Southern Derbyshire Shared Care Pathology Guidelines. Primary Hyperparathyroidism

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1 Southern Derbyshire Shared Care Pathology Guidelines Primary Hyperparathyroidism Please use this Guideline in Conjunction with the Hypercalcaemia Guideline Definition Driven by hyperfunction of one or more of the parathyroid glands, the hallmark of primary hyperparathyroidism is a circulating level of PTH which is inappropriately high for the level of calcium. Most patients are hypercalcaemic but the condition is gradually progressive and hypercalcaemia can be intermittent initially. Concurrent Vitamin D deficiency causes higher levels of PTH and can occasionally lead to misleadingly normal calcium levels. Onset of primary hyperparathyroidism most commonly occurs between years and is more common in elderly women. Aetiology Over 80% of primary hyperparathyroidism cases are caused by a single parathyroid adenoma of the parathyroid gland. Other causes include: Multiple adenomas (5%) Diffuse hyperplasia (12%) - common in lithium treated patients Carcinoma (2%) Ectopic PTH-secreting tumour (very rare) In younger patients (<40y) with primary hyperparathyroidism please consider a familial cause. Multiple adenomas or hyperplasia also suggests possible genetic aetiology. For example, co-existence of hypercalcaemia with hypertension and neurofibroma is suggestive of multiple endocrine neoplasia type 2. Clinical effects of Hyperparathyroidism The clinical features of hyperparathyroidism tend to be non-specific and are related to the aetiology of the hyperparathyroidism and the level of serum calcium. Most cases are now picked up incidentally during blood investigations- and many patients are asymptomatic. Authorised by Julia Forsyth Page 1 of 5

2 Features may include: Polyuria, thirst, weakness, vomiting Fracture risk: o a study undertaken in 2000 in Denmark looked at 674 patients with primary hyperparathyroidism, showing that those with primary hyperparathyroidism were at increased risk of vertebral, distal lower limb and forearm fractures before surgery, but not after, compared with a control group (relative risk, RR 1.8 before surgery and 1.0 after surgery) Renal calculi in 10-15% of patients Bone resorption leading to bone pain or pathological fracture: o the main affected areas are where bone turnover is most active such as in the vertebrae, phalanges, ends of long bones and the skull o In advanced disease bone resorption leads to formation of bone cysts or brown tumours, with deformities leading to fracture or bending of bones and/or a classical pepper-pot skull seen on plain XR. o These changes are now rare as cases tend to be diagnosed at an earlier stage Other features of metastatic calcification may be present such as nephrocalcinosis, and corneal calcification Rarely, primary hyperparathyroidism may present as acute pancreatitis Investigations and Initial Diagnosis For the initial diagnosis of Primary Hyperparathyroidism please refer to the Hypercalcaemia Guideline. For patients presenting with hypercalcaemia without a known cause, dependent upon clinical details provided the laboratory measures: PTH Alkaline Phosphatase Phosphate U & E Be aware that primary hyperparathyroidism may coexist with cancer, resulting in PTH levels that are normal or elevated despite cancer being present- relevant clues to this occurrence would be rapidly progressive hypercalcaemia and/or symptoms of the relevant malignancy Authorised by Julia Forsyth Page 2 of 5

3 When to Refer It is recommended that after the initial diagnosis of Primary Hyperparathyroidism has been made the patient is referred to a Consultant Endocrinologist for: Confirmation of diagnosis Excluding other possible co-existing causes of hypercalcaemia Assessment of Vitamin D status o Advice on Vitamin D supplements if required o Advice on dietary calcium intake If appropriate, treatment with a bisphosphonate or alternatives to protect bone from excessive resorption Assessment of Urine Calcium Excretion Index o Low levels indicate Familial Hypocalciuric Hypercalcaemia. o Falsely low calcium excretion index is seen in Vitamin D deficiency and with thiazide diuretics Assessing the need for parathyroidectomy and surgical referral. Potential indications for parathyroidectomy include: o Symptomatic disease- mild hypercalcaemia does not cause significant symptoms (ie the symptoms are non-specific and are often due to other pathologies) o People younger than 50 years of age o Kidney stones o Serum calcium concentration that is 0.25 mmol/l or more above the upper end of the reference range o egfr < 60 ml/min o Reduced bone mineral density at lumbar spine, femoral neck, total hip, or distal radius Ultrasound of the parathyroids and Nuclear Medicine Sestamibi scan are scans used for surgical planning. They are specialist investigations and are not a way of diagnosing primary hyperparathyroidism. All younger patients (<40y) should be referred to a Consultant Endocrinologist to rule out familial causes. When doing so it is especially advised that you ask the patient to provide a random urine sample (plain plastic universal container) for a urine calcium excretion index for the differential diagnosis of FHH. Young patients also have the most to gain from surgical treatment for primary hyperparathyroidism. In some cases it would be appropriate to ask advice from the Endocrinology team rather than clinical review (for example in patients where attendance to clinic is a challenge or where extent of hypercalcaemia mild). Authorised by Julia Forsyth Page 3 of 5

4 In order for this first outpatient appointment to readily identify the patient s needs and treatment please measure the following: o U&E s o Bone Profile (Ca, Phos, ALP, Alb) o PTH o Serum 25-Hydroxy Vitamin D Consider requesting a DEXA scan prior to the outpatient appointment if this has not been done in the last 3 years and the patient does not have known osteoporosis. Once an initial assessment has been undertaken, monitoring of people with asymptomatic primary hyperparathyroidism who have no indications for parathyroidectomy or who decline parathyroidectomy may be done in primary care. In Primary Care Monitor: o Serum calcium and renal function every 12 months o Blood pressure every 6 months o Bone mineral density (at lumbar spine, femoral neck, total hip, and distal radius) every 3 years (or according to instructions at the time of discharge from Endocrine clinic) Refer the person back to the endocrinologist if: o Individual criteria may be set at the time of discharge from Endocrinology clinic - check the relevant letter Typical criteria for re-referral include: o Significant symptoms of hypercalcaemia develop o Adjusted calcium persistently >2.85 mmol/l - as this is an indication to consider surgical management o Adjusted serum calcium is > 3.0 mmol/l - even if surgery is not planned this calls for a review of all treatment options and follow-up plans o At any site on bone mineral density measurement, the T-score is 2.5 or less (for peri-menopausal or postmenopausal women, and men 50 years of age or older) or the Z-score is 2.5 or less (for premenopausal women and men younger than 50 years of age)- although in many patients this is due to other factors and may not always indicate a need for parathyroidectomy o The egfr falls by >10 ml/min since first diagnosis (dependent on the rapidity of the fall in egfr, and for all patients where the egfr fall less than 30. Renal referral is more likely to be indicated in the first instance). Authorised by Julia Forsyth Page 4 of 5

5 Contacts Duty Biochemist Endocrinology Advice (8am to 7pm, Mon Fri) (9am 5pm, Mon Fri) Authors: Dr Penny Blackwell, Dr Rustam Rea January 2012 Reviewed by: Date: Expiry date: Dr P Blackwell, Dr R Stanworth, Mrs H Seddon May st May 2016 Dr P Blackwell, Dr R Stanworth, Mrs H Seddon Jan st Jan 2019 Authorised by Julia Forsyth Page 5 of 5

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