Hypothyroidism

From Anvita Health Wiki

Contents 1 More Specific Terms 2 Etiology 3 Epidemiology 4 Pathology 5 Clinical-manifestations 6 Laboratory 7 Diagnostic-procedures 8 Radiology 9 Complications 10 Differential-diagnosis 11 Management 12 More General Terms 13 Additional Terms 14 Internet Database 15 References

More Specific Terms

• cretinism (congenital hypothyroidism)
• hypothyroidism during pregnancy
• idiopathic primary hypothyroidism; atrophic autoimmune thyroiditis
• invasive fibrous thyroiditis; Riedel's fibrous thyroiditis; Riedel's struma
• myxedema
• subclinical hypothyroidism

Etiology

• primary hypothyroidism > 90%

• idiopathic primary hypothyroidism (possibly autoimmune block of TSH receptors [Graves disease variant])
• chronic lymphocytic thyroiditis (Hashimoto's) is the most common cause of goitrous hypothyroidism
• iatrogenic due to thyroidectomy or radioiodine therapy
• iodine deficiency
• postpartum (transient)
• subacute thyroidism (transient)
• drugs ( iodides, lithium, interferon-alpha, interleukin-2, p-aminosalicylate, amiodarone)
• developmental

• biosynthetic defects
• agenesis of thyroid

• secondary hypothyroidism: uncommon

• pituitary insufficiency

• hypopituitarism
• pituitary adenoma
• empty sella syndrome
• pituitary irradiation
• pituitary surgery
• pituitary lesions usually occur in association with other evidence of pituitary disease

• hypothalamic ( TRH) deficiency is rare

Epidemiology

• common, prevalence increases with age
• women > men.
• prevalence

• 1-6% of elderly [4]
• 0.2% general population [5]

• subclinical hypothyroidism (increased TSH, normal free T4 & T3) is more common than overt clinical hypothyroidism (3.9% in general population) [5]

Pathology

• cardiac

• cardiac enlargement
• reduced myocardial contractility
• pericardial effusion in 1/3
• heart failure rare in absence of associated heart disease
• incidence coronary heart disease increased 2-fold

• pulmonary - sleep apnea, obstructive & central

Clinical-manifestations

• Symptoms:

• cold intolerance, fatigue, weakness, myalgias (proximal), somnolence, memory impairment, constipation, menorrhagia, hoarseness

• Signs:

• slow deep tendon reflex relaxation*, bradycardia, non-pitting edema ( myxedema), goiter

• Rarely:

• hypoventilation, pericardial & pleural effusion, deafness, carpal tunnel syndrome, arthralgias, arthritis, tibial collapse, osteonecrosis of the hip, epiphyseal dysgenesis, ataxia

• Late manifestations:

• cardiomyopathy, proximal muscle weakness, facial & periorbital edema, thickened dry skin

• Elderly often present with non-specific signs/symptoms:

• anorexia, weakness, hearing loss, anemia slow deep tendon reflex relaxation*

• * may be only presenting sign in the elderly

Laboratory

• serum thyroid-stimulating hormone (TSH)

• serum TSH > 20 uU/mL confirms the diagnosis of primary hypothyroidism
• TSH 7-20 uU/mL may occur in non thyroidal illness
• no evidence to support routine screening with TSH [8]

• serum T4, T4 index, free T4 & free T3 are low
• high serum TSH (< 20 uU/mL) with normal free T4 occurs in subclinical hypothyroidism
• low serum TSH with low free T4 is associated with hypothyroidism secondary to pituitary- hypothalamic dysfunction
• serum Na+: hyponatremia
• lipid panel:

• hypercholesterolemia: increased LDL cholesterol
• hypertriglyceridemia

• serum creatine kinase: increased
• serum homocysteine: hyperhomocysteinemia
• tests for Hashimoto's throiditis:

• anti-TPO
• anti-thryoglobulin
• diagnosis does not affect treatment

• evidence of hypoadrenalism if hypothyroidism is confirmed

• plasma ACTH
• serum cortisol
• see Addison's disease ( hypoadrenalism)

• complete blood count ( CBC)

• mild anemia
• mildly increased MCV

• serum prolactin may be elevated (< 200 ng/mL)

Diagnostic-procedures

• electrocardiogram:

• low voltage
• T wave abnormalities

Radiology

• MRI not necessary for hyperprolactinemia when serum prolactin < 200 ng/mL [3]

Complications

• peripheral neuropathy in treated hypothyroidism [14]
• hyperprolactinemia is commonly caused by hypothyroidism
• myxedema coma

Differential-diagnosis

• subclinical hypothyroidism

Management

• thyroxine ( T4, levothyroxine, Synthroid, Levoxyl)

• begin 50-100 ug/day;

• 12.5-25 ug/day if heart disease suspected*
• 25-50 ug/day if > 60 years of age [3]

• increase to 75-150 ug/day after 3-4 months

• dose increases every 6 weeks
• dose increments 12.5-25 ug/day

• adjust to normalize serum TSH

• target serum TSH 1.0-2.5 uIU/mL [3]
• low-normal serum TSH of no added benefit [13]

• in the elderly [4]

• begin 25 ug/day
• increase by 25 ug every 6 weeks
• average dose to normalize TSH is 75 ug QD

• measure TSH after 3-4 months (decrease is slow)
• increases of thyroxine of may be required with:

• pregnancy (25-50 ug/day, 30%) [9]

• increase dose of thyroxine by 1/3 as soon as pregnancy is confirmed [10]

• with progression of thyroid destruction in Hashimoto's thyroiditis
• following thyroidectomy or radioiodine ablation of the thyroid

• decreases of thyroxine may be required with:

• spontaneous disappearance of TSH-receptor blocking autoantibodies
• increases in stimulatory TSH-receptor autoantibodies ( reactivation of Grave's disease)
• emergence of autonomy & hyperfunction in patients with nodular goiter

• combination of T3/ T4 offers no benefit over T4 alone [6,7] but some patients claim they feel better on T3/T4# [11]

• Caution:
• * coronary artery disease may be exacerbated by treatment of hypothyroidism. Start thyroxine 12.5-25 ug/day. Increase slowly.
• * adrenal failure may be associated with both primary & secondary hypothyroidism & may be exacerbated by therapy.
  
• Emergency therapy ( hypotension, hypoventilation) [rarely necessary]

• 50-100 ug thyroxine every 6 hours for 24 hours, monitor EKG, administer hydrocortisone.
  

• # propranolol & glucocorticoids may inhibit conversion of T3 to T4 [11]

More General Terms

• thyroid disease
• chronic endocrine disease
• sign/symptom

Additional Terms

• Addison's disease (primary adrenal failure)
• free thyroxine index (fT4I)
• Hashimoto's thyroiditis; chronic lymphocytic thyroiditis; struma lymphomatosa; lymphadenoid goiter; primary myxedema
• T3 total in serum/plasma
• thyroid-stimulating hormone (TSH) in serum
• thyroid-stimulating hormone (TSH) or thyrotropin
• thyroxine (T4)
• thyroxine [T4] (free) in serum
• thyroxine [T4] (total) in serum
• triiodothyronine [T3] (free) in serum

Internet Database

OMIM: 241850

References

1. Manual of Medical Therapeutics, 28th ed, Ewald & McKenzie (eds), Little, Brown & Co, Boston, 1995, pg 465
2. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 54, 749
3. Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 15 American College of Physicians, Philadelphia 1998, 2006, 2009
4. Solomon DH, in: UCLA Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 12-15, 2001
5. Journal Watch 22(7):51, 2002 Hollowell JG et al Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab 87:489, 2002 PMID: [1]
6. Journal Watch 23(23):185-86, 2003 Walsh JP et al Combined thyroxine/liothyronine treatment does not improve well-being, quality of life, or cognitive function compared to thyroxine alone: a randomized controlled trial in patients with primary hypothyroidism. J Clin Endocrinol Metab 88:45431, 2003 PMID: [2]
   - Sawka AM et al Does a combination regimen of thyroxine (T4) and 3,5,3'- triiodothyronine improve depressive symptoms better than T4 alone in patients with hypothyroidism? Results of a double-blind, randomized, controlled trial. J Clin Endocrinol Metab 88:4551, 2003 PMID: [3]
7. Journal Watch 24(2):16, 2004 Clyde PW et al Combined levothyroxine plus liothyronine compared with levothyroxine alone in primary hypothyroidism: a randomized controlled trial. JAMA 290:2952, 2003 PMID: &dopt=Abstract
   - Cooper DS Combined T4 and T3 therapy--back to the drawing board. JAMA 290:3002, 2003 PMID: [4]
8. Journal Watch 24(5):41, 2004 US Preventive Services Task Force (USPSTF) Screening for thyroid disease: recommendation statement. Ann Intern Med 140:125, 2004 <PubMed> PMID: [5] <Internet> [6]
   - Helfand M; U.S. Preventive Services Task Force. Screening for subclinical thyroid dysfunction in nonpregnant adults: a summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 140:128 <PubMed> PMID: [7] <Internet> [8]
   - Surks MI et al Subclinical thyroid disease: scientific review and guidelines for diagnosis and management. JAMA 291:228, 2004 PMID: [9]
9. Journal Watch 24(16):130-31, 2004 Alexander EK, Marqusee E, Lawrence J, Jarolim P, Fischer GA, Larsen PR. Timing and magnitude of increases in levothyroxine requirements during pregnancy in women with hypothyroidism. N Engl J Med. 2004 Jul 15;351(3):241-9. PMID: [10]
10. Prescriber's Letter 11(9): 2004 Management of Hypothyroidism in Pregnancy Detail-Document#: [11] (subscription needed) [12]
11. Prescriber's Letter 12(5): 2005 Combination Liothyronine (T3) and Levothyroxine (T4) Supplementation for Hypothyroidism Detail-Document#: [13] (subscription needed) [14]
12. Roos A, Linn-Rasker SP, van Domburg RT, Tijssen JP, Berghout A. The starting dose of levothyroxine in primary hypothyroidism treatment: a prospective, randomized, double-blind trial. Arch Intern Med. 2005 Aug 8-22;165(15):1714-20. PMID: [15]
13. Walsh JP, Ward LC, Burke V, Bhagat CI, Shiels L, Henley D, Gillett MJ, Gilbert R, Tanner M, Stuckey BG. Small changes in thyroxine dosage do not produce measurable changes in hypothyroid symptoms, well-being, or quality of life: results of a double-blind, randomized clinical trial. J Clin Endocrinol Metab. 2006 Jul;91(7):2624-30. Epub 2006 May 2. PMID: [16]
14. Orstavik K et al, Pain and small fiber neuroapathy in patients with hypothyroidism. Neurology 2006, 67:786 PMID: [17]

hypothyroidism