Download Parathyroid Glands - bushelman-hap

yes no Was this document useful for you?
   Thank you for your participation!

* Your assessment is very important for improving the work of artificial intelligence, which forms the content of this project

Document related concepts

Hormone replacement therapy (male-to-female) wikipedia, lookup

Growth hormone therapy wikipedia, lookup

Osteoporosis wikipedia, lookup

Hypothyroidism wikipedia, lookup

Iodine-131 wikipedia, lookup

Hyperthyroidism wikipedia, lookup

Anatomy & Physiology
• 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
• 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 Glands (posterior view of thyroid)
Parathyroid Glands are located on the posterior aspect
of the thyroid; sometimes the tissue is embedded
within thyroid tissue.
Anatomy & Physiology
Usually four – two on each side (2-8 is normal) Parathyroid
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
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
• 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
• PTH also inhibits phosphate reabsorption (at the
Proximal convoluted tubule) and bicarbonate
• 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
50,000 new cases yearly
Incidence increases w/ age
Most in > 50 years old
– 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
• Tertiary Hyperparathyroidism
– After prolonged over-compensatory
stimulation, hyperplastic gland develops
autonomous function
• Hypercalcemia can be from other
sources. Intact PTH measurement and
elevated PTH level very sensitive for
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
• Calcium phosphate or Calcium oxalate
• Severe renal damage
• Hypertension secondary to renal
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
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
• Rarely can become acutely ill
• Rapidly developing weakness, N/V, weight
loss, fatigue, drowsiness, confusion,
• 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
– Steroids - take up to a week
– Mithramycin - rapidly inhibiting bone
• Only Curative treatment Parathyroidectomy
• Who should have surgery?
– Many found incidentally, during routine
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
• Must find all four glands
• Intraoperative frozen section, PTH
measurement useful
• If single gland enlarged, removal usually
• 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
– Increasingly used in initial operation
– limits dissection
– Limits operative time
• May need mediastinoscopy