Serum calcitonin

Although blood calcitonin levels are normally low, excessive levels have been found in association with medullary carcinoma of the thyroid and more rarely carcinoid tumors of the bronchus and stomach. Serum calcitonin levels are used to screen and monitor patients who have or are suspected of having medullary carcinoma of the thyroid. 

C) She may have medullary carcinoma of the thyroid. Therefore, serum calcitonin, ret-Pro-Oncogene determination, and ultrasound of the thyroid should be obtained. 

Serum calcitonin Male < 8 ng/L (< 2.3 Test not indicated Test not indicated... 

MTC occurs as a sporadic disease and as part of the syndromes of MEN-2A, MEN-2B, and familial MTC (EMTC). "" MEN-2A and MEN-2B are autosomal dominant inherited multiglandular syndromes with age-related penetrance and variable expression. AH forms of MTC combined account for 5% to 10% of thyroid malignancies. Sporadic MTC is believed to comprise approximately 75% of all MTC. The routine measurement of serum calcitonin in nodular thyroid diseases assists in detecting unsuspected sporadic With the advent of... 

Measurement and interpretation of serum calcitonin are complicated by the heterogeneity circulating of calcitonin and large differences in the sensitivity and specificity of calcitonin immunoassays. 

Kaplan MM, Stall GM, Cmnmings T, MacAulay A, MacAulay A, Motte P, Wolfe HJ, et al. High-sensitivity serum calcitonin assays applied to screening for thyroid C-celi disease in multiple endocrine neoplasia type 2A. Henry Ford Hosp Med J 1992 40 227-31. 

Mulder H, Hackeng WHL, Silberbusch J, den Ottolander GJ, van der Meer C. Value of serum calcitonin estimation in chnical oncology. Br J Cancer 1981 43 786-92. 

Pacini F, FontaneUi M, Fugazzola L, Elisei R, Ehsei R, Romei C, Di Coscio G, et al. Routine measurement of serum calcitonin in nodular thyroid diseases allows the preoperative diagnosis of unsuspected sporadic medullary thyroid carcinoma. J Clin Endocrinol Metab 1994 78 826-9. 

Rieu M, Lame MC, Richard A, Lissak B, Lissak B, Sambort B, et al. Prevalence of sporadic medullary thyroid carcinoma the importance of routine measurement of serum calcitonin in the diagnosis and evaluation of thyroid nodules. Clin Endocrinol (Oxf) 1995 42 453-60. 

Rude RK, Singer FR. Comparison of serum calcitonin levels after a 1-minute calcium injection and after pentagastrin mjection in the diagnosis of medullary thyroid carcinoma. J Clin Endocrinol Metab 1977 44 980-3. 

Weissel M, Kainz H, Tyl E, Ogunyemi E, Woloszczuk W. Clinical evaluation of new assays for determination of serum calcitonin concentrations, Acta Endocrinol (Copenhagen)1991 124 540-4. 

Zink A, Blind E> Raue F. Determination of serum calcitonin by immunometric two-site assays in normal subjects and patients with medullary thyroid carcinoma. Eur J Clin Chem Clin Biochem 1992 30 831-5. 

Much evidence exists to support the contention that boron has beneficial effects on bone. The effects of boron, however, are most evident in the presence of suboptimal status of another nutrient important in bone formation or remodeling. In chicks, boron deprivation (0.465 mgkg diet) exacerbates the distortion of marrow sprouts (location of calcified scaffold erosion and new bone formation) and delay in imtiation of cartilage calcification in bones during marginal vitamin D deficiency (Hunt 1996). In humans, estrogen therapy to maintain bones increases serum 17P-estra-diol this increase is depressed when dietary boron intake is low (0.25-0.35 g per day) (Nielsen 1996, 1997). Boron deprivation also can exacerbate the increase in serum calcitonin and osteocalcin caused by low dietary copper and magnesium in humans. 

Serum thyroid-stimulating hormone (TSH) and thyroid hormone levels should be measured in any patient with a goiter to determine the hormonal status. TSH concentrations increase with age, but the levels remain within the normal range in the healthy population throughout life up to 100 years of age (Canaris et al., 2000 Mariotti et al, 1995). See Chapter 106 by Diez and Iglesias on Hypothyroidism in the Middle Aged and Elderly Clinical Aspects for details of thyroid hormone changes in the elderly. Serum calcitonin levels are not needed unless there is a family history of medullary thyroid cancer or multiple endocrine neoplasia (MEN) type 2. 

Nishiyama S, Nakamura T, Higashi A, et al. 1991. Infusion of zinc inhibits serum calcitonin levels in patients with various zinc status. Calcif Tissue Res 49(3) 179-182. 

The steroid hormone 1,25-dihydroxy vitamin D3 (calcitriol) slowly increases both intestinal calcium absorption and bone resorption, and is also stimulated through low calcium levels. In contrast, calcitonin rapidly inhibits osteoclast activity and thus decreases serum calcium levels. Calcitonin is secreted by the clear cells of the thyroid and inhibits osteoclast activity by increasing the intracellular cyclic AMP content via binding to a specific cell surface receptor, thus causing a contraction of the resorbing cell membrane. The biological relevance of calcitonin in human calcium homeostasis is not well established. 

Utility. There Is general agreement that the concentration of Immunoreactlve CT In normal serum Is extremely low (< 200 pg/ml). However, there Is evidence for Immunohetero-genelty of calcitonin In the serum of MTC patients (21) and It Is possible that studies In the future will demonstrate this phenomenon In normal sera as well. This might explain some reports of higher concentrations of Immunoreactlve CT In normal subjects (22). 

Hill, C. S. Jr. "Immunoassay of Human Calcitonin Clinical Measurement, Relation to Serum Calcium and Studies in Patients With Medullary Carcinoma". N. Engl. J. Med. (1970), 283. 890-895. 

More than 99% of total body calcium is found in bone the remaining less than 1% is in the ECF and ICE Calcium plays a critical role in the transmission of nerve impulses, skeletal muscle contraction, myocardial contractions, maintenance of normal cellular permeability, and the formation of bones and teeth. There is a reciprocal relationship between the serum calcium concentration (normally 8.6 to 10.2 mg/dL [2.15 to 2.55 mmol/L]) and the serum phosphate concentration that is regulated by a complex interaction between parathyroid hormone, vitamin D, and calcitonin. About one-half of the serum calcium is bound to plasma proteins the other half is free ionized calcium. Given that the serum calcium has significant protein binding, the serum calcium concentration must be corrected in patients who have low albumin concentrations (the major serum protein). The most commonly used formula adds 0.8 mg/dL (0.2 mmol/L) of calcium for each gram of albumin deficiency as follows ... 

Calcitonin is a polypeptide hormone that (along with PTH and the vitamin D derivative, 1,25-dihydroxycholecalciferol) plays a central role in regulating serum ionized calcium (Ca2+) and inorganic phosphate (Pi) levels. The adult human body contains up to 2 kg of calcium, of which 98 per cent is present in the skeleton (i.e. bone). Up to 85 per cent of the 1 kg of phosphorus present in the body is also found in the skeleton (the so-called mineral fraction of bone is largely composed of Ca3(P04)2, which acts as a body reservoir for both calcium and phosphorus). Calcium concentrations in human serum approximate to 0.1 mg ml-1 and are regulated very tightly (serum phosphate levels are more variable). 

Calcitonin lowers serum Ca2+ and Pi levels, primarily by inhibiting the process of bone resorption, but also by decreasing resorption of Pi and Ca2+ in the kidney. Calcitonin receptors are predictably found primarily on bone cells (osteoclasts) and renal cells, and generation of cAMP via adenylate cyclase activation plays a prominent role in hormone signal transduction. 

Calcitonin is released from the thyroid gland when serum calcium is elevated. Salmon calcitonin is used clinically because it is more potent and longer lasting than the mammalian form. Calcitonin is reserved as a third-line agent because efficacy is less robust than with the other antiresorptive therapies. 

The Ca2+ -responsive conformationally changeable membrane may be a good model of a new drug-delivery system, where calcitonin or parathyloid hormone can be released for the homeostasis of serum Ca2+ level. 

Calcitonin release is normally stimulated by rising serum calcium levels and suppressed by hypocalcemia. The major physiological effects of calcitonin are inhibition of bone resorption and deposition of postabsorp-tive calcium into bone following a meal, which prevents postprandial hypercalcemia. 

The regulation of calcitonin synthesis and release from the parafollicular C cells of the thyroid gland is calcium dependent. Rising serum calcium is the principal stimulus responsible for calcitonin synthesis and release. Other hormones, such as glucagon, gastrin, and serotonin, also stimulate calcitonin release. Calcitonin has been isolated in tissues other than the parafollicular C cells (parathyroid, pancreas, thymus, adrenal), but it is not known whether this material is biologically active. 

Calcitonin is also effective in reducing serum calcium levels in life-threatening hypercalcemia however, it is not as rapid or as effective as the bisphosphonates. Subcutaneous administration of salmon (Calcimar) or human (Cibacalcin) calcitonin reduces serum calcium levels within 3 to 5 days in 75 to 90% of malignant hypercalcemias. 

With the exception of the possible development of a hypervitaminosis associated with high-dose administration of vitamin D2 or D3, the compounds discussed in this chapter are relatively safe. Allergic reactions to the injection of calcitonin and PTH have occurred and chronic use of some bisphosphonates has been associated with the development of osteomalacia. The principal side effects of intravenous bisphosphonates are mild and include low-grade fever and transient increases in serum creatinine and phosphate levels. Oral bisphosphonates are poorly absorbed and can cause esophageal and gastric ulceration. They should be taken on an empty stomach the individual must remain upright for 30 minutes after ingestion. 

Calcitonin has proved useful as ancillary treatment in a large number of patients. Calcitonin by itself seldom restores serum calcium to normal, and refractoriness frequently develops. However, its lack of toxicity permits frequent administration at high doses (200 MRC units or more). An effect on serum calcium is observed within 4-6 hours and lasts for 6-10 hours. Calcimar (salmon calcitonin) is available for parenteral and nasal administration. 

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