Parathyroid adenoma differential diagnosis

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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]

Overview

Differential Diagnosis

Differential diagnosis of parathyroid adenoma on the basis of hypercalcemia
Disorder Mechanism of hypercalcemia Clinical features Laboratory findings Imaging & diagnostic modalities
PTH Calcium Phosphate Other findings
Primary hyperparathyroidism (Parathyroid adenoma) Increase in secretion of parathyroid hormone (PTH) from a primary process in parathyroid gland. Parathyroid hormone causes increase in serum calcium.
  • Usually asymptomatic
  • Hypercalcemia detected on routine biochemical panel
 ↑ ↑ ↓/Normal Normal/↑ calcitriol Findings of bone resorption:

Preoperative localization of hyperfunctioning parathyroid gland:

Predicting post-operative success:

Secondary hyperparathyroidism Increase in secretion of parathyroid hormone (PTH) from a secondary process. Parathyroid hormone causes increase in serum calcium after long periods. ↑ ↓/Normal ↑ --
Tertiary hyperparathyroidism Continuous elevation of parathyroid hormone (PTH) even after successful treatment of the secondary cause of elevated parathyroid hormone. Parathyroid hormone causes increase in serum calcium. ↑ ↑ ↑ --
Familial hypocalciuric hypercalcemia This is a genetic disorder caused my mutation in calcium-sensing receptor gene.
  • A benign condition
  • Does not require treatment
 Normal/↑ Normal/↑ -- --
  • Urinary calcium/creatinine clearance ratio
Malignancy[1][2] Humoral hypercalcemia of malignancy[3][4][5][6] Tumor cells secretes parathyroid hormone-related protein (PTHrP) which has similar action as parathyroid hormone. -- ↑ ↓/Normal ↑ PTHrP

Normal/↑ calcitriol

Osteolytic tumors[7][8] Multiple myeloma produces osteolysis of bones causing hypercalcemia. Osteolytic metasteses can cause bone resorption causing hypercalcemia. ↓ ↑ -- --
Production of calcitirol[9] Some tumors has ectopic activity of 1-alpha-hydroxylase leading to increased production of calcitriol. Calcitriol is active form of vitamin D and causes hypercalcemia. -- ↑ -- ↑ Calcitriol
Ectopic parathyroid hormone[10] Some tumors leads to ectopic production of parathyroid hormone. ↑ ↑ ↓/Normal Normal/↑ calcitriol
Medication induced Lithium[11] Lithium lowers urinary calcium and causes hypercalcemia. Lithium has been reported to cause an increase in parathyroid hormone and enlargement if parathyroid gland after weeks to months of therapy. ↑ ↑ -- --
Thiazide diuretics[12] Thiazide diuretics lowers urinary calcium excretion and causes hypercalcemia. -- ↑ -- -- --
Nutritional Milk-alkali syndrome Hypercalcemia is be caused by high intake of calcium carbonate. -- ↑ -- ↓ calcitriol
Vitamin D toxicity[13][14][15] Excess vitamin D causes increased absorption of calcium from intestine causing hypercalcemia. -- ↑ -- ↑ Vitamin D (calcidiol and/or calcitriol) --
Granulomatous disease Sarcoidosis[18] Hypercalcemia is causes by endogeous production of calcitriol by disease-activated macrophages. -- ↑ -- ↑ Calcitriol

↑ ACE levels

References

  1. ↑ Mirrakhimov AE (2015). "Hypercalcemia of Malignancy: An Update on Pathogenesis and Management". N Am J Med Sci. 7 (11): 483–93. doi:10.4103/1947-2714.170600. PMC 4683803. PMID 26713296.
  2. ↑ Stewart AF (2005). "Clinical practice. Hypercalcemia associated with cancer". N Engl J Med. 352 (4): 373–9. doi:10.1056/NEJMcp042806. PMID 15673803.
  3. ↑ Ratcliffe WA, Hutchesson AC, Bundred NJ, Ratcliffe JG (1992). "Role of assays for parathyroid-hormone-related protein in investigation of hypercalcaemia". Lancet. 339 (8786): 164–7. doi:10.1016/0140-6736(92)90220-W. PMID 1346019.
  4. ↑ Ikeda K, Ohno H, Hane M, Yokoi H, Okada M, Honma T, Yamada A, Tatsumi Y, Tanaka T, Saitoh T (1994). "Development of a sensitive two-site immunoradiometric assay for parathyroid hormone-related peptide: evidence for elevated levels in plasma from patients with adult T-cell leukemia/lymphoma and B-cell lymphoma". J. Clin. Endocrinol. Metab. 79 (5): 1322–7. doi:10.1210/jcem.79.5.7962324. PMID 7962324.
  5. ↑ Horwitz MJ, Tedesco MB, Sereika SM, Hollis BW, Garcia-Ocaña A, Stewart AF (2003). "Direct comparison of sustained infusion of human parathyroid hormone-related protein-(1-36) [hPTHrP-(1-36)] versus hPTH-(1-34) on serum calcium, plasma 1,25-dihydroxyvitamin D concentrations, and fractional calcium excretion in healthy human volunteers". J. Clin. Endocrinol. Metab. 88 (4): 1603–9. doi:10.1210/jc.2002-020773. PMID 12679445.
  6. ↑ Stewart AF, Vignery A, Silverglate A, Ravin ND, LiVolsi V, Broadus AE; et al. (1982). "Quantitative bone histomorphometry in humoral hypercalcemia of malignancy: uncoupling of bone cell activity". J Clin Endocrinol Metab. 55 (2): 219–27. doi:10.1210/jcem-55-2-219. PMID 7085851.
  7. ↑ Roodman GD (2004). "Mechanisms of bone metastasis". N Engl J Med. 350 (16): 1655–64. doi:10.1056/NEJMra030831. PMID 15084698.
  8. ↑ Guise TA, Yin JJ, Taylor SD, Kumagai Y, Dallas M, Boyce BF; et al. (1996). "Evidence for a causal role of parathyroid hormone-related protein in the pathogenesis of human breast cancer-mediated osteolysis". J Clin Invest. 98 (7): 1544–9. doi:10.1172/JCI118947. PMC 507586. PMID 8833902.
  9. ↑ Seymour JF, Gagel RF, Hagemeister FB, Dimopoulos MA, Cabanillas F (1994). "Calcitriol production in hypercalcemic and normocalcemic patients with non-Hodgkin lymphoma". Ann Intern Med. 121 (9): 633–40. PMID 7944070.
  10. ↑ VanHouten JN, Yu N, Rimm D, Dotto J, Arnold A, Wysolmerski JJ, Udelsman R (2006). "Hypercalcemia of malignancy due to ectopic transactivation of the parathyroid hormone gene". J. Clin. Endocrinol. Metab. 91 (2): 580–3. doi:10.1210/jc.2005-2095. PMID 16263810.
  11. ↑ Mallette LE, Khouri K, Zengotita H, Hollis BW, Malini S (1989). "Lithium treatment increases intact and midregion parathyroid hormone and parathyroid volume". J. Clin. Endocrinol. Metab. 68 (3): 654–60. doi:10.1210/jcem-68-3-654. PMID 2918061.
  12. ↑ Griebeler ML, Kearns AE, Ryu E, Thapa P, Hathcock MA, Melton LJ; et al. (2016). "Thiazide-Associated Hypercalcemia: Incidence and Association With Primary Hyperparathyroidism Over Two Decades". J Clin Endocrinol Metab. 101 (3): 1166–73. doi:10.1210/jc.2015-3964. PMC 4803175. PMID 26751196.
  13. ↑ Hoeck HC, Laurberg G, Laurberg P (1994). "Hypercalcaemic crisis after excessive topical use of a vitamin D derivative". J. Intern. Med. 235 (3): 281–2. PMID 8120527.
  14. ↑ Jacobus CH, Holick MF, Shao Q, Chen TC, Holm IA, Kolodny JM, Fuleihan GE, Seely EW (1992). "Hypervitaminosis D associated with drinking milk". N. Engl. J. Med. 326 (18): 1173–7. doi:10.1056/NEJM199204303261801. PMID 1313547.
  15. ↑ Sharma OP (1996). "Vitamin D, calcium, and sarcoidosis". Chest. 109 (2): 535–9. PMID 8620732.
  16. ↑ Jacobus CH, Holick MF, Shao Q, Chen TC, Holm IA, Kolodny JM, Fuleihan GE, Seely EW (1992). "Hypervitaminosis D associated with drinking milk". N. Engl. J. Med. 326 (18): 1173–7. doi:10.1056/NEJM199204303261801. PMID 1313547.
  17. ↑ Hoeck HC, Laurberg G, Laurberg P (1994). "Hypercalcaemic crisis after excessive topical use of a vitamin D derivative". J. Intern. Med. 235 (3): 281–2. PMID 8120527.
  18. ↑ Dusso AS, Kamimura S, Gallieni M, Zhong M, Negrea L, Shapiro S, Slatopolsky E (1997). "gamma-Interferon-induced resistance to 1,25-(OH)2 D3 in human monocytes and macrophages: a mechanism for the hypercalcemia of various granulomatoses". J. Clin. Endocrinol. Metab. 82 (7): 2222–32. doi:10.1210/jcem.82.7.4074. PMID 9215298.
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