Primary Hyperparathyroidism. Schweizerische Gesellschaft für Endokrinologie und Diabetologie - SGED

Transkript

1 Primary Hyperparathyroidism

2 Changing Clinical Presentation of PHPT Nephrolithiasis % % Hypercalciuria 36 % 40 % Overt skeltal disease % % Asymptomatic % % Fraser WD, Lancet 374: 145, 2009

3 PHPT Diagnosis 3 Laboratory cut-offs Pitfalls Increased albumincorrected or ionized plasma calcium Ca corr. > 2.6 mmol/l Ca ion. > 1.3 mmol/l Non-suppressed plasma PTH (2nd/3rd generation assay) > 30 ng/l Normocalcemic phpt Age and Vitamin D dependent PTH cut-offs Interfering drugs Thiazides Bisphosphonates Denosumab Lithium Ca-Malabsorption Kidney function PTH if egfr < 60 ml/min

4 Ionized Calcium (mmol/l) Ionized vs. Albumin-corrected Calcium in Patients with phpt Proportion with normocalcemic phpt Alb-corrected Ca - 22% (11/51) Ionized Ca - 2% (1/51) Albumin-corrected Calcium (mmol/l) 4 51 subsequent patients with PHPT at the KSSG

5 PHPT Diagnosis recommendations Eastell R et al, JCEM 99: 3570, 2014 In borderline cases 5 Replete 25-OH Vitamin D3 to > 50 (better 75) nmol/l «Cautious replenishment with vitamin D would seem to be prudent» Stopp Thiazides Measure ionized plasma calcium Consider normocalcemic phpt: increased PTH with Repeatedly normal ionized and albumin-corrected calcium Normal 25-OH-Vitamin D 3 (> 75 nmol/l) Normal kidney function (egfr > 60 ml/min) No interfering drugs

6 Vitamin D in PHPT High prevalence of Vitamin D deficiency < 50 nmol/l: 81 vs. 60% (controls) < 25 nmol/l: 33 vs. 20% Association of Vitamin D levels with : Increased plasma calcium Increased bone turnover Decreased BMD Pathophysiology: Increased 1,25 (OH)2 D3 following increased 1α-Hydroxylation increases 24-Hydroxylase and subsequent 25-OH D-catabolism Bollerslev EJE 165: 851,

7 «Genetic» phpt 10% diagnosed < 45 Y Eastell R et al, JCEM 99: 3570,

8 When should genetic testing be performed? Age < 30 years Multiglandular disease (independent of age) Suspicion of MEN1 in patient ( 2 NET) Suspicion/diagnosis of MEN1 in 1st degree relative Parathyroid carcinoma or atypical adenoma Suspicion of FHH based on clinical/laboratory results Eastell R et al, JCEM 99: 3570, 2014 Lassen T et al, JCEM 99: 3983,

9 DD of mild PHPT: Familial Hypocalcuric Hypercalcemia Inactivating mutation of the calcium-sensing receptor (CASR) Failure to respond to increased calcium tubular reabsorption of calcium mild hypercalcemia, relative hypocalcuria, increased PTH, hypophosphtemia Autosomal-dominant inheritence, variable penetrance Lifelong, mild hypercalcemia No complications of phpt Calcium to creatinine clearance < 1.0% (fractional excretion of calcium) Eastell R et al, JCEM 99: 3570, 2014 Varghese et al, Endocr Pract 17 (Suppl.1): 13,

10 Suggested Algorithm to diagnose/ rule out FHH Median FECa in our Patients with surgically cured phpt 1.8%, 22% below 1.0% Hughe increase in genetic testing Currently not in reimbursed Eastell R et al, JCEM 99: 3570,

11 Lundstam K et al, JCEM 100: 1359, 2015 Randomized Study of Surgery vs. Observation in Asymptomatic/Mild PHPT Lumbar spine Z-Score PTH (pmol/l) Baseline Calcium (mmol/l) Baseline 5 Years Femoral neck Z-Score Baseline 11 5 Years 5 Years Surgery -0.5 Schweizerische Gesellschaft für Observation

12 Summary of new bone and kidney data Lumbar spine BMD does not accurately bone microarchitecture in PHPT and is an imperfect surrogate for vertebral fracture risk/underestimates fracture risk Spine X-ray, trabecular bone score (TBS) Distal forearm BMD and total hip/fermoral neck BMD more accurately reflect fracture risk Distal forearm BMD mandatory Asymptomatic renal stone disease is very prevalent Renal imaging (X-ray, CT, US) 12

13 Bollerslev J et al, JCEM 94: 2255, 2009 PHPT and cardiovascular risk Hype rtensi on Diabetes phpt Dysli pidemia LVH IMT No improvement of cv risk factors following PTX 13

14 PHPT and Neurocognitive Function At this time, there is insufficient evidence of predictable improvement of specific symptoms in a given patient to recommend PTX on the basis of neurological or psycho-logical symptoms, although some patients do experience symptomatic improvements after surgery. There are also insufficient data to recommend formal neuropsychiatric or neurocognitive testing in PHPT Silverberg SJ et al, JCEM 99: 3580,

15 Bilezikian JP et al, JCEM 99: 3561,

16 Bilezikian JP et al, JCEM 99: 3561,

17 Peacock M JCEM 96, E9 2011, Kebig A DMW Cinacalcet Calcimimetic at the CASR Decreases PTH-secretion Inconsistent data on bone turnover No increase in calciuria > 70% achive normal Calcium Expensive, GI adverse effects 17

18 Pharmacological Therapy Recomendations Pharmacological management of PHPT should be targeted to patients who have failed surgery, have contraindications to surgery, or are unwilling to undergo parathyroidectomy. Marcocci C et al, JCEM 99:3607,

19 51 subsequent patients with PHPT at the KSSG Preoperative localisation of parathyroid adenomas with ultrasound, sestamibi scintitgraphy and ultrasound guided FNA Sensitivity PPV Accuracy Scintigraphy Ultrasound US-FNA