Endocrine - Parathyroid disease Flashcards

Question

Investigations for asymptomatic primary hyperparathyroidism

Answer 1

Biochemistry: * Calcium, Phosphate, ALP * Urea. Creatinine, eGFR (treatment guidance) * 25 hydroxyvitamin D (for deficiency) * PTH by immunoassay Bone: * DXA scan for BMD (at distal radius, hip or lumbar spine) for osteoporosis * Vertebral spine assessment by X-ray or Vertebral fracture assessment by DXA Urine: 24h urine calcium and creatinine Abdominal: Urinary stones by KUB, USG, CT Optional: Bone turnover markers, TBS score by DXA, High-res peripheral quantitative CT

Answer 2

Age under 50 Serum calcium \>0.25 mmol/L DXA T-score \< -2.5 at lumbar spine, total hip, femoral neck or distal radius Renal: * Creatinine clearance \<60cc/ min * 24h urine calcium \> 400mg/day * Presence of nephrolithiasis or nephrocalcinosis by imaging

Answer 3

Annual serum calcium measurement DXA scan ever 1-2 years at 3 sites X-ray of VFA spine if indicated Renal: Annual eGFR, serum creatinine Renal stone suspected: 24h biochemical stone profile, renal imaging

Answer 4

Surgical planning by imaging: * Parathyroid ultrasound (pre-op or intra-op) * Nuclear scintigraphy (Tc-99m Sestamibi scan)/ SPECT * CT with contrast - 4DCT scan * MRI

Answer 5

Tc-99m taken up by mitochondria-rich oxyphil cells in parathyroid gland Planar images obtained shortly after injection and again at 2 hours to find foci of retained radio tracer activity

Answer 6

Minimal invasive approach Multi-glandular disease: * Subtotal parathyroidectomy - resect 3.5 glands and preserve 50-80mg vascularized gland * Total thyroidectomy - with autotransplantation to forearm or cryopreservation for later transplant

Answer 7

PTH half-life - 4 minutes in pt with normal renal function Drop in serum PTH: 5-10mins Miami Criterion - 50% fall in PTH compared to highest of either pre-manipulation or pre-excision sample *Serum calcium takes 1-2 days to fall so NOT USED for intra-op monitoring*

Answer 8

Advantages: * Improve cosmesis * Short hospital stay * Decrease wound pain * Reduce morbidity * Decrease overall cost Pre-requisites * Pre-operative or intra-operative localization * Intra-operative PTH assay monitoring

Answer 9

Secondary: Physiological response to hypocalcemic state \> increase PTH secretion Tertiary: Prolonged secondary hyperparathyroidism \> Parathyroid hyperplasia \> autonomous secretion of PTH

Answer 10

**Calcimimetics**: mimic calcium by allosteric action on Calcium Sensing Receptor Indication: * Surgery not appropriate or contraindicated * Severe hypercalcemia unable to undergo parathyroidectomy * Only normalize serum Ca, no effect on BMD + regular monitoring of annual serum Ca, DXA of 3 sites and Xray spine + eGFR and Creatinine + biochemical stone profile and imaging if needed

Answer 11

Lung (Squamous cell) Breast head and neck (Squamous) Kidney Myeloma Lymphoma

Answer 12

1. PTH-related peptide - **PTHrP** secretion 2. **Bone metastases** with direct local destruction or induction of local osteolysis by tumor cells 3. **Lymphokine production that activate osteoclasts** by hematological cancer (e.g. Multiple Myeloma) 4. Extra-renal production of 1,25 dihydroxy-vitamin D (e.g. Adult T-cell lymphoma)

Answer 13

Serum Ca under 1.9mmol/L

Answer 14

hypoCa leads to generalized hyperexcitability, symptomatic when [Ca] \<2mmol/L Sequence: sensory symptoms → latent tetany → gross spasm → laryngospasm → arrhythmia CATS - Convulsion, Arrhythmia, Tetany, Seizures and sensory changes □ Sensory changes: paraesthesia, perioral numbness □ Tetany: muscle spasms, convulsions, stridor (laryngeal spasm) → Carpopedal spasm: hand and feet spasms with hand adopting characteristic ‘main d’accoucheur’ appearance71 → Chvostek’s sign: tapping CN VII branches triggers facial twitching → Trousseau’s sign: inflation of BP cuff \>sysBP triggers carpal spasm within 3min □ Seizures: generalized tonic-clonic, absence, focal □ Heart: long QT, T wave inversion, arrhythmias (eg. TdP)

Answer 15

screen for occult malignancy should be done: □ CXR for CA lung □ Serum/urine protein electrophoresis for multiple myeloma □ Mammogram □ CT abdomen, thorax

Answer 16

Management: □ Acute Tx for severe hyperCa → IV saline, bisphosphonate ± calcitonin □ Novel agents MAb vs RANKL, eg. denosumab Recombinant OPG □ Monitor underlying tumour status ± modification of Tx (frequently a sign of tumour progression

Answer 17

□ Chronic effects: → Neurological: basal ganglion calcification, generalized epilepsy, psychosis → Musculoskeletal: rickets, osteomalacia, dental hypoplasia → Dermatological: alopecia, brittle nails, dry skin → Others: cataract

Answer 18

look for causes and treat accordingly! Severe or symptomatic: Ca \< 1.9 → IV 10% Ca gluconate infusion → Close monitoring of serum Ca →ECG and cardiac monitoring Mild: Ca \> 1.9 First-line: Oral Ca replacement - Caltrate, Oscal, Calcium gluconate Second-line: add vitamin D Third-line: 1,25-(OH)2-D3 added

Answer 19

Mechanism: → ↓renal Ca reabsorption → ↓renal vitamin D3 formation → PO4 retention → ↑bound Ca + metastatic calcification → Uraemia → poor appetite → ↓GI/oral intake → Uraemia → bone resistance to PTH

Answer 20

classically a/w hypoK + hypoCa refractory to replacement □ Mechanism: ↓PTH action and secretion □ Mx: IV MgSO4 if severe, Mylanta / Mg tri if mild

Answer 21

PseudohypoPTH (PHP): □ Cause: maternal GNAS1 mutation (encoding for Gsα gene important for PTHr) ``` □ S/S: typically presents with Biochemical hypoPTH (↓Ca, ↑PO4) with ↑PTH and parathyroid hyperplasia Albright hereditary osteodystrophy (AHO) with mental retardation, short stature and shortened 4th and 5th metacarpals ``` □ Diagnosis: genetic testing

Answer 22

failure: a/w a biochemical picture of ↓Ca ↓PO4 □ Causes: ↓intake: malnutrition, malabsorption ↓metabolism: ↓di-hydroxylation (liver disease), ↓hydroxylation (renal disease) ↓response: type II vitamin D-dependent rickets, type I vitamin D-dependent rickets ↑clearance of calcitriol: nephrotic syndrome, drugs (Dilantin, alcohol, glutethimide)

Answer 23

25-(OH)-D3 reflects level of intake and production - Low → nutritional insufficiency 1,25-(OH)2-D3 reflects level of active hormone - High/normal → type II vitamin D-dependent rickets (VDDR) Cause: vitamin D receptor defect, NOT amenable to calcitriol replacement - Low → type I vitamin D-dependent rickets (VDDR) Cause: 1α-hydroxylase deficiency, amenable to calcitriol replacement