PANCE Blueprint Endocrinology (7%)

Hyperparathyroidism

Patient will present as → a 62-year-old female complaining of joint pain, polyuria, polydipsia, and generalized fatigue. The patient reports a history of recurrent kidney stones and depression. Radiographs show osteopenia and subperiosteal resorption on the phalanges (bones, stones, abdominal groans, and psychic moans).

Hyperparathyroidism is a condition in which one or more of the parathyroid glands become overactive and secrete too much parathyroid hormone (PTH). This causes the levels of calcium in the blood to rise

  • Most patients with calcium levels < 12 are asymptomatic
  • Symptoms usually begin as the calcium level rises above 12, and the symptoms will worsen as the calcium level continues to rise
  • Initially, patients may complain of nausea and vomiting with a loss of appetite.  They may feel muscle weakness and fatigue, and constipation may be present
  • As the calcium level rises, they may become confused and lethargic.  Polyuria can occur with renal failure. Cardiac arrhythmias can occur and even coma.

Hyperparathyroidism always = ↑ PTH

Parathyroid hormone has only one function: to correct hypocalcemia and maintain the serum level of calcium within narrow limits. If the serum calcium is low, the four parathyroid glands secrete PTH, which is made and stored in the glands. When released, PTH works with and through vitamin D to restore the calcium level to normal.

 There are three types of hyperparathyroidism - primary, secondary, and tertiary

  1. Primary = ↑ PTH usually caused by a PTH secreting parathyroid ADENOMA
  2. Secondary =↑ PTH by a physiologic response to hypocalcemia or vitamin D deficiency. Chronic kidney disease is the most common cause of secondary hyperparathyroidism
  3. Tertiary hyperparathyroidism is a situation where individuals who have had secondary hyperparathyroidism for many years develop primary hyperparathyroidism. In tertiary hyperparathyroidism parts of the parathyroid gland start making parathyroid hormone independently of blood calcium levels - resulting in hypercalcemia.

The symptoms of primary hyperparathyroidism can be remembered as stones, thrones, bones, groans, and psychiatric overtones - Osteoporosis, renal calculi, bone pain, GI symptoms, depression, psychosis, fatigue

  • Stones = for calcium-based kidney stones or gallstones that can form
  • Thrones refers to the toilet to remind you of the polyuria or frequent urination that results from impaired sodium and water reabsorption
  • Bones is for bone pain that results after chronic hormone-driven demineralization in order to release calcium
  • Groans is for constipation and muscle weakness, both of which are partly due to decreased muscle contractions
  • Psychiatric overtones refers to symptoms like a depressed mood and confusion

The symptoms of secondary hyperparathyroidism are the same four - ‘stones, thrones, bones, groans, and psychiatric overtones’ +  bone resorption (osteodystrophy) + calcification in blood vessels and soft tissues, because the high levels of phosphate cause it to find and stick to any available calcium, which forms bone-like crystals in places that they shouldn’t be

Tertiary hyperparathyroidism causes all of the same symptoms, but can also have elevated phosphate levels and as a result deposits of calcium-phosphate can settle in blood vessels and soft tissues

Serum Ca Serum Phos Serum PTH
Primary
Secondary normal or ↓
Tertiary

↑ Calcium is the most common metabolic abnormality associated with hyperparathyroidism

↑ PTH secretion from the parathyroid raises the blood calcium level by:

  1. Breaking down the bone (where most of the body's calcium is stored) and causing calcium release
  2. Increasing the body's ability to absorb calcium from food from the GI tract
  3. Increasing the kidney's ability to hold on to calcium that would otherwise be lost in the urine

This results in increased serum and urinary calcium, osteoporosis, and renal calculi.

Labs

  • ↑ Calcium is the most common metabolic abnormality
  • Blood: ↑ PTH, ↑ Calcium, ↓ phosphorus
  • Urine: hyperphosphaturia, hypercalciuria this makes sense because all that calcium and phosphorus must go somewhere, so they go out through the kidneys and into the urine
  • PTH inhibits the reabsorption of phosphate by the kidney. Therefore, with too much PTH there is less reabsorption of the phosphate leading to a low phosphate level in the blood
CT, ultrasonography, SPECT and scintigraphy of intra-thyroid parathyroid adenoma

CT, ultrasonography, SPECT, and scintigraphy of intra-thyroid parathyroid adenoma

Remove the PARATHYROID adenoma, subtotal parathyroidectomy (3 1/2 of gland removed), or total parathyroidectomy

  • If it is secondary, then once you replace the cause (Vitamin D and Calcium supplementation) you will have fixed the problem.
  • If the calcium is very high - treat with IV fluids, furosemide, or calcitonin
  • May need to treat osteoporosis with Bisphosphonates.

osmosis Osmosis
Picmonic
Primary Hyperparathyroidism Picmonic

IM_MED_PrimaryHyperparathyroidism_V1.2_ASSETS_

Primary Hyperparathyroidism is characterized by an increase in parathyroid hormone (PTH) secretion, which regulates serum calcium and phosphorus levels by stimulating bone resorption of calcium, renal tubular reabsorption of calcium, and the activation of Vitamin D.

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Parathyroid Gland Overview

parathyroid-gland_5110_1472585798

The parathyroid gland is a series of four small glands located in the neck on the rear surface of the thyroid gland. It serves primarily in calcium homeostasis and has a blood calcium sensor that detects when blood calcium levels are abnormally low. It responds by releasing parathyroid hormone (PTH) which stimulates osteoclasts into action. Osteoclasts resorb bone and release a large amount of calcium. This calcium enters the blood and results in increased blood calcium levels. PTH can also activate vitamin D by promoting the activity of an enzyme that converts inactive vitamin D to active vitamin D

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Question 1
Which of the following laboratory results is most indicative of primary hyperparathyroidism?  
A
Elevated serum calcium and low parathyroid hormone (PTH)
Hint:
This pattern suggests a non-PTH mediated cause of hypercalcemia, such as malignancy or vitamin D intoxication.
B
Low serum calcium and elevated parathyroid hormone (PTH)
Hint:
This is indicative of secondary hyperparathyroidism, often seen in chronic kidney disease.
C
Elevated serum calcium and elevated parathyroid hormone (PTH)
D
Low serum calcium and low parathyroid hormone (PTH)
Hint:
This suggests hypoparathyroidism or other causes of hypocalcemia unrelated to PTH.
E
Normal serum calcium and elevated parathyroid hormone (PTH)
Hint:
While PTH may be elevated, primary hyperparathyroidism typically presents with hypercalcemia.
Question 1 Explanation: 
Primary hyperparathyroidism is characterized by hypercalcemia (elevated serum calcium) and inappropriately elevated levels of parathyroid hormone (PTH). This condition typically results from a benign tumor (adenoma) in one or more of the parathyroid glands, leading to excessive production of PTH, which in turn increases serum calcium levels.
Question 2
Which of the following laboratory results is most consistent with a diagnosis of secondary hyperparathyroidism?
A
Elevated serum calcium and low parathyroid hormone (PTH)
Hint:
This pattern is more indicative of primary hyperparathyroidism or conditions causing hypercalcemia independent of PTH.
B
Low serum calcium and elevated parathyroid hormone (PTH)
C
Elevated serum calcium and elevated parathyroid hormone (PTH)
Hint:
This combination suggests primary hyperparathyroidism, where the parathyroid glands produce excessive PTH, leading to hypercalcemia.
D
Low serum calcium and low parathyroid hormone (PTH)
Hint:
This pattern suggests hypoparathyroidism or other conditions causing hypocalcemia without appropriate PTH response.
E
Normal serum calcium and elevated parathyroid hormone (PTH)
Hint:
While PTH may be elevated, the hallmark of secondary hyperparathyroidism is the combination of low serum calcium with elevated PTH.
Question 2 Explanation: 
Secondary hyperparathyroidism is characterized by low serum calcium levels and compensatory elevation of parathyroid hormone (PTH). This condition often occurs in response to chronic kidney disease, where impaired renal function leads to decreased calcium absorption and increased phosphate retention, subsequently lowering serum calcium levels. The parathyroid glands respond to this hypocalcemia by increasing PTH production in an attempt to normalize calcium levels.
Question 3
A 60-year-old man with recurrent kidney stones undergoes evaluation for a potential underlying cause. His serum calcium is elevated, and PTH is inappropriately normal. What is the most appropriate next step in the evaluation of this patient?
A
24-hour urine calcium excretion test
Hint:
Useful in the evaluation but does not localize the source of hyperparathyroidism.
B
Thyroid function tests
Hint:
Important in overall endocrine evaluation but not specific for parathyroid gland pathology.
C
Sestamibi scan of the parathyroid glands
D
Bone density scan
Hint:
Can assess for bone loss due to hyperparathyroidism but does not confirm the diagnosis.
E
Serum phosphate level
Hint:
Typically low in hyperparathyroidism but does not localize the parathyroid pathology.
Question 3 Explanation: 
A sestamibi scan of the parathyroid glands is an appropriate next step in evaluating a patient with suspected hyperparathyroidism, especially in the context of recurrent kidney stones and elevated serum calcium with inappropriately normal PTH levels. This imaging test helps localize overactive parathyroid glands, which can be a cause of hyperparathyroidism.
Question 4
A 50-year-old woman is diagnosed with primary hyperparathyroidism. She has osteoporosis and a history of nephrolithiasis. Her serum calcium level is 11.2 mg/dL. What is the most appropriate treatment for this patient?
A
Oral calcium supplements
Hint:
Not indicated in hypercalcemia due to hyperparathyroidism.
B
Parathyroidectomy
C
Thiazide diuretics
Hint:
Can increase serum calcium levels and are not recommended in hypercalcemia.
D
Calcitonin injections
Hint:
Used to lower calcium levels temporarily but not a definitive treatment for hyperparathyroidism.
E
Bisphosphonates
Hint:
Used in osteoporosis but do not treat the underlying hyperparathyroidism.
Question 4 Explanation: 
In a patient with primary hyperparathyroidism who has osteoporosis, a history of nephrolithiasis, and significant hypercalcemia (serum calcium >11.0 mg/dL), parathyroidectomy is the most appropriate treatment. Surgical removal of the overactive parathyroid gland(s) can effectively cure the hyperparathyroidism and prevent complications related to hypercalcemia.
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References: Merck Manual · UpToDate

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Parathyroid disorders (PEARLS) (Prev Lesson)
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