בהמשך למחלת הגרייבס

תודה על הסבר מהות המחלה. מהן הסיבות להופעתה? האם יתכן מדיאטה דרסטית? האם יתכם ממתח מופרז? והאם ניתן וכיצד למנוע את תופעת "עיני העגל" במחלה? אגב, אני מטופלת בכדור ptu כדור אחד ליום 25 מ"ג

קשה לומר מה גורם להופעת המחלה או התפרצותה כיון שמדובר בחוסר איזון בסיסי (לא מסוכן, במקרה זה ) במערכת החיסונית. מאוד ייתכן כי דיאטה קיצונית, מתח נפשי או פיזי ייגרמו להופעתה. "עיני העגל" הן תופעה אופיינית. איזון תפקודי הבלוטה יועיל. במקרים מסוימים נותנים סטרואידים לתקופה מסויימת, אבל זה תלוי במספר גורמים נוספים. הדבר מצריך ייעוץ אנדוקרינולוג ורופא עיניים המתמצא בתחום. PTU הוא טיפול מתאים בשלבים ראשוניים. מן הסתם, יש אופציות נוספות אשר בודאי דנת עליהן עם הרופא המטפל. בכל מקרה, מה שחשוב הוא איזון תפקודי בלוטת התריס, דבר שלעתיתם לוקח זמן. אל דאגה, המחלה שכיחה ביותר וברוב המקרים מושג איזון רצוי לתקופה ממושכת. תהיי בריאה.

Chapter 49. Metabolic Bone Disease Contributor: Lawrence G. Raisz The skeleton is a metabolically active organ that undergoes continuous remodeling throughout life, not only to provide structural integrity and strength to support the body and protect vital organs, but also to store essential minerals, particularly calcium. (see page 468) The hematopoietic function of bone also changes with age. (see page 672) 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. Bone loss in the elderly may be normal, in which bone density is within 1 SD of the young adult mean; osteopenic, in which bone density is between 1 and 2.5 SD below the young adult mean; or osteoporotic, in which bone density is > 2.5 SD below the young adult mean. In the USA, the estimated prevalence of osteopenia is 15 million in women and 3 million in men. The estimated prevalence of osteoporosis is 8 million in women and 2 million in men. Osteopenia and osteoporosis are major public health problems, resulting in substantial morbidity and estimated health costs of > $14 billion annually. Classification and Etiology Primary osteoporosis in the elderly can be classified as type I or II. Type I (menopausal) osteoporosis occurs mainly in persons aged 51 to 75, is six times more common in women, and is associated with vertebral and Colles' fractures. (see Table 48-1) Type II (senescent) osteoporosis occurs in persons > 60, is two times more common in women, and is associated with vertebral and hip fractures. Overlap between types I and II is substantial, so this classification is of limited clinical use. Primary osteoporosis in premenopausal women and younger men, which is rare, is classified as idiopathic. Primary osteoporosis is thought to result from the hormonal changes that occur with age, particularly decreasing levels of sex hormones (estrogen in women, testosterone in men). Several other factors are probably contributory. Secondary osteoporosis accounts for only a small proportion of osteoporosis cases among the elderly, in whom primary and secondary osteoporosis often occur together. It accounts for a much greater proportion of cases among premenopausal women and younger men. Secondary osteoporosis may be due to many causes, including hyperparathyroidism, hyperthyroidism, malignancy, immobilization, gastrointestinal disease, renal abnormality (eg, idiopathic hypercalciuria), and use of drugs that cause bone loss (eg, anticonvulsants). Mild to moderate vitamin D deficiency, which is common in elderly persons, may give rise to osteoporosis rather than to osteomalacia. (see page 483) Glucocorticoid-induced osteoporosis is of particular concern in the elderly, who may already have calcium deficiency and impaired bone formation, both of which are worsened by glucocorticoids. Screening for secondary osteoporosis is important in patients of all ages, because many of the causes are treatable or have an important effect on prognosis (see Figure 49-1) Pathogenesis and Risk Factors Diminished bone mass can result from failure to reach an optimal peak bone mass in early adulthood, from increased bone resorption, or from decreased bone formation after peak bone mass has been achieved. All three of these factors probably play a role in most elderly persons. Low bone mass, rapid bone loss, and increased fracture risk correlate with high rates of bone turnover (ie, resorption and formation). Presumably, in osteoporosis, the rate of formation is inadequate to offset the rate of resorption and maintain the structural integrity of the skeleton. The major risk factors for osteoporosis are increased age, female sex, white or Asian race, positive family history of osteoporosis, and thin body habitus. Other risk factors include decreased lifelong exposure to estrogen, low calcium intake, sedentary lifestyle, and cigarette smoking. Age: The effect of age on the skeleton is complex. Bone resorption rates appear to be maintained or even to increase with age; bone formation rates tend to decrease. Loss of template due to complete resorption of trabecular elements or to endosteal removal of cortical bone produces irreversible bone loss. Age-related microdamage and death of osteocytes may also increase skeletal fragility. However, osteoporosis is not an inevitable consequence of aging; many persons maintain good bone mass and structural integrity into their 80s and 90s. Sex: The greater frequency of osteoporotic fractures in women has many causes. Women have lower peak bone mass and lower muscle mass than men. They experience accelerated bone loss at menopause and may also lose bone during the reproductive years, particularly with prolonged lactation. The smaller periosteal diameter of bones in women also increases skeletal fragility. Another reason for female predominance is that women live longer than men. Race: Although osteoporosis is more prevalent among persons of white and Asian descent than among blacks, the reasons are not well understood; prevalence also varies among ethnic groups. Whites have lower peak bone mass than do blacks, but the difference in fracture risk appears to be independent of the difference in bone density. Differences in body composition, skeletal structure, and bone turnover may play a role. Heredity: About 50 to 80% of peak bone mass is genetically determined. A positive family history of osteoporosis increases fracture risk, independent of bone density. Genetic studies comparing osteoporotic patients with healthy persons have shown several differences in specific genes for collagen, hormone receptors, and local factors. Many genes probably play a role. Body habitus: The increased risk of fracture associated with a thin body habitus is probably multifactorial. Thin women produce less estrogen from androgen (this conversion occurs in fat tissue), especially after menopause. Obesity may be associated with increased muscle mass, greater weight-bearing impact on the skeleton, and greater protection of the skeleton, particularly of the hip, by subcutaneous fat. Systemic hormones: Age-related changes in estrogen levels increase fracture risk. In addition, increased levels of parathyroid hormone and decreased levels of the growth hormone/insulin-like growth factor I system appear to decrease bone mass and increase fracture risk. Although excess glucocorticoids and thyroid hormone can contribute to secondary osteoporosis, they have not been shown to play a role in primary osteoporosis. Local factors: Animal studies suggest that the interaction of systemic hormones with local regulators of bone remodeling, including cytokines and prostaglandins, plays a critical role in the increase in bone resorption and relative impairment of bone formation that occurs after oophorectomy. However, evidence implicating these local factors in human osteoporosis is limited. Interleukin-1 activity may be increased in osteoporosis; although interleukin-6 activity appears to increase with age, no correlation with osteoporosis has been demonstrated. Inhibition of prostaglandin production by nonsteroidal anti-inflammatory drugs (NSAIDs) results in a small increase in bone mass. Symptoms and Signs Osteoporosis has been termed a silent disease because, until a fracture occurs, symptoms are absent. A loss of height may indicate a vertebral compression fracture, which occurs in many patients without trauma or other acute precipitant. Dorsal kyphosis with exaggerated lordosis (dowager's hump) may result from multiple compression fractures. In some fracture patients, pain may be acute and severe and then subside slowly over several weeks. Chronic back pain in the elderly can be due to vertebral compression from osteoporosis but is as likely to be due to joint or disk disease. Osteoporotic fractures commonly affect the hip because the elderly tend to fall sideways or backwards, landing on this joint. (see page 223) Younger, more agile persons tend to fall forward, landing on the outstretched wrist, thus fracturing the distal radius (see page 220). Osteoporosis is also associated with other fractures of the extremities and pelvis and with vertebral fractures, but not with fractures of the head and face. Diagnosis The history should focus on primary risk factors and secondary causes of osteoporosis. A complete history of menstrual function, pregnancy, and lactation should be obtained in women, and a history of sexual function should be obtained in men, in whom decreased libido and erectile dysfunction may be due to low testosterone levels. Neurologic deficits and drugs that might increase the risk of falls should be analyzed. The family history should include fractures and evidence of endocrinopathy or renal calculi. One of the most important predictors of osteoporotic fractures is a history of a fracture after age 40 due to minimal or moderate trauma. In such persons, the fracture risk may be increased severalfold. The physical examination is often unremarkable. Spinal deformity and tenderness over the lower back should be sought. X-ray findings are generally insufficient for the diagnosis of primary osteoporosis; x-rays may detect osteopenia only when bone loss is > 30%. Vertebral compression fractures can be seen on x-ray, but anterior wedging may have been present since adolescence (Scheuermann's disease), and some degree of age-related wedging can occur in the absence of marked bone loss. X-ray findings can also suggest other causes of metabolic bone disease, such as the lytic lesions in multiple myeloma and the pseudofractures characteristic of osteomalacia. (see page 484) Bone densitometry is the only method for diagnosing or confirming osteoporosis in the absence of a fracture. The National Osteoporosis Foundation recommends that bone densitometry be performed routinely in all women > 65, particularly in those who have one or more risk factors. However, such a routine approach is costly. Densitometry can also be used for monitoring the response to therapy. Currently available densitometric systems have many pitfalls. The relationship between bone density and fracture risk is continuous and graded; with densitometry, diagnostic cutoffs are arbitrary and must be considered in light of other risk factors. In general, a difference of 1 SD from the young adult mean equals a 10 to 12% difference in bone density. There is a 2.7-fold increase in the relative risk of hip fracture for a 1 SD decrease in femoral neck bone density from the young adult mean; the increase in relative risk is somewhat less (about 1.5- to 2.0-fold increase for 1 SD decrease) when density is measured at sites other than the femoral neck. In women > 75, even 1 SD below the age-adjusted norm is highly predictive of fractures. Furthermore, peripheral densitometry measurement may not reflect central measurement and is subject to artifacts. In the elderly, measurement of the lumbar spine is often complicated by osteoarthritic changes, disk disease, and calcification of the underlying aorta. Another limitation of densitometry is that current criteria are based on data from white postmenopausal women and that appropriate diagnostic criteria for other populations are not established. In addition, bone density values vary with the technique used and the position of the patient. Dual energy x-ray absorptiometry (DEXA) can be used to measure bone mineral density in the spine, hip, wrist, or total body. Radiation exposure is minimal, and the procedure is rapid. However, the standard apparatus is expensive and not portable. Small DEXA machines that can measure the forearm, finger, or heel are less expensive and are portable. Also, DEXA measures areal density (ie, g/cm2) rather than true volumetric density. Quantitative CT measures true volumetric density and can be limited to regions of interest (eg, trabecular bone in the spine); however, the apparatus is expensive, and radiation exposure is somewhat larger than with DEXA. Ultrasound densitometry can assess the density and structure of the skeleton and appears to predict fracture risk in the elderly. The apparatus is relatively inexpensive, portable, and uses no radiation but can be used only in peripheral sites (eg, the heel), where bone is relatively superficial. X-ray absorptiometry can be used to measure bone density in the hand in comparison with density in a standardized metal wedge. Its value in predicting fractures is not well established. Differential diagnosis: To confirm the diagnosis of primary osteoporosis, one must exclude secondary osteoporosis, osteomalacia, and malignancy. The probability of secondary osteoporosis in an elderly patient, with or without typical osteoporotic fractures, is low, but a limited diagnostic assessment is warranted (see Figure 49-1), particularly when serum and urine calcium levels are abnormal. Because vitamin D deficiency usually responds to ordinary supplementation, which is part of the routine care of osteoporotic patients, measurement of 25-hydroxyvitamin D3 levels may be indicated only if malabsorption is evident. The use of biochemical markers of bone turnover in the evaluation of osteoporosis has not been established because, although high turnover is associated with increased bone loss and fracture risk, individual variation is great. However, markers such as collagen cross-links and bone-specific alkaline phosphatase levels can be used to assess the response to therapy. Prognosis and Treatment Osteoporosis does not directly cause death. However, an excess mortality of 10 to 20% occurs in patients with established osteoporosis, particularly those with hip fractures. Prevention of osteoporotic fractures is critical to avoid a worldwide, costly epidemic. Prevention programs should be developed for patients at risk and for patients with diagnosed osteoporosis. Approaches include adequate intake of calcium and vitamin D, regular weight-bearing exercise and other efforts to minimize the risk of falls, smoking cessation, and good general nutrition. Calcium and vitamin D: The typical diet of elderly Americans provides only about 600 mg/day of calcium and = 1200 mg/day of elemental calcium and >= 400 IU/day of vitamin D; a somewhat larger intake of calcium and vitamin D may be beneficial and is generally considered safe. However, vitamin D intoxication can occur if intake is >= 50,000 IU/week. Calcium supplements are generally well tolerated in the elderly, but gastrointestinal complaints, particularly constipation, are common. In these persons, the use of alternative calcium salts (eg, calcium citrate) and efforts to increase dietary calcium are often effective. A good diet should include an adequate amount of vitamin K, because vitamin K deficiency is associated with increased fracture risk. A limited sodium intake may also be helpful, because high sodium intake can result in increased urinary calcium losses. Exercise: The effects of weight-bearing and muscle-strengthening exercise on bone density are relatively small. (see page 296) However, improved balance and muscle strength decrease the likelihood of falls and improve cardiovascular health. Antiresorptive therapy: Persons with low bone mass and multiple risk factors, particularly those who have already had an osteoporotic fracture, should be considered for antiresorptive therapy. Antiresorptive drugs include estrogens, bisphosphonates, selective estrogen receptor modulators, and calcitonin. Estrogen can prevent menopausal bone loss in most women. Estrogen replacement therapy (ERT) is the treatment of choice for postmenopausal women, (see page 1211) particularly those who had an early menopause, and for women who have had a hysterectomy. ERT is particularly effective during the first few years after menopause when bone loss is most rapid.(see page 469) Hormone replacement therapy (HRT), which contains a combination of estrogen and progestin, is necessary to prevent endometrial hyperplasia and avoid the increased risk of uterine malignancy in women who have a uterus. Other potential benefits of ERT and HRT include diminished risk of cardiovascular disease and Alzheimer's disease, but these benefits are not as well established. Many women start ERT or HRT during menopause because it provides short-term relief of menopausal symptoms. These women often discontinue therapy after a few years, which leads to resumption of rapid bone loss. The decision to discontinue ERT or HRT might be aided by densitometry. If discontinued, ERT or HRT can be restarted at any age. Estrogen decreases bone resorption and increases bone mass in women in their late 70s and 80s. In these patients, lower doses of estrogen may be effective and produce fewer adverse effects. Epidemiologic studies and the few prospective clinical trials of estrogen suggest that ERT or HRT decreases the risk of osteoporotic fractures by 30 to 50%. Because other antiresorptive drugs may have an additive effect when given with estrogen, combination therapy should be considered in patients who have very low bone density, continue to lose bone, or incur a fracture while taking ERT or HRT. Bisphosphonates are potent antiresorptive drugs that directly inhibit osteoclast activity. For women who cannot tolerate estrogen or have contraindications (eg, preexisting breast cancer, risk factors for breast cancer), bisphosphonates are considered the next choice; these drugs increase bone mass and decrease the risk of fractures, particularly in patients taking glucocorticoids. Bisphosphonates, particularly alendronate, have also decreased the incidence of vertebral and nonvertebral fractures by >= 50% in large cohorts of postmenopausal women. Alendronate is used to prevent (5 mg/day) and treat (10 mg/day) osteoporosis. Pamidronate is available IV for treatment of hypercalcemia of malignancy and Paget's disease but has been used in osteoporosis. A major problem with oral administration of bisphosphonates is poor absorption. Usually 60 in the USA. The prevalence varies widely in different regions of the world. The relative risk is increased about sevenfold in first-degree relatives of patients with Paget's disease. The etiology has not been established, but genetic factors and a paramyxovirus infection may be involved. A genetic locus for susceptibility to Paget's disease has been identified on chromosome 18q in some large kindreds of patients, but not all kindreds show this locus, suggesting genetic heterogeneity. Structures resembling viral nucleocapsids have been identified in pagetic osteoclasts, but the results of studies of viral RNA expression in pagetic bone are inconsistent. Pathology Pagetic lesions may be single or multiple and can involve any part of the skeleton, most commonly the pelvis, femur, spine, skull, and tibia. Pagetic osteoclasts are large and have many more nuclei than normal. Similarly, the osteoblastic response is exuberant and disorganized, producing "mosaic" bone with a woven pattern of collagen deposition. The adjacent marrow is vascular and often shows fibroblastic proliferation and decreased hematopoiesis. The hypercellularity may diminish, leaving sclerotic bone with little cellular activity, the so-called "burned-out" phase of Paget's disease. Frequently, all phases of the pagetic process occur simultaneously in a patient or even in a single lesion. Symptoms and Signs Patients may be asymptomatic for many years. Deformities, neurologic impairment, pathologic fractures, bone pain, hypervascularity, and arthritic changes in adjacent joints may be the initial symptoms. Changes in the skull often lead to impaired central nervous system function, particularly hearing loss due to involvement of the petrous bone. Involvement of the base of the skull may produce platybasia and basilar invagination, which leads to the rare, but serious, complication of brain stem compression. Vertebral deformity may lead to spinal cord compression. Although pagetic long bones often show increased density, their irregular structure leads to skeletal deformity with fragility and increased risk of fracture. The bone deformity can lead to damage to articular cartilage with consequent osteoarthritis, especially in the knee and hip. The hypervascularity of pagetic bone may produce palpable local warmth, increase cardiac output, and aggravate coexisting heart disease. Angioid streaks in the retina may occur but rarely impair vision. Neoplastic changes in pagetic bone probably occur in = 50,000 U/week may be needed. Close monitoring of serum and urine calcium levels is critical. 25-Hydroxyvitamin D3 (calcidiol) 25 to 50 µg can be used in patients with severe malabsorption or with hepatic disease. Calcidiol is better absorbed than is ordinary vitamin D and bypasses any defect in 25-hydroxylation in the liver. In renal disease, the defect is in 1-hydroxylase, and 1,25-dihydroxyvitamin D3 (calcitriol) should be administered. Because calcitriol is the potent hormonal form of vitamin D, the margin of safety is the smallest. Replacement doses range from 0.25 to 2 µg/day, and patients should be monitored for hypercalcemia and hypercalciuria. Calcitriol can reverse the bone lesion in neoplastic osteomalacia; finding and removing the tumor also cures the osteomalacia. In hypophosphatemic disorders, including congenital and renal or gastrointestinal forms, phosphate replacement is critical. However, phosphate tends to cause diarrhea. To minimize this effect, potassium and sodium phosphate should be given in divided doses that are increased gradually to bring the phosphate concentration at least into the low-normal range. Elemental phosphorus 250 mg should be given >= 4 times/day with a full glass of water. In patients with severe hypophosphatemia, the dosage may be increased to as much as 3 g/day po or 2.5 to 5.0 mg/kg in 0.9% saline solution IV. Excessive phosphate administration or too-rapid repletion may result in hypocalcemia. All patients with osteomalacia need to maintain adequate intakes of calcium (1000 to 1500 mg/day). In cases of malabsorption or severe vitamin D resistance, parenteral calcium may be required. In patients with the rare autosomal recessive form of osteomalacia in which the vitamin D receptor is defective, the skeletal abnormalities respond to parenteral administration of calcium and phosphorus.