After completing this note you will be able to recognise, investigate and initiate appropriate management of common calcium and parathyroid disorders seen in Kenyan clinical rotations, while knowing where to verify drug choices and dosing against the Kenya MoH guideline and your hospital formulary.
Definition
Disorders of calcium homeostasis encompass hypercalcaemia, hypocalcaemia, and parathyroid gland disease (primary, secondary and tertiary hyperparathyroidism). They are defined by serum total calcium (or ionised calcium) that is persistently above or below the laboratory reference range and by inappropriate parathyroid hormone (PTH) concentrations relative to the calcium level.
Anatomy and physiology you need
| Structure | Key Function | Clinical relevance |
|---|---|---|
| Parathyroid glands (4) | Secrete PTH in response to low Ca²⁺ | PTH drives renal Ca²⁺ reabsorption, bone resorption, and 1‑α‑hydroxylase activation |
| Thyroid C‑cells | Release calcitonin when Ca²⁺ high | Minor role in humans; helps lower Ca²⁺ |
| Kidney (proximal & distal tubules) | Reabsorb filtered Ca²⁺; convert 25‑OH‑vit D to 1,25‑(OH)₂‑D | Impaired renal function → secondary hyperparathyroidism |
| Bone (cortical & trabecular) | Reservoir of Ca²⁺; remodeling regulated by PTH & vitamin D | Excess PTH → bone loss; low Ca²⁺ → osteomalacia/rickets |
| Gastrointestinal tract | Absorbs Ca²⁺ under influence of 1,25‑(OH)₂‑D | Malabsorption (e.g., celiac, TB enteritis) → hypocalcaemia |
Causes and risk factors
Hypercalcaemia
| Category | Common causes in Kenya |
|---|---|
| Malignancy | Squamous cell carcinoma of cervix, breast, lung; lymphoma |
| Primary hyperparathyroidism | Parathyroid adenoma, hyperplasia |
| Granulomatous disease | Pulmonary TB, sarcoidosis |
| Vitamin D intoxication | Unregulated supplementation |
| Medications | Thiazide diuretics, lithium |
| Immobilisation | Prolonged bed rest, spinal injury |
Hypocalcaemia
| Category | Common causes in Kenya |
|---|---|
| Vitamin D deficiency | Limited sunlight, malnutrition, dark skin, HIV/TB therapy |
| Secondary hyperparathyroidism | Chronic kidney disease, renal osteodystrophy |
| Acute pancreatitis | Saponification of Ca²⁺ |
| Magnesium deficiency | Diarrhoea, malabsorption, alcoholism |
| Medications | Phenytoin, rifampicin, bisphosphonates |
| Acute severe illness | Sepsis, severe malaria, sickle‑cell crisis |
Parathyroid disorders
| Disorder | Typical aetiology |
|---|---|
| Primary hyperparathyroidism | Parathyroid adenoma, MEN‑1 |
| Secondary hyperparathyroidism | CKD, vitamin D deficiency, chronic malabsorption (e.g., TB enteritis) |
| Tertiary hyperparathyroidism | Long‑standing secondary disease, renal transplant |
Pathophysiology
Hypercalcaemia
Low‑PTH → ↑ bone resorption (PTH‑independent) → ↑ serum Ca²⁺ → ↓ PTH (feedback) → renal Ca²⁺ wasting (limited) → symptoms.
Primary hyperparathyroidism
Parathyroid adenoma → autonomous PTH ↑ → ↑ bone resorption + ↑ renal Ca²⁺ reabsorption + ↑ 1‑α‑hydroxylase → serum Ca²⁺ ↑ → suppressed phosphate → nephrolithiasis.
Granulomatous disease
Macrophage 1‑α‑hydroxylase ↑ → excess 1,25‑(OH)₂‑D → ↑ intestinal Ca²⁺ absorption → hypercalcaemia.
Hypocalcaemia
Vitamin D deficiency → ↓ intestinal Ca²⁺ absorption → ↓ serum Ca²⁺ → ↑ PTH (secondary hyperparathyroidism) → bone resorption ↑ but may be insufficient → persistent hypocalcaemia.
Secondary hyperparathyroidism
CKD → ↓ phosphate excretion → hyperphosphataemia + ↓ 1‑α‑hydroxylase → ↓ 1,25‑(OH)₂‑D → ↓ Ca²⁺ absorption → ↑ PTH → bone turnover ↑ (renal osteodystrophy).
Tertiary hyperparathyroidism
Chronic secondary stimulus → parathyroid hyperplasia → autonomous PTH secretion despite normal/high Ca²⁺ → severe hypercalcaemia.
Clinical features
| Aspect | Key questions to ask | Why it matters / what it explains |
|---|---|---|
| General | Fatigue, weakness, weight loss or gain, recent illness, change in appetite | Hyper‑ or hypocalcaemia can produce nonspecific malaise; weight changes may hint at underlying malignancy or chronic disease (e.g., TB, HIV). |
| Skeletal | Bone pain, fractures with minimal trauma, deformities, difficulty climbing stairs, history of renal stones | PTH excess → bone resorption → pain, fractures; PTH deficiency → low turnover bone disease. Nephrolithiasis is classic for hypercalcaemia. |
| Renal | Polyuria, polydipsia, nocturia, history of kidney stones, recent change in urine colour, flank pain | Hypercalcaemia impairs concentrating ability → polyuria/polydipsia; calcium nephrolithiasis produces flank pain. Hypocalcaemia can cause reduced renal concentrating ability as well. |
| Neuromuscular | Tingling, numbness around mouth, carpopedal spasm, muscle cramps, tetany, seizures, confusion, lethargy, depression | Low ionised calcium lowers neuronal threshold → paresthesiae, tetany, seizures; high calcium depresses neuromuscular excitability → lethargy, confusion. |
| Cardiovascular | Palpitations, chest pain, syncope, shortness of breath on exertion | Hypercalcaemia shortens QT interval → arrhythmias; severe hypocalcaemia can cause prolonged QT and ventricular arrhythmias. |
| Gastro‑intestinal | Nausea, vomiting, constipation, abdominal pain, loss of appetite | Hypercalcaemia reduces gut motility → constipation, nausea; hypocalcaemia may cause dysphagia or oesophageal spasm. |
| Endocrine / systemic | History of neck surgery, radiation to head/neck, family history of endocrine tumours, known HIV, TB, sickle‑cell disease, chronic kidney disease, use of thiazides, lithium, vitamin D supplements | Identifies secondary causes (e.g., secondary hyperparathyroidism in CKD, drug‑induced PTH changes, granulomatous disease producing excess 1‑α‑hydroxylase). |
| Medication / supplement | Current drugs (thiazides, lithium, bisphosphonates, calcimimetics), calcium or vitamin D intake, antacids | Certain agents raise calcium or suppress PTH; others lower calcium. |
| Pregnancy / lactation | Current pregnancy status, recent delivery, breastfeeding | Pregnancy alters calcium handling; lactation can precipitate hypocalcaemia if dietary intake is inadequate. |
Examination findings and rationale
| Finding | What it indicates | Pathophysiological basis |
|---|---|---|
| Chvostek sign (facial twitch on tapping) | Hypocalcaemia | Low extracellular calcium increases neuronal excitability. |
| Trousseau sign (carpopedal spasm on BP cuff) | Hypocalcaemia | Same mechanism as Chvostek; provokes latent tetany. |
| Prolonged QT interval on ECG (clinically noted as “wide QT”) | Severe hypocalcaemia | Calcium influences cardiac repolarisation. |
| Shortened QT interval | Hypercalcaemia | Faster repolarisation due to high extracellular calcium. |
| Muscle weakness (proximal > distal) | Hypercalcaemia | Calcium depresses neuromuscular transmission. |
| Bone tenderness / deformities (e.g., brown tumours) | Chronic hyperparathyroidism | Excess PTH causes osteoclastic bone resorption. |
| Renal bruit or palpable kidneys | Chronic kidney disease | CKD is a common cause of secondary hyperparathyroidism. |
| Thyroid/neck mass | Parathyroid adenoma or carcinoma | Enlarged parathyroid may be palpable in thin necks. |
| Signs of chronic infection (e.g., TB scar, lymphadenopathy) | Granulomatous disease causing hypercalcaemia | Activated macrophages produce 1‑α‑hydroxylase → excess active vitamin D. |
| Sickle‑cell crisis features (painful vaso‑occlusive episodes) | May precipitate hypocalcaemia during acute crises | Shifts of calcium into cells during ischemia. |
Differential diagnosis
| Condition | Points toward it | How to separate from other calcium disorders |
|---|---|---|
| Primary hyperparathyroidism | Hypercalcaemia, low‑normal phosphate, high/intact PTH, solitary neck mass | PTH is inappropriately high; renal stones common; bone disease (brown tumours). |
| Secondary hyperparathyroidism (CKD) | CKD, low/normal calcium, high phosphate, high PTH | Phosphate retention and low vitamin D drive PTH; calcium usually low‑normal, not high. |
| Tertiary hyperparathyroidism | Long‑standing CKD, hypercalcaemia with very high PTH after renal transplant | PTH remains autonomous despite corrected calcium; distinguishes from primary by history of renal disease. |
| Vitamin D intoxication | Hypercalcaemia, suppressed PTH, high 25‑OH vitamin D | PTH suppressed; history of excess supplementation. |
| Granulomatous disease (TB, sarcoidosis) | Hypercalcaemia, low/normal PTH, high 1,25‑OH vitamin D | Elevated active vitamin D despite normal 25‑OH; look for pulmonary or lymph node signs. |
| Malignancy‑associated hypercalcaemia | Hypercalcaemia, suppressed PTH, high PTH‑related peptide (if solid tumour) or osteolysis | Low PTH, high PTHrP or bone metastases; rapid onset, weight loss, night sweats. |
| Hypoparathyroidism | Hypocalcaemia, low PTH, high phosphate | Low PTH is the hallmark; postoperative neck surgery common cause. |
| Pseudohypoparathyroidism | Hypocalcaemia, high PTH, short stature, brachydactyly | End‑organ resistance to PTH; PTH is elevated, unlike true hypoparathyroidism. |
| Drug‑induced (e.g., thiazides, lithium) | Hypercalcaemia with normal/high PTH (thiazides) or hypercalcaemia with normal PTH (lithium) | Medication history clarifies; thiazides reduce renal calcium excretion, lithium shifts set‑point. |
| Acute pancreatitis | Hypocalcaemia, low PTH, abdominal pain | Saponification of fat consumes calcium; lipase elevation helps differentiate. |
Investigations
| Test | What it answers | Interpretation |
|---|---|---|
| Serum total calcium (corrected for albumin) | Presence of hypo‑ or hyper‑calcaemia | Low = hypocalcaemia; high = hypercalcaemia |
| Ionised calcium | Clinically active calcium level | Confirms true calcium status, especially in albumin abnormalities |
| Serum phosphate | Helps differentiate PTH‑related disorders | Low in primary hyperparathyroidism; high in secondary hyperparathyroidism |
| Intact PTH | Determines if calcium abnormality is PTH‑mediated | High in primary/secondary/tertiary hyperparathyroidism; low in vitamin D intoxication, malignancy |
| 25‑OH vitamin D | Vitamin D stores | Low → deficiency; high → intoxication |
| 1,25‑OH vitamin D | Active vitamin D level | Elevated in granulomatous disease, lymphoma |
| PTH‑related peptide (PTHrP) | Malignancy‑associated hypercalcaemia | High suggests humoral hypercalcaemia of malignancy |
| Renal function panel (creatinine, eGFR, urea) | Kidney contribution | CKD → secondary/tertiary hyperparathyroidism |
| Urinary calcium excretion (24‑h) | Distinguish familial hypocalciuric hypercalcaemia | Low urinary calcium despite hypercalcaemia suggests familial form |
| Neck ultrasound | Localise parathyroid adenoma/carcinoma | Hypoechoic lesion posterior to thyroid; guides surgery |
| Sestamibi scan (Tc‑99m) | Functional localisation of hyperfunctioning parathyroid tissue | Positive uptake confirms adenoma/carcinoma |
| ECG | Cardiac effect of calcium abnormality | Short QT (hyper), prolonged QT (hypo) |
| Bone densitometry (DXA) | Chronic bone loss from PTH excess | Low BMD supports long‑standing hyperparathyroidism |
| Chest X‑ray / CT (if TB/sarcoidosis suspected) | Granulomatous disease evidence | Hilar lymphadenopathy, cavitary lesions suggest TB; bilateral hilar nodes suggest sarcoidosis |
| Serum alkaline phosphatase | Bone turnover | Elevated in high‑turnover bone disease (primary hyperparathyroidism). |
Diagnosis and severity
Diagnostic algorithm (summary)
- Confirm calcium abnormality – use ionised calcium; if abnormal, proceed.
- Measure intact PTH –
- High PTH → PTH‑mediated hypercalcaemia (primary, secondary, tertiary).
- Low/undetectable PTH → PTH‑independent hypercalcaemia (vitamin D intoxication, malignancy, granulomatous disease).
- Assess phosphate, vitamin D metabolites, renal function – pattern distinguishes primary from secondary/tertiary hyperparathyroidism and identifies vitamin D‑related causes.
- Targeted imaging (ultrasound, sestamibi) when primary hyperparathyroidism is likely.
- Special tests (PTHrP, urinary calcium) for malignancy or familial hypocalciuric hypercalcaemia.
Severity grading (clinical focus)
| Calcium level (ionised) | Clinical severity | Typical management urgency |
|---|---|---|
| Severe hypercalcaemia (> 1.75 mmol/L) | Neurologic impairment, cardiac arrhythmia, renal failure | Immediate IV hydration, rapid‑acting agents, urgent endocrine referral |
| Moderate hypercalcaemia (1.45–1.75 mmol/L) | Mild neuro‑cognitive symptoms, polyuria, stones | Prompt outpatient work‑up, oral agents, close monitoring |
| Mild hypercalcaemia (1.30–1.44 mmol/L) | Often asymptomatic | Observation, address reversible causes |
| Severe hypocalcaemia (< 0.9 mmol/L) | Tetany, seizures, prolonged QT | Immediate IV calcium gluconate, treat underlying cause |
| Moderate hypocalcaemia (0.9–1.1 mmol/L) | Paresthesiae, muscle cramps | Oral calcium/vitamin D, monitor |
| Mild hypocalcaemia (1.1–1.2 mmol/L) | Usually asymptomatic | Observe, ensure adequate intake |
Severity guides urgency of intervention, need for inpatient care, and frequency of monitoring. The underlying aetiology ultimately determines definitive therapy (surgical removal of adenoma, vitamin D repletion, treatment of CKD, anti‑resorptive therapy for malignancy, etc.).
Management
Immediate stabilisation
- Severe symptomatic hypocalcaemia (tetany, seizures, cardiac arrhythmia, laryngeal spasm): give rapid intravenous calcium gluconate via a central line or large‑bore peripheral line; monitor cardiac rhythm and serum calcium every 15 min until symptoms improve.
- Severe hypercalcaemia (mental status change, ECG shortening of QT, renal failure, >14 mg/dL): initiate aggressive isotonic saline hydration, consider loop diuretic after euvolemia, and give intravenous bisphosphonate or calcitonin for rapid reduction; treat underlying malignancy or hyperparathyroidism thereafter.
Definitive treatment
| Disorder | First‑line definitive therapy | Rationale |
|---|---|---|
| Primary hyperparathyroidism | Parathyroidectomy (focused or bilateral neck exploration) | Removes source of autonomous PTH, cures hypercalcaemia |
| Secondary hyperparathyroidism (CKD‑MBD) | Phosphate binders, active vitamin D analogues, calcimimetics | Controls phosphate load, suppresses PTH, prevents bone disease |
| Hypoparathyroidism | Oral calcium salts + active vitamin D (calcitriol) | Replaces calcium and the missing 1‑α‑hydroxylation step |
| Pseudohypoparathyroidism | High‑dose oral calcium + active vitamin D; monitor for hypercalciuria | Overcome end‑organ resistance to PTH |
| Hungry bone syndrome post‑parathyroidectomy | Continue calcium and vitamin D, monitor for rapid fall in serum calcium | Bone remineralisation sequesters calcium |
Monitoring and follow‑up
- Serum calcium, phosphate, magnesium, creatinine every 6–12 h during acute management; then daily until stable.
- Intact PTH after the acute phase to confirm adequacy of treatment (e.g., low after parathyroidectomy, high in persistent disease).
- ECG for QT interval (hypocalcaemia) or shortened QT (hypercalcaemia) during correction.
- Urinary calcium excretion when on high‑dose calcium or vitamin D to detect nephrolithiasis risk.
- Bone mineral density 6–12 months after definitive therapy for hyperparathyroidism.
Contra‑indications & safety
- Avoid rapid IV calcium infusion in patients with digitalis toxicity or severe coronary artery disease without cardiac monitoring.
- Bisphosphonates are contraindicated in severe renal impairment (eGFR < 30 mL/min).
- Calcimimetics require caution in patients with hypocalcaemia; stop if calcium falls below the lower normal limit.
- Active vitamin D analogues can precipitate hypercalcaemia in sarcoidosis or granulomatous disease; monitor calcium closely.
Complications and prognosis
- Chronic hyperparathyroidism → renal stones, nephrocalcinosis, osteoporosis, cardiovascular calcification, neurocognitive decline; surgical cure markedly improves long‑term survival.
- Hypoparathyroidism → recurrent tetany, basal ganglia calcifications, cataracts, renal stones from hypercalciuria; good prognosis with diligent calcium/vitamin D replacement.
- Hungry bone syndrome after parathyroidectomy → prolonged hypocalcaemia, requires weeks of supplementation; resolves with bone remineralisation.
- Secondary hyperparathyroidism (CKD) → vascular calcification, bone pain, fractures; aggressive phosphate control and calcimimetics improve morbidity.
- Malignancy‑associated hypercalcaemia → high short‑term mortality; prognosis depends on underlying cancer stage; rapid calcium lowering improves quality of life.
High‑yield exam points
- Look‑alike conditions: Distinguish primary hyperparathyroidism (high PTH, high calcium) from familial hypocalciuric hypercalcaemia (high calcium, inappropriately normal/low PTH, low urinary calcium).
- Common wrong first step: Giving oral calcium for severe symptomatic hypocalcaemia before IV calcium; examiners expect immediate IV therapy.
- Bedside examiner questions:
- “What ECG change do you expect in severe hypocalcaemia?” (Prolonged QT).
- “Why is a low urinary calcium excretion suggestive of familial hypocalciuric hypercalcaemia?” (Defective calcium‑sensing receptor).
- “What is the mechanism of action of cinacalcet in secondary hyperparathyroidism?” (Allosteric activation of CaSR → ↓ PTH).
- Key mnemonic: “CHOP” – Calcium, Hormone (PTH), Phosphate, Symptoms – always assess together.
Clinical case
Case: A 58‑year‑old Kenyan woman with known CKD stage 4 presents with generalized bone pain, pruritus, and recent onset of muscle cramps. Blood tests show: serum calcium 8.2 mg/dL (low), phosphate 6.5 mg/dL (high), intact PTH 850 pg/mL (markedly elevated). 24‑hour urinary calcium is low.
Questions
- What is the most likely diagnosis?
Secondary hyperparathyroidism due to chronic kidney disease.
- Which class of drug should be added to her regimen to control PTH levels?
Calcimimetic (e.g., cinacalcet) – it increases CaSR sensitivity, lowering PTH.
- What long‑term complication must be monitored for, and how?
Vascular and soft‑tissue calcification; monitor by serial serum calcium‑phosphate product and periodic imaging (e.g., cardiac echo, plain radiographs).
Practice questions
Question 1
A 32‑year‑old man with a recent diagnosis of sarcoidosis presents with fatigue, polyuria, and a serum calcium of 12.5 mg/dL. His PTH is suppressed. What is the most appropriate next step?
A. Start oral calcium supplements
B. Give intravenous bisphosphonate
C. Begin high‑dose vitamin D
D. Initiate glucocorticoids
Answer: D. Initiate glucocorticoids – they reduce granuloma‑mediated 1‑α‑hydroxylase activity, lowering calcium.
Question 2
A patient with severe hypocalcaemia (serum calcium 6.0 mg/dL) is seizing. Which intervention is contraindicated until the seizure stops?
A. Intravenous calcium gluconate
B. Intravenous magnesium sulfate
C. Intravenous diazepam
D. Rapid infusion of normal saline
Answer: B. Intravenous magnesium sulfate – magnesium can worsen neuromuscular irritability in acute seizures; calcium is the priority.
Question 3
Which laboratory pattern best distinguishes familial hypocalciuric hypercalcaemia (FHH) from primary hyperparathyroidism?
A. High calcium, high PTH, high urinary calcium
B. High calcium, low PTH, low urinary calcium
C. High calcium, normal/low PTH, low urinary calcium
D. Low calcium, high PTH, high urinary calcium
Answer: C. High calcium, normal/low PTH, low urinary calcium – due to defective CaSR causing reduced urinary excretion.
Question 4
A 70‑year‑old man with metastatic prostate cancer has a calcium of 15 mg/dL, ECG shows shortened QT, and he is mildly dehydrated. Which therapy should be given first?
A. Calcitonin subcutaneously
B. Intravenous bisphosphonate
C. Aggressive isotonic saline hydration
D. Oral phosphate binders
Answer: C. Aggressive isotonic saline hydration – restores intravascular volume and promotes renal calcium excretion before other agents.
Question 5
Post‑parathyroidectomy, a patient develops profound hypocalcaemia with tingling and Chvostek sign. Which phenomenon explains this?
A. Rebound hyperparathyroidism
B. Hungry bone syndrome
C. Acute renal failure
D. Vitamin D deficiency
Answer: B. Hungry bone syndrome – rapid bone remineralisation sequesters calcium, causing low serum levels.
Drafted with AI assistance from standard references and reviewed for structure. Check details against your lecture notes and the Kenya MoH guideline.