pth

Question 1

Parathyroid Glands

Answer 1

Chief cells – basic cell type, contain granules of PTH
Express calcium sensing receptor
Recall G-Protein Calcium Sensor for PTH release
Synthesize and secrete PTH in response to low calcium
Oxyphil cells – appear at puberty, present as single cells of small clusters
Have many mitochondria; secretory granules are absent

Question 2

activity of the PT glands is controlled by the

Answer 2

evel of free (ionized) calcium in the bloodstream
Decreased levels of free calcium stimulate the synthesis and secretion of PTH
An increased level of free calcium, in turn, inhibits PTH secretion

Question 3

Hypercalcemia

Answer 3

Serum PTH levels are inappropriately elevated for serum calcium levels
Clinically apparent hypercalcemia
Malignancies
Solid cancers secrete PTH related protein (PTHrp)
Solid tumors (lung, breast, head and neck and renal cancers) and hematologic malignancies mostly multiple myeloma

Question 4

Primary hyperparathyroidism

Answer 4

Autonomous, spontaneous overproduction of PTH by PT tissue
Cyclin D1 and MEN1 mutations
5-10% are familial-associated with MEN 1 and MEN 2A syndromes

Question 5

PT Hyperplasia

Answer 5

Sporadic/component of MEN syndrome
All 4 glands or asymmetric involvement with sparing of 1 or 2 glands

Question 6

Parathyroid carcinomas

Answer 6

May involve 1 gland, gray-white irregular masses that exceed 10g, cytological similarity to adenomas
Invasion of surrounding tissues and metastasis are only reliable criteria for malignancy

Question 7

Morphologic changes in other organs

Answer 7

Increased osteoclastic activity results in increased bone resorption
Increased osteoblastic activity results in formation of new bony trabeculae
Resultant bone comprises of widely spaced thin trabeculae and in severe cases, marrow with hemorrhage, cyst formation and fibrosis
Occasionally form masses composed of giant cells and hemorrhagic debris
Urinary tract – urinary tract stones, nephrocalcinosis (calcification of renal interstitium and tubules)

Question 8

Secondary hyperparathyroidism

Answer 8

Due to conditions causing chronic DECREASED calcium which lead to compensatory PT hyperplasia
Chronic renal failure is most common cause – decreases phosphate excretion leading to elevated serum phosphate levels that directly depress serum calcium levels
Loss of renal substance reduces availability of alpha-1-hydroxylase

Question 9

Tertiary hyperparathyroidism

Answer 9

When PT activity becomes autonomous and excessive with resultant hypercalcemia
Treatment – parathyroidectomy

Question 10

Hypoparathyroidism

Answer 10

ongenital absence, surgery/radiation, autoimmune, familial
Clinical manifestations – related to severity and chronicity of hypocalcemia
Tetany, neuromuscular irritability
Anxiety and depression, confusional states, hallucinations, and frank psychosis
Calcifications of basal ganglia, Parkinsonian-like movement disorders, and increased intracranial pressure with resultant papilledema
Characteristic prolongation of QT interval in ECG

Question 11

Pseudohypoparathyroidism

Answer 11

Hypoparathyroidism occurs because of end-organ resistance to actions of PTH
Serum PTH levels are normal or elevated

Question 12

C cells of thyroid

Answer 12

Secrete the hormone calcitonin
Lowers serum calcium

Question 13

Goitrogens

Answer 13

Chemical agents that inhibit function of thyroid gland
Suppress T3/T4 synthesis

Question 14

Hyperthyroidism

Answer 14

Hypermetabolic state caused by elevated circulating levels of free T3 and T4
Primary
Diffuse hyperplasia (Graves disease) – 85% of cases
Toxic multinodular goiter, toxic adenoma, iodine-induced hyperthyroidism, neonatal thyrotoxicosis
Secondary – TSH-secreting pituitary adenoma

Question 15

Thyroid storm

Answer 15

Abrupt onset of severe hyperthyroidism; results from an acute elevation in catecholamine levels,

Question 16

Apathetic hyperthyroidism

Answer 16

Thyrotoxicosis occurring in elderly where typical features are blunted
Diagnosis is often made during lab work-up for unexplained weight loss or worsening CV disease

dx via Lab findings – low TSH (most useful), elevated free T4/free T3, radioactive iodine uptake test

Question 17

Graves disease

Answer 17

Most common cause of endogenous hyperthyroidism is characterized by a triad of clinical findings
Hyperthyroidism – diffuse, hyperfunctional enlargement of thyroid
Infiltrative ophthalmopathy with resultant exophthalmos
Localized, infiltrative dermopathy
Thyroid-stimulating immunoglobulin – IgG antibody binds to TSH receptor and mimics the action of TSH
Increased risk for other autoimmune diseases, such as SLE, DM1, etc
Lab findings – elevated free T4/T3 levels, depressed TSH levels,

Question 18

Hypothyroidism

Answer 18

Structural or functional derangement that interferes with production of adequate levels of thyroid hormone
Fairly common disorder – population prevalence of overt hypothyroidism is 0.3%, while subclinical hypothyroidism can be found in >4%
Nearly 10x more common in women than men
Can result from a defect anywhere in hypothalamic-pituitary-thyroid axis
Primary (more common)
Congenital
Acquired – surgical or radiation-induced ablation, drugs
Autoimmune – most common cause in iodine-sufficient areas (Hashimoto)
Lab findings – elevated TSH, low T4

Question 19

Secondary hypothy

Answer 19

Pituitary failure/hypothalamic failure
Lab findings – low TSH, low T4
Classical clinical manifestations
Cretinism – develops in infancy or early childhood, clinically characterized by short stature, severe Mental Retardation (MR) and coarse facial features
Myxedema – older child or adult, patients are listless, cold-intolerant,
cause:Thyroiditis – inflammation of thyroid gland, cause of primary hypothyroidism

Question 20

Hashimoto thyroiditis

Answer 20

Most common cause of hypothyroidism in areas where iodine levels are sufficient
Characterized by gradual thyroid failure because of autoimmune destruction of thyroid gland
Most prevalent between 45-65 years of age
Female predominance
Morphology – diffusely enlarged with intact capsule

Question 21

Riedel thyroiditis

Answer 21

extensive fibrosis involving thyroid and contiguous neck structures
Clinically stimulates a thyroid carcinoma

Question 22

Subacute lymphocytic (painless) thyroiditis

Answer 22

Middle-aged women, characterized by mild painless symmetric thyroid enlargement
Postpartum thyroiditis – occurs in postpartum period in up to 5% of women, circulating anti-thyroid peroxidase Abs

Question 23

Goiter

Answer 23

Enlargement of thyroid, most common manifestation of thyroid disease
Degree of thyroid enlargement is proportional to level and duration of thyroid hormone deficiency
Pathogenesis – impaired synthesis of thyroid hormone, compensatory rise in serum TSH level, hypertrophy/hyperplasia of thyroid follicular cells to ensue a euthyroid metabolic state
In case compensatory responses are inadequate, the result is goitrous hypothyroidism

Question 24

Diffuse non-toxic (simple) goiter

Answer 24

colloid goiter
Endemic goiter – in areas where soil, water, and food supply contain low levels of iodine
Particularly dietary substances – goitrogens
Sporadic goiter – less frequent

Question 25

Multinodular goiter

Answer 25

most extreme thyroid enlargements
Virtually all long standing simple goiters convert to MNG because of recurrent episodes of hyperplasia and involution

Question 26

Solitary nodule

Answer 26

1-10% in US, more common in women
Common causes – majority are non-neoplastic
Neoplasms – benign outnumber malignant (10:1), more likely neoplastic if solitary, younger, male, history of radiation, cold on radioactive studies
FNA is critical part of evaluation

Question 27

Follicular adenomas

Answer 27

Discrete solitary, majority present as unilateral painless mass, majority are nonfunctional
Encapsulated lesion, composed of uniform-appearing follicles containing colloid

Question 28

Carcinomas of thyroid

Answer 28

female predominance
Risk factors – ionizing radiation, deficiency of iodine, genetic factors
Major subtypes (4) – papillary carcinoma (>85%), follicular carcinoma (5-15%), anaplastic carcinoma (<5%), medullary carcinoma (5%)

Question 29

Papillary carcinomas

Answer 29

RET/PTC rearrangements and BRAF point mutations
Accounts for 85% of primary thyroid malignancies, 25-50 years

Question 30

Follicular carcinomas

Answer 30

RAS and PIK3CA mutations and PAX8-PPARG fusion genes
5-15% of primary thyroid cancers, more common in women, 40-60 years
More frequent in areas with dietary iodine deficiency,

Question 31

Anaplastic (undifferentiated) carcinomas

Answer 31

inactivation of p53 or activation of B-catenin
<5% of thyroid tumors, aggressive (mortality rate near 100%), older patients, mean age of 65 years

Question 32

Medullary carcinomas

Answer 32

RET proto oncogene mutations
Neuroendocrine neoplasms derived from parafollicular cells (C cells) and therefore secrete calcitonin, ACTH, VIP