ENDOCRINOLOGY

Editor: Chloe de Crecy, MD
Reviewed by: Sally Friedman, MD

Adrenal Incidentalomas

Author: Matthew Gonzalez

Background

Adrenal mass >1cm, discovered by chance on radiographic imaging
Less than 1% are malignant
Supportive of benign: <4cm in size, smooth borders, homogenous appearance, <10 HU (Hounsfield units), rapid (>50% washout) contrast washout (on "adrenal phase" imaging)
Supportive of malignancy: >4cm in size, irregular borders, >20 HU on unenhanced CT, delayed contrast washout (<50% washout), tumor calcifications, increase in size over time, presence in young pts and hx cancer

Evaluation

All incidentalomas should be screened for pheochromocytoma (~3% incidence) before operative intervention (24h urine fractionated metanephrines, catecholamines, plasma fractionated metanephrines)
Cortisol secreting adenoma (~6% incidence) causing Cushing's syndrome: baseline serum DHEAS, low dose (1mg) overnight dexamethasone suppression test
Aldosterone secreting adenoma (<1% incidence) causing hyperaldosteronism: if hypertensive (HTN) or hypokalemic order plasma aldosterone and renin, confirmatory testing with sodium loading (oral vs IV) and 24h urine aldosterone, sodium, and creatinine

Management

If benign appearing and not hormone-producing: interval imaging in ~1 year, and repeat hormone work up
Unilateral adrenal incidentaloma
If progression free (stable size, and not hormone producing) can consider monitoring cessation after 4 years
Pheochromocytomas should undergo surgical evaluation for removal
Alpha blockade (phenoxybenzamine) + propranolol prior to resection to avoid HTN crisis
Aldosteronoma: should undergo surgical evaluation for definitive treatment; if unable to undergo surgery can use mineralocorticoid antagonist (e.g. spironolactone)
Cortisoloma: if clinical significant should undergo surgical removal, will need perioperative glucocorticoid administration to avoid iatrogenic adrenal insufficiency
Macroadenomas (masses >4cm) are usually malignant and should be considered for surgical resection due to higher risk of carcinoma
Bilateral adrenal incidentalomas
Surgical evaluation + will need adrenal venous sampling to confirm laterality in hormone producing tumors

Additional Information

There can be coexisting adrenal incidentaloma and bilateral secretion of aldosterone – may require adrenal venous sampling to confirm
Not all hyperaldosterone states will have both HTN and hypokalemia
Subclinical Cushing's syndrome may be present based on initial dexamethasone suppression test, perform additional testing to determine if clinically significant

Adrenal Insufficiency

Author: Griffin Bullock

Background

Differential: Primary (Adrenals) vs Secondary (Pituitary):
Exogenous steroid use (>10mg for >3wks) undergoing severe physiologic stress or sudden discontinuation of steroid
Autoimmune adrenal insufficiency (Addison's)
Infection/Infiltration: tuberculosis, sarcoidosis, malignancy
Hemorrhage (Waterhouse-Friderichsen syndrome)
Pituitary mass/tumor, infarct, infiltration, surgery
Trauma

Presentation

Generalized weakness, lightheaded, abdominal pain, nausea, weight loss, fatigue
Lab Abnormalities: hyponatremia, hyperkalemia, hypoglycemia

Evaluation

Inpt Setting
Draw AM cortisol and ACTH (ideally 8am) → 0.25mg cosyntropin → cortisol 1h after
- Cortisol level ≥18-20 rules out primary adrenal insufficiency (and most secondary)
Outpt Setting
Draw AM cortisol level for screening (>15 rules typically rules out adrenal insufficiency)
ACTH stimulation for confirmation

Management

Consult endocrine if ACTH stimulation test is abnormal
Outpt: physiologic replacement doses usually with hydrocortisone (dosed 8am and ~2-4pm to mimic physiology). Can be dosed based on BSA or estimation based on weight. Ranges from ~20-40mg total daily (ex. 15mg AM, 10mg PM). Pt to increase if acute illness.
Adrenal crisis (if concerned, treat first, test later)
BMP, glucose monitoring, ACTH level, serum cortisol
Fluid resuscitation: NS or D5NS. Do not use hypotonic saline.
Hydrocortisone 100mg x1 followed by 50mg q8h

Central Diabetes Insipidus

Author: Chloe de Crecy

Definition

Lack of antidiuretic hormone results in free water excreted at kidneys

Etiology

Idiopathic, autoimmune, tumors (primary or secondary), infiltrative (Langerhans cell histiocytosis), congenital, trauma, surgery, severe shock/ischemia

Presentation

Polyuria, nocturia, polydipsia
Elevated Na and osmolality, only if impaired thirst. Can be normal due to compensatory thirst
Decreased bone mineral density (unclear pathophysiology)

Evaluation

Confirm polyuria w/ low Uosm (DDx: psychogenic polydipsia, central DI, nephrogenic DI)
Water restriction. If urine concentrates (Uosm>700), it is primary polydipsia not DI.
Desmopressin trial (after Na >145) to differentiate between nephrogenic vs central. Central DI responds to desmopressin.
MRI to investigate cause

Management

Desmopressin (ADH analog) - PO, IV forms. Given at bedtime.
Goal: reduce nocturia to improve sleep
Risk: hyponatremia

Diabetic Ketoacidosis (DKA)

Author: Will Bassett, Matthew Gonzalez

Background

Classically in type 1 diabetes but can also occur in insulin-dependent type 2 diabetes
Definition: ↑ blood glucose (typically >350) w/ high anion gap and ketones in blood/urine
If glucose is significantly elevated but little to no ketones/anion gap present, you likely have HHS, which is typically associated with ↑ serum osm and BG > 600

Evaluation

Labs: BMP with anion gap (AG), CBC, phos, blood gas, serum osms, UA, consider beta-hydroxybutyrate
Workup aimed at discovering the underlying cause (The "I's"):
Infection/Inflammation: CBC, CXR, UA/UCx, LFTs; consider BCx, lipase (pancreatitis). Note: Leukocytosis will be present in DKA, even if infection isn't the precipitating factor
Ischemia (MI, CVA, mesenteric ischemia): EKG, Troponin, CT(A) if clinical suspicion
Intoxication - Ethanol (can cause ketosis with or without acidosis), cocaine, MDMA
Impregnation - Beta HCG if appropriate
Insulin-openia/Iatrogenic: steroids, SGLT2 inhibitors, other meds, insulin delivery failure (pump failure, insulin degraded by heat, etc.)
Remember to correct sodium for hyperglycemia (Na + 2.4mEq * (BG-100))

Management

Initial monitoring: q2-4h BMPs (monitor K closely), q1h BG finger sticks
Can space less frequently once gap is closed x 2 and pt off insulin infusion
Ensure IV access
Start IV fluids, insulin, and potassium as below
Start insulin gtt
Start subcutaneous long-acting insulin as soon as insulin drip/IV insulin is started
- Either start home long-acting (dose reduce as needed) or if insulin naïve, Lantus 0.2-0.3u/kg/day
Lactated ringers' preferred fluid if no contraindication
Dextrose should be added when BG <200 (or clear liquid diet)
Turn off insulin drip when anion gap is closed/bicarb has normalized on two consecutive BMPs
Consult endocrinology early
Management algorithm on next page (Diabetes Care. 2009 Jul; 32(7): 1335–1343)
Note: pts are usually deficient in total body potassium even if serum potassium is high

Additional Information

Pts on insulin drip can be admitted to stepdown (8MCE) with order set
Pts can be admitted to stepdown on a subcutaneous insulin protocol with mild DKA with endocrinology guiding insulin management
Avoid ordering C-peptide if concern for new type 1 diabetes, beta islet cells can be "stunned" with recent hyperglycemic states and may be falsely low
SGLT2 inhibitors, are being prescribed much more often and can cause a euglycemic DKA, where acidosis and ketosis present but no elevated BG

Hyperthyroidism

Author: Griffin Bullock, Lauren Waskowicz

Background

Excess thyroid hormone caused by increased synthesis, excessive release of preformed thyroid hormone or endogenous/exogenous release of hormone from extrathyroid source
Low TSH and High T4 and/or T3 (primary): Graves', Toxic goiter, TSH-producing adenoma, hyperemesis gravidarum, subacute granulomatous thyroiditis, amiodarone, radiation, excessive replacement, struma ovarii
Low TSH/Normal T4 and T3: Subclinical hyperthyroidism, central hypothyroidism, non-thyroidal illness, recovery from hyperthyroidism, pregnancy (physiologic)
Subclinical Hyperthyroidism: repeat testing to verify abnormality is not transient

Presentation

Sx: Heat intolerance, tremor, palpitations, anxiety, weight loss (w/ normal/increased appetite), increased BM frequency, SOB
Physical Exam: Goiter, tachycardia/Afib, stare/lid lag, marked muscle weakness (rare presentation of thyrotoxic periodic paralysis), hyperreflexia
Graves Specific Findings: proptosis/exophthalmos, infiltrative dermopathy (localized or pretibial myxedema)

Evaluation

TSH, free T4, free T3 (only T3 or T4 may be elevated, though both often are)
Biotin affects assay, causes falsely ↓ TSH and falsely ↑ FT4/FT3
CBC: may have a normocytic anemia due to increased plasma volume

Management

Methimazole, PTU, beta blockers, radioiodine ablation, surgery
Endocrine referral

Hypoglycemia

Author: Will Bassett

Background

Definition: BG <70mg/dL
Generally worse outcomes than hyperglycemia
Causes: infection, liver failure, iatrogenic (e.g. insulin not adjusted for AKI or being NPO)
Symptoms vary from tremor, palpitations, delirium, dizziness, AMS, coma (can mimic stroke)

Management

Give PO carbohydrate load (15-20g oral glucose) if pt is alert and tolerates PO
Give IV D50 if severe (<50), or cannot take PO
Repeat measurements every 15 minutes in the first hour and treat again as needed
Give glucagon 0.5-1mg SQ/IM if no IV access and impaired consciousness
Effect is transient and IV access should be obtained ASAP for glucose infusion
DO NOT hold basal insulin for T1DM: treat the low, then reduce dose if needed

Hypothyroidism

Author: Griffin Bullock

Background

Elevated TSH and low FT4 (primary hypothyroidism)
Hashimoto's (autoimmune) thyroiditis, iodine deficiency, drugs (amiodarone, dopamine antagonists), adrenal insufficiency, thyroid hormone resistance (genetic), non-thyroidal illness (recovery phase), post-surgery or ablation for hyperthyroidism
Elevated TSH and normal FT4: subclinical hypothyroidism
Low-Normal TSH, low FT4: central hypothyroidism, sick euthyroid

Presentation

Often non-specific and vague: fatigue, cold intolerance, weight gain, constipation, dry skin, myalgia, edema, menstrual irregularities, depression, mental dysfunction
Goiter, bradycardia, diastolic hypertension, delayed relaxation following reflex testing
Lab abnormalities: microcytic anemia, hypercholesterolemia, hyponatremia, elevated CK

Evaluation

TSH: If elevated repeat TSH and obtain T4
Lipid panel, CBC, BMP

Management

Treatment required if ↓ T4, significantly ↑ TSH (>10), or symptoms with any lab abnormality
Titrate therapy to a normal TSH (unless central hypothyroidism, then target free T4 levels)
Observation of asymptomatic pts with subclinical hypothyroidism (normal T4, mild ↑ TSH)
Treatment is with formulation of T4 (full replacement is approximately 1.6 mcg/kg/day)
Initial Dose:
Young/healthy pts: full anticipated dose
Older pts or pts with CAD, atrial fibrillation: 25-50 mcg daily
Increased doses required for: pregnancy, estrogen therapy, weight gain, PPI therapy, GI disorders (↓ absorption), ferrous sulfate therapy
Risks of overtreatment: cardiac effects, increase risk of osteoporosis

Additional Information

Pts should take Levothyroxine alone, 1h prior to eating to ensure appropriate absorption. Calcium, iron, PPIs interfere the most with absorption.
Of note, missed doses can be taken along with the next dose.
Symptoms improve in 2-3 weeks. TSH steady state requires 6 weeks.
Dose can be titrated every 6 weeks based on TSH.
Pregnancy: Pregnancy causes lab changes due to differing levels thyroid binding globulin. Use tables based on trimester to interpret values.
TPO antibody testing should be conducted, as if abnormal this affects risk of complications
Hypothyroid pts are at increased risk for preeclampsia, placental abruption, preterm labor/delivery
Refer to endocrine for close monitoring and adjustment to avoid fetal complications

Inpatient Diabetes Mellitus (DM)

Author: Will Bassett, Sebastian Hinojosa

Background

Blood glucose (BG) goal
Wards: <140mg/dL fasting; <180mg/dL random;
ICU: 140-180mg/dL (NICE-SUGAR Trial)
Avoiding hypoglycemia (≤70mg/dL) is more important than targeting ideal BG
For pts with terminal illness, limited life expectancy, or high risk for hypoglycemia (E.g. pts with liver disease, impaired kidney function, elderly, poor caloric intake, low BMI), a less aggressive insulin regimen and higher BG target ranges may be reasonable
Qs to ask diabetic pt inpt: Type, age of onset, outpt provider, home regimen, method of checking sugars, last HgbA1c, steroids, complications, hypoglycemia (episodes and awareness)

Management

Insulin therapy should be initiated for the treatment of persistent hyperglycemia starting at ≥180 mg/dL (checked on at least two occasions)
Basal (long acting), prandial (premeal, short acting), and correction (sliding scale) insulin is the preferred regimen for most pts
Initial orders on admission
Typically HOLD all home oral diabetes medications
Order set "SUBCUTANEOUS INSULIN ORDER(S)"
Hemoglobin A1c: Obtain on all pts with diabetes or hyperglycemia (BG >140mg/dL) if not performed in the prior 3 months
Fingerstick blood glucose: Typically AC/HS (before meals and nightly)
Hypoglycemia management: Select all of these
Basal insulin: Select insulin glargine
Type 2 DM, consider ↓ home dose (50-60% to home dose) as often inpts have reduced PO intake and ↓ renal function
Type 1 DM, DO NOT hold basal insulin, and avoid ↓ < 80% of home dose
Insulin lispro meal: ↓ home dose by 50%, do not give while NPO
Insulin lispro correction: Start with low or medium sliding scale and ↑ prn
Carb-controlled or carb-restricted diet ('no concentrated sweets' at VA)

Insulin Adjustments

If BGs persistently ≥180
Calculate all insulin needs over 24h (basal + mealtime + sliding scale)
- Give 50% as basal and other 50% as 3 divided mealtime doses
- E.g. 10 basal + 0 mealtime + 14 sliding scale total = 24 units total daily = 12u basal + 4u TID with meals
- In insulin naïve pts, consider weight-based dosing as outlined under additional information
- In insulin naïve pts at high risk for hypoglycemia, may be reasonable to start with basal plus correctional insulin alone and readjust after 24-48 hours
If BGs < 70
If overnight/AM, reduce basal insulin dose
If daytime/post-prandial hypoglycemia, reduce mealtime and sliding scale
If endocrine consulted for inpt glucose management, notify >24h prior to discharge for recommended discharge regimen

Steroid-Induced Hyperglycemia

Steroids increase insulin resistance causing elevated postprandial BG
Insulin adjustments
Double mealtime + correction dose while leaving basal dose the same
Modified basal-bolus regimen (30% basal, 70% bolus)
Add NPH once daily (weight + dose based, per below*) if on daily prednisone
- Prednisone 10 mg = 0.1 u/kg NPH
- Prednisone 20 mg = 0.2 u/kg NPH up to 0.4 u/kg daily
*lower dose if AKI, administer at the same time as prednisone dosing
On discharge, if steroids will be longstanding, increase home insulin regimen per inpt requirements. If steroids will be tapered or discontinued soon after, either continue hospital regimen for remainder of steroid course or return to home regimen (hyper >hypoglycemia).

Additional Information

Weight-based insulin dosing
Used when starting insulin on pts with type 2 DM who are insulin naïve and hyperglycemic in the hospital
Calculate total daily dosing (TDD) between 0.3 to 0.5 units/kg/day. Then split into 50% bolus and 50% as 3 divided prandial doses
E.g. 80kg pt using low start of 0.3 u/kg/day would have TDD of 24 units. This equals 12u basal and 4u prandial insulin
Consider lower starting insulin TDD of 0.2 units/kg in pts at high risk for hypoglycemia
Tube feeds
For continuous tube feeds, dose regular insulin q6h (not TID AC as they don't have distinct "meals")
Consolidate for bolus feedings based on 24-hour insulin needs prior to discharge
Insulin pumps
Individuals who are comfortable using their diabetes devices, such as insulin pumps and CGM, should be allowed to use them in an inpt setting if they are well enough to care of the devices and have brought the necessary supplies. This requires a Diabetes Consult.
Order POC BG checks AC/HS for nurse to chart and fill out MedEx pump contract

Outpatient Diabetes

Author: Matthew Lu

Background

Type I Diabetes - insulin deficiency (GAD65, IA2, ZnT8 antibodies positive, Insulin and C-peptide inappropriately low)
Type II Diabetes - insulin resistance (generally associated with obesity)
Classification by HgA1c: Pre-diabetes: 5.7 to 6.4%; Diabetes: >= 6.5

Management

Lifestyle Changes

Exercise 175 minutes weekly
Caloric restriction for weight loss of 10%
Low carb or Mediterranean diet, reduce normal portions by 10-20%, limit sugary drinks, drink large glass of water before meals

BP Goal generally < 130/80

ACE-inhibitor is first-line anti-hypertensive

Manage Complications of Diabetes

Increased cardiovascular risk (2-4x risk of MI, CVA or death)
High intensity statin if clinical ASCVD present
Moderate intensity statin if age > 40 or with ASCVD risk factors (LDL >100, HTN, smoking, FHx of CVD, CKD)
Consider aspirin if ASCVD > 10% (balanced against bleeding risk)
Smoking cessation
Baseline ECG at diagnosis
Retinopathy – annual retinal exams
Peripheral Neuropathy – annual foot exams, can use gabapentin if present
Autonomic Neuropathy – ED, orthostatic hypotension, gastroparesis
Nephropathy – annual creatinine and urine microalbumin (albumin/creatinine ratio) - need repeat measurements 3mo apart to confirm albuminuria
Normal: < 30mg/g
Moderate albuminuria: 30-300 mg/g (consider starting ACE-I)
Severe albuminuria: > 300 mg/g (should be on ACE-I)
If persistent despite ACE-I, start SGLT2 inhibitor (if GFR allows)
If persistent despite SLGT2 inhibitor, start finerenone
Consider involving nephrology

Glycemic Goals

Fasting glucose 80-130 mg/dL, postprandial (90-120 min after meal) < 180mg/dL
A1c goal: generally < 7%, < 7.5% for 65 yrs, < 8% for poor health or life expectancy < 10 yrs

Medications for Glycemic Control

For pre-diabetes, encourage lifestyle management and consider starting metformin
If initial HgA1c < 9%
1st agent: metformin (usually decreases HgA1c by 1-2%) – start at 500mg daily and increase by 500mg every 1-2 weeks if no GI side effects up to goal 2000mg daily
- If eGFR < 45, then half dose
- If eGFR < 30, then discontinue
2nd agent (if HgA1c still not at goal within 3 months):
- GLP-1 agonist generally preferred (best weight loss benefit, usually decreases HgA1c by 1%)
- SGLT2 inhibitor preferred if pt has HF or DM nephropathy (usually decreases HgA1c by 1%)
- Consider sulfonylurea if pt on HD
3rd agent (if HgA1c still not at goal after additional 3 months)
- GLP-1 agonist or SGLT2 inhibitor (whichever was not started as second agent)
If initial HgA1c > 9%
Start metformin AND GLP-1/DDP4-I OR insulin

How to Initiate Insulin

Start with long-acting insulin nightly (10 units or 0.1 units/kg/d)
Check fasting glucose daily and increase insulin by 2 units q 2-3 days until fasting glucose within goal (80-130mg/dL)
If hypoglycemia occurs, decrease insulin by 4 units or 10% (whichever is greater)
If A1c > 7% after 3mo, add mealtime insulin
Check post-prandial glucose and start with 4 units short acting insulin at meals where post-prandial glucose > 180. Adjust by 2 units q 3 days until post-prandial glucose < 180.
When HgA1c < 6.5% consider de-escalating medications
Other medication class options: sulfonylureas, DDP4-I, thiazolidinediones

Osteoporosis

Author: Claire Lo

Background

Definition: decreased bone mass leading to increased risk of fracture
Differential: malignancy (e.g., multiple myeloma), elder abuse (e.g., spiral fractures of long bones), hyperparathyroidism, Paget's disease

	Post-Menopausal Women	Pre-Menopausal Women
Risk Factors	current smoker, >3 alcoholic drinks/day, chronic glucocorticoids (>4 weeks), previous fracture, parental history of fracture, RA, low weight bearing status	Female Athlete Triad (disordered eating, amenorrhea, bone loss)
Presentation	height loss, fragility fracture (GLF, minor trauma)	repetitive long bone stress fractures, atypical fractures (pubic ramus, femoral neck, non-metatarsal foot bones)
Screening	all women 65yo+ (Grade B USPSTF)	women <65yo w/ clinical risk factors via FRAX score (Grade B USPSTF)
Tests	Gold Standard: DEXA hip and lumbar spine Labs: 25[OH]D, calcium, phos, albumin, total protein, LFTs (ALP), PTH
Diagnosis	T score ≤ -2.5 at femoral neck or spine OR fragility fracture of vertebra, pelvis, wrist, humerus, rib
Management	vitamin D supplementation, calcium if necessary, smoking cessation, weight bearing activity, Rx
Monitoring	DEXA q 2 years (for osteoporosis), q 4 years (for osteopenia), q15 years (for normal BMD).

Evaluation

Interpretation of DEXA Score
Osteoporosis: T score ≤ -2.5
Osteopenia: -1.0 > T score > -2.5
Normal bone mineral density: T score ≥ -1.0
Interpretation of FRAX (Fracture Risk Assessment Tool):
10-year risk of major osteoporotic fracture (Google "FRAX tool.")

Pharmacologic Management

Indications: T score ≤ -2.5 (osteoporosis) OR -1.0 > T score > -2.5 with FRAX>3% for hip fracture
First line: oral bisphosphonates (alendronate 10mg qd, at least 30min before food)
If eGFR<30: refer to endocrinology for IV zoledronic acid or IV denosumab
If severe (T score< -3.0): consider anabolic (e.g., teriparatide) as first line agent

Additional Information

There is currently no recommendation to screen men for osteoporosis.
Nodules that do not meet FNA criteria, US findings determine the timing for follow-up imaging:
High suspicion: 6-12mo
Low to intermediate suspicion: 12-24mo
Nodules >1cm with very ↓ suspicion OR pure cyst: >24mo if at all
Nodules <1cm with very ↓ suspicion OR pure cyst: no further imaging necessary

Outpatient Medical Weight Loss

Author: Liana Mosley

Background

74% of US adults are overweight/obese
Target weight loss of 5-7% body weight for prevention of co-morbidities
In general, encourage lifestyle modifications (dietary interventions, exercise) first
See Obesity/Nutrition under Outpt Medicine

Management

Consider referral to medical weight loss: BMI ≥ 30 or ≥ 27 with with ≥ 1 co-morbidity
Referral to surgical weight loss: BMI ≥ 35 or ≥ 30 with with ≥ 1 co-morbidity

Medical Weight Loss

Medication	Mechanism	Side Effects	Other considerations
Metformin	Unclear MOA, potentially appetite suppression	N/V/D, lactic acidosis in renal failure	1st line, low cost, T2DM prevention/treatment
Orlistat (Xenical)	Reduces fat absorption	Fatty diarrhea, gas, abdominal pain	Significant side effect profile
Phentermine-topiramate (Qsymia)	Appetite suppression, early satiety	Constipation, dizziness, dry mouth, taste changes, anxiety, insomnia, HTN, tachycardia, cognitive slowing	Risk of rebound weight gain Discontinuing can lead to withdrawal
Phentermine (Ionamin)	Reduces appetite, FDA-approved for short-term use (up to 12 wks)	Constipation, dizziness, dry mouth, taste changes, anxiety, insomnia, HTN, tachycardia	Risk of rebound weight gain Discontinuing can lead to withdrawal
Naltrexone-bupropion (Contrave)	Appetite suppression, early satiety	Constipation, diarrhea, dizziness, dry mouth, HA, increased BP, tachycardia, insomnia, liver damage, N/V, SI	Risk of rebound weight gain Discontinuing can lead to withdrawal
Liraglutide (Saxenda)	GLP-1 agonist Appetite suppression Victoza: low dose formulation, FDA approved for T2D but not weight loss	N/V/D, constipation, abdominal pain, HA, tachycardia, dizziness, injection site reaction, pancreatitis	Contraindicated: pancreatitis, medullary thyroid ca, MEN2A/MEN2B
Semaglutide (Wegovy/Ozempic/Rybelsus)	GLP-1 agonist Appetite suppression Rybelsus = PO option, FDA approved for T2D but not weight loss	N/V/D, abdominal pain, constipation, injection site reaction, pancreatitis	STEP8 RCT: Semaglutide >Liraglutide Contraindicated: pancreatitis, medullary thyroid ca, MEN2A/MEN2B
Tirzepatide (Mounjaro/Zepbound)	GLP-1 agonist + GIP receptor agonist	N/V/D, abdominal pain, constipation, injection site reaction, pancreatitis	T2DM: superior to GLP1 agonist (lowered A1c 2.0-2.5%) Obesity: weight loss of 15-20% from bl Contraindicated: pancreatitis, medullary thyroid ca, MEN2A/MEN2B

Panhypopituitarism

Author: Chloe de Crecy

Etiology

Originates from hypothalamus vs anterior pituitary. Time course: acute vs insidious.
Hypothalamic: mass (benign vs malignant), radiation, infiltrative dz (sarcoid), infections (TB), TBI, stroke
Pituitary: mass (adenoma, cysts), surgery, radiation, infiltrative dz (hypophysitis, hemochromatosis), infection, infarction, apoplexy, genetic mutations, empty sella

Evaluation

Not all hormones are always affected. Secretion of GH and gonadotropins more likely affected than ACTH and TSH.
Consult Endocrine

Axis	Symptoms	Testing	Replacement
CRH – ACTH – Cortisol (Adrenals)	Fatigue, weight loss, hypoglycemia	AM cortisol(↓) ACTH (↓) Cosyntropin Stim test	Hydrocortisone (~15-25mg total daily) Prednisone
TRH – TSH – T4/T3 (Thyroid)	Fatigue, cold intolerance, constipation, bradycardia, skin changes, anemia, delayed reflexes	TSH, T4, T3 (all ↓)	Levothyroxine
GnRH – LH/FSH - Estrogen, androgens (Gonads)	Hypogonadism F: anovulation, hot flashes, vaginal atrophy, decreased bone density M: decreased energy/libido, low energy, decreased muscle mass, decreased spermatogenesis	F w/ amennorhea: LH, FSH, estradiol, medroxyprogesterone challenge (withdrawal bleeding) M: LH	F: estradiol (+ progestin if uterus) M: Testosterone (injection, gel, patch) or hCG if trying to conceive
GHRH – Growth hormone – liver, fat	Children: short stature Adults: decrease in lean body mass, decrease in bone density, dyslipidemia	IGF-1 (↓)	Recombinant growth hormone
Dopamine (inhibitor) – Prolactin – mammary glands	Inhibited lactation	Not done	Not done

Severe Hypertriglyceridemia (HTG)

Author: Chloe de Crecy

Background

Elevated triglycerides (TG) on a fasting lipid panel
Normal: <150 mg/dL
Moderate HTG: 150-499 mg/dL
Moderate to severe HTG: 500-999 mg/dL
Severe HTG: >1000 mg/dL
Nearly all pts with severe HTG have a genetic predisposition + additional risk factor (e.g. DM, alcohol abuse, oral estrogen, hypothyroidism, nephrotic syndrome, propofol, ART)
Risks of hypertriglyceridemia: pancreatitis (requires serum TG >500 mg/dL), ASCVD
Signs: xanthomas, hepatosplenomegaly, lipemia retinalis, milky appearance of plasma
Sxs: short-term memory loss, abdominal pain, flushing with ETOH

Evaluation

Lipid panel: usual outpt screening, acute pancreatitis, cutaneous xanthomas, familial HTG, monitoring HTG treatment
Note: Na, glucose, amylase, LDL readings can be affected by HTG
Consider sending A1c, Cr, TSH
Assess medication list for secondary causes

Management

HTG Induced Pancreatitis

If pt has hypocalcemia, lactic acidosis, or multi-organ dysfunction
Initiate plasmapheresis and monitor serum TG after each cycle until <500
Severe dietary fat restriction (<5%) until TG <1000
If none of the above and pt is hyperglycemic
Start insulin gtt, IVF, monitor q1h BG and q12h TG
Discontinue insulin when serum TG <500
Severe dietary fat restriction (<5%) until TG <1000
If none of the above and pt is euglycemic
Start insulin gtt + dextrose, Monitor q12h TG until <500
Severe dietary fat restriction (<5%) until TG <1000

Long-term Management (once TG <1000, otherwise decreased efficacy)

Pharmacologic: fibrates (most commonly fenofibrate), statins, niacin, omega-3 fatty acids
Nonpharmacologic: discontinue ETOH use, dietary fat and sugar restriction (target fat intake at <10% of calorie intake), exercise

Steroid Conversion Chart

Author: Neil Phillips

Drug Name	Equivalent doses (mg)	Anti-inflammatory activity relative to hydrocortisone	Duration of action (hrs)
Hydrocortisone (cortisol)	20	1	8 to 12
Cortisone acetate	25	0.8	8 to 12
Prednisone	5	4	12 to 36
Prednisolone	5	4	12 to 36
Methylprednisolone	4	5	12 to 36
Triamcinolone	4	5	12 to 36
Dexamethasone	0.75	30	36 to 72
Betamethasone	0.6	30	36 to 72

Stress Dose Steroids

Author: Griffin Bullock

Primary Options

Dexamethasone 4mg IV: does not affect cortisol assays, ideal if diagnosis uncertain
Hydrocortisone 100mg IV bolus then 50mg q8h until stable: greater mineralocorticoid activity. Ideal if adrenal insufficiency known/confirmed or if hyperkalemic (K>6.0)

When to Use

Concern for adrenal crisis
Pts with known adrenal insufficiency:
Minor Illness: ↑ dose x3 for 3 d or until clinically improved & acute stress resolved
Surgery: dependent on severity of operation
Minor (e.g. hernia repair): hydrocortisone 25mg for 1 day
Moderate (e.g. cholecystectomy): 50-75mg day of surgery and post-op day 1
Major (e.g. CABG): 100-150mg daily 2-3 days (would consult endocrine in this case)

Thyroid Nodules

Author: Terra Swanson

Background

~50% of adults will have a thyroid nodule on ultrasound
Benign: goiter, cyst, inflammatory, Hashimoto's, follicular adenoma (microadenoma)
Malignant: follicular, papillary, medullary, anaplastic, metastatic, thyroid lymphoma
Risk factors for malignancy: age <30, head or neck radiation, family history of thyroid cancer

Evaluation

Initial work-up after a nodule is found (either clinically or incidentally on imaging)
TSH, Free T4, Thyroid U/S

Management

If Low TSH: Likely a hyperfunctioning nodule (benign in 95% of cases)

Order Iodine-123 or technetium-99m thyroid scan
If hyperfunctioning → measure T3/free T4 if ↑, treat for hyperthyroidism
If non-functioning → proceed as if TSH were normal

Normal or elevated TSH:

FNA indicated based on U/S findings listed below (determined by TI-RADS system)
Nodules >1cm that have high- or intermediate-suspicion pattern
Nodules >1.5cm that have low-suspicion pattern
Nodules >2cm that have very-low-suspicion pattern
FNA cytology determines the plan of action:
Benign → periodic US monitoring at 12-24mo, then at increasing intervals
Indeterminate → repeat FNA in 3-12 months
Malignant → surgical referral

Thyroid Storm

Author: Ben French

Exaggerated signs/symptoms of thyrotoxicosis causing multi-organ dysfunction in the presence of a precipitating insult.
Common precipitants: amiodarone, Graves' disease, surgery (especially thyroid surgery), pregnancy, infection, MI, PE, medication non-compliance, iodine loads
Common presenting symptoms: tachycardia/arrythmia, new CHF, AMS, hyperthermia, diaphoresis, GI upset, new jaundice
If concerned for thyroid storm, use the Burch-Wartofsky Point Scale (BWPS), available on MDCalc
45 is highly suggestive
25-44 impending thyroid storm
<25 unlikely to represent thyroid storm
NOTE: the degree of free thyroid hormone elevation has not been shown to correlate with the incidence of thyroid storm

Management

ENDOCRINE EMERGENCY – ASAP consult to Endocrinology
Treatment of underlying precipitant
Supportive care including cooling blankets, vasopressors, and intubation if indicated
Decrease T4 to T3 conversion (give both medications):
PO propranolol 60-80mg every 4 hours (use cautiously in acute CHF, avoid in shock)
IV hydrocortisone 300mg load, followed by 100mg every 8 hours
Block thyroid hormone synthesis and secretion (PTU or MMI, plus Lugol's):
PTU: 500-1000mg loading dose, followed by 250mg every 4 hours (PO, rectal)
Methimazole: 20mg every 4-6 hours (PO, rectal, IV)
Lugol's solution 8 drops (0.4ml) every 6 hours, starting at least one hour after initiation of PTU or methimazole. (Lugol's is an iodine-containing solution. Iodine suppresses thyroid hormone release via the Wolff-Chaikoff effect.)
Refractory storm: plasmapheresis and plasma exchange

After recovery, patients should be recommended for definitive treatment with radioactive iodine therapy or thyroidectomy.