Anne Rosenthal, M.D.
Jacek Skarbinski, M.D.
Umesh Masharani, M.D.
Hyperthyroidism and thyroid storm
1. Etiologies: Hashimoto’s, iodine deficiency, drugs (lithium, iodide, propylthiouracil, sulfonamides, amiodarone), infiltrative disease (e.g. sarcoid), genetic enzyme defects, after therapy for other thyroid disease, and secondary to hypopituitarism.
2. Signs and symptoms: early symptoms and signs include fatigue, cold intolerance, constipation, dry skin, thinning hair, delayed DTRs; late symptoms and signs include slow speech, brawny edema, hoarseness, weight change (usually gain), puffy face/eyelids, thickened tongue, bradycardia, hypotension, hypothermia.
3. Lab: T4 low to normal, TSH increased (in pituitary disease the TSH will be normal or low), increased cholesterol, increased transaminases, increased CK, increased prolactin, hyponatremia, hypoglycemia, macrocytic anemia. Anti-thyroglobulin and anti-thyroperoxidase antibodies are often positive.
4. Complications:
· Coronary artery disease.
· CHF precipitated by vigorous thyroid replacement
· Increased susceptibility to infection
· Organic psychosis
· Myxedema coma: severe hypothermia, hypoventilation, hyponatremia, hypoxia, hypocapnia, hypotension, convulsions, confusion ® lethargy ® coma; often induced by underlying infection, cardiac, respiratory, or CNS illness, cold exposure, illicit drug use
5. Therapy:
· Levothyroxine: start low, especially in the elderly or those with coronary artery disease and go slow (don’t precipitate atrial fibrillation or MI). It takes 4-6 weeks for TSH levels to reflect effects of therapy.
· Myxedema coma (endocrine consult): levothyroxine 300-400 mcg IV load, then daily 50-100 mcg IV, consider adrenal insufficiency, treat underlying precipitant
1. Etiologies: Graves disease (most common, diffuse enlargement of thyroid,± exophthal, ± dermopathy, other autoimmune disorder, thyroid-stimulating immunoglobulin (TSI) is positive in 80%), autonomous toxic adenomas (single – Plummer’s disease, multiple – toxic multinodular goiter), subacute thyroiditis (viral infection, hyperthyroid then hypothyroid), Jodbasedow (iodine-induced), thyrotoxicosis factitia, struma ovarii (dermoid tumors), pituitary TSH secreting adenoma, early Hashimoto’s, amiodarone induced, pregnancy (hCG activation), trophoblastic tumors (hCG activation).
2. Signs and symptoms include: restlessness, heat intolerance, diaphoresis, diarrhea, weight change (usually loss), palpitations, lid lag, tachycardia, atrial fibrillation, tremor, moist skin, hyperreflexia, fine hair, heart failure, osteoporosis.
3. Lab: FT4, T3 increased, TSH decreased except in pituitary disease, ESR increased in subacute thyroiditis, TSH-receptor antibodies in Graves disease.
4. Complications:
· Atrial fibrillation with rapid ventricular response.
· Hypercalcemia, osteoporosis, nephrolithiasis.
· Thyroid storm: delirium, tachycardia, vomiting, diaphoresis, dehydration, hyperthermia; often induced by illness, surgery, or iodine administration.
5. Therapy:
· Propranolol for symptoms (blocks adrenergic effects and conversion of T4 ® T3).
· Thioureas (methimazole, propylthiouracil – blocks hormone synthesis) can be used as treatment for up to 18 months (high rate of recurrence) or to prepare for definitive treatment (surgery or I-131).
· Radioactive iodine I131 or surgery for definitive therapy.
· Thyroid storm (endocrine consult): propranolol q 4-6 hours until HR <100 (use cautiously in heart failure), PTU 250 mg q 6 hours (can be given rectally if NPO), hydrocortisone 50 mg IV q 6 hours x 48 hrs (blocks peripheral T4 ® T3 conversion). If severe consider iodine after initiation of other medications to decrease hormone release (KI 10 drops bid).
1. TSH alone is usually an adequate screening test for outpatients (unless you suspect pituitary disease); for hospitalized patients get a full thyroid panel.
2. If TSH is abnormal, get FT4 and T3.
3. When interpreting TFT's:
· TSH assay precision is higher than precision for FT4 and T3.
· In a hospitalized patient, remember to think about sick euthyroid syndrome (SES). The TFT's can be varied but the most common variant is low TSH, low or normal FT4. Sick euthyroid usually causes only mild perturbations in thyroid function tests: markedly abnormal values are usually not due to SES.
4. IV levothyroxine dosing is half the PO dose.
1. Many possible etiologies:
· Primary adrenal insufficiency (AI) or Addison’s disease – lesions of bilateral adrenal glands: autoimmune adrenalitis (often accompanied by other autoimmune diseases), TB, fungus, CMV, malignancy, hemorrhage, infiltrative disease, drugs that impair steroidogenesis (e.g. ketoconazole).
· Secondary AI – loss of trophic influence of ACTH from pituitary: exogenous steroids, pituitary adenoma, hypothalamus or pituitary mets, ischemic necrosis / pituitary apoplexy, infiltrative pituitary disease, empty sella.
2. Signs and symptoms include:
· Chronic: weakness, fatigue, malaise, anorexia, weight loss, abdominal discomfort, nausea, hypotension. With primary AI: hyperpigmentation (increased MSH, ACTH), hyponatremia, hyperkalemia.
· Acute (from rapid destruction of adrenal tissue or acute illness in a patient with compensated chronic AI): hypothermia, hypoglycemia, hypotension, ¯ responsiveness to pressors, AMS.
3. Lab: AM cortisol greater than 20 mcg/dl reflects intact adrenal function. If this is the case, there is no need to proceed to a cosyntropin stimulation test. ACTH: increased in primary AI, decreased in secondary AI.
4. Therapy:
· Primary AI: requires near-total destruction of adrenal gland; must replace both glucocorticoid (20-30 mg hydrocortisone qd = 5 mg prednisone qd = 0.5 mg dexamethasone qd) and mineralocorticoid (0.05-0.20 mg fludrocortisone qd).
· Secondary AI: loss of ACTH effect but normal mineralocorticoid activity; replace only glucocorticoid, as above.
· If patient is very unstable, “stress doses” of hydrocortisone = 100 mg IV q 8 hrs, with taper over about 5 days. For common stressors (mild-moderate illness, surgery), doses of 25-100 mg IV/PO qd generally adequate, with rapid taper once stress resolved.
Oelkers W. Adrenal insufficiency. N Engl J Med. 1996 Oct 17;335(16):1206-12.
Coursin DB, Wood KE. Corticosteroid supplementation for adrenal insufficiency. JAMA. 2002 Jan 9;287(2):236-40.
1. Screens for primary and secondary adrenal insufficiency. Must be off glucocorticoids for 24-48 hours. If you suspect adrenal insufficiency in an unstable patient, give steroids and test later. Decadron is the one option for "stress-dose steroids" that will not interfere with the serum cortisol test later.
2. Protocol:
1. Type 1 and type 2 patients have different insulin requirements. Type 1 patients require less insulin (about 0.5 U/kg/day) than type 2’s (1.0 U/kg/day and up depending on resistance). Remember type 1 patients need basal insulin even when NPO (i.e. approximately 1/2-1/3 their usual dose).
2. Think about basal insulin levels with long acting insulins such as NPH, glargine, or ultralente.
3. You can create a sliding scale for type 2 diabetics with NPH at bedtime and regular or lispro insulin sliding scale before meals. Type 1 diabetics need a basal insulin level using NPH BID and regular sliding scale before meals.
4. Type 1: type 1 patients require less insulin than type 2’s. They need basal insulin (even when NPO) to prevent DKA and extra insulin with each meal. If patients are carbohydrate counting, allow patient to help determine meal insulin bolus. Sample type 1 pre-meal scale along with basal insulin (e.g. NPH 8 U SQ BID). Again, this scale is not intended for bedtime insulin coverage or patients that are not eating.
|
FBS |
TID before meals |
|
FBS |
TID before meals |
|
< 80 |
no insulin |
|
201-250 |
4 U Reg or lispro SQ |
|
80-120 |
1 U Reg or lispro SQ |
|
251-300 |
5 U Reg or lispro SQ |
|
121-160 |
2 U Reg or lispro SQ |
|
> 300 |
6 U Reg or lispro SQ |
|
161-200 |
3 U Reg or lispro SQ |
|
|
|
5. Type 2: for an average type 2 patient on orals meds as an outpatient consider the following sliding scale pre-meals (do not use these levels of insulin at bedtime) along with 5-10 units NPH qhs:
|
FBS |
TID before meals |
|
<100 |
no insulin |
|
100-150 |
2 U Reg or lispro SQ |
|
151-200 |
4 U Reg or lispro SQ |
|
201-250 |
6 U Reg or lispro SQ |
|
251-300 |
8 U Reg or lispro SQ |
|
>300 |
10 U Reg or lispro SQ |
6. Sliding scale advice:
· For BG < 80 mg/dl, give a patient that can take PO’s 20 grams of fast acting carbohydrate (6 oz. fruit juice or soda, 4 glucose tabs, or 12 oz. low fat milk). If the patient can not take PO’s, give 25 cc of D50 IV push. Check the fingerstick glucose q15 minutes until BG > 100 mg/dl.
· May need to decrease doses in renal failure (insulin is not as rapidly cleared).
· May need to increase doses for patients who are septic or treated with steroids (insulin resistance).
· Patients on TPN/PPN may need an insulin drip (insulin can be added to TPN).
· Mild hyperglycemia is better than hypoglycemia.
· Do not discharge patients on insulin sliding scales; instead, find an appropriate outpatient regimen before discharge.
7. Oral hypoglycemics in the hospital:
· If a patient is to be NPO sulfonylureas should be held to prevent hypoglycemia, thiozolidines may be continued.
· Hold metformin when patients are admitted since it's hard to predict who may be getting a large IV contrast load at some point (and metformin plus IV contrast may equal renal failure and lactic acidosis).
· Many patients are placed on an insulin sliding scale in house as patients' PO intake in the hospital is unpredictable and rarely the same as their usual diet. Once patients are stabilized/awaiting placement, it usually makes sense to put them back on their oral agents.
1. Occurs as initial manifestation of type 1 DM, in setting of increased insulin requirement in type 1 or type 2 DM with stressor (infection, infarction, incision (surgery), intoxication, etc.), insulin pump failure, or poor compliance. Work-up and treat precipitating cause and if a patient is admitted with DKA as their first presentation with diabetes, make sure they get adequate diabetic teaching before discharge. Mortality just under 5%.
2. Signs and symptoms: preceded by polyuria, polydipsia, progresses to nausea/vomiting, lethargy ® stupor ® coma, deyhydration, tachypnea, “fruity” odor of acetone, hypotension, tachycardia, mild hypothermia (normal or increased temperature suggests infection), abdominal pain.
3. Lab: key to diagnosis, as the name suggests, is ketones and acidosis, also hyperglycemia (DKA can occur with glucoses as low as 250-300), hyperkalemia (from acidosis and hypovolemia despite total body depletion due polyuria and vomiting), leukocytosis with or without infection.
4. Diagnostic criteria:
|
|
DKA |
Hyperosmolar Coma |
|
Serum HCO3 |
Low ( < 15 meq/L) |
Normal or slightly low |
|
pH |
> 7.3 |
|
|
Blood glucose |
< 800 mg/dL & can be normal |
Often > 800 mg/dL |
|
Serum Ketones |
> 5 mmol/L |
< 5 mmol/L |
|
Urine Ketones |
Large |
Small |
5. Relevant formulas:
· Calculated osmolality: 2 (Na + K) + glucose/18 + BUN/2.8. Coma occurs when the calculated osmolality > 340.
6. Treatment principles: The goal is to close the anion gap, not to reduce hyperglycemia. Usually, the serum glucose will normalize before the gap is closed. Note that the anion gap is a better indicator of patient's status than ketones, as the lab test for ketones at most of the hospitals misses betahydroxybutyrate (the primary ketone in DKA).
7. Fluid and electrolyte management:
· Fluids: assume about 10% dehydration (100 ml/kg). Give 1 liter/hour for 4 hours and then 250-500 cc/hour for the next 2-4 hours; then 100-250 cc/hour. Correct fluid deficit over 36-48 hours. Give NS initially; give ½ NS if corrected Na is >150 meq/l. Change to D5NS or D5½NS when BG < 200 mg/dl. During therapy, hyperchloremic non-gap acidosis may develop as ketones cleared and bicarbonate deficit replaced with chloride ions from saline.
· Potassium replacement: potassium will initially be falsely elevated due to acidosis and hypovolemia, but can drop quickly. Wait until potassium is 4.0-4.5, then begin replacement aggressively: e.g. add 20 mEq KCl to each liter of fluid (you may also need to give potassium orally or through a different line). Max KCl administration rate: central line – 20 mEq/hour, peripheral line – 10 mEq/hour.
· Phosphate replacement: generally replacement not recommended despite anticipated fall during days 1 and 2.
- may administer only if serum PO4 < 1 mg/dL
- Use sodium phosphate (3 mmol PO4/cc; 4 mEq Na/cc).
- Give 0.3-0.6 mmol PO4/kg/day. Give phosphate ordered in millimoles over 6 hours. Do not use if patient has hypercalcemia or renal failure. Monitor Ca, PO4, and Na.
· Magnesium: administer only if serum Mg < 1.8 mg/dL or if patient has tetany.
· Bicarbonate: generally replacement not recommended. May administer only if pH < 7.0; give 50 mEq NaHCO3 in ½ NS with KCl 20 meq/L over 1 hour. The non-gap acidosis that occurs in the recovery phase of DKA generally does not require management.
8. Insulin:
General guidelines for adjusting insulin infusion rate:
· When BG > 200 mg/dl:
- If BG has decreased by < 50 mg/dl in the one hour period, double the insulin drip rate. Note that this is a general recommendation to cover patients who are insulin resistant; some patients may require less of an increase.
- If BG has decreased by > 200 mg/dl in the 1 hr period, decrease the insulin drip rate by 50%.
· When BG < 200 mg/dl: Usually, starting the insulin infusion rate at approximately 2-4 units/hour is adequate. Generally, the insulin infusion rate should be 1 unit/hour for every 100 cc/hour of D5½NS (e.g., if D5½NS is set at 200 cc/hour, then the insulin infusion rate should be 2 units/hour).
· You can change to SQ insulin using a modified sliding scale once the anion gap closes. Some points to remember about this are:
- Divide the amount of insulin the patient would be getting on the insulin drip into NPH and regular, using the following formula:
a. 2/3 as NPH, 1/3 as regular
b. 2/3 in the morning, 1/3 in the evening
- This is also a good way to determine a home regimen for a newly diagnosed diabetic who has been on a sliding scale in the hospital.
- Only discontinue the insulin drip 1-2 hours after starting the sliding scale to prevent rebound hyperglycemia and DKA. For instance, once the anion gap is closed and the patient is eating, give the first dose of NPH about an hour before their meal, then let them eat, then discontinue the insulin/D5 drips about an hour later.
9. Sample orders:
· Diet: NPO
· Initial laboratory work (if not done in Emergency Department):
- CBC, Na, K, Cl, CO2, Glucose, BUN, Creatinine, Ca, PO4, Mg, Serum Ketones, Serum Osmolality, urinalysis, ABG.
· Subsequent laboratory orders – run all labs STAT
- Check blood glucose (BG) q1 hour with glucose meter. If BG > 500 mg/dl send to lab.
- Do not use fingertip for blood sample if patient is hypotensive or in shock.
- Na, K, Cl, CO2, urine ketones q2 hours x 3, then q4 hours.
· IV Fluids (See fluid and electrolyte management above).
· Monitor I/O’s q2 hours.
· Initial insulin therapy:
- IV Insulin Bolus: give 0.1 units/kg IV push (if not done in ED)
- Insulin Infusion: start insulin infusion at 5 U/hour.
- Aim to correct BG by 75-100 mg/dl per hour. Write to check blood glucose q1 hour. Once glucose is in the 200-250 range, change IV solution to a D5 containing solution. This allows you to continue using insulin to clear ketones while preventing hypoglycemia and reducing the likelihood of cerebral edema from too rapid a decline.
- Sample scale for insulin drip:
|
Blood glucose (mg/dl) |
Action |
|
< 80 |
STOP insulin infusion and call MD Do not restart insulin infusion until BG ³ 100 mg/dl |
|
80 – 120 |
Decrease drip by 0.5 U/hr |
|
121 – 180 |
No change in drip rate |
|
181 – 250 |
Increase drip by 0.5 U/hr |
|
> 250 |
Bolus 5 U reg insulin and increase drip by 0.5 U/hr |
- For a BG < 80 mg/dl or > 400 mg/dl, call MD.
- BG <80 mg/dl but >60 mg/dl, stop insulin infusion. Check BG q15 minutes.
- BG £60 mg/dl, stop insulin infusion; give 50 cc D50 IV push; check BG q15 minutes and repeat treatment until BG >100 mg/dl, then call MD for new infusion orders.
Delaney
MF, Zisman A, Kettyle WM. Diabetic ketoacidosis and hyperglycemic hyperosmolar
nonketotic syndrome. Endocrinol Metab Clin North Am. 2000 Dec;29(4):683-705, V.
1. Significant hyperglycemia in absence of ketosis with hyperosmolality and dehydration.
2. Mortality 40-50% given incidence in elderly who often have comorbidities and insidious onset delaying presentation due to lack of ketosis.
3. Precipitating event similar to DKA: infection, infarction, incision (surgery), intoxication, non-compliance most often present.
4. Signs and symptoms: polyuria, polydipsia, weakness, convulsions, lethargy, confusion (serum osm > 310) ® stupor ® coma (serum osm > 330).
5. Lab: severe hyperglycemia, pseudohyponatremia ® corrected hypernatremia, prerenal azotemia
· Corrected Na = measured Na + 2.2 (plasma glucose-100)/100.
6. Therapy: treated much the same way as DKA—mainstays of treatment are fluids, insulin drip, and careful monitoring and repletion of electrolytes
· Fluid replacement: fluid deficit often 6-10 liters. Replace with NS initially (4-6 liters in first 8-10 hours) to treat hypovolemia, then follow with NS or ½NS at 150-400 cc/hour to keep urine output > 30 cc/hours. Some points to remember:
- Watch for pulmonary edema and volume overload, especially for patients with coronary artery disease or renal insufficiency.
- When glucose less than 250 mg/dl, switch to D5 solution to maintain glucose of 200-250 mg/dl while insulin continued in order to prevent hypoglycemia, and reduce the likelihood of cerebral edema from too rapid a decline .
- It may be useful to place an NG tube to give free water boluses. This way, you can avoid repleting free water solely IV (you won't have to use as much NS, or worse, wage the war between D5W and the insulin drip), and can theoretically lessen the risk of pulmonary edema and volume overload.
· Insulin: loading dose of 0.2 U/kg IV (usually 10 units IV is the amount needed to saturate all receptors) followed by maintenance drip of 0.1 U/kg/hour. Try to decrease glucose by 75-100 mg/dl/hour. Switch to SQ insulin with a sliding scale when glucoses in a better range (about 200 mg/dl). Wait 1-2 hours after starting SQ insulin to discontinue drip to prevent rebound hyperglycemia.
· Potassium repletion: less depleted since absence of acidosis, though repletion necessary from insulin therapy.
1. There is accumulating data to suggest that hospitalized patients with hyperglycemia have better outcomes when treated with an insulin infusion. The caveat is that your hospital and hospital setting (i.e. floor vs. ICU) must be equipped to monitor these patients closely for hypoglycemia.
2. Discontinue all previous insulin orders. Also discontinue any oral hypoglycemics.
3. IV fluids: start a dextrose-containing (e.g. D5NS) at a maintenance rate (50-100 cc/hour). If the patient cannot tolerate that high of a fluid rate, use D10NS or similar IV fluid solution. Consider adding potassium 20 mEq/L in most cases.
4. Insulin infusion: standard insulin solution (prepared by the pharmacy) is 25 units regular insulin mixed in 250 cc NS (1 unit/10 cc fluid). Flush the first 50 cc through the tubing before connecting to the patient. Before starting the infusion, check a fingerstick blood glucose.
5. Initial infusion rate: start the infusion rate as follows when fingerstick glucose > 100 mg/dl.
· 1.0 unit/hour for patients who were previously diet-controlled, on oral hypoglycemics only, or who take < 30 units of insulin/day at home.
· 1.5 units/hour for patients taking > 30 units of insulin/day at home.
6. Adjusting the infusion rate:
7. Monitoring:
- If blood glucose is 60-80 mg/dl, stop the infusion and check fingersticks q 15 minutes.
- If blood glucose < 60 mg/dl, stop insulin infusion and give 50 cc D50 IV push; check blood glucose q 15 minutes and repeat D50 until blood glucose > 100 mg/dl.
- When blood glucose > 100 mg/dl the MD should reassess the insulin infusion rate (you will likely have to lower it).
- If blood glucose > 400 mg/dl, the MD should reassess the insulin infusion rate (you will likely have to increase it).
8. Remember to adjust the infusion rate if there is any change in parenteral or enteral feedings (started or stopped). When converting to SQ insulin, give dose 30 minutes prior to discontinuing insulin infusion.
Based on the UCSF Adult Insulin Infusion Orders, 2001.
van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in the critically ill patients. N Engl J Med 2001; 345:1359-67.