| It is important to adjust serum calcium concentration for the concentration of albumin
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| Many acute and chronic illnesses lead to a decrease in serum albumin, which in turn decreases serum total calcium concentration. It is important that adjusted calcium is calculated in clinical situations. A serum-adjusted calcium that is below the reference range (<2.20 mmol/L; 8.8 mg/dL) may occur commonly in clinical practice. Changes in ionized calcium can result from pH changes in plasma - particularly alkalemia (Chapter 23), which increases the protein binding of calcium, causing decreased concentrations of ionized calcium.
|
| Clinical signs of hypocalcemia are, in the main, due to neuromuscular irritability and are more obvious and severe when the onset of hypocalcemia is acute. In some cases, this irritability may be demonstrated by eliciting specific clinical signs. Chvostek's sign is the presence of twitching of the muscles around the mouth (circumoral muscles) in response to tapping the facial nerve anterior to the ear, and Trousseau's sign is the typical contraction of hand in response to reduced blood flow in the arm induced by inflation of a blood-pressure cuff. Numbness, tingling, cramps, tetany and even seizures may be stimulated by hypocalcemia.
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| Hypocalcemia may be due to a low PTH concentration, secondary hyperparathyroidism or to tissue resistance to PTH
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| Causes of hypocalcemia can be divided into those associated with low PTH(1-84), those in which the decreased serum calcium results in secondary HPT, and rare cases in which there is PTH resistance (Table 24.2). Development of hypocalcemia indicates that the normal physiologic compensatory mechanisms controlled by PTH have failed and there are disturbed fluxes of calcium between bone, kidney, and intestine.
|
|
Table 24-2.
Causes of hypocalcemia. |
| Body_ID: None |
| Causes of hypocalcemia |
| Body_ID: T024002.50 |
| Hypoparathyroid | Nonparathyroid | PTH resistance |
| Body_ID: T024002.100 |
| postoperative | vitamin D deficiency | pseudohypoparathyroidism |
| Body_ID: T024002.150 |
| idiopathic | malabsorption | hypomagnesemia |
| Body_ID: T024002.200 |
| acquired hypomagnesemia neck irradiation | liver disease renal disease | |
| Body_ID: T024002.250 |
| anticonvulsant therapy | vitamin D resistance hypophosphatemia | |
| Body_ID: T024002.300 |
| The most common cause of hypoparathyroidism is as a complication of neck surgery, particularly that for pharyngeal or laryngeal tumors, thyroid disease, or parathyroid disease.
|
| The group of pseudohypoparathyroidism syndromes is characterized by hypocalcemia, hyperphosphatemia, and increased concentrations of PTH(1-84) (markedly increased in some patients).
|
| The classical type of pseudohypoparathyroidism (PHP) is due to end-organ resistance to PTH, caused by a genetic defect resulting in an abnormal regulatory subunit of the G-protein of the adenylate cyclase complex. Confirmation of the diagnosis is made by demonstrating a lack of increase in plasma or urinary cAMP in response to the infusion of PTH.
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| Abnormal metabolism of vitamin D
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| Hypocalcemia resulting from abnormalities in vitamin D metabolism can be due to vitamin D deficiency, acquired or inherited disorders of vitamin D metabolism, and vitamin D resistance.
|
In addition, tissue insensitivity to 1,25(OH)2D3 results in the characteristic findings of hypocalcemia, secondary HPT, and increased 11,25(OH)2D3. Individually or in combination, the most common causes of vitamin D deficiency are:
- reduced exposure to sunlight: this is common in institutionalized elderly persons and immigrants to western Europe from the Middle East or Indian subcontinent who wear traditional dress;
- poor dietary intake: most Western diets contain sufficient vitamin D, but diets such as strict vegetarian or lactovegetarian have inadequate vitamin D content and, in the long term, may result in deficiency;
- malabsorption of vitamin D may be caused by celiac disease, Crohn's disease, pancreatic insufficiency, inadequate bile-salt secretion, and nontropical sprue (see Chapter 9).
|
| Magnesium in hypoparathyroidism |
| Patients with a low plasma magnesium concentration develop a state of functional hypoparathyroidism and end-organ resistance to PTH; these patients tend not to respond to treatment with calcium supplementation alone. Secretion of PTH from the parathyroid gland requires a finite amount of magnesium to allow fusion of the secretory granules with the membrane and release of PTH (see Fig. 24.3); thus, in order to restore normal parathyroid gland function and normocalcemia, magnesium supplementation is essential. |
| page 355 |  | | page 356 |
| Prevention and treatment of osteoporosis |
Estrogen has a pivotal role in the maintenance of bone mass in women. An increased rate of osteoclast-mediated bone loss is observed immediately after the menopause, as a result of ovarian failure and the decrease in estrogen secretion. This can be prevented by HRT, which can be given as cyclical or continuous combined estrogen and progesterone in women with an intact uterus, or as estrogen alone in women who have had their uterus surgically removed (by hysterectomy). The Women's Health Initiative (WHI) trial established an excess of adverse events including increased breast cancer, thromboembolic disease, stroke and cardiovascular events in women receiving greater than 5 years of continuous combined HRT. Although short-term therapy is valuable for menopausal symptoms long-term use of this type of HRT is no longer recommended as prophylaxis or treatment for osteoporosis. |
| Other treatments that are recommended are bisphosphonates, selective estrogen receptor modulators (SERMs), nightly injections of PTH, calcitonin, and, in elderly patients, calcium with vitamin D supplementation. |
| Abnormalities of vitamin D metabolism are observed, among others, in patients with liver disease (deficient 25-hydroxylation, malabsorption), and renal failure (1α-hydroxylase deficiency).
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