Hyperparathyrodism

Hypoparathyrodism

Calcium Regulation
99% of body calcium in skeleton Miscible Pool: 40% bound to protein, 13% complexed w/ anions, 47% free ionized PTH: Increased Ca, Decreased PO4, Increased Vitamin D Vitamin D: Increased Ca, Increased PO4, Decreased PTH (slow) Kidney, Bones, GI Tract

Calcium Regulation

Localization
4 glands in 87 % of patients ; range 2 - 6 glands Internal carotid artery to AP window Superior parathyroid glands within 1 cm of RLN piercing cricothyroid membrane

Biologic Effects of PTH

To regulate ionized [Ca2+] levels by concerted effects on three principal target organs: bone, intestinal mucosa, and kidney Other hormones related to Calcium : Vitamin D, Calcitonin Inhibits the reabsorption of phosphate in the renal proximal tubule

Hyperparathyrodism
Usually asymptomatic Fatigue and weakness Bone and joint pain (fracture of long bone), stones and hematuria(reflect decreased bone density & nephrolithiasis) Osteitis fibrosa cystica (Brown tumor) and nephrocalcinosis rare

Etiology of hyperparathyrodism
Primary hyperPTH (most common) Parathyroid adenoma (85%), Parathyroid hyperplasia (15%) Parathyroid carcinoma (< 1%) Secondary HyperPTH Usually renal failure Tertiary HyperPTH Chronic Renal Failure; low or normal Ca
Frank hypercalcemia

HYPERCALCEMIA
Hypercalcemia total serum calcium > 10.5 mg/dl ( >2.5 m mol/L)) or ionized serum calcium > 5.6 mg/dl ( >1.4 m mol/L )

Normal serum calcium levels are 8 to 10 mg/dl

GRADING OF HYPERCALCEMIA

Clinical manifestation of hypercalcemia

Hyperpolarization of cell membranes

Ca 10.5 11.9 mg /dl can be asymptomatic

Ca > 12 mg/dl multisystem manifestations :
Renal : polyuria , nephrolithiasis GI : anorexia , nausea , vomiting , constipation , pancreatitis Neuro - psychiatric : weakness , fatigue , confussion, psychosis, stupor , coma

Cardiovascular : Shortened QT interval on ECG, bradyarrhythmias and heart block and cardiac arrest Cornea : band keratopathy

PATHOPHYSIOLOGY

Diagnosis of Hyper-PTH
Elevated serum Ca X 3 Elevated PTH Other :

Albumin Alkaline Phosphatase Phosphorous BUN/Cr 24-hour urine Ca Bone Mineral Density

Medical Management
Severe Hypercalcemia

Saline-furosemide diuresis Bisphosphonates (onset of action 2448h) Calcitonin (immediate onset) Hemodialysis

Surgical Management
NIH Guidelines (2002)
Serum calcium is greater than 1 mg/dL above the upper limits of normal Previous episode of life-threatening hypercalcemia Creatinine clearance is reduced below 70% of normal; Kidney stone is present Urinary calcium is markedly elevated (> 400 mg/24 h); BMD at the lumbar spine, hip, or distal radius is substantially reduced (> 2.5 SD below peak bone mass; T score < 2.5) < 50 years of age Long-term medical surveillance is not desired or possible

Surgical Management
Adenoma Unilateral vs. Bilateral Exploration rPTH vs. Frozen Section Hyperplasia/Multiple adenomata Subtotal less hypocalcemia Subtotal w/ autotransplantation MEN, Renal Failure Total w/ Cryopreservation up to 1 year

Hypoparathyrodism
Etiology Iatrogenic Neck irradiation Surgically induced Infiltrative Diseases Hemachromatosis Sarcoidosis Thalassemia Wilson's disease Amyloidosis Metastatic carcinoma

Neonatal 2 to maternal hyperparathyroidism Autoimmune Genetic or developmental disorders DiGeorge Syndrome Calcium sensor mutation

Sign and Symptoms of Hypocalcemia

Neuro: Paresthesias, fasciculations, muscle spasm, tetany, irritability, movement disorder, SEIZURE, psychosis Visual: Cataracts, optic neuritis, papilledema Pulmonary: Bronchospasm CV: Prolonged QT, CHF, Hypotension GI: Dysphagia, abdominal pain, biliary colic

Signs of hypocalcaemia
Chvosteks sign:
Tap facial nerve twitching of facial muscles

Trousseaus sign:
Inflate arm cuff > diastolic BP 3 minutes carpopedal spasm
Flexion at Wrist

Flexion at MCP joints

Flexion of thumb against palm Extension of PIP joints and DIP joints Adduction of fingers (forms a cone)

Treatment of hypocalcemia due to HypoPTH

Calcium gluconate in saline Vitamin D Calcium Calcitriol Thiazide

MULTIPLE ENDOCRINE NEOPLASM (MEN)

Multiple Endocrine Neoplasma

MEN type 1 :

tumors of the parathyroid tumor of anterior pituitary pancreatic islets tumor

MEN tipe IIa :
medullary carcinoma of the thyroid, pheochromocytoma, hyperparathyroidism

Osteoporosis
Osteoporosis is a disease characterized by low bone
mass and microarchitectural deterioration of bone tissue, leading to Enhanced bone fragility Increase in fracture risk 1 in 2 white and Asian postmenopausal and at least 1 in 8 older and of other racial are likely to have an osteoporotic fracture at some time during their lifetime. World Health Organization issued diagnostic criteria for postmenopausal women based on measurements of bone mineral density (BMD) or bone mineral content.

Osteoporosis
Clinical manifestations are vertebral and hip fractures, although fractures can occur at any skeletal site.
Osteoporosis is defined as a BMD T score of 2.5 standard deviations below the young adult mean value

Epidemiology
Osteoporosis health problem especially postmenopausal women Osteoporosis affects >10 million individuals in the US, but only a small proportion are diagnosed and treated Increased hip fractur in Asia global issue health care, social and economic problems.
Claus Christiansen, Am J Med 1993 dan WHO 1998

Osteoporosis
Primary Osteoporosis Osteoporosis tipe 1 Osteoporosis tipe 2 Osteoporosis Juvenile Osteoporosis Adulthood
Secondary Osteoporosis

Fracture of Osteoprosis

Vertebrae Distal Radius Collum femoris

Risk Factor
Non-Modifiable :
History OP in 1st degree relative History of fracture in adult Sex Advanced age Race

Modifiable :
Smoking Low Body Weight Early menopause Alcoholism Low Ca intake Inadequate physical activity Disease n drugs

PATHOGENESIS OF OSTEOPOROSIS FRACTURES

Heredity Inadequate Peak bone mass Low bone density

Aging

Menopause Increased Bone loss

Fractures
Local Factors

Trauma

Sporadic factors

Diagnostic
X-ray exam > 40% bone loss Bone mineral density DEXA - Dual Energy X-ray Absorptiometry (gold stardard) Biochemical exam. blood : calsium, PTH, osteocalcin urine : urine calcium, NTx (N-telopeptide)

Bone loss typically seen in X ray exam if bone density less then 40% or more

USG as diagnostic tool for OP

Dual Energy X-ray Absorptiometry (DEXA) 10

CLASSIFICATION OF BONE MINERAL DENSITY LEVELS

DESCRIPTIONS
Normal BMD Low BMD or osteopenia

MEANING
BMD above 1 SD from the young normal mean BMD between - 1 SD and 2.5 SD BMD is reduced < 2.5 SD BMD is reduced < 2.5 SD in the presence of fractures

Osteoporosis
Severe or established osteoporosis

WHO Technical Report Series. Geneva: WHO, 1994

WHO SHOULD HAVE BMD MEASSURE?

The National Osteoporosis Foundation recommend BMD measurements: for postmenopausal women > 65 yrs, those < 65 yrs should have one or more risk factors of osteoporosis besides menopause The International Society for Clinical Densitometry (ISCD) recommed BMD measurement: for postmenopausal women > 65 yrs, and men > 70 yr those younger than postmenopausal women and men < 50 y.o. with one or more risk factors

Osteoporosis therapy
Increase bone density
Sodium fluorida Paratiroid hormone Steroid anabolic Calcium

Inhibit bone resorption

Estrogen ( Primarin, Livial) Calcitonin ( Miacalcic) Bisphosphonate ( Risendronate, alendronate) SERMs Selective Estrogen Receptor Modulators (Raloxifen)

Calcium
A G E (year) < 0.5 0.5 1 1 10 11 24 25 49 Menopause (with estrogen R/) < 65 Menopause (without estrogen R/) < 65 Pregnant or breast feeding Women > 65 CALCIUM (mg) 400 600 800 1200 1500 1000 1000 1500 1200 1500 1500

How to prevent Osteoporosis

Calcium supplement Stop smoking Stop alcohol Exercise ( osteoporosis exercise)