Sandbox : anmol
|
Hyperparathyroidism Microchapters |
|
Diagnosis |
|---|
|
Treatment |
|
Case Studies |
|
Sandbox : anmol On the Web |
|
American Roentgen Ray Society Images of Sandbox : anmol |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Anmol Pitliya, M.B.B.S. M.D.[2]
Classification
| Classification of hyperparathyridism | |||
|---|---|---|---|
| Features | Primary hyperparathyroidism | Secondary hyperparathyroidism | Tertiary hyperparathyroidism |
| Pathology | Hyperfunction of parathyroid cells due to hyperplasia, adenoma or carcinoma. | Physiological stimulation of parathyroid in response to hypocalcaemia. | Following long term physiological stimulation leading to hyperplasia. |
| Cause | |||
| Associations | May be associated with multiple endocrine neoplasia. | Usually due to chronic renal failure or other causes of Vitamin D deficiency. | Seen in chronic renal failure. |
| Serum calcium | High | Low/Normal | High |
| Serum phosphate | Low/Normal | High | High |
| Management | Usually surgery if symptomatic. Cincacalcet can be considered in those not fit for surgery. | Treatment of underlying cause. | Usually cinacalcet or surgery in those that don't respond. |
Causes
Genetic causes
- HRPT2 gene mutations:[1]
- HRPT2 gene code for parafibromin protein.
- HRPT2 gene mutations are found in a type of familial hyperparathyroidism, hyperparathyroidism-jaw tumor (HPT-JT) syndrome.
- HRTP2 gene mutations increases risk of parathyroid carcinoma.
- Cyclin D1 gene (CCND1)/PRAD1 gene:[2][3]
- PRAD1 (parathyroid adenoma 1) is a protooncogene located on chromosome 11q13.
- Cyclin D1 gene translocation and oncogene action observerd in 8% of adenomas
- Cyclin D1 gene overexpression is pbserved in 20% to 40% of parathyroid adenomas
- MEN1 gene:[2][4]
- MEN1 is a tumor supressor gene on chronosome 11q13.
- Somatic loss of single MEN1 allele is observed in 25% to 40% of sporadic parathyroid adenomas.
Pathogenesis
Associated conditions
ECG
X-ray
CT scan
MRI
Ultrasound
TC-99m Sestamibi Scintigraphy
SPECT
PET
- 11C-methionine PET along with CT scan (MET-PET/CT) may be used for preoperative localization of hyper-functioning gland.[5][6]
- MET-PET/CT may be used as an complimentary imaging modality for localizing hyper-functioning parathyroid glands in patients with negative Tc-99m sestamibi scintigraphy/SPECT results.[7]
DXA
- Low bone mineral density (BMD) is caused by primary hyperparathyroidism. Distal forearm is affected most commonly.
- DXA of distal forearm should be done in all patients of primary hyperparathyroidism. Worst T-score of distal forearm is observed in patients with primary hyperparathyroidism.[8]
Other diagnostic studies
Intraoperative parathyroid hormone (IOPTH)
- Measurement of intraoperative parathyroid hormone (IOPTH) by using a modified sensitive assay (immunoradiometric assay) is beneficial for long term surgical outcomes.Post-surgical success is defined as postoperative normocalcemia.
- Patients with hyperparathyroidism due to lesion in a single gland shows a rapid decline of intact parathyroid hormone. The levels of intact parathyroid hormone reached to indetectable levels within hours of resection.[9]
- After resection of parathyroid adenoma, intact parathyroid hormone levels decrease by 85% is observed in first 15 minutes. This fall in parathyroid hormone levels is due to short half-life of parathyroid hormone.[10]
- The fall in parathyroid hormone level is significantly more after resection of parathyroid adenoma than after resection of parathyroid hyperplasia.
- A fall in level of parathyroid hormone 15 minutes after resection of hyper-functioning parathyroid glands may help differentiating sigle gland disease from multi gland disease.[11][12]
- IOPTH monitoring has a predictive accuracy of 97%. [13]
Technique for intraoperative parathyroid hormone (IOPTH) monitoring
- When the enlarged parathyroid gland is first visualized intraoperatively, the baseline sample should be obtained.[14]
- The baseline samples should never be obtained before induction of anesthesia. It is due to the fact that an increase in parathyroid hormone level may be observed after general anesthesia.
- After excision of enlarged gland, 2nd and 3rd samples are collected at 5 and 10 minutes respectively.
- Several criteria are used for predicting post-operative normocalcemia including:
- A decline in parathyroid hormone levels of ≥60% from baseline value at 15 minutes.
- A decline in parathyroid hormone levels of ≥50% from baseline value at 10 minutes.
Super Selective Venous Sampling
Selective arteriography
- Selective transarterial hypocalcemic stimulation is combined with nonselective venous sampling to perform selective arteriography.[15]
- Sodium citrate is injected to induce hypocalcemia. Simultaneous arteriography is performed.
- Samples are taken for superior vena cava at basaeline and timed intervals (20 sec, 40 sec, and 60 sec).
- An increase in the parathyroid hormone level to 1.4 times above the baseline or a clear blush observed on arteriography is considered as positive localization.
- Arterial stimulation venous sampling is performed simultaneously with arteriogram due to similarly high PPV.
Angiography
- Superselective arterial digital subtraction angiography (DSA) and superselective conventional angiography (CA) may be used for preoperative localization of hyper-functioning parathyroid glands in which noninvasive imaging modalities are negative or inconclusive.[16]
- Sensitivity of superselective digital subtraction angiography appears to be similar to conventional angiography.
- Superselective arterial digital subtraction angiography may be more sensitive than conventional angiography for preoperative localization of mediastinal hyper-functioning parathyroid glands.
References
- ↑ Shattuck TM, Välimäki S, Obara T, Gaz RD, Clark OH, Shoback D; et al. (2003). "Somatic and germ-line mutations of the HRPT2 gene in sporadic parathyroid carcinoma". N Engl J Med. 349 (18): 1722–9. doi:10.1056/NEJMoa031237. PMID 14585940.
- ↑ 2.0 2.1 Westin G, Björklund P, Akerström G (2009). "Molecular genetics of parathyroid disease". World J Surg. 33 (11): 2224–33. doi:10.1007/s00268-009-0022-6. PMID 19373510.
- ↑ Hsi ED, Zukerberg LR, Yang WI, Arnold A (1996). "Cyclin D1/PRAD1 expression in parathyroid adenomas: an immunohistochemical study". J Clin Endocrinol Metab. 81 (5): 1736–9. doi:10.1210/jcem.81.5.8626826. PMID 8626826.
- ↑ Agarwal SK, Kester MB, Debelenko LV, Heppner C, Emmert-Buck MR, Skarulis MC; et al. (1997). "Germline mutations of the MEN1 gene in familial multiple endocrine neoplasia type 1 and related states". Hum Mol Genet. 6 (7): 1169–75. PMID 9215689.
- ↑ Tang BN, Moreno-Reyes R, Blocklet D, Corvilain B, Cappello M, Delpierre I; et al. (2008). "Accurate pre-operative localization of pathological parathyroid glands using 11C-methionine PET/CT". Contrast Media Mol Imaging. 3 (4): 157–63. doi:10.1002/cmmi.243. PMID 18781582.
- ↑ Weber T, Maier-Funk C, Ohlhauser D, Hillenbrand A, Cammerer G, Barth TF; et al. (2013). "Accurate preoperative localization of parathyroid adenomas with C-11 methionine PET/CT". Ann Surg. 257 (6): 1124–8. doi:10.1097/SLA.0b013e318289b345. PMID 23478517.
- ↑ Traub-Weidinger T, Mayerhoefer ME, Koperek O, Mitterhauser M, Duan H, Karanikas G; et al. (2014). "11C-methionine PET/CT imaging of 99mTc-MIBI-SPECT/CT-negative patients with primary hyperparathyroidism and previous neck surgery". J Clin Endocrinol Metab. 99 (11): 4199–205. doi:10.1210/jc.2014-1267. PMID 25029418.
- ↑ Wood K, Dhital S, Chen H, Sippel RS (2012). "What is the utility of distal forearm DXA in primary hyperparathyroidism?". Oncologist. 17 (3): 322–5. doi:10.1634/theoncologist.2011-0285. PMC 3316917. PMID 22258698.
- ↑ Nussbaum SR, Thompson AR, Hutcheson KA, Gaz RD, Wang CA (1988). "Intraoperative measurement of parathyroid hormone in the surgical management of hyperparathyroidism". Surgery. 104 (6): 1121–7. PMID 3194839.
- ↑ Bergenfelz A, Isaksson A, Ahrén B (1994). "Intraoperative monitoring of intact PTH during surgery for primary hyperparathyroidism". Langenbecks Arch Chir. 379 (1): 50–3. PMID 8145618.
- ↑ Irvin III, George L.; Dembrow, Victor D.; Prudhomme, David L. (December 1993). "Clinical usefulness of an intraoperative "quick parathyroid hormone" assay". Surgery. 114 (6): 1019–1023.
- ↑ Bergenfelz A, Isaksson A, Lindblom P, Westerdahl J, Tibblin S (1998). "Measurement of parathyroid hormone in patients with primary hyperparathyroidism undergoing first and reoperative surgery". Br J Surg. 85 (8): 1129–32. doi:10.1046/j.1365-2168.1998.00824.x. PMID 9718013.
- ↑ Boggs JE, Irvin GL, Molinari AS, Deriso GT (1996). "Intraoperative parathyroid hormone monitoring as an adjunct to parathyroidectomy" (PDF). Surgery. 120 (6): 954–8. doi:10.1016/S0039-6060(96)80040-7. PMID 8957480.
- ↑ Westerdahl J, Lindblom P, Bergenfelz A (2002). "Measurement of intraoperative parathyroid hormone predicts long-term operative success". Arch Surg. 137 (2): 186–90. doi:10.1001/archsurg.137.2.186. PMID 11822958.
- ↑ Powell AC, Alexander HR, Chang R, Marx SJ, Skarulis M, Pingpank JF; et al. (2009). "Reoperation for parathyroid adenoma: a contemporary experience". Surgery. 146 (6): 1144–55. doi:10.1016/j.surg.2009.09.015. PMC 3467310. PMID 19958942.
- ↑ Miller DL, Chang R, Doppman JL, Norton JA (1989). "Localization of parathyroid adenomas: superselective arterial DSA versus superselective conventional angiography". Radiology. 170 (3 Pt 2): 1003–6. doi:10.1148/radiology.170.3.2644666. PMID 2644666.