Hiperparatiroid

Dr. dr. Shahrul Rahman, Sp.PD, FINASIM

Departemen Ilmu Penyakit Dalam

Fakultas Kedokteran
Universitas Muhammadiyah Sumatera Utara
Parathyroid

Four glands located

behind the thyroid
Length 6 millimeters
Width 3 millimeters
Thickness 2
millimeters
Often accidentally
removed
Normal function with
at least 2 glands
 Parathyroid Actions

Increases calcium
Regulates intestinal absorption
25-OH vitamin D 1,25-OH vitamin D
Renal absorption of calcium/excretion of phosphorus
Bone reabsorption
Osteolysis

PTH also lowers blood phosphorus levels by increasing

excretion of phosphorus in the urine
Why are calcium and
phosphorous so important?
Calcium is essential for good health. It plays an
important role in bone and tooth development
and in maintaining bone strength. Calcium is
also important in nerve transmission and
muscle contraction.
Phosphorus is found in all bodily tissue. It is a
main part of every cell with many roles in each.
Combined with calcium, phosphorus gives
strength and rigidity to your bones and teeth.
Definition
Hyperparathyroidism describes proliferation of the
parathyroid hormone (PTH)secreting cells, or chief
cells, in one or more of the 4 parathyroid glands.

The cause may be due to a genetic mutation, as in

primary hyperparathyroidism, or to a variety of
underlying conditions that produce secondary
hyperparathyroidism due to hypocalcemia, such as
intestinal malabsorption, or high serum phosphorus
levels, such as with chronic renal failure.
Definition

Tertiary hyperparathyroidism usually exists in

situations of secondary hyperparathyroidism. Tertiary
hyperparathyroidism occurs when parathyroid
hyperplasia becomes so severe that removal of the
underlying cause does not eliminate the stimulus for
PTH secretion and hypertrophic chief cells become
autonomous.
Pathophysiology
While the exact mechanism causing increased PTH
secretion is not certain, a loss of sensitivity of these
proliferating chief cells to normal extracellular calcium
concentrations occurs.

In 1996, Kifor et al showed that the parathyroid cell

surface G proteincoupled calcium-sensing receptor is
reduced by approximately 50% in parathyroid
adenoma cells as compared to normal parathyroid
controls.
Pathophysiology

This reduction is associated with an increased amount

of circulating calcium, which is required to suppress
PTH secretion.

The reduction may be caused by genetic mutation (eg,

familial hypocalciuric hypercalcemia, neonatal severe
hyperparathyroidism), multiple endocrine neoplasia
(MEN), or conditions that would normally stimulate
compensatory PTH secretion
Pathophysiology
Conditions include calcium or vitamin D malabsorption,
accumulation of phosphate with inability to excrete it (eg,
chronic renal failure), and uremia.

In addition, some genetic mutations have been described in

primary hyperparathyroidism, including relocation of the
PTH gene to a site next to an oncogene.

Loss of one copy of a tumor suppressor gene on

chromosome 11 has also been reported in some patients
with multiple endocrine neoplasia type 1 (MEN I) syndrome
Pathophysiology
PTH indirectly stimulates bone resorption by attaching
to the osteoblast PTH receptor, which then signals the
osteoblast to produce a variety of substances, among
them proinflammatory cytokine interleukin-6 and
osteoclast differentiating factor, both of which can
stimulate osteoclast differentiation and proliferation.

The osteoblast also acts as a brake on osteoclastic

activity by producing osteoprotegerin. Exactly how the
osteoblast governs osteoclastogenesis is not fully
understood
 Bone metabolism
Parathyroid
hormone (PTH)
Calcium
Phosphorus
Vitamin D
Calcitonin
Mortality/Morbidity
The morbidity from primary hyperparathyroidism is most often due
to hypercalcemia.

This can take the form of bradycardia and heart block and
dehydration due to polyuria, nausea, vomiting, and poor fluid
intake. Pancreatitis has also been reported.

Other causes of morbidity observed with primary

hyperparathyroidism may be due to effects of associated tumors,
such as jaw tumors or Wilms tumor.

Morbidity from secondary hyperparathyroidism usually involves

demineralization of bones with subsequent pain, fracturing, or
deformity.
History

Primary hyperparathyroidism
o Most commonly, patients present without symptoms.
Hyperparathyroidism may be diagnosed in an otherwise
asymptomatic patient by incidental discovery during routine blood
chemistry analysis of hypercalcemia.
o Symptoms of early disease, when present, are specific to
hypercalcemia.
They include muscle weakness, depression, increased
sleepiness, nausea, vomiting, acute abdominal pain (which
might be the result of pancreatitis), constipation, and
polydipsia.
Frequent and occasionally painful urination and dysuria
and/or back pain may be observed, the latter from
nephrolithiasis.
History

Secondary hyperparathyroidism

Patients with secondary hyperparathyroidism usually

present with a history of underlying disease such as
renal or intestinal conditions.
Symptoms are musculoskeletal in nature, including
bone pain, muscle weakness, and previous fracture.
Physical Exam.

Primary hyperparathyroidism
o Signs of dehydration due to hypercalcemia, such as
tenting of skin, prolonged capillary refill time, and dry
mucous membranes.
o Bradycardia. With or without irregular heartbeat.

o Decreased muscle tone and somnolence.

Physical Exam.

Secondary hyperparathyroidism
Skeletal deformity

Decreased muscle tone

Bone pain on palpation

Short stature
Eitiology
Primary hyperparathyroidism - Genetic mutation.

Secondary hyperparathyroidism - May develop as a response to

hypocalcemia caused by intestinal disease resulting in calcium
and vitamin D malabsorption .
1. Chronic renal insufficiency

2. Insufficient vitamin D and calcium intake: Insufficient intake in

children may cause rickets. rickets are a major cause of
secondary hyperparathyroidism in developing countries,
especially those countries in which children are kept out of
the sun while parents work.
Eitiology

3. Iatrogenic causes: Iatrogenic causes, such as lithium

administration, may decrease the ability of circulating
levels of calcium that are within the reference range
to suppress PTH secretion. The mechanism for this is
not presently clear.
4. Cholestatic liver disease: Contrary to previous belief,
not all children with chronic cholestatic liver disease
have secondary hyperparathyroidism. Many of these
patients, as well as adults with chronic liver disease,
have levels of PTH within the reference range.
Lab Studies
One key difference between primary and secondary
hyperparathyroidism is that patients with primary disease
are always hypercalcemic, while those with secondary
disease are almost always normocalcemic.

For blood studies, serum calcium concentrations and

immunoreactive PTH levels using immunoradiometric assay
(IRMA) to detect intact PTH molecules are most important.
These can be used to distinguish primary from secondary
hyperparathyroidism.
In primary disease, high levels of calcium and PTH are
observed, while in secondary disease, levels of calcium are
within the reference range and levels of PTH are high.
Lab Studies

Serum levels of phosphorus are not always helpful with

respect to diagnosis.

Serum phosphorus levels in primary hyperparathyroidism are

mainly in the low-normal range.
Serum levels in secondary hyperparathyroidism due to renal failure
serum phosphorus levels are elevated because of the inability of
the kidney to excrete phosphorus.
In the absence of dialysis therapy, phosphorus levels are elevated.
Imaging Studies

Radiography
The value of skeletal radiographs in diagnosis of primary
hyperparathyroidism is questionable because relatively few
cases exhibit stigmata of hyperparathyroidism.
Radiographs may be useful in defining the extent of damage in
secondary hyperparathyroidism.
Radiographs reveal the following in some cases of primary and
most cases of secondary hyperparathyroidism:

Multiple areas of subperiosteal bone resorption of the distal

phalanges
Tapering of the clavicles
Brown tumors of the long bones and a salt-and-pepper
appearance of the skull
Imaging Studies

Bone densitometry
Another way to monitor the severity of bony involvement is
with bone densitometry, determined by dual energy x-ray
absorptiometry (DEXA). This technique can be used to
quantify bone mineral content of a specific region in g, bone
area in cm2, and density in g/cm2.

This is an areal or 2-dimensional measurement, but it can be

followed longitudinally to evaluate the severity of the effect on
bone and the effectiveness of therapy.
Imaging Studies

Many patients with severe primary

hyperparathyroidism have reduced bone mineral
density at multiple sites
Cont.

Other Tests:
The only other tests of value are those that are used to
diagnose the underlying cause of secondary
hyperparathyroidism, associated genetic defects, or tumors
accompanying primary hyperparathyroidism.

Procedures:
No diagnostic procedures are pertinent to diagnosis, except
those that are used to diagnose an underlying disease in
secondary hyperparathyroidism.
Medical Care
Medical management of primary hyperparathyroidism is not
satisfactory because no agents presently exist that can produce
either sustained blockage of PTH release by parathyroid glands or
sustained blockage of hypercalcemia.

However, research is currently underway to develop

calcimimetics, which can stimulate up-regulation of parathyroid
calcium-sensing receptor and potentially blunt abnormally
increased PTH secretion.

In addition, human osteoprotegerins, which can block PTH-

induced hypercalcemia, are also undergoing clinical studies.
Medical Care
For secondary hyperparathyroidism that occurs with chronic renal
failure, parenteral administration of calcitriol is helpful; however,
this manner of administration is feasible only for those patients
receiving hemodialysis.

For those individuals receiving therapy with peritoneal dialysis,

oral administration of calcitriol is the only alternative. This route of
administration may not be as effective as the intravenous route;
however, some preliminary clinical trials have been conducted for
calcimimetics in this condition, as well as in primary
hyperparathyroidism. Early results are encouraging.
Medical Care

For other forms of secondary hyperparathyroidism, such as

that resulting from chronic cholestatic liver disease, no
standard treatment guidelines exist.

Therefore, treatment should be aimed at ameliorating the

underlying condition and supplying sufficient dietary
calcium, phosphorus, vitamin D, and magnesium.

This ensures that hyperparathyroidism is not exacerbated

by nutritional insufficiency.
Medical Care
The treatment of acute severe hypercalcemia (serum calcium level
>14.0 mg/dL), which may or may not result from
hyperparathyroidism, would include hydration with isotonic sodium
chloride solution to restore extracellular fluid volume that may be
depleted secondary to vomiting and to induce calciuresis.

Consider the addition of loop diuretics, such as furosemide, only

after normal hydration is restored.

In extreme cases, either hemodialysis or peritoneal dialysis with

low or zero calcium dialysate could be employed.
Medical Care
Although not routinely used in pediatrics, more studies are
demonstrating that the bisphosphonates, antiresorptive agents,
can be safely used in children and may lower serum calcium
levels by decreasing bone resorption.

Also, mobilization should be encouraged to prevent the

hypercalcemia that occurs secondary to bed rest.
Surgical Care
Parathyroidectomy
For primary hyperparathyroidism, subtotal or total
parathyroidectomy is the treatment of choice, depending on
the number of glands involved with tumors.

Parathyroidectomy can result in reference range serum

calcium levels, an increase in bone mineral density, and
successful prevention of kidney stones.

Also, in uremic patients, subtotal or total parathyroidectomy is

an option when medical management with calcitriol or one of
its analogs is unsuccessful or when tertiary
hyperparathyroidism that is independent of external feedback
develops
Surgical Care

Surgical complications
Postoperative complications include transient hypocalcemia
because parathyroids regain their sensitivity to circulating
calcium.

Hungry bone syndrome, a prolonged period of hypocalcemia,

can occur postoperatively in those cases of primary
hyperparathyroidism that demonstrated significant bone
demineralization. Bones reaccumulate calcium at the expense
of circulating levels.

Finally, as in thyroid surgery, a risk of damage to the recurrent

laryngeal nerve resulting in permanent hoarseness of the voice
exists.
Diet
No strict dietary requirements are necessary for management of
primary hyperparathyroidism.

For secondary hyperparathyroidism, dietary management

depends on the underlying disease state.

For renal disease, phosphate may be restricted depending on the

success of dialysis treatment or oral phosphatebinding therapy.

For liver disease or malabsorptive syndromes, oral or intravenous

supplementation of calcium, phosphate, magnesium, and vitamin
D would be helpful to minimize inadequacy of these nutrients
caused by malabsorption or other loss.
Treatment

1) Vitamin D analogs
These agents regulate serum calcium levels via actions on
calcium and phosphorus metabolism at intestinal, renal, and
skeletal sites.
The kidney appears to play a central role in this system. It
produces calcitriol (ie, 1,25-dihydroxyvitamin D, the primary
active metabolite of vitamin D3), which acts on distal organs,
and at the same time is the target organ for PTH, calcitonin,
and possibly calcitriol.
Calcitriol is administered to help suppress excessive PTH
release and blunt the hyperparathyroid response to chronic
renal failure.
Treatment (Vitamin D analogs )

Calcitriol (Calcijex, Rocaltrol)

Used in attempted suppression of PTH secretion
stimulated by inability of the kidneys to excrete
phosphate, with its consequent accumulation in
blood.
Increases calcium levels by promoting absorption of
calcium in the intestines and retention in the
kidneys.
Has not been tried in patients with other causes of
secondary hyperparathyroidism.
Treatment (Vitamin D analogs )

Dose
0.01-0.04 mcg/kg/d PO
IV dose is not established; not to exceed adult dose.

Precautions
Maternal hypersensitivity to vitamin D during pregnancy may
lead to Williams syndrome; growth arrest may result in children
fed ergocalciferol 1800 U/d; major precaution involves
monitoring to avoid hypercalcemia
Treatment

2) Isotonic crystalloids
Sodium chloride 0.9% fluid is used to supply
intravenous hydration to replace fluids lost by
emesis for patients with acute hypercalcemia of
any etiology.
Treatment

3) Loop diuretics
Once hydration has been established, use of a
diuretic (eg, furosemide) can help increase
calciuresis without adding to the dehydration
caused by hypercalcemia.
Furosemide (Lasix) -- Increases excretion of water
by interfering with chloride-binding cotransport
system, which in turn inhibits sodium and chloride
reabsorption in the ascending loop of Henle and
the distal renal tubule.
Treatment (Loop diuretics )

Dose
1 mg/kg IV; may cautiously increase dose by 1
mg/kg q2h; not to exceed 6 mg/kg/dose
Treatment

4) Bisphosphonates
Bisphosphonates are antiresorptive agents that are used to
help preserve bone mass. They are available in oral and
parenteral forms.
The inhibition of bone resorption produces a hypocalcemic
effect.
Used in the management of conditions associated with
increased bone resorption (eg, osteoporosis, Paget disease
of bone, management of hypercalcemia [especially that
associated with malignancy]).
Treatment (Bisphosphonates)

In case of acute hypercalcemia with vomiting,

parenteral therapy is recommended. By reducing
bone resorption, a calcium-lowering effect in the
blood may occur.
Tretment (Bisphosphonates)
Pamidronate (Aredia)
IV bisphosphonate that acts as an antiresorptive agent.

Inhibits normal and abnormal bone resorption.

Appears to inhibit bone resorption without inhibiting bone

formation and mineralization.

Currently accepted uses include the treatment of

hypercalcemia associated with neoplasms and metastases
as well as for treatment of Paget disease.
Pamidronate (Aredia) cont.

This category of drugs is not approved for the treatment of

hypercalcemia secondary to hyperparathyroidism, but in
practice can be used for this as well as in the management
of postmenopausal osteoporosis.

Now being used in pediatrics to treat osteogenesis

imperfecta and idiopathic juvenile osteoporosis.

Preliminary study results on its use to prevent bone loss

following severe burns appear promising.
Tretment (Bisphosphonates)
Dose
Not established; some studies have used 1.5 mg/kg/dose IV
infused over 8 h; not to exceed 90 mg/dose; prepare IV by
mixing 1 L of dextrose 5% and water
Precautions
Monitor hypercalcemia-related parameters, such as serum
levels of calcium, phosphate, magnesium, and potassium once
treatment begins.
adequate intake of calcium and vitamin D is necessary to
prevent severe hypocalcemia.
caution when administering bisphosphonates in patients with
active upper GI problems (eg, gastric irritation, nausea, GI
pain) .
Complications

Complications of primary hyperparathyroidism include

consequences of hypercalcemia such as
nephrolithiasis, dehydration, and cardiac arrhythmias.

Complications of secondary hyperparathyroidism are

mainly skeletal and involve fractures, decreased bone
density, bone pain, and muscle weakness.
Prognosis

For primary hyperparathyroidism, parathyroidectomy should

be curative if the condition occurs in isolation. However, if it
is associated with other tumors, then prognosis depends on
the management of accompanying tumors.

For secondary hyperparathyroidism, prognosis depends

entirely on the success of the physician or surgeon in
managing the primary disease process.
Patient Education

Patients with primary hyperparathyroidism must

understand the following:

1. Location and function of parathyroid gland and parathyroid

hormone.
2. Effects of hypercalcemia on the body (eg, arrhythmia, stones,
bone demineralization, increased fracture risk).
3. Lack of success in managing primary hyperparathyroidism
medically, need for surgical consultation, and possible
removal of one or more parathyroid glands.
Patient Education

Patients with secondary hyperparathyroidism must

understand the following:

1. The mechanism by which the underlying condition causes

secondary hyperparathyroidism
2. Effects on the body (eg, bone pain, bone demineralization,
increased fracture risk, muscle weakness)
3. Proper management of secondary hyperparathyroidism in
each individual case
Thank You