Calcium is critical for neuromuscular excitability, cardiac conduction, coagulation, bone mineralisation, and intracellular signalling. The body maintains serum calcium within a very narrow range (~2.1–2.55 mmol/L) because even small deviations cause life-threatening symptoms — arrhythmias, seizures, tetany, confusion. ^[1]

High-Yield — PTH Physiological Effects (directly from lecture slides):

• Increase calcium resorption from bone via osteoblasts & osteoclasts
• Increase reabsorption of calcium from distal convoluted tubules
• Increase uptake of calcium from intestine via its effect on the formation of 1,25(OH)₂D₃
• Decrease phosphate reabsorption from proximal convoluted tubules ^[1]

Why PTH lowers phosphate: PTH inhibits the NaPi-IIa cotransporter in the proximal tubule → phosphaturia. This is crucial because if both Ca and PO₄ rise simultaneously, calcium-phosphate product increases → metastatic soft-tissue calcification. Nature designed PTH to raise Ca without raising PO₄.

High-Yield — Vitamin D Physiological Effects:

• Increase calcium uptake in intestine by increasing calcium-binding protein (calbindin)
• Increase intestinal absorption of phosphate
• Increase calcium resorption from bone (if in high doses) ^[1]

High-Yield — Calcitonin Physiological Effects:

• Decrease osteoclast-mediated bone resorption
• Decrease reabsorption of calcium from kidney ^[1]

High-Yield — Calcium Homeostasis: Other Factors (from lecture):

• Albumin: 50% of plasma calcium is protein-bound (mostly albumin). Low albumin → low total Ca, but ionised Ca is normal = pseudohypocalcaemia
• Phosphate: Affects ionic balance of calcium
• pH: Alkalosis increases protein binding of Ca²⁺ → lower ionised Ca → symptoms of hypocalcaemia even with normal total Ca. Acidosis does the opposite. ^[1]

Why pH matters clinically: A hyperventilating anxious patient develops respiratory alkalosis → increased Ca-albumin binding → reduced ionised Ca → perioral tingling and carpopedal spasm. This is not true hypocalcaemia — total Ca is normal.

High-Yield — Classification of Hypercalcaemia (from lecture):

Severity	Serum Ca (corrected)	Clinical State
Mild	< 3.0 mmol/L	Asymptomatic or mildly symptomatic
Moderate	3.0–3.5 mmol/L	Symptomatic, needs active management
Severe	> 3.5 mmol/L	Medical emergency
[1]

High-Yield — Complete List from Lecture Slides:

Why TB/sarcoidosis cause hypercalcaemia: Activated macrophages in granulomas express 1α-hydroxylase independently of PTH → unregulated production of 1,25-(OH)₂D₃ → increased intestinal Ca absorption and bone resorption. This is why glucocorticoids are the specific treatment — they suppress macrophage calcitriol production.

Adrenal Insufficiency and Hypercalcaemia (from lecture): Two mechanisms:

1. Hypovolaemia → ↓ GFR → ↓ calcium filtered → ↑ renal calcium reabsorption
2. ↑ 1α-hydroxylase activity → ↑ intestinal calcium absorption ^[1]

High-Yield Mnemonic from Lecture: "Bones, Stones, Abdominal Groans & Psychiatric Overtones" ^[1]

The key discriminator is PTH level — this divides hypercalcaemia into PTH-mediated and PTH-independent causes.

High-Yield — Common Clinical Scenarios Table (from lecture slide 70): ^[1]

From lecture:

• Avoid factors that could aggravate hypercalcaemia
• Maintain adequate hydration
• Avoid high calcium diet (> 1000 mg/day) ^[1]

Also: stop thiazides, stop calcium/vitamin D supplements, avoid immobilisation.

High-Yield — Principles (from lecture):

1. Rapid control of calcium levels esp. for moderate and severe hypercalcaemia
2. Early diagnosis of the cause ^[1]

Step-by-Step Management Algorithm

High-Yield (from lecture):

• Most common cause of hypercalcaemia
• Prevalence ~1–2/1000
• Peak incidence: 6th–7th decade
• F:M ~2–3:1
• Causes:
  • Solitary parathyroid adenoma (~85%)
  • Hyperplasia (~10–15%)
  • Double adenomas (1–2%)
  • Parathyroid carcinoma (~1%) ^[1]

Why a single adenoma is the most common: This is usually a sporadic somatic mutation in one gland. Hyperplasia (all four glands) should prompt investigation for MEN syndromes (MEN1 or MEN2A).

From lecture (most common modern presentation):

• Incidental finding of mild hypercalcaemia — this is how most patients present today ^[1]

For symptomatic patients: weakness, tiredness, anorexia, nausea, vomiting, constipation, thirst, polyuria, dry mouth, confusion, drowsiness, renal stones, nephrocalcinosis, hypertension, renal failure, osteoporosis, bone pain, fractures, epigastric pain, joint pain (chondrocalcinosis), and rarely multiple endocrine neoplasia. ^[1]

From lecture:

• Continuously high PTH (e.g. PHPTH) → Bone resorption (cortical bone worse than trabecular bone)
• Intermittent low dose PTH (e.g. Teriparatide) → Anabolic action with increase in BMD ^[1]

Why this matters: This is why teriparatide (recombinant PTH 1-34) is used to TREAT osteoporosis — pulsatile PTH stimulates osteoblasts preferentially. But the constant elevation in PHPTH drives net resorption. Cortical bone (e.g. distal radius) is preferentially affected over trabecular bone (e.g. lumbar spine).

From lecture:

• Osteitis fibrosa cystica — rarely seen now
• Subperiosteal resorption — most evident on phalanges (radial side of middle phalanges)
• Bone cysts — central medullary portions of MCP shafts, ribs, pelvis
• Brown tumours (osteoclastomas) — multinucleated osteoclasts in jaw, long bones, ribs
• Skull "salt and pepper" appearance
• Pathological fractures
• Low BMD especially in cortical bone (e.g. distal 1/3 forearm) — more common presentation now ^[1]

From lecture (JCEM 2018 guidelines):

Biochemistry panel:

• Ca, PO₄, ALP
• Urea, Creatinine, eGFR
• 25-OH Vitamin D (disease more active when insufficient < 20 ng/mL or deficient < 10 ng/mL)
• PTH (2nd or 3rd generation immunoassay)

Bone assessment:

• DXA for BMD at lumbar spine, hip, AND distal one-third radius (cortical site preferentially affected)
  • T-score ≤ −2.5 for postmenopausal women and men ≥ 50
  • Z-score ≤ −2.5 for premenopausal women and men < 50
• Vertebral spine assessment (X-ray or VFA by DXA)

Renal assessment:

• 24-hour urine for calcium and creatinine → calculate fractional excretion of calcium (to exclude FHH)
• Abdominal imaging (KUB, USG, CT) for urinary stones ^[1]

Key surgical indications (from lecture/JBMR 2022):

• Serum calcium > 0.25 mmol/L (1 mg/dL) above upper limit of normal
• T-score ≤ −2.5 at any site, or vertebral fracture
• eGFR < 60 mL/min/1.73m²
• Nephrolithiasis or nephrocalcinosis
• 24-hr urine calcium > 10 mmol/day (400 mg/day) with increased stone risk
• Age < 50 years ^[1]

Key lecture point: Localisation is to GUIDE the surgeon, NOT a diagnostic procedure. Negative or discordant imaging should NOT inhibit referral to an experienced parathyroid surgeon. ^[1]

Minimally invasive parathyroidectomy (from lecture):

• Image-guided, focused operation
• Under local/regional anaesthesia, small incisions
• Curative results > 98%, nerve injury < 1%
• Prerequisites: preoperative localisation + intraoperative PTH assay

Intraoperative PTH Assay Monitoring (from lecture):

• PTH half-life: 3.5–4 minutes (normal renal function)
• Drop in PTH: 5–10 minutes
• Drop in Ca: 24–48 hours
• Miami Criterion: Fall of 50% in PTH compared to the highest of either pre-manipulation or pre-excision sample ^[1]

For multi-gland disease (e.g. MEN1):

• Subtotal parathyroidectomy: resection of 3½ glands; preserve 50–80 mg vascularised gland
• Total parathyroidectomy with immediate autotransplantation to forearm + cryopreservation for possible delayed autotransplantation ^[1][5]

Post-operative complications (from surgery notes):

• RLN injury
• Reactionary haemorrhage
• Hungry bone syndrome: rapid, profound hypocalcaemia due to sudden PTH drop → rapid Ca deposition into demineralised bone → treat with Ca + Vit D ^[5]
• Transient or permanent hypoparathyroidism

Cinacalcet (Calcimimetic) — from lecture:

• Allosteric activator of calcium-sensing receptor (CaSR) → makes parathyroid think Ca is higher → reduces PTH secretion
• Indications: Patients where parathyroidectomy is indicated but surgery is NOT clinically appropriate or is contraindicated
• Effective at lowering/normalising serum calcium
• Effects on PTH less pronounced
• No consistent effects on BMD ^[1]

For osteoporosis in PHPTH: bisphosphonates or denosumab can be used if surgery not pursued.

From lecture:

• Secondary hyperparathyroidism: Physiological PTH response to chronic hypocalcaemia (e.g. CKD, Vit D deficiency)
• Tertiary hyperparathyroidism: Prolonged secondary HPT → parathyroid hyperplasia → autonomous PTH secretion → hypercalcaemia (even after the initial stimulus is removed, e.g. post-renal transplant) ^[1]

From lecture: F/52, history of total thyroidectomy a few weeks ago, bilateral hand and perioral numbness, normal kidney function, low serum calcium, high phosphate, PTH at low normal range → Post-surgical hypoparathyroidism ^[1]

From lecture: Symptoms typically develop when adjusted serum calcium falls below 1.9 mmol/L, although this threshold varies. Also depends on the rate of fall of serum calcium. ^[1]

A rapid fall (e.g. post-thyroidectomy) produces symptoms at higher levels than a chronic, slow decline (e.g. CKD).

Complete list from lecture:

Most important: To confirm genuine hypocalcaemia! Look at serum albumin levels; measured ionised calcium ^[1]

From lecture:

• Perioral and digital paraesthesiae
• Neuromuscular irritability:
  • Trousseau's sign: Inflate BP cuff above systolic for 3 minutes → carpopedal spasm (more specific)
  • Chvostek's sign: Tap facial nerve anterior to ear → ipsilateral facial muscle twitching (less specific — positive in 10% normal people)
• Tetany and carpopedal spasm
• Convulsions
• Laryngeal spasm (life-threatening)
• ECG: Prolonged QT interval ^[1]

Why these signs occur: Low ionised Ca²⁺ increases neuronal membrane excitability by lowering the threshold for action potential firing. Voltage-gated Na⁺ channels open more easily → spontaneous depolarisation of motor neurons → muscle spasm.

High-Yield — Treatment Algorithm from Lecture:

Severe or Symptomatic (Adjusted Ca < 1.9 mmol/L):

• ECG and cardiac monitoring
• IV calcium gluconate by infusion
  • E.g. 10% calcium gluconate 20 mL IV over 10–15 minutes, then 30 mL 10% calcium gluconate in 500 mL NS/D5 Q4–6H/pint
• Monitor serum calcium closely (e.g. Q6–8H) ^[1]

Mild (Adjusted Ca > 1.9 mmol/L):

• Oral calcium replacement:
  • Caltrate = 600 mg elemental Ca per tab
  • Oscal = 250 mg elemental Ca per tab
  • Calcium gluconate = 27 mg elemental Ca per tab
• Vitamin D: Consider adding if no response after 2–4 g elemental calcium ^[1]

"Most important: Look out for Causes and Treat Accordingly" ^[1]

From the GC Interactive Tutorial (Endo-Hypoparathyroidism): A 49-year-old woman with paraesthesia and painful muscle cramps 2 weeks after thyroidectomy. ^[8]

Why this happens: During thyroidectomy, the parathyroid glands (located behind the thyroid lobes) may be inadvertently removed, devascularised, or bruised. This leads to transient or permanent hypoparathyroidism → ↓ PTH → ↓ Ca, ↑ PO₄.

Management approach:

1. Confirm genuine hypocalcaemia (corrected Ca or ionised Ca)
2. Check PTH — if low → hypoparathyroidism confirmed
3. Check Mg²⁺ — correct if low
4. Treat as per severity algorithm above
5. Long-term: oral calcium + active vitamin D (calcitriol/alfacalcidol) — because without PTH, the kidney cannot convert 25(OH)D to 1,25(OH)₂D₃