4.2 Endocrinology & Diabetes Mellitus

4.2 Endocrinology & Diabetes Mellitus

Diabetes Mellitus: ADA Guidelines and Glycemic Targets

The American Diabetes Association (ADA) defines the diagnostic criteria for diabetes as a Fasting Plasma Glucose (FPG) >=126 mg/dL, a 2-hour Plasma Glucose >=200 mg/dL during an Oral Glucose Tolerance Test (OGTT), an A1C >=6.5%, or a random plasma glucose >=200 mg/dL in a patient with classic symptoms of hyperglycemia. For nonpregnant adults, the general glycemic targets are an A1C <7.0%, preprandial capillary plasma glucose of 80-130 mg/dL, and a peak postprandial capillary plasma glucose <180 mg/dL. Individualization is key; tighter targets (e.g., <6.5%) may be appropriate for younger patients without significant cardiovascular disease, while less stringent targets (e.g., <8.0%) are acceptable for patients with severe hypoglycemia history, limited life expectancy, or advanced microvascular/macrovascular complications.

Oral and Non-Insulin Antidiabetic Agents

Biguanides (Metformin)

Metformin remains a foundational therapy for Type 2 Diabetes (T2DM). It primarily decreases hepatic glucose production and improves peripheral insulin sensitivity. It carries a low risk of hypoglycemia and provides modest weight loss. Metformin is contraindicated in patients with an eGFR <30 mL/min/1.73m2 due to the increased risk of lactic acidosis. For eGFR 30-45 mL/min/1.73m2, initiation is not recommended, and current doses should be reduced by 50%. Long-term use is associated with Vitamin B12 deficiency, requiring periodic monitoring. Metformin must be withheld prior to iodinated contrast imaging in patients with eGFR <60 mL/min/1.73m2 to prevent lactic acidosis.

Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors

Agents like empagliflozin, dapagliflozin, and canagliflozin block glucose reabsorption in the proximal convoluted tubule, promoting glucosuria. Landmark trials (e.g., EMPA-REG OUTCOME, DECLARE-TIMI 58) demonstrated significant cardiovascular mortality benefits and a reduction in heart failure hospitalizations. Furthermore, SGLT2 inhibitors provide profound renal protection, reducing the progression of albuminuria and eGFR decline. They are highly recommended for patients with T2DM and established ASCVD, heart failure, or CKD. Adverse effects include genitourinary infections (vulvovaginal candidiasis, UTIs), volume depletion, an increased risk of euglycemic diabetic ketoacidosis (DKA), and a rare but serious risk of Fournier's gangrene.

Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RAs)

Semaglutide, liraglutide, and dulaglutide are incretin mimetics that enhance glucose-dependent insulin secretion, suppress inappropriate postprandial glucagon secretion, slow gastric emptying, and increase satiety. They are highly efficacious for both A1C reduction and weight loss. Trials such as LEADER and SUSTAIN-6 established the ASCVD benefits of liraglutide and subcutaneous semaglutide, making them preferred agents for patients with high cardiovascular risk. GLP-1 RAs are contraindicated in patients with a personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN2). Gastrointestinal side effects (nausea, vomiting, diarrhea) are common and dose-dependent.

Insulin Regimens and Conversions

Insulin is indicated for all Type 1 Diabetes patients and T2DM patients with severe hyperglycemia (A1C >10% or BG >=300 mg/dL).

• Basal Insulins: Glargine, detemir, and degludec provide a continuous peakless supply of insulin, suppressing hepatic glucose production overnight and between meals.
• Bolus (Prandial) Insulins: Lispro, aspart, and glulisine cover postprandial glucose excursions.
• NPH and Regular: Older, less predictable options. NPH peaks at 4-12 hours, posing a higher risk for nocturnal hypoglycemia.

When converting between insulin regimens, a 1:1 unit conversion is generally used, with two major exceptions that require a 20% dose reduction to prevent hypoglycemia:

1. Converting from NPH given twice daily to insulin glargine given once daily.
2. Converting from insulin glargine 300 units/mL (Toujeo) to insulin glargine 100 units/mL (Lantus).

Thyroid Disorders: Hypothyroidism and Hyperthyroidism

Hypothyroidism, most commonly Hashimoto's thyroiditis, is managed with levothyroxine (T4). The full replacement dose is 1.6 mcg/kg/day using Ideal Body Weight (IBW). In elderly patients or those with coronary artery disease, lower starting doses (e.g., 12.5-25 mcg/day) are mandatory to prevent cardiac ischemia. Levothyroxine has a narrow therapeutic index; TSH should be monitored every 4-6 weeks after any dose adjustment. It must be taken on an empty stomach, 60 minutes before breakfast or at bedtime (at least 3 hours after the last meal), and separated from polyvalent cations (calcium, iron, antacids) by 4 hours. Amiodarone and lithium are notable drugs that can induce hypothyroidism.

Hyperthyroidism (e.g., Graves' disease) is managed with thionamides: methimazole (preferred due to once-daily dosing and lower hepatotoxicity) or propylthiouracil (PTU, preferred in the first trimester of pregnancy and thyroid storm due to its ability to block peripheral T4 to T3 conversion). Both carry a risk of agranulocytosis.

Adrenal Insufficiency

Adrenal insufficiency involves inadequate cortisol production.

• Primary Adrenal Insufficiency (Addison's Disease): Destruction of the entire adrenal cortex results in deficiencies of both glucocorticoids and mineralocorticoids. Management requires hydrocortisone (provides glucocorticoid and some mineralocorticoid activity) typically given in divided doses (e.g., two-thirds in the morning, one-third in the late afternoon to mimic diurnal rhythm) AND fludrocortisone (a potent mineralocorticoid to maintain blood pressure and sodium balance).
• Secondary Adrenal Insufficiency: Caused by pituitary dysfunction or chronic exogenous steroid use, leading to decreased ACTH. Mineralocorticoid production is preserved (as it is regulated by the RAAS system). These patients require only glucocorticoid replacement.

During times of severe physiologic stress (e.g., major surgery, trauma, severe infection), patients with adrenal insufficiency cannot mount an adequate stress response and require "stress dosing" of corticosteroids (e.g., IV hydrocortisone 50-100 mg every 6-8 hours) to prevent life-threatening adrenal crisis, characterized by profound hypotension, hypoglycemia, and shock.