ParathyroidGlands

HistologyAnatomy & 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 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

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

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.

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 1,25-dihydroxy 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 1-hydroxylation 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 5-15%

– 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 3-7%

• 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