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.

Clinical

Hyperparathyroidism

Classification

  • Primary.
  • Secondary.
  • Tertiary.

Hypercalcemia DDx

Mnemonic GRIMED:[1]

  • 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.[2]
    • Other causes are assoc. with a decreased PTH.

Primary hyperparathyroidism

Cause:[3]

Familial causes of primary hyperparathyroidism:

  • MEN 1.
  • MEN 2.
  • Familial hypocalciuric hypercalcemia.
    • Autosomal dominant.
    • CASR (calcium sensing receptor) gene defect.[4]

Classic manifestations moans, stones, bones, (abdominal) groans, psychiatric overtones.[5][6]

  • Moans = bone pain.
  • Stones = nephrolithiasis (kidney stones).
  • Bones = bone pathology, e.g. osteitis fibrosa cystica.[7]
  • 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.[2]

Other causes:[8]

  • Autoimmune hypoparathyroidism.
  • Autosomal dominat hypoparathyroidism.
  • Familial isolated hypoparathyroidism.
  • Congenital absence (DiGeorge syndrome).

Normal parathyroid glands

General

  • Identification of normal can be tricky.

Gross

  • No distinctive features - surgeons thus send 'em to pathologists.

Microscopic

Features:[9]

  • 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[10] - key feature.
    • Surrounded by a thin fibrous capsule.
  • High power:
    • Mixed cell population:[11]
      • Chief cells - predominant cell type, small, cytoplasm has variable staining (hyperchromatic-clear-eosinophilic).
      • Oxyphil cells (acid staining cells[12]) - abundant cytoplasm.
      • Adipocytes - increased with age, may be used to help differentiate from thyroid - key feature.


Name Staining (cytoplasm) Quantity of cells Cytoplasm (quantity) Function
(parathyroid) chief cells intense hyperchromatic to eosinophilic (see note) abundant moderate manufacture PTH
oxyphil cells moderate/light hyperchromatic to eosinophilic rare abundant ?

Notes:

  • Cytoplasmic staining varies considerably on H&E preparations - it may vary from hyperchromatic[13] to clear to eosinophilic[14].
  • Chief cells tend to stain more intensely than oxyphil cells.

Thyroid vs. parathyroid (see: parathyroid image):

  • Parathyroid cytoplasm:
    • Hyperchromatic.

Parathyroid vs. lymphoid tissue (see parathyroid image):

  • Parathyroid:
    • No germinal centres.
    • Gland-like/follicular-like arrangement -- much smaller than normal follicles of
    • Occasional cell with rim of clear cytoplasm (oxyphil?).

Images:

Specific entities

Parathyroid hyperplasia

General

  • Chief cell hyperplasia - associated with MEN 1, MEN 2A.[15]
  • Parathyroid hyperplasia - classically assoc. with renal failure.
  • Classically all parathyroid glands are involved; however, some may be spared making it difficult to differentiate this from parathyroid adenoma.[16]

Microscopic

Features:[16]

  • Similar to parathyroid adenoma.
  • +/-Water-clear cells ("water-clear cell hyperplasia").

Parathyroid adenoma

General

  • One parathyroid is big... the others are small.
  • Associated with MEN I and MEN IIa/b (II/III).

MEN I:

MEN IIa/IIb (II/III):

Image: Parathyroid adenoma (med.utah.edu).[17]

Microscopic

Chief cell adenoma

Features:[3]

  • Chief cells:
    • Small central nucleus.
    • Moderate cytoplasm.
  • +/-Scattered oxyphil cells:
    • Large cells.
    • Abundant cytoplasm.

Image:

Oxyphil adenoma

Features:[3]

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

DDx:

Parathyroid carcinoma

General

  • Extremely rare.

Microscopic

Features:[18]

  • 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:

See also

References

  1. ↑ TN06 Emerg.
  2. ↑ 2.0 2.1 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
  3. ↑ 3.0 3.1 3.2 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.
  4. ↑ Online 'Mendelian Inheritance in Man' (OMIM) 601199
  5. ↑ 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.
  6. ↑ URL: http://www.usmleforum.com/files/forum/2010/1/505388.php. Accessed on: 4 December 2011.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ http://www.medicalhistology.us/twiki/pub/Main/ChapterFourteenSlides/b56b_parathyroid_40x_he_labeled.jpg
  10. ↑ http://pathology.mc.duke.edu/research/Histo_course/parathyroid2.jpg
  11. ↑ http://www.bu.edu/histology/p/15002loa.htm
  12. ↑ http://dictionary.reference.com/search?q=oxyphil%20cell
  13. ↑ http://www.deltagen.com/target/histologyatlas/atlas_files/endocrine/parathyroid_and_thyroid_glands_20x.jpg
  14. ↑ http://instruction.cvhs.okstate.edu/Histology/HistologyReference/hrendo.htm
  15. ↑ URL: http://www.pathconsultddx.com/pathCon/diagnosis?pii=S1559-8675%2806%2970475-2. Accessed on: 29 July 2010.
  16. ↑ 16.0 16.1 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.
  17. ↑ URL: http://library.med.utah.edu/WebPath/EXAM/IMGQUIZ/enfrm.html. Accessed on: 6 December 2010.
  18. ↑ 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.
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