The document discusses parathyroid glands and parathyroid hormone (PTH). It notes that parathyroid glands secrete PTH, which regulates calcium levels in the blood. PTH acts on bone, kidneys, and stimulates vitamin D production. Secondary hyperparathyroidism occurs in kidney disease and is caused by low calcium and vitamin D levels stimulating increased PTH secretion. Treatment focuses on controlling calcium, phosphate, PTH, and vitamin D levels through diet, binders, analogs, and calcimimetics. For refractory cases, parathyroidectomy may be required.

1. K.SRINIVAS
Ist yr pg
Department of general medicine

2. PARATHYROID GLANDS
 Two pairs of parathyroid
glands positioned
behind the outer wings
of thyroid.
 Superior and inferior
parathyroid glands.
 Secretes parathyroid
hormone

3. PARATHYROID HORMONE(PTH)
 84 aminoacid single chain peptide.
 Primary function is to maintain the ECF calcium
concentration with in normal range.
 Acts directly on
bone(calcium resorption)
kidney(calcium reabsorption)
 Stimulates 1 alpha hydroxylase activity, increases
production of 1,25(OH)2D,which increases the
efficiency of calcium absorption.

4.  PTH secretion increases steeply to a maximum value
of about 5 times the basal rate of secretion as calcium
concentration falls to the range of 7.5-8mg/dl.
 ECF calcium controls PTH secretion by interaction
with a calcium sensor, a G protein coupled
receptor(GPCR)

6. PTHrP(parathyroid hormone related protein)
 Responsible for most instances of hypercalcemia of
malignancy.
 A syndrome that resembles hyperparathyroidism but
without elevated PTH levels.
 Produced by brain,pancreas,heart,lung,mammory
tissue,placenta and endothelial cells.

7. PRIMARY HYPER PARATHYROIDISM.
 A generalized disorder of calcium,phosphate and
bone metabolism due to increased secretion of
PTH leading to hypercalcemia and
hypophosphatemia.

8.  parathyroid tumors
solitary adenoma
rarely a parathyroid carcinoma
 MEN syndromes.
MEN1 (wermers syndrome)
MEN2A
 Hyperparathyroid jaw tumors.
 Non syndromic familial isolated hyperparathyroidism.
Etiology

9. Secondary hyperparathyroidism
Is an adaptive process that develops in response to
declining kidney function, impaired phosphate excretion
and failure to bioactivate vitD.
Teritiary hyperparathyroidism
Is a state of severe hyperparathyroidism in patients with
renal failure that requires surgery .

10. SECONDARY HYPERPARATHYROIDISM
Etiology
 Kidney failure requiring dialysis.
 Stomach or intestine bypass surgery for obesity surgery.
 Celiac disease.
 Crohns disease.
 Severe vit D deficiency.

11. Pathophysiology
 Continuous stimulation of the parathyroid glands by a
combination of
increased phosphate concentration and
decreased calcium concentration and markedly reduced
serum calcitriol
increased PTH secretion and synthesis
parathyroid hyperplasia

14. vitaminD
 Is an essential factor for regulation of calcium and
phophorous.
 Active form is 1,25dihydroxy vitaminD .
 Increases the intestinal absorption of calcium and
phosphorous.
 Increase reabsorption of calcium and phosphorous in the
renal tubules.
 Direct effect on the parathyroid glands to supress PTH
secretion

15. Vitamin D metabolism

16. FGF23(fibroblast derived growthfactor)
 Secreted mainly by osteocytes (and possibly osteoblasts).
 Now consider to be the most important factor for
regulation of phosphorous homeostasis.
 Acts mainly on the kidneys to increase phosphorous
clearance.
 Inhibits 1αhydroxylase activity causing a low 1,25, dihydroxy
vitamin D level.
 Hyperphosphatemia is the main stimulant for FGF23

18. Calcium and phosphorous metabolism in renal
failure
 When GFR falls,the phopsphorous clearance decrease
leading to phopshate retention.
 Hyperphosphatemia induces PTH secretion by 3 ways
1. Direct stimulatory effect on parathyroid.
2. Induction of mild hypocalcemia by precipitating with
calcium to form (caHpo4).

19. 3. Stimulation of FBG23
Decreased 1αhydroxylase
Decreased 1,25 dihydroxyvitaminD
Down regulation of vitD receptors
parathyroidgland

21. Clinical features
Renal osteodystrophy
 bone and joint pains.
 bone deformation and fractures during late stages .
 Some times called as silent crippler .
 Osteitis fibrosis cystica.
 A dynamic or aplastic bone disease.

22. Osteitis fibrosis cystica
 Classic and former most common form of osteodysrophy.
 High bone turn over caused by high circulating PTH.
 Histologically ,an increase in gaint multinucleated
osteoclasts on the surface of the bone and replacement of
normal cellular and marrow elements with fibrofatty
tissue.
 Xray changes include sub periosteal resorption of the
phalangeal tufts.

23. Subperiostel resorption

24. Aplastic or adynamic bone disease
 Low bone turn over by excessive supression of PTH during
late stages of disease.
 The number of PTH receptors is downregulated in the
skeleton leading to skeletal resistance.
 It is a normal mechanism of the bone to defend itself
against high circulating levels of PTH.

26. Treatment
 Management of secondary hyperparathyroidism in CKD
should start at the beginning of stage 3
 It can be divided in to 3 steps
1. Optimize the levels of serum calcium and phosphate.
2. Control of PTH and vitaminD
3. The dosages of phosphate binders, calcimimmetics and
vitD analogues should be adjusted to achieve K/DOQI
value

27.  1st step is to optimize the levels of serum phosphate and calcium
through dietary restriction of phosporous and phosphate
binders
 Dietary restriction of phosphorous
 For ptnts with CKD stage 3 and 4 when serum phosphorous is
more than 4.6 and 5.5 mg/dl in CKD 5.
 Dietary restriction of phosphorous to 800-1000mg/day
 Two main sources dietary proteins and phosphorous additives
 Additives are manily present in the processed foods such as
meat,beverages,cheese and dietary products.

29. Phosphate binders
 main stay of therapy in secondary hyperparathyroidism.
 To limit the dietary absorption of phopsphorous.
Aluminium hydroxide forms aluminium precipitates in the
intestine and lowers phosphatemia levels.
 Used when serum phosphorous is >7mg/dl for lessthan 4 weeks
 Aluminium toxicity leads to severe refractory microcytic
anemia,osteomalacia,dementia
Calcium salts as calcium carbonates and calcium acetates

30.  Sevelamer hydrochloride is non calcium,non aluminium and
non magnesium compound.
 it forms a cationic polymer that binds to dietary phosphorous
through ion exchange.
 Sevelamer carbonate replacement of chloride ion with a
carbonate.
 decrease s the chances of metaboilic acidosis caused by sevalmer
hydrochloride.
 Lanthum carbonates is a rare earth element and has the
property of phosphorous binding.

31. Step 2 is to control of PTH and vitD by the use of vit D
analogues and calcimimetics.
vitD and its derivatives is the oldest treatment for secondary
hyperparathyroidism.
 Calcitriol deficiency and resistance are the major contributors to
the pathophysiology of the disease.
 Calcitriol(1,25dihydroxyvitaminD3)is the natural form of vitamin
D produced by the humanbody.
 Intermittent and IV administration is more effective than oral
calcitriol
Ergocalciferol s vitamin D2 or the nutritional vitamin D
 Is only indicated if 25-hydoxy vitamin D levels<30ng/ml;

32. Selective vitamin D analogues are paricalcitol and
doxercalciferol.
 Selective agents that have more affinity towards kidney rather
than intestinal receptors.
Calcimimetics are the newer agents that allosterically
increase the sensitivity to calcium and calcium sensing receptors
in the parathyroid gland thus supressing PTH.
 Cinacalcet is indicated in dialysis patients when
sercalcium>8.4mg/dl and PTH levels>300pg/ml.
 Side effects include GI symptoms and qt prolongation syndrome.

33. parathyroidectomy
Indications
 Medical therapy is insuccessful
 Extraskeletal calcification.
 Calciphylaxis
 Refractory pruritis
 Severe hypercalcemia
 PTH levels>800pg/ml

34.  It can be performed by either subtotal or total
parathyroidectomy with autotransplantation.
 Small amounts of resected parathyroid tissue can be
autografted in the muscles of the forearm or neck as
well as in subcutaneous tissues of chest or abdomen.
 Hungry bone syndrome is the lack of osteoclastic
activity caused by decreased PTH postoperatively
causes fall in calcium levels.
 Monitoring of calcium levels is important in follow up
after surgery.