44. Pathology of the parathyroid glands (hyperplasia, adenoma, causes of hypoparathyreoidism). Multiple endocrine neoplasms

Last updated on April 16, 2020 at 19:20

Introduction

The parathyroid glands are four oval-shaped glands embedded in the posterior surface of the thyroid gland. They’re comprised of chief cells, pale cells that produce PTH, and oxyphil cells. The parathyroid glands produce parathyroid hormone (PTH) in response to decreased levels of free (ionised) calcium in the blood. PTH has the following effects:

  • Increases the renal tubular reabsorption of calcium
  • Increases the urinary excretion of phosphate, lowering serum phosphate levels – phosphate binds to ionized calcium in the blood
  • Increases the production of vitamin D in the kidney, which increases calcium absorption from the GI tract
  • Enhances osteoclastic activity, causing bone resorption and liberation of calcium from bone

The net result of PTH is an increase in free calcium in the blood.

Hyperparathyroidism

The activity of the parathyroid glands is increased when the serum calcium levels are chronically low, such as in chronic renal failure. This is called secondary hyperparathyroidism. More important for us in this subject is the primary hyperparathyroidism, which is due to adenomas, hyperplasia or carcinomas of the glands.

The most common cause of primary hyperparathyroidism is sporadic parathyroid adenoma, which accounts for around 95% of cases. Abnormalities in two specific genes are commonly associated with sporadic parathyroid adenoma, namely Cyclin D1 inversion and MEN1 mutations. 20-30% of parathyroid tumors not Associated With MEN-1 syndrome have mutations in both copies of MEN-1 gene.

 Parathyroid adenoma always occurs in only one of the four parathyroid glands. The remaining glands are normal in size or slightly smaller, due to feedback inhibition.

Parathyroid hyperplasia usually affects all four glands equally. It can be idiopathic or associated with all types of multiple endocrine neoplasia.

Parathyroid carcinoma is very rare. It is impossible to distinguish an adenoma from a carcinoma by histology; the diagnosis of carcinoma is based on the presence of metastasis and local invasion.

The consequences of hyperparathyroidism are the following:

  • Abdominal pain
  • Acute pancreatitis
  • Nephrolithiasis
  • Gall stones
  • Metastatic calcification – most commonly of the kidney
  • Osteitis fibrosa cystica generalisata – tumor-like lesions of bones due to increased osteoclast activity
  • Bone pain

We should know the differential diagnosis for hypercalcaemia:

  • Primary hyperparathyroidism
  • Paraneoplastic syndrome – tumor produced parathyroid hormone-related peptide (PTHrP)
  • Vitamin D toxicity
  • Thiazide diuretics
  • Metastasis into bone
  • Multiple myeloma
  • Immobilization – which increases osteoclast activity

In all cases except primary and secondary hyperparathyroidism the level of PTH is decreased.

Hypoparathyroidism

hypoparathyroidism is very rare. It’s most commonly due to surgical removal, due to tumours or hyperplasia, or due to thyroidectomy. The result is hypocalcemia.

Multiple endocrine neoplasia

The multiple endocrine neoplasias (MEN) are autosomal dominant syndromes that increase the risk for certain hormone-producing neoplasias, to the point where they’re almost guaranteed to develop at least one of these neoplasms during their lifetime. They occur due to germ-line mutations in genes that are often involved in certain neoplasms. There are three types:

  • Multiple endocrine neoplasia type 1
    • Associated with mutations in the MEN1 gene
    • Increased risk for:
      • Pituitary adenoma
      • Pancreatic tumor
      • Parathyroid adenoma
  • Multiple endocrine neoplasia type 2a
    • Associated with mutations in the RET gene
    • Increased risk for:
      • Medullary thyroid carcinoma
      • Pheochromocytoma
      • Parathyroid adenoma
  • Multiple endocrine neoplasia type 2b
    • Associated with mutations in the RET gene
    • Increased risk for:
      • Medullary thyroid carcinoma
      • Pheochromocytoma
      • Marfanoid habitus – long limbs, tall stature

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45. Causes and clinical consequences of hyperplasia and atrophy of the suprarenal gland. Cortical tumours of the suprarenal gland (morphology, clinical syndromes) Cortical insufficiency of the suprarenal gland. Tumors of the adrenal medulla.

7 thoughts on “44. Pathology of the parathyroid glands (hyperplasia, adenoma, causes of hypoparathyreoidism). Multiple endocrine neoplasms”

  1. The title of the question says “causes of hypoparathyroidism” is there a reason why you don’t cover that at all?

    1. Whoops. You can study it in pathophys 2 topic 68 though. There’s not much to say about it so it shouldn’t be a big deal.

  2. hello greek doctor,
    in parathyriod abnormalities topic in pathophys, you mentioned that hypercalcaemia, never develops in secondary hyperparathyrioidism:
    ;In secondary hyperparathyroidism the calcium level is mostly normal.
    Hypercalcaemia does not develop.;
    then , how come secondary hayperparathyriodism , is DDx for hypercalcaemia in this topic?

    thanks alot.

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