Parathyroid hegazy

 1849 Sir Richard owen provided 1st accurate
description of normal parathyroid glands
after examining Indian Rhinoceros
 1879 Anton Wölfer described tetany in a
patient after total thyroidectomy
 Ivar Sandström a Swedish medical student
grossly and microscopically described
parathyroid glands

 Calcium measurement possible in 1909 and
association with parathyroids established
 1925- 1st successful parathyroidectomy on 38
yr old man with severe bone pain secondary
to osteitis fibrosa cystica.

 The parathyroid glands develop at 6 weeks and
migrate caudally at 8 weeks
 The paired superior parathyroid glands develop with
the thyroid gland from the fourth branchial pouch
and are generally consistent in position, residing
lateral and posterior to the upper pole of the thyroid
at the level of the cricothyroid cartilage.
 The paired inferior glands descend with the thymus
from the third branchial pouch and occasionally
migrate to the level of the aortic arch or, rarely, fail
to migrate, remaining in the high neck.

 Number of glands can vary from 4-6
 The parathyroid glands are usually embedded
between the posterior border of the thyroid gland
and its fibrous capsule.
 At times, the parathyroids may be intrathyroidal.
 They measure 6 x4x2 mm in maximum diameter
and weigh 25-40 mg each.

7
 4 pea-sized glands found on back of thyroid gland

 Superior glands usually dorsal to the RLN at level of
cricoid cartilage
 Inferior glands located ventral to nerve

 Usually derive most of blood supply from branches
of inferior thyroid artery, although branches from
superior thyroid supply at least 20% of upper
glands.
 Glands drain ipsillaterally by superior, middle, and
inferior thyroid veins

 Composed mostly of chief cells and oxyphil
cells within an adipose stroma.
 Oxyphil cells derived from chief cells and
increase as one ages
 Both types make Parathyroid hormone

 The parathyroid cells rely on a G-protein-coupled membrane
receptor designated the calcium-sensing receptor (CASR), to
regulate PTH secretion by sensing extracellular calcium levels
 PTH secretion also is stimulated by low levels of 1,25-
dihydroxy vitamin D, catecholamines, and hypomagnesemia.

Parathyroid Hormone Vitamin D Calcitonin
Gastrointestinal tract No direct effect Stimulates calcium
and phosphate
absorption
No direct effect
Skeleton Stimulates calcium
and phosphate
resorption
Stimulates calcium
and phosphate
transport
Inhibits calcium and
phosphate
resorption
Kidneys Stimulates calcium
resorption
Inhibits phosphate
resorption
No direct effect Inhibits calcium and
phosphate
resorption
Hormonal Regulation of Calcium and Phosphate metabolism

 PTH is synthesized in the
parathyroid gland as a
precursor
hormone,preproparathyroid
hormone, which is cleaved
first to proparathyroid
hormone and then to the
final 84-amino-acid PTH.
 Secreted PTH has a half-life
of 2 to 4 minutes. In the
liver, PTH is metabolized
into the active N-terminal
component and the
relatively inactive C-
terminal fraction

 The calcium-sensing receptor (CASR) is expressed
on the surface of the parathyroid cell and senses
fluctuations in the concentration of extracellular
calcium.
 Increased PTH secretion leads to an increase in
serum calcium levels by increasing bone resorption
and enhancing renal calcium reabsorption.
 PTH also stimulates renal 1- Hydroxylase activity,
leading to an increase in 1,25-dihydroxy vitamin D,
which also exerts a negative feedback on PTH
secretion

 PTH functions to regulate
calcium levels via its actions
on three target organs, the
bone, kidney, and gut.
 PTH increases the
resorption of bone by
stimulating osteoclasts and
promotes the release of
calcium and phosphate into
the circulation.

 At the kidney, PTH acts to limit calcium excretion at the distal
convoluted tubule via an active transport mechanism.
 PTH also inhibits phosphate reabsorption (at the Proximal
convoluted tubule) and bicarbonate reabsorption.
 PTH and hypophosphatemia also enhance 1-hydroxylation of
25-Hydroxyvitamin D, which is responsible for its indirect
effect of increasing intestinal calcium absorption.

 Hypercalcaemia in the presence of
inappropriately raised serum PTH levels is
due to enlargement of one or more glands
and hypersecretion of PTH.
 The normal response to hypercalcaemia is
PTH suppression.

 Affects approximately 100,000 patients a year
 Primary hyperparathyroidism occurs in 0.1 to 0.3%
of the general population and is more common in
women (1:500) than in men (1:2000).
 Primary hyperparathyroidism is characterized by
increased parathyroid cell proliferation and PTH
secretion which is independent of calcium levels.

 Etiology unknown, but radiation exposure, and
lithium implicated, associated with MEN1, and MEN
2A
 Enlargement of a single gland or parathyroid
adenoma in approximately 80% of cases, multiple
adenomas or hyperplasia in 15 to 20% of patients
and parathyroid carcinoma in 1% of patients

 Primary HPT is more commonly sporadic
than familial.
 The prevalence of sporadic primary HPT
increases with age and it affects women more
than men.
 On biochemical screening approximately 1%
of adults are hypercalcaemic.

 Familial HPT occurs as part of the following
genetically determined conditions:
• MEN-1 (multiple endocrine neoplasia type 1;
Werner’s syndrome)
• MEN-2A (Sipple’s syndrome) and rarely MEN-
2B.
• familial isolated HPT.

 Single adenoma:the majority (85%) of
patients with sporadic primary HPT have a
single adenoma.
 Hyperplasia: approximately 13% have
hyperplasia affecting all four glands
 Adenoma or a Carcinoma:about 1% will have
more than one adenoma or a carcinoma.
 In familial disease, multiple gland
enlargement is the norm.

 There is a weak correlation between the size
of an adenoma and the level of PTH.
 The histological differentiation between
adenoma and hyperplasia can be difficult and
the macroscopic findings are an important
determinant in making the diagnosis.

Operative photograph showing the normal left inferior parathyroid (IPG) and
large left superior parathyroid adenoma (SPG).

(a) Mobilised right thyroid lobe showing enlarged superior (1) and inferior (2)
parathyroid glands. Note how the superior gland has migrated posterior and inferior to
the inferior thyroid artery (3). (4) Recurrent laryngeal nerve.
(b)Total parathyroidectomy specimens.

 A single enlarged gland with three small
normal glands is characteristic of a single
adenoma, regardless of the histology, which
may show considerable overlap between
hyperplastic and an adenomatous gland.
 Multiple adenomas occur more frequently in
older patients.

 Parathyroid hyperplasia by definition
affects all four glands.
 Parathyroid carcinomas are large
tumours and typically much more
adherent or even frankly invasive than
large adenomas.
 Histology demonstrates a florid
desmoplastic reaction with dense fibrosis
and capsular and vascular invasion.

 The classic quartet of ‘stones, bones,
abdominal groans and psychic moans’ is
rarely observed in developed countries where
the diagnosis is usually made on serum
calcium estimation well before the full picture
of severe bone disease (von Recklinghausen’s
disease), renal calculi and calcinosis,
pancreatitis and psychiatric disorder
develops.

 Incidentally detected hypercalcaemia is
rarely truly ‘asymptomatic’ and most patients
experience an improved sense of well-being
after surgery.
 Careful enquiry into family history is always
appropriate and may reveal an index case for
familial disease, including familial primary
HPT, MEN syndromes and familial
hypocalciuric hypercalcaemia.

 Kidney stones, painful bones, abdominal groans,
psychic moans, and fatigue overtones
 Kidney stones calcium phosphate and oxalate
 Osteopenia, osteoporosis, and osteitis fibrosa cystica,
is found in approximately 15% of patients with
PHPT. Increased bone turnover can usually be
determined by documenting an elevated blood
alkaline phosphatase level.
 Peptic ulcer disease, pancreatitis
 Psychiatric manifestations such as florid psychosis,
obtubdation, coma, depression, anxiety, fatigue

 Although ionised calcium is the
physiologically active circulating element,
total serum calcium is a satisfactory measure.
 The effect of calcium binding to serum
proteins must be corrected by upward or
downward correction to a serum albumin
level of 40 g l–1.
 Inappropriate (elevated or normal) PTH levels
in the presence of high serum calcium are
diagnostic of primary HPT.

 Hypophospataemia and elevated urine
calcium excretion are confirmatory.
 Intact PTH measurement and elevated PTH
level very sensitive for hyperparathyroidism
 Hypercalcemia can be from other sources.

 Endocrine
Primary hyperparathyroidism
Thyrotoxicosis
Phaeochromocytoma
Adrenal crisis
 Renal failure
Tertiary hyperparathyroidism
 Malignant disease
Skeletal secondaries
Myeloma

 Nutritional
Milk alkali syndrom
Excess vitamin D intake
 Granulomatous disease
Tuberculosis
Sarcoidosis
 Immobilisation
 Inherited disorders
Hypercalciuric hypercalcaemia

 Advanced malignancy is the most common
cause of hypercalcaemia in hospital patients,
resulting from parathyroid hormone-related
peptide (PTHrP) or bone metastases.
 The PTH level is suppressed.

 Familial hypocalciuric hypercalcaemia is an
autosomal dominant disorder characterised
by mild elevation of calcium and PTH levels
secondary to a missense mutation in the cell
membrane calcium receptor.
 The low urinary excretion of calcium will
discriminate this from HPT.
 Parathyroidectomy is not required.

 However, neonatal HPT is rare but associated
with severe hypercalcaemia in homozygous
patients and urgent near-total
parathyroidectomy is required.

 There has been a paradigm shift in the use of
preoperative imaging in primary HPT.
 Until a few years ago the maxim that the‘only
localisation test necessary was to locate a
good endocrine surgeon’ (Doppman) was
apposite when opinion favoured
conventional bilateral neck exploration.

 Skilled surgeons can achieve cure rates of about
98%, with lack of success the result of an ectopic
adenoma not accessible through a cervical
incision or occasionally the failure to recognise
multiple gland disease.
 Although there should be minimal morbidity
associated with a bilateral neck exploration, an
image-guided targeted approach reduces this
even further and has become routine in most
major centres.

 Concerns remain that subtle abnormalities will
be missed if all glands are not routinely
visualised but, to date, these have not been
translated into a significant clinical issue.
 There remains a cohort of patient in whom
preoperative imaging does not localise an
adenoma and the experience of the surgeon
remains paramount in achieving a high cure rate.
 The predictive value of ultrasonography,
magnetic resonance imaging, or thallium-
technetium dual isotope scintigraphy ranges
from 40 to 80 percent

 High-frequency neck ultrasound is non-
invasive and should identify 75% of enlarged
glands.
 It gives better resolution but reduced
penetration and it cannot visualise the
mediastinum
 Nodular thyroid disease is a confounding
factor.

 Technetium-99m (99mTc)-labelled sestamibi
(MIBI) isotope scans also identify 75% of
abnormal parathyroid glands.
 The area scanned must include the
mediastinum to detect ectopic glands.
 99mTechnetium-labeled Sestamibi, aka
Cardiolite, was initially introduced for cardiac
imaging and is concentrated in mitochondria-
rich tissue.

Sestamibi scans
Left lower parathyroid adenoma Mediastinal parathyroid adenoma

 It was subsequently noted to be useful for
parathyroid localization because of the
delayed washout of the radionuclide from
hypercellular parathyroid tissue when
compared to thyroid tissue.
 In one prospective study of 387 patients the
sensitivity for single adenomas was 90
percent, but 27 percent of double adenomas
and 55 percent of hyperplastic glands were
missed

 Single-photon emission computerised
tomography (SPECT) gives a three-dimensional
image that may influence the surgical approach.
 Single-photon emission computed tomography
(SPECT), when used with planar sestamibi, has
particular utility in the evaluation of ectopic
parathyroid adenomas, such as those located
deep in the neck or in the mediastinum.
Specifically, SPECT can indicate whether an
adenoma is located in the anterior or posterior
mediastinum.

 Concordance between ultrasound and
sestamibi scans permits a targeted approach
with confidence.
 However, the size of the adenoma is
important and imaging and concordance
decline with glands weighing less than 500
mg.

 CT, PET and MRI are not indicated prior to
first-time neck exploration.

 Intraoperative parathyroid hormone testing
 introduced 1993
 Used to determine the adequacy of parathyroid
resection.
 When the PTH falls by 50% or more in 10 minutes
after removal of a parathyroid tumor, as compared
to the highest preremoval value, the test is
considered positive and the operation is terminated.

 At present, surgery is the only curative option
and should be offered to all patients with
significant hypercalcaemia provided that they
are otherwise fit for the procedure.
 There are a number of medical strategies and
therapies, particularly in mild HPT, including
 Simple expectant treatment until the calcium
level or symptoms reach a level at which
surgery becomes more attractive,

 a low-calcium diet,
 withdrawal of drugs (diuretics and lithium)
that aggravate hypercalcaemia and, more
recently,
 calcium-reducing agents such as
bisphosphanates and
 the calcium receptor agonist cinacalcet.

Occasionally, patients present with a
parathyroid crisis and severe hypercalcaemia
(serum calcium greater than 3.5 mmol l–1).
This results in confusion,
 nausea,
 abdominal pain,
 cardiac arrhythmias and
 hypotension with
 acute renal failure.

 Intravenous saline and bisphosphonate
therapy (pamidronate) are required to correct
the dehydration and hypercalcaemia.
 This is best done in a high-dependency unit or
even an intensive therapy unit setting to
monitor the major physiological fluxes that
result.

 Urinary tract calculi
 Reduced bone density
 High serum calciuma(Variously set between
2.85 and 3.00 mmol l–1)
 ? All in younger age group < 50 years
 Deteriorating renal function
 Symptomatic hypercalcaemia

 Bilateral neck exploration is “gold standard”
 With pre-operative imaging techniques can have minimally
invasive focused surgery towards adenoma
 Can have 99-Tc Sestamibi timed within 3 hours of surgery to
intra-operatively localize parathyroid adenoma using hand
held geiger probe
 Can have sequential Sestamibi scan and repeat technetium
injection 10 minutes prior to surgery
 In this setting intra-operative PTH level testing questionable

 Cancer of the parathyroid is rare, accounting for 1%
of cases of HPT.
 Typical features are very high calcium and PTH
levels, often with a palpable neck swelling or
occasionally lymphadenopathy.
 Scanning may support the diagnosis.

 The diagnosis is rarely known at the time of
exploration but, if suspected, operation should
include excision of the tumour mass with en bloc
thyroid lobectomy and node dissection when
indicated.

 The diagnosis is difficult to make histologically and
may only become apparent when recurrent disease
presents with hypercalcaemia, increased serum PTH
and evidence of local recurrence.

 Adjuvant or palliative radiotherapy may be
indicated and overall survival, as in most endocrine
cancers, is reasonable with a 5-year survival rate of
85%.
 1% of cases of primary hyperparathyroidism
 15% of patients have lymph node metastases and
33% have distant metastases at presentation.

 Intraoperatively, cancer is suggested by the
presence of a large, gray-white to gray-brown
parathyroid tumor that is adherent to or invasive
into surrounding tissues
 bilateral neck exploration, with en bloc excision of
the tumor and the ipsilateral thyroid lobe.
 Modified radical neck dissection is recommended in
the presence of lymph node metastases

 If on exploration, hyperplasia found, can remove and
reimplant, or preferably subtotal parathyroidectomy leaving
approx 50 mg of tissue (as reimplantation has 5% failure
rate).
 Bilateral upper cervical thymectomy also performed with
hyperplasia because of supernumerary glands occur in 20%
of patients
 With autotransplantation, 12 to 14 pieces inserted into belly
of brachioradialis muscle
 Sternotomy performed to find a missing gland, generally not
at initial operation, and after localizing studies performed
 Intra-op PTH measuring helpful as well during sternotomy to
make sure got the gland

 Chronic renal failure results in secondary HPT.
 The kidney cannot convert vitamin D into the
physiologically active 1,25-cholecalciferol.
 Reduced intestinal absorption of calcium
resulting in a low serum calcium, and
elevated phosphate due to renal failure to
excrete phosphate, increases secretion of
PTH.

 Prolonged stimulation results in parathyroid
hyperplasia.
 Initially this is reversible following renal
transplantation but when autonomous
hyperfunction progresses after
transplantation this is termed tertiary HPT.
 Secondary HPT also occurs in vitamin D-
deficient rickets,malabsorption and
pseudohypoparathyroidism.

 These include bone pain, pruritus, muscle
weakness, renal osteodystrophy and soft-
tissue calcification.
 Calciphylaxis (calcific uraemic arteriolopathy)
is the end-stage of this condition with
arteriolar occlusion resulting in cutaneous
ulceration and gangrene.

 The systemic effects of these changes result
in a high mortality rate and urgent
parathyroidectomy may be required if the
PTH is excessively high.

 In pts with chronic renal failure
 Deficiency of 1,25-dihydroxy vitamin D as a result of
loss of renal tissue,
 low calcium intake,
 decreased calcium absorption, and abnormal
parathyroid cell response

 Medical treatment of secondary HPT includes
 dietary phosphate restriction and
 calcium and vitamin D supplementation.

Surgical treatment is indicated and recommended for
patients with
 bone pain,
 pruritus, and a calcium-phosphate product >=70,
 Ca greater than 11 mg/dL with markedly elevated PTH
 Calciphylaxis
 progressive renal osteodystrophy,
 soft-tissue calcification

 Patients are prepared with high-dose vitamin D
(calcitriol) to reduce the severity of the profound
hypocalcaemia that would otherwise follow
parathyroidectomy.
 Preoperative dialysis is obligatory.

 Long standing renal failure s/p renal transplant autonomous
parathyroid gland function and tertiary HPT.
 Can cause problems similar to primary hyperparathyroidism
 Operative intervention
 symptomatic disease
 autonomous PTH secretion persists for more than 1 year
after a successful transplant
 subtotal or total parathyroidectomy with
autotransplantation

 Hypocalcemia (Chvostek’s and
Trousseau’s sign)
 Vocal cord paralysis after RLN injury

 Although there are rare congenital(DiGeorge)
and medical (autoimmune polyglandular and
Wilson) syndromes causing
hypoparathyroidism, for practical purposes,
postoperative hypoparathyroidism is the
dominant management issue in surgical
practice.
 This results from trauma to or removal or
devascularisation of the parathyroid glands.

 The symptoms and signs of acute
hypoparathyroidism are related to the level
of serum calcium and range from mild
circumoral and digital numbness and
paraesthesia to tetanic symptoms with
carpopedal or laryngeal spasms, cardiac
arrhythmias and fits.

 Chronic hypoparathyroidism can lead to
abnormal bone demineralisation, cataracts,
calcification in basal ganglia and consequent
extrapyramidal disorders.

 Percussion of the facial nerve just below the
zygoma causes contraction of the ipsilateral
facial muscles (Chvostek’s sign).
 Carpopedal spasm can be induced by
occlusion of the arm with a blood pressure
cuff for 3 min (Trousseau’s sign).
 Electrocardiogram changes include
prolonged QT intervals and QRS complex
changes.

 Acute symptomatic hypocalcaemia is a
medical emergency and requires urgent
correction by
 Intravenous injection of calcium.

 Magnesium supplements may also be
required.
 Oral calcium (1 g three or four times daily)
supplemented by 1–3 μg daily of 1- alpha-
vitamin D if necessary should be given with a
view to gradual withdrawal over the next 3–
12 months

■ Check serum calcium within 24 hours of
total thyroidectomy or earlier if
symptomatic.
■ Medical emergency if the level is < 1.90
mmol l–1: correct with 10 ml of 10%
calcium gluconate intravenously; 10 ml of
10% magnesium sulphate intravenously
may also be required

■ Give 1 g of oral calcium three or four times
daily
■ Give 1–3 μg daily of oral 1-alpha-vitamin D
if necessary

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Parathyroid hegazy

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