Parathyroid glands

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The parathyroid glands are an endocrine organ that is important in calcium regulation. They often make an appearance in the context of thyroid surgery.

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]

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]

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.
  • 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.

Images

  • Parathyroid gland - intermed. mag. (WC)

  • Parathyroid gland - cropped - high mag. (WC)

  • Parathyroid gland - high mag. (WC)

www:

Parathyroid cell types

Name Staining (cytoplasm) Quantity of cells Cytoplasm (quantity) Function
(parathyroid) chief cells intense hyperchromatic to eosinophilic (see note) abundant moderate manufacture parathyroid
hormone (PTH)
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:

DDx:

Parathyroid adenoma

General

  • One parathyroid is big... the others are small.
  • Associated with MEN 1 and MEN 2A.

MEN 1:

MEN 2A:

Subtypes

Histologic subtyping:[25]

  1. Chief cell parathyroid adenoma.
    • Common.
  2. Oxyphil parathyroid adenoma.
  3. Mixed.

Microscopic

Features - general:

  • Classically have a rim of normal parathyroid gland around it.[24]

Note:

Chief cell parathyroid adenoma

Features:[6]

  • Chief cells - key feature:
    • Small central nucleus.
      • Round with stippled chromatin - important.
    • Moderate cytoplasm.
  • +/-Scattered oxyphil cells:
    • Large cells.
    • Abundant cytoplasm.
  • Architecture:
    • Nests.
    • Circular formations - often around capillaries (perivascular pseudorosettes).
Images

  • Parathyroid adenoma - low mag. (WC/Nephron)

  • Parathyroid adenoma - high mag. (WC/Nephron)

Oxyphil parathyroid adenoma

Features:[6]

  • Oxyphil cells:
    • Large cells.
    • Abundant cytoplasm.

DDx:

Image:

Sign out

Note:

  • One should not say "negative for malignancy".
Parathyroid Gland, Excision:
- Chief cell parathyroid adenoma with adjacent normal parathyroid.

Parathyroid Gland (Submitted as "Right Superior Parathyroid Adenoma"), Excision:
- Parathyroid adenoma with adjacent normal parathyroid.

Block letters

PARATHRYOID GLAND, EXCISION:
- CHIEF CELL PARATHYROID ADENOMA.

Micro

The section shows an adenoma consisting predominantly of chief cells. A rim of normal parathyroid is seen adjacent to the adenoma. A small amount of unremarkable adipose tissue is present.

Parathyroid carcinoma

General

  • Extremely rare.

Microscopic

Features:[28]

  • 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.[29]
    • Parathyroid adenomas and hyperplasias ~ 3%.

See also

References

  1. ↑ 1.0 1.1 URL: http://emedicine.medscape.com/article/127351-overview. Accessed on: 24 January 2013.
  2. ↑ URL: http://emedicine.medscape.com/article/127351-overview#aw2aab6b5. Accessed on: 24 January 2013.
  3. ↑ URL: http://emedicine.medscape.com/article/127351-overview#aw2aab6b6. Accessed on: 24 January 2013.
  4. ↑ 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. ↑ 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
  6. ↑ 6.0 6.1 6.2 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.
  7. ↑ Online 'Mendelian Inheritance in Man' (OMIM) 601199
  8. ↑ 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.
  9. ↑ URL: http://www.usmleforum.com/files/forum/2010/1/505388.php. Accessed on: 4 December 2011.
  10. ↑ 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.
  11. ↑ 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.
  12. ↑ 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.
  13. ↑ 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.
  14. ↑ http://www.medicalhistology.us/twiki/pub/Main/ChapterFourteenSlides/b56b_parathyroid_40x_he_labeled.jpg
  15. ↑ http://pathology.mc.duke.edu/research/Histo_course/parathyroid2.jpg
  16. ↑ http://www.bu.edu/histology/p/15002loa.htm
  17. ↑ http://dictionary.reference.com/search?q=oxyphil%20cell
  18. ↑ 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.
  19. ↑ http://www.deltagen.com/target/histologyatlas/atlas_files/endocrine/parathyroid_and_thyroid_glands_20x.jpg
  20. ↑ http://instruction.cvhs.okstate.edu/Histology/HistologyReference/hrendo.htm
  21. ↑ 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/.
  22. ↑ URL: http://www.pathconsultddx.com/pathCon/diagnosis?pii=S1559-8675%2806%2970475-2. Accessed on: 29 July 2010.
  23. ↑ 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.
  24. ↑ 24.0 24.1 24.2 Taxy, J.; Husain, A; Montag, A. (2009). Biopsy Interpretation: The Frozen Section (1st ed.). Lippincott Williams & Wilkins. pp. 191. ISBN 978-0781767798.
  25. ↑ Moran, CA.; Suster, S. (Nov 2005). "Primary parathyroid tumors of the mediastinum: a clinicopathologic and immunohistochemical study of 17 cases.". Am J Clin Pathol 124 (5): 749-54. doi:10.1309/WJEL-N05L-9A06-9DU0. PMID 16203274.
  26. ↑ Fleischer, J.; Becker, C.; Hamele-Bena, D.; Breen, TL.; Silverberg, SJ. (Dec 2004). "Oxyphil parathyroid adenoma: a malignant presentation of a benign disease.". J Clin Endocrinol Metab 89 (12): 5948-51. doi:10.1210/jc.2004-1597. PMID 15579742.
  27. ↑ URL: http://library.med.utah.edu/WebPath/EXAM/IMGQUIZ/enfrm.html. Accessed on: 6 December 2010.
  28. ↑ 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.
  29. ↑ 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.
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