This document provides an overview of parathyroid dysfunction, including: 1. It discusses the embryology, anatomy, physiology, genetics, and types of hyperparathyroidism related to parathyroid function. 2. It describes primary hyperparathyroidism which is caused by an adenoma or hyperplasia in most cases, and presents with high calcium and PTH levels. Investigations include biochemical tests, ultrasound, scintigraphy, CT, and MRI to localize abnormal glands. 3. Secondary hyperparathyroidism is caused by chronic kidney disease or vitamin D deficiency which shifts the calcium set point, causing parathyroid cell hyperplasia over time. 4. T

1. PARATHYROID DYSFUNCTION
DR MANOHAR, RESIDENT
INHS ASVINI

2. • Embryology
• Anatomy
• Physiology
• Genetics
• Types of hyperparathyroidism

3. Embryology

7. ANATOMY
 Number, size, shape, colour and location
• Pseudocapsule
 Positional symmetry
 Blood supply
 Nerve supply
- Vasomotor and not secretomotor

8. Microscopy

9. Physiology
 Parathyroid hormone
o Pre-pro PTH
o ProPTH
o Active form: 1-34 N-terminal fragment
 Calcium-sensing receptor

10.  Actions of Parathyroid hormone
• Types of PTH receptors
• Action in kidney
• Action on osteoblast
• Vitamin D3

11.  PTHrP
o Hypercalcaemia of malignancy
o Acts via all receptors
o Calcium level in breast milk

12.  Vitamin D
o Precursor 7-dehydro-cholesterol
o 25-hydroxycholecalciferol
o Calcitriol (Vit D3)
o Action of Vitamin D on intestine and bone

13.  Calcitonin
o Parafollicular cells
o 32 amino acid polypeptide
o Calcium sensing receptors on ‘C’ cells
o Osteoclast and Proximal convoluted tubules

14. Calcium homeostasis

15. Genetics of hyperparathyroidism
 PRAD-1
-Chromosome 11
-Overexpression of regulatory protein
cyclin D1
-Sporadic parathyroid adenomas (50%)

16.  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

17.  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

18.  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

19.  Gene on chromosome Xp11
• Refractory secondary HPT seen in chronic renal
failure
• Nodular hyperplasia

20.  Gene for CSR
o Heterozygous mutations
- FHH
o Homozygous mutations
- Neonatal Severe hyperparathyroidism (NSHPT)
- Profound hypercalcaemia

21. PTH-receptor gene
 Chromosome 3
 Jansen's disease
o Dwarfism
o Hypercalcaemia

22. - Hypophosphataemia
- PTH normal or undetectable
 William's syndrome
o chromosome 7
o Infantile hypercalcaemia
o supravalvular aortic stenosis

23. o Psychomotor retardation and elfin facies
Types of Hyperparathyroidism
 Primary
 Secondary
 Tertiary

24. 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%

25. Clinical features
 Musculoskeletal
o Reduced bone mineral density
o Osteitis fibrosa cystica
 Renal
o Renal and ureteric stones

26.  Gastrointestinal
o Abdominal pain (constipation)
 Psychological
o Anxiety and depression
o dementia
o loss of concentration

27.  Metabolic syndrome
o Peripheral insulin resistance
o Blood lipid levels
o Cardiovascular disorders

28. Diagnosis:
o High serum calcium
o High PTH
 Non parathyroid hypercalcaemia
o PTH <25pg/ml
 Hypercalcaemia of malignancy

29. • PTHrP
• Chemiluminescent assay
o Serum phosphate
o Serum creatinine

30.  Pathology
o Adenoma-80%
o Hyperplasia-15-20%
o Carcinoma-1%
o Radiotherapy to head and neck

31.  Adenoma
o Usually solitary
o Lower glands commonly affected
o Generally ovoid, soft, reddish-brown tumours
o Little darker than the normal glands

32.  Microscopy
• Chief cell adenoma are common
• Peripheral rim of condensed normal parathyroid
tissue, separated by slender capsule

33.  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

34.  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

35. Investigations in Primary PTH
 Biochemical:
• Plasma calcium, albumin, vitamin D and intact
PTH
• 24 hr urine collection

36. Localisation studies
 Ultrasound
• Sensitivity 85% (unexplored neck)
and 40% in previous exploration
 Scintigraphy
• Thallium chloride, Tc99m sestamibi

37. • 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

38. • 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%

39. CT-MIBI fusion image in coronal and sagittal planes showing ectopic superior parathyroid
adenoma located superior to the thyroid lobe

40. Secondary hyperparathyroidism
o Chronic renal failure
• Lose calcium and retain phosphate
• Reduced calcium and vitamin D receptors on
parathyroid cells

41. 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

42. 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

43. THANK YOU