Endocrinal and metabolic disorders

1. Endocrinal, metabolic and nutritional bone disorders By Dr. Tarek Mansour Faculty of medicine Al-Azhar university

2. The amount of bone at any part of skeleton at ant time depend up on the balance between bone resorption and formation.

3. The three hormonal regulators include Parathormone (PTH), produced by the four parathyroid glands on the back side of the thyroid gland. The active form of vitamin D produced in the proximal renal tubule 1,25(OH)2. And calcitonin produced by the parafollicular cells in the thyroid gland.

4. PTH The major function of PTH is to prevent the dangerous reduction in the serum calcium level by: Increasing the production of 1,25,(OH)2 vitamin D in the kidney which then increases the absorption of calcium from the gut and renal tubule. PTH also activates osteoclastic mobilization of calcium from bone mineral. PTH is to promote urinary excretion of phosphorous.

5. The major function of 1,25,(OH)2 vitamin D is to activate the absorption of calcium from the gut and bone. The least important calcium regulator is calcitonin which is designed to prevent an increase of serum calcium by inhibiting the osteoclastic mobilization of calcium at the bone level.

6. Hormonal regulation of calcium and phosphate The crude inactive form of vitamin D comes from the gut and the skin that is exposed to sun light which is then transported to the liver for its first phase of activation by a hydroxylation process at the 25 position of the sterol ring. This still inactive form then goes to the kidney for its finial activation by a hydroxylation process on the 25 position of the sterol ring. This now activated vitamin D acts as a hormone similar to PTH to help absorb calcium from the gut and bone.

7. Calcium and phosphate metabolism

8. Mobilization of Ca from Bone When the serum calcium level drops below normal the parathyroid gland puts out PTH which then activates resting bone cells to differentiate into an active lytic osteoclast. On the bone surface the active brush border of the cell secrets collagenase enzyme which dissolves bone mineral thus liberating calcium and phosphorous ions which are then transported across the cell to its outer membrane Where a 1,25,(OH)2 pumping mechanism transports the calcium and phosphorous into the blood stream.

9. Metabolic, endocrinal and nutritional bone diseases affect the skeleton through too much or too little calcified bone. Too little calcified bone is either due to - Decrease bone formation. - increase bone resorption.

10. Radiographic criteria of endocrinal, metabolic and nutritional diseases They are commonly diffuse or at least multifocal, although isolated bone lesion may be found as in brown tumor. They tend to involve specific location, and tend to be symmetrical in the body.

11. Endocrinal diseases

12. Endocrinal disorders Acromegaly. Gigantism. Cushing syndrome. Hyperparathyroidism. Hypoparathyroidism. Pseudohypoparathyroidism. Pseudo- pseudohypoparathyroidism . Hyperthyroidism. Hypothyroidism.

13. Acromegaly (hyperpituitrism). Result from excess production of growth hormone by anterior pituitary gland. In adult Acromegaly. In children Gigantism

14. Radiological findings Skull Thickened calvarium. Frontal bossing. Prognathism. Enlarged mastoid air cells and sinuses. Enlargement of pituitary fossa.

15. Spine. Enlarged vertebral bodies with posterior scalloping. Increase disc height.

16. Hands. Enlarged bone and soft tissue shadow. Spade like terminal tufts or arrowhead distal phalanges.

17. Measurments Sesamoid index of the thumb. < 40 mm. in male. < 32 mm. in female. Tuftal width of the third finger. < 10 mm. in female. < 12 mm. in male. Joint space of the second MCP joint. = 2.5 mm. in both men and female. Thickness of phalangeal soft tissue < 26 mm. In male. < 23 mm. in female.

18. Joint spaces Wide joint spaces due to enlarged articular cartilage Feet Increase thickness of fat pad Long bone Elongated with prominent muscle attachment. Calcifications Ear pinna Chondrocalcificinosis Cardiomegaly + visceromegaly

19. Gigantism Imaging findings. Proportional yet exaggerated bone growth. Bone increase in length and diameter. Enlarged sella turcica.

20. Cushing disease It is hyperadrenocorticism due to Anterior lobe tu. Adrenal cortex tu. Complication of therapy. Imaging findings. Osteoporosis (more at trabecular bone). Increase insufficiency fractures in vertebra, scapula, ribs and pubic bones.

21. HYPERPARATHYROIDISM

22. Hyperparathyroidism It is defined by increase level of parathormone and parathormone peptides in the serum. It can be divided in to three types. Primary. Secondary. Tertiary.

23. Primary hyperparathyroidism May be the result of. Adenomas (single or multiple) 90% Diffuse hyperplasia. Carcinomas. In all cases : serum Ca level is increased. This disorder is due to a primary defect in the parathyroid glands >>> increased secretion of PTH >>> increase serum calcium and decrease serum phosphorus. The increase in serum calcium concentration is due in part to activation of the osteoclastic system.

24. Secondary hyperparathyroidism Is induced by any condition or circumstance that cause serum calcium to fall. It may be the result of: Vit. D deficiency. Chronic renal failure. Intestinal malabsorption of Ca (rare). In diseased kidney>>> decrease active Vit. D >>> decrease int. ca absorption>>> hypocalcaemia>>> stimulate parathyroid gland>>> increase PTH

25. Tertiary hyperparathyroidism It is result of long standing secondary hyperparathyroidism due to chronic renal failure. In tertiary hyperparathyroidism, the parathyroid glands function autonomously.

26. Clinical presentation In primary hyperparathyroidism may be: Asymptomatic hypercalcemia. In younger patients, the most common presentations are: Renal stone and Nephrocalcinosis (25-35%). High blood pressure (40-60%). Acute arthropathy (pseudogout). Other symptoms as osteoporosis, peptic ulcer, acute muscle weakness & mild non specific symptoms.

27. To understand radiological changes in PTH you have to know: An elevated level of parathormone : In early phase>>>> increase bone mass In later stages>>>> trabecular bone resorption may occur. Because HPT today is usually detected early through increased level of serum calcium , we observe more patients with more bone formation and fewer patients with less bone.

28. Radiological findings in primary hyperparathyroidism. Subperiosteal bone resorption. Subchondral bone resorption. Subligamentous bone resorption. Intracortical bone resorption. Osteopenia. Brown tumor. Erosive arthropathy. Chondrocalcinosis. Renal calculi, rarely Nephrocalcinosis. Rarely osteosclerosis.

29. Radiologic findings of HYPERPARATHYROIDISM The M/C radiologic abnormality is generalized osteopenia . Bone resorption , bone sclerosis, brown tumors , chondrocalcinosis , soft tissue calcification, and vascular calcification. Brown tumors appear as well-defined lytic lesions. After resection of parathyroid adenomas, the lesions may become sclerotic and may mimic blastic metastasis. Bone resorption , the most characteristic finding , is usually classified as subchondral, trabecular, endosteal , intracortical , subperiosteal, subligamentous , and subtendinous .

30. Subperiosteal resorption - M/C Usually occurs in the hands and feet . M/C affected site: radial aspects of the middle phalanges. Acro-osteolysis or phalangeal tufts resoption may also be present. Trabecular resorption Often seen in the diploic space of the skull, where it has a characteristic salt and pepper appearance . Subchondral resorption May be seen in the sacroiliac joints, sternoclavicular joints, acromioclavicular joints, symphysis pubis, and discovertebral junction .

31. AP radiograph of the hand in a 66-year-old woman with primary hyperparathyroidism owing to parathyroid adenoma shows subperiosteal bone resorption ( arrows) along the radial aspect of 2nd, 3rd, and 4th middle phalanges.

32. AP radiograph of the knee in a child with hyperparathyroidism shows subperiosteal bone resorption ( arrow ) along the proximal medial tibia.

33. Subchondral bone resorption Sites : Outer and sometimes inner end of the clavicle. Symphysis pubis. Sacroiliac joints. Vertebral end plates.

34. Subligamentous resorption: Sites: Greater & lesser trochanter . Ischial tuberosity Inferior calcaneum Inferior surface of clavicle.

35. Intracortical bone resorption Linear translucencies within the cortex (cortical tunnelling ), esp. tubular bones of the hands, 2-5 mm. oval or cigar shaped. Loss of corticomedullary junction. In the skull, granular or mottled appearance (pepper-pot) or salt and pepper. Not specific for hyperparathyroidism.

36. Osteopenia More common in postmenopausal women and the elderly. Loss of corticomedullary junction may occur.

37. Chondrocalcinosis Due to deposition of calcium pyrophosphate dihdrate (CPPD) in the cartilage. It can be seen in: Hand (triangular ligament). Knees ( artigular cartilage & menisci). Symphesis pubis. Less common, the shoulder and hip. Chondrocalcinosis of the symphysis pubis and nephrocalcinosis on the abdominal x ray is diagnostic of hyperparathyroidism.

38. Brown tumor ( ostitis fibrosa cystica ). These are cystic lesions within bone due to excessive osteoclastic resorption (osteopenia). Radiographically , brown tumors appear as low density multiloculated cysts that can occur in any skeletal site and may cause expansion of bones.

39. Brown tumor

40. PHPT Erosion of the terminal tufts. Resorption of the radial side of the middle phalanx of the index and middle finger. Coarsened trabeculae. Thinned cortices. Brown tumor.

41. Osteosclerosis. Occurs uncommonly in PHPT but is a common feature of SHPY secondary to chronic renal failure.

42. A, AP radiograph of the spine in a patient with secondary hyperparathyroidism shows generalized bone sclerosis, small kidneys, and left renal calculi. B, Lateral radiograph of the lumbar spine in another patient with secondary hyperparathyroidism shows horizontal, bandlike (" rugger jersey") sclerosis of the vertebral bodies ( arrows ).

43. Erosive arthropathy. Involving hands, wrists, and shoulders. Differentiate from RHD arthritis Subperiosteal resorption. Affection of distal interphalangeal joints.

44. Radiological findings of secondary hyperparathyroidism. Similar to 1ry hyperparathyroidism. Less frequent brown tumor. Calcification of arteries and soft tissue. Osteosclerosis more common.

45. Secondary Bony sclerosis; focal or generalized. Rugger -jersey appearance of spine. Soft tissue and vascular calcification. Primary Chondrocalcinosis usually seen in the menisci of the knee, the triangular fibrocartilage of the wrist, and the pubic symphysis

46. AP radiograph of the hand in a 50-year-old man with renal osteodystrophy shows acro-osteolysis ( short arrows ), subperiosteal bone resorption ( long arrows ), and vascular calcifications. Secondary HPT . Radiograph of the hand showing resorption of the first to third tufts with soft tissue calcification ( 1 ). There is articular calcification ( 2 ) , and subperiosteal and subligamentous resorption ( 3 ).

47. The differential diagnosis of HYPERPARATHYROIDISM Focal subperiosteal resorption involving a single bone Neoplasms or osteomyelitis . Bone sclerosis in patients with secondary hyperparathyroidism. Metastatic disease, radiation-induced bone disease, hypoparathyroidism , myelofibrosis , mastocytosis , sickle-cell disease, and Paget's disease. Chondrocalcinosis Pyrophosphate arthropathy (CPPD) or hemochromatosis . Brown tumors includes other focal lytic lesions, such as giant cell tumor and fibrous dysplasia.

48. Hypoparathyroidism It result from: The M/C cause is excision of or trauma to the parathyroid glands . may not be recognized for years after surgery. I 131 therapy. Clinical presentation: Neuromuscular dysfunction. Short stature. Delay or failure of tooth eruption. Gastrointestinal complaints.

49. Radiologic findings of HYPOPARATHYROIDISM Radiologic findings are varied. Bony sclerosis. = M/C finding Focal or generalized Subcutaneous calcification. Calvarial thickening Basal ganglia calcification Hypoplastic dentition Premature physeal fusion Spinal ossification. Occasionally : Osteoporosis, Enthesopathy, Dense metaphyseal bands.

50. differential diagnosis of HYPOPARATHYROIDISM Widespread bony sclerosis. Blastic metastasis, myelofibrosis , renal osteodystrophy , sickle-cell disease, and fluorosis . Dense metaphyseal. Leukemia therapy, heavy-metal poisoning, or hypothyroidism. Calcifications of the basal ganglia Toxoplasmosis or cytomegalovirus infections, after radiation therapy, and after carbon monoxide exposure. Subcutaneous calcifications. Collagen-vascular diseases, hypervitaminosis D, and renal osteodystrophy .

51. Pseudohypoparathyroidism It is an x linked genetic disorder. Normal or enlarged parathyroid gland. End organ resistance (kidney & bone).

52. Imaging findings in pseudo- hypoparathyroidism . Thickening of the skull. Basal ganglia calcification. Abnormal dentition with hypoplasia & cranial defects. Connective tissue calcification in skin, ligaments, tendons & facial planes. Coxa vara , coxa vulga and bowing of long bones. Exostosis prependicular to long bone axis.

53. Hands Short metacarpals esp. 1 st , fourth and fifth. Metacarpals & phalanges esp. 1 st digit may be wide with cone shaped epiphysis. Metatarsals may be affected. + ve metacarpal sign.

54. Hyperthyroidism Imaging findings: Generalized osteoporosis. Increased cortical striations in long bones. Thyroid acropachy : Periosteal thickening in extremities esp. hands. Exophthalmus & pretibial myxodema .

55. AP radiographs of the hand in a 46-year-old man with thyroid acropachy who presented with hand swelling and hypothyroidism 2 years after a thyroidectomy . Note the dense, solid periosteal reaction with feathery contour ( arrows) along the shafts of 2nd, 3rd, and 4th proximal and middle phalanges.

56. Thyroid acropachy. ( A,B ) Radiographs of the hands showing diaphyseal periostitis ( arrows ) and generalized swelling. ( C ) Radiograph in a different patient showing marked soft tissue prominence.

57. Differential for HYPERTHYROIDISM Thyroid acropachy Periosteal reaction involving multiple bones Hypertrophic osteoarthropathy : long bones. Feathery contour is absent. Pachydermoperiostosis : Long bones. Periosteal reaction extends to the metaphyses and epiphysis.

58. Hypothyroidism Deficiency of thyroid hormones (T4 and T3) produce a spectrum of musculoskeletal abnormalities termed (cretinism) in infant, (juvenile myxoedema), in children, and (myxoedema or hypothyroidism) in adults. It results from: Primary disorder of the thyroid gland Decrease stimulating hormones secondary to disorders of the pituitary or hypothalamus (tertiary). Rarely end organ resistance.

59. Imaging findings in hypothyroidism. Delayed skeletal maturation in children. Skull: Wormian bones. Small bowel shaped cherry sella (older children). Paranasal sinuses underdeveloped. Spine: Bullet shape vertebrae esp. thoracolumbar . Kyphosis may occur.

60. Long bones; Short. Epiphyses appear late and frahmented . Pelvis; Narrow Coxa vara deformity Slipped femoral capital epiphysis.

61. Osteoporosis & delayed closure of growth plate After treatment

62. METABOLIC DISEASES

63. METABOLIC DISORDERS Osteoporosis. Hypophosphatasia. Hyperphosphatamia.

64. Osteoporosis Definition : reduced bone mass of normal composition . Most common metabolic bone disease. One of the most prevalent conditions associated with aging.

65. Clinical definition : requires the presence of a nontraumatic fracture . Histologic definition : requires normally mineralized bone to be present in reduced quantity .

66. Ostoporosis Classification Primary osteoporosis . (idiopathic) : more common Type 1 (postmenopausal) Type 2 (age-related or senile) Secondary osteoporosis . Metabolic ( acromegaly , hypercorticism , hyperthyroidism, hyperparathyroidism, hypogonadism , pregnancy, diabetes mellitus) Congenital (osteogenesis imperfecta, Ehlers-Danlos syndrome, homocystinuria , mastocytosis , ochronosis , Gaucher's disease) Nutritional (alcoholism, malnutrition, calcium deficiency, scurvy) Drug-related (steroids, heparin).

67. osteoporosis Most common metabolic bone disease. Is defined as qualitatively normal bone present in deficient quantities. It has three major categories. Generalized: affecting majority of the skeleton. Regional: affecting one limb or section of body. Localized: focal osteopenia in one or more discrete portions of bone.

68. Imaging findings in osteoporosis Requires 30-50% bone loss to be detected by plain x ray. Bones: osteopenia with thin cortex. Resorption of horizontal trabeculae. Accentuated residual trabeculae more at weight bearing areas. Fracture neck femur is common . The bone surfaces are well defined , with sharp margins . Spine: Biconcave (cod-fish vertebrae ) and anterior wedging. Decreased density with more dense end plates (penciling in). Fracture (wedge shaped or vertebra plana).

69. DXA

70. Differential considerations for diffuse osteopenia Osteomalacia. indistinct trabeculae and poorly defined interfaces between cortical and trabecular bone. Presence of Looser's zones. Hyperparathyroidism. bone resorption at characteristic sites. Multiple myeloma. MR imaging may show areas of marrow replacement.

71. Regional or localized osteoporosis Immobilization and disuse Reflex sympathetic dystrophy syndrome (RSDS) Transient regional osteoporosis Transient osteoporosis of the hip. Regional migratory osteoporosis. Inflammatory arthritis. Tumors Infection.

72. This patient had a long - standing immobilization due to a fracture of the right humerus . The appearances in the right hand are classical for reflex sympathetic dystrophy, or Sudeck’s atrophy, and include : 1 . Pronounced demineralization of the bones, particularly in the periarticular region . 2 . No joint involvement. 3. Associated soft tissue atrophy . This condition has been recently renamed the “complex regional pain syndrome” .

73. Hypophosphatasia It is an autosomal recessive disease. Imaging findings: In sever cases exaggerated fraying of metaphysis is seen. Craniostenosis. Nephrocalcinosis. Deformities of distal phalanges and tibia.

74. Hyperphosphatamia Autosomal recessive disorder, presents in early infancy Imaging findings: Similar to Paget`s disease but occur in infancy & more symmetrical. Skull vault is thickened. Long bones are tubular, enlarged and bowed with cortical irregularity.

75. Bowed extremities with osteopenic bones and heart shaped pelvis similar to rickets Deformed bell shaped rib cage with osteopenia like ricket s

76. NUTRITIONAL DISORDERS

77. NUTRITIONAL DISORDERS Hypervitaminosis A. Hypervitaminosis D. Osteomalacia. Rickets. Scurvy (Hypovitaminosis C).

78. Hypervitaminosis A: X ray findings Subperiosteal cortical thickening. Osteoporosis. Hypervitaminosis D: X ray findings Generalized osteopenia. In young patients, alternating areas of sclerosis and lucencies in the metaphysis.

79. Hypervitaminosis A

80. Hypervitaminosis D Dense sclerotic bands seen in metaphyses similar to cretinism and phosphorous poisoning Dense calvarium as osteopetrosis

81. RICKETS AND OSTEOMALACIA

82. Rickets and osteomalacia Rickets and osteomalacia are similar histologically. Abnormality in vitamin D metabolism. Incomplete mineralization of normal osteoid tissue. Rickets Occurs in children A ffects immature bone Osteomalacia Occurs in adult Affects mature bone

83. Clinical findings of Rickets and Osteomalacia Rickets: stunted skeletal growth. Apathetic, Irritable, Hypokinetic. Frontal bossing, softening of the skull, dental caries, rachitic rosary, kyphosis, joint enlargement, or bowing of long bones. Fractures and slipped capital femoral epiphyses. Depend in part on the etiology and severity of the disorder, as well as the age of the patient at presentation

84. Clinical findings of Rickets and Osteomalacia Osteomalacia: more subtle. Fatigue, malaise, or bone pain. Proximal muscle weakness and abnormal gait may be present. Depend in part on the etiology and severity of the disorder, as well as the age of the patient at presentation

85. Osteomalacia Presence of poor quality bone (delayed or defective mineralization of osteoid matrix) due to vit. D deficiency.

86. Imaging finding in osteomalacia Generalized osteopenia with coarse, hazy appearing trabeculae . Poorly defined interfaces between cortical and trabecular bone. Pseudo fracture (Looser`s zone): narrow zone of lucency, usually perpendicular to bone cortex, usually bilateral & symmetrical. Common sites are: Femoral neck, scapula, pubic bone, ribs, occiput and long bones.

87. Looser's zone. Linear areas of undermineralized osteoid that occur in a bilateral and symmetric distribution . Characteristic sites; inner margins of femoral neck, proximal ulna, axillary margin of the scapula, pubic rami, and ribs. DDx ; Paget's disease or fibrous dysplasia.

88. Looser zone

89. Coarse trabeculae

90. Imaging finding continue Vertebrae: Penciling in of the vertebral bodies, loss of vertebral height (cod fish). Bone softening producing: Bowing of long bones Shepherd`s crook deformity Protrusio acetabulae. Basilar invagination. Compression wedge fracture (less common than osteoporosis).

91. Shepherd`s crook deformity

92. Protrusio acetabulae.

93. Basilar invagination

94. Rickets The skeletal effects are due to a lack of calcification, So, the most obvious changes are at metaphysis, where the most rapid growth is occurring.

95. Imaging findings in rickets Generalized osteopenia. Skull bossing. Epiphysis are enlarged, flaring, cupping & irregularity of metaphysis . Earliest; Slight axial widening of the physis Next; Increased lucency of the zone of provisional calcification. More advance; The physis widens and its contour becomes irregular. Thoracic kyphosis with pigeon chest . Enlarged costochondral junction ( rosary beads ). Bowing of the legs.

96. The regions of highest yield on radiologic evaluation of rickets are those that are undergoing rapid growth . Costochondral junctions of middle ribs (rachitic rosary) Distal femur Both ends of the tibia Distal radius and ulna Proximal humerus. Differential diagnosis of rickets includes Hypophosphatasia and the Schmid -type of metaphyseal chondrodysplasia .

97. The complication of rickets. Skeletal deformities. In neonates; posterior flattening and squaring of the skull, or craniotabes, may be seen. In early childhood; bowing deformities of arms and legs are common. Older children: scoliosis, vertebral end plate deformities, basilar invagination of the skull may be seen. Advance disease: Slipped capital femoral epiphysis.

98. A, AP radiograph of the knee in a 2-year-old girl with rickets shows generalized osteopenia and widening of the metaphyses of the proximal tibia and fibula. B, AP radiograph of the wrist in another child with rickets shows generalized osteopenia, as well as widening and irregularity of the metaphyses of the distal radius and ulna.

99. Rickets in a young child with growth plate widening and irregularity in the wrist ( A ) and knees ( B ). Note the small epiphyses in the knees.

100. Vitamin D-resistant rickets in a 1-year-old child. ( A ) AP radiograph of the knees showing irregularity and widening of the growth plates. The epiphyses are small and irregular as well. ( B ) Three years after high-dose vitamin D therapy, the knees appear normal. There is residual femoral bowing.

101. Rachitic rosery nodularity at costochondral junctures

102. 4 year old rachitic child with knock- knee deformity Healing rickets in 2 yr male with epiphyseal rings second to treated rickets

103. Scurvy Dietary deficiency of vit. C (rare before 6 month). Imaging findings: Small epiphysis, sharply demarcated by sclerotic rim (Weinberger's sign). Dense zone of provisional calcification at metaphysis. ( Franket`s line). Lucent zone due to defective mineralization ( Trumerfeld zone). Cortical fractures ( Pelkan`s spurs). Subperiosteal haemorrhage .

104. Hemorrhagic Periostitis in Scurvy

105. 1 year old child with multiple slipped epiphyses second to scurvy

106. Thank you