History

Fact Explanation
History of chronic kidney disease (CKD) [9] Stimuli for the development of secondary hyperparathyroidism would be elevated extracellular phosphate concentration, decreased ionized calcium concentration, and reduced serum calcitriol. Phosphate retention can occur in CKD patients together with impaired production of calcitriol. There can be resistance to the action of PTH in the bones. Decreased serum calcium is sensed by the parathyroid calcium receptors. [5] These factors can lead to hypersecretion of the parathyroid hormone by the parathyroid glands. There are evidence about fibroblast growth factor: that elevated FGF aggravates the deficiency of calcitriol, thus exacerbating the hyperparathyroidism. When the parathyroid stimulation occurs for a long time there can be hyperplasia of the parathyroid gland. [2]
Dietary vitamin D defeciency and rickets [7] Vitamin D is important in absorption of calcium from the gastrointestinal tract, tubular reabsorption of calcium and resorption of bone. Rickets is mainly due to lack of vitamin D and calcium. When the vitamin D is lacking, low calcium triggers parathyroid glands to increase the secretion of parathyroid hormone causing secondary hyperparathyroidism. They may have following features: weak tooth enamel with delay in tooth eruption and increased risk of cavities, pathological fractures, bone pain and poor growth. [7]
Renal colic [1] Hypersecreted parathyroid hormone acts on kidney, and reduce the excretion of calcium via urine. Increased calcium can precipitate as stones. [1] This nephrocalcinosis causes loin to groin pain. Most of them are calcium oxalate and occasionally calcium phosphate.
Skeletal problems [9] Renal osteodystrophy is the term used for the bone problems associated with chronic kidney disease. [6] Parathyroid hormone causes bone resorption, leading to abnormal bone mineralization, bone pain, pathological fractures and osteoporosis.
Skin pruritus [4] This may be due to calcium depositions in the skin. Secondary hyperparathyroidism developing in a patient with underlying chronic kidney disease, may exacerbate the pre existing itching due to uremia. [4]
Constipation, polyuria and polydypsia[2] Due to hypercalcaemia. [9] Hypercalcaemia can occur in severe disease.
Myopathy and muscle weakness [8] Neurological problems [8] can be occasionally associated with hyperparathyroidism.
Fatigue, shortness of breath, ankle swelling, facial puffiness There can be associated chronic kidney disease giving rise to complications [6] such as anaemia causing fatigue, shortness of breath etc, cardiovascular problems such as myocardial infarction, and peripheral oedema : ankle swelling, facial puffiness.
References
  1. ASSADI F. Hypercalcemia: an evidence-based approach to clinical cases. Iran J Kidney Dis [online] 2009 Apr, 3(2):71-9 [viewed 24 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/19395781
  2. CUNNINGHAM J., LOCATELLI F., RODRIGUEZ M.. Secondary Hyperparathyroidism: Pathogenesis, Disease Progression, and Therapeutic Options. Clinical Journal of the American Society of Nephrology [online] December, 6(4):913-921 [viewed 10 July 2014] Available from: doi:10.2215/​CJN.06040710
  3. EBERT EC. The parathyroids and the gut. J Clin Gastroenterol [online] 2010 Aug, 44(7):479-82 [viewed 24 June 2014] Available from: doi:10.1097/MCG.0b013e3181cd9d4c
  4. YONOVA D. Pruritus in certain internal diseases Hippokratia [online] 2007, 11(2):67-71 [viewed 11 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2464269
  5. RODRIGUEZ M.. The calcium-sensing receptor: a key factor in the pathogenesis of secondary hyperparathyroidism. AJP: Renal Physiology [online] 2004 September, 288(2):F253-F264 [viewed 10 July 2014] Available from: doi:10.1152/ajprenal.00302.2004
  6. SNIVELY CS, GUTIERREZ C. Chronic kidney disease: prevention and treatment of common complications. Am Fam Physician [online] 2004 Nov 15, 70(10):1921-8 [viewed 10 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/15571058
  7. HUGUENIN M, SCHACHT R, DAVID R. Infantile rickets with severe proximal renal tubular acidosis, responsive to vitamin D Arch Dis Child [online] 1974 Dec, 49(12):955-959 [viewed 11 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1649109
  8. ROY M, SAHANA PK, SENGUPTA N, DAS C, DASGUPTA R. An unusual case of episodic quadriparesis Indian J Endocrinol Metab [online] 2013 Oct, 17(Suppl1):S234-S236 [viewed 10 September 2014] Available from: doi:10.4103/2230-8210.119582
  9. BLOCK GA, MARTIN KJ, DE FRANCISCO AL, TURNER SA, AVRAM MM, SURANYI MG, HERCZ G, CUNNINGHAM J, ABU-ALFA AK, MESSA P, COYNE DW, LOCATELLI F, COHEN RM, EVENEPOEL P, MOE SM, FOURNIER A, BRAUN J, MCCARY LC, ZANI VJ, OLSON KA, DRüEKE TB, GOODMAN WG. Cinacalcet for secondary hyperparathyroidism in patients receiving hemodialysis. N Engl J Med [online] 2004 Apr 8, 350(15):1516-25 [viewed 10 September 2014] Available from: doi:10.1056/NEJMoa031633

Examination

Fact Explanation
Pallor Is seen in chronic kidney disease. Osteitis fibrosa in renal osteodystrophy [2] can aggravate the marrow fibrosis and worsen the anaemia.
Skin pigmentation, peripheral oedema Due to underlying chronic kidney disease. [2]
Features of rickets: Widening of wrist and ankle joint, [4] bowing of the legs, rickety rossery, curvature of the spine, softening of skull bones. Rickets can presents with secondary hyperparathyroidism. [4]
Arrhythmia [6] , features of heart failure: elevated jugular venous pressure. hepatomegally, peripheral oedema, fine end inspiratory bibasal crepitations Development of vascular calcification is is a complication of secondary hyperparathyroidism, due to the elevated levels of calcium and phosphorous. [5] Calcifications can affect the myocardium, the conduction system, and valves. Myocardial fibrosis can leads to left ventricular dysfunction.
Scratch marks Pruritus due to secondary hyperparathyroidism [3] and underlying chronic kidney disease.
References
  1. CUNNINGHAM J., LOCATELLI F., RODRIGUEZ M.. Secondary Hyperparathyroidism: Pathogenesis, Disease Progression, and Therapeutic Options. Clinical Journal of the American Society of Nephrology [online] December, 6(4):913-921 [viewed 10 July 2014] Available from: doi:10.2215/​CJN.06040710
  2. SNIVELY CS, GUTIERREZ C. Chronic kidney disease: prevention and treatment of common complications. Am Fam Physician [online] 2004 Nov 15, 70(10):1921-8 [viewed 10 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/15571058
  3. YONOVA D. Pruritus in certain internal diseases Hippokratia [online] 2007, 11(2):67-71 [viewed 11 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2464269
  4. JANCAR J. Rickets with Secondary Hyperparathyroidism in a Severely Subnormal Child Arch Dis Child [online] 1963 Aug, 38(200):412-414 [viewed 11 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2018945
  5. BLOCK GA, MARTIN KJ, DE FRANCISCO AL, TURNER SA, AVRAM MM, SURANYI MG, HERCZ G, CUNNINGHAM J, ABU-ALFA AK, MESSA P, COYNE DW, LOCATELLI F, COHEN RM, EVENEPOEL P, MOE SM, FOURNIER A, BRAUN J, MCCARY LC, ZANI VJ, OLSON KA, DRüEKE TB, GOODMAN WG. Cinacalcet for secondary hyperparathyroidism in patients receiving hemodialysis. N Engl J Med [online] 2004 Apr 8, 350(15):1516-25 [viewed 10 September 2014] Available from: doi:10.1056/NEJMoa031633
  6. RALSTON SH. Medical management of hypercalcaemia. Br J Clin Pharmacol [online] 1992 Jul, 34(1):11-20 [viewed 19 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1381369

Differential Diagnoses

Fact Explanation
Primary hyperparathyroidism [1] There is an autonomous production of parathyroid hormone by the parathyroid glands which leads to elevated serum parathyroid hormone and hypercalcemia/normocalcemia. Normocalcemic primary hyperparathyroidism is a variety that incidentally diagnosed with reduced bone mineral density. [2] They can also present with hypercalcaemic emergencies.
Tertiary hyperparathyroidism [4] This usually occurs after long-term history of secondary hyperparathyroidism as in the case of, chronic kidney disease, due to the hyperplasia of glands. [1] Gland will autonomously secrete parathyroid hormone after continuous stimulation. Calcium and parathyroid hormone level, both will be high as in primary hyperparathyroidism.
Familial hypocalciuric hypercalciuria [3] This is an autosomal dominant condition. The problem is in the calcium sensing receptors in the parathyroid glands. There will be low urinary calcium in 24h urine, and calcium/creatinine clearance ratio is decreased. [2] Secondary hyperparathyroidism also has low urinary calcium levels.
References
  1. PITT SUSAN C., PANNEERSELVAN RAJARAJAN, CHEN HERBERT, SIPPEL REBECCA S.. Secondary and Tertiary Hyperparathyroidism: The Utility of ioPTH Monitoring. World J Surg [online] December, 34(6):1343-1349 [viewed 25 June 2014] Available from: doi:10.1007/s0026
  2. MARTíNEZ CORDELLAT ISABEL. Hyperparathiroidism: Primary or Secondary Disease?. Reumatología Clínica (English Edition) [online] 2012 September, 8(5):287-291 [viewed 11 July 2014] Available from: doi:10.1016/j.reumae.2011.06.002
  3. AUWERX J, BRUNZELL J, BOUILLON R, DEMEDTS M. Familial hypocalciuric hypercalcaemia--familial benign hypercalcaemia: a review. Postgrad Med J [online] 1987 Oct, 63(744):835-840 [viewed 10 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2428623
  4. FRASER WD. Hyperparathyroidism. Lancet [online] 2009 Jul 11, 374(9684):145-58 [viewed 10 September 2014] Available from: doi:10.1016/S0140-6736(09)60507-9

Investigations - for Diagnosis

Fact Explanation
Serum parathyroid hormone level [7] Elevated PTH secondary hyperparathyroidism due to CKD, occurs during the early disease and signals the need for an intervention. [4] PTH level > 450 pg/dl is associated with advanced bone turnover. [4]
Serum calcium [6] Low-normal calcium is seen. But severe may have elevated serum calcium. [2]
Serum phosphate [6] High in real failure due to phosphate retention and low in vitamin D deficiency. [3]
Alkaline phosphate level May be high due to bone resorption. [6]
Vitamin D metabolite [7] Serum 25-hydroxyvitamin D levels should be measured and correction should be done in a deficiency[1].
X-ray[5] Bone resorption can be seen in several locations in the bones. Bone resorption, periosteal reaction, and brown tumors, osteoporosis, osteosclerosis, osteomalacia, and soft-tissue and vascular calcifications are the frequent pathological features seen in secondary hyperparathyroidism. [5] On X-ray imaging, brown tumors will be appearing as lytic lesions. Other changes would be osteopenia, 'salt-and-pepper' appearance on skull x-ray with trabecular resorption, subperiostal bone resorption and patchy diffuse areas of osteoclerosis.
References
  1. ASSADI F. Hypercalcemia: an evidence-based approach to clinical cases. Iran J Kidney Dis [online] 2009 Apr, 3(2):71-9 [viewed 24 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/19395781
  2. RODRIGUEZ M.. The calcium-sensing receptor: a key factor in the pathogenesis of secondary hyperparathyroidism. AJP: Renal Physiology [online] 2004 September, 288(2):F253-F264 [viewed 10 July 2014] Available from: doi:10.1152/ajprenal.00302.2004
  3. MARTIN KJ, GONZáLEZ EA. Prevention and control of phosphate retention/hyperphosphatemia in CKD-MBD: what is normal, when to start, and how to treat? Clin J Am Soc Nephrol [online] 2011 Feb, 6(2):440-6 [viewed 10 July 2014] Available from: doi:10.2215/CJN.05130610
  4. CUNNINGHAM J.. Achieving therapeutic targets in the treatment of secondary hyperparathyroidism. Nephrology Dialysis Transplantation [online] 2004 August, 19(suppl_5):v9-v14 [viewed 10 July 2014] Available from: doi:10.1093/ndt/gfh1050
  5. MURPHEY M D, SARTORIS D J, QUALE J L, PATHRIA M N, MARTIN N L. Musculoskeletal manifestations of chronic renal insufficiency.. RadioGraphics [online] 1993 March, 13(2):357-379 [viewed 11 July 2014] Available from: doi:10.1148/radiographics.13.2.8460225
  6. BLOCK GA, MARTIN KJ, DE FRANCISCO AL, TURNER SA, AVRAM MM, SURANYI MG, HERCZ G, CUNNINGHAM J, ABU-ALFA AK, MESSA P, COYNE DW, LOCATELLI F, COHEN RM, EVENEPOEL P, MOE SM, FOURNIER A, BRAUN J, MCCARY LC, ZANI VJ, OLSON KA, DRüEKE TB, GOODMAN WG. Cinacalcet for secondary hyperparathyroidism in patients receiving hemodialysis. N Engl J Med [online] 2004 Apr 8, 350(15):1516-25 [viewed 10 September 2014] Available from: doi:10.1056/NEJMoa031633
  7. SPRAGUE SM, COYNE D. Control of secondary hyperparathyroidism by vitamin D receptor agonists in chronic kidney disease. Clin J Am Soc Nephrol [online] 2010 Mar, 5(3):512-8 [viewed 10 September 2014] Available from: doi:10.2215/CJN.03850609

Investigations - Fitness for Management

Fact Explanation
Arterial blood gas analysis Hyperchloremic metabolic acidosis occur in hyperparathyroidism. [1]
Screen for diabetes mellitus [3] :HbA1c, fasting blood sugar CKD patients may have underlying diabetes mellitus that needs follow up. [2]
References
  1. ASSADI F. Hypercalcemia: an evidence-based approach to clinical cases. Iran J Kidney Dis [online] 2009 Apr, 3(2):71-9 [viewed 24 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/19395781
  2. SNIVELY CS, GUTIERREZ C. Chronic kidney disease: prevention and treatment of common complications. Am Fam Physician [online] 2004 Nov 15, 70(10):1921-8 [viewed 10 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/15571058
  3. MEHDI U, TOTO RD. Anemia, Diabetes, and Chronic Kidney Disease Diabetes Care [online] 2009 Jul, 32(7):1320-1326 [viewed 10 September 2014] Available from: doi:10.2337/dc08-0779

Investigations - Followup

Fact Explanation
Serum PTH [3] Targets of treatment: 35-70 pg/ml in stage 3, 70-110 pg/ml in stage 4 and 150-300 pg/ml in stage 5. [2]
Serum calcium level [3] This should be reduced to normal levels in stage 3 and 4, and 2.1-2.4 mmol/l in stage 5. [2]
Serum phosphate level [3] Targets for the management of hyperphosphataemia include 2.7 to 4.6 mg/dl in patients with CKD stage 3 to 4 and 3.5 to 5.5 mg/dl in CKD stage 5. [1]
References
  1. OLGAARD K., LEWIN E., SILVER J.. Calcimimetics, vitamin D and ADVANCE in the management of CKD-MBD. Nephrology Dialysis Transplantation [online] December, 26(4):1117-1119 [viewed 10 July 2014] Available from: doi:10.1093/ndt/gfq862
  2. CUNNINGHAM J.. Achieving therapeutic targets in the treatment of secondary hyperparathyroidism. Nephrology Dialysis Transplantation [online] 2004 August, 19(suppl_5):v9-v14 [viewed 10 July 2014] Available from: doi:10.1093/ndt/gfh1050
  3. SPRAGUE SM, COYNE D. Control of secondary hyperparathyroidism by vitamin D receptor agonists in chronic kidney disease. Clin J Am Soc Nephrol [online] 2010 Mar, 5(3):512-8 [viewed 10 September 2014] Available from: doi:10.2215/CJN.03850609

Investigations - Screening/Staging

Fact Explanation
Electrocardiogarm Myocardial fibrosis secondary cardiac calcification [1] can leads to left ventricular hypertrophy. Prominent R wave in V5 or V6 and prominent S wave in V1 or V2 is seen on ECG.
Echocardiogram There can be left ventricular hypertrophy and myocardial calcific deposits. [1]
DEXA scan (Dual-emission X-ray absorptiometry) [3] This is to detect osteoporosis and Z -score <-2.5 is associated with high risk of fractures. [3]
Renal function tests(blood urea, serum creatinine, serum electrolytes, glomerular filtration rate) CKD patients need regular assessment of renal functions. [2]
References
  1. CUNNINGHAM J., LOCATELLI F., RODRIGUEZ M.. Secondary Hyperparathyroidism: Pathogenesis, Disease Progression, and Therapeutic Options. Clinical Journal of the American Society of Nephrology [online] December, 6(4):913-921 [viewed 10 July 2014] Available from: doi:10.2215/​CJN.06040710
  2. SNIVELY CS, GUTIERREZ C. Chronic kidney disease: prevention and treatment of common complications. Am Fam Physician [online] 2004 Nov 15, 70(10):1921-8 [viewed 10 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/15571058
  3. BLAKE GM, FOGELMAN I. The role of DXA bone density scans in the diagnosis and treatment of osteoporosis Postgrad Med J [online] 2007 Aug, 83(982):509-517 [viewed 10 September 2014] Available from: doi:10.1136/pgmj.2007.057505

Management - General Measures

Fact Explanation
Dietary phosphate restriction [3] Hyperphosphatemia is known to be associated with the increased risk of death in patients with end stage renal failure. [1] Dietary phosphate restriction can be done if parathyroid hormone level is high. This is also important in preventing the development of hyperparathyroidism. Dietary phosphates are included in colas, nuts, peas, beans, and dairy product . [4]
Management of complications due to secondary hyperparathyroidism [5] Vascular complications, bone complications [1,2] may need specific attention. For example heart failure may needs loop diuretics.
Prevention of falls As the patients are having osteoporosis [2], they are vulnerable to fractures, [6] therefore measures should be taken to prevent falls and fractures.
Management of chronic kidney disease and its complications [3] Hypertension, dyslipidaemia, anaemia, diabetes mellitus, uremia and cardiovascular complications need appropriate management. [4]
Prevention of secondary hyperparathyroidism [3] Early diagnosis and treatment of rickets or vitamin D deficiency and proper management of chronic kidney disease is important in this aspect.[3]
References
  1. CUNNINGHAM J.. Achieving therapeutic targets in the treatment of secondary hyperparathyroidism. Nephrology Dialysis Transplantation [online] 2004 August, 19(suppl_5):v9-v14 [viewed 10 July 2014] Available from: doi:10.1093/ndt/gfh1050
  2. ASSADI F. Hypercalcemia: an evidence-based approach to clinical cases. Iran J Kidney Dis [online] 2009 Apr, 3(2):71-9 [viewed 24 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/19395781
  3. SPRAGUE SM, COYNE D. Control of secondary hyperparathyroidism by vitamin D receptor agonists in chronic kidney disease. Clin J Am Soc Nephrol [online] 2010 Mar, 5(3):512-8 [viewed 10 September 2014] Available from: doi:10.2215/CJN.03850609
  4. SNIVELY CS, GUTIERREZ C. Chronic kidney disease: prevention and treatment of common complications. Am Fam Physician [online] 2004 Nov 15, 70(10):1921-8 [viewed 10 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/15571058
  5. BLOCK GA, MARTIN KJ, DE FRANCISCO AL, TURNER SA, AVRAM MM, SURANYI MG, HERCZ G, CUNNINGHAM J, ABU-ALFA AK, MESSA P, COYNE DW, LOCATELLI F, COHEN RM, EVENEPOEL P, MOE SM, FOURNIER A, BRAUN J, MCCARY LC, ZANI VJ, OLSON KA, DRüEKE TB, GOODMAN WG. Cinacalcet for secondary hyperparathyroidism in patients receiving hemodialysis. N Engl J Med [online] 2004 Apr 8, 350(15):1516-25 [viewed 10 September 2014] Available from: doi:10.1056/NEJMoa031633
  6. BLAKE GM, FOGELMAN I. The role of DXA bone density scans in the diagnosis and treatment of osteoporosis Postgrad Med J [online] 2007 Aug, 83(982):509-517 [viewed 10 September 2014] Available from: doi:10.1136/pgmj.2007.057505

Management - Specific Treatments

Fact Explanation
Vitamin D supplementation [4] Vitamin D supplementation as alfacalcidol, and newer vitamin D analogues such as doxercalciferol, 22-oxacalcitriol, or paricalcitol is done in chronic kidney disease patients. [1] Vitamin D enhance the absorption of calcium and phosphorous from the gut , then reduce the synthesis of PTH.
Phosphate binders, and the more recent calcimimetics [1] As there is associated hyperphosphataemia, phosphate binders are used to reduce phosphate level in the blood. Calcium-free phosphate binders, (sevelamer and lanthanum carbonate) are used instead of calcium salts, as calcium salts can bring down the phosphorous levels to normal while increasing the possibility of complications such as hypercalcemia, calciphylaxis, and vascular calcifications. [1,2]
Calcimimetics eg:- Cinacalcet [3] This increases sensitivity of calcium receptors and reduce PTH secretion by the parathyroid glands. Calcimimetics also acts to reduce the vitamin D-induced vascular calcifications. [2]
Bisphosphonates [4] Reduce the rate of bone resorption. [1]
Newer therapies [4] Selective percutaneous ethanol injection therapy and direct injection with active vitamin D compounds such as calcitriol and 22-oxacalcitriol into the parathyroid gland causes enhancement of the cellular apoptosis and reduce the parathyroid hyperplasia. [1]
Parathyroidectomy [1] If the PTH levels remains >1000 pg/ml with hypercalcemia even after medical therapy or when the volume of gland is >500 mm3, surgery is recomended. [1]
References
  1. CUNNINGHAM J., LOCATELLI F., RODRIGUEZ M.. Secondary Hyperparathyroidism: Pathogenesis, Disease Progression, and Therapeutic Options. Clinical Journal of the American Society of Nephrology [online] December, 6(4):913-921 [viewed 10 July 2014] Available from: doi:10.2215/​CJN.06040710
  2. OLGAARD K., LEWIN E., SILVER J.. Calcimimetics, vitamin D and ADVANCE in the management of CKD-MBD. Nephrology Dialysis Transplantation [online] December, 26(4):1117-1119 [viewed 10 July 2014] Available from: doi:10.1093/ndt/gfq862
  3. BLOCK GA, MARTIN KJ, DE FRANCISCO AL, TURNER SA, AVRAM MM, SURANYI MG, HERCZ G, CUNNINGHAM J, ABU-ALFA AK, MESSA P, COYNE DW, LOCATELLI F, COHEN RM, EVENEPOEL P, MOE SM, FOURNIER A, BRAUN J, MCCARY LC, ZANI VJ, OLSON KA, DRüEKE TB, GOODMAN WG. Cinacalcet for secondary hyperparathyroidism in patients receiving hemodialysis. N Engl J Med [online] 2004 Apr 8, 350(15):1516-25 [viewed 10 September 2014] Available from: doi:10.1056/NEJMoa031633
  4. SPRAGUE SM, COYNE D. Control of secondary hyperparathyroidism by vitamin D receptor agonists in chronic kidney disease. Clin J Am Soc Nephrol [online] 2010 Mar, 5(3):512-8 [viewed 10 September 2014] Available from: doi:10.2215/CJN.03850609