Endocrinology

01

Calcium & Metabolic Bone Disorders

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Hypercalcemia · Workup

Causes

PHPT · lithium · thiazides · vitamin D / calcium excess · malignancy · sarcoidosis · bone mets · MM · TB · BCL · milk-alkali · hyperthyroidism

Manifestations

Stones · osteoporosis · pancreatitis · fractures · altered LOC · coma

Labs

PTH · phosphate · creatinine · 25-hydroxyvitamin D

Severe / sx

IVF NS · IV bisphosphonates

MM / BCL / sarcoid

Oral glucocorticoids

The Parathyroid Axis

Reading Ca · P · PTH together

Disorder	Ca	P	PTH	Urine Ca	Key signature
PHPT	↑	↓	↑ / nl	↑	Urine Ca:Cr `>0.02` · XR chondrocalcinosis / osteitis fibrosa cystica
FHH	↑	↓	↑	↓	Ca:Cr `<0.01` · CaSR mutation
SHPT	↓	varies	↑	—	Post-gastric (Ca citrate) · vit-D def (↑P → vit D) · CKD (↑P → vit D, P-restriction, non-Ca binders)
THPT	↑	↑	↑	—	ESRD / post-transplant → vit-D analogues, calcimimetics

PHPT · Surgery Indications

Symptomatic
Ca >0.25 mmol/L / >1 mg/dL above ULN
T-score ≤-2.5 (L-spine · hip · femoral neck · distal ⅓ radius) · vertebral fracture
Age <50y
Urine Ca >6.25 mmol/d (♀) / >7.5 mmol/d (♂) · nephrocalcinosis
CrCl <60 (stage 3 CKD)

PHPT supportive: target vit-D >75 · calcium intake 1000–1200 mg/d
High-risk osteoporosis › bisphosphonates, denosumab
Symptomatic + non-operative › cinacalcet
Mild + asymptomatic › adequate hydration
THPT surgical indications: refractory ↑PTH · severe/symptomatic hypercalcemia · calciphylaxis · progressive bone disease

Post-parathyroidectomy › Hungry Bone Syndrome: profound + sustained hypocalcemia, hypophosphatemia, hypomagnesemia within 1–4 days. Treat with PO calcium, calcitriol, and IV calcium infusions.

MEN Syndromes

All autosomal dominant

Type	Features	Gene
MEN 1	PHPT · pituitary tumors (prolactinoma, acromegaly, Cushing's) · pancreatic tumors (insulinoma, VIPoma, gastrinoma, carcinoid)	MEN1
MEN 2A	PHPT · medullary thyroid cancer · pheochromocytoma	RET
MEN 2B	Marfanoid / mucosal neuromas · medullary thyroid cancer · pheochromocytoma	RET

Hypoparathyroidism

Low Ca + low/normal PTH on two measurements >2 weeks apart.

Causes: hypoMg · hyperMg · post-thyroidectomy · post-radiation · sarcoidosis · amyloidosis · metastases · APS-1 (Whitaker's triad: chronic mucocutaneous candidiasis + Addison's + hypoPTH) · pseudohypoparathyroidism (GNAS) · DiGeorge.

Tx: oral calcium + vit D (calcitriol / alfacalcidol) › PTH therapy. Monitor urine calcium.

Hypocalcemia: paresthesia · carpopedal spasm · Trousseau · Chvostek
- Causes: hypoPTH · vit-D def · hypoMg · severe pancreatitis · rhabdomyolysis · AKI · tumor lysis
- Workup: Ca · phos · Mg · Cr · PTH · 25-OH vit D · albumin · ionized Ca · ECG (QT prolongation)
- Acute sx › IV calcium gluconate + vitamin D
- Chronic › oral calcium + vitamin D
  - CKD › calcitriol
  - CLD › 25-hydroxycholecalciferol
  - Others › cholecalciferol or ergocalciferol

Osteoporosis · Risk Factors

Age >40y + fracture · prednisone ≥2.5 mg/d >3 months · ≥2 falls/year · BMI <20 · secondary osteoporosis · smoker · ≥3 drinks/d · parental hip fracture.

Osteoporosis · Screening Triggers

Age 50–65y + fragility fracture
Age 50–64y + ≥2 RF
Age 65–69y + ≥1 RF
Age ≥70y › BMD + FRAX
Female age ≥65y
Age ≥40y › FRAX + DXA · Age <40y › BMD

T-score -1 to -2.5 › osteopenia › BMD every 3–5y
T-score ≤-2.5 or fragility fracture › osteoporosis
Pharmacotherapy indications: FRAX ≥20% · age ≥70y + T-score ≤-2.5 · fragility pelvis/humerus/vertebra/hip fracture · ≥2 fractures
Secondary screen (T1DM · osteogenesis imperfecta · hyperthyroidism · hyperparathyroidism · Cushing · RA · MM · CKD · vit-D def · hypogonadism · premature menopause · malnutrition · malabsorption · CLD) › CBC · TSH · Ca · Phos · eGFR · LFT · vit D · SPEP · anti-tTG · PTH
Spine XR indications: age ≥65y + T-score ≤-2.5 · FRAX 15–19.9% · vertebral tenderness · height loss >2 cm · occiput-to-wall >5 cm · rib–pelvis ≤2 fingers

Osteoporosis Pharmacotherapy

Ladder · CIs · key adverse effects

Agent	Dose	Adverse / Watch	Contraindications
Alendronate	`70 mg PO weekly`	Esophageal / GI intolerance · arthralgia · flu-like (zoledronate) · AFF · ONJ	CrCl `<30` (oral) · CrCl `<35` (IV) · esophageal abnormalities · hypocalcemia. Empty stomach, upright ≥30 min.
Risedronate	`5 mg PO OD` or `35 mg PO weekly`
Zoledronate	`5 mg IV annually`
Denosumab (RANKLi)	`SC 6-monthly`	Hypocalcemia · dermatitis · arthralgia · AFF · ONJ. Discontinuation › accelerated bone loss (bridge with bisphosphonate).	Hypocalcemia
Raloxifene (SERM)	Post-menopause `≤10y` + age `<60y`	VTE · MI · CVA · vasomotor symptoms · leg cramps	VTE · CVD · CVA · vaginal bleeding

Sequencing

Oral bisphosphonates × 5 y › IV zoledronate › denosumab › romosozumab or teriparatide × 2 y (recent severe vertebral # · >1 vertebral # + T-score ≤-2.5 · AFF). Plus exercise (balance + resistance), vit-D target 75–125, calcium 1000–1200 mg/d, smoking/alcohol cessation.

Bone

Paget's Disease

Isolated ↑ ALP, bone pain, fractures, hearing loss, compressive neuropathies, OA, osteosarcoma, skull enlargement, femur/tibia bowing, HFpEF.

XR › focal osteolysis · 'cotton wool' skull · thickened cortices · tunnelling · accentuated trabeculae. Skeletal survey + bone scan.

Tx indications: symptomatic · high # risk · hyperCa · ALP >2× ULN · pre-orthopedic surgery near site · weight-bearing involvement.

› IV zoledronate 5 mg annually or oral bisphosphonate or calcitonin. Annual ALP.

Bone

Osteomalacia

Fatigue · malaise · bone pain · proximal muscle weakness · hypocalcemia · hypophosphatemia · ↑ ALP · low vitamin D.

XR › Looser zones. Workup: RFT · LFT · anti-tTG.

› Treat vitamin D deficiency.

02

Thyroid Gland Disorders

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Thyrotoxicosis · Clinical Picture

Nervousness · emotional lability · sweating · heat intolerance · palpitations · diarrhea · weight loss · menstrual irregularity · tachycardia · lid lag · fine tremor · muscle wasting · proximal weakness · hyperreflexia.

Working Up Thyrotoxicosis

Read by RAIU and thyroglobulin

Pattern	Etiology	Key clues
↓ Tg	Exogenous ingestion	Factitious / iatrogenic
↑ RAIU	Graves · TMNG · toxic adenoma	Graves: goiter, ophthalmopathy, pretibial myxedema, bruit · TSHRA · TSIg · TRAb
↓ RAIU	Exogenous · subacute · postpartum · amiodarone · iodine load · ICI thyroiditis	Subacute: ↑ CRP/ESR › NSAIDs or glucocorticoids · repeat TFTs q2–3 wk

Hyperthyroidism › anti-thyroid drugs (MMZ, PTU) or total thyroidectomy + levothyroxine or RAI ablation + levothyroxine
Symptomatic › BBs
Anti-thyroid drugs › full effect 4–6 weeks · hepatotoxicity (PTU >), agranulocytosis, vasculitis, allergic reactions
PTU › 1st trimester pregnancy · thyroid storm · minor MMZ reactions
RAI CI: pregnancy · breastfeeding · moderate–severe orbitopathy · thyroid cancer · worsened orbitopathy. Delay pregnancy ≥6 months, DC MMZ ≥2–3 days
Euthyroid prior to surgery · inactive orbitopathy ≥6 months
Surgery indications: large compressive goiter · intolerance of other therapies

Graves Orbitopathy

First line: artificial tears / ophthalmic gels · selenium supplements × 6 months. Moderate / severe › IV glucocorticoids, surgery, teprotumumab, rituximab, tocilizumab.

Pregnancy

Target T4 high-normal · TSHRA in 2nd trimester. Gestational transient thyrotoxicosis › BBs if symptomatic.

Amiodarone › thyroid Doppler US
- T1 AIT: ↑ vascularity › thionamide
- T2 AIT: ↓ vascularity › glucocorticoids

Subclinical hyperthyroidism + asymptomatic › repeat TFT in 4–6 months
Treatment indications: TSH <0.1 + age ≥65y · CVD · osteoporosis

Clinical Picture

Fever · delirium · psychosis · GI symptoms · hepatic dysfunction · tachycardia · AF · HF. Trigger: surgery · infection · iodine load · untreated Graves · trauma · pregnancy. Burch-Wartofsky Point Scale.

BBs + PTU + iodine-potassium (1 h after PTU) + glucocorticoids.

Clinical Picture

Weakness · lethargy · fatigue · depression · impaired concentration · myalgia · cold intolerance · constipation · weight gain · menstrual irregularity / menorrhagia · carpal tunnel · bradycardia · hypothermia · goiter · cool dry skin · hyporeflexia · myopathy.

Causes: Hashimoto · thyroidectomy · RAI ablation · neck radiation · lithium · IFN-α · IL-2 · amiodarone.

Associated: hyperprolactinemia · hyponatremia · ↑ CK · ↑ AST · DLP. Hashimoto › anti-TPO.

Levothyroxine — empty stomach, 4 h before other medications.

Initial full-dose CI: age ≥65y · IHD
Pregnancy: target TSH ≤2.5 · increase levothyroxine dose 30–35% · TSH every 4 weeks for first half + at 30 weeks
Subclinical hypothyroidism (usually TMNG) — treat if age ≥65y + TSH >10 · age <65y + TSH >7 · symptomatic · goiter · pregnancy · anti-TPO. Repeat TFT 6–8 weeks.

Features: altered LOC · lethargy · hypothermia · hypotension · bradycardia · hyponatremia · hypoventilation
› IV glucocorticoids + IV levothyroxine +/- IV liothyronine

Thyroid nodule › TFT + US
- Low TSH › RAIU
- US high-risk features: hypo-echoic · irregular margins · micro-calcifications · extra-thyroidal extension · taller than wide · peripheral calcifications · lymphadenopathy · ≥20% increase
- FNAB indications: nodule >1 cm + suspicious · nodule <1 cm + RF
Hyperfunctioning solitary nodule › RAI ablation or hemithyroidectomy or thionamides
Surgery indications: nondiagnostic FNAB × 2 · malignant cytology · compressive · continued growth

Post-Thyroidectomy TSH Targets

High risk

+ive lymph nodes · +ive margins · extra-thyroidal extension · distant mets · RAI required › TSH <0.1

Intermediate

TSH 0.1–0.5

Low

TSH 0.5–2

Cancer

Medullary

Elevated calcitonin · RET oncogene.

› Screen family · total thyroidectomy + neck dissection.

Cancer

Papillary / Follicular

Firm nodule · fixed · vocal cord paralysis · regional lymphadenopathy. RF: FH, MEN2, radiation.

› Total thyroidectomy ± RAI therapy.

Biotin interferes with TFTs. Nonthyroidal illness syndrome: low T4/T3 with low/normal TSH › repeat TFTs in 6 weeks.

03

Glucose Metabolism Disorders

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DM · Screening & Diagnosis

Screen if

BMI ≥25 + RF · age ≥35y

Diagnose

Fasting glucose ≥7 · HbA1c ≥6.5% · 75 g OGTT 2h ≥11.1 · RBS ≥11.1 + symptoms

Symptoms

Fatigue · polyuria · polydipsia · blurry vision · weight loss · dehydration

Asymptomatic

2 confirmatory tests

HbA1c falsely low

Hemolytic anemia · EPO · kidney injury

Glycemic Categories

Stage	HbA1c	Fasting glu	2 h OGTT	Plan
Pre-DM	`5.7–6.4%`	`5.6–6.9`	—	Lifestyle › metformin
IGT	—	—	`7.8–11`	Annual testing
DM	`≥6.5%`	`≥7`	`≥11.1`	See tabs below

Antibodies: anti-GAD · anti-islet cell · zinc transporter 8
› Basal-bolus insulin (50% basal) or continuous SC insulin infusion · CGM
Screen for autoimmune disease: TSH + anti-TPO Ab every 2–5 y · AI / celiac if symptomatic
High fasting glucose › ↑ basal dose
High pre-meal glucose › ↑ bolus dose
Nocturnal hypoglycemia › ↓ basal dose · ultra-long-acting basal (Tresiba / insulin degludec)
Hypoglycemia unawareness › CGM · relax glycemic targets · modify therapy

DKA · Diagnosis

pH <7.3 · HCO₃ <18 · AG >12 · +ive ketones · glucose ≥11.1.

Triggers: intoxication · MI · CVA · insulin deficiency · infection · iatrogenic · glucocorticoids · atypical antipsychotics.

DKA · Management Order

Fluids · Potassium · Insulin · Bicarb

1. Maintenance IVF 0.9% NS 1 L/h · hyperchloremic NAGMA

2. K <5 › add KCl to IVF · K 4–5 · only start insulin once K ≥3.5

3. Insulin 0.1 U/kg/h infusion · glucose <14 › 0.05 U/kg/h

4. Glu <14 › add 5% / 10% dextrose to IVF · target glucose 8.3–11.0

5. Normalized AG + improving symptoms › transition to SC insulin with 2–3 h overlap · ensure tolerating orally

6. pH <7 › NaHCO₃ 100 mmol IV q2h

Insulin resistance · metabolic syndrome › lifestyle modification first
HbA1c ≥1.5% above target › metformin (CI eGFR <30) · vitamin B12 deficiency
Symptomatic hyperglycemia (polyuria · polydipsia · blurry vision · weight loss · volume depletion · ketosis · HHS / DKA) › insulin + metformin
BMI ≥30 / MASLD › GLP1RA (tirzepatide, semaglutide)
HF / CVD / CKD › SGLT2i (empagliflozin, dapagliflozin) and/or GLP1RA (semaglutide, liraglutide, dulaglutide, tirzepatide)
eGFR <15 › DC metformin · dialysis › DC SGLT2i
eGFR <15 or dialysis › DPP4i, insulin, pioglitazone

Watch For

SGLT2i › euglycemic DKA, GU infections, Fournier's gangrene. GLP1RA CI: medullary thyroid cancer, MEN2; caution with pancreatitis / pancreatic cancer history.

In-patient

Critical › IV insulin · BS 7.8–10. Non-critical › SC insulin (basal + prandial) · BS 5.6–10.

HHS · Diagnosis

Glucose ≥33.3 · serum osmolality >320 · decreased LOC · seizures.

Maintenance IVF 0.9% NS 1 L/h
Insulin 0.05 U/kg/h infusion
Target glucose 11.0–13.9
Improving symptoms › SC insulin 0.5–0.6 U/kg, 2–3 h overlap with IV, ensure tolerating orally

Autoimmune

LADA

Immune-mediated adult-onset diabetes.

Monogenic

MODY

Autosomal dominant · age <25y.

Ketosis-prone

KPD

C-peptide guides insulin dependence.

Secondary

Pancreatic Insufficiency

CF · chronic pancreatitis · hemochromatosis · post-Whipple.

Pregnancy Glycemic Targets

Fasting

<5.3

2 h PP

<6.7

BP target

<130/80 › nifedipine, labetalol

T1DM / T2DM › ASA 162 mg OD at 12–16 weeks until 36 weeks
T2DM › insulin
GDM screening 24–28 weeks: 50 g 1 h OGTT ≥11.1 diagnostic · 7.8–11 › 75 g 2 h OGTT ≥9
GDM at ≥15 weeks › lifestyle › insulin
GDM postpartum: 75 g OGTT 4–12 weeks · then screening every 1–3 y
Fundoscopy every trimester

HbA1c Targets

Default

≤7% · repeat 3–6 monthly

Functionally dependent

7.1–8%

Severe hypos / limited life / frail elderly / dementia

7.1–8.5%

Potential remission (T2DM)

≤6.5%

Statin Indications

CVD · age 40–75y · age >30y + DM >15y · microvascular disease · other CV RF.

Target LDL <2; CVD › LDL <1.8–2 + 50% reduction.

ACEi / ARB Indications

HTN · CVD · end-organ damage (albuminuria, retinopathy, LVH) · microvascular disease · age ≥55y + other CV RF. BP target <130/80.

CV RF: smoking · HTN · DLP · central obesity. CKD › finerenone.

Eye

Retinopathy

T2DM › screen at diagnosis; T1DM › 5 y after diagnosis; then annual.

Fundoscopy › microaneurysms · dot & blot hemorrhages · macular edema.

Proliferative › photocoagulation or anti-VEGF. Macular edema › intravitreal anti-VEGF.

Nerve

Neuropathy

Same screening schedule. Types: distal symmetric polyneuropathy · autonomic (postural hypotension, resting tachycardia, gastroparesis, overflow incontinence, ED) · mononeuropathies · diabetic amyotrophy.

Pain: anticonvulsants (pregabalin, gabapentin, valproate) › antidepressants (amitriptyline, duloxetine, venlafaxine) › topical nitrates › opioids.

ED › PDEi. Gastroparesis › small feeds, metoclopramide. Orthostatic › salt/water, compression stockings.

Kidney

Nephropathy

Same schedule · urine ACR ≥30 › annual.

› ACEi / ARB ± SGLT2i.

eGFR >20 + ACR ≥30 + max ACEi/ARB › finerenone.

Yearly

Other Annuals

Annual depression screening · annual foot examination.

Whipple's Triad

Symptoms of hypoglycemia + BS ≤3.1 + resolution with treatment. Workup: 48–72 h fast + hourly BS.

BS <3.3 › insulin · pro-insulin · C-peptide · BOHB · insulin antibody · sulphonylurea level.

Hypoglycemia · The Pattern

Reading insulin · pro-insulin · C-peptide · BOHB · antibodies

Cause	Insulin	Pro-insulin	C-peptide	BOHB	Other
Exogenous insulin	↑	↓	↓	↓	—
Insulinoma	↑	↑	↑	↓	CT abdomen
Sulphonylurea OD	↑	↑	↑	↓	↑ SU level
Insulin autoimmune	↑	↑	↑	↓	+ive insulin Ab
IGF-2 mediated	↓	↓	↓	↓	—
Starvation	↓	↓	↓	↑	—

Post-gastrectomy / gastric bypass › 5 h postprandial hypoglycemia. Treat with small mixed meals: protein + fat + high-fiber complex carbohydrates.

04

Adrenal Glands Disorders

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Addison's Disease · Clinical Picture

Weight loss · fatigue · anorexia · nausea · vomiting · abdominal pain · hyponatremia · hyperkalemia (primary AI) · orthostatic hypotension · hypoglycemia · eosinophilia · hypercalcemia · uremia · hyperpigmentation in primary AI (gingival, skin furrows, palmar creases).

Causes: autoimmune adrenalitis · insufficient glucocorticoid therapy · autoimmune polyglandular syndrome (thyroid disease, T1DM, vitiligo).

Addison's · Diagnostic Cascade

8 am cortisol › ACTH stim › locate the lesion

1. 8 am cortisol <82 › AI confirmed

2. 8 am cortisol 80–414 › ACTH stim test › rise in cortisol <500 at 30/60 min

3a. ACTH ↑ › primary AI › CT adrenals · check 21-OH antibody

3b. ACTH ↓ / normal › secondary AI › pituitary MRI

3c. Antibody -ive › CT adrenals (infiltrative · hemorrhage · infection · malignancy)

Tx. Oral hydrocortisone 15–25 mg/d + fludrocortisone (primary AI)

Adrenal Crisis

Hydrocortisone 100 mg IV then 50 mg IV QDS · or dexamethasone 4 mg (does not affect serum cortisol assay) + IVF.

Sick day rules: 2–3× hydrocortisone dose. Major stress: IV hydrocortisone 100 mg then 50 mg TDS/QDS or 200 mg/24 h infusion.

Cushing Syndrome · Clinical Picture

Proximal muscle weakness · facial plethora · supraclavicular / dorsocervical fat pads · wide violaceous striae · T2DM · HTN · hirsutism · facial rounding · centripetal obesity.

Causes: exogenous glucocorticoids · Cushing disease · ACTH-producing carcinomas / carcinoid · adrenal adenoma · adrenal carcinoma.

Cushing · Working It Up

2 of 3 screens › ACTH › localize

Screen (2/3): 1 mg DST cortisol >140 · 24 h urine free cortisol · late-night salivary cortisol

ACTH ↓ › CT/MRI adrenals (adenoma / carcinoma) › surgery + glucocorticoid replacement

ACTH ↑ › 8 mg DST › pituitary MRI ± IPSS (central-to-peripheral ACTH ratio: pituitary adenoma vs ectopic)

Rapid onset + mass effect › suspect adrenocortical carcinoma

Mineralocorticoid

Conn's Syndrome

Refractory HTN (≥3 drugs) · K <3.5 · diuretic-induced K <3 · adrenal incidentaloma + HTN · OSA + HTN.

Screen: plasma ARR >15 — must be off MRA, ACE/ARB, BB, DHP-CCB, clonidine, methyldopa, thiazide/loop diuretics, OCP, NSAIDs.

Confirm: saline suppression · oral salt load · captopril suppression.

Localize: CT adrenals › adrenal venous sampling. Unilateral › surgery or MRA. Bilateral › MRA.

Catecholamine

Pheochromocytoma

Adrenergic spells (headache · sweating · tachycardia) · adrenal incidentaloma · refractory HTN · HTN onset <20y · idiopathic CM · HTN with anesthesia / surgery / angiography / BB.

Associations: VHL · MEN 2 · NF1.

Screen: 24 h urine total metanephrines + catecholamines · plasma free metanephrines / normetanephrines. Confirm: MR abdomen.

Tx: α-blocker (phenoxybenzamine, doxazosin) › β-blocker › surgery (after 2 weeks).

Intra-op HTN crisis › nitroprusside or phentolamine.

Adrenal Incidentaloma · Workup

Non-contrast CT.

Suspicious for malignancy: >4 cm · HU >10 · <50% delayed contrast washout · calcifications · extension · lymphadenopathy · heterogeneous › endocrine referral or repeat CT in 12 months.

Functional workup: 1 mg DST · 24 h urine/plasma metanephrines (>10 HU) · ARR (if HTN, hypokalemia).

Hyperandrogenism (voice deepening · ↑ libido · progressive hirsutism · rapid virilization · menstrual irregularity) › testosterone · androstenedione · DHEAS.

MACS (HTN · hyperglycemia · obesity · DLP · vertebral fractures): 1 mg DST + low ACTH + low DHEAS. >4 cm › surgery.

05

Pituitary Gland Disorders

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Pituitary Adenoma

Headaches · visual disturbance / field defects (bitemporal hemianopsia) · CN dysfunction › pituitary MRI › prolactin + IGF-1.

Size: microadenoma <1 cm · macroadenoma ≥1 cm.

Hyperfunction: prolactinoma · acromegaly · Cushing disease · TSHoma.

Hypofunction order: GH › LH/FSH › TSH › ACTH › prolactin.

Symptomatic › FSH · LH · morning cortisol · ACTH · TSH · T4 · testosterone (men).

Non-functioning microadenoma › repeat MRI in 1–3 y (<1 cm) or 6 months (≥1 cm).

Prolactin

Hyperprolactinemia

Galactorrhea · amenorrhea › pregnancy test · TFT (hypothyroidism).

Medications (psychotropics, TCAs, anti-epileptics, metoclopramide, domperidone, CCBs, methyldopa, opioids, protease inhibitors) › prolactin <150.

Macroprolactinoma › prolactin >200.

Symptomatic › cabergoline or bromocriptine › surgery.

GH

Acromegaly

Macrognathia · macroglossia · ↑ ring/shoe/collar/glove size · OSA · coarsened facial features · gap between incisors · carpal tunnel · OA · T2DM · field defects · cranial neuropathies · spade-like hands and feet.

Screen: IGF-1. Confirm: 75 g OGTT.

› Surgery.

ACTH

Cushing Disease

Normal / elevated ACTH › surgery.

TSH

TSHoma

Goiter · hyperthyroidism · elevated T4 · normal/elevated TSH › surgery.

Pituitary Surgery Indications

Mass effect · visual field defects · hypopituitarism · unresponsive to dopamine agonists · abutting optic chiasm · GH / TSH / ACTH excess.

Post-op › SIADH.

Empty Sella Syndrome

↑ CSF · tumor · previous pituitary surgery / radiation / infarction. MRI › excessively small / non-visualized pituitary.

Workup: prolactin · cortisol · ACTH · IGF-1 · TSH · T4 · LH · FSH · testosterone (men).

Acute

Pituitary Apoplexy

Sudden headache · visual change · ophthalmoplegia · altered mental status.

Postpartum

Sheehan Syndrome

Postpartum · obstetric hemorrhage · hypotension › amenorrhea · inability to lactate · fatigue.

Autoimmune

Lymphocytic Hypophysitis

Pregnancy · postpartum · immunotherapy.

Anterior Pituitary Hormone Deficiencies

Match the axis to the symptoms

Axis	Features	Replacement
ACTH	Fatigue · nausea · vomiting · weight loss · abdominal pain · ↓ cortisol	Hydrocortisone first
TSH	Cold intolerance · weight gain · constipation	Thyroxine after hypoadrenalism treatment · monitor T4
FSH / LH	Amenorrhea · loss of libido · ED · chronic opioid use	Men › androgen · pre-menopausal women › estrogen
GH	Loss of muscle mass	—
Posterior	Polydipsia · polyuria · nocturia	See DI

Diabetes Insipidus · Diagnostic Setup

Polydipsia · polyuria · nocturia · hypernatremia >145 · elevated Sosm >295 · low Uosm · post-neurosurgery › water deprivation test (Sosm <295 · Na <145 · low Uosm).

DI · Reading the Desmopressin Challenge

Type	Mechanism	Desmopressin response	Treatment
Central DI	AVP deficiency · neurosurgery · trauma	+ive › MRI pituitary	Desmopressin
Nephrogenic DI	AVP resistance · lithium · sickle cell nephropathy	-ive › renal US	Thiazide. Lithium › amiloride
Psychogenic polydipsia	Excessive intake	Sosm `<295` · Na `<145` · Uosm `<100` · ↑ Uosm with water dep	Fluid restriction

06

Reproductive Disorders

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Menopause

Menses cessation ≥12 months · hot flashes · night sweats · vaginal dryness · dyspareunia · mood changes · osteopenia / osteoporosis · sleep disruption.

HRT indications: symptomatic + age <60y · symptomatic + <10y from menopause.

HRT CI: MI · CVA · VTE · breast / endometrial cancer · unexplained vaginal bleeding · active liver disease.

Uterus › estrogen + progesterone. No uterus › estrogen.

Non-hormonal: SSRI / SNRI · gabapentin · oxybutynin · CBT · fezolinetant.

Definition: absent menses at age 16y · absent sexual characteristics at age 13y
Workup: pregnancy test · karyotype (Turner) · FSH · estradiol · TSH · T4 · prolactin · US pelvis
Müllerian present › anatomic obstruction · Turner X0 · βhCG · FSH · LH · pituitary · PCOS
Müllerian absent › karyotype (XY) · androgen insensitivity · 5α-reductase deficiency · testosterone

Definition: no menses >3 months + previously regular · no menses >6 months + previously irregular
Workup: pregnancy test · FSH · estradiol · TSH · T4 · prolactin › HRT until menstruation or age 51y
↓ estradiol + ↓ / normal FSH › hypogonadotropic hypogonadism: hypothyroidism · hyperprolactinemia · hypothalamic (stress, weight loss, exercise) · pituitary (tumor, Sheehan, hemochromatosis)
↓ estradiol + ↑ FSH › hypergonadotropic hypogonadism: POI · chemotherapy · pelvic radiation
Structural: bicornuate uterus · endometriosis · Asherman's
Hyperthyroidism · PCOS · pregnancy · OCP

Rotterdam Criteria · 2 of 3

Menstrual irregularity · biochemical / clinical hyperandrogenism (hirsutism · acne · androgenic alopecia) · polycystic ovaries on US.

Workup: elevated LH:FSH · prolactin · TSH · 17-OHP · testosterone · DHEAS · estradiol · US pelvis
Screening: fasting BG · 2 h OGTT · lipid profile · sleep study · BP · weight
Management: weight loss + COCP
- Pre-DM / T2DM › metformin
- Hirsutism › spironolactone
- Fertility › clomiphene or letrozole

Loss of ovarian activity at age <40y · high FSH · low estradiol
Workup: karyotype (Turner) · fragile X · anti-adrenal Ab · anti-TPO Ab › HRT until age 51y
Causes: autoimmune · radiation · chemotherapy · fragile X (intellectual disability, ataxia)
Screen BMD

Features: acne · voice changes · mood changes · hirsutism · clitoromegaly · menstrual abnormalities
Workup: testosterone · DHEA-S · 17-OH progesterone · prolactin · TSH · FSH/LH · US pelvis · CT adrenals
Causes: hypothyroidism · liver disease · anabolic steroids · CAH · PCOS · Cushing disease
Tumor-related: virilization (↑ muscle bulk · voice · clitoromegaly) · ↑ DHEA-S · ↑ testosterone › CT adrenals

Clinical Picture

↓ morning / spontaneous erections · ↓ libido · infertility · gynecomastia · ↓ male-pattern hair · ↓ mood/energy · ↓ muscle strength / bulk / stamina · poor sleep · poor concentration.

Workup: low morning total testosterone × 2 › LH · FSH · prolactin.

Localizing Male Hypogonadism

Pattern	Causes	Next step
↑ FSH / LH (primary)	Klinefelter XXY · chemotherapy · testicular trauma · mumps orchitis · autoimmune · systemic illness · pelvic radiation · hemochromatosis	Karyotype
↓ FSH / LH (secondary)	OSA · pituitary tumor · hyperprolactinemia · hemochromatosis · anabolic steroids · obesity · opioids · T2DM · glucocorticoids	Iron studies · MRI pituitary

Anabolic steroids › acne · muscular hypertrophy · testicular atrophy · gynecomastia · erythrocytosis
Klinefelter syndrome: small firm testes · long arm span · long leg length · NHL · bronchiectasis · SLE · diabetes · osteopenia · breast cancer › karyotype
Testosterone replacement › monitor hematocrit (erythrocytosis) + PSA (if high-risk prostate cancer)

Definition: subareolar glandular tissue diameter >0.5 cm · protruded nipples
Workup: hCG · LH · prolactin · testosterone · estradiol › SERM
Causes: medications (spironolactone, cimetidine, antiandrogens, estrogens, 5α-reductase inhibitors, protease inhibitors) · opioids · cirrhosis · CKD · hypogonadism · hyperthyroidism · testicular germ cell tumors
Hypogonadism › testosterone › ↑ libido, lean muscle mass, fat-free mass, bone density, secondary sexual characteristics

Female infertility › >1 y intercourse without contraception age <35y; >6 months if age ≥35y. Begin with ovulatory function assessment, then evaluate partner.

07

Obesity & Metabolic Syndrome

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BMI Classification

Class	BMI
Class I	`30–34.9`
Class II	`35–39.9`
Class III	`≥40`

Risk Markers & Screening

Waist circumference ≥102 cm (♂) / ≥88 cm (♀) › ↑ risk T2DM · CVD · all-cause mortality.

Screen: TSH · LFTs · lipid profile · fasting glucose · OGTT · HbA1c.

Comorbidities: metabolic disease (T2DM, CVD) · cancer (colon, kidney, esophageal, endometrium, post-menopausal breast).

Target weight loss 0.5–1 kg/week, total 10% · medical nutrition therapy + physical activity ± psychological interventions.

Pharmacotherapy Indications

BMI ≥30 · or BMI ≥27 + ≥1 complication (T2DM, gallbladder disease, NAFLD, gout).

Anti-Obesity Pharmacotherapy

Agents · doses · cautions

Agent	Dose	Notes / Cautions
Semaglutide	`2.4 mg SC weekly`	GLP-1 / GIP-GLP-1: GI upset · headache · nasopharyngitis · medullary thyroid cancer, pancreatitis
Tirzepatide	`5 / 10 / 15 mg SC weekly`
Liraglutide	`3 mg SC OD`	Same GLP-1 class effects
Naltrexone–bupropion	`16 / 180 mg BD`	CI: seizures, uncontrolled HTN, opioid / opioid-agonist use
Phentermine–topiramate	—	CI: pregnancy, glaucoma, hyperthyroidism
Orlistat	`120 mg PO TID`	Diarrhea, oily stools

Bariatric Surgery

Indications: BMI 30–35 + 1 serious comorbidity (T2DM, DLP, CAD, HTN, IIH, OHS, debilitating OA, NAFLD, OSA, severe GERD) · BMI ≥35.

Procedures: Roux-en-Y gastric bypass · sleeve gastrectomy · laparoscopic adjustable gastric banding.

Bariatric · Complications

Stomal obstruction · gastric perforation · GI bleed · biliary stones · hernia · dumping syndrome · post-prandial hypoglycemia · malabsorption (iron, B12, folate, calcium, vitamin ADEK, thiamine, pyridoxine, zinc, selenium, copper). Annual BMD.

A study guide to endocrinology.

The Parathyroid Axis

MEN Syndromes

Osteoporosis Pharmacotherapy

Paget's Disease

Osteomalacia

Working Up Thyrotoxicosis

Medullary

Papillary / Follicular

Glycemic Categories

LADA

MODY

KPD

Pancreatic Insufficiency

Retinopathy

Neuropathy

Nephropathy

Other Annuals

Hypoglycemia · The Pattern

Conn's Syndrome

Pheochromocytoma

Hyperprolactinemia

Acromegaly

Cushing Disease

TSHoma

Pituitary Apoplexy

Sheehan Syndrome

Lymphocytic Hypophysitis

Anterior Pituitary Hormone Deficiencies

DI · Reading the Desmopressin Challenge

Localizing Male Hypogonadism

BMI Classification

Anti-Obesity Pharmacotherapy