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Internal Medicine

Hypothyroidism

Thyroid hormone deficiency.

Actress Sofia Vergara is doing her part to raise awareness about hypothyroidism — a condition she was diagnosed with following a bout with thyroid cancer that resulted in the removal of her thyroid gland. | Huffington Post

Thyroid hormone deficiency.

  • M/C disorder arising from hormone deficiency.

History:

Events influencing the evolution of treatment trends in hypothyroidism: Initial strategies for thyroid hormone replacement included thyroid transplantation, but efficacious pharmacologic strategies soon won favor. Natural thyroid preparations containing T4 and T3, such as desiccated thyroid, thyroid extracts, or thyroglobulin, were the initial pharmacologic agents. Synthetic agents were synthesized later. Early clinical trials demonstrated the efficacy of synthetic and natural agents, but concerns arose regarding consistency of natural thyroid preparations and adverse effects associated with T3-containing preparations (natural or synthetic). With the demonstration of peripheral T4-to-T3 conversion and the availability of the serum TSH radioimmunoassay in the early 1970s, there was a major trend in prescribing preference toward l-thyroxine monotherapy. | BMR = basal metabolic rate; DT = desiccated thyroid; IV = intravenous; RIA = radioim-munoassay; T3 = triiodothyronine; T4 = thyroxine; TG = thyroglobulin; TSH = thyroid-stimulating hormone. | McAninch, E. A., & Bianco, A. C. (2016). The History and Future of Treatment of Hypothyroidism. Annals of internal medicine, 164(1), 50–56. https://doi.org/10.7326/M15-1799

Aetiology

Primary hypothyroidism:

Disorder of thyroid gland causing decreased synthesis and secretion of thyroid hormones.
  • Chronic autoimmune thyroiditis (50% cases): ↑ Antithyroid antibodies (anti-TPO & antithyroglobulin antibodies)
  • Silent thyroiditis: Mild, of recent onset hyperthyroidism due to secretion of thyroid hormones in circulation, due to cell lysis and subsides in 6-12 weeks or is transformed in 50% of the cases to transient hypothyroidism, which subsides in 2-12 weeks
  • Iodine insufficiency: Presents with large goiter
  • Iatrogenic causes:
    • Partial thyroidectomy (for hyperthyroidism)
    • External radiotherapy
    • Drugs: Amiodarone and lithium
    • Antithyroid drug therapy (in pregnant women): Hypothyroidism in newborn infants.
  • Thyroid agenesis/dysgenesis: Children and infants
Causes of primary and secondary (central) hypothyroidism | Kostoglou-Athanassiou, I., & Ntalles, K. (2010). Hypothyroidism – new aspects of an old disease. Hippokratia, 14(2), 82–87.

Secondary (central) hypothyroidism.

Caused by a disorder of the pituitary or the hypothalamus, leading to decreased TSH secretion and consequently to decreased synthesis and secretion of thyroid hormones. Secondary hypothyroidism is also reported as central and is divided in secondary and tertiary when the causes are in the pituitary and the hypothalamus, respectively.
Differences between central and primary hypothyroidism | Gupta, V., & Lee, M. (2011). Central hypothyroidism. Indian journal of endocrinology and metabolism, 15(Suppl 2), S99–S106. https://doi.org/10.4103/2230-8210.83337

Peripheral (ponsumptive) hypothyroidism (rare):

Caused by aberrant expression of the deiodinase 3 enzyme (which inactivates thyroid hormone) in tumour tissues resulting in peripheral resistance to thyroxine
  • Infantile hepatic haemangiomatosis
  • Vascular and fibrotic tumours
  • Gastrointestinal stromal tumours (GIST)
  • Rare genetic syndromes

Clinical features

Clinical manifestations of hypothyroidism range from life threatening to no signs or symptoms.

hypothyroidism
The Calgary Guide | http://calgaryguide.ucalgary.ca/

Mild/subclinical hypothyroidism:

Asymptomatic presentation

Overt/clinical primary hypothyroidism:

Defined as thyroid-stimulating hormone (TSH) concentrations above the reference range and free thyroxine concentrations below the reference range.

The most common symptoms in adults are fatigue, lethargy, cold intolerance, weight gain, constipation, change in voice, and dry skin, but clinical presentation can differ with age and sex, among other factors

Percentage of symptoms and signs in clinical hypothyroidism | Georgiou E, Ntalles K, Proukakis Ch, Anousis ST. Clinical manifestations and use of microcomputer in the differential diagnosis between hypothyroid and obese women. Arch Hell Med. 1987;4:30–33.

Complications

Myxedema coma/gull disease (rare):

Outcome of long-standing untreated and severe hypothyroidism
  • Altered mental status, hypothermia, progressive lethargy, and bradycardia and can eventually result in multiple organ dysfunction syndrome and death.
  • Additional symptoms include swelling of the arms and legs and ascites. | By Herbert L. Fred, MD and Hendrik A. van Dijk – http://cnx.org/content/m15004/latest/, CC BY 2.5, https://commons.wikimedia.org/w/index.php?curid=30826142
  • Man with myxedema or severe hypothyroidism showing an expressionless face, puffiness around the eyes and pallor | By Herbert L. Fred, MD and Hendrik A. van Dijk – http://cnx.org/content/m15004/latest/, CC BY 2.5, https://commons.wikimedia.org/w/index.php?curid=30826141

Congenital hypothyroidism/cretinism:

Condition of severely stunted physical and mental growth owing to untreated congenital deficiency of thyroid hormone (congenital hypothyroidism) usually owing to maternal hypothyroidism.
Infant with congenital hypothyroidism. A – 3 month old infant with untreated CH; picture demonstrates hypotonic posture, myxedematous facies, macroglossia, and umbilical hernia. B – Same infant, close up of face, showing myxedematous facies, macroglossia, and skin mottling. C – Same infant, close up showing abdominal distension and umbilical hernia. | Rastogi, M. V., & LaFranchi, S. H. (2010). Congenital hypothyroidism. Orphanet journal of rare diseases, 5, 17. https://doi.org/10.1186/1750-1172-5-17

Diagnosis

The diagnosis of hypothyroidism is made from the history, the clinical picture and the laboratory measurements.

Thyroid function test:

TSH and FT4 measurement are the laboratory examinations necessary for the diagnosis of hypothyroidism and the differential diagnosis between primary (clinical or subclinical) and secondary one.
  • Primary hypothyroidism:
    • ↑ TSH & ↓/N FT4
    • ↑ Anti-TPO or anti-Tg antibodies (autoimmune thyroiditis)
    • Clinical type: ↑ TSH & ↓ FT4
    • Subclinical type: ↑ TSH & normal FT4
  • Secondary (central) hypothyroidism:
    • ↓/N TSH & ↓ FT4
    • TRH test:
      • Normal response: Pituitary cause
      • Abnormal response: Hypothalamic cause
Interpretation of thyroid function tests associated with hypothyroidism | TSH=thryoid-stimulating hormone. TRH=thyrotropin-releasing hormone. *TSH can also be suppressed. | Chaker, L., Bianco, A. C., Jonklaas, J., & Peeters, R. P. (2017). Hypothyroidism. Lancet (London, England), 390(10101), 1550–1562. https://doi.org/10.1016/S0140-6736(17)30703-1

Radiological investigations:

To differentiate between central causes of hypothyroidism
Pituitary hyperplasia due to primary hypothyroidism. | Ahmed Imran Siddiqi MBBS, MRCP Stephanie E. Baldeweg MD, FRCP, FRCP Et al Radiology Case Reports ,Volume 10, Issue 2, 2015, 1099

Management

Thyroid hormone replacement therapy:

Levothyroxine monotherapy in solid formulation, taken on an empty stomach, is the treatment of choice
Diagnosis and treatment of primary hypothyroidism | TSH=thryoid-stimulating hormone. | Chaker, L., Bianco, A. C., Jonklaas, J., & Peeters, R. P. (2017). Hypothyroidism. Lancet (London, England), 390(10101), 1550–1562. https://doi.org/10.1016/S0140-6736(17)30703-1

Myxedema coma/gull disease:

ICU management
  • Thyroid replacement: 0.50mg T4 or 0.10 μg T3 IV/oral every 4-6 hours
  • If temperature < 30°C:
    • Broad-spectrum antibiotics IV
    • Hydrocortisone (divided doses)

Thyroxine absorption test:

For individuals in whom high TSH concentrations persist after treatment and other causes have been excluded, the possibility of non-adherence, a common cause of therapy failure, should be considered and made to undergo a supervised thyroxine absorption test
Thyroxine absorption test: Protocol for supervised thyroxine absorption test, followed by weekly supervised thyroxine administration. Adapted from reference 115, by permission of Elsevier. TSH=thryoid-stimulating hormone. *Laboratory test values, especially an increase in free thyroxine, can be interpreted already at this stage. †Adequate free thyroxine rise is estimated to be roughly 50% from baseline at 120 min. | Walker JN, Shillo P, Ibbotson V, et al. A thyroxine absorption test followed by weekly thyroxine administration: a method to assess non-adherence to treatment. Eur J Endocrinol 2013; 168: 913–17

Summary

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