23: Parathyroid Flashcards
Which 3 findings are associated with multiple endocrine neoplasia type 2a (MEN2a)?
- Parathyroid hyperplasia
- Medullary carcinoma of the thyroid
- Pheochromocytoma (often bilateral, nearly always benign)
What percent of time are the following conditions the cause of primary hyperparathyroidism and what is the treatment for each?
- Single adenoma
- Multiple adenomas
- Diffuse hyperplasia
- Parathyroid adenocarcinoma
- Single adenoma: 80% of patients; Treatment is resection (inspect other glands to rule out hyperplasia or multiple adenomas)
- Multiple adenomas: 4% of patients; Treatment is resection (inspect other glands to rule out hyperplasia and ensure all adenomas are removed)
- Diffuse hyperplasia: 15% of patients (patients with MEN1 or MEN2a have 4-gland hyperplasia); Resect 3 and 1/2 glands or total parathyroidectomy with autoimplantation
- Parathyroid adenocarcinoma: Very rare; Radical parathyroidectomy with ipsilateral thyroid lobectomy
[Intra-op frozen section to confirm resected tissue is parathyroid tissue.]
Where should one look if there is a missing parathyroid gland intraoperatively?
- Check inferiorly in the thymus (can resect the tail of the thymus and see if PTH drops)
- Check near the carotids
- Check near the vertebral bodies
- Check superior to the pharynx
- Check the thyroid
[If still cannot find the gland then close and follow PTH. If PTH remains elevated, get a sestamibi scan to localize.]
What are the indications for surgery in a patient with primary hyperparathyroidism?
- Symptomatic disease
- Asymptomatic disease with calcium >13
- Asymptomatic disease with decreased Cr clearance
- Asymptomatic disease with kidney stones
- Asymptomatic disease with substantially decreased bone mass
- Pregnancy (increased risk of stillbirth if not resected)
[Best time for resection in pregnancy is 2nd trimester.]
[UpToDate: Patients with symptomatic primary hyperparathyroidism (PHPT) (nephrolithiasis, symptomatic hypercalcemia) should have parathyroid surgery, which is the only definitive therapy. Parathyroidectomy is an effective therapy that cures the disease, decreases the risk of kidney stones, improves bone mineral density (BMD), and may decrease fracture risk and modestly improve some quality of life measurements.
The widespread identification of individuals with asymptomatic PHPT raises the question of if and when these individuals should undergo surgery. The primary goal is to identify the asymptomatic individuals at risk for disease progression, as well as those who have features of the disease that may improve following parathyroidectomy.
For asymptomatic individuals who meet the Fourth International Workshop on Asymptomatic Primary Hyperparathyroidism guidelines, we suggest surgical intervention as opposed to observation (Grade 2C).
Guidelines for surgical intervention were developed based upon risk for end-organ effects and for disease progression. Parathyroidectomy should be performed only by surgeons who are highly experienced and skilled in the operation.]
What tests should be ordered in working up a patient with hyperparathyroidism?
- Presumably elevated calcium has already been determined
- CXR: Rule out bony metastases, sarcoidosis, and pulmonary tumors
- Excretory urogram: Rule out nephrolithiasis and renal tumors (rare)
- Serum protein electrophoresis: Rule out multiple myeloma
- 24-hour urinary calcium: Rule out benign familial hypocalciuric hypercalcemia
- Genetic analysis: Rule out multiple endocrine neoplasia (usually MEN1)
[Workup should begin with a careful history including medications, symptoms, prior head and neck XRT, and other endocrinopathies in the patient and the patient’s family.]
Which 3 findings are associated with multiple endocrine neoplasia type 1 (MEN1)?
- Parathyroid hyperplasia
- Pancreatic islet cell tumors (Usually gastrinoma)
- Pituitary adenoma (usually prolactinoma)
Which type of lung cancer can release parathyroid hormone-related peptide (PTHrP), resulting in hypercalcemia?
Squamous cell lung cancer
[Breast cancer with metastasis to bone can release PTHrP also.]
[UpToDate: Hypercalcemia is not uncommon in patients with malignancy, and it is associated with a poor prognosis. The most common tumors that cause hypercalcemia are breast cancer, multiple myeloma, lymphoma, and squamous cell cancers.
There are three major mechanisms by which hypercalcemia of malignancy can occur:
- Tumor secretion of parathyroid hormone-related protein (PTHrP)
- Osteolytic metastases with local release of cytokines
- Tumor production of 1,25-dihydroxyvitamin D
Hypercalcemia in patients with tumors secreting PTHrP is due to both increased bone resorption and distal renal tubular calcium reabsorption, whereas hypercalcemia in patients with osteolytic metastases is primarily due to increased bone resorption and release of calcium from bone. In patients with tumoral production of 1,25-dihydroxyvitamin D, hypercalcemia is the result of a combination of increased intestinal calcium absorption and bone resorption.
The initial approach to determining the mechanism of hypercalcemia in the presence of a low-normal or low serum parathyroid hormone (PTH) concentration (<20 pg/mL) includes measurement of PTHrP and vitamin D metabolites.
If PTHrP and vitamin D metabolites are not elevated, another source for the hypercalcemia must be considered. Additional laboratory data (including serum and urine protein electrophoresis and serum free light chain assay for possible multiple myeloma, thyroid-stimulating hormone [TSH], and vitamin A) will often lead to the correct diagnosis.]
What are the below characteristics of multiple endocrine neoplasia (MEN) syndrome?
- Inheritance pattern
- Penetrance
- Inheritance pattern: Autosomal dominant
- Penetrance: 100%
How can one differentiate between bone hunger and aparathyroidism in a post-parathyroidectomy patient with hypocalcemia?
- Bone hunger: Normal PTH, decreased HCO3
- Aparathyroidism: Decreased PTH, normal HCO3
Which type of multiple endocrine neoplasm (MEN) syndrome is associated with the following?
- MENIN gene mutation
- RET proto-oncogene mutation
- Marfan’s habitus
- Pheochromocytoma
- Medullary thyroid cancer
- Pituitary adenoma
- Parathyroid hyperplasia
- Mucosal neuromas
- Pancreatic islet cell tumors
- MENIN gene mutation: MEN1
- RET proto-oncogene mutation: MEN2a and MEN2b
- Marfan’s habitus: MEN2b
- Pheochromocytoma: MEN2a and MEN2b
- Medullary thyroid cancer: MEN2a and MEN2b
- Pituitary adenoma: MEN1
- Parathyroid hyperplasia: MEN1 and MEN2a
- Mucosal neuromas: MEN2b
- Pancreatic islet cell tumors: MEN1
What is Mithramycin and what is it used for?
- Osteoclast inhibitor (decreases serum calcium)
- Used to treat hypercalcemia in malignancy or when conventional treatment has failed
[It has hematologic, liver, and renal side effects.]
What does parathyroid hormone (PTH) do and what are the 3 ways it does it?
- PTH increases serum calcium
- Mechanism of action:
- Increases kidney calcium reabsorption (decreases PO4 absorption) in the distal convoluted tubule
- Increases osteoclasts in bone to release calcium and PO4
- Increases vitamin D production in kidney leading to increased calcium-binding protein in the intestine and increased intestinal reabsorption
[Normal calcium levels 8.5-10.5. Nomal ionized calcium 4.4-5.5.]
What are the following characteristics of parathyroid cancer?
- Most common location of metastasis
- Treatment
- Rate of recurrence
- 5-year survival
- Most common location of metastasis: Lung
- Treatment: Wide en bloc excision (parathyroidectomy and ipsilateral thyroidectomy)
- Rate of recurrence: 50%
- 5-year survival: 50%
[Parathyroid cancer is a rare cause of hypercalcemia.]
What does calcitonin do and what are the 2 ways it does it?
- Calcitonin decreases serum calcium
- Mechanism of action:
- Decreases bone calcium resorption by inhibiting osteoclasts
- Increases urinary calcium and PO4 excretion
[Normal calcium levels 8.5-10.5. Nomal ionized calcium 4.4-5.5.]
What are the below characteristics of multiple endocrine neoplasia (MEN) syndromes?
- # 1 cause of death in MENIIb
- # 1 cause of death in MEN2a
- First neoplasia to be symptomatic in MEN1
- First neoplasia to be symptomatic in MEN2a
- First neoplasia to be symptomatic in MEN2b
- # 1 cause of death in MENIIb: Medullary thyroid cancer
- # 1 cause of death in MEN2a: Medullary thyroid cancer
- First neoplasia to be symptomatic in MEN1: Parathyroid hyperplasia (urinary symptoms)
- First neoplasia to be symptomatic in MEN2a: Medullary thyroid cancer (diarrhea)
- First neoplasia to be symptomatic in MEN2b: Medullary thyroid cancer (diarrhea)
What is Osteitis fibrosa cystica and which condition is it characteristic of?
- Bone lesions from calcium resorption
- Characteristic of hyperparathyroidism
[UpToDate: The classic manifestation of Primary hyperparathyroidism (PHPT) bone disease is osteitis fibrosa cystica, which is characterized clinically by bone pain and radiographically by subperiosteal bone resorption on the radial aspect of the middle phalanges, tapering of the distal clavicles, a “salt and pepper” appearance of the skull, bone cysts, and brown tumors of the long bones. Brown tumors result from excess osteoclast activity and consist of collections of osteoclasts intermixed with fibrous tissue and poorly mineralized woven bone. The brown coloration is due to hemosiderin deposition.
Osteitis fibrosa cystica is now very rare in the United States. It occurs more typically in patients with severe disease, especially those with parathyroid carcinoma. In a review of 97 cases of mild PHPT, as an example, conventional radiography revealed signs of bone disease in only one patient. On the other hand, bone disease remains a major problem in patients with secondary hyperparathyroidism due to chronic renal failure.]
From which pharyngeal pouches do the superior and inferior parathyroids originate and which organ is each associated with during embryogenesis?
- Superior parathyroids: 4th pharyngeal pouch; associated with thyroid complex
- Inferior parathyroids: 3rd pharyngeal pouch; associated with thymus
What is a sestamibi scan of the parathyroid good at detecting and what is it bad at detecting?
- Good at detecting parathyroid adenomas and ectopic glands
- Bad at detecting 4-gland hyperplasia
[There will be preferential uptake by the overactive parathyroid gland.]
Where are the superior and inferior parathyroids usually found?
- Superior parathyroids are found on the posterior surface of the superior portion of the thyroid gland, lateral to the recurrent laryngeal nerves and superior to the inferior thyroid artery
- Inferior parathyroids are found more anterior, medial to the recurrent laryngeal nerves, and below the inferior thyroid artery
[The inferior parathyroids have more variable location and are more likely to be ectopic (occasionally found in the tail of the thymus - most common ectopic site).]
What percent of people have all 4 parathyroid glands and what is the most common ectopic site for the inferior parathyroids?
- 90% have all 4 parathyroid glands
- Tail of the thymus
[Other ectopic sites include: intra-thyroid, mediastinal, and near tracheoesophageal groove.]
Which vessel supplies blood supply to the following?
- Superior parathyroid glands
- Inferior parathyroid glands
- Superior parathyroid glands: Inferior thyroid artery (sometimes also from superior thyroid artery)
- Inferior parathyroid glands: Inferior thyroid artery
[Inferior thyroid artery supplies blood to both superior and inferior parathyroid glands.]
[UpToDate: In most patients, the inferior and superior parathyroid glands will both be supplied by branches of the inferior thyroid artery. Each parathyroid gland usually has its own end-artery. Most parathyroid glands have a single arterial supply (80%), some have a dual artery supply (15%), and a minority have multiple arterial supply (5%)
Superior parathyroid glands — The superior parathyroid glands receive most of their blood supply from the inferior thyroid artery and also are supplied by branches of the superior thyroid artery in 15% to 20% of patients. A superior parathyroid gland that is supplied by the superior thyroid artery will usually be located in close proximity to the superior pole of the thyroid. A subcapsular dissection on the posterior lateral surface can assist in the identification of parathyroid glands.
Inferior parathyroid glands — The inferior parathyroid glands receive their end-arterial blood supply from the inferior thyroid artery. Therefore, gentle medial mobilization of the parathyroid rim from the thyroid capsule and preservation of the lateral arteriole going to the parathyroid gland is important for preserving functioning inferior parathyroid glands. Ligation of the branches of the inferior thyroid artery close to the thyroid parenchyma and medial to the recurrent laryngeal nerve may help preserve intact parathyroid vascularity.]
