Thyroid-2 & Parathyroid Glands

Question 1

The normal plasma level of PTH is……, its receptor mechanism is….

Answer 1

10-55 pg/ml
Gs (inc cAMP)

Question 2

Describe effect of PTH in skeleton

Answer 2

Bone resorption & mobilization of ionic Ca & PO4 through:
1. Immediate effect: begins within minutes to hrs, stimulates bound Ca++ pumps, thus inc permeability of osteoblastic-osteocytic bone membrane to Ca++, so amorphous Ca is transferred from bone fluid to plasma
2. Delayed effect takes days to weeks, inc numer & activity of osteoclasts which breakdown hydroxyapatite crystals leading to localised dissolution of bone & Ca release.

Question 3

Compare the two forms of bone Ca

Answer 3

1. Labile pool: 1%, soluble, amorphous, in physicochemical equilibrium with ECF. The site of rapid PTH action.
2. Stable pool: 99%, insoluble hydroxyapatite crystals. Site of delayed PTH action

Question 4

Describe effect of PTH on kidney

Answer 4

Stimulate reabsorption of calcium & magnesium in distal convoluted tubules & excretion of phosphate from proximal convoluted tubules
Inc formation of active form of vitamin D

Question 5

Describe effect of PTH on intestine

Answer 5

Inc Ca absorption by inc formation of calcitriolwhich inc intestinal absorption by inc production of intestinal Ca binding protein known as calbindin.

Question 6

Describe regulation of PTH

Answer 6

Regulated by blood Ca levels rather than another gland, ionized Ca acts directly on parathyroid gland in -ve feedback fashion, they key to this regulation is Ca++ sensing receptor on parathyroid gland, when plasma Ca++ is high, PTH secretion is inhibited & Ca++ is deposited in bone & vice versa.
PTH is inc by:
1. Dec ionized Ca, plasma Mg, calcitriol
2. Inc PO4 level

Question 7

A paracrine factor with PTH activity is called…., secreted by…..
Desribe its function

Answer 7

Parathyroid hormone-related protein
Teeth, keratinocytes, brain, placenta
It has marked effect on growth & development of cartilage in utera, involved in Ca++ transport across placenta. Inhibits excitotoxic damage to developing neurons in brain.

Question 8

Normal Ca blood level is….

Answer 8

8.5-10.5 mg/dl

Question 9

List manifestations of hyperparathyroidism

Answer 9

1. Bones soften & deform with bone cyst formation, osteotits fibrosa cystical
2. Inc Ca filtration in renal tubules leading to renal colic, hematuria, nephrocalciunosis & eventually renal failure due to dec tubular & glomerular function.
3. Peptic ulcer (inc gastric acid secretion), acute pancreatitis (activation of trypsinogen). N&V& constipation.
4. Dec neuromuscular excitability with skeletal muscle weakness, dec alertness, poor memory.
5. Shortening of QT interval

Question 10

Describe microscopic features of:
1. follicular adenoma
2. Oncocytic adenoma

Answer 10

1. It is has well-formed capsule, composed of well-differentiated follicles containing colloid resembling normal thyroid tissue, micro or macrofollicles, focal nuclear pleomorphism & atypia may be notes.
2. Hurthe cell adenoma, most of the cells are large with granular acidophilic cytoplasm and a large vesicular nucleus.

Question 11

Describe clinical features of thyroid adenoma

Answer 11

1. Mostly painless nonfunctional nodules
2. Toxic manifestations in small proportion
3. Large adenomas cause pressure symptoms

Question 12

List major subtypes of thyroid carcinoma & their frequency

Answer 12

Papillary carcinoma (85%)
Follicular carcinoma (5 to 15%)
Medullary carcinoma (5%)
Anaplastic carcinoma (5%)

Question 13

Describe role of genetic factors in thyroid cancers

Answer 13

Genetic alteration are centers around 2 oncogenic pathways: MAP kinase, (PI-3K)/AKT pathway
Follicular carcinoma: PAX8/PPARG fusion
Papillary carcinoma: chromosomal rearrangement involving RET oncogenes
Medullary carcinoma: muations of RET

Question 14

The environmental factor that predisposes to papillary carcinoma is…..while that of follicular carcinoma is……

Answer 14

Ionizing radiation
Iodine deficiency

Question 15

Describe gross features of papillary carcinoma

Answer 15

Solitary or multifocal
Encapsulated or unencapsulated/inflitrative
Less than or =1cm called microadenoma
Cut surface in granular or papillary
There may be areas of fibrosis, calcification or cystic changes

Question 16

Describe microscopic features of papillary carcinoma

Answer 16

Diagnosis is based on nuclear features: opticallu clear nuclei devoid of nucleoli, nuclear grooves, intranuclear cytoplasmic inclusions
May show papillary pattern where malignant cells are arranged in in one or more layers around fibrovascular core OR follicular variant. Psammoma bodies are common.

Question 17

Describe spread & clinical features of papillary

Answer 17

Spread may be local, lymphatic (to cervical LNs) or blood spread to lung & bone
C/P: papillary carcinomas are non-functional painless mass in neck, most are indolent lesion with survival rates more than 95%.

Question 18

Follicular carcinoma is most common in……

Answer 18

Females 40-60 yrs of age

Question 19

Describe gross & microscopic features of follicular carcinoma

Answer 19

G, fleshy, usually infiltrating the thyroid & surrounding tissues or less commonly sharply demarcated
M, CAPSULAR AND/OR VASCULAR INVASION NECESSARY FOR DIAGNOSIS, most cases are well-differentiated & fairly uniform with follicular differentiation in most cases. Hurthe cell variants of follicular carcinoma may be seen. May be widely or minimally invasive.

Question 20

Describe spread & clinical features of follicular carcinoma

Answer 20

Local infiltration, blood spread early to lung & bone, lymphatic spread rare & late.
Follicular carcinoma manifest as cold, solitary thyroid nodule
Minimally invasive type has better prognosis than widely invasive

Question 21

Anaplastic carcinoma occurs in….
Describe its microscopic picture

Answer 21

Females over 65 yrs
Highly anaplastic cells may be large pleomorphic giant cells, spindle cells with sarcomatoid appearance, or mixed.

Question 22

Medullary carcinoma arises from……, familial cases occur in setting of……

Answer 22

Parafollicular (C) cells
MEN syndrome 2A or 2B

Question 23

Describe microscopic features of medullary carcinoma

Answer 23

1. Composed of polygonal to spindle-shaped cells arranged in organoid nests, trabeculae & occasionally follicles
2. Amyloid deposits derived from calcitonin molecules
3. Calcitonin is readily demonstrable both within cytoplasm & in stromal amyloid by immunohistochemistry. EM reveals variable numbers of intracytoplasmic membrane-bound, electron-dense granules.
4. Foci of C cell hyperplasia

Question 24

List causes of 1ry hyperparathyroidism

Answer 24

1. Primary hyperpalsia, 4 enlarged glands
2. Tumors: adenoma (85%-95%) single gland, carcinoma (1%)

Question 25

Describe morphological changes in organs, caused by hyperparathyroidism

Answer 25

1. Skeletal lesions: decalcification with generalized osteoporosis, diffuse osteitis fibrosa cystica (brown tumor) in severe cases
2. Metastatic calcification resulting in urinary stones & nephrocalcinosis (calcification of renal interstitium & tubules.

Question 26

Causes of 2ry hyperparathyroidism

Answer 26

Chronic renal insufficiency is associated with dec excretion of phosphorus leading to hyperphosphatemia, the latter directly depress the Ca levels & thereby stimulate parathyroid gland activity.

Question 27

C/P of hypoparathroidism

Answer 27

1. Inc neuromuscular irritability (tingling, muscle spasms, facial grimacing & sustained carpopedal spasm or tetany)
2. Cardiac arrhythmia
3. Inc ICT & seizsure occasionally