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PARATHYROID DYSFUNCTION DR MANOHAR, RESIDENT INHS ASVINI
| Date post: | 11-Feb-2017 |
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PARATHYROID DYSFUNCTION
DR MANOHAR, RESIDENT INHS ASVINI
• Embryology
• Anatomy
• Physiology
• Genetics
• Types of hyperparathyroidism
Embryology
ANATOMY
Number, size, shape, colour and location
• Pseudocapsule
Positional symmetry
Blood supply
Nerve supply
- Vasomotor and not secretomotor
Microscopy
Physiology
Parathyroid hormone
o Pre-pro PTH
o ProPTH
o Active form: 1-34 N-terminal fragment
Calcium-sensing receptor
Actions of Parathyroid hormone
• Types of PTH receptors
• Action in kidney
• Action on osteoblast
• Vitamin D3
PTHrP
o Hypercalcaemia of malignancy
o Acts via all receptors
o Calcium level in breast milk
Vitamin D
o Precursor 7-dehydro-cholesterol
o 25-hydroxycholecalciferol
o Calcitriol (Vit D3)
o Action of Vitamin D on intestine and bone
Calcitonin
o Parafollicular cells
o 32 amino acid polypeptide
o Calcium sensing receptors on ‘C’ cells
o Osteoclast and Proximal convoluted tubules
Calcium homeostasis
Genetics of hyperparathyroidism
PRAD-1
-Chromosome 11
-Overexpression of regulatory protein
cyclin D1
-Sporadic parathyroid adenomas (50%)
MEN-1
o Chromosome 11q13
o 25% sporadic parathyroid adenoma
o Parathyroid, pancreatic islets and pituitary
tumours
Ret proto-oncogene (MEN-2 gene)
o Chromosome 10
Two subtypes: MEN-1 and MEN-2
cRET genetic mutation (90%)
Mutational analysis of cRET
RB gene
o Chromosome I3qI4
o Allelic deletion of the RB gene
Gene on chromosome 1 b
o Chromosome1q2I-q3I
o Sporadic parathyroid adenomas (40%)
o Mandibular and maxillary tumours, Wilm's
tumour, adult nephroblastoma and increased risk of
parathyroid cancer
Gene on chromosome Xp11
• Refractory secondary HPT seen in chronic renal
failure
• Nodular hyperplasia
Gene for CSR
o Heterozygous mutations
- FHH
o Homozygous mutations
- Neonatal Severe hyperparathyroidism (NSHPT)
- Profound hypercalcaemia
PTH-receptor gene
Chromosome 3
Jansen's disease
o Dwarfism
o Hypercalcaemia
- Hypophosphataemia
- PTH normal or undetectable
William's syndrome
o chromosome 7
o Infantile hypercalcaemia
o supravalvular aortic stenosis
o Psychomotor retardation and elfin facies
Types of Hyperparathyroidism
Primary
Secondary
Tertiary
Primary Hyperparathyroidism
o Immediate effect of lowered calcium
o Persistance of stimulus
o stimulus for extensive period of time
Incidence
o Men-0.3% and women 1-3%
Clinical features
Musculoskeletal
o Reduced bone mineral density
o Osteitis fibrosa cystica
Renal
o Renal and ureteric stones
Gastrointestinal
o Abdominal pain (constipation)
Psychological
o Anxiety and depression
o dementia
o loss of concentration
Metabolic syndrome
o Peripheral insulin resistance
o Blood lipid levels
o Cardiovascular disorders
Diagnosis:
o High serum calcium
o High PTH
Non parathyroid hypercalcaemia
o PTH <25pg/ml
Hypercalcaemia of malignancy
• PTHrP
• Chemiluminescent assay
o Serum phosphate
o Serum creatinine
Pathology
o Adenoma-80%
o Hyperplasia-15-20%
o Carcinoma-1%
o Radiotherapy to head and neck
Adenoma
o Usually solitary
o Lower glands commonly affected
o Generally ovoid, soft, reddish-brown tumours
o Little darker than the normal glands
Microscopy
• Chief cell adenoma are common
• Peripheral rim of condensed normal parathyroid
tissue, separated by slender capsule
Parathyroid hyperplasia
o Affects more than one gland
o Enlarged glands are rounded or grossly lobulated
o Grey-brown in colour
Microscopy
o Primary chief-cell or nodular hyperplasia
Parathyroid carcinoma
o 1% of primary hyperparathyroidism
o Very high levels of calcium and PTH
o >2cm in size
• Microscopy
o Invasion of capsule, vascular invasion, focal areas of
necrosis, cellular atypia
Investigations in Primary PTH
Biochemical:
• Plasma calcium, albumin, vitamin D and intact
PTH
• 24 hr urine collection
Localisation studies
Ultrasound
• Sensitivity 85% (unexplored neck)
and 40% in previous exploration
Scintigraphy
• Thallium chloride, Tc99m sestamibi
• 87% solitary adenoma
• 55% abnormal glands with multiglandular disease
• 75% persistent or recurrent lesions in previously
explored neck
Selective venous sampling and angiography
• Previously failed exploration
• Most modern multiphase 4D-CT techniques report a
sensitivity and specificity >90%
• MRI-ectopic mediastinal glands, with sensitivity >80%
PET scan
• 11C methionine
• Sensitivity 83%, sepecificity 100%, accuracy to locate
88%
CT-MIBI fusion image in coronal and sagittal planes showing ectopic superior parathyroid adenoma located superior to the thyroid lobe
Secondary hyperparathyroidism
o Chronic renal failure
• Lose calcium and retain phosphate
• Reduced calcium and vitamin D receptors on
parathyroid cells
o Shifting of CSR set point to right
o Parathyroid cell replication and hyperplasia
o Metabolic acidosis
Vitamin D deficiency
o Dark skin
o Poor diet and malabsorption syndrome
o Lithium therapy
o Malabsorption syndrome
o Long term TPN
Tertiary Hyperparathyroidism
o CSR set point irreversibly shifted to right
o Failure to normalize parathyroid function upon
withdrawal of stimulus
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