Endocrinology

Diabetic Ketoacidosis

Diabetic ketoacidosis (DKA) is a life-threatening hyperglycemic emergency characterized by severe metabolic acidosis, elevated anion gap, and ketonemia. Early recognition and aggressive management are essential.

Precipitating Factors (The "I"s)

• Insulin noncompliance - Most common precipitant in known diabetics
• Infection - Pneumonia, urinary tract infection, sepsis
• Inflammation - Pancreatitis, myocarditis, gastroenteritis
• Ischemia - Myocardial infarction, stroke, mesenteric ischemia
• Intoxication - Alcohol, cocaine, other substances
• Iatrogenic - Corticosteroids, antipsychotics, SGLT2 inhibitors
• Trauma - Motor vehicle collision, fall, burn injury

Clinical Presentation

Rapid Onset

DKA symptoms may develop over hours. Classic presentation includes polyuria, polydipsia, nausea/vomiting, and progressive altered mental status.

Symptoms: - Polyuria and polydipsia (osmotic effect of hyperglycemia) - Nausea and vomiting (from acidosis and ketonemia) - Abdominal pain (may mimic acute abdomen) - Dyspnea and Kussmaul's respirations (compensatory for metabolic acidosis) - Altered mental status progressing to coma

Physical Examination: - Signs of dehydration (tachycardia, hypotension, poor skin turgor) - Kussmaul's respirations - deep, rapid breathing with fruity odor - Altered mental status or frank coma - Abdominal tenderness (may be present despite benign imaging)

Laboratory Findings

Pseudohyponatremia

Severe hyperglycemia causes water shifts from intracellular to extracellular space, decreasing measured serum sodium. Calculate corrected sodium: Corrected Na = Measured Na + [2.4 × (Glucose - 100)/100]

Expected Laboratory Pattern:

Test	Finding	Explanation
Glucose	>250 mg/dL	Severe hyperglycemia
pH	<7.35	Metabolic acidosis
Bicarbonate	<15 mEq/L	Consumed by buffering acid
Anion gap	>12	Elevated from ketoacids (acetoacetate, beta-hydroxybutyrate)
Potassium	Often elevated	Acidosis drives K+ out of cells despite total body depletion
BUN/Creatinine	Elevated	Dehydration concentrates urine
Osmolality	>320 mOsm/kg	Markedly elevated from glucose and electrolytes
Urinalysis	Positive ketones	Ketonuria from accelerated lipolysis

DKA vs Hyperosmolar Hyperglycemic State (HHS)

Feature	DKA	HHS
Glucose	Usually 250-600	Often >600
Serum osmolality	<320	>320
Arterial pH	<7.35	>7.35
Bicarbonate	<15	>15
Anion gap	Elevated	Normal
Ketones	Present	Absent/minimal
Mental status	Variable	More altered
Mortality	1-5%	5-15%

Initial Diagnostic Workup

Urgent Laboratory Studies: - Comprehensive metabolic panel (electrolytes, glucose, BUN, creatinine) - Arterial or venous blood gas (assess pH and bicarbonate) - Serum ketones or beta-hydroxybutyrate (more specific than urine ketones) - Urinalysis with ketones - Complete blood count (assess for infection as precipitant) - Venous or arterial lactate - Pregnancy test (if female of childbearing age) - Magnesium level (depletions common)

Assess for Precipitants: - Blood cultures if infection suspected - Chest X-ray - Electrocardiogram (rule out MI as precipitant) - Abdominal imaging if abdominal pain prominent - Urine drug screen if intoxication possible

DKA Management Algorithm

Critical Management Points

Potassium Paradox

Despite total body potassium depletion, initial serum potassium is often elevated due to acidosis. As insulin and fluids are given, potassium will fall dramatically. Monitor closely and supplement proactively to avoid hypokalemia-induced arrhythmias.

Fluid Resuscitation: - Start aggressive crystalloid replacement: 1-2L in first 1-2 hours - Route electrolytes based on corrected sodium - After initial bolus: 250-500 mL/hr based on sodium level - When glucose <250: switch to D5-containing solution (prevents hypoglycemia) - Target restoration of circulating volume, which dramatically improves glucose clearance

Insulin Therapy: - Initial bolus: 10 units regular IV (optional; some protocols omit) - Continuous infusion: 0.1 U/kg/hour (e.g., 70 kg patient = 7 U/hr) - Goal: decrease blood glucose 75-100 mg/dL per hour - As anion gap closes (usually 8-12 hours), transition to subcutaneous insulin - Critical: Do NOT stop IV insulin immediately; overlap with subcutaneous

Potassium Management: - If K+ >5: monitor, no replacement - If K+ 3.5-5: add 10-20 mEq/hour to IV fluids - If K+ <3.5: HOLD insulin immediately, give aggressive potassium (PO + IV) - Check level q2-4h initially, then q4-6h as situation stabilizes

Bicarbonate: - Rarely indicated; avoid unless pH <6.9 - If given: 100 mmol sodium bicarbonate in 200 mL sterile water at 200 mL/hour - May worsen hypokalemia and hypomagnesemia - Repeat only if pH remains <7.0 after 2 hours

Monitoring: - BMP every 4 hours until patient stable - Point-of-care glucose checks every 1-2 hours - Continuous cardiac monitor (especially for potassium changes) - Reassess anion gap to confirm resolution

---

Inpatient Diabetes Management

Managing diabetes in hospitalized patients differs significantly from outpatient management. The goal is to prevent hyperglycemia complications while avoiding hypoglycemia.

General Inpatient Principles

Stop Oral Agents

Discontinue all oral diabetes medications upon admission. Their metabolic effects are unpredictable in acute illness. Use insulin-based regimens exclusively.

Key Rules: - Hold all oral antidiabetic agents (metformin, sulfonylureas, GLP-1 agonists, DPP-4 inhibitors) - Type 1 diabetes MUST receive some basal insulin (risk of DKA if omitted) - Type 2 diabetes on insulin alone should resume home dose (adjusted for acute illness) - Type 2 diabetes on oral agents: start sliding scale insulin

Total Daily Insulin (TDI) Calculation

Calculate basal-bolus insulin dosing based on body weight:

$$\text{TDI (units/day)} = 0.4 \text{ units/kg}$$

Alternative for elderly (>70 years), renal insufficiency (Cr >1.5), or tight glycemic control goal: $$\text{TDI} = 0.3 \text{ units/kg}$$

Distribution: - Basal insulin: 50% of TDI given as long-acting insulin (insulin glargine/degludec) once daily at bedtime - Bolus insulin: 50% of TDI divided among meals (roughly 1/3 at each meal)

Example TDI Calculation

Patient: 80 kg male, standard dosing

$$\text{TDI} = 0.4 \times 80 = 32 \text{ units/day}$$

• Basal: Insulin glargine 16 units subcutaneous once nightly
• Bolus: 16 units total distributed at meals
• Breakfast: ~5 units rapid-acting insulin
• Lunch: ~5 units rapid-acting insulin
• Dinner: ~6 units rapid-acting insulin

Supplemental Sliding Scale

Correct for glucose above target with rapid-acting insulin:

$$\text{Supplemental insulin} = \frac{\text{Current BG} - 100}{30} \text{ units}$$

Example: BG 280 mg/dL → (280 - 100)/30 = 6 units additional insulin

Adjusting Insulin Regimen

Review the previous day's blood glucose values and supplemental insulin use:

1. Calculate total supplemental insulin given over 24 hours
2. Divide by 2: One-half of supplemental insulin increases basal dosing, one-half increases bolus dosing
3. Apply adjustment:
4. Increase basal insulin by ½ of supplemental amount
5. Increase next day's bolus dosing by ½ of supplemental amount

Example: Patient received 20 units total supplemental insulin over 24 hours - Increase basal insulin by 10 units (basal: 16 → 26 units) - Increase bolus insulin by 10 units total (bolus: 16 → 26 units divided among meals)

Glycemic Targets

Prevent Both Extremes

Avoid both hypoglycemia (<70 mg/dL) and excessive hyperglycemia (>300 mg/dL). Tight control (110-140 mg/dL) increases hypoglycemia risk and may increase mortality.

General Hospital Target: 140-180 mg/dL fasting and premeal

ICU Target: 140-180 mg/dL (avoid tight targets <110 mg/dL due to hypoglycemia risk)

Special Populations: - Cardiac ICU: may target slightly tighter (120-160) - Pregnant patients with gestational diabetes: tighter control (fasting <95, 1-hour postmeal <140)

---

Hyperthyroidism

Hyperthyroidism represents excessive thyroid hormone production. Management depends on etiology and severity.

Etiologic Classification by Radioactive Iodine Uptake

The radioactive iodine uptake (RAIU) scan differentiates hyperthyroid etiologies:

RAIU Pattern	Likely Diagnosis	Management
Diffuse uptake	Graves' disease (immune-mediated)	Antithyroid drugs, beta-blockade, or radioactive iodine
Heterogeneous uptake	Multinodular goiter (toxic multinodular)	Antithyroid drugs or radioactive iodine
Single focus	Toxic nodule (single autonomous nodule)	Radioactive iodine or surgical removal
Low/no uptake	Thyroiditis (subacute, viral, post-partum) OR exogenous thyroid hormone	Supportive care; discontinue exogenous hormone if applicable

Thyroid Storm

Thyroid storm is a rare but life-threatening complication of uncontrolled hyperthyroidism characterized by severe thyrotoxicosis with systemic manifestations.

Medical Emergency

Thyroid storm has mortality approaching 10% even with treatment. Mortality is higher if diagnosis is delayed or treatment is inadequate.

Diagnostic Criteria (not standardized): - High fever (often >39°C) - Extreme tachycardia (often >140 bpm) - Altered mental status (confusion, delirium, coma) - Gastrointestinal symptoms (nausea, vomiting, diarrhea, hepatomegaly) - Precipitants: acute infection, anesthesia, iodine administration, beta-blocker withdrawal

Emergency Management:

Treatment Sequence (CRITICAL - order matters): 1. Beta-blocker first (propranolol) - blocks peripheral conversion T4→T3 AND reduces cardiac manifestations 2. Antithyroid drug (PTU preferred for faster action) - blocks new hormone synthesis 3. Wait 1 hour - allows antithyroid drug to prevent the iodine from being incorporated into new hormone 4. Iodine (Lugol or SSKI) - inhibits release of preformed hormone; NEVER give without antithyroid drug 5. Glucocorticoid (hydrocortisone) - reduces conversion T4→T3 and provides adrenal support 6. Supportive care - cooling measures, aggressive fluid resuscitation, antibiotics if infection present

---

Hypothyroidism

Hypothyroidism is thyroid hormone deficiency, classified as primary (thyroid gland failure) or secondary (pituitary/hypothalamic failure).

Primary vs Secondary Hypothyroidism

Parameter	Primary Hypothyroidism	Secondary Hypothyroidism
Affected level	Thyroid gland	Pituitary or hypothalamus
TSH	Elevated	Low or normal
Free T4	Low	Low
Common causes	Hashimoto's, iodine deficiency, post-thyroidectomy	Hypopituitarism, pituitary adenoma, post-transsphenoidal surgery

Etiologies of Primary Hypothyroidism

Most Common: - Hashimoto's thyroiditis - autoimmune thyroid destruction, anti-TPO/anti-thyroglobulin antibodies - Iodine deficiency - world's most common preventable cause - Post-ablative - radioactive iodine, surgery, external radiation

Medication-Induced: - Antithyroid drugs (propylthiouracil, methimazole) - Amiodarone (high iodine content) - Lithium - Thionamides - Beta-interferon, interleukin-2

Clinical Stages

Early/Subclinical Hypothyroidism: - Elevated TSH with normal free T4 - Often asymptomatic - Screen for cardiac risk factors before treating

Overt Hypothyroidism: - Elevated TSH with low free T4 - Fatigue and lethargy - Cold intolerance - Weight gain (average 5-10 pounds) - Constipation, dry skin, hair loss - Bradycardia, decreased cardiac contractility

Myxedema (Severe Hypothyroidism): - Severe metabolic slowing - Facial and periorbital edema - Pleural effusions, ascites, pericardial effusion - Altered mental status - Severe bradycardia and hypotension

Myxedema Coma (Rare, Medical Emergency): - Life-threatening complication of profound, untreated hypothyroidism - Extreme bradycardia, hypotension, hypothermia - Altered consciousness progressing to coma - Often triggered by infection, anesthesia, or medication

Hypothyroidism Treatment

Clinical Scenario	Levothyroxine Dosing	Recheck TSH	Special Considerations
New diagnosis, uncomplicated	1.7 mcg/kg/day (~100-125 mcg for average adult)	6-8 weeks	Adjust by 25-50 mcg increments based on TSH
Elderly or cardiac risk	Start lower: 0.3-0.5 mcg/kg/day (~25-50 mcg)	6-8 weeks	Titrate slowly to avoid cardiac stress
Severe hypothyroidism with cardiac disease	Start very low: 12.5-25 mcg daily	4-6 weeks	May need stress testing before treatment
Myxedema coma	ICU care: loading dose 200-400 mcg IV then 50-100 mcg IV daily	Continuous monitoring	Add T3 (liothyronine 5-20 mcg q4-6h IV) if unstable

Myxedema Coma Management

Medical Emergency

Myxedema coma requires ICU admission and intensive monitoring. Mortality exceeds 50% even with treatment.

Immediate Interventions:

1. IV Levothyroxine Loading: 200-400 mcg IV bolus, then 50-100 mcg IV once daily
2. Bypass GI absorption; IV route preferred for reliable delivery

3. Loading dose rapidly repletes central hormone stores

4. Add Liothyronine (T3) if Unstable:

5. 5-20 mcg IV q4-6h
6. T3 has more rapid action than T4

7. Use in severely ill/cardiovascular unstable patients

8. Empiric Hydrocortisone:

9. 100 mg IV q6-8h initially
10. Prevents adrenal crisis (adrenal insufficiency may coexist)

11. Taper as clinical improvement occurs

12. Supportive Care:

13. Passive external rewarming (avoid active rewarming - can cause shock)
14. Mechanical ventilation if respiratory depression
15. Careful fluid administration (avoid fluid overload; myxedema patients have total body water excess)

16. Treat precipitant (infection with antibiotics, manage medication withdrawal, etc.)

17. Monitoring:

18. Continuous cardiac monitoring (risk of arrhythmias)
19. Frequent vital signs
20. Serial TSH and free T4 levels
21. Transition to oral levothyroxine when stable and able to tolerate PO

---

Adrenal Insufficiency

Adrenal insufficiency results from inadequate cortisol and/or aldosterone production. Recognition is essential to prevent life-threatening hypotension and electrolyte abnormalities.

Classification

Primary Adrenal Insufficiency (Addison's Disease): - Direct adrenal gland failure - Low cortisol, elevated ACTH (appropriate response) - Loss of both cortisol and aldosterone

Secondary Adrenal Insufficiency: - Pituitary or hypothalamic failure - Low cortisol, low ACTH (inappropriately low response) - Aldosterone production preserved

Common Etiologies

Primary Adrenal Insufficiency: - Autoimmune - 70% of cases in developed countries - Tuberculosis - most common cause worldwide - Vascular - hemorrhage (sepsis, anticoagulation), thrombosis - Metastatic disease - lung, breast, lymphoma - Medications - azole antifungals, etomidate (single doses can cause adrenal suppression)

Secondary Adrenal Insufficiency: - Chronic glucocorticoid use - most common cause - Pituitary adenoma or apoplexy - Hypothalamic/pituitary surgery or radiation - Traumatic brain injury

Clinical Presentation

Acute Adrenal Crisis: - Profound hypotension (often <80 mmHg systolic) - Tachycardia with severe symptoms - Severe dehydration - Hyponatremia and hyperkalemia - Abdominal pain with or without acute abdomen finding - Altered mental status - Fever (infection may be precipitant)

Chronic Primary Adrenal Insufficiency: - Fatigue and weakness - Hyperpigmentation (from elevated ACTH) - Salt craving - Weight loss - Orthostatic hypotension

Chronic Secondary Adrenal Insufficiency: - Fatigue and weakness - Hypoglycemia (loss of cortisol's counter-regulatory effect) - No hyperpigmentation (ACTH not elevated) - Often subtle presentation

Diagnostic Approach

Screening - Early Morning Cortisol: - Cortisol <5 μg/dL - highly suggestive of insufficiency (further testing needed) - Cortisol >18 μg/dL - adequately rules out insufficiency - Cortisol 5-18 μg/dL - borderline, requires confirmatory testing

Confirmation - ACTH Stimulation Test (Cosyntropin Test): - Administer cosyntropin 250 mcg IV - Measure cortisol at baseline, 30, and 60 minutes - Normal response: cortisol rises to >20 μg/dL - Abnormal: cortisol <18-20 μg/dL at 30-60 minutes = AI confirmed

Differentiate Primary vs Secondary: - Elevated ACTH (>100 pg/mL) = Primary insufficiency - Low or normal ACTH = Secondary insufficiency

Localize Secondary Insufficiency: - Primary insufficiency: abdominal CT (assess for TB, hemorrhage, adrenal enlargement) - Secondary insufficiency: brain MRI (assess pituitary, hypothalamic structure)

Acute Adrenal Crisis Management

Life-Threatening Emergency

Do not wait for confirmatory testing in suspected acute adrenal crisis. Start glucocorticoids immediately - risk of not treating far outweighs risk of inappropriate treatment.

Immediate Interventions:

1. Hydrocortisone IV:
2. Initial: 100 mg IV bolus immediately
3. Maintenance: 50-100 mg IV q6h × first 24 hours

4. Taper over 1-3 days as clinical stability improves

5. Aggressive Fluid Resuscitation:

6. Normal saline 1-2 L in first 1-2 hours
7. Additional 1-2 L over 2-4 hours
8. Restore intravascular volume, correct hyponatremia through dilution

9. Avoid hypotonic fluids (worsens hyponatremia)

10. Identify and Treat Precipitant:

11. Sepsis: broad-spectrum antibiotics after cultures
12. Medication withdrawal: resume medication

13. Surgery/trauma: continue hydrocortisone coverage

14. Monitoring and Transition:

15. Continuous cardiac monitoring (hypokalemia risk)
16. Monitor BP, heart rate, electrolytes
17. As hemodynamically stable, begin oral glucocorticoid replacement
18. Usually transition to prednisone 5-10 mg daily

Chronic Adrenal Insufficiency Maintenance

Glucocorticoid Replacement: - Prednisone 5 mg each morning (matches normal cortisol production) - Or hydrocortisone 15-25 mg divided (15 mg AM, 5-10 mg PM) - Adjust based on clinical response

Mineralocorticoid Replacement (Primary AI only): - Fludrocortisone 0.05-0.2 mg once daily - Goal: maintain BP, normalize sodium and potassium - Essential in primary insufficiency; NOT needed in secondary

Sick Day Rules: - During acute illness, fever, surgery: increase glucocorticoid dose 2-3 fold - Infection: 50-100 mg hydrocortisone q6-8h or prednisone 20-30 mg q6-8h - Resume baseline dosing when acute illness resolves

Emergency Preparedness: - Provide patient with dexamethasone 4 mg IM prefilled syringe for emergency use - Medic-Alert bracelet/card - Written emergency action plan - Educate family members on recognition and emergency management

Key Management Points

Prevention of Crisis

Patient education about stress-dosing, recognizing symptoms, and emergency access to medications prevents most adrenal crises. Patients must understand they require lifelong replacement therapy and cannot stop medications suddenly.

Patient Education: - Adrenal insufficiency is a chronic condition requiring lifelong treatment - NEVER discontinue glucocorticoids without medical supervision - Increase dose during stress, illness, or fever - Always carry emergency glucocorticoid (dexamethasone syringe) - Wear medical alert identification - Notify all healthcare providers of condition before any procedures

---

Last update: April 20, 2026