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!
- 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)
- Evans syndrome
- Smear findings can be very helpful in diagnosing different types of hemolytic anemias. Schistocytes 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
- MAHA: TTP, HUS, HELLP, DIC, HTN
- Valve disorder
- 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)
- Transfusion reaction
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:
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!
- 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!
- Longstanding untreated hyperthyroidism
- Thyroid/non-thyroidal surgery
- Acute iodine load
- 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
- CV (>60% of cases)
- AMS (considered by many to be essential to diagnosis)
- Agitation, anxiety, delirium, psychosis, stupor, coma
- Features associated with worse outcomes?
- Older age >60
- Mechanical ventilation
- Not using antithyroid drugs or beta blockers
- 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)
- ICU admission!
- 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)
- 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)
Today Eric presented an interesting case of a young Filipino man with no medical history, presenting with chronic intermittent proximal > distal muscle weakness affecting mainly his lower extremities, with associated tremors, weight loss, sweats. He was found to be profoundly hypokalemic on presentation.
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)
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
Remember that prolactin is inhibited by dopamine!
In panhypopituitaryism, the anterior pituitary hormones are more commonly affected than the posterior pituitary hormones and there is a spectrum for how much of the HPA axis is still preserved depending on the etiology of the panhypopituitaryism.
The hormones that need replacement in adults are T4 and cortisol. Testosterone can be replaced if needed in men. Estrogen and progesterone can be replaced in pre-menopausal women who do not want fertility at that time or in post-menopausal women to relieve post-menopausal symptoms. If a woman desires fertility and has enough HPA axis preserved then patients can get pulsatile GnRH to stimulate FSH and LH production to induce ovulation.
To screen for adrenal insufficiency, check a morning cortisol at 8am.
- Cortisol < 3 = likelihood high – check ACTH to determine primary versus secondary adrenal insufficiency
- Cortisol 3-18 = indeterminate – do further stimulation testing
- Cortisol > 18 = likelihood low – pursue other diagnosis
- Cosyntropin test – give cosyntropin (synthetic ACTH) and then measure cortisol level 1 hour later – normal is cortisol level > 18; if less than that, then likely primary adrenal insufficiency
- Insulin induced hyperglycemia test – give 0.1U/kg of insulin and check glucose at 15, 30, 60, 90, 120 minutes. Once glucose reaches < 50 then cortisol should be > 18
- Metyrapone testing – blocks 11B hydroxylase which leads to a drop in cortisol and increase in ACTH and increase in 11-deoxycortisol
- Insufficient dosing of steroids
- Failure to increase dosage of steroids with acute illness
- Persistent vomiting or diarrhea causing malabsorption of steroids
- Can commonly see isolated ACTH presentation in panhypopituitaryism
- Dexamethasone if adrenal insufficiency not yet diagnosed because it does not interfere with cortisol testing
- Hydrocortisone if pre-existing diagnosis
Remember – if you suspect adrenal insufficiency, give stress dose steroids immediately without waiting for further testing!