Step 3 · 5–7%

Endocrine System

Diabetes in the office and the hospital, thyroid, adrenal, pituitary, calcium and bone.

Diabetes in the office

Confirm the diagnosis and the type, set an A1c goal that fits the person, choose drugs by heart, kidney and weight, and keep up with yearly complication checks.

Rules to know

A1c ≥6.5%, fasting glucose ≥126 or 2-hour OGTT ≥200 → diabetes; confirm with a second abnormal result unless symptomatic with random glucose ≥200
A1c 5.7–6.4% or fasting glucose 100–125 → prediabetes; structured lifestyle program, recheck yearly
Prediabetes with BMI ≥35, age under 60 or prior gestational diabetes → consider metformin
A1c unreliable (hemolysis, transfusion, pregnancy, advanced CKD, iron deficiency) → rely on glucose readings, fructosamine or CGM
Lean adult with weight loss, ketosis or quick failure of oral agents → GAD65 and other islet antibodies, C-peptide; autoimmune diabetes needs insulin
Young, lean, antibody-negative mild diabetes running through generations → MODY; genetic testing (GCK needs no drug, HNF1A responds to sulfonylurea)
Most nonpregnant adults → A1c below 7%; tighter if safe, looser (below 8%) with frequent hypoglycemia, frailty or limited life expectancy
Type 2 diabetes without heart or kidney disease → metformin plus lifestyle change; extended-release or slow titration for GI upset
Type 2 with atherosclerotic disease → GLP-1 receptor agonist or SGLT2 inhibitor with proven cardiovascular benefit, regardless of A1c
Type 2 with heart failure, reduced or preserved → SGLT2 inhibitor regardless of A1c
Type 2 with CKD and albuminuria (eGFR ≥20) → SGLT2 inhibitor; add GLP-1 agonist as needed; finerenone if albuminuria persists on ACE inhibitor or ARB
Type 2 with obesity → GLP-1 agonist or tirzepatide to lower glucose and weight together
Metformin with eGFR below 30 → stop it; do not start at 30–45; hold around iodinated contrast if eGFR is under 30 or AKI
SGLT2 inhibitor → genital yeast infection, volume depletion, euglycemic ketoacidosis; pause during acute illness or prolonged fasting
GLP-1 agonist → nausea, gallstones, rare pancreatitis; contraindicated with personal or family medullary thyroid cancer or MEN2
Sulfonylurea in an older adult or with CKD → hypoglycemia risk; avoid glyburide, glipizide if one is needed
Pioglitazone → fluid retention, weight gain and fractures; avoid in heart failure
A1c ≥10%, glucose ≥300, weight loss or ketosis → start insulin now; it can often be simplified later
Starting basal insulin → 10 units or 0.1–0.2 units/kg nightly, raise 2 units every 3 days to fasting 80–130
Basal above 0.5 units/kg, large bedtime-to-morning drop or hypoglycemia → stop raising basal; add GLP-1 agonist or mealtime insulin
High fasting glucose despite basal increases → check overnight values (CGM or 3 a.m. reading) before changing the dose
Type 1 diabetes → basal-bolus or pump with CGM, automated delivery when possible; screen TSH and celiac serology
Glucose below 70 in an alert patient → 15–20 g fast-acting carbohydrate, recheck in 15 minutes, repeat if still low, then a snack
Severe hypoglycemia unable to swallow → nasal or injected glucagon at home, IV dextrose in hospital; prescribe glucagon to every insulin user
Hypoglycemia on a sulfonylurea → observe for many hours or admit; lows recur as the drug lingers
Hypoglycemia unawareness → raise targets and avoid all lows for 2–3 weeks; CGM with alarms
Sick day with diabetes → keep basal insulin, check ketones in type 1, pause metformin and SGLT2 inhibitor while dehydrated
Every diabetes visit → blood pressure goal below 130/80; statin for ages 40–75, high intensity with ASCVD or high risk
Albuminuria on 2 of 3 urine samples → ACE inhibitor or ARB; screen urine albumin-to-creatinine ratio and eGFR yearly
Retinal exam → at type 2 diagnosis, 5 years after type 1 diagnosis, then every 1–2 years
Yearly comprehensive foot exam with monofilament and pulses → inspect feet at every visit if neuropathy or prior ulcer
Painful diabetic neuropathy → pregabalin, duloxetine or gabapentin; foot care and glucose control slow damage

Traps that cost points

Waiting for metformin to fail before adding an SGLT2 inhibitor in heart failure→ Heart, kidney and atherosclerotic disease call for an agent with proven organ benefit now, independent of A1c or metformin use.
Pushing a frail 85-year-old to an A1c of 6.5%→ Hypoglycemia causes falls, arrhythmia and confusion; relax the goal to about 8% or simply avoid symptomatic highs and any lows.
Raising basal insulin indefinitely while mealtime glucose stays high→ Beyond about 0.5 units/kg basal adds hypoglycemia without fixing postprandial highs; add a GLP-1 agonist or prandial insulin.
Combining a DPP-4 inhibitor with a GLP-1 agonist→ They act on the same pathway and add little; stop the DPP-4 inhibitor when starting the GLP-1 agonist.
Prescribing semaglutide to a patient whose sister had medullary thyroid cancer→ Personal or family medullary thyroid cancer or MEN2 contraindicates GLP-1 agonists; choose an SGLT2 inhibitor or other agent.
Telling a type 1 patient with vomiting to skip insulin→ Basal insulin must continue even without food; check ketones, drink fluids and seek care if ketones rise.
Diagnosing diabetes from one A1c of 6.6% in a patient without symptoms→ Confirm with a repeat test or a second abnormal test; one value is not enough without hyperglycemic symptoms.
Assuming every lean adult with new diabetes has type 2→ Check islet antibodies; latent autoimmune diabetes progresses to insulin dependence and fails oral agents.

DKA, HHS & hospital glucose

In the Brain

Fluids before insulin, potassium before insulin when it is low, dextrose before stopping insulin, and basal-bolus orders instead of sliding scale; plus the workup for hypoglycemia without diabetes.

Rules to know

Ketonemia with pH below 7.3 or bicarbonate below 18 → diabetic ketoacidosis when glucose is ≥200 or diabetes is known
Glucose ≥600, effective osmolality above 300, little ketosis, pH ≥7.3 → hyperosmolar hyperglycemic state
DKA or HHS at arrival → isotonic crystalloid 500–1,000 mL/hour, labs, ECG, search for trigger (infection, missed insulin, MI, SGLT2 inhibitor)
Potassium below 3.5 in DKA → hold insulin and replace potassium first
Potassium 3.5–5.0 → add 20–40 mEq per liter while insulin runs; above 5.0 → start insulin, recheck every 2 hours
DKA insulin → IV regular insulin infusion near 0.1 units/kg/hour, continued even as glucose falls
Glucose below 250 during DKA treatment → add dextrose to the fluids and keep insulin running until ketoacidosis clears
DKA resolved (pH ≥7.3, bicarbonate ≥18, ketones cleared) and eating → subcutaneous basal insulin 1–2 hours before stopping the infusion
Bicarbonate in DKA → only when pH is below 7.0
Phosphate in DKA → replace only below 1.0 mg/dL or with heart failure or respiratory weakness
Ketoacidosis with glucose under 250 on an SGLT2 inhibitor → euglycemic DKA; stop the drug, give dextrose with insulin from the start
Child in DKA with headache, falling consciousness or slowing pulse during treatment → cerebral edema; mannitol or hypertonic saline before imaging
HHS → larger fluid deficit; start insulin once glucose stops falling with fluids alone; lower glucose and osmolality gradually
Measured sodium during hyperglycemia → add about 1.6 mEq/L for each 100 mg/dL glucose above 100
Eating inpatient who needs insulin → basal plus mealtime plus correction doses; sliding scale alone is inadequate
Inpatient glucose goal → 140–180 for most ward and ICU patients; persistent ICU readings over 180 → insulin infusion
Insulin-naive inpatient → about 0.3–0.5 units/kg/day total (less if elderly or CKD), half basal and half prandial
NPO patient on insulin → continue basal, usually reduced about 20%, plus correction; never stop basal in type 1
Admission with hyperglycemia → A1c if none in the past 3 months; it guides the discharge regimen
Morning prednisone with afternoon and evening hyperglycemia → morning NPH sized to the steroid dose, reduced as the steroid tapers
Night before surgery → about 75–80% of usual long-acting insulin; half the morning NPH; hold oral agents and mealtime insulin
SGLT2 inhibitor before elective surgery → stop 3 days ahead (4 for ertugliflozin) to prevent ketoacidosis
Perioperative glucose → keep 100–180 mg/dL around surgery
Alert inpatient who manages an insulin pump → may continue it with endocrine input; confused or critically ill → switch to IV or basal-bolus
Hypoglycemia without diabetes → confirm Whipple triad; during a low draw insulin, C-peptide, proinsulin, beta-hydroxybutyrate and sulfonylurea screen
High insulin with low C-peptide → exogenous insulin (factitious or given by someone else)
High insulin and C-peptide, positive sulfonylurea screen → secretagogue ingestion
High insulin and C-peptide, negative drug screen → insulinoma; 72-hour fast if needed, CT, MRI or endoscopic ultrasound, then resection
Low glucose with suppressed insulin → sepsis, liver or kidney failure, adrenal insufficiency, alcohol or IGF-2 secreting tumor
Necrolytic migratory erythema, new diabetes and weight loss → glucagonoma; glucagon level and pancreatic imaging

Traps that cost points

Starting the insulin drip before the potassium returns→ Insulin drives potassium into cells and can cause fatal arrhythmia; if potassium is below 3.5, replace it before any insulin.
Stopping the insulin infusion once glucose reaches 200→ Glucose falls faster than ketones clear; add dextrose and continue insulin until acidosis and ketosis resolve.
Turning off the drip and giving the first basal dose at the same time→ IV insulin lasts minutes; give subcutaneous basal 1–2 hours before stopping the infusion to avoid rebound ketoacidosis.
Giving bicarbonate for a DKA pH of 7.1→ Bicarbonate does not speed recovery above pH 7.0 and can worsen hypokalemia and cerebral edema.
Covering inpatients with sliding-scale insulin alone→ Reactive dosing chases highs and causes swings; use scheduled basal and prandial insulin with a correction scale.
Stopping basal insulin in an NPO type 1 patient→ Without basal insulin ketoacidosis starts within hours; continue a reduced basal dose and add correction insulin.
Sending a confused child in DKA to CT before treating→ Cerebral edema is a clinical diagnosis; give mannitol or hypertonic saline first, then image.
Missing DKA because glucose is only 180 in a patient on empagliflozin→ SGLT2 inhibitors cause ketoacidosis with near-normal glucose; check ketones and blood gas in any ill patient taking them.

Thyroid

In the Brain

TSH first, then free T4. Uptake or antibodies explain thyrotoxicosis, nodules go through TSH, ultrasound and size-based FNA, and storm or myxedema coma is treated before the labs return.

Rules to know

Suspected thyroid disease in a stable outpatient → TSH first; free T4 if TSH is abnormal
High TSH with low free T4 → primary hypothyroidism, usually Hashimoto; levothyroxine about 1.6 mcg/kg in young healthy adults
Older adult or coronary disease starting levothyroxine → 25–50 mcg daily, increase slowly
Any levothyroxine dose change → recheck TSH after 6–8 weeks; yearly once stable
TSH 4.5–10 with normal free T4 → repeat in 2–3 months with TPO antibodies; treat if TSH ≥10 or pregnant or planning pregnancy
Mildly raised TSH in someone over 70 → often normal for age; usually do not treat
Low free T4 with low or normal TSH → central hypothyroidism; check cortisol and pituitary MRI; dose by free T4, not TSH
Central hypothyroidism with possible ACTH deficiency → hydrocortisone before levothyroxine to avoid adrenal crisis
Hypothyroid woman with a positive pregnancy test → raise levothyroxine about 25–30% at once; TSH every 4 weeks in the first half
Low TSH with high free T4 or T3 → TSH-receptor antibodies or radioactive iodine uptake to find the cause
Diffuse high uptake, eye signs or positive receptor antibodies → Graves disease
Graves disease → beta-blocker plus methimazole for 12–18 months; radioactive iodine or thyroidectomy are definitive options
Sore throat or fever on methimazole or PTU → stop the drug and check a neutrophil count
Graves disease in the first trimester → PTU; switch to methimazole after the first trimester
Graves with active eye disease → no radioactive iodine if moderate-to-severe, steroid cover if mild; stop smoking
Large compressive goiter, suspicious nodule or severe eye disease → thyroidectomy
Hot nodule or patchy uptake → toxic adenoma or multinodular goiter; radioactive iodine or surgery, since drugs do not cure
Tender thyroid after a viral illness, high ESR, low uptake → subacute thyroiditis; NSAID or prednisone plus beta-blocker, no methimazole
Thyrotoxicosis with low uptake and low thyroglobulin → exogenous thyroid hormone
Painless thyrotoxicosis 1–4 months postpartum, low uptake → postpartum thyroiditis; beta-blocker, then watch for hypothyroidism
Amiodarone therapy → TSH at baseline and every 3–6 months; hypothyroidism gets levothyroxine while amiodarone continues
Amiodarone thyrotoxicosis → type 1 (iodine-driven) gets methimazole; type 2 (destructive) gets glucocorticoids
Fever, delirium, AF and heart failure in hyperthyroidism → thyroid storm; ICU, propranolol, PTU, iodine an hour later, hydrocortisone, cooling
Hypothermia, stupor, low sodium and hypoventilation in hypothyroidism → myxedema coma; ICU, IV hydrocortisone, then IV levothyroxine
Critically ill patient with low T3 and low-normal TSH → nonthyroidal illness; do not treat, retest after recovery
High free T4 with normal or high TSH → exclude assay interference (biotin), then TSH-secreting adenoma; pituitary MRI
Thyroid nodule ≥1 cm → TSH first; low TSH → radionuclide scan, and hot nodules need no biopsy
Nodule with normal or high TSH → ultrasound; FNA for suspicious nodules ≥1 cm, low-suspicion ≥1.5 cm; pure cysts need none
Indeterminate FNA cytology → molecular testing, repeat FNA or diagnostic lobectomy
Papillary thyroid cancer → lobectomy or thyroidectomy by size and risk; radioiodine for higher risk; follow thyroglobulin
Medullary thyroid cancer or high calcitonin → RET testing; exclude pheochromocytoma before thyroid surgery
Newborn screen with high TSH → confirm serum TSH and free T4 and start levothyroxine immediately

Traps that cost points

Giving methimazole for painful subacute thyroiditis→ Hormone leaks from a damaged gland; synthesis is not increased. Use beta-blockers and anti-inflammatories.
Titrating levothyroxine to TSH in pituitary disease→ TSH is unreliable when the pituitary fails; aim free T4 at mid-to-upper normal.
Starting levothyroxine before cortisol in hypopituitarism→ Thyroid hormone speeds cortisol clearance and can trigger adrenal crisis; replace glucocorticoid first.
Ordering radioactive iodine uptake in a pregnant or breastfeeding woman→ Radioiodine is contraindicated; use TSH-receptor antibodies and clinical features instead.
Sending a hot nodule for FNA→ Autonomous nodules are rarely malignant; treat the hyperthyroidism rather than biopsy.
Treating low T3 in a septic ICU patient→ Nonthyroidal illness is adaptive; hormone replacement does not help. Recheck after recovery.
Giving iodine before the thionamide in thyroid storm→ Iodine first can fuel new hormone synthesis; give PTU or methimazole and wait about an hour.
Starting 100 mcg levothyroxine in an 80-year-old with angina→ Full doses can provoke ischemia or AF; start low and titrate every 6–8 weeks.

Adrenal disorders

In the Brain

Treat a suspected adrenal crisis before the result returns, screen for Cushing in the right order, and work up every incidentaloma for hormones and imaging features.

Rules to know

Fatigue, weight loss, darkened skin, low sodium, high potassium → primary adrenal insufficiency; 8 a.m. cortisol with ACTH, then cosyntropin test
Low peak cortisol after cosyntropin → adrenal insufficiency; high ACTH means primary, low or normal means pituitary or steroid suppression
Primary adrenal insufficiency → 21-hydroxylase antibodies; if negative, adrenal CT for tuberculosis, hemorrhage or metastases
Hypotension unresponsive to fluids, abdominal pain, vomiting, known steroid use → adrenal crisis; hydrocortisone 100 mg IV now plus saline with dextrose
Suspected adrenal crisis → draw cortisol and ACTH only if no delay; never wait for results before hydrocortisone
Primary adrenal insufficiency maintenance → divided-dose hydrocortisone plus fludrocortisone; secondary disease needs no fludrocortisone
Any adrenal insufficiency → double or triple dose for fever, injectable hydrocortisone kit, medical alert ID
Prednisone ≥20 mg daily for over 3 weeks or cushingoid → assume axis suppression; taper and give stress doses for surgery
Glucocorticoid course under 3 weeks → stop without taper
Ritonavir or cobicistat with inhaled, nasal or injected fluticasone or triamcinolone → iatrogenic Cushing, then adrenal suppression
Purple striae, proximal weakness, easy bruising, facial plethora → test for Cushing after excluding exogenous steroids
Cushing testing → two of: late-night salivary cortisol, 24-hour urine free cortisol, 1-mg overnight dexamethasone test (cortisol above 1.8 abnormal)
Confirmed hypercortisolism with low ACTH → adrenal CT; adenoma → adrenalectomy with glucocorticoid cover afterward
ACTH-dependent Cushing → pituitary MRI; small or no adenoma → inferior petrosal sinus sampling; pituitary source → transsphenoidal surgery
Rapid hypercortisolism with severe hypokalemia and very high ACTH → ectopic ACTH (small cell lung cancer, carcinoid); chest CT
Adrenal mass found on imaging → 1-mg dexamethasone test for all; metanephrines unless clearly lipid-rich; aldosterone-renin if hypertensive or hypokalemic
Nonfunctioning incidentaloma under 4 cm, homogeneous, ≤10 HU unenhanced → benign adenoma; no further imaging
Indeterminate incidentaloma (over 10 HU, heterogeneous or ≥4 cm) → washout CT, MRI or PET, or adrenalectomy; biopsy only after metanephrines
Episodic headache, sweating and palpitations with hypertension → plasma free or 24-hour urine fractionated metanephrines
Positive metanephrines → adrenal CT or MRI; alpha-blocker 1–2 weeks with fluids, beta-blocker only after alpha, then adrenalectomy
Pheochromocytoma or paraganglioma → germline genetic testing for every patient (MEN2, VHL, NF1, SDH)
Hypertension with low potassium, resistance, adrenal mass, AF or sleep apnea → morning aldosterone-to-renin ratio
High aldosterone with suppressed renin → confirmatory testing unless obvious, adrenal CT, then adrenal vein sampling if surgery is wanted
Unilateral aldosterone-producing adenoma → laparoscopic adrenalectomy; bilateral hyperplasia → spironolactone or eplerenone
Hypertension and hypokalemia with low renin and low aldosterone → licorice, Liddle syndrome or other mineralocorticoid excess
Anticoagulated or septic patient with flank pain and shock → bilateral adrenal hemorrhage; hydrocortisone
Large adrenal mass with rapid virilization or mixed hormone excess → adrenocortical carcinoma; surgical resection
Child with abdominal mass crossing the midline or opsoclonus-myoclonus → neuroblastoma; urine catecholamine metabolites and imaging
Addison disease with hypoparathyroidism and chronic mucocutaneous candidiasis → autoimmune polyglandular syndrome type 1; with thyroiditis or type 1 diabetes → type 2

Traps that cost points

Waiting for a cosyntropin test before treating suspected adrenal crisis→ Hydrocortisone first; a delay can be fatal. Confirm the diagnosis once the patient is stable.
Starting a beta-blocker first for pheochromocytoma hypertension→ Unopposed alpha stimulation can cause a hypertensive crisis; begin alpha blockade and add a beta-blocker only afterward.
Biopsying an adrenal mass before checking metanephrines→ Needling a pheochromocytoma can trigger a crisis; adrenal biopsy is rarely useful and only after biochemical exclusion.
Adding fludrocortisone for adrenal insufficiency caused by long-term prednisone→ Secondary insufficiency spares the renin-aldosterone axis; glucocorticoid replacement alone is enough.
Screening for Cushing with a random morning cortisol→ A single cortisol neither confirms nor excludes Cushing; use late-night saliva, 24-hour urine or low-dose dexamethasone testing.
Testing for Cushing during acute illness or heavy drinking→ Stress, alcohol, depression and severe obesity raise cortisol physiologically; test when the condition settles.
Stopping long-term prednisone abruptly before surgery→ A suppressed axis cannot mount a stress response; continue it and add perioperative stress dosing.
Sending a 55-year-old with primary aldosteronism and a CT adenoma straight to surgery→ Nonfunctioning adenomas are common with age; adrenal vein sampling confirms which side secretes before adrenalectomy.

Pituitary & water balance

In the Brain

Prolactin, IGF-1 and the morning hormones name the pituitary problem. Dopamine agonists come before surgery for prolactinomas, cortisol replacement always comes first, and polyuria is sorted by a water deprivation test.

Rules to know

Galactorrhea, amenorrhea or low libido → prolactin after pregnancy test, TSH, creatinine and drug review
Raised prolactin on an antipsychotic or metoclopramide → drug effect; switch drug or add aripiprazole rather than a dopamine agonist
High prolactin with no drug, pregnancy, kidney or thyroid cause → pituitary MRI
Prolactinoma of any size, even with visual loss → cabergoline first; surgery if resistant or intolerant
Large pituitary mass with only mildly high prolactin → stalk effect from a nonfunctioning tumor, or hook effect; ask the lab to dilute
Prolactinoma in pregnancy → stop cabergoline for microadenoma; macroadenoma needs visual field checks each trimester
Larger hands and jaw, sweating, sleep apnea, new diabetes → acromegaly; IGF-1 first, then glucose-suppressed GH, then MRI
Acromegaly → transsphenoidal surgery; residual disease → somatostatin analog or pegvisomant; screen with colonoscopy and echocardiogram
Nonfunctioning macroadenoma with visual field loss → transsphenoidal surgery after full hormone testing
Incidental pituitary microadenoma → hormone screen; repeat MRI at 1 year if nonfunctioning
Sudden severe headache, vision loss, ophthalmoplegia, hypotension in a pituitary tumor → apoplexy; IV hydrocortisone, MRI, neurosurgery
Severe postpartum hemorrhage, then failed lactation, amenorrhea, fatigue → Sheehan syndrome; check cortisol and free T4
Hypopituitarism → replace cortisol first, then thyroid, then sex steroids and growth hormone
Headache and fatigue on a checkpoint inhibitor → hypophysitis; check ACTH, cortisol, TSH and free T4
Child with headache, bitemporal field loss, poor growth, calcified suprasellar mass → craniopharyngioma; surgery
Polyuria over 3 L/day of dilute urine → exclude glucose, calcium and potassium causes, then water deprivation test
Urine concentrates only after desmopressin → central diabetes insipidus (AVP deficiency); desmopressin, watch sodium
No urine response to desmopressin → nephrogenic diabetes insipidus (AVP resistance) from lithium or hypercalcemia; thiazide, amiloride for lithium
Polyuria with low-normal sodium, urine concentrates during deprivation → primary polydipsia
After pituitary surgery → check sodium daily; DI, then SIADH, then lasting DI may follow
Euvolemic hyponatremia with concentrated urine → exclude hypothyroidism and adrenal insufficiency before calling it SIADH
Hyperparathyroidism plus pituitary tumor or pancreatic neuroendocrine tumor → MEN1; genetic testing and family screening
Medullary thyroid cancer plus pheochromocytoma → MEN2; RET testing, prophylactic thyroidectomy in childhood for carriers
Mucosal neuromas and marfanoid build → MEN2B; thyroidectomy within the first year of life

Traps that cost points

Sending a macroprolactinoma with visual loss to surgery first→ Cabergoline usually shrinks the tumor and restores vision within days to weeks; surgery is for resistance or intolerance.
Checking a random growth hormone level for acromegaly→ GH is pulsatile; screen with IGF-1 and confirm with failure of GH suppression after glucose.
Giving thyroid hormone before hydrocortisone in panhypopituitarism→ Raising metabolism with untreated cortisol deficiency can precipitate adrenal crisis; cortisol comes first.
Treating a large tumor with prolactin of 80 as a prolactinoma→ Stalk compression raises prolactin modestly; a nonfunctioning macroadenoma needs surgery, and a giant prolactinoma may read falsely low until diluted.
Labeling hyponatremia as SIADH without thyroid and cortisol tests→ Hypothyroidism and adrenal insufficiency mimic SIADH and need hormone replacement, not fluid restriction.
Prescribing desmopressin for lithium-induced polyuria→ The kidney cannot respond to vasopressin; stop lithium if possible and use amiloride or a thiazide.
Adding cabergoline to an antipsychotic for drug-induced hyperprolactinemia→ Dopamine agonists can worsen psychosis; switch or add aripiprazole, or replace sex hormones if needed.
Treating recurrent ulcers and kidney stones separately without checking calcium→ Hypercalcemia with gastrinoma points to MEN1; screen calcium, PTH and the pituitary, and test relatives.

Calcium, parathyroid & bone

In the Brain

PTH sorts hypercalcemia, clear criteria decide parathyroidectomy, and osteoporosis care runs on DXA, fracture risk, the right first drug and a planned drug holiday.

Rules to know

High calcium → confirm with albumin-corrected or ionized calcium, then intact PTH
High or inappropriately normal PTH with high calcium → primary hyperparathyroidism; check 24-hour urine calcium and creatinine
Mild hypercalcemia, very low urine calcium (clearance ratio below 0.01), family history → familial hypocalciuric hypercalcemia; no surgery
Primary hyperparathyroidism → surgery if symptomatic, calcium >1 above normal, age under 50, osteoporosis or vertebral fracture, eGFR under 60, stones or hypercalciuria
Parathyroid imaging (sestamibi, ultrasound, 4D-CT) → only to plan surgery after biochemical diagnosis, never to make it
Primary hyperparathyroidism managed without surgery → yearly calcium and creatinine, DXA every 1–2 years; cinacalcet for calcium, bisphosphonate for bone
Hypercalcemia with suppressed PTH → PTHrP, 1,25-vitamin D, 25-vitamin D, protein electrophoresis and free light chains, TSH
High 1,25-vitamin D with low PTH → granulomatous disease or lymphoma; glucocorticoids lower the calcium
Calcium above 14 or confusion → IV saline, calcitonin, then zoledronic acid (denosumab if kidney failure); loop diuretic only for overload
Mild hypercalcemia on a thiazide → stop it and recheck in 3 months; persistent elevation suggests underlying hyperparathyroidism
Long-term lithium with high calcium and PTH → lithium-associated hyperparathyroidism; manage like primary disease
High PTH with normal calcium → check 25-vitamin D and kidney function; replete vitamin D before diagnosing normocalcemic hyperparathyroidism
Perioral tingling, cramps, Chvostek or Trousseau sign after neck surgery → hypocalcemia from parathyroid injury
Tetany, seizure or long QT with low calcium → IV calcium gluconate on a monitor, then oral calcium and calcitriol
Hypocalcemia that will not correct → check and replace magnesium first
Low calcium with high PTH → vitamin D deficiency, CKD, pancreatitis, or PTH resistance (short fourth and fifth metacarpals)
Chronic hypoparathyroidism → calcium plus calcitriol, aim for low-normal calcium, monitor urine calcium for stones
Bone pain, weakness, low phosphate, high alkaline phosphatase, pseudofractures → osteomalacia; replace vitamin D and calcium
Assessing vitamin D status → measure 25-hydroxyvitamin D; 1,25-vitamin D only for hypercalcemia or kidney disease workups
Women 65 and older, or younger postmenopausal women with risk factors → DXA screening; test men with fractures, steroids or hypogonadism
Who needs osteoporosis drug therapy → T-score ≤ −2.5, hip or vertebral fragility fracture, or osteopenia with 10-year FRAX hip ≥3% or major ≥20%
Before osteoporosis drugs → calcium, creatinine, 25-vitamin D, TSH, alkaline phosphatase; testosterone in men; electrophoresis with vertebral fracture
First-line osteoporosis drug → oral alendronate or risedronate, fasting, plain water, upright 30 minutes
Esophageal stricture, cannot sit upright, CrCl under 35 or low calcium → no oral bisphosphonate; zoledronic acid or denosumab instead
After a hip fracture → start osteoporosis therapy; zoledronic acid lowers new fractures and death
Very high fracture risk (recent fracture, T ≤ −3.0, fracture on therapy) → anabolic first (teriparatide, abaloparatide, romosozumab), then an antiresorptive
Romosozumab → avoid if MI or stroke in the past year
Denosumab → never stop without a follow-on bisphosphonate (rebound vertebral fractures); severe hypocalcemia risk in advanced CKD
Five years of oral or 3 of IV bisphosphonate, now lower risk → 2–3 year drug holiday; high risk continues to 10 oral or 6 IV
Thigh or groin ache on long-term bisphosphonate → atypical femur fracture; bilateral femur x-rays, stop the drug
Planned high-dose IV bisphosphonate or denosumab for cancer → dental evaluation first to lower osteonecrosis of the jaw risk
Older adult, bone pain, high ALP with normal GGT → Paget disease; x-ray and bone scan, zoledronic acid if symptomatic; watch hearing and skull growth

Traps that cost points

Ordering a sestamibi scan to diagnose primary hyperparathyroidism→ The diagnosis is biochemical; imaging only localizes the gland once surgery is planned, and a negative scan does not exclude disease.
Sending familial hypocalciuric hypercalcemia for parathyroidectomy→ Check the urine calcium-to-creatinine clearance ratio first; FHH is benign and surgery does not correct it.
Starting with furosemide for severe hypercalcemia→ Patients are volume depleted; give IV saline first and use a loop diuretic only for fluid overload.
Stopping denosumab without a plan→ Bone loss and multiple vertebral fractures rebound within months; transition to a bisphosphonate.
Ordering 1,25-dihydroxyvitamin D to look for deficiency→ 1,25-vitamin D can be normal or high in deficiency because PTH rises; 25-hydroxyvitamin D reflects stores.
Replacing calcium repeatedly in a hypomagnesemic patient→ Low magnesium blocks PTH release and action; correct magnesium and calcium will follow.
Continuing alendronate indefinitely in a low-risk woman→ Reassess at 5 years; lower-risk patients take a holiday to limit atypical fracture and jaw osteonecrosis.
Withholding treatment for a vertebral fragility fracture because the T-score is −2.0→ A hip or vertebral fragility fracture establishes osteoporosis regardless of the T-score; treat.

Growth, puberty & reproductive hormones

In the Brain

Growth velocity and bone age separate normal variants from disease, LH separates central from peripheral puberty, and testosterone is prescribed only after two low morning levels and a fertility conversation.

Rules to know

Short child, normal velocity, bone age matching age, short parents → familial short stature; reassure
Short child with normal velocity, delayed bone age, late-blooming parent → constitutional delay; expect normal adult height
Child crossing height percentiles downward → disease likely; CBC, metabolic panel, celiac serology, TSH, IGF-1, bone age, karyotype in girls
Weight falling before height → nutritional or GI disease (celiac, IBD); height falling with weight kept or gained → endocrine cause
Short girl with webbed neck, broad chest or delayed puberty → Turner syndrome; karyotype, echocardiogram, renal ultrasound
Low IGF-1 with slow growth → growth hormone stimulation testing and pituitary MRI; GH therapy if deficient
Breast development before 8 or testicular growth before 9 → bone age and basal LH, with GnRH stimulation if unclear
Central precocious puberty with pubertal LH → brain MRI (all boys, girls under 6); GnRH agonist to protect adult height
Precocious puberty with suppressed LH → peripheral source: CAH, gonadal or adrenal tumor, McCune-Albright, exposure to testosterone gel
Isolated breast buds in a toddler with normal growth and bone age → premature thelarche; observe
Isolated pubic hair and body odor with normal growth, mildly high DHEA-S → premature adrenarche; observe
No breast development by 13 or no testicular enlargement by 14 → bone age, LH, FSH, prolactin, TSH
Delayed puberty with high FSH → primary gonadal failure; karyotype for Turner or Klinefelter
Delayed puberty with low LH and FSH and no sense of smell → Kallmann syndrome; sex steroid replacement
Tall adolescent with small firm testes, gynecomastia, high FSH → Klinefelter syndrome (47,XXY); testosterone and fertility referral
Newborn at 1–2 weeks with vomiting, low sodium, high potassium, shock → salt-wasting 21-hydroxylase CAH; IV saline, hydrocortisone, fludrocortisone
Virilized 46,XX newborn or high 17-hydroxyprogesterone on screening → CAH; karyotype, electrolytes, no early sex assignment
Woman with hirsutism and irregular cycles resembling PCOS → early-morning follicular 17-hydroxyprogesterone for nonclassic CAH
CAH with hypertension → 11-beta-hydroxylase deficiency if virilized; 17-alpha-hydroxylase if no puberty and low potassium
Primary amenorrhea, breasts present, absent uterus, scant pubic hair → androgen insensitivity (46,XY); remove testes after puberty
Ambiguous genitalia at birth with virilization at puberty → 5-alpha-reductase deficiency
Rapid virilization in an adult woman (deep voice, clitoromegaly) → testosterone and DHEA-S; very high levels → image ovaries and adrenals
Man with low libido, erectile dysfunction or fatigue → two early-morning fasting total testosterone levels before any diagnosis
Confirmed low testosterone → LH and FSH; high means testicular failure; low or normal → prolactin, iron studies, drug review, MRI if very low
Hypogonadal man hoping to father a child soon → avoid testosterone, which suppresses sperm; hCG or clomiphene instead
Before testosterone therapy → hematocrit and PSA in men over 40; avoid with hematocrit over 50%, untreated severe sleep apnea, prostate or breast cancer
Man on testosterone → hematocrit and testosterone at 3–6 months, then yearly; hold therapy if hematocrit exceeds 54%
Muscular athlete with small testes, acne, high hematocrit, low gonadotropins → anabolic steroid use; stop, recovery is slow
New gynecomastia in an adult man → drug and alcohol review, testicular exam, hCG, LH, testosterone, estradiol, TSH, liver and kidney tests
Gynecomastia with testicular mass or high hCG → testicular ultrasound for germ cell or Leydig cell tumor
Hard, eccentric, fixed breast mass or bloody discharge in a man → mammogram and biopsy for breast cancer
Recent painful drug-related gynecomastia → stop the drug; tamoxifen if persistent; long-standing fibrotic tissue needs surgery

Traps that cost points

Starting testosterone in a hypogonadal man who wants a child this year→ Exogenous testosterone shuts down spermatogenesis; use hCG or clomiphene to raise testosterone and preserve fertility.
Diagnosing hypogonadism from one afternoon testosterone level→ Testosterone peaks in the morning and varies day to day; confirm with two early fasting samples.
Prescribing growth hormone for familial short stature→ Normal velocity with bone age matching age is a normal variant; reassure and track growth.
Skipping a karyotype in a short girl without obvious features→ Turner syndrome can be subtle; any girl with unexplained short stature or delayed puberty needs a karyotype.
Ordering brain MRI for isolated premature thelarche in a toddler→ Normal growth, normal bone age and no other pubertal signs point to a benign variant; observe.
Assigning sex at birth before evaluating ambiguous genitalia→ Check karyotype, 17-hydroxyprogesterone and electrolytes and involve a specialist team; watch for salt-wasting crisis.
Attributing adult gynecomastia to weight without labs→ Check hCG and testicular exam; a testicular tumor can present this way.
Leaving testosterone running with a hematocrit of 56%→ Erythrocytosis raises clot risk; hold or reduce therapy until the hematocrit falls, then resume at a lower dose.