazole – preferred unless pregnant, 10-20 mg daily up to 40 mg TID, may reduce to 5-10 mg daily once euthyroid
    • Both drugs can cause a rash, arthralgias, fever, agranulocytosis early in therapy
    • Max effect can take 4-6 months. Remission only 20-30%.  Usually, need 12-18 month trial. Monitor every 1-3 months
  • Can use non-selective Beta-blockers (primarily propranolol, may use nadolol). Use mostly for symptom relief or acutely during Thyroid storm.
  • Iodines: Lugol solution has a limited efficacy of 7-14 days.

Thyroid Storm:

  • AVOID NSAIDS IN THYROID STORM
  • Life-threatening: caused by trauma, infection, antithyroid agent, withdrawal, severe thyroiditis, post-ablative therapy

Treatment:

  • Ablation is the treatment of choice
  • propylthiouracil – 500-1000 mg, then 250 mg every 4 hours
  • methimazole – 60-80 mg daily
  • Iodine therapy 1 hour after PTU
  • Beta-blocker therapy: propranolol or esmolol for symptoms
  • APAP for fever. No NSAIDS.  They displace protein-bound thyroid hormone
  • Prednisone 300 mg IV, then 100 mg every 8 hours.

You can use PTU in the first trimester of pregnancy (causes hepatotoxicity) and methimazole at the start of 2nd trimester (can cause embryopathy in first)

Thyroid Disorders: Hypothyroid

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Hypothyroid Disorders:

  • Hashimoto’s disease:
    • Most common. Iodine deficiency most common cause worldwide.  Can also be due to pituitary insufficiency or drug-induced (amiodarone, lithium).
    • Diagnose with low free T4, elevated TSH, thyroid antibodies
    • Symptoms: cold intolerance, dry skin, fatigue, weight gain, bradycardia, slow reflexes, coarse skin and hair, periorbital swelling, goiter, menstrual irregularities
    • Levothyroxine is the drug of choice at 1.6 mcg/kg per day.  If cardiovascular disease, 12.5-25 mcg/kg per day. Dose on empty stomach apart from other meds. Increase or decrease in 12.5-25 mcg/day increments.
    • May take 4-8 weeks.
    • Adverse effects: hyperthyroidism, tachyarrhythmias, angina, myocardial infarction, some risk of fracture
      Liothyronine, liotrix and desiccated thyroid not recommended

Myxedema Coma

  • Severe and life-threatening hypothyroid
  • Precipitating causes: trauma, infections, heart failure, meds (sedatives, narcotics, anesthesia, lithium, amiodarone).  “Coma” is a misnomer, it usually doesn’t cause coma.
  • Treatment:
    • IV thyroid: T4 100-500 mg loading dose followed by 75-100 mcg/day. Change to PO when tolerated.
    • Antibiotic therapy for common causes. Some advocate broad spectrum.
    • Corticosteroids: Hydrocortisone 100 mg every 8 hours

Adrenal Disorders

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Acromegaly – bromocriptine or octreotide
Hyperprolactinemia – surgical resection, cabergoline or bromocriptine

Cushings Disease-

  • Diagnosed by a dexamethasone suppression test or 24-hour urinary cortisone test.
  • Symptoms: central obesity, peripheral fat, myopathies, osteoporosis, back pain, diabetes, hirsutism, hypertension
  • Treatment:
    • Surgical resection if possible
    • Pasireotide: 0.6-0.9 mg BID subQ (adverse effects: hypoglycemia, hypocortisolism, diarrhea, nausea, gallstones, headache, bradycardia)
    • Ketoconazole: Hinders cortisol production, 200 mg BID up to 400 mg TID (adverse effects: gynecomastia, abdominal discomfort, increased LFTs)
    • Mitotane: 500-1000mg daily
    • Etomidate: 0.3 mg/kg IV
    • Metyrapone: 500 mg TID

Primary Aldosteronism-

  • Spironloactone is drug of choice.  25-50 mg/day (adverse effects: hyperkalemia, gynecomastia, abdominal discomfort)
  • Eplerenone and amiloride are alternatives

Hyposecretory Adrenal Disorders or “Addison’s Disease”-

  • Hydrocortisone: 15 mg/day
  • Fludrocortisone (replaces mineralcorticoid): 0.05-0.2 mg/day
  • Dehydrocopiandrosterone: 25-50 mg/day for libido in women

Glucocorticoid Equivalent Dosing:

GlucocorticoidDose
Cortisone25
Hydrocortisone20
Prednisone5
Prenisolone5
Triamcinolone4
Methylprednisone4
Dexamathasone0.75

PCOS:

  • Improve fertility with clomiphene citrate or gonadotropin
  • Symptoms improve with estrogen and progestin combination
  • Spironolactone can help with hirsutism

Obesity

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BMI Defined:

  • 18.5-24.9 – Normal
  • 25.0-2939 – Overweight
  • 30-34.9 – Class I Obesity
  • 35-39.9 – Class II Obesity
  • 40 or greater – Class III Obesity

Treatment:

  • Orlistat – AE: Hepattoaxity and kidney stones
  • Lorcaserin: AE: headaches, dizziness, nausea and vomiting, dry mouth, memory or attention problems, hypoglycemia.  DC if 5% weight not lost in 12 weeks.
  • Phentermine: AE: Dry mouth, paresthesias, constipation, dysgeusia
  • Bupropion/naltrexone: AE: Nausea and vomiting, dizziness, insomnia. DC if 5% weight not lost in 12 weeks.
  • Liraglutide: Different dose than for diabetes: 0.6 mg daily, target to 3 mg.  DC if 4% weight not lost in 16 weeks.

Diabetes

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This is a very simply rundown of diabetes.  The diabetes information on the ambulatory care board exam is more complex.  Knowing the basics of how to diagnose diabetes, goals, how to change insulin and which drugs not to use in which patients is probably enough for the BCPS.

Pre-Diabetes

  • Fasting Plasma Glucose: 100-125 mg/dl
  • 2-hour plasma glucose test: 140-199 mg/dl
  • A1C = 5.7-6.4%

Diagnostic Criteria:

  • Fasting plasma glucose >=126 mg/dl
  • Casual plasma glucose >= 200 mg/dl
  • 2-hour post load glucose >= 200 mg/dl
  • A1C >= 6.5%
  • *Must have 2 positive tests before diagnosis.
  • C-peptide can be a sign of type 2 diabetes.

Goals:

  • A1C < 7.0 (some sources say 6.5).  If at goal, measure every 6 months, if not measure every 3
  • FPG or pre-meal = 80-130 mg/dl
  • Post-prandial (1-2 hours after meal): <180 mg/dl
  • Acute complications: Hypoglycemia, DKA, hyperglycemia, hyperosmolar non-ketonic syndrome
  • Long-term complications:
    • microvascular: retinopathy, nephropathy, neuropathy
    • macrovascular: cardiovascular disease, cerebrovascular disease, peripheral vascular disease

Gestational Diabetes:

  • Fasting plasma glucose of 92 or greater or 1-hour OGTT >180, 2-hr >153
  • Goals are different: FPG <95, 1-h PP <140, 2 h-pp <120

Insulin Therapy Management:

  • Estimate total daily insulin requirement (0.3 to 0.6 unit/kg/day).  May need less at start of therapy (honeymoon phase)
  • Old school: give 2/3 dose before morning meal (2/3 as NPH, 1/3 as regular) and 1/3 before evening meal (2/3 as NPH, 1/3 as regular)
  • Newer method: Give 50% as basal insulin (determir, glargine or degludec) and 50% as fast acting (aspart, lispro, glulisine) three times a day before meals.

PO Medications:

  • Metformin is drug of choice.  Reduces A1C by 1-2 %. Do not give if CHF or increased CR (lactic acidosis is possible).
  • Sulfonylureas: Can cause hypoglycemia.  Reduce A1C by 1-2% (glyburide, glipizide, glimepiride).
  • Meglitinides: They are basically rapid acting sulfonylureas. Can also cause hypoglycemia. Reduce A1C by 0.5-1.5% (repaglinide or nateglinide)
  • Thiazolidinediones: contraindicated in hepatic impairment and class III/IV heart failure.  Reduces A1C by 0.5-1.4%  Also reduces HDL (pioglitazone and rosiglitazone.
  • DPP-4 Inhibitors: Reduce A1C by 0.5-0.8%.  No hypoglycemia. Can cause respiratory infections, UTI, joint pain, headache, angioedema, Stevens-Johnson, pancreatitis (sitagliptin, saxagliptin, linagliptin, alogliptin).
  • SGLT-2 Inhibitors: Reduce A1C by 0.3-1.0%.  Can cause UTI, hypotension (canagliflozin, dapaliflozin, empagliflozin).

Ketoacidosis

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Ketoacidosis is more common in type 1 diabetes than in type 2.  The goal treatment is to stop ketosis, not to normalize glucose.

Common symptoms: polyuria, polydipsia, vomiting, dehydration, weakness, altered mental status, coma, abdominal pain, Kussmaul respirations, tachycardia, hyponatremia, hyperkalemia

Treatment:

  1. Fluid replacement: start with 0.45-0.9% NS, change to 5% dextrose or dextrose containing saline when glucose is less than 200 mg/dl.
  2. Correct serum sodium(for every 100mg/dL increase over 100 in glucose, increase sodium by 1.6).  Usually, 0.9% NS, do not rapidly correct sodium ever.
  3. If potassium is less 3.3 mEq/L, replace KCl before giving insulin.
  4. Insulin: 0.1 unit/kg bolus and then infusion ONLY if KCl is greater than 3.3 mEq/L.  Keep glucose 150-200 mg/dl until DKA resolves.
  5. If pH <= 6.9 – Give bicarb over 1-2 hours
  6. DKA is resolved when serum glucose is less than 200 and 2 of the following:
    Venous pH >  7.3
    Bicarb 15 mEq or greater
    Anion gap of 12 mEq or less

If you prefer charts, here’s one I downloaded for my notes.

Diabetes Insipidus

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Decreased anti-diuretic hormone (ADH) production or lack of ADH effect.
Symptoms: polydipsia, polyuria, lethargy, and confusion
Treatment: desmopressin, chlorpropamide, carbamazepine for central DI, thiazide, low sodium diet and indomethacin in nephrogenic DI.