Brief summary on the causes, types, workup and management of hyperparathyroidism

1. Hyperparathyroidism

2. 84–amino acid polypeptide hormone
Responsible for maintaining ECF [Ca2+]
secretion is regulated directly by the
ECF [Ca2+]
Stimuli
Decreased serum [Ca2+]
Mild decreases in serum [Mg2+]
An increase in serum phosphate
Parathyroid hormone

4. increases ECF [Ca2+]by
increasing the release of calcium and phosphate
from bone matrix
increasing calcium reabsorption by the kidney
increasing renal production of 1,25-
dihydroxyvitamin D-3 (calcitriol), which increases
intestinal absorption of calcium
causes phosphaturia, decreasingserum
phosphate levels
Mechanism of Action

6. Primary
Secondary
Tertiary

8. unregulated overproduction of parathyroid
hormone (PTH) resulting in abnormal calcium
homeostasis
21- 25 cases per 100,000 person-years.
The mean age at diagnosis - between 52 and
56 years
female-to-male ratio of 3:1 to 4:1

9. 85% of cases, primary hyperparathyroidismis
caused by
single adenoma
15% of cases, multiple glands are
involved
Rarely, primary hyperparathyroidism is
caused by parathyroid carcinoma (<1%)

10. Familial
Multiple endocrine neoplasia syndromes (MEN 1
or MEN 2a)
Hyperparathyroid-jaw tumor (HPT-JT) syndrome
Familial isolated hyperparathyroidism (FIHPT)
Familial hypocalciuric hypercalcemia

11. Loss of negative feedback of serum
Calcium levels on PTH
Chronic excessive resorption of calcium
from bone results in osteopenia
Pathophysiology

12. Most patients now diagnosed on routine lab
testing or non-specific symptoms.
Classically, bones, stones, abdominal groans, and
psychic moans
Wide spectrum from severe bone
disease, kidney stones to asymptomatic
hypercalcemia
Muscle weakness
volume depletion
nausea and vomiting

13. Osteitis fibrosacystica
subperiosteal resorption of the distal phalanges
tapering of the distal clavicles
salt-and-pepper appearance of the skull
brown tumors of the long bones
Skeletal manifestations
selective cortical bone loss
bone and joint pain
pseudogout
chondrocalcinosis
osteitis fibrosa cystica

16. Renal manifestations
polyuria
kidney stones
hypercalciuria
nephrocalcinosis.
Gastrointestinal manifestations
anorexia
nausea
vomiting
abdominal pain
constipation
peptic ulcer disease
acute pancreatitis.

17. Cardiovascularmanifestations
hypertension
bradycardia
shortened QT interval
left ventricular hypertrophy
Neuropsychiatric manifestations
depression
confusion
Fatigue

18. familial benign hypocalciuric hypercalcemia
PHPT-JT Syndrome
PTHrp of Malignancy
Diagnosis
 Elevated Serum [Ca2+] i.e >10.5 mg/dL
 Elevated Serum PTH or inappropriately normal
 24h urinary Ca2+ > 200mg
Differential Diagnosis

19. all potential causes of secondary
hyperparathyroidism should be excluded
low calcium intake
gastrointestinal disorders
renal insufficiency
vitamin D deficiency
hypercalciuria of renal origin
secondary and tertiary hyperparathyroidism are
typically diagnosed based on their clinical
context
cancer-induced hypercalcemia
low parathyroid hormone level
possibly a high PTHrp

20. Laboratory studies
total serum calcium and albumin levels or
ionized calcium levels
hypercalcemia should be documented on more
than one occasion
intact parathyroid hormone level is the core of
the diagnosis
elevated intact parathyroid hormone level with
an elevated ionized serum calcium level is
diagnostic of primary hyperparathyroidism
24-hour urine calcium measurement is necessary
to rule out FHH.

21. other biochemicalabnormalities
mild hyperchloremic acidosis
hypophosphatemia
mild-to-moderate increase in urinary calcium
excretion rate.
Imaging studies
Aid in making a decision about whether to
pursue surgical therapy
If a limited parathyroid exploration is to be
attempted, a localizing study is necessary

22. USG of theneck
capable of a high degree of accuracy
operator dependent
not reliable in detecting multigland
disease
Technetium-99 labelled Sestamibi (MIBI)
scan
Nuclear imaging using
radiolabelled dye

24. CT scanning andMRI
locate abnormal parathyroid glands
Standard CT scanning has inadequate sensitivity.
Newer techniques of CT scanning with dynamic
contrast images (4D-CT) accuracy 88%.
MRI - particularly in cases of
 recurrent
 persistent disease
 ectopic locations such as the mediastinum.

25. Dual-energy X-rayabsorptiometry (DEXA)
demonstrate the skeletal involvement in primary
hyperparathyroidism
Hyperparathyroidism affects the cortical bone at
the radius (distal third)
Skeletal radiographs
salt-and-pepper degranulation in the skull
subperiosteal bone resorption in the phalanges.

27. Nonsurgical care
should be carefully monitored
maintain a moderate daily elemental calcium
intake of 800-1000 mg
vitamin D intake appropriate for their age
and sex.
participation in regular exercise activity
avoid immobilization
avoid thiazides, diuretics, and lithium
Treatment

28. Pharmacotherapy
Bisphosphonates
Calcimimetic drugs
activate the calcium-sensing receptor and inhibit
parathyroid cell function - cinacalcet
HRT/ SERM generally not indicated

29. Monitoring of patients withasymptomatic
PHPT
serum calcium: annually
DEXA scan: 1-2 yearly
Serum Creat. + eGFR: annually
Further imaging for nephrollithiasis if
suspected

30. excision of the abnormal parathyroid glands
the only definitive curative treatment for
primary hyperparathyroidism.
surgical treatment should be offered to all
patients with symptomatic disease.
Surgical treatment

31. Indications forsurgery in asymptomatic PHPT
1 mg/dL above the upper limit of the reference
range for serum calcium
24 hour urinary calcium excretion greater than
400 mg
Creatinine clearance <60ml/min
Bone mineral density T-score below -2.5 at any
site or a vertebral fracture
Age < 50 years
Nephrolithiasis or Nephrocalcinosis

32. Surgical approaches
should be offered to most patients
standard operative approach is complete neck
exploration,identification of all parathyroid
glands and removal of all abnormal glands.
85% of cases caused by a single adenoma
full neck exploration might be an unnecessary
dissection
directed parathyroidectomy
preoperative imaging studies to localize the
abnormal gland
removal only that gland

33. Localisation
sestamibi scanning orultrasonography.
intraoperative parathyroid hormone assay
radio-guided parathyroidectomy
detecting the labeled sestamibi in the abnormal gland
using a handheld probe
for familial disease
total parathyroidectomy with autotransplantation
to the forearm and cryopreservation of some
parathyroid tissue

34. Outcome after Surgery ?

35. Othertreatments
Percutaneous alcohol injection to parathyroids
ablation with ultrasound energy

36. in 4-glandhyperplasia
3.5-gland (subtotal) parathyroidectomy
50-70 mg of the most normal-appearing tissue is
left

37. Hungry bone syndrome
calcium and phosphorus are rapidly deposited in
the bones after PTH levels drop.
Lowest by 3rd post-day
If persists
 oral supplementation
calcium (2-4 g/day)
vitamin-D: Calcitriol 0.5 μg x BD
IV Calcium if severe, symptomatic

38. overproduction of parathyroid hormone
secondary to a chronic abnormal stimulus for its
production
Typically
chronic renal failure
vitamin D deficiency
Secondary hyperparathyroidism (SHPT) develops
early in CKD before dialysis is required
In chronic kidney disease, overproduction of
parathyroid hormone occurs in response
Hyperphosphatemia
Hypocalcemia
impaired 1,25-dihydroxyvitamin D production
Secondary
Hyperparathyroidism

39. Medical management is the mainstay
Correcting vitamin Ddeficiency
Dietary phosphate restriction
Phosphate binders
calcium-based phosphate binders
 calcium carbonate
 calcium acetate
non-calcium-based phosphate binders
 sevelamer hydrochloride
 lanthanum carbonate
Calcium supplementation should be limited
to less than 2 g/d

40. Indications for surgery
bone pain or fracture
Pruritus (refractory)
Calciphylaxis
Extraskeletal nonvascular calcifications
elevated parathyroid hormone levels despite
appropriate medical therapy
persistent serum levels of intact parathyroid
hormone greater than 800 pg/mL after 6-8
months of 6-8 wk of Calcitriol therapy

41. Development of autonomous hypersecretion
of PTH on a background of hyperplasia i.e
secondary hyperparathyroidism
four-gland involvement occurs in most
patients.
Tertiary Hyperparathyroidism

42. Pathophysiology
observed in patients with chronic secondary
hyperparathyroidism and often after renal
transplantation.
hypertrophied parathyroid glands fail to
return to normal
continue to oversecrete despite serum
calcium levels normal or elevated
phosphate level is often dangerously
elevated.
diffuse calcinosis may occur.

43. Treatment
Total parathyroidectomy with
autotransplantation
subtotal parathyroidectomy

44. Recent advances
Carbon-11 Choline:
• Radiotracer trialled by Mayo Clinic for detection of
parathyroid adenomas, showed promising results.
• 100 % sensitivity, lower radiation dose
4D-CT:
• Dynamic CT with time-phased
ontrast.
• Higher sensitivity, especially for
ectopic lesions
Eticalcetide
• Recently approved Calcimetic. In RCTs superior to Cinalcet
inreducing PTH levels in 2° HPTH