Parathyroid glands

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Micrograph of a parathyroid gland. H&E stain.

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

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.

Parathyroid Gland, Excision:
- Chief cell parathyroid adenoma with adjacent normal parathyroid tissue.

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

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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