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PLASMA
Dietary Iodide Iodide Traping
FOLLICULAR CELL
Iodide Peroxidase Iodine +Tyrosil Residues Iodine + Tyrosil Residues DeiodoTyrosinase MIT + DIT Thyroglobulin MIT + DIT
COLLOID
T4 + T3
Thyroglobulin
T4 + T3
T4 + T3
T4 Protease MIT
T3 DIT
Brain
Depression Decreased Concentration General Lack of Interest
Liver
Increased LDL Cholesterol Elevated Triglycerides
Heart
Decreased Heart Rate Increased/Decreased Blood Pressure Decreased Cardiac Output
Intestines
Constipation Decreased GI Activity
Reproductive System
Decreased Fertility Menstrual Abnormalities May Harm Development of Infant
Kidneys
Decreased Function Fluid Retention and Edema
18 16 14 12 10 8 6 4 2 0
Males Females
At <40 years of age, prevalence is relatively low and similar between males and females At 40 years of age, a higher percentage of female patients have elevated TSH levels
Women
8% 5.9% 12%
Men
3% 2.3% NA
Colorado* (2000)
Rotterdam (1993) NHANES* (2002)
4%21% 3%16%
1%13% 1%10%
Sawin CT, et al. Arch Intern Med. 1985;145:1386-1388. Vanderpump MP et al. Clin Endocrinol (Oxf). 1995;43:55-68. Canaris GJ, et al. Arch Intern Med. 2000; 160:526-534. Hak AE, et al. Ann Intern Med. 2000;132:270-278. Hollowell JG, et al. J Clin Endocrinol Metab. 2002;87:489-499.
Ladenson PW, et al. Arch Intern Med. 2000;160:1573-1575. Braverman LE, et al. Werner & Ingbars The Thyroid. A Fundamental and Clinical Text. 8th ed. 2000. Zophel K, et al. Nuklearmedizin. 1999;38:150-155.
5 TSH, IU/mL
10
Braverman LE, et al. Werner & Ingbars The Thyroid. A Fundamental and Clinical Text. 8th ed. 2000. Canaris GJ, et al. Arch Intern Med. 2000;160:526-534. Vanderpump MP, et al. Clin Endocrinol (Oxf). 1995;43:55-68.
Free T4
0.7-1.8 ng/dL
TPOAb, TgAb
Negative
Hyperthyroidism
Restore a eumetabolic state 3 treatments available: antithyroid drugs, radioactive iodine (131I), and thyroid surgery
Singer PA, et al. JAMA. 1995;273:808-812.
Types of Hypothyroidism
Primary hypothyroidism: caused by decreased production of T4 and T3 due to thyroid dysfunction Secondary hypothyroidism: caused by decreased thyroidal stimulation by TSH; may be caused by pituitary (TSH) or hypothalamic (TRH) disease
Braverman LE, et al. Werner & Ingbars The Thyroid. A Fundamental and Clinical Text. 8th ed. 2000.
Rare
Infiltration Dysgensis Thyroid hormone resistance Iodine deficiency Iodine excess (WolffChaikoff effect)
Braverman LE, et al. Werner & Ingbars The Thyroid. A Fundamental and Clinical Text. 8th ed. 2000.
Abnormal Euthyroid
270
267
238
239
230 226 223 216 220 210 209 200 <0.3 0.3- >5.1- >10- >15- >20- >40- >60- >80 5.1 10 15 20 40 60 80
TSH, IU/mL
229
Bradycardia Cardiac and lipid abnormalities Cold intolerance Delayed reflexes Goiter Hair and skin changes
Braverman LE, et al. Werner & Ingbars The Thyroid. A Fundamental and Clinical Text. 8th ed. 2000.
levothyroxine, LT4)
Chemically stable T4 converted to T3 in periphery
Other therapies (T3 or T3 and T4 mixtures) Thyroid USP, liothyronine, liotrix, thyroglobulin Some disadvantages, no advantages versus levothyroxine
Singer PA, et al. JAMA. 1995;273:808-812.
levothyroxine or who have had their dosage, type, or brand of thyroid preparation changed, the TSH concentration should be measured after 8 to 12 weeks.
Patient Euthyroid
Go to Next Step
Singer PA, et al. JAMA. 1995;273:808-812. Demers LM, Spencer CA, eds. The National Academy of Clinical Biochemistry Web site. Available at: http://www.nacb.org/lmpg/thyroid_lmpg.stm. Accessed July 1, 2003.
Demers LM, Spencer CA, eds. The National Academy of Clinical Biochemistry Web site. Available at: http://www.nacb.org/lmpg/thyroid_lmpg.stm. Accessed July 1, 2003. Ayala AR, et al. Cleve Clin J Med. 2002;69:313-320. Ayala AR, et al. The Endocrinologist. 1997;7:44-50. Endocr Pract. 2002;8:457-469.
Hypothyroidism Treatment
Levothyroxine sodium is the treatment of choice for the routine management of hypothyroidism
Adults: about 1.7 g/kg of body weight/d Children up to 4.0 g/kg of body weight/d Elderly <1.0 g/kg of body weight/d
Clinical and biochemical evaluations at 6- to 8-week intervals until the serum TSH concentration is normalized Given the narrow and precise treatment range for levothyroxine therapy, it is preferable to maintain the patient on the same brand throughout treatment
Singer PA, et al. JAMA. 1995;273:808-812. Endocr Pract. 2002;8:457-469.
6-8 Weeks
TSH >4 IU/mL Repeat TSH Test TSH <0.5 IU/mL
TSH 0.5- 2.0 IU/mL Symptoms Resolved Increase Levothyroxine Dose by 12.5 to 25 g/d Continue Dose Measure TSH at 6 Months, Then Annually or When Symptomatic Decrease Levothyroxine Dose by 12.5 to 25 g/d
Singer PA, et al. JAMA. 1995;273:808-812. Demers LM, Spencer CA, eds. The National Academy of Clinical Biochemistry Web site. Available at: http://www.nacb.org/lmpg/thyroid_lmpg.stm. Accessed July 1, 2003.
Age and weight Cardiovascular health Severity and duration of hypothyroidism Concomitant disease states and treatment
Endocr Pract. 2002;8:457-469. Singer PA, et al. JAMA. 1995;273:808-812.
Therapy Monitoring
Clinical and laboratory monitoring enable
Evaluation of the clinical response Assessment of patient compliance Assessment of drug interactions, if applicable Adjustment of dosage, as needed
Undiagnosed hypothyroidism in pregnant women may adversely affect fetuses Treating maternal hypothyroidism during pregnancy appears to be beneficial, even when treatment falls short of euthyroid status Screening for hypothyroidism before or very early in pregnancy may be warranted
Special Considerations
Levothyroxine Therapy With Other Populations
Pregnant women
Thyroid failure may impede the intellectual development of the child Increased LT4 doses may be necessary TSH levels should be monitored each trimester
Postpartum thyroiditis
Can lead to symptomatic thyrotoxicosis and/or hypothyroidism Reported prevalence varies from 2% to 21% Has been associated with postpartum depression Can lead to chronic hypothyroidism
Synthroid [package insert]. Abbott Laboratories; 2003. Braverman LE, et al. Werner & Ingbars The Thyroid. A Fundamental and Clinical Text. 8th ed. 2000.
Incidence
2.1% to 3.8% per year in thyroid antibody-positive patients 0.3% per year in thyroid antibody-negative patients
McDermott MT, et al. J Clin Endocrinol Metab. 2001;86:4585-4590. Caraccio N, et al. J Clin Endocrinol Metab. 2002;87:1533-1538. Biondi B, et al. Ann Intern Med. 2002;137:904-914.
McDermott MT, et al. J Clin Endocrinol Metab. 2001;86:4585-4590. Braverman LE, Utiger RD, eds. The Thyroid: A Fundamental and Clinical Text. 8th ed. Philadelphia, Pa: Lippincott, Williams & Wilkins; 2000;1001.
30
20 10 0 0
2 Number of Symptoms
Endogenous factors
Previous subacute or silent thyroiditis Hashimoto thyroiditis
Patients, %
50
Euthyroid Women
The study's objective was to investigate whether mild thyroid failure and thyroid autoimmunity are associated with aortic atherosclerosis and myocardial infarction
Subclinical Hypothyroid
Euthyroid Subclinical Hyperthyroid Hyperthyroid Total-C* LDL-C* HDL-C* Triglycerides
100
50
Mild Thyroid Failure Treated With Levothyroxine Therapy: Effects on Total Cholesterol
Gorman et al, 1979 Change in Total Cholesterol (mg/dL), % 0 -5 -10 -15 -20 Elder et al, Wiseman et al, 1990 1993
-25
-30 -35 -40
Tanis BC, et al. Clin Endocrinol. 1996;44:643-649.
250
LDL-C
145
2
0
LT4 Placebo
230
LT4 Placebo
140
LT4 Placebo
Before
After
Reduced Absorption
Colestipol hydrochloride to T3 Clearance Sucralfate Amiodarone Ferrous sulfate Selenium deficiency Food (eg, soybean formula) Other Mechanisms Aluminum hydroxide Lovastatin Cholestyramine Sertraline Sodium polystyrene sulfonate
Braverman LE, Utiger RD, eds. The Thyroid: A Fundamental and Clinical Text. 8th ed. 2000. Synthroid [package insert]. Abbott Laboratories; 2003.
Overtreated >20%
60.1
Undertreated >18%
17.6 0.7
Hypothyroid
Under-Replacement Risks
Switching between different levothyroxine
Over-Replacement Risks
Switching a narrow therapeutic index drug, such as LT4,
without retesting and retitrating can cause inconsistent TSH control, resulting in over-replacement Over-replacement risks (TSH <0.5 IU/mL) Iatrogenic thyrotoxic state Increased heart rate and myocardial contractility For cardiac patients, increased risk of angina and MI Reduced bone density/osteoporosis Psychiatric symptoms, such as anxiety, sleep disturbance, irritability, and fatigue
Summary
Hypothyroidism increases in prevalence and incidence among the elderly. Autoimmune thyroiditis is the most common cause of hypothyroidism Levothyroxine sodium is the treatment of choice for the routine management of hypothyroidism Treatment and management of subclinical hypothyroidism and population screening are still controversial Special considerations may apply in planning treatment due to changes in the metabolic clearance of thyroid hormone, drug interactions and potential adverse reaction
PARATHYROID GLANDS
The parathyroid glands are embedded on the posterior surfaces of the lateral lobes of the thyroid principal cells produce parathyroid hormone oxyphil cells function is unknown Parathyroid hormone (PTH) regulates the homeostasis of calcium and phosphate increase blood calcium level decrease blood phosphate level increases the number and activity of osteoclasts increases the rate of Ca+2 and Mg+2 from reabsorption from urine and inhibits the reabsorption of HPO4-2 so more is secreted in the urine promotes formation of calcitriol, which increases the absorption of Ca+2, Mg+2,and HPO4-2 from the GI tract
Principles of Human Anatomy and Physiology, 11e 58
Principal cells produce parathyroid hormone (PTH) Oxyphil cell function is unknown
59
Figure 1813
High or low blood levels of Ca+2 stimulate the release of different hormones --- PTH or Calcitonin
Principles of Human Anatomy and Physiology, 11e 62
Biosynthesis, Storage & Secretion of PTH PTH is synthesized as the preprohormone (Preproparathyroid Hormone) by parathyroid gland chief cells The active form of PTH is cleaved from the preprohormone before release from the gland PTH is synthesized continously (it is either released from the gland or degraded) PTH is released by exocytosis in response to reduced plasma calcium Vitamin D feeds back to reduce PTH secretion as a secondary mechanism
Calcitonin
Calcitonin is a peptide hormone secreted by the parafollicular or C cells of the thyroid gland It is synthesized as the preprohormone & released in response to high plasma calcium Calcitonin acts on bone osteoclasts to reduce bone resorption. Net result of its action is a decline in plasma calcium & phosphate
Calcium Metabolism:
Hypoparathyroidism
Abnormally low PTH levels Usually caused by parathyroid damage in thyroid surgery
69
Hyperparathyroidism
The incidence of the disease increases dramatically after the age of 50 and it is 24 folds more common in women. A single adenoma occurs in about 80% of patients with primary hyperparathyroidism. Four glands hyprplasia account for 1520% of cases. A parathyroid carcinoma could be the etiology in a rare incidence of less then 1%.
Hypoparathyroidism
Diagnosis:
In the absence of renal failure the presence of hypocalcaemia with hyperphosphataemia is virtually diagnostic of hypoparathyroidism. Undetectable serum iPTH confirms the diagnosis or it can be detectable if the assay is very sensitive.
Treating Hypoparathyroidism
It seems logical that PTH would be beneficial in treating hypoparathyroidism. However few studies are available that have looked at this traetment possibility. Study among patients with hypoparathyroidism to PTH twice a day or calcium and calcitriol to attain normal calcium concentration. Calcium, phosphorus and magnesium levels did not differ between the group. No significant BMD between the group. PTH however does not have the FDA indication for hypoparathyroidism (Painter and Camacho,2007)
77
Hypoparathyroidism Treatment:
The mainstay of treatment is a combination of oral calcium with pharmacological doses of vitamin D or its potent analogues. Phosphate restriction in diet may also be useful with or without aluminum hydroxide gel to lower serum phosphate level.
Bone reabsorption exceeds deposition Osteoclasts mobilize Ca++ to plasma Factors: inadequate Ca++ intake, genes, hormones, smoking
81
Definition of osteoporosis
a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, leading to enhanced bone fragility and a consequent increase in fracture risk.
Normal
Osteoporosis
Osteopenia
T-Score
-2.5
-1