1. Dr Malith Kumarasinghe MBBS (Colombo)

2.  Swedish Medical Student  Discovered Parathyroid gland In 1880  Last major organ Identified in humans

3. Parathyroid glands - Anatomy 1. Usually four – two on each side (2-8 is normal) 2. Lie on the posterior surface of thyroid 3. May be embedded within thyroid gland 4. Required for life

4. Parathyroid Glands are located on the posterior aspect of the thyroid; sometimes the tissue is embedded within thyroid tissue.

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8.  Renal effects (steady state maintenance) ◦ Inhibition of phosphate transport ◦ Increased reabsorption of calcium ◦ Stimulation of 25(OH)D-1alpha-hydroxylase  Bone effects (immediate control of blood Ca) ◦ Causes calcium bone release within minutes ◦ Chronic elevation increases bone remodeling and increased osteoclast- mediated bone resorption ◦ However, PTH administered intermittently has been shown to increase bone formation and this is a potential new therapy for osteoporosis

9.  Parathyroid related ◦ Primary Hyperpara, Li tx, Familial Hypocalcuric Hypercalcemia  Malignancy ◦ Solid tumor, Hematologic  Excessive Vitamin D ◦ Intoxication, Granulomatous Disease  High bone turnover ◦ Hyperthyroid, Immobilization, Vit A  Renal Failure ◦ 2ndary Hyperpara, Aluminum, Milk-Alkali

10.  **Primary hyperparathyroidism and cancer account for 90% of cases of hypercalcemia

11.  Estimated incidence is 1 case per 1000 men and 2-3 cases per 1000 women ◦ Incidence increases above age 40 ◦ Most patients with sporadic primary hyperparathyroidism are postmenopausal women with an average age of 55 years

12.  Causes ◦ Solitary Adenoma ◦ Parathyroid Carcinoma (rare) ◦ Multiple endocrine neoplasia (rare)  Hypersecretion of PTH ◦ Hypercalcemia, ◦ HypOphosphatemia

13.  ~80% asymptomatic  Stones (Kidneys) ◦ Calcium deposition and nephrolithiasis ◦ Urinary tract obstruction  Bones ◦ Osteitis Firosa Cystica  Increased osteoclasts  Increased bone turnover  Reduced cortical bone density  Moans ◦ Fatigue, Depression, Confusion

15.  Other ◦ N/V, Constipation, Polyuria ◦ Short QT  Severe – “Parathyroid Crisis” ◦ Renal Failure from nephrocalcinosis ◦ Coma, Cardiac Arrest

16.  Diagnosis ◦ Elevated serum PTH immunoassay (high sens), high calcium, low or normal phos (decr prox tubular reabsorption) ◦ Elevated 1,25(OH) 2 D (low spec)  Imaging ◦ 99m-technetium sestamibi ◦ Ultrasound

17. Scintigraphy Images Traditional Sestamibi Sestamibi-SPECT

18.  Treatment ◦ Surgical Indications  Ca > 11.5, T-score < -2.5, renal stones ◦ Medical  Replace volume  Facilitate calciuresis (loop diuretics)  Bisphosphonates – decrease bone reabsorption.  Calcitonin  Hormonal Therapy – Raloxifene, other SERMs  Cinacalcet (not FDA approved)

19. Familial Syndromes  MEN I  MEN IIA  Familial Hypocalciuric Hypercalcemia  Hyperparathyroidism-jaw tumor syndrome –Fibro-osseous jaw tumors –Renal cysts –Solid renal tumors  Familial isolated hyperparathyroidism

20. MEN I  MEN I –1 in 30,000 persons – Features:  Hyperparathyroidism (95%) –Most common and earliest endocrine manifestation  Gastrinoma (45%)  Pituitary tumor (25%)  Facial angiofibroma (85%)  Collagenoma (70%)  HPT in MEN I –Early onset –Multiple glands affected –Post-op hypoparathyroidism more common (more extensive surgery) –Successful subtotal parathyroidectomy followed by recurrent HPT in 10 years in 50% of cases

21. STIGMATA OF MEN I Lipomas Collagenomas Angiofibromas

22. MEN IIA (Sipple’s Syndrome)  Features: –MTC(95%) –Pheochromocytoma(50%) –HPT(20%)  RET mutation (98%)  1 in 30,000-50,000 people  Usually single adenoma but may have multi-gland hyperplasia

23. 1. Vit. D deficiency 2. Primary decreased calcium absorption in elderly 3. Increased phosphate in acute or chronic renal failure

24.  Treatment ◦ Phos Binders ◦ Vitamin D analogs  negative feedback on PTH gene transcription  Limited use in setting of hypercalcemia ◦ Cinacalcet (Sensipar)

25.  Tertiary Hyperparathyroidism is essentially secondary hyperparathyroidism that is no longer responsive to medications.  Also occurs after renal transplant, where hypertrophied glands continue to oversecrete PTH (set point alteration)  May require surgery

28.  Features of Hypocalcaemia ◦ Tetany ◦ Depression ◦ Perioral paraesthesiae ◦ Carpopedal spasm-Trousseau’s sign ◦ Cataract ◦ Facial muscle twitch-Chvostek’s sign

29.  Addison’s  Pernicious anaemia  Hypothyroidism  Hypogonadism

30.  Alfacalcidol Lifelong follow up needed