PHYSIOLOGY

ENDOCRINE
PARATHYROID GLAND
Dr. Anayan

OUTLINE EMBRYOLOGY
I. Embryology
II. Anatomy and Histology 4th branchial SUPERIOR
III. Blood supply pouch gives rise to PARATHYROID
IV. Hyperparathyroidism the ff: GLAND
a. Primary THYROID GLAND
Hyperparathyroidism
b. Secondary 3rd branchial INF. PARATHYROID
Hyperparathyroidism puoches give rise GLAND
c. Tertiary to the ff: THYMUS
Hyperparathyroidism
V. Hypoparathyroidism Truly ectopic superior parathyroid glands
are rare but may be found in the middle or
posterior mediastinum or in the
aortopulmonary window.

ANATOMY AND PHYSIOLOGY

• Most have four parathyroid glands.
• Normal parathyroid glands are gray
and semitransparent in newborns but
appear golden yellow to light brown
in adults.
• Parathyroid color depends on
cellularity, fat content, and
vascularity.
• Located in loose tissue or fat and are
ovoid
• They measure up to 7 mm in size.
• Weigh approximately 40 to 50 mg
each.

BLOOD SUPPLY

Inf. Thyroid Artery

Sup. Thyroid Artery At least 20% of
upper gland
Thyroidea ima, and Also found
vessels to the
trachea, esophagus,
larynx, and
mediastinum
The parathyroid glands drain ipsilaterally
by the superior, middle, and inferior
thyroid veins.

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 PHYSIOLOGY
ENDOCRINE
PARATHYROID GLAND
Dr. Anayan

HYPERPARATHYROIDISM
• Hyperfunction of the parathyroid
glands may be classified as:

PARATHYROID HORMONE-CALCITONIN 1. Primary

VITAMIN D INTERACTION 2. Secondary
3. Tertiary

PRIMARY HYPERPARATHYROIDISM
• Common
• Occurs in 0.1% to 0.3% of the general
population
• More common in women (1:500) than
in men (1:2000)
• Increased PTH production leads to
hypercalcemia via increased GI
absorption of calcium, increased
production of vitamin D3, and
reduced renal calcium clearance.
• PHPT is characterized by increased
parathyroid cell proliferation and PTH
secretion that is independent of
calcium levels.

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 PHYSIOLOGY
ENDOCRINE
PARATHYROID GLAND
Dr. Anayan

ETIOLOGY Renal Disease Gastrointestinal

The exact is unknown, although • Kidney stones Complications
exposure to low-dose therapeutic ionizing • Hypertension • Peptic ulcer
radiation and familial predisposition disease
(GENETICS) account for some cases. • Hypergastrinemia

Other causes: Bone Disease Neuropsychiatric

• Renal leak of calcium and declining • Osteopenia Complication
renal function with age. • Osteoporosis • Florid psychosis
• Alteration in the sensitivity of • Osteitis • Obtundation
parathyroid glands to suppression by fibrosa cystica • Coma
calcium.
• After radiation exposure, most cases Other Features
occurring 30 to 40 years. • Fatigue
• Patients who have been exposed to • Muscle weakness
radiation have similar clinical
presentations and calcium levels PHYSICAL FINDINGS
when compared to patients without a • Seldom palpable except in patients
history of radiation exposure. with profound hypercalcemia or
• However, the former tends to have parathyroid cancer.
higher PTH levels and a higher • Patients also may demonstrate
incidence of concomitant thyroid evidence of band keratopathy, a
neoplasms. deposition of calcium in Bowman’s
• Lithium therapy has been known to membrane just inside the iris of the
shift the set point for PTH secretion eye.
in parathyroid cells, thereby resulting • Fibro-osseous jaw tumors, and/or the
presence of familial disease in
Most patients present with: patients with PHPT and jaw tumors, if
• Weakness present, should alert the physician to
• Fatigue the possibility of parathyroid
• Polydipsia carcinoma.
• Polyuria
• Nocturia
• Bone and joint pain
• Constipation
• Decreased appetite
• Nausea
• Heartburn
• Pruritus
• Depression
• Memory loss

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 PHYSIOLOGY
ENDOCRINE
PARATHYROID GLAND
Dr. Anayan

Patients with PHPT also typically have:

• Decreased serum phosphate (∼50%)
• Elevated 24-hour urinary calcium
concentrations (∼60%).
• A mild hyperchloremic metabolic
acidosis

Radiologic Tests

DIAGNOSTIC INVESTIGATIONS
Biochemical Studies:
• Elevated serum calcium and intact
PTH or two-site PTH levels, without
hypocalciuria, establishes the
diagnosis of PHPT with virtual
certainty.
• Although extremely rare, a patient
with hypercalcemia may have a tumor
that secretes PTH.

FNAB of such a tumor for PTH levels or

selective venous catheterization of the veins
draining such tumors can help clarify the
diagnosis.

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 PHYSIOLOGY
ENDOCRINE
PARATHYROID GLAND
Dr. Anayan

part, to the fact that there is little

agreement on what constitutes an
asymptomatic patient.

Medical options for treating PHPT and

its complications include:
• Antiresorptive treatments such as
bisphosphonates
• Hormone replacement therapy
(HRT), and selective estrogen
receptor modulators such as
raloxifene

It is recommended that parathyroidectomy

should be offered to virtually all patients
except those in whom the operative risks are
prohibitive.

(Please see the Index for table 38-12:

Commonly Used Parathyroid Localization
Studies)
TREATMENT
Indications for Parathyroidectomy and OPERATIVE APPROACHES
Role of Medical Management: • Unilateral parathyroid exploration
• Nonoperative management of these • Standard Bilateral neck exploration
patients with mild PHPT based on • Radio-guided parathyroidectomy
observational studies, which • Endoscopic approaches include:
suggested relative stability of o Video-assisted
biochemical parameters over time. o Total endoscopic techniques
• However, the consensus panel
considered certain patients to be
candidates for surgery based on
testing or other information
indicating end-organ effects or a
higher likelihood of disease
progression, and this led to the
establishment of initial guidelines for
parathyroidectomy.
• Most authorities agree that patients
who have developed complications
and have “classic” symptoms of PHPT
should undergo parathyroidectomy.
However, the treatment of patients
with asymptomatic PHPT has been
the subject of controversy, due in

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 PHYSIOLOGY
ENDOCRINE
PARATHYROID GLAND
Dr. Anayan

SPECIAL SITUATIONS

NORMOCALCEMIC
HYPERPARATHYROIDISM
• Presence of an elevated PTH level
with normal calcium (including
ionized calcium) levels.

PARATHYROID CARCINOMA
• Presence of severe symptoms, serum
calcium levels >14 mg/dL,
significantly elevated PTH levels (five
times normal), and a palpable
parathyroid gland. Local invasion is
quite common.

FAMILIAL HYPERPARATHYROIDISM
• PHPT may occur as a component of
various inherited syndromes such as
MEN1 and MEN2A. Inherited PHPT
also can occur as isolated familial HPT
(non- MEN) or familial HPT with jaw
tumors.

NEONATAL HYPERPARATHYROIDISM
• Infants with neonatal HPT present
with severe hypercalcemia, lethargy,
hypotonia, and mental retardation.
This disorder is associated with
homozygous mutations in the CASR
gene.

PARATHYROMATOSIS
INDICATIONS FOR STERNOTOMY • Parathyromatosis is a rare condition
characterized by the finding of
• A sternotomy is usually not
multiple nodules of hyperfunctioning
recommended at the initial operation,
parathyroid tissue throughout the
unless the calcium level is >13 mg/dL.
neck and mediastinum, usually
• Lower parathyroid glands tend to
following a previous
migrate into the anterior
parathyroidectomy.
mediastinum in the thymus or
perithymic fat and usually can be
approached via a cervical incision.
• A sternotomy is needed to deliver
these tumors in approximately 5% of
cases.

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 PHYSIOLOGY
ENDOCRINE
PARATHYROID GLAND
Dr. Anayan

POSTOPERATIVE CARE AND FOLLOW-UP

• Patients who have undergone
parathyroidectomy are advised to
undergo calcium level checks 2 weeks
postoperatively, at 6 months, and
then annually.
• Recurrences are rare (<1%), except in
patients with familial HPT.
• Recurrence rates of 15% at 2 years
and 67% at 8 years have been
reported for MEN1 patients.

PERSISTENT AND RECURRENT

HYPERPARATHYROIDISM
• Persistence is defined as
hypercalcemia that fails to resolve
after parathyroidectomy and is more
common than recurrence, which
refers to HPT occurring after an
intervening period of at least 6
months of biochemically documented
normocalcemia.
• Recurrent disease is far less common
than persistent HPT; however, both
occur more frequently in the setting
of familial HPT and MEN1, in
particular.

The most common causes for both these

states include:
o Ectopic parathyroid The most common sites of ectopic
o Unrecognized hyperplasia parathyroid glands in patients with
o Supernumerary glands persistent or recurrent HPT are:
o Parathyroid carcinoma • Paraesophageal (28%)
o Missed adenoma in a normal • Mediastinal (26%)
position • Intrathymic (24%)
o Incomplete resection of an • Intrathyroidal (11%)
abnormal gland • Carotid sheath (9%)
o Parathyromatosis • High cervical or undescended
o Inexperienced surgeon (2%)

o Once the diagnosis of persistent or

recurrent HPT is suspected, it should
be confirmed by the necessary
biochemical tests.

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 PHYSIOLOGY
ENDOCRINE
PARATHYROID GLAND
Dr. Anayan

o Other causes of an elevated serum be used to lower serum calcium

PTH such as renal insufficiency, renal levels.
calcium leak, and GI tract • Occasionally, in life-threatening cases,
abnormalities should be considered. hemodialysis may be of benefit.
o A detailed family history should be
performed to screen for familial
disease, as this will influence the
operative approach.

HYPERCALCEMIC CRISIS
• Patients with PHPT may occasionally
present acutely with nausea,
vomiting, fatigue, muscle weakness,
confusion, and a decreased level of
consciousness—a complex referred to
as hypercalcemic crisis.
• These symptoms result from severe
hypercalcemia from uncontrolled PTH
secretion, worsened by polyuria,
dehydration, and reduced kidney
function and may occur with other
conditions causing hypercalcemia.
• Calcium levels are markedly elevated
and may be as high as 16 to 20 mg/dL.
• Parathyroid tumors tend to be large
or multiple and may be palpable.
• Patients with parathyroid cancer or
familial HPT are more likely to
present with hypercalcemic crisis.

TREATMENT
• Therapies to lower serum calcium
levels followed by surgery to correct
HPT.
• The mainstay of therapy involves:
o Rehydration with a 0.9% saline
solution to keep urine output
>100 cc/h.
o Once urine output is
established, diuresis with
furosemide (which increases
renal calcium clearance) is
begun. If these methods are
unsuccessful, other drugs may

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 PHYSIOLOGY
ENDOCRINE
PARATHYROID GLAND
Dr. Anayan

SECONDARY HYPERPARATHYROIDISM • Tertiary HPT can cause problems like

• Commonly occurs in patients with PHPT, such as pathologic fractures,
chronic renal failure but also may bone pain and worsened bone
occur in those with hypocalcemia disease, renal stones, peptic ulcer
secondary to inadequate calcium or disease, pancreatitis, and mental
vitamin D intake or malabsorption. status changes.
• The pathophysiology of HPT in • Like patients with secondary HPT,
chronic renal failure is complex and many patients with tertiary HPT are
appears to be related to being treated with cinacalcet.
hyperphosphatemia (and resultant • Parathyroidectomy has been shown
hypocalcemia), deficiency of 1,25- to lead to a more immediate and
dihydroxy vitamin D due to loss of dramatic reduction in hypercalcemic
renal tissue, low calcium intake, symptoms.
decreased calcium absorption, and • The traditional surgical management
abnormal parathyroid cell response to of these patients consisted of subtotal
extracellular calcium or vitamin D in or total parathyroidectomy with auto
vitro and in vivo. transplantation and an upper
• Patients generally are hypocalcemic thymectomy.
or normocalcemic.
COMPLICATIONS OF PARATHYROID
SURGERY
MEDICAL TREATMENT
• Parathyroidectomy can be
• Low-phosphate diet
accomplished successfully in >95% of
• Phosphate binders patients with minimal mortality and
• Adequate intake of calcium morbidity.
• 1, 25-dihydroxy vitamin D • Specific complications include
• A high-calcium, low-aluminum transient and permanent vocal cord
dialysis bath. palsy and hypoparathyroidism.
• Calcimimetics • Patients with symptomatic
hypocalcemia or those with calcium
o Parathyroidectomy should be levels <8 mg/dL are treated with oral
considered if PTH levels remain high calcium supplementation (up to 1–2 g
despite therapy that includes every 4 hours).
calcimimetics. • 1,25-Dihydroxy vitamin D (calcitriol
o Patients should undergo routine [Rocaltrol] 0.25–0.5 μg bid) may also
dialysis the day before surgery to be required, particularly in patients
correct electrolyte abnormalities. with severe hypercalcemia and
elevated serum alkaline phosphatase
TERTIARY HYPERPARATHYROIDISM levels preoperatively and with osteitis
• Generally, renal transplantation is an fibrosa cystica.
excellent method of treating • Intravenous calcium supplementation
secondary HPT, but some patients rarely is needed.
develop autonomous parathyroid
gland function and tertiary HPT.

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 PHYSIOLOGY
ENDOCRINE
PARATHYROID GLAND
Dr. Anayan

• Furthermore, hypocalcemia is more

likely to occur in patients with high-
turnover bone disease as evidenced
by elevated preoperative alkaline
phosphatase levels.
• Vocal cord paralysis and
hypoparathyroidism are considered
permanent if they persist for >6
months.
• Fortunately, these complications are
rare, occurring in approximately 1%
of patients undergoing surgery by
experienced parathyroid surgeons.

HYPOTHYROIDISM
• Acute hypocalcemia results in
decreased ionized calcium and
increased neuromuscular excitability.
• Patients initially develop circumoral
and fingertip numbness and tingling.
Mental symptoms include anxiety,
confusion, and depression.

PHYSICAL EXAMINATION REVEALS:

o Chvostek’s sign
o Trousseau’s sign
o Tetany
“
TREATMENT:
o Oral calcium
o vitamin D supplements

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 PHYSIOLOGY
ENDOCRINE
PARATHYROID GLAND
Dr. Anayan

INDEX

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