Parathyroid Adenoma - Surgical Oncology Case

Overview

Pathology

Figure: Parathyroid gland adenoma, 1.2 g, in primary hyperparathyroidism - (a) external surface; (b) transected surface. Scott-Brown's Otorhinolaryngology, Vol. 1

• Parathyroid carcinoma
• Parathyroid adenoma
• Secondary, mesenchymal and other tumors

Pathophysiology

1. Bone resorption - PTH increases osteoclast maturation, shifting bone balance toward destruction and freeing stored calcium
2. Renal calcium reabsorption - PTH acts on the distal tubule to increase reabsorption; paradoxically, sustained PTH elevation causes hypercalciuria (predisposing to nephrolithiasis)
3. Activation of vitamin D - PTH stimulates 1-alpha-hydroxylase in the kidney, converting 25-OH-D3 to active 1,25-(OH)2-D3, increasing intestinal calcium absorption

Clinical Presentation

• Nephrolithiasis/Renal: Calcium oxalate/phosphate stones, nephrocalcinosis, polyuria
• Skeletal: Osteoporosis, fractures, osteitis fibrosa cystica (severe/long-standing)
• GI/Abdominal: Nausea, constipation, peptic ulcers, pancreatitis
• Neuropsychiatric: Depression, anxiety, cognitive impairment, fatigue

• Calcium >14 mg/dL
• PTH >5x upper limit of normal
• Palpable neck mass
• Idiopathic hoarseness

Diagnosis / Biochemistry

• MEN1 (hyperparathyroidism + pituitary + pancreatic tumors)
• MEN2A (hyperparathyroidism + medullary thyroid carcinoma + pheochromocytoma)
• Familial isolated hyperparathyroidism
• HPT-JT syndrome (jaw tumor syndrome)

Preoperative Localization

Ultrasound

• First-line, widely available, no radiation
• Sensitivity ~70-80% for single adenomas
• Limited for ectopic/mediastinal/deep glands

Sestamibi Scintigraphy (Tc-99m)

• Retained in mitochondria-rich oxyphil cells of hyperfunctioning parathyroids
• Planar: Sensitivity limited (12-25% negative)
• SPECT: 3D; sensitivity 87-91% for single adenomas
• SPECT/CT: Sensitivity up to 96% for single adenomas; significantly less radiation than 4D-CT; improved MGD detection
• Negative correlates with: small gland size, coexisting thyroid disease, superior location, calcium channel blocker use, MGD

4D-CT (Four-Dimensional CT)

• Dynamic contrast CT (3 spatial dimensions + time)
• Exploits rapid contrast uptake and washout by adenoma vs. surrounding tissue
• Excellent anatomic detail, useful for ectopic glands and reoperative cases
• Higher radiation dose than SPECT/CT

Concordant localization (two modalities agreeing) = strongest indication for focused/minimally invasive parathyroidectomy (MIP).

Indications for Surgery

Surgical Approaches

1. Minimally Invasive Parathyroidectomy (MIP)

• Focused unilateral exploration through a small incision
• The adenoma is identified, circumferentially dissected, and excised
• Careful preservation of the recurrent laryngeal nerve (RLN)
• Hilar vessels clamped and ligated; gland sent for histology

2. Bilateral Neck Exploration (BNE)

3. Intraoperative PTH Monitoring (IOPTH) - "Miami Criterion"

• PTH half-life ~3-5 minutes
• Cure criterion: PTH falls by >50% from pre-excision baseline at 10 minutes post-excision
• Predictive of cure in ~98% of cases
• If PTH does not drop adequately, continued exploration is mandatory
• Replaces the need for bilateral exploration in focused surgery

Intraoperative Gland Recognition

Embryology & Ectopic Glands

Complications of Parathyroidectomy

Postoperative Care

• Calcium and PTH levels checked at 4-6 weeks to confirm cure
• Routine oral calcium supplementation on discharge (minimum 24-48 hours)
• Day-case procedure is standard in most centers; 4-6 hour minimum observation
• Wound review and biochemistry at 6-week follow-up
• Up to 10% of patients relapse, sometimes after many years

Concomitant Thyroid Disease

• Fischer's Mastery of Surgery, 8th Edition - Ch. 39 (Primary Hyperparathyroidism)
• Scott-Brown's Otorhinolaryngology Head & Neck Surgery, Vol. 1 - Ch. 58, 77
• Henry's Clinical Diagnosis and Management by Laboratory Methods

Anaemia in Pregnancy

Definition

Physiological Changes of Pregnancy (Understanding the Baseline)

Figure: Hematologic changes during pregnancy. Blood volume peaks ~34-35 weeks, plasma volume increases ~47% while RBC mass increases only ~17%, producing physiologic hemodilution. Creasy & Resnik's Maternal-Fetal Medicine

Classification & Causes

1. Iron Deficiency Anaemia (IDA) - Most Common (~75%)

• Total iron requirement of pregnancy = ~1130 mg (range 580-1340 mg)

• Most women enter pregnancy with marginal iron stores (~two-thirds of healthy women have minimal marrow iron stores)
• Estimated average daily iron requirement in pregnancy = 22-23 mg/day; median dietary intake is only 15 mg/day
• IDA increases from 8% (1st trimester) to 62% (3rd trimester) even with average supplementation

1. Prelatent: Decreased serum ferritin only (marrow stores depleted)
2. Latent: Abnormal iron studies (↓ serum iron, ↑ TIBC, ↓ transferrin saturation); Hb normal
3. Manifest IDA: ↓ Hb, then ↓ MCV (microcytic hypochromic anaemia)

• Serum ferritin - most accurate single test for IDA in pregnancy
  • Ferritin < 12 µg/L = IDA; < 20 µg/L = iron deficiency (used by some authors)
  • Caveat: ferritin is an acute phase reactant - may be falsely normal in infection/inflammation
  • Measuring Hb alone is inadequate (only 6% of women with ferritin <20 µg/L have anaemia)
• Soluble transferrin receptor (sTfR): Not affected by inflammation; elevated value supports IDA; limited by lack of standardization
• Blood film: Microcytic, hypochromic RBCs, pencil cells, anisocytosis, poikilocytosis

2. Megaloblastic Anaemia

• Folate requirement increases from 400 µg/day (non-pregnant) to 600 µg/day during pregnancy
• Critical from periconception: adequate folate before and during first weeks of pregnancy reduces neural tube defects (spina bifida, anencephaly) by ~50-70%
• Higher requirement in: multiple pregnancy, haemolytic anaemia
• Absorption decreased by: anticonvulsants, oral contraceptives, alcohol, sulfa drugs
• Folate deficiency defined as serum level < 2.5-3 ng/mL

• Dietary B12 absorbed via intrinsic factor (gastric parietal cells)
• Risk factors: strict vegetarianism/veganism, pernicious anaemia, gastrectomy
• Blood film: macrocytic anaemia, hypersegmented neutrophils
• Serum B12 level falls physiologically in pregnancy (not always true deficiency)

3. Haemoglobinopathies

• Maternal complications: more frequent pain crises, increased risk of VTE, preeclampsia, pyelonephritis, pulmonary complications
• Treatment of pain crises: same as in non-pregnant patients
• Hydroxyurea is CONTRAINDICATED in pregnancy (known teratogenicity)
• Blood transfusion for severe anaemia; prophylactic transfusion in some centres

• Alpha-thalassaemia trait: usually mild microcytic anaemia; Hb Bart's disease (hydrops fetalis) lethal
• Beta-thalassaemia trait: microcytic hypochromic anaemia, Hb A2 >3.5%; partner screening essential
• Beta-thalassaemia major: requires transfusion support throughout pregnancy (rare to reach reproductive age without treatment)

4. Autoimmune Haemolytic Anaemia (AIHA)

• Warm-reactive antibodies (IgG): directed against Rh antigens; associated with lupus, lymphoproliferative disorders, drugs (penicillin, methyldopa)
• Cold-reactive antibodies (IgM): against I/i antigens; associated with Mycoplasma, EBV
• Diagnosis: hyperproliferative macrocytic anaemia + positive direct Coombs test + peripheral smear showing spherocytes, polychromatophilia
• Treatment: blood transfusion, corticosteroids (~80% respond with warm AIHA), immunosuppression; splenectomy (second-line, ~60% effective for warm AIHA); rituximab (anti-CD20) used successfully in refractory cases during pregnancy without adverse maternal/fetal outcomes

5. G6PD Deficiency

• X-linked; affects >400 million people worldwide
• G6PD maintains glutathione in reduced state to protect RBCs from oxidant stress
• Female heterozygotes generally unaffected but some may have low G6PD activity (Lyon hypothesis)
• Haemolytic crises triggered by: oxidant drugs, infections, fava beans
• Drugs to avoid: primaquine, nitrofurantoin, sulfa drugs, dapsone, aspirin (high dose)

6. Aplastic Anaemia in Pregnancy

• Rare; may be pregnancy-induced (some cases remit after delivery)
• Pancytopenia; hypocellular bone marrow
• Treatment: supportive transfusions, immunosuppression; haematopoietic stem cell transplant deferred until after delivery

7. Anaemia of Chronic Disease / Inflammation

• Normocytic normochromic anaemia; both serum iron and TIBC decreased; transferrin saturation usually normal; ferritin normal or elevated

Laboratory Reference Ranges in Pregnancy (Creasy & Resnik's)

Management

Screening (FIGO 2025 Guideline)

• Screen all pregnant women at booking and again at 28 weeks with full blood count (FBC), or packed cell volume/Hb where FBC is unavailable.

Iron Deficiency Anaemia

• Supplementation with 60 mg elemental iron/day during second and third trimesters meets daily requirements
• Iron supplementation reduces incidence of anaemia by up to 73%
• National Academy of Medicine: offer supplementation to women with ferritin < 20 µg/L
• Routine supplementation (regardless of ferritin) is common practice in the US

• First-line for mild-moderate IDA; second and second/third trimester
• Ferrous sulfate 200 mg TDS (65 mg elemental iron each) or ferrous gluconate/fumarate
• Take on empty stomach or with vitamin C to enhance absorption
• Side effects: nausea, constipation - may limit compliance

• Contraindicated in first trimester (anaphylaxis risk + limited safety data)
• Treatment of choice for IDA in third trimester and for severe IDA in second trimester
• Also used when oral iron is not tolerated or insufficient
• Formulations: ferric carboxymaltose, iron sucrose, low-molecular-weight iron dextran
• A 2024 Cochrane review (PMID: 39145520) confirmed daily oral iron supplementation during pregnancy reduces maternal anaemia and improves haemoglobin at term

Folate Deficiency

• Folic acid 5 mg/day for treatment of established megaloblastic anaemia
• 400 µg/day for prevention in low-risk pregnancies (start periconception)
• 5 mg/day periconceptionally for high-risk (previous NTD, epilepsy, malabsorption, twins, haemolytic anaemia)

Vitamin B12 Deficiency

• Cyanocobalamin or hydroxocobalamin supplementation
• IM injections if malabsorption/pernicious anaemia

Severe / Symptomatic Anaemia

• Blood transfusion when Hb <7 g/dL or symptomatic (dyspnoea at rest, cardiac decompensation)
• Threshold may be higher (Hb <8-9 g/dL) in haemoglobinopathies or those with poor tolerance
• Always use leukodepleted, CMV-negative blood in haemoglobinopathy patients (to minimise alloimmunisation)

Malaria / Helminth Prophylaxis (FIGO 2025)

• In endemic regions: intermittent preventive treatment with sulphadoxine-pyrimethamine (IPTp-SP) reduces malaria-associated anaemia
• Anti-helminthic chemoprophylaxis (mebendazole/albendazole) in endemic areas reduces hookworm-associated IDA - give after first trimester

Maternal and Fetal Consequences

Key Points Summary

• Anaemia in pregnancy = Hb < 11 g/dL (all trimesters, WHO/FIGO)
• IDA is most common (~75%); serum ferritin is the best single diagnostic test
• Plasma volume rises disproportionately to RBC mass → physiologic hemodilution
• Three-stage progression of IDA: ferritin ↓ → iron studies abnormal → Hb ↓ → MCV ↓
• Oral iron is first-line; IV iron is preferred in 3rd trimester and severe IDA; avoid in 1st trimester
• Folate 400 µg/day periconceptionally prevents neural tube defects; 5 mg/day for high-risk women
• Screen at booking and at 28 weeks (FIGO 2025)
• Hydroxyurea is contraindicated in pregnancy (sickle cell)

• Creasy & Resnik's Maternal-Fetal Medicine, 8th Edition, Ch. 55
• Goldman-Cecil Medicine, 27th Edition, Ch. 150
• Rosen's Emergency Medicine, 9th Edition, Ch. 177
• FIGO Good Practice Recommendations on Anemia in Pregnancy, 2025 (PMID: 41031541)
• Cochrane Review: Daily oral iron supplementation during pregnancy, 2024 (PMID: 39145520)