Parathyroid glands
The parathyroid glands are an endocrine organ that is important in calcium regulation. They often make an appearance in the context of thyroid surgery.
File:Parathyroid gland high mag.jpg
Micrograph of a parathyroid gland. H&E stain.
They produce parathyroid hormone (PTH). PTH acts to increase serum calcium and is important in the regulation of the calcium balance.
Clinical
Hyperparathyroidism
- Definition: increased secretion of parathyroid hormone (PTH).[1]
What PTH does:[1]
- Increase serum calcium.
- Decrease serum phosphate.
Classification
- Primary.
- Secondary.
- Tertiary.
Overview in a table
| Type | PTH | Calcium | Common causes |
|---|---|---|---|
| Primary hyperparathyroidism | high | high | parathyroid adenoma (~85-90% of cases), parathyroid hyperplasia (~10-15% of cases) |
| Secondary hyperparathyroidism | high | low or normal | chronic renal failure, vitamin D deficiency[2] |
| Tertiary hyperparathyroidism | high | high | persistent hyperparathyroidism after renal transplant[3] |
Hypercalcemia DDx
Mnemonic GRIMED:[4]
- Granulomatous disease (tuberculosis, sarcoidosis).
- Renal disease.
- Immobility.
- Malignancy (esp. squamous cell carcinoma, plasmacytoma).
- Endocrine (primary hyperparathyroidism, tertiary hyperparathyroidism, familial hypocalciuric hypercalcemia (FHH)).
- Drugs (thiazides ... others).
Note:
- Hyperparathyroidism and FHH are assoc. with an increased PTH.[5]
- Other causes are assoc. with a decreased PTH.
Primary hyperparathyroidism
Cause:[6]
- Parathyroid adenoma ~90%.
- Parathyroid hyperplasia ~10%.
- Parathyroid carcinoma ~1%.
Familial causes of primary hyperparathyroidism:
- MEN 1.
- MEN 2A.
- Familial hypocalciuric hypercalcemia.
- Autosomal dominant.
- CASR (calcium sensing receptor) gene defect.[7]
Classic manifestations moans, stones, bones, (abdominal) groans, psychiatric overtones.[8][9]
- Moans = bone pain.
- Stones = nephrolithiasis (kidney stones).
- Bones = bone pathology, e.g. osteitis fibrosa cystica.[10]
- Groans = constipation.
- Psychiatric overtones = CNS pathology.
- Can include: lethargy, fatigue, depression, memory loss, psychosis, ataxia, delirium, and coma.
Hypoparathyroidism
- Rare vis-à-vis hyperparathyroidism.
- Classically iatrogenic, i.e. the surgeon removing 'em.[5]
Other causes:[11]
- Autoimmune hypoparathyroidism.
- Autosomal dominat hypoparathyroidism.
- Familial isolated hypoparathyroidism.
- Congenital absence (DiGeorge syndrome).
- Drugs - proton pump inhibitors.[12][13]
Normal parathyroid glands
- The cytology is dealt with in normal parathyroid cytology.
General
- Identification of normal can be tricky.
Gross
- No distinctive features - surgeons thus send 'em to pathologists.
Microscopic
Features:[14]
- Low power:
- May vaguely resemble lymphoid tissue - may have hyperchromatic cytoplasm.
- Does not have follicular centres like a lymph node.
- May form gland-like structure and vaguely resemble the thyroid at low power.
- Cytoplasm may be clear[15] - key feature.
- Surrounded by a thin fibrous capsule.
- May vaguely resemble lymphoid tissue - may have hyperchromatic cytoplasm.
- High power:
- Mixed cell population:[16]
- Chief cells - predominant cell type, small, cytoplasm has variable staining (hyperchromatic-clear-eosinophilic).
- Oxyphil cells (acid staining cells[17]) - abundant cytoplasm.
- Adipocytes - dependent on age, body habitus, PT hormone, size of gland.[18]
- Increased with age, may be used to help differentiate from thyroid - key feature.
- Mixed cell population:[16]
Images
- Parathyroid gland intermed mag.jpg
Parathyroid gland - intermed. mag. (WC)
- Parathyroid gland high mag.jpg
Parathyroid gland - cropped - high mag. (WC)
- Parathyroid gland high mag cropped.jpg
Parathyroid gland - high mag. (WC)
www:
Parathyroid cell types
| Name | Staining (cytoplasm) | Quantity of cells | Cytoplasm (quantity) | Function | Image |
|---|---|---|---|---|---|
| (parathyroid) chief cells | intense hyperchromatic to eosinophilic (see note) | abundant | moderate | manufacture parathyroid hormone (PTH) |
File:Parathyroid adenoma - chief cells -- high mag.jpg Chief cells (WC) |
| oxyphil cells | moderate/light hyperchromatic to eosinophilic | rare | abundant | ? |
Notes:
- Cytoplasmic staining varies considerably on H&E preparations - it may vary from hyperchromatic[19] to clear to eosinophilic.[20]
- Chief cells tend to stain more intensely than oxyphil cells.
Thyroid versus parathyroid
- Parathyroid cytoplasm:
- Hyperchromatic.
See: Parathyroid image (okstate.edu).
Parathyroid versus lymphoid tissue
- Parathyroid:
- No germinal centres.
- Gland-like/follicular-like arrangement may be present but usually much smaller than normal thyroid follicles.
- May be confused with thyroid microfollicules.
- Occasional cell with rim of clear cytoplasm (oxyphil?).
- Nuclei are different:
- Slightly larger than in lymphocytes (1.2-1.5x the size)
- Stippled chromatin (unlike lymphocytes).
Images:
Specific entities
Parathyroid hyperplasia
General
- Chief cell hyperplasia - associated with MEN 1, MEN 2A.[22]
- Parathyroid hyperplasia - classically assoc. with renal failure.
Gross
- Classically all parathyroid glands are involved; however, some may be spared making it difficult to differentiate this from parathyroid adenoma.[23]
Microscopic
Features:[23]
- Classically have abundant adipose tissue.
- +/-Water-clear cells ("water-clear cell hyperplasia").
Note:
- Generally, it is impossible to discern between parathyroid adenomas and parathyroid hyperplasias by histology alone.[24]
- One requires information of the size of the other glands to make the diagnosis.
DDx:
- Parathyroid adenoma - classically have a rim of normal parathyroid gland around it.
Parathyroid adenoma
Main article: Parathyroid adenoma
Parathyroid carcinoma
General
- Extremely rare.
Microscopic
Features:[25]
- Histologically normal parathyroid cells.
- Cytologic features not reliable for diagnosis.
- Fibrous capsule.
- Invasion of surrounding tissue - key feature.
- +/-Metastasis - diagnostic feature.
Note:
- Diagnosis of parathyroid carcinoma is like that of malignant pheochromocytoma - cytology useless, tissue invasion and metastases are the key features.
Image:
IHC
- Ki-67 >6% of cells positive - supports diagnosis.[26]
- Parathyroid adenomas and hyperplasias ~ 3%.
See also
References
- ↑ 1.0 1.1 URL: http://emedicine.medscape.com/article/127351-overview. Accessed on: 24 January 2013.
- ↑ URL: http://emedicine.medscape.com/article/127351-overview#aw2aab6b5. Accessed on: 24 January 2013.
- ↑ URL: http://emedicine.medscape.com/article/127351-overview#aw2aab6b6. Accessed on: 24 January 2013.
- ↑ Shiau, Carolyn; Toren, Andrew (2006). Toronto Notes 2006: Comprehensive Medical Reference (Review for MCCQE 1 and USMLE Step 2) (22nd edition (2006) ed.). Toronto Notes for Medical Students, Inc.. pp. Emerg.. ISBN 978-0968592861.
- ↑ 5.0 5.1 Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson; Aster, Jon (2009). Robbins and Cotran pathologic basis of disease (8th ed.). Elsevier Saunders. pp. 1129. ISBN 978-1416031215.
Cite error: Invalid
<ref>tag; name "Ref_PBoD8_1129" defined multiple times with different content - ↑ Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson; Aster, Jon (2009). Robbins and Cotran pathologic basis of disease (8th ed.). Elsevier Saunders. pp. 1127. ISBN 978-1416031215.
- ↑ Online 'Mendelian Inheritance in Man' (OMIM) 601199
- ↑ Lienert, D.; Rege, S. (Feb 2008). "Moans, stones, groans, bones and psychiatric overtones: lithium-induced hyperparathyroidism.". Aust N Z J Psychiatry 42 (2): 171-3. PMID 18350681.
- ↑ URL: http://www.usmleforum.com/files/forum/2010/1/505388.php. Accessed on: 4 December 2011.
- ↑ França, TC.; Griz, L.; Pinho, J.; Diniz, ET.; Andrade, LD.; Lucena, CS.; Beserra, SR.; Asano, NM. et al. (Apr 2011). "Bisphosphonates can reduce bone hunger after parathyroidectomy in patients with primary hyperparathyroidism and osteitis fibrosa cystica.". Rev Bras Reumatol 51 (2): 131-7. PMID 21584419.
- ↑ Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson; Aster, Jon (2009). Robbins and Cotran pathologic basis of disease (8th ed.). Elsevier Saunders. pp. 1130. ISBN 978-1416031215.
- ↑ Deroux, A.; Khouri, C.; Chabre, O.; Bouillet, L.; Casez, O. (Oct 2014). "Severe acute neurological symptoms related to proton pump inhibitors induced hypomagnesemia responsible for profound hypoparathyroidism with hypocalcemia.". Clin Res Hepatol Gastroenterol 38 (5): e103-5. doi:10.1016/j.clinre.2014.03.005. PMID 24736034.
- ↑ Toh, JW.; Ong, E.; Wilson, R. (Aug 2014). "Hypomagnesaemia associated with long-term use of proton pump inhibitors.". Gastroenterol Rep (Oxf). doi:10.1093/gastro/gou054. PMID 25138239.
- ↑ http://www.medicalhistology.us/twiki/pub/Main/ChapterFourteenSlides/b56b_parathyroid_40x_he_labeled.jpg
- ↑ http://pathology.mc.duke.edu/research/Histo_course/parathyroid2.jpg
- ↑ http://www.bu.edu/histology/p/15002loa.htm
- ↑ http://dictionary.reference.com/search?q=oxyphil%20cell
- ↑ Iwasaki, A.; Shan, L.; Kawano, I.; Nakamura, M.; Utsuno, H.; Kobayashi, A.; Kuma, K.; Kakudo, K. (Jul 1995). "Quantitative analysis of stromal fat content of human parathyroid glands associated with thyroid diseases using computer image analysis.". Pathol Int 45 (7): 483-6. PMID 7551007.
- ↑ http://www.deltagen.com/target/histologyatlas/atlas_files/endocrine/parathyroid_and_thyroid_glands_20x.jpg
- ↑ http://instruction.cvhs.okstate.edu/Histology/HistologyReference/hrendo.htm
- ↑ Johnson, SJ.; Sheffield, EA.; McNicol, AM. (Apr 2005). "Best practice no 183. Examination of parathyroid gland specimens.". J Clin Pathol 58 (4): 338-42. doi:10.1136/jcp.2002.002550. PMC 1770637. PMID 15790694. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1770637/.
- ↑ URL: http://www.pathconsultddx.com/pathCon/diagnosis?pii=S1559-8675%2806%2970475-2. Accessed on: 29 July 2010.
- ↑ 23.0 23.1 Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson; Aster, Jon (2009). Robbins and Cotran pathologic basis of disease (8th ed.). Elsevier Saunders. pp. 1128. ISBN 978-1416031215.
- ↑ Taxy, J.; Husain, A; Montag, A. (2009). Biopsy Interpretation: The Frozen Section (1st ed.). Lippincott Williams & Wilkins. pp. 191. ISBN 978-0781767798.
- ↑ Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson; Aster, Jon (2009). Robbins and Cotran pathologic basis of disease (8th ed.). Elsevier Saunders. pp. 1128. ISBN 978-1416031215.
- ↑ Abbona, GC.; Papotti, M.; Gasparri, G.; Bussolati, G. (Feb 1995). "Proliferative activity in parathyroid tumors as detected by Ki-67 immunostaining.". Hum Pathol 26 (2): 135-8. PMID 7860042.