L10 – Pathology of the Parathyroid Glands Flashcards by Max Kam

Typical number and anatomical location of parathyroid glands?

Range from 3 to 6
Normally 4

Located at upper and lower poles of thyroid gland on each side

could be found along lines of descent from pharyngeal pouch (ectopic)

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Are parathyroid glands encapsulated into the thyroid gland?

Can be over the surface or invaginated into thyroid

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3 main types of parathyroid gland cells? Function?

Chief cell = Produce, store, secrete PTH

Oxyphil cells = Function unknown

Water-clear cells = chief cells with accumulated glycogen

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Compare staining of chief vs Oxyphil cells in parathyroid gland?

Chief = Pale Eosinophilic cytoplasm with vacuoles

Oxyphil = dense, eosinophilic cytoplasm

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Normal arrangement of Parathyroid gland cells?

intermixed in variable proportions

Arranged in nests / trabeculae / acinar

separated by abundant adipose tissue

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Function of PTH?

Decreased free, ionized calcium stimulates parathyroid glands

> > PTH regulate increase calcium levels at:

1) Kidney
2) Bone
3) Intestines

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Effect of PTH on Kidneys? (3)

Increase distal tubular reabsorption of calcium

Increase PCT phosphate excretion through urine = less phosphate deplete calcium in serum

↑ conversion of vitamin D to 1,25 dihydroxy-D3 = increase calcium absorption from GIT

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Effect of PTH on Bone?

Stimulates osteoclastic activity

> > resorb / erode lamellar bones

> release, mobilize ionized calcium into the blood

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Effect of PTH on GIT?

Stimulated by calcitriol from kidney

> > increase calcium absorption

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What is the most common cause of hypercalcemia in adults?**

Cancer/malignancies

squamous cell carcinoma of the lung or breast carinoma produce PTH-related protein (PTHrP)

> > Bind to PTH receptor

> > exerts effects like PTH on kidneys, bones (without increase in PTH)

> > hypercalcemia

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Define primary hyperparathyroidism?

(excess secretion of PTH in the absence of any known stimulus

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Primary hyperparathyroidism: male or female affected more?

Female predom.

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Symptoms of primary hyperparathyroidism?

Mostly asymptomatic

 Bone pain, fractures
 Renal colic (stones)
 Polyuria, polydipsia (excessive thirst / excess drinking)
 Constipation, nausea
 Peptic ulcers, pancreatitis, gallstones

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CNS effects of primary parathyroidism?

severe, exceptional cases:

 Depression, lethargy
 Seizures
 Weakness, hypotonia

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Serum test results in primary hyperparathyroidism?

Increased serum PTH

Increased Ca, Low PO4

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Pathological changes to bones caused by primary hyperparathyroidism?

Osteopenia = thinning bone cortices
Osteitis fibrosa cystica = loss of bone in BM, fibrosis + haemorrhage + cystic chnage
BROWN TUMOUR of hyperparathyroidism = aggregates of osteoclastic reactive giant cells

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Which type of tumour closely resembles the pathological appearance of primary hyperparathyroidism?

giant cell tumor of bone = similar to brown tumor of hyperparathyroidism

Brown due to old hemoorhage and hemosiderin deposit

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Systemic complications of primary hyperparathyroidism?

 Nephrolithiasis (urinary tract stones)

 Nephrocalcinosis (interstitial, tubular calcification)

 Metastatic calcification in stomach, lungs, heart, BV, skin

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Calcification due to primary hyperparathyroidism is identical to dystrophic calcification. T or F?

False

Metastatic calcification is not Dystrophic cal.

Dystrophic = calcium deposits are secondary to tissue necrosis

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What is the most common cause of primary hyperparathyroidism?

Parathyroid adenoma

85-95%

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Define the genetic mutations asso. with Sporadic and Hereditary Parathyroid adenoma?

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Sporadic = MEN1 +/- Cyclin D1/ PTH rearrangement

Familial = MEN1 or MEN2A

List 3 causes of primary hyperparathyroidism?

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parathyroid Adenoma 85% to 95%
Primary hyperplasia (diffuse or nodular) 5% to 10%
Parathyroid carcinoma 1%

What medical history is asso. with sporadic parathyroid adenoma?

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exposure to ionizing radiation in the childhood, or secondary to lithium therapy

List some endocrine lesions caused by MEN1 mutation

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Parathyroid hyperplasia**

Pituitary adenoma **

Adrenal cortical adenoma** and hyperplasia

(Neuroendocrine tumours in pancreas, duodenum, thymus…)

List some endocrine lesions caused by MEN2 mutation?

parathyroid hyperplasia** or adenomas; thyroidmedullary carcinoma adrenal pheochromocytomas**

List some non-endocrine lesions caused by MEN1 mutation

angiofibromas, collagenomas lipomas, leiomyomas. meningiomas, ependymomas,

Gross appearance of parathyroid adenoma?

well-circumscribed, soft, tan nodular mass thin, delicate capsule Other normal parathyroid glands are feedback inhibited by Ca >> shrink

Histological appearance of Parathyroid adenoma?

predominantly of chief cells, acinar structure/ admixture Severe nuclear atypia but not malignant***** (no mitotic figures)

Extent of involvement, etiology of parathyroid hyperplasia?

Usually diffuse = all 4 glands Sometimes isolated to 1-2 glands (looks similar to adenoma) 5-25% Hereditary: MEN1 and MEN2A

How to tell whether parathyroid hyperplasia is primary or secondary by histology?

Primary = Chief cell + water-clear cells hyperplasia Secondary = Oxyphil cell hyperlasia

Histological appearance of parathyroid hyperplasia?

DIFFUSE/ MULTINODULAR proliferation Decrease intraglandular adipose tissue (same as adenoma, tricky to tell apart)

Gross appearance of parathyroid carcinoma?

Large, weigh >10 g 1. thick, dense fibrous capsule (gray-white) ** NOT THIN, DELICATE LIKE IN ADENOMA** 2. Irregular – invasion of surrounding structures, vascular and lymphatic spaces **NOT WELL-CIRCUMSIZED LIKE ADENOMA**

Clinical presentation, extent of involvement and genetic mutation asso. with parathyroid carcinoma?

One gland involved Sporadic or asso. MEN1 and MEN2A Typical hyperparathyroidism symptoms, death by uncontrolled hypercalcemia Elevated Serum calcium, PTH, Alkaline phosphatase

Histological appearance of parathyroid carcinoma?

Trabeculae/ Nodules of Cancer cells*** uniform nuclei with prominent nucleoli many mitotic figures*** = malignancy

List 2 causes of secondary hyperparathyroidism?

Chronic renal failure/ insufficiency******* Dietary: - Low Vit D - Low Calcium - Malabsorption of Ca

Explain how chronic renal failure leads to secondary hyperparathyroidism?

1. Decreased phosphate excretion = elevated serum phosphate suppress serum calcium 2. Decrease in α1-hydroxylase activity = less production of calcitriol= less intestinal absorption of calcium Chronic low Ca = PTH hyperplasia

Symptoms of secondary hyperparathyroidism?? *think about underlying cause**

KIDNEY FAILURE * Fluid/electrolytes imbalance (dehydration, edema, hyperkalemia, metabolic acidosis). * Anaemia (Low EPO) * Hypertension, uraemic pericarditis. * Skin (pruritis, dry skin, hyperpigmentation)

Define the serum calcium, phosphate and PTH levels in secondary hyperparathyroidism?

- Serum Ca normal/ slightly low - Compensatory increase PTH - High PO4

Complication of high PO4 in secondary hyperparathyroidism?

Calcium phosphate deposit in BV Narrow BV lumen > ischemia > Calciphylaxis (gangrene)

Pathogenesis of tertiary hyperparathyroidism?

long-standing secondary hyperparathyroidism >> prolonged stimulation >> Chief cell hyperplasia >> autonomous PTH secretion independent of Ca level >> very high PTH

How to differentiate primary and tertiary hyperparathyroidism?

Symptoms: 1° (asymptomatic / renal osteodystrophy) vs. 3°(CRF) Serum: Primary = High Ca, Low PO4, High PTH Tertiary = High Ca, HIGH PO4, VERY HIGH PTH

Treatment of tertiary hyperparathyroidism?

Parathyroidectomy

List 5 causes of Hypercalcaemia with DECREASED PTH?

- Hypercalcemia of malignancy*** (PTH-r protein mediated osteolytic metastases) - Vit D toxicity - Immobilization - Drugs (thiazide) - Granulomatous disease (sarcoidosis)

Most common causes of hypercalcemia and hypoparathyroidism respectively?

Hypercalcemia = Malignancy, PTHrP Hypoparathyroidism = Iatrogenic most common

List 3 causes of hypoparathyroidism?

- Iatrogenic: en bloc parathyroid gland removal surgically (treat thyroid or HNN malig.) - Autoimmune: AIRE mutation = AutoAb against endocrine organs - Congenital: Di George syndrome ( thymic aplasia and cardiac defects)

Clinical manifestation of acute hypoparathyroidism?

secondary to hypocalcemia: C – Convulsion A – Arrhythmia (irregular heartbeat) T – Tetany (involuntary contraction of muscles – Chvostek’s sign) S – Spasm (Trousseau’s sign) - Rarely increase ICP and seizures

Clinical manifestation of chronic hypoparathyroidism?

cataracts, calcification of the cerebral basal ganglia, dental abnormalities

Expected serum level findings in hypoparathyroidism?

Low Ca High PO4 Low PTH

Which type of scan is used to ddx parathyroid adenoma and hyperplasia?

technetium-99 radionuclide scan Hyperplasia: >1 gland will demonstrate increased uptake >=2 glands are abnormal = favor hyperplasia

What procedure is done to examine parathyroid glands for intra-operative dx

intraoperative frozen section Resect gland and store in OCT medium > transfer to cryostat for frozen section dx

Define the features seen in intra-operative frozen section of parathyroid glands that favour adenoma vs hyperplasia dx?

Adenoma = Visible thin fibrous capsule with a rim of ‘normal’ parathyroid gland tissue Hyperplasia = >=2 glands are abnormal Both have decreased fat content: adenoma has almost none

Limitations of frozen section dx of parathyroid pathologies?

- Single abnormal gland cannot ddx adenoma and hyperplasia (morphologically same) - Capsule is thin, not always visible - varying degrees of loss of intra-glandular fat

L10 – Pathology of the Parathyroid Glands Flashcards

(52 cards)