1. Hyperparathyroidism

Types

• Adenoma - 85-95% (solitary, single gland; other glands are normal or atrophied due to feedback inhibition)
• Primary hyperplasia (diffuse or nodular) - 5-10% (multiglandular)
• Parathyroid carcinoma - 1%

• Cyclin D1 gene rearrangement (chromosome 11 inversion) - drives excess PTH cell proliferation
• MEN1 tumour suppressor gene mutations (~30-35% of sporadic cases)

Clinical Features of Primary HPT

• Increased osteoclastic activity → bone resorption → osteoporosis, pathological fractures
• Osteitis fibrosa cystica (severe cases): cortical thinning, bone cysts, brown tumours (masses of osteoclasts, reactive giant cells, haemorrhagic debris - can mimic neoplasm)
• Subperiosteal bone resorption (radial aspect of middle phalanx - classic X-ray finding)

• Nephrolithiasis (calcium oxalate/phosphate stones) - most common presentation
• Nephrocalcinosis (calcification of renal interstitium and tubules)

• Nausea, vomiting, constipation, anorexia
• Peptic ulcer disease (hypercalcaemia stimulates gastrin)
• Acute pancreatitis

• Depression, anxiety, cognitive dysfunction, muscle weakness, fatigue

• Hypertension
• Metastatic calcification (stomach, lungs, myocardium, blood vessels)
• Most cases today are asymptomatic - picked up incidentally on routine calcium measurement

Investigations of Primary HPT

• Serum calcium - elevated (hallmark)
• Serum PTH - inappropriately elevated (intact PTH assay - key test to confirm primary)
• Serum phosphate - low (PTH reduces phosphate reabsorption)
• Serum alkaline phosphatase - elevated (active bone resorption)
• Urine calcium - elevated (hypercalciuria) - also helps exclude familial hypocalciuric hypercalcaemia (FHH), where urine calcium is low
• Urine cAMP - elevated
• Serum chloride:phosphate ratio >33 suggests primary HPT
• Vit D (25-OH) and creatinine - baseline

• Sestamibi (Tc-99m) parathyroid scan - most sensitive; identifies adenoma location
• Neck ultrasound - first line; can identify adenoma
• 4D CT - CT with contrast in arterial + venous phases; excellent for ectopic glands
• MRI - used for re-exploration or ectopic parathyroid
• SPECT - functional imaging combined with sestamibi

• DEXA scan - assess osteoporosis (T-score)
• X-ray - subperiosteal resorption, brown tumours

Management of Primary HPT

• Parathyroidectomy is the only cure
• Indications for surgery (NIH guidelines):
  • Serum calcium >1 mg/dL above upper limit of normal
  • Urinary calcium >400 mg/24 hours
  • Creatinine clearance reduced >30%
  • Bone density T-score < -2.5 at any site
  • Age <50 years
  • Symptomatic disease (stones, osteitis fibrosa, neuromuscular symptoms)

• Focused/minimally invasive parathyroidectomy (if single adenoma confirmed on imaging) - most common
• Bilateral neck exploration with 4-gland identification (if hyperplasia suspected/MEN)
• Intraoperative PTH assay (Miami criterion: PTH falls >50% within 10 min of excision = cure)

• Cinacalcet (calcimimetic) - reduces PTH secretion by increasing calcium receptor sensitivity; controls serum calcium but does not cure
• Bisphosphonates (alendronate) - protect bone density
• Hydration and dietary calcium moderation
• Avoid thiazide diuretics, lithium, calcium supplements, immobilization

2. Choledochal Cyst

Todani Classification

Clinical Features

• Classical triad: Jaundice + RUQ abdominal pain + RUQ mass (only present in ~10-30% together)
• 60% diagnosed before age 10 years
• Fever (cholangitis)
• Pancreatitis (common presentation in adults - due to anomalous pancreaticobiliary junction)
• Increased risk of cholangiocarcinoma (risk increases with age at diagnosis)

Investigations

• Ultrasound - confirms cystic dilatation
• MRCP/MRI - gold standard; defines anatomy, especially the relationship of the lower bile duct and pancreatic duct
• CT scan - useful for extent of intra/extrahepatic involvement
• ERCP - shows anomalous pancreaticobiliary junction (long common channel)
• HIDA scan - assesses biliary function

Management

• Radical excision of the cyst + Roux-en-Y hepaticojejunostomy - treatment of choice (types I, II, IVa, IVb)
  • Complete excision important due to risk of cholangiocarcinoma
  • Roux-en-Y also reduces stricture formation and recurrent cholangitis
• Type III: Endoscopic sphincterotomy ± biopsy to exclude dysplasia
• Type V (Caroli disease): Segmental hepatic resection if localized; liver transplantation if diffuse

3. Hydatid Cyst of Liver

Cyst Structure

• Pericyst: Outer fibrous capsule derived from host tissue
• Ectocyst: Outer gelatinous (laminated) membrane of the cyst
• Endocyst (germinal layer): Inner layer; produces brood capsules and scoleces
• Hydatid sand: Free brood capsules and scoleces in hydatid fluid
• Daughter cysts: True replicas of the mother cyst

Clinical Features

• 75% are in the right lobe of the liver; usually solitary
• Males = females; average age ~45 years
• Most are asymptomatic until complications occur
• Symptoms: RUQ pain, dyspepsia, vomiting
• Signs: Hepatomegaly (most common), jaundice (~8%), fever (~8%)
• Complications:
  • Rupture into biliary tree → obstructive jaundice, cholangitis, hydatid material in stool
  • Rupture into peritoneum/pleura/pericardium → disseminated echinococcosis or anaphylactic shock (life-threatening)
  • Bacterial superinfection → pyogenic abscess
  • Calcification (does not always mean dead cyst)

Investigations

• Ultrasound - first line; most commonly used worldwide
  • Well-circumscribed cyst with "budding sign"
  • "Rosette appearance" when daughter cysts present
  • Wall calcifications = highly suggestive
• CT/MRI - defines anatomic relations; evaluates extrahepatic disease
• Chest X-ray - lung involvement
• Serology: ELISA, indirect haemagglutination test, Casoni test (now outdated) - low sensitivity/specificity
• Eosinophilia on FBC
• ERCP/PTC - if biliary involvement suspected
• AVOID diagnostic aspiration (risk of anaphylaxis and dissemination)

Management (Bailey & Love + Sabiston)

• Asymptomatic and inactive cysts - monitor by ultrasound; can be left alone
• Active cysts - treat first with albendazole (benzimidazole drug; pre- and post-operative)
• Surgical options (customised to patient):
  • PAIR (Puncture, Aspiration, Injection of scolicidal agent, Re-aspiration) - minimally invasive; scolicidal agents = hypertonic saline or povidone-iodine
  • Laparoscopic marsupialization (deroofing): Aspirate, instil scolicidal agent, oversew biliary communications, omentoplasty
  • Pericystectomy with omentoplasty: Remove entire pericyst
  • Hepatic segmentectomy/resection: For large/complex/superficial cysts at experienced centres
  • Cystopericystectomy: Total excision of intact cyst (preferred if feasible)
• Best managed in a tertiary hepatobiliary unit with MDT (surgeon + physician + interventional radiologist)

4. Phyllodes Tumour of Breast

Classification

Pathology

• Stromal cells are always monoclonal (unlike fibroadenoma which can be polyclonal) - key distinguishing feature
• Cut surface shows classical leaf-like appearance with gelatinous, solid and cystic areas
• Cystic areas = sites of infarction and necrosis
• Connective tissue composes the bulk
• Malignant phyllodes: stroma contains liposarcomatous or rhabdomyosarcomatous elements (rather than fibrosarcomatous)
• Stroma has greater cellular activity than fibroadenoma

Clinical Features

• Peak age: 40-50 years (older than fibroadenoma)
• Large, rapidly growing breast mass
• Smooth, bosselated surface; well-demarcated
• May become very large (giant phyllodes)
• Skin may become stretched/shiny but ulceration is rare
• Lymph node metastases are rare - haematogenous spread more common (lungs, bone) in malignant cases

Investigations

• Mammography: Cannot reliably distinguish benign from malignant; calcifications and necrosis do not help differentiate
• Ultrasound: Hypoechoic mass, smooth margins, internal cystic spaces
• Core needle biopsy - preferred over FNAC; needed to show stromal component
• Histology with mitotic count, margin assessment and stromal atypia is key to grading

Management (Schwartz's Principles of Surgery)

• Wide local excision (WLE) with 1 cm clear margin for all phyllodes (benign and malignant)
• If positive margin at initial excision → re-excision to achieve 1 cm clear margin
• Simple mastectomy for large tumours where adequate margins cannot be achieved with WLE
• Axillary dissection is NOT recommended - axillary lymph node metastases are rare
• Radiation therapy: sometimes used in malignant phyllodes after excision
• Chemotherapy: for systemic metastatic disease (sarcoma-based regimens)
• Local recurrence is common especially in borderline and malignant types

5. Multinodular Goitre (MNG)

Types

Pathogenesis

• Iodine deficiency (most common worldwide cause)
• Repeated cycles of hyperplasia and involution lead to nodule formation
• Toxic MNG: Genetic mutations within specific nodules → clonal expansion → autonomous TSH-independent hormone secretion
• Jod-Basedow effect: Iodine load (e.g. IV contrast) can precipitate hyperthyroidism in iodine-deficient patients with MNG

Clinical Features

• Neck swelling (bilateral, asymmetric, multinodular)
• Cosmetic concern
• Compressive symptoms (pressure effects):
  • Dysphagia (compression of oesophagus)
  • Dyspnoea (tracheal compression/deviation), worse at night
  • Stridor, hoarseness (rare - recurrent laryngeal nerve compression)
  • SVC syndrome (rarely, with retrosternal goitre)
• Pemberton's sign: Facial flushing and venous congestion when arms raised above head (retrosternal goitre)
• Thyroid function: Euthyroid

• Older patients (>50 years) - occurs later in the natural history
• Thyroid hyperfunction is less marked than Graves' disease
• Cardiovascular symptoms predominate: Palpitations, atrial fibrillation, tachyarrhythmias
• Weight loss, heat intolerance (may be subtle)
• Pre-existing goitre of long duration before thyrotoxicosis appears
• Classical eye signs of Graves' (exophthalmos) are absent

Investigations

• TFTs: TSH (suppressed in toxic), free T4, free T3
• Ultrasound: First-line for nodule characterisation; multiple isoechoic nodules with varying cystic change = almost certainly benign; assesses extent, tracheal deviation
• CT neck/thorax (non-contrast): For retrosternal extension, tracheal narrowing
• FNAC of dominant nodule: To exclude malignancy
• Radionuclide scan (Tc-99m or I-123): Identifies hot (autonomous) and cold (potentially malignant) nodules; useful in toxic MNG
• Chest X-ray: Tracheal deviation, retrosternal shadow

• Solid and hypoechoic
• Ill-defined margins
• Microcalcifications
• "Taller than wide" shape
• If none of these features present → NPV for malignancy >97%

Management

• Observation if small and asymptomatic
• Surgery (total/near-total thyroidectomy) for:
  • Moderate-to-severe compressive symptoms
  • FNAC suspicious for malignancy
  • Patient preference (cosmesis)
  • Retrosternal goitre
• Radioiodine (RAI, I-131): For patients who refuse surgery or have surgical comorbidities; can reduce goitre size by up to 60%; favoured in small goitres in younger patients

• Anti-thyroid drugs (carbimazole/propylthiouracil): To achieve euthyroid state before definitive treatment
• Definitive treatment with radioiodine (preferred in older patients, if not too large)
• Surgery (thyroidectomy): If compressive symptoms, large goitre, or suspected malignancy
• Beta-blockers: For symptomatic cardiovascular control (AF, tachycardia)
• Suppressive thyroid hormone therapy is outdated - associated with subclinical hyperthyroidism and increased risk of osteoporosis and cardiovascular disease