DISORDERS OF MINERAL

METABOLISMXu, Mingtong

Department of Endocrinology, The Second Affiliated Hospital of Sun Yat-

Sen University

Introduction:

Mineral Metabolism Clinical Disorders Hyperparathyroidism Hypoparathyroidism Osteoporosis

Introduction: Mineral Metabolism

Calcium ions phosphate ionsExtracellular Con. total in serum 2.510-3M 1.010-3M free 1.210-3M 0.8510-3M Function bone mineral bone mineral blood coagulation membrane excitability

Introduction: Mineral Metabolism

Calcium ions phosphate ionsIntracellular Con. 10-7M 1-210-7M Function signal for: structural role neuronal activation high energy bonds hormone secretion regulation of proteins muscle contraction by phosphorylation

Calcium and Phosphate Homeostasis

Parathyroid Hormone (PTH)

Calcitonin

Vitamin D

Calcium and Phosphate Homeostasis

Parathyroid Hormone BONE

1. Activate osteoclasts 2. Osteoclast development 3. Proteases to digest matrix 4. Inhibit collagen synthesis 5. Inhibit osteoblast development 6. Stimulate osteoblasts via release of

matrix growth factors 7. Stimulate osteoblasts via IGF I

Parathyroid Hormone

KIDNEY 1. Stimulate calcium reabsorption 2. Inhibit phosphate and bicarbonate

reabsorption

3. Stimulate synthesis of 1,25(OH)2D3 in the proximal tubule by activating 25(OH) 2D3

Parathyroid Hormone

INTESTINE

Stimulate calcium absorption

Calcitonin BONE

Stimulate osteoblasts Inhibit osteoclast

KIDNEY Inhibit calcium and

phosphate reabsorption INTSTINE

Inhibit calcium absorption

Vitamin D

INTSTINE Stimulate calcium absorption

BONE Stimulate osteoclast and osteoblasts

KIDNEY Stimulate calcium and phosphate

reabsorption

CLINICAL DISORDERHypercalcemic Disorder

Parathyroid-Dependent Hypercalcemia

Primary Hyperparathyroidism

Familial Hypocalciuric Hypercalcemia

Lithium-induced Hypercalcemia

Parathyroid-Independent Hypercalcemia

HYPERCALCEMIA DISORDER

Parathyroid-Independent Hypercalcemia Hypercalcemia of Malignancy Vitamin D Intoxication Sarcoidosis and Other Granulomatous Hyperthyroidism Vitamin A Intoxication Adrenal Insufficiency Thiazide Diuretics Milk-alkali Syndrome Renal failure

CLINICAL DISORDER

Hypocalcemic Disorder

Parathyroid-Related Disorder

Vitamin D-Related Disorder

Neoplasms

Neonatal Hypocalcemic

CLINICAL DISORDER Hyperphosphatemia

Impaired Renal Phosphate Excretion Increased Extracellular Phosphate

Hypophosphatemia Reduced Renal Tubular Phosphate Reabsorption Impaired Intestine Phosphate Absorption Shifts of Extracellular Phosphate into Cells/ Bone

HYPERPARATHYROIDISM

Primary Hyperparathyroidism

Primary abnormality of the parathyroid glands leads to inappropriate secretion of PTH.

Secondary Hyperparathyroidism

PRIMARY HYPERPARATHYROIDISM

ETIOLOGY Parathyroid Adenoma 75-80% Primary Parathyroid Hyperplasia 20%, all glands Parathyroid carcinoma 1-2% Multiple Endocrine Neoplasia (MEN I) parathyroid, anterior pituitary and pancreatic islet Multiple Endocrine Neoplasia (MEN II) medullary carcinoma of thyroid, pheochromocytoma and parathyroid

PRIMARY HYPERPARATHYROIDISM

CLINICAL MANIFESTATION relative benign, asymtomatic women are affected often between age of 15 and 65

Hypercalcemia Bone Kidney

HYPERCALCEMIA Nuropsychiatric symptoms: weakness,

fatigue, apathy, difficulty in concentrating, depression, dementia, psychosis, coma, irritability, memory loss, emotional lability

Neuromuscular symptoms: symmetrical proximal weakness, gait disturbance, muscle atrophy

Hypertension

HYPERCALCEMIA

Gastrointestinal symptoms: anorexia, nausea, vomiting, constipation, abdominal pain, peptic ulcer, acute and chronic pancreatitis

Ectopic calcification: conjunctival calcification, band

keratopathy

Skeletal InvolvementBone pain and tendernessPathologic fractureDeformityRadiographic feature: generalized demineralization of bone, subperiosteal resorption, brown tumors, pathologic fracture, skull: mottled,groundglass;

dental erosion

骨质疏松时骨折好发部位

骨皮质变薄

纤维囊性骨炎

棕 色 瘤

棕 色 瘤

骨 质 疏 松

Renal Manifestation

Calcium nephrolithiasis recurrent , severe

NephrocalcinosisFunction abnormalities

impaired concentrating ability renal failure

LABORATORY TEST

Serum Ca P ALP Urine Ca /+ P

PTH Radiography: bone, kindeyLocalization: ultrasonography, CT, MRI, 99Tc-sestamibi

DIAGNOSIS

Serum Ca

Urine Ca

PTH

MANAGEMENTSurgical TreatmentTherapy for Severs Hypercalcemia Serum calcium3.75mmol/L Disturbances of nervous system and

gastrointestinal function: fatigue, lethargy, confusion, coma, anorexia, nausea, constipation, abdominal pain

Polyuria,nocturia and polydipsia

Therapy for Severs Hypercalcemia

Rehadration 2-4L/d 0.9%NaCl

Bisphosphonates Diuretic Calcitonin Dialysis Glucocorticoid

HYPOPARATHYROIDISM

Parathyroid disease PTH

Pseudohypoparathyroidism:

resistance to the PTH PTH

HYPOPARATHYROIDISM

ETIOLOGY 1. Congenital of Inherited Parathyroid

disorders

2. Impaired PTH Secretion

3. Postsurgical Hypoparathyroidism

4. Infiltrative Disorders

HYPOPARATHYROIDISM

CLINICAL MANIFESTATION1. Neuromuscular irritability perioral paresthesia tingling of the fingers and toes spontaneous or latent tetany Chovestek’ sign Trousseau’s sign

CLINICAL MANIFESTATION

2. Cardiovescular disorders EKG: QT intervals ventricular arrhythmias3. Calcification of basal ganglia

extrapyramidal disorders4. Cataract5. Defects in mineralization of new bone

and calcification of teeth

LABORATORY TEST

Serum total calcium 2mmol/L free calcium protein-bound component

Serum free calcium can be affected by variety of factors: hypoalbuminemia, alkalosis etc. Serum phosphate Urine Ca, P PTH

DIAGNOSIS

Serum Ca Urine Ca PTH

TREATMENT

Acute Hypocalcemia

1. 10% calcium gluconate 10-20ml iv

2. Sedative

3. Magnesium replacement

4. Monitoring of calcium level

TREATMENTChronic Hypocalcemia

1. Dietary2. Exogenous calcium replacement 1-1.5g daily3. Vitamin D4. Monitoring of calcium level

OSTEOPOROSIS

A disease characterized by low bone

mass and microarchitectural

deterioration of bone tissue, leading

to enhanced bone fragility and a

consequent increase in fracture risk.

OSTEOPOROSIS

OSTEOPOROSIS Primary osteoporosis

Type I osteoporosis

(postmenopaused osteoporosis)

vertebral fracture

Type II osteoporosis (senile osteoporosis)

hip fracture

Secondary osteoporosis

PATHOGENESIS

Primary osteoporosis 1. Fail to achieve optimal peak bone

mass; 2. Bone loss caused by increased bone

resorption; 3. Inadequate replacement of lost bone

as a result of decreased bone formation.

PATHOGENESIS Secondary osteoporosis

1. Endocrine disorders 2. Hematopoietic disorder 3. Connective tissue disorders 4. Drug-induced disorders 5. Immobilization 6. Renal disease 7. Nutritional and gastrointestinal

disorders

CLINICAL FEATURES

Vertebral crush fracture back pain, height loss, kyphosis, impairment of chest wall function

Hip fracture femoral neck, the base of greater

trochanterColles fracture

LABORATORY TEST

Biochemical measurements 1. Markers of bone resorption

fasting urinary calcium excretion

urinary hydroxyproline excretion

urine pyridinoline or deoxypyridinoline

Tartrate-resistant acid phosphatase

LABORATORY TEST

Biochemical measurements 2. Markers of bone formation

alkaline phosphatase

osteocalcin

amino- and carboxy-terminal extension peptides of procollagen

LABORATORY TEST

Bone densitometry

dual-energy X-ray absorptiometry

Bone biopsy

Radiographs and Bone scans

DIAGNOSIS Category DefinitionNormal A value for BMD/BMC1SD of the young adult reference mean.Low bone mass A value for BMD/BMC1SD and 2.5 (osteopenia) SD lower than the young adult mean.Osteoporosis A value for BMD/BMC 2.5SD lower than the young adult mean.Severe A value for BMD/BMC 2.5SD lowerOsteoporosis than the young adult mean in the presence of one or more fragility fractures.

TREATMENT

1. Nutrition and calcium replacement2. Exercise and lifestyle3. Hormone replacement therapy4. Bisphosphonates5. Calcitonin6. Estrogen analogues