Parathyroid Glands

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Parathyroid Glands Histology Anatomy & Physiology Diseases

description

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. - PowerPoint PPT Presentation

Transcript of Parathyroid Glands

Page 1: Parathyroid Glands

ParathyroidGlands

HistologyAnatomy & Physiology

Diseases

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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

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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.

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Parathyroid

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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.

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Parathyroid

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Anatomy & Physiology

Usually four – two on each side (2-8 is normal) Parathyroid glands

1. Yellow-brown 2. oval or lentiform structures3. weigh ~ 50 mg each4. 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

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Parathyroid Hormone

• Synthesized in chief cells as large precursor – pre-proparathyroid 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

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Calcium Homeostasis

• 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.

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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

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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 1,25-dihydroxy vitamin D, which also exerts a negative feedback on PTH secretion

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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.

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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 1-hydroxylation of 25-Hydroxyvitamin D, which is responsible for its indirect effect of increasing intestinal calcium absorption.

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Parathyroid Diseases

• Benign adenoma a. Relatively common b. Usually results in hyperparathyroidism

• Cancers are rare a. Surgical removal gives > 90%

cure rate

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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

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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?

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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

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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

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Hyperparathyroidism

• Hypercalcemia can be from other sources. Intact PTH measurement and elevated PTH level very sensitive for hyperparathyroidism

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Hypercalcemia – Etimology

• Hyperparathyroidism (most common)• Malignancy (most common in hospitalized)

– Lytic metastases to bone – PTHrP producer

• Sarcoidosis / granulomatous disease• Hyperthyroidism• Familial hypocalciuric hypercalcemia

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Renal Complications

• Generally the most severe clinical manifestations

• Calcium phosphate or Calcium oxalate• Severe renal damage

• Hypertension secondary to renal impairment

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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 5-15%

– Subperiosteal resorption – pathognomonic of hyperparathyroidism

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Generalized skeletal demineralization due to an increased rate of bone destruction resulting from hyperparathyroidism

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Gastrointestinal Manifestations

• Peptic Ulcer disease • Pancreatitis • Cholelithiasis – 25-35%

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Emotional Disturbances

• Hypercalcemia of any cause – assoc w/ neurologic or psychiatric disturbances– Depression, anxiety, psychosis, coma

• Severe disturbances not usually correctable by parathyroidectomy

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Articular and Soft Tissue

• Chondrocalcinosis and Pseudogout 3-7%

• Deposits of Calcium pyrophosphate in articular cartilages and menisci

• Vascular and Cardiac calcifications

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Neuromuscular complications

• Muscular weakness, fatigue• More commonly in proximal muscles• Sensory abnormalities also possible

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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

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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

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Treatment

• Only Curative treatment - Parathyroidectomy

• Who should have surgery? – Many found incidentally, during routine

physicals

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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

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Standard Neck Exploration

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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

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• Superior parathyroid• easier to find• more consistent position• just on dorsal surface of

upper thyroid• careful for superior

thyroid artery and superior laryngeal nerve

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• Inferior gland• less consistent

location• may be near thymus

or inside thyroid• careful for recurrent

laryngeal nerve betw trachea / esophagus

• inferior thyroid artery

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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