4.1 Endocrine
Key Takeaways
- The Endocrine System is 8% of the PANRE blueprint, with diabetes mellitus, thyroid disorders, and metabolic syndrome the highest-yield topics for recertifying PAs
- Type 2 diabetes is generally diagnosed by an A1C of 6.5% or higher, a fasting plasma glucose of 126 mg/dL or higher, or a 2-hour OGTT value of 200 mg/dL or higher, each confirmed on repeat testing
- Metformin remains the typical first-line oral agent for type 2 diabetes unless contraindicated, while GLP-1 receptor agonists and SGLT2 inhibitors are favored when there is established cardiovascular or kidney disease
- Primary hypothyroidism shows a high TSH with a low free T4 and is treated with levothyroxine; Graves disease is the most common cause of hyperthyroidism
- Primary adrenal insufficiency (Addison disease) classically presents with hyperpigmentation, hyponatremia, hyperkalemia, and a low cortisol that fails to rise with cosyntropin stimulation
The Endocrine System is 8% of the NCCPA PANRE blueprint. For a recertifying Physician Assistant (PA), the testable skill is rapid pattern recognition: read a lab panel, name the disorder, and pick the first-line therapy. Diabetes, thyroid disease, and metabolic syndrome dominate the section because they are the conditions PAs manage most often in primary and acute care.
Diabetes Mellitus: Diagnosis
Diabetes mellitus (DM) is a group of disorders of chronic hyperglycemia. The American Diabetes Association (ADA) diagnostic criteria are tested heavily. Any one of the following, confirmed on a repeat test (unless the patient has unequivocal hyperglycemia with classic symptoms), establishes the diagnosis.
| Test | Diabetes | Prediabetes |
|---|---|---|
| Hemoglobin A1C | 6.5% or higher | 5.7% to 6.4% |
| Fasting plasma glucose | 126 mg/dL or higher | 100 to 125 mg/dL |
| 2-hour OGTT | 200 mg/dL or higher | 140 to 199 mg/dL |
| Random glucose + symptoms | 200 mg/dL or higher | N/A |
A1C reflects average glycemia over roughly the prior 3 months and does not require fasting. It can be unreliable in conditions that alter red cell turnover, such as hemoglobinopathies, recent transfusion, or pregnancy.
Type 1 vs Type 2
- Type 1 DM results from autoimmune beta-cell destruction with absolute insulin deficiency; patients require insulin and are prone to diabetic ketoacidosis (DKA).
- Type 2 DM results from insulin resistance with relative deficiency; it is strongly associated with obesity and metabolic syndrome.
Diabetes Mellitus: Management
Glycemic targets are individualized. A common A1C goal for many nonpregnant adults is below 7%, with less stringent goals for limited life expectancy or high hypoglycemia risk.
Metformin is typically the first-line oral agent unless contraindicated (advanced kidney disease, acute illness with hypoxia or instability). Drug class selection increasingly follows comorbidity, not just glucose level:
- SGLT2 inhibitors are favored with heart failure or chronic kidney disease; they also lower cardiovascular risk.
- GLP-1 receptor agonists are favored with atherosclerotic cardiovascular disease and support weight loss.
- Insulin is added when oral and noninsulin agents do not achieve targets, and is required in type 1 DM.
Acute Complications
DKA (more typical of type 1) shows hyperglycemia, anion-gap metabolic acidosis, and ketosis; management centers on fluids, insulin, and careful potassium replacement. Hyperosmolar hyperglycemic state (HHS) (more typical of type 2) produces severe hyperglycemia and marked hyperosmolarity with minimal ketosis.
Thyroid Disorders
Thyroid questions hinge on interpreting thyroid-stimulating hormone (TSH) with free thyroxine (free T4).
| Pattern | TSH | Free T4 | Typical Interpretation |
|---|---|---|---|
| Primary hypothyroidism | High | Low | Hashimoto thyroiditis is the most common cause in the U.S. |
| Subclinical hypothyroidism | High | Normal | Often monitored; treat selectively |
| Primary hyperthyroidism | Low | High | Graves disease is the most common cause |
| Subclinical hyperthyroidism | Low | Normal | Risk of atrial fibrillation and bone loss |
Hypothyroidism is treated with levothyroxine, titrated to TSH. Graves disease is an autoimmune cause of hyperthyroidism and may present with a diffuse goiter and ophthalmopathy; treatment options include antithyroid drugs (methimazole), radioactive iodine, or surgery. Thyroid storm is a life-threatening hyperthyroid emergency.
Adrenal Disorders
- Primary adrenal insufficiency (Addison disease): low cortisol with hyperpigmentation, fatigue, hyponatremia, and hyperkalemia. The cosyntropin (ACTH) stimulation test shows a blunted cortisol rise. Adrenal crisis is treated emergently with stress-dose glucocorticoids and fluids.
- Cushing syndrome: cortisol excess causing central obesity, striae, hypertension, and hyperglycemia. Exogenous steroids are the most common cause overall.
- Pheochromocytoma: catecholamine-secreting tumor causing episodic hypertension, palpitations, headache, and sweating.
Pituitary Disorders
- Prolactinoma is the most common functioning pituitary tumor, causing galactorrhea, menstrual changes, or low libido.
- Acromegaly results from growth hormone excess in adults.
- Diabetes insipidus causes dilute polyuria from deficient or ineffective antidiuretic hormone, distinct from diabetes mellitus.
Calcium and Bone Metabolism
Primary hyperparathyroidism is a common cause of outpatient hypercalcemia (high calcium, high or inappropriately normal parathyroid hormone). Osteoporosis is screened with bone density testing; management combines calcium, vitamin D, weight-bearing activity, and pharmacologic therapy such as bisphosphonates in higher-risk patients.
Lipids and Metabolic Syndrome
Metabolic syndrome is a cluster of cardiometabolic risk factors: central adiposity, elevated triglycerides, low HDL cholesterol, elevated blood pressure, and elevated fasting glucose. Statins are the cornerstone of pharmacologic lipid management for atherosclerotic cardiovascular disease risk reduction, layered onto lifestyle change.
Exam Strategy
Lead with the lab pattern, then the diagnosis, then first-line therapy. Watch for distractors that swap primary and secondary disease, or that pick a second-line drug when a first-line option is not contraindicated.
A 54-year-old patient with obesity has two separate fasting plasma glucose values of 142 mg/dL and 136 mg/dL and an A1C of 7.1%. There are no acute symptoms. What is the most appropriate interpretation and initial pharmacologic step?
A 38-year-old reports fatigue, salt craving, and weight loss. Exam shows hyperpigmentation. Labs show hyponatremia, hyperkalemia, and a low morning cortisol. Which test best confirms the suspected diagnosis?
A patient has a low TSH with an elevated free T4, a diffuse goiter, and ophthalmopathy. Which is the most likely diagnosis?