Hyperparathyroidism. When to Suspect, How to Diagnose, When and How to Intervene. Johanna A. Pallotta, MD, FACP, FACE

Transcription

1 Hyperparathyroidism When to Suspect, How to Diagnose, When and How to Intervene Johanna A. Pallotta, MD, FACP, FACE

2 Potential conflicts of interest: None Johanna A. Pallotta, MD

3 Outline Definition of hyperparathyroidism (Primary, Secondary, Tertiary) Primary Hyperparathyroidism Changing presentation of primary hyperparathyroidism Clinical manifestations of primary hyperparathyroidism Indications for surgery Localization techniques for primary hyperparathyroidism Surgical techniques for primary hyperparathyroidism Management for ongoing hyperparathyroidism

4 Calcium Homeostasis Calcium Vitamin D Bicarbonate + Bone CALCIUM + + Parathyroid Hormone (PTH) Gut 1 alpha Hydroxylase + Liver Skin/Gut 1,25-Dihydroxy Vitamin D Kidney 25-Hydroxy Vitamin D 25-alpha Hydroxylase Vitamin D

5 Hypercalcemia Hyperparathyroidism When to Suspect Routine labs (asymptomatic patients) Bone density changes Nephrolithiasis Other causes of hypercalcemia: Malignancy, granulomatous disease, vitamin intoxication (A,D), medications (lithium, thiazides, calcium, theophylline), hyperthyroidism, immobilization Elevated PTH in the setting of hypercalcemia = hyperparathyroidism

6 1 0 Hyperparathyroidism 80-85% caused by a single adenoma 15 20% caused by 4-gland hyperplasia or double adenomas 0.5 2% caused by parathyroid carcinoma Treatment is surgical removal of enlarged, hypercellular gland(s)

7 1 0 Hyperparathyroidism 1. Establish diagnosis 2. Review indications for surgery 3. Localize abnormal gland(s) 4. Operate Keep in this order!

8 Captain Martell First patient diagnosed with hyperparathyroidism 1918

9 Bone Disease in Hyperparathyroidism

10 Berson and Yalow

11 Changing Presentation of Primary HPT Silverberg et al. Am J Med 1990;89:327

12 1 0 Hyperparathyroidism Clinical Manifestations Asymptomatic Kidney stones Polyuria Depression Memory loss Fatigue Constipation Osteoporosis Calciphylaxis Hypercalcemic crisis Musculoskeletal pain Peptic ulcers Pancreatitis Brown tumors

13 1 0 Hyperparathyroidism Diagnosis Elevated calcium and PTH levels Note normocalcemic hyperparathyroidism Low phosphorous level 24 hour urine calcium level Normal or elevated FHH (24 hour level < 100 mg) Low Ca/Cr ratio Genetic testing available Vitamin D levels

14 FHH Familial hypocalcuric hypercalcemia Gene mutation for the CaSR AD with high penetrance Mildly elevated serum Ca and PTH Low urinary calcium excretion (<100 mg/day) Calculate Ca/Cr clearance ratio Ca/Cr Clearance = <0.01

15 Indications for Parathyroid Surgery in Asymptomatic HPT New Guidelines Serum calcium > 1 mg/dl above normal Low bone density (T score < -2.5 L. spine, total hip, femoral neck, distal 1/3 radius) Vertebral fracture on films (x-ray, CT, MRI, VFA) Decreased renal fxn GFR < 60 ml/min 24 h urine Ca > 400 mg, stones (x-ray, U/S, CT), increased stone risk on biochemical analysis Age < 50 Bilezikian et al. Guidelines for the Management of Asymptomatic Primary Hyperparathyroidism: Summary Statement from the 4 th International Workshop. JCEM 2014.

16 Bilezikian et al. JCEM. October 2014

17 Indications for Parathyroid Surgery Other Things to Consider Neuropsychiatric symptoms and QOL Bone density and fracture risk Data confirms improvement s/p surgery Cardiovascular disease and survival Age and operative risk

18 Changes in Bone Density Over Time in Patients Who Undergo Observation Versus Surgery Silverberg et al JCEM 94:351.

19 Normocalcemic Hyperparathyroidism 62 yo female Ca 10.3, ionized 1.30 [normal range: ] PTH 85 Bone density femoral neck -2.2, spine -2.6 U/S: Heterogeneous thyroid c/w Hashimoto's. No obvious parathyroid adenoma. Small hypoechoic lesion right lower pole mildly suspicious for an enlarged parathyroid gland Sestamibi scan negative Does this patient have HPT? Is surgery likely to have a positive impact? Is a neck exploration warranted?

20 37 patients Average age 58 (range 32 to 78) Calcium 9.4 +/- 0.1 (SEM), PTH 93 +/-5 7 patients (19%) became hypercalcemic, all within three years Some persistently normocalcemic patients developed evidence for progressive hyperparathyroid disease

21 Normocalcemic hyperparathyroidism Considerations at the initial presentation.. Exclude all possible causes of secondary hyperparathyroidism. Take a detailed history, including h/o fragility fractures, recurrent nephrolithiasis and use of thiazides or lithium Laboratory studies: 25-OH vitamin D level renal function urine calcium excretion serum phosphorus

22 Prevalence of Normocalcemic Hyperparathyroidism Cusano et al., Journal of Clin Dens 2013

23 Relation between vitamin D and PTH Singhellakis et al. Hormones 2011

24 Ongoing Care of Hyperparathyroidism

25 If No Indication For Surgery How to Follow? Bilezikian et al. JCEM. October 2014

26 Management of Patients with Ongoing Hyperparathyroidism Continue to follow patient closely Hydration and exercise Calcium (1000 to 1200 mg/day) Don t cut out all calcium from the diet. Vitamin D - keep level >30 ng/ml ( IU/day) Avoid drugs that increase Ca (eg. Lithium, Thiazides)

27 Medications to Control Ca, PTH and Preserve Bone Density Calcitonin for acute hypercalcemia Bisphosphonates Zoledronic acid and pamidronate (IV, for acute Rx) Alendronate and risedronate (oral, for long term Rx) Cinacalcet Inhibits PTH secretion and drops Ca level No effect on BMD Increases urinary calcium excretion

28 Cinacalcet Effects on Calcium and PTH Peacock et al JCEM Jan;96(1):E9-18.

29 Parathyroid Locations Kronenberg H. Williams Textbook of Endocrinology, 11 th Edition.

30 Failed Parathyroid Exploration 41 yo woman presents after failed parathyroid exploration During first pregnancy, developed intractable kidney stones and noted to be hypercalcemic (10.3) PTH 143, Ph 2.7, 25OHD 29 At 28 weeks, she underwent parathyroid exploration During surgery: 2 glands were removed, a total thyroidectomy was done along with a cervical thymectomy without obvious parathyroid adenoma

31 Failed Parathyroid Exploration Pathology of glands removed was normal Referred to us Non-invasive studies including sestamibi and U/S were negative Vein catheterization was done

32 Venous Sampling

33 Selective Venous Sampling for Patient VW 09/29/ :25 #1 RT SUPERIOR 71* #2 LOW RT SUPERIOR 82* #3 ORIGIN RIGHT VERTEBRAL 70* #4 LEFT VERTEBRAL 94* #5 LEFT SUPERIOR 83* # 6 LOW LEFT SUPERIOR 82* #7 LEFT INTERNAL MAMMARY 81* #8 THYMIC 67* #9 THYMIC >5000* #10 COMMON INFERIOR TRUNK 260* #11 LEFT SIDE LEFT INOMINATE 83* #12 MID LEFT INOMINATE 80* #13 RT SIDE LEFT INOMINATE 470* #14 RT INOMINATE 165* #15 SVC 207*

34 Right internal mammary artery 2 3 Final images after ablation 6 1 Parathyroid adenoma Subselective catheterization Parathyroid adenoma Coils V.W. Parathyroid ablation 4 5 Persistent staining Adenoma prior to starting ablation Adenoma after contrast ablation-note swelling

35 Selective left inferior thyroid Superselective injection Coils following ablation Mediastinal adenoma Post angiography Post injection of Hyperosmolar contrast Selective arteriography and ablation

36 1. 2a. 2b. 3. Arterial phase Tissue phase Arteriogram

37 Case # 3 M.T. 63 yo female Dx with primary HPT Neck exploration March 2006 Pre-op sestamibi right lower gland Enlarged right lower gland removed Pathology hypercellular Identified 3 normal glands iopth remained elevated

38 Post-operative labs Calcium PTH 142 Case # 3 M.T. 63 yo female Bone density osteoporosis Symptoms Extreme fatigue, bone/joint pain

39 Case # 3 M.T. 63 yo female Sestamibi and U/S negative Venous sampling c/w right sided lesion

40 Patient M.T. 63 yo female What next?

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43 Case # 3 M.T. 63 yo female Focused exploration Parathyroid adenoma TE groove at the level of the thoracic inlet Blood supply arising superiorly Likely descended right upper gland Intraoperative PTH 215 to 9 Post-operative labs Ca 9.5, PTH 26

44 Take Home Points Parathyroid disease is a biochemical diagnosis Imaging should be reserved for when you are planning on taking the patient to surgery U/S, sestamibi, and 4D-CT scan are the first line imaging modalities to locate a parathyroid adenoma Only experienced parathyroid surgeons should be used

45 Take Home Points Patients who require only medical follow up need close observation Difficult cases require referral for more sophisticated diagnostic studies Don t rush patients to surgery if unsure of diagnosis or indications If you don t know what to do, don t do anything -Robert Loeb, MD

46 Acknowledgements Long-standing collaborators: Dr. Barry Sacks Dr. Harvey Eisenberg Endocrine Fellows Patients

47 Question 1 Chose the answer that includes, in all 3 listed, indications for surgery in primary HPT, as outlined in the recent consensus conference: A. Osteoporosis, hypercalcuria, calcium > 11 B. Osteoporosis, age < 50, calcium > 12 C. Osteopenia, kidney stones, musculoskeletal pain

48 Question 2 The best laboratory data supporting the diagnosis of primary HPT is: A. calcium, PTH, albumin, phosphorous B. calcium, albumin, PTH, phosphorous, 24-hour urine calcium, vitamin D C. calcium, albumin, phosphorous, vitamin D

49 Question 3 Treatment recommendation for normocalcemic hyperparathyroidism: A. Cinecalcet and bisphosphonates B. Surgical exploration C. Close monitoring for progression of disease and complications

50 Question for Panel The patient has a high calcium level and hyperparathyroidism, and you suggest that they take 1000mg of calcium daily, preferably in their diet. When they question your recommendation based on their high calcium level, how do you answer them?