Hyperparathyroidism 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
There are three types of hyperparathyroidism (primary, secondary, and tertiary) and should be differentiated between each other. Hyperparathyroidism should be differentiated from other causes of hypercalcemia. Causes of hypercalcemia other than hyperparathyroidism include familial hypocalciuric hypercalcemia, hypercalcemia related to malignancy, medication-induced hypercalcemia, hypercalcemia due to nutritional disorders, and hypercalcemia related to granulomatous diseases.
Differentiating hyperparathyroidism from other diseases
There are three types of hyperparathyroidism (primary, secondary, and tertiary) and should be differentiated between each other. Hyperparathyroidism should be differentiated from other causes of hypercalcemia. Causes of hypercalcemia include:
- Parathyroid related
- Hyperparathyroidism
- Primary hyperparathyroidism
- Secondary hyperparathyroidism
- Tertiary hyperparathyroidism
- Familial hypocalciuric hypercalcemia
- Hyperparathyroidism
- Non-parathyroid related
- Malignancy
- Humoral hypercalcemia of malignancy
- Osteolytic tumors
- Production of calcitriol by tumors
- Ectopic parathyroid hormone production
- Medication-induced
- Nutritional
- Granulomatous disease
- Surgical
- Immobilization
- Malignancy
Differential diagnosis of hyperparathyroidism on the basis of hypercalcemia | ||||||||
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Disorder | Mechanism of hypercalcemia | Clinical features | Laboratory findings | Imaging & diagnostic modalities | ||||
PTH | Calcium | Phosphate | Other findings | |||||
Hyperparathyroidism | Primary hyperparathyroidism | Increase in secretion of parathyroid hormone (PTH) from a primary process in parathyroid gland. Parathyroid hormone causes increase in serum calcium. |
|
↑ | ↑ | ↓/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. |
|
↑ | ↓/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. |
|
Normal/↑ | Normal/↑ | -- |
| ||
Malignancy[1] | Humoral hypercalcemia of malignancy[2][3][4] | Tumor cells secretes parathyroid hormone related protein (PTHrP) which has similar action as parathyroid hormone. |
|
-- | ↑ | ↓/Normal | ↑ PTHrP
Normal/↑ calcitriol |
|
Osteolytic tumors | Multiple myeloma produces osteolysis of bones causing hypercalcemia. Osteolytic metastasis can cause bone resorption causing hypercalcemia. |
|
↓ | ↑ | -- | -- |
| |
Production of calcitirol | 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[5] | Some tumors leads to ectopic production of parathyroid hormone. |
|
↑ | ↑ | ↓/Normal | Normal/↑ Calcitriol |
| |
Medication induced | Lithium[6] | Lithium lowers urinary calcium and causes hypercalcemia. Lithium has been reported to cause an increase in parathyroid hormones and enlargement if parathyroid gland after weeks to months of therapy. |
|
↑ | ↑ | -- | -- |
|
Thiazide diuretics | Thiazide diuretics lowers urinary calcium excretion and causes hypercalcemia. |
|
-- | ↑ | -- | -- | -- | |
Nutritional | Milk-alkali syndrome | Hypercalcemia is be caused by high intake of calcium carbonate. |
|
-- | ↑ | -- | -- |
|
Vitamin D toxicity | Excess vitamin D causes increased absorption of calcium from intestine causing hypercalcemia. | -- | ↑ | -- | ↑ Vitamin D (calcidiol and/or calcitriol) | -- | ||
Granulomatous disease | Sarcoidosis[9] | Hypercalcemia is causes by endogeous production of calcitriol by disease-activated macrophages. |
|
-- | ↑ | -- | ↑ Calcitriol
↑ ACE levels |
|
References
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.