Endocrine Pathology II: Parathyroid Glands

Question 1

1. Where are the parathyroid glands derived from?
2. How many are there normally? In 10% of people?
3. Where else can they be found?

Answer 1

1. pharyngeal pouches
2. 2 or 3 glands
3. carotid sheath, thymus, anterior mediastinum

Question 2

What are the 3 cell types in the parathyroid gland?

Describe the histology and function of each

Answer 2

1. Chief cells: polygonal w/ central round uniform nuclei; produce PTH, contain glycogen; cytoplasm may appear clear
2. Oxyphil cells: found in groups, pink granular cytoplasm due to tightly packed mitochondria;
3. Fat

Question 3

Function of Parathyroid

1. What controls its release?
2. What does Parathyroid do to osteoclasts?
3. What does it do to renal tubular reabsorption?
4. What does it do to vitamin D?
5. What does it do to serum phosphate? How?
6. What does it do to the GI tract?

Answer 3

1. Ca levels in serum; low Ca increases release
2. activates them, mobilizing Ca from bone
3. increases it
4. converts it to its active form
5. increases urinary excretion of phosphate, drops its serum levesl
6. augments GI absorption

Question 4

1. What causes clinically apparent hypercalcemia most often?
2. What causes clinically inapparent hypercalcemia most often?
3. What is another cause of elevated PTH?
4. What are some causes of decreased PTH hypercalcemia?

Answer 4

1. malignancy, such as lung, breast, head and neck, and multiple myeloma
2. hyperparathyroidism (primary, secondary, tertiary)
3. Familial hypocalciuric hypercalcemia (FHH)
4. Hypercalcemia of malignancy, Vitamin D toxicity, Immobilization, thiazide diuretics, granulomatous disease (sarcoidosis)

Question 5

Hypercalcemia of Malignancy

1. What are 2 ways a malignancy can produce hypercalcemia?
2. Prognosis?

Answer 5

1. osteolytic metastases: tumor creates cytokines which cause local osteolysis by promoting maturation of osteoclasts
2. Tumor releases PTH-related protein –> bone resorption (part of paraneoplastic syndrome)
3. poor, pts present at advanced stage

Question 6

Primary Hyperparathyroidism

1. Who gets it?
2. What are the underlying lesions? (3)
3. What genetic syndromes are associated with familial hyperparathyroidism? What are the mutations? (3)

Answer 6

1. adults (about 50 y/o); females>males
2. Parathyroid Adenoma (85-95%), Primary Hyperplasia (diffuse/nodular), Parathyroid Carcinoma
3. MEN1- inactivation of MEN1 gene on chromosome 11q13 (tumor suppressor gene)
4. MEN 2A- activating mutation of RET (tyrosiine kinase receptor) gene on chromosome 10q
5. Familial hypocalciuric hypercalcemia- autosomal dominant disorder- mutation in parathyroid calcium sensing receptor gene (CASR) on chromosme 3q

Question 7

Parathyroid Adenoma

1. Solitary of Multiple?
2. What test can be used?
3. Histology?
4. What can usually be seen, but is normal?

Answer 7

1. almost always solitary
2. radionuclide scan shows 1 nodule taking up more
3. sheets or nests of chief/oxyphil cells; encapsulated; no fat; is an oxyphil adenoma is totally made up of oxyphil cells
4. bizarrea and pleomorphic nuclei within adenoma (endocrine atypia), but is not malignancy

Question 8

Parathyroid Hyperplasia

1. solitary or multiple
2. diffuse or nodular?
3. Histo look

Answer 8

1. multiple,
2. may be either diffuse or nodular
3. looks like an adenoma, there is no way to tell it apart from adenoma only by histology

Question 9

Parathyroid Carcinoma

1. Histo look
2. What is diagnostic?
3. What skeletal changes occur?
4. What happens in kidney? (2)
5. What may happen difffusely?

Answer 9

1. cells resemble normal parathyroid cells and are arranged in trabeculae or nodules with dense fibrous capsule with intervening fibrous bands
2. local invasion of surrounding tissue and metastasis
3. increased bone resorption due to increased osteoclast activity, looks like osteoporosis; brown tumor may form
4. formation of stones, calcification of renal interstitium and tubules
5. Metastatic calcification in organs like stomach, lung, myocardium, blood vessels

Question 10

Primary Hyperparathyroidism: Clinical Manifestations

1. How is it caught if asymptomatic?
2. What are the constellation of symptoms if symptomatic?
3. What may the symptoms be due to (2)?

Answer 10

1. routine chemistry profile
2. “painful bones, renal stones, abdominal groans, and psychic moans”
3. elevated PTH (bone and kidneys), hypercalcemia

Question 11

Secondary Hyperparathyroidism

1. Define
2. Most common cause
3. why? (2)
4. Other etiologies
5. What are the pathologic findings similar to?

Answer 11

1. process of chronic depression or decrease in calcium that causes compensatory over-activity of the parathyroid glands
2. renal failure
3. renal insufficiency causes decreased phosphate –> hyperphosphatemia –> decreased serum Ca –> increased PTH;
4. depressed renal mass –> alpha-1 hydroxylase deficiency –> deficiency of active Vitamin D –> less absorption of Ca from GI tract and eventually PTH stimulation
5. decreased dietary Ca, steatorrhea, Vit D deficiency
6. similar to parathyroid hyperplasia

Question 12

Secondary Hyperparathyroidism: Clinical Manifestations

1. 2 organ systems
2. What happens to vasculature?

Answer 12

1. chronic renal failure, skeletal changes (not as severe as primary)
2. vascular calcifications –> signficiant ischemic damage to skin (calciphylaxis)

Question 13

Tertiary Hyperparathyroidism

1. What causes it?
2. What is used to control symptoms?

Answer 13

1. autonomous hyperparathyroidism with symptomatic hypercalcemia
2. Parathyroidectomy or medications

Question 14

Hypoparathyroidism

1. Etiologies (5)

Answer 14

1. Surgically induced- may be removed inadvertently during thyroidectomy, lymph node dissection, or large portion taken during parathyroidetomy
2. Autoimmune hypoparathyroidism- assoc w/ mucocutaneous candidiasis and adrenal insufficiency
3. Autosomal Dominant hypoparathyroidism- gain of function mutation in Calcium sensing receptor gene (CASR)–> hypercalciuria and hypocalcemia
4. Familial isolated hyperparathyroidism- rare disorder due to mutation in gene encoding PTH precursor peptide
5. Congenital absence of parathyroid as part of DiGeorge syndrome or 22q11 syndrome

Question 15

Hypoparathyroidism:

1. Clinical Manifestations (
2. What is the Chvostek sign?
3. Trousseau sign?
4. Mental status changes?

Answer 15

1. Tetany: neuromuscular irritability including: circumoral numbness, parasthesias (tingling) of distal extremities, carpopedal spasm, laryngospasm, and seizures
2. tap along course of facial nerve and observe the contractions of the muscles of mouth, eye or nose
3. occlude the circulation in the forearm by tying a BP cuff, observe carpal spasms
4. emotional instability, anxiety, depression, confusion, hallucinations, and frank psychosis

Question 16

Hypoparathyroidism

1. Intracranial Manifestations
2. Ocular Disease
3. CV manifestation
4. Dental abnormalities

Answer 16

1. calcifications of basal ganglia, Parkinson like movement disorders, and increased intracranial pressure with papilledema
2. Catarct formation
3. conduction defect w/ prolonged QT interval
4. especially evident if hypocalcemia present during early development, dental hypoplasia, failure of eruption, defective enamel and root formation; carious teeth

Question 17

Pseduohypoparathyroidism

1. What is the serum Ca? serum PTH?
2. Cause of disease?

Answer 17

1. hypocalcemia; increased/normal PTH

2. end organ resistance to the actions of PTH