Endocrine Pathology
Parathyroid
Dr. Atif Ali Bashir
Faculty of Medicine
Majmaah University, 2013
Parathyroid Glands
 The four parathyroid glands are mainly composed of chief
cells which secrete parathyroid hormone (PTH)
 Parathyroid gland activity is controlled by the level of free
(ionized) calcium in the
 Low levels of free Ca++ stimulate PTH which in turn:
 Increases osteoclast activity (releasing Ca++and PO43-)
 Increases small bowel Ca++and PO43- absorption (through vitamin
D)
 Increases renal resorption of Ca++ (distal tubule) and PO43excretion (proximal tubule)
 This results in increased free Ca++ levels, which then inhibit
PTH secretion (feedback loop)
Primary Hyperparathyroidism
 Overproduction of PTH due to intrinsic gland disorder,
which include:
 Adenoma (up to 95%)
 Primary hyperplasia (up to 10%)
 Parathyroid carcinoma (<1%)
 It is one of the most common endocrine disorders
which leads to hypercalcemia
 Adult women are more affected (4 : 1)
Parathyroid Adenoma
 A solitary parathyroid adenoma is the most common cause of
primary hyperparathyroidism
 It is usually sporadic, however, there are important associations
with familial syndromes, which include:
 Multiple endocrine neoplasia-1 (MEN-1): Parathyroid, pancreatic, and
pituitary tumors
 Multiple endocrine neoplasia-2 (MEN-2): Medullary thyroid cancers
(MTC), pheochromocytoma, and parathyroid tumors (MEN2a)
 Familial hypocalciuric hypercalcemia: Autosomal-dominant disorder
causing decreased sensitivity to free Ca++ and incresed PTH
 Cyclin D1 gene inversions are important pathogenic
mechanism leading to over-expression and increased cellular
proliferation
Parathyroid Adenoma
 Usually solitary, ranging from
0.5 to 5.0 gm
 It is a well-circumscribed,
soft, tan to reddish-brown
nodule surrounded by
delicate capsule
Technetium-99m-sestamibi
radionuclide scan
Normal Parathyroid
Primary Hyperparathyroidism
 Parathyroid adenomas are mostly
composed of fairly uniform, polygonal
chief cells with small, centrally placed
nuclei
 Primary parathyroid hyperplasia usually
involves all 4 glands (up to 1 gm total). It
is composed of chief cells and can be
sporadic or associated to MEN
In parathyroid hyperplasia, there is little or no adipose tissue, but any or all
cell types normally found in parathyroid are present.
Note the pink oxyphil cells here.
This is actually "secondary hyperparathyroidism" with enlarged glands as a
consequence of chronic renal failure with impaired phosphate excretion.
The increased serum phosphate tends to drive serum calcium down, which in
turn drives the parathyroids to secrete more parathyroidhormone.
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Parathyroid hyperplasia is shown here.
Three and one-half glands have been removed (only half the gland at
the lower left is present).
Parathyroid hyperplasia is the second most common form of
primary hyperparathyroidism, with parathyroid carcinoma the least
common form.
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Primary Hyperparathyroidism
Clinical Features
Most often it presents with asymptomatic hypercalcemia. If it manifests
clinically, the symptoms relate to high PTH and Ca++ levels:
"PAINFUL BONES, RENAL STONES, ABDOMINAL GROANS, AND PSYCHIC
MOANS”
1. Osteitis fibrosa cystica: Resorption of bone leading to fibrosis, cystic
degeneration and osteoporosis
2. Nephrolithiasis: Formation of Ca++ oxalate stones in 20% of patients
can cause obstruction and chronic renal insufficiency
3. Constipation, peptic ulcers, gallstones and acute pancreatitis
4. CNS alterations including depression, lethargy and seizures
5. Neuromuscular abnormalities (weakness and fatigue)
6. Aortic /mitral valve calcifications
Primary Hyperparathyroidism
Clinical Features
 The laboratory findings include:
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High serum PTH
High serum Ca++
Low serum PO43High urinary cAMP
High serum Alkaline Phosphatase
 Surgical removal is the primary mode of treatment.
Intraoperative PTH monitoring and frozen section are helpful
adjunctive tools
Secondary
Hyperparathyroidism
 Caused by chronic hypocalcemia (of any etiology)
resulting in compensatory overactivity of the parathyroid
gland
 Renal failure is the most common cause (others include low
Ca++ intake, malabsorption, vitamin D deficiency)
 Renal failure leads to decreased phosphate excretion
(hyperphosphatemia)
 Elevated serum PO43- binds to free Ca++ decreasing its
levels in the serum and stimulating parathyroid activity (all
glands)
 Vitamin D resulting from renal failure reduces intestinal
absorption of Ca++
Secondary
Hyperparathyroidism
 Laboratory findings:
 High PTH levels
 Low serum Ca++
 High serum PO43 High alkaline phosphatase
 The clinical features primarily relate to renal failure
 Renal Osteodystrophy: High PTH levels cause bone Resorption
 Calciphylaxis: Calcification of vessel walls can result in ischemic
damage to skin and other organs
 Management: Vitamin D supplementation and phosphate
binders (decrease hyperphosphatemia)
From AAFPweb
h13
Tertiary Hyperparathyroidism
 After a long period of secondary hyperparathyroidism,
parathyroid gland becomes autonomous and can
secrete PTH
 Results in hypercalcemia
 Parathyroidectomy is often treatment of choice
Hypoparathyroidism
It is a rare condition leading to low PTH levels. Main causes
include:
 Acquired Hypoparathyroidism is usually secondary to
surgical removal of parathyroid glands during
thyroidectomy, cervical lymph node biopsy or in treatment
of parathyroid adenoma
 Autoimmune hypoparathyroidism results from destruction of
parathyroid glands due to autoantibodies (Autoimmune
Regulator gene mutations)
 DiGeorge syndrome: Congenital absence of parathyroid
glands in association with other malformations (thymic
aplasia, cardiovascular defects)
Hypoparathyroidism
Clinical Features
All symptoms relate to low PTH and low serum Ca++:
 Muscular irritability (tetany, spasms)
 Range from circumoral numbness or paresthesias (tingling) of the
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distal extremities to life-threatening laryngospasm and generalized
seizures
Chvostek sign: Tapping along facial nerve induces contractions of
eye, mouth, or nose muscles
Trousseau sign: Carpal spasms elicited by filling of a blood pressure
cuff
Mental status changes (anxiety, depression, confusions,
hallucinations, psychosis)
Calcifications of the basal ganglia and lens (cataract formation)
Cardiovascular conduction defects produce long QT interval in EKG
Dental abnormalities are seen if hypocalcemia is present during
early development (dental hypoplasia, defective enamel and root
formation)
Pseudohypoparathyroidism
 Caused by end-organ resistance to PTH
 Lab findings include:
 Normal or high serum PTH levels
 Low serum Ca++
 High serum PO43-
 Autosomal dominant form is associated with short
stature and short 4th and 5th digits
 Some forms show multi-hormone end-organ resistance
to TSH and FSH/LH, besides PTH