1. THE PARATHYROID

2. PTH/Calcium Homeostasis

3. PTH Renal effects (steady state maintenance)
Inhibition of phosphate transport
Increased reabsorption of calcium
Stimulation of 25(OH)D-1alpha-hydroxylase
Bone effects (immediate control of blood Ca)
Causes calcium bone release within minutes
Chronic elevation increases bone remodeling and increased osteoclast-mediated bone resorption
However, PTH administered intermittently has been shown to increase bone formation and this is a potential new therapy for osteoporosis

4. Disorders of the Parathyroid Glands
Calcitonin is released by the “C” cells (parafollicular cells in the thyroid gland) in response to small increases in plasma ionic calcium. It acts on the kidney and bones to restore the level of calcium to just below a normal set point which in turn inhibits secretion of the hormone. Calcitonin is therefore the physiological antagonist of PTH. The two hormones act in concert to maintain normal concentration of calcium ion in the extracellular fluid

5. Classification of disease of parathyroid
Hormone excess
-primary
primary hyperpara (adenoma, ca, hyperplasia)
tertiary after prolong secondary
-secondary
secondary hyperpara (CRF) ,malabsorption, vit D deficincy

6. Hormone def- post surgical, autoimmune, inherted
H hypersensitivity-hypercalcemic hypocalciuria
H resistance-pseudohypoparathyroidism
familial hypocalciuric hypercalc.
--Parathyroid carcinoma

7. Primary HPT: Clinical Features
Symptomatic:
Osteitis fibrosa cystica
Nephrolithiasis
Pathologic fractures
Neuromuscular disease
Life-threatening hypercalcemia
?Peptic Ulcer Disease
?Asymptomatic:
Fatigue
Subjective muscle weakness
Depression
Increased thirst
Polyuria
Constipation
Musculoskeletal aches and pains

8. X-rays:
sub-periosteal resorption pepper pot skull rugger jersey spine cystic brown tumours

9. X-rays: sub-periosteal resorption pepper pot skull rugger jersey spine cystic brown tumours

10. Diagnosis
*High s. Ca, high PTH *Serum phosphate is usually low but may be normal. *Hypercalcaemia is common *blood alkaline phosphatase (of bone origin) *urinary hydroxyproline concentrations elevated *Nephrogenous CAMP is elevated in about 80%

11. Pre-Operative Imaging
High-resolution ultrasound
Sensitivity 65-85% for adenoma; 30-90% for enlarged gland
Results suboptimal in pts with multinodular thyroid disease, pts with short thick neck, ectopic glands (15-20%)
May be useful in detecting sestamibi scan negative adenomas
CT with contrast/thin section
Sensitivity of 46-87%
Good for ectopic glands in the chest
MRI
Sensitivity of 65-80%
Good for ectopic glands
Sestamibi
85-95% accurate in localizing adenoma in primary HPT
Sestamibi-SPECT
Sensitivity 60% for enlarged gland and 98% for solitary adenomas

12. Medical Management
Asymptomatic patients may elect to be closely followed and managed medically
A recent study of pts with asymptomatic primary HPT showed that the majority of pts followed for ten years did not demonstrate an increase in serum calcium or PTH levels—25% of patients had progressive disease including worsening hypercalcemia, hypercalciuria and reduction in bone mass—younger patients more likely to have progression of disease
Patients opting not to have surgery should have a serum calcium level drawn every 6 months and should have annual bone densiometry at all three sites
Estrogen
Bisphosphonates
Studies have shown increase in lumbar spine and femoral neck mineral density
Calcium/Vitamin D
Surgery

13. Surgical Treatment
Clinical indications for surgery in patients with primary hyperparathyroidism
Significant symptoms of hypercalcemia
Nephrolithiasis
Decreased bone mass
Serum Calcium > 12 mg/dl
Age< 50 years
Infeasibility of longterm follow up

14. Secondary Hyperparathyroidism
Decreased GFR leads to reduced inorganic phosphate excretion and consequent phosphate retention
Retained phosphate has a direct stimulatory effect on PTH synthesis and on cellular mass of the parathyroid glands
Retained phosphate also causes excessive production and secretion of PTH through lowering of ionized Ca2+ and by suppression of calcitriol production
Reduced calcitriol production results both from decreased synthesis due to reduced kidney mass and from hyperphosphatemia.

15. Secondary HPT Clinical presentation Usually asymptomatic Diagnosis
Elevated PTH in the setting of low or normal serum calcium is diagnostic
If phosphorous is elevated, cause is renal
If phosphorous is low, other causes of vit D deficiency should be sought
Prevention
Vit D replacement
Phosphorus binders [Sevelamer]
Treatment
Medical
Calcimimetic agents
Surgical
Considered in cases of refractory
severe hypercalcemia, severe
bone disease, severe pruritis,
calciphylaxis, severe myopathy

16. Hypoparathyroidism Clinical Features: Neuromuscular
Parathesia
Tetany
Convulsion
Signs of latent tetany
Chvostek sign
Trousseau sign
Extrapyramidal signs (due to basal ganglia calcification) Other clinical manifestation
Posterio lenticular cataract
Cardiac manifestation:
Prolonged QT interval in the ECG
Refractory heart failure with cardiomegally
3.Dental
4.malabsorption

17. CALCIUM HEMOSTASIS

18. Hypercalcemia
I.Parathyroid-related -Primary hyperparathyroidism -Lithium therapy -Familial hypocalciuric hypercalcemia II. Malignancy-related -Solid tumor with metastases (breast) -Solid tumor with humoral mediation of hypercalcemia (lung, kidney) -Hematologic malignancies (multiple myeloma, lymphoma, leukemia) III. Vitamin D-related -Vitamin D intoxication -↑ 1,25(OH)2D; sarcoidosis and other granulomatous diseases -Idiopathic hypercalcemia of infancy IV. Associated with high bone turnover -Hyperthyroidism -Immobilization -Thiazides -Vitamin A intoxication V. Associated with renal failure -Severe secondary hyperparathyroidism -Aluminum intoxication -Milk-alkali syndrome
**Primary hyperparathyroidism and cancer account for 90% of cases of hypercalcemia

19. Differential Diagnosis
Causes of Hypercalcemia
Parathyroid - related
Vitamin D – related
Primary hyperparathyroidism
Solitary adenomas
Multiple endocrine neoplasia
Lithium therapy
Familial hypocalciuric hypercalcemia
Vitamin D intoxication
1,25(OH)2D; sarcoidosis and other granulomatous diseases
Idiopathic hypercalcemia or infancy

20. Differential Diagnosis
Causes of Hypercalcemia
Associated with high bone turnover
Malignancy - related
Solid tumor with metastases(breast)
Solid tumor with humoral mediation of hypercalcemia (lung kidney)
Hematologic malignancies (multiple myeloma, lymphoma, leukemia)
Hyperthyroidism
Immobilization
Thiazides
Vitamin A intoxication
Assocated with Renal Failure:
Severe secondary hyperparathyroidism
Aluminum intoxication
Milk alkali syndrome

21. Etiologies of Hypocalcemia
Decreased GI Absorption Poor dietary intake of calcium Impaired absorption of calcium Vitamin D deficiency Poor dietary intake of vitamin D Malabsorption syndromes Decreased conversion of vit. D to calcitriol Liver failure Renal failure Low PTH Hyperphosphatemia Decreased Bone Resorption/Increased Mineralization PTH resistance Vitamin D deficiency / low calcitriol Hungry bones syndrome Osteoblastic metastases
Increased Urinary Excretion
Low PTH
s/p thyroidectomy
s/p I131 treatment
Autoimmune hypoparathyroidism
PTH resistance
Vitamin D deficiency / low calcitriol

22. HyPOCALCEMIA Disease CAL Ca+ Ph PTH Alkalosis - low - -or high
Vit D def low low low high
CRF low low high high
Hypopara low low high low
Psudohypo low low high high
Pancreatitis low low low high
Hypoalbumin low

23. Pharmacologic options of hypercalcemia
Normal Saline 2-4 L IV daily for 1-3 days
Enhances filtration and excretion of CA++.
Indication: Ca > 14 mg/dl, moderate Calcium with symptoms
Caution: may exacerbate heart failure in elderly patients. Lowers Calcium by 1-3 mg/dl

24. Pharmacologic options
Furosemide mg IV as necessary
Inhibits calcium resorption in distal renal tubule.
Indication: following aggressive hydration
Caution: hypokalemia, dehydration if used before intravascular volume is restored

25. Pharmacologic options
Bisphosphonates
Pamidronate
Zoledronic acid
Inhibits osteoclast action and bone resporption
Indication: hypercalcemia of malignancy

27. Management of hypocalcemia
Dependent on the underlying cause and severity
Administration of calcium alone is only transiently effective
Mild asymptomatic cases: Often adequate to increase dietary calcium by 1000 mg/day
Symptomatic: Treat immediately (Ca gluconate 20% 20cc in 20 min).
Consider activated Vit D
Respiratory alkalosis (treat accordingly)

28. Osteoporosis
- Idiopathic osteoporosis - normal investigations - In old patients we have to role out malignancy and multiple myeloma - Younger patients must be fully investigated - Several causes may be involved - Osteoporosis can be associated with osteomalacia

29. Osteoporosis
Symptoms & Signs - Bony aches - Easy fractures spine - lower radius - femoral neck - Rib fracture , chest pain - Normal biochemistry

30. Osteoporosis
X-rays - Decrease bone density - Wedging or biconcave vertebrae - Thin cortex and deformities - Dexa Scan - Biopsy

31. Osteoporosis
Treatment - Treat underlying cause - Idiopathic , extremely difficult - Calcium and vitamin D - Fluoride and triple therapy - Calcitonin , Diphosphonate - Treat fractures