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Transcript
Parathyroid
Glands
Histology
Anatomy & Physiology
Diseases
Histology
• 50/50 parenchymal
cells, stromal fat
• Composed mostly of
chief cells and oxyphil
cells within adipose
stroma (fat)
• Oxyphil cells: derived
from chief cells and
increase as one ages
• Both types make
Parathyroid hormone
Anatomy
• Superior glands usually imbedded in fat
on posterior surface of middle or upper
portion of thyroid lobe
• Inferior glands near the lower part of
thyroid gland
• 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.
Parathyroid
Parathyroid Glands (posterior view of thyroid)
Parathyroid Glands are located on the posterior aspect
of the thyroid; sometimes the tissue is embedded
within thyroid tissue.
Parathyroid
Anatomy & Physiology
Usually four – two on each side (2-8 is normal) Parathyroid
glands
1. Yellow-brown
2. oval or lentiform structures
3. weigh ~ 50 mg each
4. Measure 3-10 mm x 2-6 mm x 1-4 mm
• Lie on the posterior surface of thyroid
• May be embedded within thyroid gland
• Regulate calcium/phosphate levels
• Required for life
Parathyroid Hormone
• Synthesized in chief cells as large precursor – preproparathyroid hormone
• Cleaved intracellularly into proparathyroid
hormone then to final 84 AA PTH
• PTH then metabolized by liver into hormonally
active N-term and inactive C-term
Calcium Homeostasis
• The parathyroid cells rely on a G-proteincoupled 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.
Calcium Homeostasis
• 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
Calcium homeostasis
• The calcium-sensing receptor (CASR) 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 1,25dihydroxy vitamin D, which also exerts a
negative feedback on PTH secretion
Calcium homeostasis
• 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.
Calcium homeostasis
• 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 1hydroxylation of 25-Hydroxyvitamin D, which is
responsible for its indirect effect of increasing
intestinal calcium absorption.
Parathyroid Diseases
• Benign adenoma
a. Relatively common
b. Usually results in hyperparathyroidism
• Cancers are rare
a. Surgical removal gives > 90%
cure rate
Parathyroid Diseases
• Hyperparathyroidism
a. Affects about 100,000 patients per 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).
– Normal feedback of Ca is disturbed,
causing increased production of PTH (does
not depend on calcium concentration)
– Acts on bone, kidneys, small intestines
Primary Hyperparathyroidism
Epidemiology
–
–
–
–
–
25/100,000
50,000 new cases yearly
F>M
Incidence increases w/ age
Most in > 50 years old
Etiology
– Unknown cause
– Ionizing radiation exposure?
Hyperparathyroidism Symptoms
• 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
Hyperparathyroidism (cont.)
• Secondary Hyperparathyroidism
– Defect in mineral homeostasis leading to a
compensatory increase in parathyroid gland
function
• Tertiary Hyperparathyroidism
– After prolonged over-compensatory
stimulation, hyperplastic gland develops
autonomous function
Hyperparathyroidism
• Hypercalcemia can be from other
sources. Intact PTH measurement and
elevated PTH level very sensitive for
hyperparathyroidism
Hypercalcemia – Etimology
• Hyperparathyroidism (most common)
• Malignancy (most common in hospitalized)
– Lytic metastases to bone
– PTHrP producer
• Sarcoidosis / granulomatous disease
• Hyperthyroidism
• Familial hypocalciuric hypercalcemia
Renal Complications
• Generally the most severe clinical
manifestations
• Calcium phosphate or Calcium oxalate
• Severe renal damage
• Hypertension secondary to renal
impairment
Bone Disease
• Osteitis fibrosa cystica
– Generalized skeletal demineralization due
to an increased rate of bone destruction
resulting from hyperparathyroidism
– In early descriptions of disease, many had
severe bone disease (50-90%), but now 515%
– Subperiosteal resorption – pathognomonic
of hyperparathyroidism
Generalized skeletal demineralization
due to an increased rate of bone
destruction resulting from
hyperparathyroidism
Gastrointestinal Manifestations
• Peptic Ulcer disease
• Pancreatitis
• Cholelithiasis – 25-35%
Emotional Disturbances
• Hypercalcemia of any cause – assoc w/
neurologic or psychiatric disturbances
– Depression, anxiety, psychosis, coma
• Severe disturbances not usually
correctable by parathyroidectomy
Articular and Soft Tissue
• Chondrocalcinosis and Pseudogout 37%
• Deposits of Calcium pyrophosphate in
articular cartilages and menisci
• Vascular and Cardiac calcifications
Neuromuscular complications
• Muscular weakness, fatigue
• More commonly in proximal muscles
• Sensory abnormalities also possible
Hyperparathyroid Crisis
• Most patents w/ hyperparathyroidism
chronically ill w/ renal and skeletal
abnormalities
• Rarely can become acutely ill
• Rapidly developing weakness, N/V, weight
loss, fatigue, drowsiness, confusion,
Azotemia
• Uncontrolled PTH production, hyperCa,
polyuria, dehydration, reduced renal
function, worsening hyperCa
Hyperparathyroid Crisis
• Definitive therapy - resection
• Must reverse hyperCa first
– Diuresis - Saline hydration then Lasix to
excrete Ca
– Calcitonin - rapid affect, inhibits bone
resorption
– Steroids - take up to a week
– Mithramycin - rapidly inhibiting bone
resorption
Treatment
• Only Curative treatment Parathyroidectomy
• Who should have surgery?
– Many found incidentally, during routine
physicals
Who should have surgery?
• NIH Consensus statement 1991
• All symptomatic
• If Assymptomatic
–
–
–
–
–
–
Markedly elevated serum Ca
H/o episode life-threatening hypercalcemia
Reduce renal function
Kidney stone on Radiograph
Markedly elevated urinary Ca excretion
Substantially reduce bone mass
Standard Neck Exploration
Parathyroidectomy
• Must find all four glands
• Intraoperative frozen section, PTH
measurement useful
• If single gland enlarged, removal usually
curative
• If multiple glands enlarged, removed. Normal
just biopsied
• If all 4 enlarged (generalized parathyroid
hyperplasia) - subtotal (3 1/2 removed)
– Can reimplant into forearm muscle
•
•
•
•
Superior parathyroid
easier to find
more consistent position
just on dorsal surface of
upper thyroid
• careful for superior
thyroid artery and
superior laryngeal nerve
• Inferior gland
• less consistent location
• may be near thymus or
inside thyroid
• careful for recurrent
laryngeal nerve betw
trachea / esophagus
• inferior thyroid artery
Success of Surgery
• 95% of cases cured at initial neck exploration
• If failed intial procedure, can try to localize w/
Radionuclide, detect w/ gamma probe
– Sestamibi concentrates in parathyroid
tissue
– Increasingly used in initial operation
– limits dissection
– Limits operative time
• May need mediastinoscopy