1. Diseases of thyroid & parathyroid glands (2 of 2)
Ali Al Khader, M.D.
Faculty of Medicine
Al-Balqa’ Applied University

2. Thyroid neoplasms
Most of the time hot nodules are benign, while 10% of cold nodules are malignant
Malignant
from parafollicular C cells
Benign
Majority are nonfunctional…cold
nodule on thyroid scan (taking less
radioactive material than the surrounding
normal tissue)
Carcinomas
Medullary
Adenomas
Anaplastic
(undifferentiated)
Papillary
(85% of
the cases)
Minority are oversecreting (toxic adenomas)
…hot nodule on thyroid scan & associated
with hyperthyroidism
Follicular
Mutations
TSH receptor
from follicular epithelial cells
Gain of function
GNAS
RAS
Toxic adenoma
Nonfunctioning adenomas
…also seen in follicular carcinoma
Also seen in toxic multinodular goiter

3. Thyroid adenoma Solitary, well-circumscribed and encapsulated
Usually as a painless nodule
in neck examination and on ultrasound
…if large may compress adjacent structures
and cause dysphagia for example
Hurthle cell adenoma (the cells show
abundant finely granular eosinophilic
cytoplasm)
Endocrine atypia (focal nuclear pleomorphism, atypia,
and prominent nucleoli) is accepted
*The most important to differentiate from follicular
carcinoma is the integrity of the capsule and absence
of vascular invasion…so FNA (fine needle aspiration cytology)
cannot tell us if it is a follicular adenoma or follicular carcinoma
…we need in this case to remove the nodule and assess the capsule
(histopathologcal examination)
Follicular adenoma
*Resembling normal follicles

4. Thyroid carcinoma, epidemiology & risk factors
Females more in early and middle adult years, but equal in childhood and late adult life
The most important risk factor: Ionizing radiation…especially papillary carcinoma
Iodine deficiency goiter multinodular goiter minor risk for
follicular carcinoma

5. Papillary carcinoma
*Single or multiple painless nodules, nonfunctioning
*Lymphatic invasion is usually present & metastases to adjacent cervical lymph nodes occur in up to one-half of cases…may be detected first
*Hematogenous spread is much less common
*Papillae are not mandatory
and nuclear features are enough
…e.g., the most common variant is
encapsulated follicular variant
(follicles not papillae)
MAP kinase pathway activation
is the most common
(especially BRAF oncogene)
Psammoma body
*FNA is good for diagnosis
*Indolent, 10-year survival 95%
*Poor prognosis factors: age >40,
extrathyroid extension and distant
metastases
*Lymph node involvement is
less important in prognosis
= ground-glass
*The treatment is total thyroidectomy
(because of the risk for multicentricity)
also nuclear grooves (coffee bean nuclei)

6. Follicular carcinoma *The 2nd most common thyroid carcinoma
*at older age than papillary (40-60)
*a much higher percentage in areas with dietary iodine deficiency
Capsule invasion…the most important for diagnosis
*mostly presents as a solitary cold nodule
…in rare cases, may be hyperfunctional
*Tendency for hematogenous spread
…especially to the lungs & bone
*Regional lymph node metastasis is uncommon
We need histopathological examination
to assess for this. FNA is not beneficial in
differentiating follicular adenoma from carcinoma
*Removed by surgery…metastases can be ablated
by radioactive iodine

7. Anaplastic carcinoma *Undifferentiated
*mostly conversion from well-differentiated (papillary or follicular) but may be de novo
*TP53 mutations
*Aggressive, large, with extrathyroid extension into the adjacent structures in the neck
*Metastasis common
*Mortality rate 100%...usually in less than 1year (due to the extension into vital neck structures)
*Usually older ages (>60)
*Undifferentiated cells (anaplastic)…large or spindle
*Adjacent foci of well differentiated tumor may be found

8. Medullary carcinoma *a neuroendocrine tumor
*from parafollicular C cells
*secretes calcitonin
…its measurement is important for diagnosis and postoperative followup
*in some cases, secretion of other hormones like somatostatin, serotonin & vasoactive intestinal peptide
*70% are sporadic and 30% familial:
-MEN 2A
-MEN 2B
-Familial medullary thyroid carcinoma without associated MEN syndrome
*RET receptor tyrosine kinase gain of function mutations…in sporadic and familial cases
*5th & 6th decades…sporadic and familial not associated with MEN
*MEN 2A and MEN 2B can occur even in children
*Multicentricity is especially common in familial cases
*polygonal to spindle-shaped cells, which may form nests, trabeculae, and even follicles. Amyloid deposits, derived from altered calcitonin molecules, are present in the adjacent stroma in many cases
We can offer prophylactic thyroidectomy
*Immunohistochemical staining shows positivity for calcitonin
…in both the cytoplasm of tumor cells and the amyloid material
*Multicentric C cell hyperplasia in the surrounding
thyroid parenchyma…seen only in familial cases
…may be a precursor lesion

9. Parathyroid hormone actions, introduction
The activity of the parathyroid glands is controlled by the level of free (ionized) calcium in the blood

10. Parathyroid (hormone) diseases
3ry
Hyperparathyroidism
Hypoparathyroidism
*far less common than hyper
*causes:
-surgical ablation (with
thyroidectomy for example)
-congenital absence (Di George)
-autoimmune hypoparathyroidism
(AIRE mutation)
*symptoms: neuromuscular irritability
(carpopedal spasm, tetany, facial grimacing)…cataracts if chronic
…arrhythmia, increased intracranial
pressure and seizures may occur
If activity increases until hypercalcemia
…parathyroidectomy is needed
1ry
*adults
*women more
*Causes:
-adenoma (most common)
-hyperplasia (diffuse or nodular)
-carcinoma
*Genetic abnormalities in
parathyroid tumors:
-Cyclin D1 (oncogene)
-MEN1 (tumor suppressor)…not only in familial cases
*adenoma is usually solitary & encapsulated
*Most parathyroid adenomas weigh between 0.5 and 5 g
*hyperplasia usually more than 1 gland, but may be one
*Carcinoma usually irregular and may exceed 10g
*Invasion of surrounding tissues and metastasis are
the only definitive criteria to say: carcinoma
2ry
*with chronic renal failure
*less excretion of phosphate
…so it increases in blood and
binds free Ca
*less α1-hydroxylase activity
production by the kidney so
less active vitamin D so less calcium
absorption from gut
*hyperplasia of the parathyroids will occur
*Bone changes similar to 1ry may also occur… = renal osteodystrophy
and metastatic calcification (driven by hyperphosphatemia) may also occur
*serum calcium is near normal
*painful bones, renal stones, abdominal groans, and
psychic moans
*What is osteitis fibrosa cystica?
*What is brown tumor
also

11. = sestamibi scan Parathyroid adenoma
Compressed rim of the remaining normal tissue
capsule
Adenoma
= sestamibi scan
Less fat
-Mainly chief cells
-Endocrine atypia is accepted
The other glands are normal in size or somewhat shrunken
The most common cause of hypercalcemia in outpatients is: 1ry hyperparathyroidism
The most common cause of hypercalcemia in inpatients is: malignancy

12. = Werner syndrome
= Sipple syndrome

13. Thank You