History

Fact Explanation
Malaise, fatigue, weakness, myalgia [2][4] Hyperparathyroidsm is mostly seen in post menopausal women and they mostly present with these vague symptoms. [1] Parathyroid increases calcium levels by increasing its release from bone, increasing absorption from intestine and reabsorption in renal tubules.
Depression, mood disturbances, dementia, confusion, and stupor [1] Whether neuropsychological complaints may improve with surgery or not, is not consistent, thus it is not considered as an indication for surgery. [2]
Constipation [4] Occurs due to hypercalcaemia.
Loin pain, dysuria, haematuria [3][4] Formation of renal stones occurs due to hypercalcaemia, this may later lead to urinary tract infection and patient may present with its symptoms. [3] This may also lead to renal impairment and hypertension, symptoms of which may also be patient's presentation.[3] [6]
Polyuria, polydipsia and dehydration[1] Nephrogenic diabetes insipidus is caused by hypercalcaemia.
Fracture after trivial injury Pathological fractures may occur in hyperparathyroidism. [3]
Bone pain, deformity, bony lumps Due to osteoporosis, fractures and bone tumors.[3][7]
Features of chronic kidney disease: anorexia, nausea, dry skin, pruritus, restless leg, reduced urine output Chronic kidney disease results in reduced formation of active vitamin D which subsequently results in reduced calcium level which is a stimulant to parathyroid glands resulting in secondary hyperparathyroidism. [1] Nephrocalcinosis and renal stone formation seen in hyperparathyroidism itself can lead to renal impairment. [6]
Recurrent acute pancreatitis : Acute severe abdominal pain, radiating to the back, relieved by bending forwards. [5] Hypercalcemia, may activate trypsinogen to trypsin leading to auto digestion of pancreas causing pancreatitis or may lead to formation of pancreatic calculi obstructing the duct leading to acute or chronic pancreatitis [5]
Family history Multiple endocrine neoplasia syndromes (MEN-1, MEN-2) is associated with hyperparathyroidism. [1]
Exposure to radiation: external-beam radiotherapy Irradiation for acne [1] Irradiation for acne has 2-3 fold increase in this disease. MEN-1 gene mutation is also associated with irradiation. [1]
Drug history: Lithium, anticonvulsants [1] Prolonged use of lithium (as used in psychiatric diseases) or anticonvulsant is associated with primary hyperparathyroidism. [1]
Diet history: milk allergy/ lactose intolerence, intake of ample phytates along with meal [1] Reduced calcium intake or absorption will lead to hypocalcaemia and secondary hyperparathyroidism. [1]
Exposure to sun light [1] Reduced exposure may result in vitamin D deficiency leading to hypocalcaemia and subsequent secondary hyperparathyroidism. [1]
Lactation/ growth [1] These states are associated with high demand to vitamin D and calcium and lack of it leads to secondary hyperparathyroidism.
References
  1. FRASER WD. Hyperparathyroidism. [online] Lancet. 2009 Jul 11; Volume 374, Issue 9684, Pages 145-58. [Viewed on: 17/04/2014] Available from: http://www.researchgate.net/profile/William_Fraser/publication/26664087_Hyperparathyroidism/file/d912f5102c877a923e.pdf
  2. KHAN A Aliya, BILEZIKIAN P John, POTTS T John Jr. ASYMPTOMATIC Primary hyperparathyroidism: A commentary on thr revised guidelines. [online]Endocrine Practice. 2009 Jul-Aug; Volulme 15, Issue 5, Pages 494–498. [Viewed on: 19/04/2014] Available from: doi: 10.4158/EP09162.CO
  3. KEYNES WM, The Symptoms of Hyperparathyroidism. [online] Britisih Medical Journal. Jan 28, 1961; Volume 1, Issue 5221, Pages 239–242. [Viewed on: 19/04/2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1953054/
  4. CHAN AK, DUH QY, KATZ MH, SIPERSTEIN, CLARK OH. Clinical manifestations of primary hyperparathyroidism before and after parathyroidectomy. A case-control study. [online] Annals of Surgery. Sep 1995; Volume 222, Issue 3, Pages 402–414. [Viewed on: 19/04/2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1234827/
  5. MISGAR A Raiz, MATHEW Vivek, PANDIT Kaushik, CHOWDHURY Subhankar. Primary hyperparathyroidism presenting as recurrent acute pancreatitis: A case report and review of literature. [online] Indian Journal of Endocrinology and Metabolism. 2011 Jan-Mar, Volume 15, Issue 1, Pages 54–56. [Viewed on: 17/04/2014] Available from: doi: 10.4103/2230-8210.77588
  6. HAMDY AT Neveen. A patient with persistent primary hyperparathyroidism due to a second ectopic adenoma. [online] Nature Clinical Practice Endocrinology & Metabolism (2007) Volume 3, Pages 311-315 [Viewed on: 19/04/2014] Available from: doi: doi:10.1038/ncpendmet0448
  7. MEYDAN Nezih, BARUTCA Sabri et al. Brown tumors mimicking bone metastases. [online] Journal National Mediccal Association. Jun 2006; Volume 98, Issue 6, Pages 950–953. [Viewed on: 19/04/2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2569361/

Examination

Fact Explanation
Bony "tumors", mostly seen at facial bones, clavicle, ribs, pelvis, and/or femur Due to brown tumors which arise at the terminal stages of bone remodelling that occurs in hyperparathyroidism. [1]
Signs of dehydration: presence of tear, enophthalmos, skin turgor, capillary refilling time Hyperthyroidism is associated with nephrogenic diabetes insipidus leading to dehydration. It should be addressed immediately if present. [3]
Blood pressure [2] Hypertension is associated with hyperparathyroidism. [2]
Features of chronic failure may present: dry skin, scratch marks, oedema, basal crepitations in lung This may have lead to secondary hyperparathyroidism. [3]
References
  1. GUIMARAES Luiz Sena, SILVA Luciano Marques et al. Peripheral brown tumour of hyperparathyroidism in the oral cavity. [online] Oral Oncology Extra Volume 42, Issue 3, March 2006, Pages 91–93 [Viewed on: 17/04/2014] Available from: http://www.sciencedirect.com/science/article/pii/S1741940905000865
  2. ANDERSSON Patrik, RYDBERG Erik, WILLENHEIMER Ronnie. Primary hyperparathyroidism and heart disease — a review. [online] European Heart Journal Volume 25, Issue 20, p. 1776-1787. [Viewed on: 17/04/2014] Available from: doi: 10.1016/j.ehj.2004.07.010
  3. FRASER WD. Hyperparathyroidism. [online] Lancet. 2009 Jul 11; Volume 374, Issue 9684, Pages 145-58. [Viewed on: 17/04/2014] Available from: http://www.researchgate.net/profile/William_Fraser/publication/26664087_Hyperparathyroidism/file/d912f5102c877a923e.pdf

Differential Diagnoses

Fact Explanation
Primary hyperparathyroidism: Adenoma (single or multi gland adenoma) of the parathyroid gland or presence of an ectopic parathyroid gland [1] Primary hyperparathyroidism is when the parathyroid gland secretes excess parathyroid hormone without any stimulus. Ectopic parathyroid gland maybe found in mediastinum along with thymus, within thyroid gland or at the angle of jaw. [1]
Secondary hyperparathyroidism can be caused by: liver/biliary disease, Vitamin D dependent or resistant rickets or osteomalacia, Chronic kidney disease, Pseudohypoparathyroidism, Bisphosphonate treatment, Lactation/post-lactation Secondary hyperparathyroidism is when the parathyroid gland secretes excess parathyroid hormone in response to a stimulus. Liver/biliary disease causes reduced bile salt secretion leading to vitamin D deficiency which causes hypocalcaemia triggering parathyroid gland. In pseudohypoparathyroidism, there is a parathyroid hormone-receptor abnormality causing parathyroid hormone resistance. [1]
Tertiary hyperparathyroidism: Chronic secondary hyperparathyroidism or chronic treatment with phosphates. Chronic stimulation of parathyroid gland causes hyperplasia of gland resulting in autonomous secretion of excess parathyroid hormone which is known as tertiary hyperparathyroidism. The commenest cause is chronic kidney disease. It is also found where phophate is used as treatment for a long time such as in X-linked hypophosphataemic rickets, adult onset hypophosphataemic rickets (autosomal dominant) and in oncogenic osteomalacia. [1]
Quaternary hyperparathyroidism Tertiary hyperparathyroidism is thought to progress to quaternary hyperparathyroidism. [2]
Familial benign hypocalciuric hypercalcaemia (FBHH) [1] FBHH also presents with signs and symptoms caused by hypercalcaemia. Calcium creatinine clearance ratio of less than 0·01 suggests of FBHH than primary hyperparathyroidism. [1]
Other causes of hypercalcaemia: haematological malignancies, multiple myeloma, vitamin D excess, sarcoid, toxicosis, immobilisation [1] Consider if parathyroid hormone levels are <3·0 pmol/L [1]
References
  1. FRASER WD. Hyperparathyroidism. [online] Lancet. 2009 Jul 11; Volume 374, Issue 9684, Pages 145-58. [Viewed on: 17/04/2014] Available from: http://www.researchgate.net/profile/William_Fraser/publication/26664087_Hyperparathyroidism/file/d912f5102c877a923e.pdf
  2. ANAFOROGLU Inan, ERSOY Kerem, ALGUN Ekrem. Parathyroid adenoma with coeliac disease: primary or quaternary hyperparathyroidism? [online] Polish journal of endrocrinology. Volume 63, Number 1/2012 [Viewed on: 19/04/2014] Available from: http://czasopisma.viamedica.pl/ep/article/view/25201/20030

Investigations - for Diagnosis

Fact Explanation
Plasma albumin-adjusted calcium >2·65 mmol/L on two occasions [1] Primary hyperparathyroidism is the most common cause of hypercalcaemia[1]
Parathyroid hormone [1] Should be measured before it is altered by any medical intervention. If >3·0 pmol/L it is caused by hyperparathyroidism, if <3·0 pmol/L non-parathyroid related causes may have caused the hypercalcaemia
Urine calcium creatinine clearance ratio [1] To exclude familial benign hypocalciuric hypercalcaemia(FBHH), if <0·01 FBHH is more likely than hyperparathyroidism. [1]
X ray Depending on patients symptoms necessary images are obtained. Nephrocalcinosis, renal calculi, osteopenic changes, changes due to demineralization, Brown tumour, 'Salt and pepper' appearance in skull, fracture of femur, pathological fracture could be seen. [2]
2D echocardiography [4] Cardiac and valvular calcification maybe present. Also hyperparathyroidism is associated with hypertension which in turn might cause left ventricular hypertrophy(LVH). LVH is also a powerful predictor of cardiovascular mortality which is the common cause of death in hyperparathyroidism. [4]
CT abdomen Renal stones and calcification[5], changes of acute pancretitis if presented with it can be seen. [3]
Ultrasonography neck [3] Enlarged parathyroid gland is visualised as hypoechoic lesion
CT/ Magnetic resonance of the gland [6] They are used to locate the pathological gland pre operatively. Magnetic resonance with gadolinium and fat suppression helps to visualise the anatomy of neck clearly. [6]
Parathyroid scintigraphy [5] 99'Tc-Sestamibi is the agent of choice, since its not uptaken by thyroid gland and the abnormal parathyroid gland is clearly visualised. [5]
Positron emission tomography/computed tomography (PET/CT) [6] Disease extend and response to treatment is well demonstrated in parathyroid cancer by PET CT. [6]
References
  1. FRASER WD. Hyperparathyroidism. [online] Lancet. 2009 Jul 11; Volume 374, Issue 9684, Pages 145-58. [Viewed on: 17/04/2014] Available from: http://www.researchgate.net/profile/William_Fraser/publication/26664087_Hyperparathyroidism/file/d912f5102c877a923e.pdf
  2. SHAW MT, DAVIES M. Primary hyperparathyroidism presenting as spinal cord compression. [online] British Medical Journal Oct 26, 1968, Volume 4, Issue 5625, Pages 230–231. [Viewed on: 17/04/2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1912178/
  3. MISGAR A Raiz, MATHEW Vivek, PANDIT Kaushik, CHOWDHURY Subhankar. Primary hyperparathyroidism presenting as recurrent acute pancreatitis: A case report and review of literature. [online] Indian Journal of Endocrinology and Metabolism. 2011 Jan-Mar, Volume 15, Issue 1, Pages 54–56. [Viewed on: 17/04/2014] Available from: doi: 10.4103/2230-8210.77588
  4. ANDERSSON Patrik, RYDBERG Erik, WILLENHEIMER Ronnie. Primary hyperparathyroidism and heart disease — a review. [online] European Heart Journal Volume 25, Issue 20, p. 1776-1787. [Viewed on: 17/04/2014] Available from: doi: 10.1016/j.ehj.2004.07.010
  5. MORITA ET, KWAN WP, CLARK OH. Technetium Tc 99m sestamibi for parathyroid imaging. Western Journal of Medicine. [online] Oct 1994; Volume 161, Issue 4, Pages 413. [Viewed on: 19/04/2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1022628/
  6. EVANGELISTA Laura, SORGATO Nadia, TORRESAN Francesca, MERANTE Isabella et al. FDG-PET/CT and parathyroid carcinoma: Review of literature and illustrative case series World Journal of Clinical Oncology. [online] Oct 10, 2011; Volume 2, Issue 10, Pages 348–354. [Viewed on: 19/04/2014] Available from: doi: 10.5306/wjco.v2.i10.348

Investigations - Fitness for Management

Fact Explanation
Basic investigations for surgery: Chest x-ray, ECG, full blood count, haemostasis, renal function, random glucose[1] Should be tailor made according to ASA (American Society of Anesthesiologists) grade the individual patient would fall in.[1]
References
  1. Guideline for Preoperative Investigations in Patients Undergoing Elective Surgery. Preoperative Tests: The Use of Routine Preoperative Tests for Elective Surgery.[online] NICE Clinical Guidelines, No. 3. National Collaborating Centre for Acute Care (UK). London 2003 Jun. [viewed on 19/04/2013] Available from: http://www.ncbi.nlm.nih.gov/books/NBK48482/

Investigations - Followup

Fact Explanation
Serum calcium and creatinine annually and dual-energy x-ray absorptiometry (DEXA) annually or 2 yearly according to clilnical judegment. [1] These tests are done on patient who do not undergo surgery but are under medical management only. [1]
Post operative serum calcium 4 hourly for 2 days and then daily for 7-14 days till the levels are stable, and parathyroid hormone levels. [2] Most patients may develop hypocalcaemia which could be easily treated with calcium supplements but only few will need long term calcium supplements. Persistently elevated parathyroid hormone level needs to be addressed and sometime re-exploration maybe needed. [2]
References
  1. BILEZIKIAN P John, KHAN A Aliya, POTTS T John Jr. Guidelines for the Management of Asymptomatic Primary Hyperparathyroidism: Summary Statement from the Third International Workshop [online] Journal of Clinical Endocrinology and Metabolism. Feb 2009; 94(2): 335–339. [Viewed on: 20/04/2014] Available from: doi: 10.1210/jc.2008-1763 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3214274/#!po=65.0000
  2. SAUNDERS RN, KAROO R, METCALFE MS, NICHOLSON ML. Four gland parathyroidectomy without reimplantation in patients with chronic renal failure. [online] Postgraduation Medical Journal 2005;81:255–258. [Viewed on: 20/04/2014] Available from: doi: 10.1136/pgmj.2004.026450 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1743255/pdf/v081p00255.pdf

Investigations - Screening/Staging

Fact Explanation
DNA sequence testing [1] Used to screen patients with asymptomatic hyperparathyroidism or hypercalcemia [1]
Serum 25-hydroxyvitamin D levels [1] In patients with asymptomatic primary hyperparathyroidism there could be associated vitamin D insufficiency which should be treated if present. [1]
Estimated glomerular filtration rate (GFR) [1] This determines the renal function and if GFR is less than 60 ml/min.1.73 m² in established asymptomatic primary hyperparathyroidism surgery should be considered. [1]
Regular serum calcium and three-site bone mineral density (BMD) [2] Should be done in follow up of those who have not undergone surgery for asymptomatic primary hyperparathyroidism because some patients develop decreased BMD after 8-10 years. [2]
References
  1. EASTELL R, ARNOLD A, BRANDI ML, BROWN EM et al. Diagnosis of asymptomatic primary hyperparathyroidism: proceedings of the third international workshop. [online] Journal of Clinical Endocrinology and Metabolism. 2009 Feb; Volume 94, Issue 2, Pages 340-50. [Viewed on: 17/04/2014] Available from: doi: 10.1210/jc.2008-1758.
  2. SILVERBERG SJ, LEWIECKI FM, MOSEKILDE L, PEACOCK M, RUBIN MR. Presentation of asymptomatic primary hyperparathyroidism: proceedings of the third international workshop. [online] Journal of Clinical Endocrinology and Metabolism. 2009 Feb, Volume 94, Issue 2, Pages 351-65. [Viewed on: 17/04/2014] Available from: doi: 10.1210/jc.2008-1760.

Management - General Measures

Fact Explanation
Rehydration with NaCl. Patients are usually dehydrated and rehydration with NaCl will replenish the lost volume, decrease uraemia and improve calcium excretion in urine. [1]
References
  1. FRASER WD. Hyperparathyroidism.[online]Lancet. 2009 Jul 11; Volume 374, Issue 9684, Pages 145-58. [Viewed on: 17/04/2014] Available from: http://www.researchgate.net/profile/William_Fraser/publication/26664087_Hyperparathyroidism/file/d912f5102c877a923e.pdf

Management - Specific Treatments

Fact Explanation
Medical management Bisphosphonates, hormone replacement therapy, raloxifene and calcimimetics (cinacalcet) [1][4] Reduces the serum calcium and parathyroid hormone levels. Consider in patient with no indication or contraindications to surgery. [4] Calcimimetics, mimic calcium on parathyroid receptors and reduces its response to hypocalcaemia.
Surgical management Serum albumin-adjusted calcium > 0·25 mmol/L above the upper limit of local laboratory reference range, urine calcium > 10 mmol/24 hours, in creatinine clearance ≥ 30%, bone mineral density T score < –2·5, age < 50 years, on patient's request/ when adequate follow-up is unlikely.[1] Even in asymptomatic primary hyperparathyroidism surgery is considered if renal impairment is present or bone density T-score of lumbar spine, hip, or distal one third radius is -2.5 or less. [2][3] Minimally invasive parathyroidectomy has low morbidity and high patient satisfaction [1] Adenoma is removed or in cases of hyperplasia of all 4 glands, 3 1/2 of the gland is removed. [5] Total or subtotal parathyroidectomy is performed in tertiary hyperparathyroidism [1] Surgery leads to long-term improvement in bone mineral density of spine, hip, and radius in asymptomatic primary hyperparathyroidism . [3]
References
  1. FRASER WD. Hyperparathyroidism. [online] Lancet. 2009 Jul 11; Volume 374, Issue 9684, Pages 145-58. [Viewed on: 17/04/2014] Available from: http://www.researchgate.net/profile/William_Fraser/publication/26664087_Hyperparathyroidism/file/d912f5102c877a923e.pdf
  2. EASTELL R, ARNOLD A, BRANDI ML, BROWN EM et al. Diagnosis of asymptomatic primary hyperparathyroidism: proceedings of the third international workshop. Journal of Clinical Endocrinology and Metabolism. [online] 2009 Feb; Volume 94, Issue 2, Pages 340-50. [Viewed on: 17/04/2014] Available from: doi: 10.1210/jc.2008-1758.
  3. SILVERBERG SJ, LEWIECKI FM, MOSEKILDE L, PEACOCK M, RUBIN MR. Presentation of asymptomatic primary hyperparathyroidism: proceedings of the third international workshop. [online] Journal of Clinical Endocrinology and Metabolism. 2009 Feb, Volume 94, Issue 2, Pages 351-65. [Viewed on: 17/04/2014] Available from: doi: 10.1210/jc.2008-1760.
  4. PALLAN S,KHAN A. Primary hyperparathyroidism: Update on presentation, diagnosis, and management in primary care. [online] Canadian Family Physician. 2011 Feb, Volume 57, Issue 2, Pages 184-9. [Viewed on: 17/04/2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3038812/
  5. Primary Hyperparathyroidism, University of Southern California Department of Surgery, Keck School of Medicine of USC. [Viewed on: 17/04/2014] Available from: http://www.surgery.usc.edu/uppergi-general/endocrinesurgery-parathyroidsurgery-primaryhyperparathyroidism.html