What is the diagnosis and treatment for a patient with a history of Hashimoto's thyroiditis, currently taking levothyroxine (T4), Caplyta (lumateperone), propranolol, lorazepam, naltrexone, venlafaxine, testosterone oil, and lamotrigine, presenting with hypomania, reduced sleep, out-of-body experiences, chills, uncontrollable thirst, and excessive sweating, with normal hemoglobin A1c (HbA1c) and fasting glucose levels?

Differential Diagnosis and Immediate Management

This patient is experiencing acute adrenal insufficiency (adrenal crisis) precipitated by increased metabolic demands from hypomania and inadequate cortisol response, requiring immediate evaluation and treatment before any thyroid medication adjustments. 1

Primary Diagnostic Considerations

Adrenal Insufficiency (Most Urgent)

The constellation of symptoms—out-of-body sensation, uncontrollable thirst, chills requiring hot bath, and profuse sweating after fluid/food intake—strongly suggests adrenal crisis, particularly given:

• Hyponatremia is present in 90% of newly presenting adrenal insufficiency cases 1
• Patients with Hashimoto's thyroiditis have increased risk of concurrent autoimmune adrenal insufficiency (Addison's disease) 1
• The patient's hypomanic state with reduced sleep (3-4 hours) creates increased metabolic stress that can unmask or precipitate adrenal crisis 1
• Treatment of suspected acute adrenal insufficiency should never be delayed by diagnostic procedures 1

Critical Diagnostic Steps Required Immediately

Before adjusting any thyroid medication, rule out adrenal insufficiency with:

• Early morning (8 AM) serum cortisol and plasma ACTH levels 1
• Serum electrolytes (sodium, potassium) to assess for hyponatremia and hyperkalaemia 1
• If cortisol <250 nmol/L with acute illness symptoms, this is diagnostic of primary adrenal insufficiency 1
• If cortisol <400 nmol/L with acute illness, this raises strong suspicion requiring immediate treatment 1
• Consider short cosyntropin stimulation test (0.25 mg IM or IV) with peak cortisol <500 nmol/L diagnostic of adrenal insufficiency 1

Secondary Diagnostic Considerations

Thyroid dysfunction complications:

• Hashimoto's thyroiditis can present with thyrotoxicosis (Hashitoxicosis) when stored thyroid hormones are released from destroyed follicles, which could explain hypomania and reduced sleep 2
• Severe hypothyroidism can paradoxically present as acute mania with psychotic features, though less likely given patient is on levothyroxine 3
• TSH levels may be elevated (4-10 IU/L range) in primary adrenal insufficiency due to lack of cortisol's inhibitory effect on TSH production 1

Drug-induced considerations:

• Lumateperone (Caplyta) combined with venlafaxine increases serotonin syndrome risk, though symptoms don't fully match 1
• Propranolol may mask thyrotoxicosis symptoms (palpitations, tremors, heat intolerance) 1
• Lamotrigine levels can be affected by thyroid status changes 1

Immediate Management Algorithm

Step 1: Emergency Assessment (Do Not Delay)

If adrenal crisis is suspected based on clinical presentation:

• Draw blood for cortisol, ACTH, electrolytes, glucose immediately 1
• Start treatment immediately without waiting for results: Hydrocortisone 100 mg IV bolus, then 50-100 mg IV every 6-8 hours 1
• Aggressive IV fluid resuscitation with normal saline 1
• Monitor for hypoglycemia and treat if present 1

Step 2: Confirm Etiology Once Stabilized

After acute stabilization, determine cause:

• Measure 21-hydroxylase (anti-adrenal) autoantibodies to confirm autoimmune etiology 1
• If antibodies negative, obtain CT imaging of adrenal glands 1
• Assess for other autoimmune conditions associated with Hashimoto's (APS-2 syndrome) 1

Step 3: Thyroid Function Assessment

Only after ruling out/treating adrenal insufficiency:

• Measure TSH, free T4, and free T3 to assess current thyroid status 1
• Never start or increase thyroid hormone before ensuring adequate cortisol replacement, as this can precipitate fatal adrenal crisis 1
• If both adrenal insufficiency and hypothyroidism present, start corticosteroids at least 1 week before initiating/adjusting levothyroxine 1

Step 4: Psychiatric Symptom Management

Address hypomania while treating underlying endocrine disorder:

• Continue Caplyta (lumateperone) for mood stabilization 3
• Severe hypothyroidism can present as mania with psychosis; correction of thyroid status improves antipsychotic response 3
• Conversely, thyrotoxicosis from Hashimoto's can cause anxiety, tremors, and hypermetabolic symptoms masked by propranolol 1

Critical Pitfalls to Avoid

• Never adjust levothyroxine dose without first ruling out adrenal insufficiency in patients with Hashimoto's thyroiditis 1
• Do not attribute all symptoms to psychiatric illness when endocrine emergency may be present 1
• Failing to recognize that hyponatremia with normal glucose/HbA1c points toward adrenal insufficiency rather than diabetes insipidus 1
• Missing the association between autoimmune thyroid disease and autoimmune adrenal insufficiency (occurs in 10-15% of Hashimoto's patients) 1
• Starting thyroid hormone replacement before cortisol replacement can precipitate cardiovascular collapse and death 1

Long-Term Management Considerations

Once acute crisis resolved and diagnoses confirmed:

• All patients with adrenal insufficiency should wear medical alert identification and carry steroid emergency card 1
• Stress-dose steroids required for illness, surgery, or significant physiological stress 1
• Monitor thyroid function every 6-8 weeks while titrating levothyroxine, then every 6-12 months once stable 4
• Screen for other autoimmune conditions annually (celiac disease, type 1 diabetes, vitiligo, alopecia) 5
• Ensure adequate calcium (1200 mg/day) and vitamin D (1000 units/day) intake for bone health 4