Parathyroid hyperplasia and tumours
How parathyroid chief cells set blood calcium, why a single adenoma is the usual cause of primary hyperparathyroidism, how hyperplasia arises in MEN1 and kidney disease, and how high calcium affects bones, kidneys, gut and brain.
By the end, you can
- Describe the calcium–PTH–vitamin D feedback loop and the role of the calcium-sensing receptor on chief cells.
- Compare parathyroid adenoma, multiglandular hyperplasia and carcinoma by their causes, gross and microscopic appearance, and relate them to MEN1 and MEN2A.
- Explain the mechanisms of secondary and tertiary hyperparathyroidism in chronic kidney disease.
- Relate high PTH and calcium to their effects on bone (including brown tumours), kidneys, gut and nervous system.
- Distinguish PTH-driven hypercalcaemia from high calcium caused by cancer through PTH-related protein, bone deposits or myeloma.
- Recognise the classic appearances, inherited syndromes and the calcium, PTH, phosphate, vitamin D and sestamibi tests of parathyroid disease, and explain how parathyroidectomy, calcimimetics, phosphate binders, fluids and bisphosphonates act on the mechanism.
What it is
Hyperparathyroidism is excess parathyroid hormone (PTH). In primary hyperparathyroidism the glands themselves are at fault: usually a single benign adenoma, less often enlargement of all four glands (hyperplasia, often inherited) and rarely a carcinoma; calcium is high. In secondary hyperparathyroidism the glands respond to low calcium or vitamin D, most often in chronic kidney disease, and in tertiary hyperparathyroidism long-stimulated glands become autonomous.
5 types to tell apart
- Parathyroid adenoma
- A benign clonal tumour of one gland; the cause of most primary hyperparathyroidism.
- Multiglandular disease (primary hyperplasia)
- Enlargement of all glands, sporadic or in MEN1 and MEN2A; the current WHO term is multiglandular parathyroid disease.
- Parathyroid carcinoma
- A rare malignant tumour defined by invasion or metastasis, with very high calcium.
- Secondary hyperparathyroidism
- An appropriate response of all glands to low calcium or calcitriol, mostly in chronic kidney disease.
- Tertiary hyperparathyroidism
- Autonomous secretion after long secondary stimulation, so calcium becomes high.
US spelling: tumours → tumors.
Normal function
Chief cells, the calcium sensor and PTH
Most people have four , each about the size of a grain of rice, on the back of the . The lower pair descend with the thymus in the embryo, so a gland is sometimes found lower in the neck or in the chest. Each gland is made mostly of chief cells, which make PTH, with oxyphil cells and fat cells that increase with age.
Chief cells carry the calcium-sensing receptor (CaSR) on their surface. When ionised calcium in the blood rises, the receptor is activated and PTH release falls within minutes; when calcium falls, PTH release rises. Over days and weeks, low calcium, low active vitamin D and high phosphate also increase PTH synthesis and make chief cells multiply.
PTH raises calcium in three ways. It makes bone cells signal osteoclasts to resorb bone, releasing calcium and phosphate; it makes the kidney reabsorb more calcium but excrete more phosphate; and it makes the kidney activate vitamin D to calcitriol, which increases calcium absorption from the gut. Calcium and calcitriol in turn suppress PTH, closing a negative feedback loop.
Simplified. FGF23 from bone also lowers calcitriol and PTH. An adenoma shifts the set point; in kidney disease the signals into the loop are abnormal.
Underlying change · Step 1 of 5
Primary hyperparathyroidism: the adenoma
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Underlying change · Step 2 of 5
Multiglandular disease, MEN syndromes and carcinoma
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Disrupted function · Step 3 of 5
Secondary and tertiary hyperparathyroidism
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Disrupted function · Step 4 of 5
Effects of high PTH and calcium: bones, stones, groans, moans
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Consequences · Step 5 of 5
Other causes of high calcium, grading and staging
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Symptoms and signs
Symptoms, signs and findings
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Exam detail
Exam detail
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Treatment
How treatment works
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Recap
Recap
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Self-check
Check your understanding
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .