Endocrine parathyroid overview

Question 1

How common is a supernumerary parathyroid
gland, and where is the supernumerary gland
most likely to be found?

Answer 1

The incidence of a supernumerary parathyroid gland is up to 15%. They are most often found in the thymus, thyrothymic tract, and carotid sheath.

Question 2

Where do the superior and inferior parathyroid

glands obtain their blood supply?

Answer 2

Most of the blood supply comes from the inferior thyroid
artery, although occasionally the superior glands may get their blood supply from the superior thyroid artery (in 15%
of cases).

Question 3

What options are available for minimally invasive

parathyroidectomy?

Answer 3

Minimally invasive parathyroidectomy is gaining popularity
among surgeons. Typically, a technetium-99 sestamibi scan preoperatively determine a single hyperfunctioning parathyroid adenoma, and exploration of that gland alone is done using intravenous (IV) sedation and intraoperative
parathyroid hormone assay monitoring.

Question 4

When conducting a subtotal parathyroidectomy,

what tissue should be left behind?

Answer 4

Approximately three and one-half glands should be excised
and the remaining half of a gland left to its blood supply.
Most prefer to leave a portion of an inferior parathyroid
gland because there would less risk to the recurrent
laryngeal nerve.

Question 5

How can PTH levels be used intraoperatively to determine the completeness of a parathyroidectomy?

Answer 5

PTH has a half-life of 2–5 minutes, so PTH levels can be
drawn from the patient before incision and then 5 to 10 minutes after excision. If there is at least a 50% decrease in the PTH level, into the normal or near normal range, the
excised gland was likely the offending gland.

Question 6

What structures have been described as landmarks to identify the superior parathyroid gland?

Answer 6

About 80% of superior parathyroid glands are found on the posterior aspect of the thyroid gland within a 1-cm
diameter centered 1 cm superior to the intersection of the
recurrent laryngeal nerve and inferior thyroid artery.

Question 7

What branchial pouch gives rise to the superior and inferior parathyroid glands?

Answer 7

The fourth branchial pouch gives rise to the superior parathyroid gland and C cells. The third branchial pouch
gives rise to the inferior parathyroid gland and thymus.

Question 8

How does PTH maintain calcium levels?

Answer 8

PTH increases calcium absorption from the gut, mobilizes
calcium from the bones, inhibits calcium excretion from the
kidneys, and stimulates renal hydroxylase to maintain
activated vitamin D levels.

Question 9

What is the most potent regulator of PTH release?

Answer 9

Serum calcium levels

Question 10

Where can one find PTH receptors, and what downstream effects do they have in each location?

Answer 10

PTH binds to PTH receptors in two locations: bone and
kidney. In bone, PTH receptors on osteoblasts cause release of receptor activator of nuclear factor-κ ligand, which then activates osteoclasts, which break down bone to increase serum calcium. In the kidney, PTH binds to renal tubule cells and induces reabsorption of calcium and decreases reabsorption of phosphate from the filtrate. It also induces
the expression of an enzyme that converts the inactive form
of vitamin D (25-hydroxyvitamin D) to the active form
(1,25-dihydroxyvitamin D).

Question 11

When monitoring total calcium levels in a patient, what factor do you also need to note?

Answer 11

Albumin level. Total calcium can vary with albumin level. In
a patient with normal albumin, total calcium can be monitored. In a patient with abnormal albumin levels, the corrected total calcium can be calculated (total serum calcium decreases by 0.8 g/dL for every 1-g/dL decrease in albumin), or the ionized calcium level can be followed.

Question 12

What test results support the diagnosis of familial hypocalciuric hypercalcemia?

Answer 12

Hypercalcemia with 24-hour urinary calcium:creatinine clearance ratio below 0.01, as well as one or more first-degree relatives with hypercalcemia

Question 13

What are common symptoms of chronic hypercalcemia?

Answer 13

The symptoms of chronic hypercalcemia can be remembered by the mnemonic “bones, stones, abdominal groans, and psychiatric moans,” referring to renal calculi, bone
pains, abdominal pain, and depression, anxiety, cognitive
dysfunction or other psychiatric problems.

Question 14

What testing is necessary to diagnose primary

hyperparathyroidism?

Answer 14

Elevated albumin-corrected serum calcium or ionized
calcium and elevated PTH. Imaging serves as an adjunct but is not part of the diagnostic criteria of primary hyper-
parathyroidism.

Question 15

Name the most common cause of hypercalcemia

in an outpatient clinic setting.

Answer 15

Parathyroid adenoma

Question 16

Name the most common cause of hypercalcemia

in an inpatient hospital setting.

Answer 16

Underlying malignancy

Question 17

A patient has hypercalcemia and low or undetectable PTH levels. What is the likely diagnosis?

Answer 17

Primary hyperparathyroidism is ruled out by the low or undetectable PTH level. This patient likely has a paraneoplastic-induced hypercalcemia mediated by PTH-related protein.

Question 18

What is the incidence of primary hyperparathy-

roidism in Western countries?

Answer 18

22 cases per 100,000 persons per year
The incidence has increased since the 1970s because of
increased detection of asymptomatic patients with elevated
calcium levels. In postmenopausal women, the most
common demographic, the incidence may be as high as 1 per 1,000/year.

Question 19

What are the different types of parathyroid

hyperplasia?

Answer 19

Parathyroid hyperplasia is predominantly caused by proliferation of the chief cells within the gland. Very rarely, water clear cell hyperplasia, which is a proliferation of
vacuolated water clear cells, can be found. The water clear
cell variant is clinically more severe and predominantly
occurs in females.

Question 20

Describe the typical patient population with

primary hyperparathyroidism.

Answer 20

Most cases occur in women (74%); incidence peaks in the seventh decade of life. Before age 45, incidence in men and women is similar.

Question 21

What causative factors are associated with primary hyperparathyroidism?

Answer 21

● Head and neck radiation in childhood
● Long-term lithium therapy
● Genetic predisposition

Question 22

What are the guidelines for surgical treatment
(parathyroidectomy) in an asymptomatic patient
with primary hyperparathyroidism?

Answer 22

Despite being devoid of classic symptoms, some patients
should be treated for hyperparathyroidism, including those
with serum calcium greater than 1.0 mg/dl above the upper
limit of the normal reference range, those with a calculated creatinine clearance less than 60 ml/minute, those with bone mineral density T score less than –2.5 at any site or previous fragility fracture. Patients younger than 50 years should also be considered to prevent long-term damage from elevated calcium.

Question 23

What are the typical laboratory values of calcium, PTH, and phosphate in secondary hyperparathyroidism?

Answer 23

In secondary hyperparathyroidism, one would expect low-normal calcium and elevated PTH. Phosphate levels vary based on the etiology (high in renal insufficiency, low in
vitamin D deficiency).

Question 24

What are some possible causes of secondary

hyperparathyroidism?

Answer 24

Secondary hyperparathyroidism can occur from renal failure, which causes a decline in the formation of activated
1,25 vitamin D and calcium absorption in the gut. Phosphate excretion is also impaired, which together cause
low serum calcium. It can also result from low vitamin D
levels in the setting of adequate renal function, such as in
cases of dietary insufficiency. In addition, patients with
short gut syndrome or a history of gastric bypass surgery are at risk for secondary disease resulting from malabsorption of both calcium and vitamin D. In all cases, low serum calcium triggers secretion of PTH and growth of the
parathyroid glands.

Question 25

What is the treatment of secondary hyperparathyroidism?

Answer 25

● Correction of the underlying cause, such as renal trans-
plant in patients with renal failure or vitamin D therapy in
vitamin D deficiency
● Patient symptoms from secondary disease may improve with medications such as cincalcet or bisphosophate
therapy.
● There is a role for subtotal parathyroidectomy if medical management fails.

Question 26

What is tertiary hyperparathyroidism?

Answer 26

Tertiary hyperparathyroidism is a state of excess secretion of PTH after long-standing secondary hyperparathyroidism.
Phosphate levels in tertiary hyperparathyroidism are decreased; however, renal dysfunction may lead to hyper-phosphatemia despite elevated PTH levels. A classic example is hyperparathyroidism persisting after renal
transplantation.

Question 27

What is the pathophysiology of tertiary hyper-

parathyroidism?

Answer 27

The hypertrophied parathyroid glands become autonomous in their function and hypersecrete PTH, leading to hyper-
calcemia despite withdrawal of calcium and calcitriol. High calcium levels can cause diffuse calcinosis.

Question 28

What is the treatment of tertiary hyperparathy-

roidism?

Answer 28

Total parathyroidectomy with autotransplantation or sub-total parathyroidectomy (3 and 1⁄2 gland resection)

Question 29

What are the components of hyperparathyroid-

ism-jaw tumor syndrome?

Answer 29

Recurrent parathyroid adenomas, fibroosseous tumors of the mandible, and Wilms tumors

Question 30

How do the symptoms of acute and chronic

hypoparathyroidism differ?

Answer 30

Acute hypoparathyroidism, such as after surgery, can cause dramatic hypocalcemia and associated paresthesias, muscle
spasms, tetany, and seizures. The hypocalcemia induced by chronic hypoparathyroidism is gradual in onset and may not present until the patient develops blurry vision from
cataracts.

Question 31

What are the most common causes of hypoparathyroidism?

Answer 31

By far, the most common cause of hypoparathyroidism is
iatrogenic, by either treatment of hyperparathyroidism or injury during thyroid surgery. The next most common
causes are congenital, when the third and fourth branchial arches fail to develop properly.