Patho sheet # 13 -Shadi jarrar

بسم الله الرحمن الرحيم

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بسم الله الرحمن الرحيم

Parathyroid gland

Parathyroid gland is different than any gland inside the body in its control, it's not controlled by the anterior lobe of the pituitary gland but by the concentration of the ionized calcium in the blood.

Parathyroid disorders

Hyperparathyroidism

Hyperparathyroidism is represented in increased secretion of parathyroid hormone which can be primary, secondary or tertiary. Primary hyperparathyroidism is an important cause of hypercalcaemia. 75% of hypercalcemaemia cases are due to adenomas in the parathyroid gland,while 10-15% of hypercalcaemia cases are due to primary hyperplasia in the gland.Only about 5% of hypercalaemia cases were developed by malignances in parathyroid gland. Some cases of hyperparathyroidism are associated with multiple neoplasia type I.

Hyperparathyroidism is a disease of adults occurring in the 50s of person's life or older. It's more common in females than males considering that most cases are sporadic.

Pathology of hyperparathyroidism

Abnormal cells of parathyroid adenoma are monoclonal. PRAND-1 gene was found to be relocated in 10-20% of adenomas. MEN-1 gene mutation is associated with familial cases and 20% of sporadic adenomas.

Morphology

Parathyroid adenomas are almost always solitary in one of the four parathyroid glands and in contrast to parathyroid hyperplasia,other glands than the affected gland are shrunken due to the negative feedback of calcium high concentrations of the blood which depletes their secretions ..and hence, atrophy in the glands other than the affected one is the result.

Ademas are composed mainly of chief cells and few oxyphil cells surrounded by a rim of normal compressed or nonneoplastic cells on the margins of the adenomas.


Primary hyperplasia occurs sporadically or with association with MEN-1 or MEN-2. Classicly the 4 parathyroid glands are involved but sparing of one or two glands is possible.

Most common pattern of primary hyperplasia is chief cell hyperplasia which maybe diffuse or nodular.

Parathyroid carcinomas usually involve only one gland and maybe related to invasion or metastisis.


Skeletal changes related to hyperparathyroidism

(1) Osteitis fibrosa cystica : this is related to high parathyroid hormone concentrations which has resorptive effect on the bones. This results in cysts in which giant cells can accumulate forming masses called brown tumors of parathyroid gland. The importance of these tumors is that they can be confused with giant cell carcinomas of the bone. Giant cell tumors in the bone are usually found as solitary tumors while brown tumors of hyperparathyroidism are multiple.(2)Formation of stones in the urinary tract.(3)Nephrocalcinosis in the kidneys-which is calcifications in the parenchyma of the kidneys as a result of metastatic calcification*.(4) Nephrolithiasis: The process of forming a kidney stone.(5) In the brain, depression and seizure are possible.(6)Ulceration in the stomach is related to changes in gastrin secretions.(7)Plyurea is a result of changes in absorptive function of the kidneys.(8) Pancreatitis.(9) Cardiac mitral or aortic calcification.

Clinicla course

The most common feature is high ionized calcium concentration of the blood. But as malignancy is the most common cause of high calcium concentration, we need to exclude malignancy as hypercalcaemia cause before thinking in hyperparathyroidism. Recent researches have found that if hypercalcaemia is asymptomatic, it is more likely to be due to hyperparathyroidism. On the other hand, if symptoms are seen, malignancy is more likely to be the underlying cause.

Considering parethyroid hormone concentrations in hypercalcaemia disorders, high concentrations are related to primary hyperparathyroidism, but if hypercalcaemia is due to external cause, parathyroid hormone concentration is normal.

Using radioimmunoassay, detection of parathyroid hormone-related globulin is related to tumors that secrete this globulin.

Secondary hyperparathyroidism
Icreased secrtion of parathyroid hormone which is associated to law calcium concentration appears most commonly as a response to chronic renal failure.** Other reasons include (1) low calcium intake(2) steatorrhea, which means excretion of fat with stools. Loss of fat leads to loss of fat-soluble vitamins-vitamin D which is responsible somehow in increasing blood concentrations of calcium is fat-soluble vitamin.(3)

* Metastatic calcification is different than dystrophic calcification. Metastatic calcification is associated with high calcium concentrations of calcium in the blood while dystrophic calcification is not. Dystrophic calcification is seen in necrotic tissues where there is calcific material even blood calcium concentration is normal.
** Chronic renal failure leads to increased phosphate reabsorption and hence increased phosphate concentrations in the blood will depletes calcium concentrations.
In secondary hyperparathyroidism, high concentrations of parathyroid hormone restore the normal concentration of calcium, so that is secondary hyperparathyroidism calcium levels are normal or slightly less than normal.

Histologically, parathyroid gland are hyperplastic in secondary hyperparathyroidism with increased number of chief cells. Bone changes and metastatic calcification are also seen.[I know that thi s is confusing piece of information as we've said that metastatic calcification is related with increased calcium concentration ..while in secondary hyperparathyroidism calcium is normal!].

Some patients respond to hypocalcaemia by excessive secretion of parathyroid hormone as the parathyroid glands become autonomous and do not respond to calcium concentration in the blood, excessive parathyroid secretion in this case is called tertiary hyperparathyroidism. [Calcium concentration here rises over the normal situation]

Hypoparathyroidism
Hypoparathyroidism is less common than hyperparathyroidism. It could be surgically induced by passive removal of parathyroid gland along with thyroid gland in thyroidictomies. In Dejar? Syndrome congenital, all parathyroid glands are abcent and hypoparathyroidism is the result. Hypoparathyroidism can be iodopathic represented by autoimmune disease. It could be familial associated with coetaneous candidiasis and primary adrenal insufficiency.

Clinical manifestations
Clinical manifestations include tremors, circumoral numbness, laryngeal spasm ,mental status changes, Parkinson-like movements, papilledema* cataract,long QT interval in ECGs, and even seizures.
Abraded carious teeth gingival hyperplasia and defects in enamel teeth are oral manifestations of hypoparathyroidism.





Papilledema is swelling in the optical disc. *



Pseudohypoparathyroidism

It is a disorder that is represented by resistance of target organs to normal or even high concentrations parathyroid hormone. It's classified into types:
1- type one is decreased response of cAMP to parathyroid hormone.
2- normal mediation of cAMP but with decreased response of second messenger.

In both cases hypocalcaemia is manifestated but with high concentrations of parathyroid hormone.




Thyroid gland pathology

Thyrotoxicosis is a disorder of thyroid gland in which thyroid hormones(T3/T4) increased in the blood regardless the source. Hyperthyroidism refers to increased secretion of (T3/T4) by thyroid hormone.

Thyrotoxicosis manifestations

Thyrotoxicosis manifestations result from sympathetic stimulation represented by
nervousness, palpitation, heat intolerance, increased metabolism, staring gaze, tremors and eye changes.

Another sign is lid lag sign, that is..if you ask the patient to look to an objest moving down, his eye ball will move downm first and later on his eye's upper lid will drop down.

Opthalmopathy is only a sign that is seen in Graves disease.

Hyperplasia in thyroid hormone represented in what's called Graves disease involves about 85% of endogenous thyrotoxicosis. Other causes include hyperactive adenomas, exogenous thyroid and thyroiditis.Most common cause of thyrotoxicosis is exogenous thyroid hormones consumption.

Thyrotoxicosis could be primary due to defect in thyroid gland or secondary due to other defects such as over secretion of thyroid stimulating hormone (TSH) by the pituitary gland. Another example is tertomas in the ovaries that secreate throid hormone.

Tests

We can use TSH,T3 and T4 to diagnose thyrotoxicosis. When T3 and T4 are high in concentration. TSH is low of the negative feedback. TSH is law in primary hyperparathyroidism but is high in secondary hyperparathyroidism.

Radioactive iodine can be given to the patient to observe the function of thyroid gland. Hypersecretion is represented by high gamma radiations.

T3 thyrotoxicosis is a case in which there is law concentrations of TSH, normal T4 but high T3. So that, T4 measuring is not enough. T3 thyrotoxicosis is a result of increased periphral conversion of T3 to T4.

Treatment

Beta blockers, thyronamides? To block hormone synthesis in the thyroid synthesis, Iodine to agent block peripheral conversion, radioactive iodine that is different than that we use in diagnosis.



Shadi B. Jarrar
Patho 13
Dr Caramella