Hypothermia and Myxedema Coma – 11/13/18

Thanks to Austin for presenting the case of an elderly woman with h/o psychiatric disorder who presented with acute/subacute onset of AMS, severe hypothermia, sinus bradycardia, and hypotension with work up revealing hypothyroidism suspicious for myxedema coma!


Clinical Pearls

  • Exam findings for hypothermia change depending on severity of hypothermia (see below).
  • It is crucial to measure core body temperature for accuracy especially when you are rewarming the patient (esophageal is the best, rectal/bladder are ok prior to rewarming but can remain low in spite of increasing core body temp so do not rely on these metrics alone)
  • Think of etiologies of hypothermia broadly within the categories of increased loss or decreased heat generation.
  • The most common causes of hypothermia are sepsis, exposure, and hypoglycemia.
  • The hallmarks of myxedema coma are AMS, hypothermia, and a precipitating event (i.e. infection, exposure, meds, etc.)
  • Myxedema coma is a medical emergency with a high mortality rate.  So consult endocrine early when you are suspecting it.
  • Always treat myxedema coma with levothyroxine AND steroids until you have ruled out a concurrent adrenal insufficiency.

HYPOTHERMIA

Types:

  • Mild (32-35°C)
    • Clinical manifestations
      • Shivering, rigors
      • ↑ HR, ↑ RR, ↑ BP, hyperventilation
      • Cold diuresis
        • Body’s attempt to preserve heat.  When peripheral vasoconstriction occurs to keep blood closer to vital organs, BP rises.  Kidneys see this rise in BP and act to correct it by dumping fluid! (Oh kidneys…)
    • Treatment
      • Passive, external
        • Blankets
        • Humidified inspired air
  • Moderate (28-32°C)
    • Clinical manifestations
      • ↓ shivering
      • Confusion, slurred speech
      • ↓ HR, hypoventilation
      • Can also start to notice other cardiac manifestations such as prolonged QTc, QRS, osborn (J) waves, ST elevations/depressions.
      • ↓ renal blood flow
    • Treatment
      • Passive, external (see above) PLUS
      • Active external
        • Forced heated air
        • Warm blankets
        • Warm water immersion
      • Active internal
        • Warm humidified air (42°C)
        • Warm IV fluids (42°C)
        • Body cavity lavage (in trauma patients only)
  • Severe (<28°C)
    • Clinical manifestations
      • NO shivering
      • Edema (due to poor renal blood flow) of extremities and lung
      • ↓ HR, ↓ BP (due to drop in cardiac output), hypoventilation, ventricular arrhythmias
      • Cardiac manifestations more common as with moderate hypothermia
      • AMS
      • Paradoxical undressing
        • mechanism is poorly understood but thought to be due to paralysis of the nerves regular vascular muscle tone leading to vasodilation and sensation of a heat flush which results in the patient wanting to take their clothes off.
    •  Treatment
      • Any of the above (passive external, active external, active internal) and/or
      • Extracorporeal
        • HD
        • ECMO

Etiologies of hypothermia:

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Items in red above are the most common causes of hypothermia.

Lab findings:

  • Less reliable since labs have to be warmed prior to processing
    • ABG is often inaccurate
    • Coagulopathy may be masked
    • Hyperkalemia due to rewarming

Complications of rewarming:

  • Hypotension due to peripheral vasodilation
  • Ileus and urinary retention
  • Worsening coagulopathy
  • Arrhythmias
  • Hyperkalemia
  • Core temperature after-drop (a condition in which cold peripheral blood gets shunted to the core and results in further decline in temperature.  You can avoid this by active internal rewarming like warmed IV fluids)

MYXEDEMA COMA 

Learn all about it from our prior blog post here.

Metastatic… Insulinoma? 11/7/2018

Yonglu presented a middle age man with no medical history presenting with syncope. In the preceding months, he has been having non-specific fatigue, decreased exercise tolerance, dizziness, and diaphoresis. He was found to be hypoglycemic after this syncopal episode, and in the hospital his labs were consistent with hyperinsulinism when he was in a hypoglycemic state. CT revealed diffuse liver masses concerning for HCC, as well as a lesion on his left iliac crest appearing to be an osteosarcoma. He was also found to have a pancreatic mass as well…

Three malignant processes? Octreotide scan revealed increased uptake at these regions, and biopsy of the liver revealed a diagnosis of a neuroendocrine tumor!


Hypoglycemia

When we think about hypoglycemia, its pattern can actually give us a clue.

  • Fasting: Most common
  • Post-prandial: non-insulinoma pancreatogenous hypoglycemia syndrome (NIPHS), post-bariatric surgery hyperinsulinemic hypoglycemia
  • Both: Insulin autoantibody, insulinoma

hypoglycemic-differential-hypoglycemia-malignancy-diagnosis-original

Source: grepmed


Insulinoma

Epidemiology

  • Rare, not enough data
  • Small cohort: median age 48 years, 77% men
  • MEN Type 1: Younger presentation, 20s

Pathophysiology

  • Pancreatic islet cell origin
  • Generally benign, single vs multiple
  • Rare to be malignant (10%)

Presentation

  • Pattern: fasting hypoglycemia mainly but can be both
  • May have some sympathoadrenal sx i.e. palpitations, diaphoresis (seen in this patient), tremulousness
  • Likes to spread to liver, rarely can have bony mets (~13%)

Whipple’s Triad: Presence of all three demonstrates “true” hypoglycemia

  • Symptoms of hypoglycemia
  • Low plasma glucose at time of symptoms
  • Relief of symptoms when glucose is back to normal

Diagnosis

  • Evidence of inappropriately high serum insulin during episode of hypoglycemia
  • 72 hour fasting plasma glucose test: Supervised fast in order to bring on hypoglycemia in order to evaluate etiology. If pt has underlying hyperinsulinism, 95-99% of the time they will be hypoglycemia within 48 hours of fasting.
    • Blood test is drawn when pt has sx of hypoglycemia
    • Test: Glucose, insulin, proinsulin, and c-peptide level.
    • Normal: suppression of endogenous insulin
    • Abnormal: Inappropriately elevated insulin, pro-insulin, and c-peptide in setting of hypoglycemia.
  • Octreotide scan: Increased uptake seen in tumors of neuroendocrine etiology, more sensitive than US, CT, or MRI for detection of somatostatin receptor positive tumors
  • Evidence of hyperinsulinism
    • Low BHB
    • High insulin level
    • High C-peptide
    • High pro-insulin
  • Chromogranin A: used to help diagnose carcinoid tumors (NET of the digestive tract and lungs). Nowadays carcinoid is generally used to refer to well differentiated NETs originating in the lungs. GI tract tumors are now termed NET.

Management

  • Localized lesion: Surgical resection is curative
  • Hypoglycemia
    • Somatostatin analogy
      • Octreotide: Inhibits growth hormone secretion, can switch to Q-monthly formulation
      • Lanreotide
    • Diazoxide: Diminishes insulin secretion, side effects include hirsutism and edema
  • Radiation therapy: Data also limited in utility but can be consider if evidence of bony mets (which is also rare for NET)
  • Chemo:
    • Minority of NET, namely high-grade, well differentiated with Ki67 index > 20%, are rare and there is no consensus on how to treat these patients. These patients generally respond poorly to platinum/etoposide based regimens used to treat most NETs.
    • Other options: Temozolomide, Sunitinib (RTK inhibitor), Everolimus (mTOR inhibitor)

Helpful table for hypoglycemia work up.

Beta-hydroxybutyrate (BHB) is by product of alternate metabolism (more specifically ketone bodies) in a fasting state, so it can be elevated in setting of prolonged fasting (not just DKA).

Also thanks to Arathi for pointing out that insulin has a negative feedback on this process, hence in a hyperinsulinemic state (despite concurrent hypoglycemia), beta hydroxybutyrate would be very low!

Insulinomas can appear like hypoglycemia secondary to oral glycemic agents, but the key is the oral glycemic agent screen would be positive in the latter case!

IGF-omas can cause s/sx hypoglycemia due to similarity with insulin. Expect IGF2 levels to be elevated in such cases and elevated BHB.

Capture.JPG

Please refer to this helpful review article if you want to know more about NETs!

Also please refer to this paper for a case report on AFP-producing pancreatic NET (AFP elevated in this patient!)

Adrenal insufficiency, lupus flare, and mixed AIHA- 9/6/18

Thanks to Becky for presenting the case of a middle-aged woman with h/o SLE and Evans syndrome who presenting with subacute onset of fatigue after her prednisone dose was reduced, found to have iatrogenic adrenal insufficiency, lupus flare, and mixed autoimmune hemolytic anemia!


Clinical Pearls:

  • Evans syndrome describes AIHA + ITP, a rare condition associated with SLE and often precedes the diagnosis of SLE by a few years.
  • Hematologic manifestations of SLE are many and include the following
    • Anemia (chronic disease, iron deficiency, medication-induced, warm AIHA>>cold AIHA, pure red cell aplasia, MAHA, and pernicious anemia)
    • Leukopenia
    • Thrombocytopenia
    • Pancytopenia
    • Evans syndrome
  • Smear findings can be very helpful in diagnosing different types of hemolytic anemiasSchistocytes are a very specific for MAHA, valve disorders, AVMs, APLS whereas AIHA would result in spherocytes. 
    • The negative predictive value of spherocytes is low.  So a smear without spherocytes does not rule out AIHA!
  • Lastly, the most common cause of adrenal insufficiency (AI) is iatrogenic.
    • General rule of thumb for when risk of AI is high and you should taper steroids slowly is if someone is on prednisone > 20 mg for > 3 weeks.  Keep in mind that people with smaller BSA would be more susceptible to AI and at risk with even lower doses.

Hemolytic anemia work up

Check smear

  • Schistocytes
    • MAHA: TTP, HUS, HELLP, DIC, HTN
    • Valve disorder
    • AVMs
    • APLS
  • No schistocytes (+ spherocytes)
    • Intrinsic RBC defect
      • Enzyme deficiency (G6PD)
      • Hemoglobinopathy (sickle cell)
      • Membrane defect (hereditary spherocytosis)
    • Extrinsic RBC defect
      • Liver disease
      • Splenic sequestration
      • Infections (clostridium perfringens, babesia, malaria, bartonella)
      • Meds/toxins (dapsone, nitrites, lead, copper, snake venom)
      • AIHA (warm and cold)
    • Intravascular
      • Transfusion reaction
      • Infections
      • PNH

Lab findings in AIHA: 

  • ↑ retic
  • ↑ indirect bili
  • ↑ LDH
  • ↓ haptoglobin
  • + DAT (but keep in mind that DAT can be negative in 3% of patients with WAIHA)
  • + spherocytes

Summary of AIHAs:

Picture1

 

Thyroid storm! Or is it?… 8/28/18

Thanks Hong for presenting the case of a middle-aged woman with recent diagnosis of Grave’s disease off methimazole who presented with A fib with RVR and congestive heart failure, raising a debate on thyroid storm!


Clinical Pearls:

  • Thyroid storm is an extremely rare (1 in 500,000) but life-threatening diagnosis (up to 30% mortality) that should not be missed.
  • Degree of thyroid hormone elevation or TSH suppression is not a criteria for diagnosing thyroid storm! In fact, levels are typically similar to those of patients with uncomplicated thyrotoxicosis.
  • Common clinical feature is cardiovascular symptoms (heart failure, arrhythmia, tachycardia) but more specific finding is AMS.
  • Scoring criteria to screen for thyroid storm include Burch/Wartofsky and the Akamizu criteria, but they have not been validated.
  • Consult endocrine early if you suspect thyroid storm!

Thyroid storm: 

Risk factors:

  • Longstanding untreated hyperthyroidism
  • Precipitants:
    • Thyroid/non-thyroidal surgery
    • Trauma
    • Infection
    • Acute iodine load
    • Parturition
    • Irregular use or discontinuation of antithyroid treatment

Etiology: not clearly understood, but possibly related to the following

  • Rapid rate of increase in thyroid hormone levels?
  • Increased responsiveness to catecholamines?
  • Enhanced cellular responses to thyroid hormone?
  • The degree of thyroid hormone elevation or TSH suppression is not typically more profound than uncomplicated thyrotoxicosis

Clinical features:

  • CV (>60% of cases)
    • Tachycardia
    • CHF
    • Arrhythmias
  • Hyperpyrexia
  • AMS (considered by many to be essential to diagnosis)
    • Agitation, anxiety, delirium, psychosis, stupor, coma
  • Features associated with worse outcomes?
    • AMS
    • Older age >60
    • Mechanical ventilation
    • Not using antithyroid drugs or beta blockers

Diagnosis: 

  • Clinical! No universally accepted criteria or validated clinical tools.  Degree of hyperthyroidism is not a criterion for diagnosis.  Some to know of that might be helpful:
    • Burch and Wartofsky (sensitive, not specific)
      • > 45: highly suggestive of thyroid storm
      • 25 – 44: impending storm
      • <25: thyroid storm unlikely
    • Akamizu (Japanese) system developed in 2012 (less sensitive but more specific)

Treatment

  • ICU admission!
  • Regimen
    • Beta blockers ⇒ control symptoms from increased adrenergic tone
    • Thionamide ⇒ block new hormone synthesis. PTU is preferred because it blocks peripheral conversion of T4 to T3.
    • Iodine solution ⇒ block release of thyroid hormone (saturated solution of potassium iodide)
    • Iodinated radiocontrast agent (not available anymore in most places) ⇒  inhibit peripheral conversion of T4 to T3
    • Glucocorticoids ⇒ reduce T4 to T3 conversion, promote vasomotor stability, and treat any associated relative adrenal insufficiency
    • Bile acid sequestrants ⇒ decrease enterohepatic recycling of thyroid hormones (only in very severe cases)
  • Principles
    • Start with beta blockers + PTU, and stress dose steroids
    • 1 hour later: start SSKI q6h (after hormone synthesis has been halted with PTU, otherwise SSKI can make thyroid storm worse)

Myxedema Coma – 12/12/17

What is it?

  • Severe hypothyroidism leading to AMS and hypothermia
  • Can have other symptoms related to the slowing down of organs

Who gets it?

  • Usually older females with long standing hypothyroidism triggered by a precipitating event

How does it present?

  • Change in mental status (rarely presents as true overt coma)
  • Hypothermia
  • Hypotension
  • Bradycardia
  • Hyponatremia
  • Hypoglycemia
  • Hypoventilation

What labs should you check?

  • TSH, FT4
  • Cortisol (to rule out concurrent adrenal insufficiency)

What is the treatment?

  • IV T3 and/or T4 – data is mixed
    • Use IV because patient likely has gut edema so PO form may have decreased absorption
    • T3 has better bioavailability and is the active form
    • In acute illness, body’s normal conversion of T4 to T3 is impaired
    • Monitor patients on telemetry because biggest concern is arrhythmias
    • Use lower dosing in elderly patients or those with cardiac disease
    • Recheck TSH in one week – goal is drop by > 50%
  • Stress dose steroids (hydrocortisone 100 mg every 8 hours)
    • Until you rule out concomitant adrenal insufficiency
  • Supportive measures
    • Avoid dilute fluids which can worsen hyponatremia
    • Use passive rewarming
    • Pressors if needed