What is the approach to a hormone work-up and subsequent management of hormonal imbalances?

Comprehensive Approach to Hormone Work-up and Management

A systematic diagnostic approach to hormonal imbalances should begin with targeted testing of specific hormonal axes based on clinical presentation, followed by appropriate hormone replacement or modulation therapy guided by laboratory results.

Initial Diagnostic Evaluation

Thyroid Function Assessment

• Check TSH and Free T4 as first-line screening for all patients with suspected hormonal imbalance 1
• Consider adding T3 levels in highly symptomatic patients with minimal FT4 elevations 1
• For abnormal results:
  • Low TSH with low FT4: Evaluate for central hypothyroidism (hypophysitis) 1
  • High TSH with normal/low FT4: Primary hypothyroidism 1
  • Low TSH with high FT4: Thyrotoxicosis (consider TSH receptor antibodies if features of Graves' disease present) 1

Adrenal Function Assessment

• Morning cortisol (8 AM) with simultaneous ACTH is the first-line test 2
• ACTH stimulation test (cosyntropin 250 μg IV/IM) for indeterminate results 2
  • Peak cortisol <500 nmol/L indicates adrenal insufficiency
  • Basal cortisol <85 nmol/L is highly specific for adrenal insufficiency
  • Basal cortisol >350 nmol/L effectively rules out the condition
• Primary vs. secondary adrenal insufficiency differentiation:
  • Primary: High ACTH, low cortisol, often with electrolyte abnormalities (↓Na, ↑K)
  • Secondary: Low ACTH, low cortisol, normal electrolytes 1

Pituitary Function Assessment

For suspected hypophysitis or multiple hormone abnormalities:

• Evaluate ACTH, cortisol, TSH, FT4, and electrolytes 1
• Consider LH, FSH, testosterone (males) or estradiol (premenopausal females) 1
• MRI brain with pituitary/sellar cuts for patients with multiple endocrine abnormalities, severe headaches, or vision changes 1

Management Strategies by Hormonal System

Thyroid Disorders Management

Primary Hypothyroidism

• Prescribe levothyroxine supplementation for symptomatic patients with any TSH elevation or asymptomatic patients with TSH >10 mIU/L 1
• Dosing:
  • For patients <70 years without cardiac disease: 1.6 mcg/kg/day based on ideal body weight 1
  • For elderly (>70 years) or patients with cardiac disease: Start with 25-50 mcg and titrate up 1
• Monitor TSH every 6-8 weeks while titrating to goal TSH within reference range 1
• Important considerations:
  • Administer on empty stomach, 30-60 minutes before breakfast 3
  • Separate from calcium, iron supplements, and antacids by at least 4 hours 3
  • Monitor for signs of overtreatment (palpitations, anxiety, insomnia, weight loss) 3

Thyrotoxicosis

• Beta-blockers (e.g., atenolol, propranolol) for symptomatic relief 1
• Monitor thyroid function every 2-3 weeks after diagnosis to catch transition to hypothyroidism 1
• For persistent thyrotoxicosis (>6 weeks), consider endocrine consultation 1

Adrenal Disorders Management

Primary Adrenal Insufficiency

• Initiate replacement therapy with hydrocortisone (15-20 mg daily in divided doses) with the first dose immediately after waking 1, 2
• Add fludrocortisone (0.05-0.1 mg/day) for mineralocorticoid replacement 1, 2
• Titrate hydrocortisone to maximum of 30 mg daily total dose for residual symptoms 1
• For adrenal crisis (severe symptoms):
  • Immediate IV hydrocortisone 100 mg bolus
  • Followed by continuous infusion of 200 mg/24h or 100 mg every 6-8 hours
  • Rapid infusion of isotonic saline (at least 2L) 2

Secondary Adrenal Insufficiency (Hypophysitis)

• Corticosteroid replacement with hydrocortisone (15-20 mg in divided doses) 1
• Important: Always start corticosteroids several days before thyroid hormone to prevent precipitating adrenal crisis 1
• For multiple hormone deficiencies, add other hormone replacements after stabilizing on corticosteroids 1

Pituitary Disorders Management

• Hormone replacement based on specific deficiencies:
  • Adrenal: Hydrocortisone as above
  • Thyroid: Levothyroxine with goal FT4 in upper half of reference range (TSH is not accurate in central hypothyroidism) 1
  • Gonadal: Testosterone for males or estrogen therapy for premenopausal females without contraindications 1

Critical Patient Education Points

1. All patients with adrenal insufficiency need:

   • Education on stress dosing (doubling or tripling glucocorticoid dose during illness/stress) 1, 2
   • Medical alert bracelet or necklace 1, 2
   • Emergency injectable steroids and instructions for use 1
   • Endocrine consultation prior to any surgical procedures 1, 2

2. Thyroid medication considerations:

   • Take at consistent time daily, preferably on empty stomach 3
   • Avoid interacting medications that affect absorption 3
   • Report symptoms of under or over-replacement 3

Common Pitfalls and Caveats

1. Never delay treatment if adrenal crisis is suspected - give hydrocortisone immediately and obtain blood samples for cortisol and ACTH before treatment 2

2. Patients on corticosteroids for other conditions will have low morning cortisol as a result of iatrogenic secondary adrenal insufficiency. Laboratory confirmation should not be attempted until treatment with corticosteroids for other disease is ready to be discontinued 1

3. When managing multiple hormone deficiencies, always start corticosteroids first before initiating thyroid hormone replacement to avoid precipitating adrenal crisis 1

4. TSH is not accurate for monitoring thyroid replacement in central hypothyroidism - follow FT4 levels instead 1

5. Elevated TSH can be seen in recovery phase of thyroiditis - in asymptomatic patients with normal FT4, monitor before treating to determine if there is recovery within 3-4 weeks 1