Serum conc of 2.65 mmol / L or higher- On two occasions Usual range 2.15 to 2.60 mmol /L ( 8.8 -10.4 mg/dL ) Albumin adjusted levels Can be ◘ Mild 2.65 to 3.00 mmol/L ◘ Moderate 3.01 to 3.40 ( can be symptomatic ) ◘ Severe > 3.40 ADMIT Severity of symptoms also depends on the rate of onset Often incidental finding in asymptomatic patients
90 % of times Primary hyperparathyroidism ○ excessive and inappropriate secretion of PTH ○ most common cause of ↑ Ca and relatively common disorder ○ usual age 50-60 yrs ( but can occur at any age ) ○ women twice more likely to be affected ○ usually mild , asymptomatic and sustained for yrs ○ 85 % of time- single parathyroid adenoma is the cause and Malignancy- usually rapidly progressive rise in Ca ○ second most common cause ○ can be seen in upto 20-30 % of people with cancer ○ most common with cancers of ♦ breast ♦ lung ♦ multiple myeloma ○ ↑ Cancer is usually advanced if hypercalcemia occurs ie its a late finding
Drug related ♦ Thiazide diuretics ♦ Lithium ♦ Vit D ♦ Vit A ♦ Calcium co-prescribed with antacids and Vit D preprations Granulomatous diseases eg sarcoidosis or TB CKD 4 or 5 / Transplantation Familial hypocalciuric hypercalcemia Non – parathyroid diseases as ○ Thyrotoxicosis ○ Addison’s disease ○ Phaeochromocytoma ○ VIPoma ○ Immobility eg- Paget’s disease.
Presentation-Polyuria and thirst Anorexia , nausea and constipation Mood disturbance , cognitive dysfunction & confusion / coma Renal impairment Shortened QT interval and dysarrhythmias Nephrolithiasis & nephrocalcinosis Pancreatitis peptic ulceration Hypertension Cardiomyopathy Muscle weakness Band keratopathy
Hypercalcemia leads to hyperpolarization of cell membranes Mild chronic hypercalcemia is usually asymptomatic or causes recurring stones Symptoms related not only to the absolute calcium levels but also how fast the rise has occurred When symptoms present → often non specific and can be multi-system ” stones , bones , abdominal moans and psychic groans” used for particularly Primary hyperparathyroid related symptoms Affects all organ systems but particularly more the CNS and kidneys.Bone pain Fractures ( fragility & pathological #s ).
Drowsiness , delirium , coma Fatigue , muscle weakness Impaired conc and memory Depression Neurological signs.Renal colic ( stone ) Nephrogenic diabetes insipidus Nephrocalcinosis → renal impairment.Hypertension Shortened QT interval Rarely arrythmias.
Severe hypercalcemia ie > 3.40 or severe symptoms → ADMIT Main aim is to identify underlying mechanism Detailed history focusing on ○ clinical features of hypercalcemia ○ medications ○ family history Clinical examination.
General approach –Ensure that the levels are corrected for albumin or measure ionized calcium and repeat levels ( based on clinical judgement ) Severity of symptoms also depends on the rate of onset Evaluate the degree of hypercalcaemia duration and pattern Check previous records to assess chronicity Often incidental finding in asymptomatic patients Remember ” Stones , bones , moans and groans ” Hypercalcaemia in patients on digoxin therapy or with underlying cardiac disorders can potentiate arrhythmogenic effects and can lead to a symptomatic rhythm disorder
Repeat serum Ca while not taking drugs ( eg thiazide diuretics or Lithium ) or Vit D preparations Correct for serum albumin conc or measure serum Ca 2+ or both.
PTH suppressed- PTH suppression is normal physiological response to ↑ Ca levels- a low conc excludes Primary hyperparathyroidism Symptom guided malignancy work up Consider checking ○ serum and urine protein electrophoresis ○ Parathyroid hormone related protein ○ skeletal survey ○ chest abdomen and Pelvic imaging If malignancy workup is negative Test for other endocrinopathies ○ Hyperthyroidism ○ Adrenal insufficiency ○ Acromegaly PTH would be suppressed in Vit D toxicity.
PTH high or normal –24 hr Urinary Calcium – to exclude familial hypocalciuric hypercalcemia.
Primary hyperparathyroidism –Commonest cause of hypercalcemia in the community PTH raised or mid to high normal in the setting of raised total or ionised Ca after exclusion of conditions that mimic PHPT Patients mostly present with asymptomatic hypercalcemia- detected incidentally Symptomatic patients can present with ○ fragility fractures ○ recurrent nephrolithiasis ○ nephrocalcinosis , polyuria , renal insufficiency ○ low BMD Around 80 % of cases are caused by a single parathyroid adenoma ○ rest from hyperplasia of all glands If presents before age 45 – consider Multiple endocrine neoplasia Medical surveillance involves annual measurement of serum calcium and creatinine plus BMD ( at three sites ) every 1-2 yrs Parathyroidectomy- national guidelines / evidence guide patient selection
Monitoring in Primary Care- those who have not had parathyroidectomy for any reason
Referral-Chronically elevated PTH causes ○ osteoporosis ○ renal impairment ○ renal calculi The need for referral is based on risk of developing complications and include ◘ < 70 yrs of age ◘ Ca > 2.79 mmol /L ◘ eGFR 30-44 ◘ symptomatic hypercalcaemia- including renal stones ◘ h/o osteoporosis or fracture Primary hyperparathyroidism suspected Familial hypocalciuric hypercalcaemia is suspected If drug is considered to be the cause – stop and recheck in 3 weeks – if no improvement refer If Lithium related- seek advice/ discuss with the psychiatry team Malignancy suspected Granulomatous disorders suspected like sarcoidosis Suspected Tuberculosis Acute kidney injury Known ESRF ( CKD 4 or 5 ) Non-parathyroid endocrine disease is suspected Patient is immobilized with Pagets disease Known malignancy associated hypercalcaemia Cause of hypercalcaemia cannot be found
References ; further reading CKS Hypercalcaemia http://cks.nice.org.uk/hypercalcaemia Clinical Biochemistry – Allan Gaw , Michael J Murphy , Rajeev Srivastava , Robert A Cowan , Denis St J O’Reilly Churchills Pocket Book of Differential Diagnosis Society for Endocrinology : Acute Hypercalcaemia available at https://www.endocrinology.org/policy/ docs/13-02_EmergencyGuidance-AcuteHypercalcaemia.pdf The diagnosis and management of hypercalcaemia BMJ 2015 ; 350 :h2723 A Practical Approach to Hypercalcemia Am Fam Physician . 2003 May 1;67 (9) : 1959-1966 Investigations of incidental hypercalcaemia BMJ 2009 ; 339:b4613 Diagnosis and management of Primary hyperparathyroidism BMJ 2012 Essential Endocrinology and Diabetes -Richard I.G.Holt et al North Bristol NHS Trust Diagnosis of primary hyperparathyroidism abd familial benign hypercalcaemia & Hypercalcaemia Guideline for Primary Care Amanda DeMauro Renaghan, Mitchell H Rosner, Hypercalcemia: etiology and management,Nephrology Dialysis Transplantation, Volume 33, Issue 4, April 2018, Pages 549–551,https://doi.org/10.1093/ndt/gfy054