2012.12.08

84–amino acid polypeptide hormone

responsible for maintaining ECF [Ca2+]

secretion is gulated directly by the ECF

[Ca2+]

stimuli

Decreased serum [Ca2+]

Mild decreases in serum [Mg2+]

An increase in serum phosphate

only hormone which is up regulated when the

stimulus is low

increase 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, decreasing serum

phosphate levels

4 glands - posterior to the thyroid gland Superior 2, inferior 2

some times 3, 5, or, occasionally, more glands

inferior glands - derived from the third pharyngeal pouch with the thymus migrate along with the thymus

become situated more inferiorly than the superior glands

usually located near the inferior pole of the thyroid

Can go in to superior mediastinum

superior glands - more consistent in location

just superior to the intersection of the inferior

thyroid artery and the recurrent laryngeal nerve

derived from the fourth pharyngeal pouch

occasionally found within the substance of the

thyroid gland.

Primary

Secondary

Tertiary

unregulated overproduction of parathyroid

hormone (PTH) resulting in abnormal calcium

homeostasis

21 cases per 100,000 person-years.

The mean age at diagnosis - between 52 and

56 years

female-to-male ratio of 3:1

85% of cases, primary hyperparathyroidism is

caused by

single adenoma

hyperplasia

15% of cases, multiple glands are involved

Rarely, primary hyperparathyroidism is

caused by parathyroid carcinoma.

aetiology of adenomas or hyperplasia is

unknown in most cases

Familial

multiple endocrine neoplasia syndromes (MEN 1

or MEN 2a)

hyperparathyroid-jaw tumor (HPT-JT) syndrome

familial isolated hyperparathyroidism (FIHPT)

familial hypocalciuric hypercalcemia

neonatal severe hyperparathyroidism

normal feedback on parathyroid hormone

production by extracellular calcium is lost

increase in the cell numbers is probably the

cause.

chronic excessive resorption of calcium from

bone result in osteopenia

may result in osteitis fibrosa cystica

subperiosteal resorption of the distal phalanges

tapering of the distal clavicles

salt-and-pepper appearance of the skull

brown tumors of the long bones

chronically hypercalciuria predisposes to the

formation of renal stones.

symptoms of hyperparathyroidism are due to the hypercalcemia

muscle weakness

fatigue

volume depletion

nausea and vomiting

and in severe cases, coma and death

neuropsychiatric manifestations depression

confusion

increase gastric acid secretion peptic ulcer disease

rare cases of pancreatitis

bones, stones, abdominal groans, and psychic

moans

severe bone disease, kidney stones to

asymptomatic hypercalcemia

Skeletal manifestations

selective cortical bone loss

bone and joint pain

pseudogout

chondrocalcinosis

osteitis fibrosa cystica

Renal manifestations

polyuria

kidney stones

hypercalciuria

nephrocalcinosis.

Gastrointestinal manifestations

anorexia

nausea

vomiting

abdominal pain

constipation

peptic ulcer disease

acute pancreatitis.

Cardiovascular manifestations

hypertension

bradycardia

shortened QT interval

left ventricular hypertrophy

Physical examination findings

usually noncontributory

causes of hypercalcemia + elevated

parathyroid hormone level are few

familial benign (hypocalciuric) hypercalcemia

(FHH) (see Related disorders)

lithium-induced hypercalcemia

tertiary hyperparathyroidism.

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 parathyroid hormone-related peptide level

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.

other biochemical abnormalities

mild hyperchloremic acidosis

hypophosphatemia

mild-to-moderate increase in urinary calcium

excretion rate.

Imaging studies

make a decision about whether to pursue

surgical therapy

If a limited parathyroid exploration is to be

attempted, a localizing study is necessary

USS of the neck

capable of a high degree of accuracy

operator dependent

not been reliable in detecting multigland

disease.

Nuclear medicine scanning with radiolabeled

sestamibi

CT scanning and MRI

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.

dual-energy radiographic absorptiometry

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.

Procedures

Bilateral internal jugular vein sampling

localize ectopic parathyroid adenomas

surgical excision of the abnormal parathyroid

glands

the only permanent, curative treatment for

primary hyperparathyroidism.

surgical treatment should be offered to all

patients with symptomatic disease.

The indications for surgery

1 mg/dL above the upper limit of the reference

range for serum calcium

24 hour urinary calcium excretion greater than

400 mg

30% reduction in creatinine clearance

bone mineral density T-score below -2.5 at any

site

age younger than 50 years

monitoring of patients with asymptomatic

hyperparathyroidism

serum calcium and creatinine levels every 6

months

annual bone mineral density

Management of severe hypercalcemia in the

acute setting

IV volume expansion

sodium chloride and loop diuretics, once the

intravascular volume is restore

Drugs (temporary measure prior to surgical

treatment )

calcitonin

IV bisphosphonate

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

Pharmacotherapy

Estrogen therapy in postmenopausal women

Selective estrogen receptor modulators

raloxifene

Bisphosphonates

Calcimimetic drugs

activate the calcium-sensing receptor and inhibit

parathyroid cell function - cinacalcet

Other treatments

Percutaneous alcohol injection to parathyroids

ablation with ultrasound energy

surgical care

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

Localisation

sestamibi scanning or ultrasonography.

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

in 4-gland hyperplasia

3.5-gland (subtotal) parathyroidectomy

50-70 mg of the most normal-appearing tissue is

left

Complications and postoperative care

calcium levels must be monitored

every 12 hours until stabilization

many become hypocalcemic

few become symptomatic

treatment for hypocalcemia

severe

Symptomatic

hypocalcemia after parathyroid surgery may

be due to hungry bone syndrome

calcium and phosphorus are rapidly deposited in

the bone

If hypoparathyroidism persists

oral supplementation

calcium

vitamin

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

Medical management is the mainstay

Correcting vitamin D deficiency

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

Indications for surgery

bone pain or fracture

Pruritus

Calciphylaxis

Extraskeletal nonvascular calcifications

elevated parathyroid hormone levels despite

appropriate medical therapy

severe hyperparathyroidism

persistent serum levels of intact parathyroid

hormone greater than 800 pg/mL

Medical treatment is successful in most

patients

Patients who require parathyroidectomy have

a 10% risk of recurrent or persistent disease

development of autonomous hypersecretion

of parathyroid hormone causing

hypercalcemia

aetiology is unknown

may be due to monoclonal expansion of

parathyroid cells

four-gland involvement occurs in most patients.

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

dngerous - phosphate level is often elevated.

diffuse calcinosis may occur.

Treatment

Total parathyroidectomy with

autotransplantation

subtotal parathyroidectomy

Familial benign (hypocalciuric)

hypercalcemia

loss-of-function mutation of one allele of the

gene for the calcium-sensing receptor

hypercalcemia, hypophosphatemia, and

hypermagnesemia

can be distinguished from primary

hyperparathyroidism by low 24-hour urinary

calcium excretion

Persons with FHH are asymptomatic.

parathyroidectomy is not indicated

Hypercalcemia of malignancy

caused by

tumor release of parathyroid hormone -related

peptide

over production of 1,25-dihydroxyvitamin D

local osteolytic lesions

low or undetectable intact parathyroid

hormone level

Calciphylaxis

= uremic gangrene syndrome

observed in patients with renal failure and

secondary or tertiary hyperparathyroidism.

characterized by ischemic necrosis of the

skin due to calcium phosphate crystal

deposition and subsequent inflammation in

small-to-medium–sized vessels