What is the appropriate evaluation and management for a patient with Type 1 diabetes on insulin Lispro (Humalog) and insulin glargine (Lantus) presenting with weight loss, nausea, joint pain, lethargy, irritability, and skin darkening?

Evaluation and Management of Suspected Primary Adrenal Insufficiency (Addison's Disease)

This patient requires immediate evaluation for primary adrenal insufficiency (Addison's disease), given the constellation of weight loss, hyperpigmentation, nausea, lethargy, and irritability in the setting of Type 1 diabetes—a condition with increased autoimmune comorbidity risk.

Immediate Diagnostic Workup

Critical Laboratory Tests to Order Now

• Morning (8 AM) cortisol level and ACTH level to establish the diagnosis of adrenal insufficiency and differentiate primary from secondary causes 1
• Serum electrolytes (sodium, potassium) to assess for hyponatremia and hyperkalemia, which are characteristic of primary adrenal insufficiency 1
• Blood glucose monitoring to evaluate for hypoglycemia, as adrenal insufficiency can cause decreased insulin requirements and unpredictable glucose patterns 1
• Complete metabolic panel including renal function, as adrenal crisis can precipitate acute kidney injury 1
• Thyroid function tests (TSH, free T4) since autoimmune polyglandular syndrome can affect multiple endocrine organs 1

Confirmatory Testing if Initial Results Suggest Adrenal Insufficiency

• ACTH stimulation test (cosyntropin stimulation test) is the gold standard for confirming adrenal insufficiency if morning cortisol is equivocal 1
• Adrenal autoantibodies (21-hydroxylase antibodies) to confirm autoimmune etiology, which is the most common cause in developed countries 1

Clinical Features Supporting This Diagnosis

Hyperpigmentation Pattern

• Darkening of gums and skin creases is pathognomonic for primary adrenal insufficiency, caused by elevated ACTH levels stimulating melanocytes 1
• This hyperpigmentation distinguishes primary from secondary adrenal insufficiency, where ACTH levels are low 1

Constitutional Symptoms

• 20-pound unintentional weight loss over 8 months reflects chronic glucocorticoid and mineralocorticoid deficiency 1
• Nausea, lethargy, and irritability are classic manifestations of cortisol deficiency 1
• Joint pain may represent associated autoimmune arthritis or electrolyte disturbances 1

Type 1 Diabetes Connection

• Patients with Type 1 diabetes have 10-20 times higher risk of developing other autoimmune endocrinopathies, including Addison's disease (autoimmune polyglandular syndrome type 2) 1

Immediate Management Considerations

Before Diagnosis is Confirmed

• Do NOT delay treatment if patient shows signs of adrenal crisis (hypotension, severe weakness, confusion, abdominal pain) 1
• Stress-dose hydrocortisone (100 mg IV) should be administered immediately if adrenal crisis is suspected, even before diagnostic confirmation 1
• Draw cortisol and ACTH levels BEFORE giving any corticosteroids, but do not delay treatment for test results if crisis is present 1

Insulin Management Adjustments

• Expect decreased insulin requirements once glucocorticoid replacement is initiated, as cortisol deficiency causes increased insulin sensitivity 1
• Reduce both insulin lispro and insulin glargine doses by 20-30% initially when starting hydrocortisone replacement to prevent hypoglycemia 1
• Intensify glucose monitoring to 6-8 times daily during the initial treatment period, as insulin needs will fluctuate 1

Definitive Treatment Once Diagnosis Confirmed

Glucocorticoid Replacement

• Hydrocortisone 15-25 mg daily in divided doses (typically 10 mg morning, 5 mg afternoon, 5 mg evening) to mimic physiologic cortisol secretion 1
• Higher doses during illness or stress ("sick day rules"): double or triple the dose during febrile illness, trauma, or surgery 1

Mineralocorticoid Replacement

• Fludrocortisone 0.05-0.2 mg daily to replace aldosterone in primary adrenal insufficiency 1
• Monitor blood pressure, electrolytes, and plasma renin activity to guide fludrocortisone dosing 1

Patient Education Essentials

• Emergency glucocorticoid injection kit (hydrocortisone 100 mg IM) must be prescribed and family members trained in administration 1
• Medical alert identification (bracelet or necklace) stating adrenal insufficiency diagnosis 1
• Written sick-day management plan detailing when to increase doses and when to seek emergency care 1

Critical Pitfalls to Avoid

• Do not attribute hyperpigmentation to sun exposure or ethnicity without ruling out Addison's disease—this is a common missed diagnosis 1
• Do not start corticosteroid treatment before drawing cortisol and ACTH levels unless the patient is in adrenal crisis 1
• Do not use dexamethasone for chronic replacement therapy, as it lacks mineralocorticoid activity and cannot be measured in cortisol assays 1
• Do not forget to adjust insulin doses downward when initiating glucocorticoid replacement, as failure to do so causes severe hypoglycemia 1
• Do not delay endocrinology referral—this patient requires subspecialty management for both Type 1 diabetes and adrenal insufficiency 1

Monitoring After Treatment Initiation

• Recheck electrolytes within 1-2 weeks to ensure normalization of sodium and potassium 1
• Monitor blood pressure to assess adequacy of mineralocorticoid replacement 1
• Reassess insulin requirements weekly for the first month, as glucocorticoid replacement will increase insulin needs 1
• Measure plasma renin activity to guide fludrocortisone dosing adjustments 1
• Screen for other autoimmune conditions including thyroid disease, celiac disease, and pernicious anemia 1