What is the best course of treatment for a 38-year-old Hispanic woman with no known past medical history, who presents with symptoms of weight gain, fatigue, and laboratory results indicating hyperglycemia, impaired glucose regulation, hypothyroidism, and hypertension?

Management of Newly Diagnosed Type 2 Diabetes, Severe Hypothyroidism, and Hypertension

Immediate Priority: Initiate Levothyroxine for Severe Hypothyroidism

Start levothyroxine immediately at 1.5 to 1.8 mcg/kg/day (approximately 100-125 mcg daily for this patient's weight of 81.1 kg), taken on an empty stomach 30-60 minutes before breakfast. 1, 2 This patient has severe overt hypothyroidism (TSH 53, FT4 0.1) which requires urgent treatment and likely contributes significantly to her weight gain, fatigue, and metabolic dysfunction. 2, 3

Why Thyroid Treatment Takes Priority

• Hypothyroidism directly impairs glucose metabolism and can worsen hyperglycemia, making diabetes management more difficult until thyroid function normalizes. 4
• The severely elevated TSH (53) with suppressed FT4 (0.1) indicates profound thyroid hormone deficiency requiring immediate replacement. 2
• Symptoms of fatigue, weight gain, and cold intolerance overlap significantly with hypothyroidism, and many will improve with levothyroxine alone. 2, 3
• Thyroid hormone normalization typically takes 4-6 weeks, and glucose control often improves as thyroid function normalizes. 1, 2

Levothyroxine Administration Details

• Take as a single morning dose on an empty stomach with a full glass of water, 30-60 minutes before breakfast. 1
• Avoid taking within 4 hours of iron, calcium supplements, or antacids, as these significantly decrease absorption. 1
• Recheck TSH and FT4 in 6-8 weeks to assess response and adjust dosing. 2
• Target TSH should be in the lower half of the reference range (approximately 0.5-2.5 mIU/L). 2, 3

Concurrent Initiation: Metformin for Type 2 Diabetes

Start metformin 500 mg once daily with dinner, titrating up by 500 mg weekly to a target dose of 1000 mg twice daily (with breakfast and dinner) as tolerated. 5, 6 This patient has clear type 2 diabetes (fasting glucose 221 mg/dL, HbA1c 8.8%) requiring immediate pharmacologic intervention. 5

Why Metformin is the Correct First-Line Agent

• Metformin is the preferred initial pharmacological agent for type 2 diabetes if not contraindicated and if tolerated. 5
• This patient's creatinine of 1.2 mg/dL does not contraindicate metformin use (contraindicated only if eGFR <30 mL/min/1.73m²). 5
• Metformin provides high efficacy (HbA1c reduction of 1.4% in clinical trials), low hypoglycemia risk, promotes weight loss or weight neutrality, and is inexpensive. 5, 6
• In clinical trials, metformin reduced FPG by 53 mg/dL and HbA1c by 1.4% compared to placebo in patients with similar baseline characteristics. 6

Metformin Titration and Monitoring

• Start at 500 mg once daily to minimize gastrointestinal side effects (nausea, diarrhea). 5
• Increase by 500 mg weekly as tolerated: 500 mg twice daily (week 2), then 1000 mg AM + 500 mg PM (week 3), then 1000 mg twice daily (week 4). 5
• Monitor for gastrointestinal symptoms (most common side effect) and rare lactic acidosis risk. 5
• Recheck HbA1c in 3 months to assess response. 5

Blood Pressure Management: Initiate ACE Inhibitor or ARB

Start lisinopril 10 mg daily or losartan 50 mg daily for hypertension (BP 152/91). 5 This patient requires antihypertensive therapy given her diabetes diagnosis and elevated blood pressure.

Rationale for ACE Inhibitor/ARB Selection

• Patients with diabetes and hypertension benefit from ACE inhibitors or ARBs due to renoprotective effects beyond blood pressure lowering. 5
• Target blood pressure in diabetes is generally <140/90 mmHg, though individualized targets may be appropriate. 5
• These agents reduce progression of diabetic nephropathy and cardiovascular events. 5
• Recheck blood pressure in 2-4 weeks and titrate as needed to achieve target. 5

Comprehensive Metabolic and Lifestyle Management

Diabetes Self-Management Education

• Educate on carbohydrate counting and matching food intake to activity level. 5
• Initiate home blood glucose monitoring: fasting and 2-hour postprandial readings initially. 5
• Target preprandial glucose 80-130 mg/dL and postprandial glucose <180 mg/dL. 5
• Provide education on hypoglycemia recognition and treatment, though risk is low with metformin monotherapy. 5

Intensive Lifestyle Modification

• Target 7% body weight loss (approximately 5.7 kg for this patient) through reduced calorie intake. 7
• Prescribe at least 150 minutes per week of moderate-intensity physical activity, combining aerobic and resistance exercise. 7
• This approach achieves a 58% reduction in diabetes progression in patients with prediabetes and improves glycemic control in established diabetes. 7

Stress Management and Cortisol Considerations

• Address psychological and physical stress directly, as stress elevates cortisol and other counterregulatory hormones that worsen insulin resistance and increase gluconeogenesis. 7
• The patient's weight gain pattern (central obesity in belly and face) and fatigue may reflect chronic stress-related cortisol elevation. 7
• Recommend stress reduction techniques and consider screening for depression if symptoms persist. 7

Follow-Up Schedule and Monitoring

Initial 6-8 Week Follow-Up

• Recheck TSH, FT4, fasting glucose, and blood pressure at 6-8 weeks. 2
• Assess tolerance to metformin and levothyroxine. 5, 2
• Adjust levothyroxine dose based on TSH (target 0.5-2.5 mIU/L). 2
• Titrate metformin to target dose if not yet achieved. 5

Three-Month Follow-Up

• Recheck HbA1c to assess glycemic response to metformin. 5
• If HbA1c remains >7% (or individualized target) after 3 months on maximum tolerated metformin dose, add second agent. 5
• Second-line options include sulfonylurea, DPP-4 inhibitor, GLP-1 receptor agonist, or basal insulin, selected based on patient factors including weight, hypoglycemia risk, cost, and side effect profile. 5

Ongoing Monitoring

• HbA1c every 3 months until stable at goal, then every 6 months. 5
• TSH every 6-12 months once stable on levothyroxine. 2
• Annual comprehensive diabetes evaluation including lipid panel, urine albumin-to-creatinine ratio, dilated eye exam, and foot examination. 5
• Blood pressure monitoring at each visit. 5

Critical Pitfalls to Avoid

Do Not Delay Thyroid Hormone Replacement

• Severe hypothyroidism (TSH 53, FT4 0.1) requires immediate treatment and cannot wait for diabetes stabilization. 2, 3
• Untreated hypothyroidism worsens insulin resistance and makes diabetes control more difficult. 4
• Physical examination alone cannot rule out hypothyroidism (sensitivity and specificity are poor), so always treat based on laboratory values. 8

Do Not Assume Symptoms Will Resolve with Diabetes Treatment Alone

• Many of this patient's symptoms (fatigue, weight gain, cold intolerance) are primarily due to hypothyroidism and will improve with levothyroxine. 2, 3
• Expect gradual symptom improvement over 4-8 weeks as thyroid hormone levels normalize. 2

Do Not Start Insulin Prematurely

• This patient does not require insulin at presentation despite markedly elevated glucose (221 mg/dL) and HbA1c (8.8%), as she is not acutely symptomatic with polyuria, polydipsia, or weight loss. 5
• Metformin monotherapy is appropriate initial treatment, with reassessment at 3 months. 5
• Insulin should be reserved for patients with marked symptoms, evidence of catabolism, or failure of oral agents. 5

Do Not Overlook Medication Interactions

• Levothyroxine absorption is significantly reduced by iron, calcium, antacids, and certain other medications. 1
• Instruct the patient to separate levothyroxine from these agents by at least 4 hours. 1
• Metformin may cause vitamin B12 deficiency with long-term use; consider periodic screening. 5

Do Not Ignore Cardiovascular Risk Assessment

• This patient has multiple cardiovascular risk factors: diabetes, hypertension, central obesity, and Hispanic ethnicity. 5
• Initiate statin therapy for primary prevention (consider atorvastatin 10-20 mg daily) given diabetes diagnosis and age >40 years. 5
• Recommend aspirin 81 mg daily for primary prevention if 10-year cardiovascular risk >10%. 5

Do Not Forget Pregnancy Considerations

• If this patient becomes pregnant, immediately increase levothyroxine by 30% (take 9 doses per week instead of 7, i.e., one extra dose twice weekly). 2
• Hypothyroidism in pregnancy significantly increases risk of miscarriage and fetal neurodevelopmental abnormalities. 2
• Metformin is generally considered safe in pregnancy but discuss with obstetrics if pregnancy occurs. 5