Thyrotoxicosis is a syndrome caused by either overproduction or excessive release of free thyroxine (T4) and/or triiodothyronine (T3) in the serum. The increased production of thyroid hormones is seen in toxic multinodular goiter, toxic adenoma, struma ovarii and Graves' disease while the excessive release of the hormone is secondary to inflammation or destruction of the thyroid glands e.g. autoimmune diseases, radiation, infection, chemical or mechanical injury. Increased intake of thyroid medication leads to factitious thyrotoxicosis.

Thyrotoxicosis occurs more frequently in women with Graves' disease presenting between the age of 20 and 40 years [1]. Toxic nodular goiter is prevalent amongst older adults and in individuals with low levels of iodine in their diet while autoimmune thyrotoxicosis is seen more often in those who smoke [1].

Typical manifestations of overt thyrotoxicosis are anxiety, palpitations, intolerance to heat, myopathy, asthenia, menstrual irregularities in women, tremors [2], excessive sweating, exophthalmos, tachycardia [3] and diffuse thyromegaly. Orbital involvement with protrusion of the eyeballs, diplopia, and dryness is noted in one-third of the patients with Graves' disease [3]. Sympathetic overstimulation and related symptoms like anxiety and tremors are found mostly in young thyrotoxic patients while the incidence of dyspnea, cardiac arrhythmias, atrial fibrillation (AF) and heart failure is higher in older patients [4].

Patients with subclinical thyrotoxicosis can present with non-specific symptoms although they have a higher risk of atrial fibrillation compared to patients with overt thyrotoxicosis.

• Fatigue

  All study drug-related adverse events were mild and included headache and fatigue for sorafenib, and headache, increased alanine aminotransferase and glutamate dehydrogenase, fatigue, and nervousness for levothyroxine. [ncbi.nlm.nih.gov]

  […] recall: thyroid = metabolism, so everything is revved up: Hyperactivity, Irritability, Dysphoria, Insomnia *Heat Intolerance, Sweating Palpitations Fatigue, Weakness Weight Loss, Hyperphagia, Frequent bowel movements Oligo- or amenorrhea Tremor, Insomnia [quizlet.com]

  Thyrotoxicosis is characterized by NERVOUSNESS; TACHYCARDIA; FATIGUE; WEIGHT LOSS; heat intolerance; and excessive SWEATING. [connects.catalyst.harvard.edu]

• Anemia

  Thrombotic thrombocytopenic purpura (TTP) may be seen in association with autoimmune disorders such as immune hemolytic anemia and systemic lupus erythematosus, but rarely has it been associated with Graves' disease. [ncbi.nlm.nih.gov]

  This autoimmune condition may be associated with other autoimmune diseases, such as pernicious anemia, myasthenia gravis, vitiligo, adrenal insufficiency, celiac disease, and type 1 diabetes mellitus. [emedicine.medscape.com]

  Adverse effects : 1) Rare but warranting discontinuation of thionamide treatment: Agranulocytosis, aplastic anemia; acute hepatitis (propylthiouracil), obstructive jaundice (methimazole); vasculitis with antineutrophil cytoplasmic antibodies, lupus-like [empendium.com]

  Graves disease (like Hashimoto thyroiditis ) sometimes occurs with other autoimmune disorders, including type 1 diabetes mellitus, vitiligo, premature graying of hair, pernicious anemia, connective tissue disorders, and polyglandular deficiency syndrome [merckmanuals.com]

• Vomiting

  A 32-year-old man presented with vomiting and diarrhea. Laboratory data showed that he had transient hypercalcemia, primary thyrotoxicosis due to painless thyroiditis and panhypopituitarism. [ncbi.nlm.nih.gov]

• Nausea

  A 28-year-old G2P1 Thai woman presented with severe nausea and vomiting at 12 weeks' gestation. The initial diagnosis was hyperemesis gravidarum. She was clinically euthyroid. Physical examination revealed no thyroid gland enlargement. [ncbi.nlm.nih.gov]

  Acute infection (fever, tachycardia) Central nervous system disorder, with increased intracranial pressure (nausea, vomiting, mental status changes) Primary hepatic disorder with failure (nausea, vomiting, jaundice, mental status changes) Primary cardiac [clinicaladvisor.com]

  Precise criteria for thyroid storm have been defined and include fever, tachycardia, arrhythmias, congestive heart failure, hypotension, hyperpyrexia, agitation, delirium, psychosis, stupor and coma, as well as nausea, vomiting, diarrhea, and hepatic [shifrinmd.com]

  This is "thyrotoxic myopathy" Diarrhoea, nausea and vomiting Increased metabolic rate; increased demand for metabolic substrate. [derangedphysiology.com]

• Myalgia

  He consulted for 15 days prior to the intervention, with palpitations, fever greater than 104°F, myalgia, arthralgia and hiporexia. [omicsonline.org]

• Hyperhidrosis

  Dermatological causes: primary, idiopathic hyperhidrosis Psychoautonomic causes: physical and emotional stress (e.g., hypoglycemia, agitation, anxiety ) Endocrinological causes Hyperthyroidism Menopause, pregnancy Pheochromocytoma Cushing's syndrome [amboss.com]

  Beta-blockers : The indications include tachycardia and supraventricular arrhythmias, eyelid retraction, tremor, and hyperhidrosis. If antithyroid drugs alone are effective, beta-blockers are not required. [empendium.com]

• Tremor

  Tremor, usually limb tremor, has been observed in 78% of patients with thyrotoxicosis. 1 Here we report isolated abdominal tremor, reminiscent but different from belly dancer’s dyskinesia, in a patient with thyrotoxicosis. [neurology.org]

  Typical manifestations of overt thyrotoxicosis are anxiety, palpitations, intolerance to heat, myopathy, asthenia, menstrual irregularities in women, tremors, excessive sweating, exophthalmos, tachycardia and diffuse thyromegaly. [symptoma.com]

  Abstract A 50-year-old lady presented with chest pain, tremor, weight loss and intermittent ST elevation in her ECG associated with elevated markers of myocardial injury. [ncbi.nlm.nih.gov]

  Thyrotoxicosis An excess of thyroid hormones in the blood, causing a variety of symptoms that include rapid heart beat, sweating, anxiety, and tremor. Basedow, Karl Adolph von, German physician, 1799-1854. [medical-dictionary.thefreedictionary.com]

• Insomnia

  […] recall: thyroid = metabolism, so everything is revved up: Hyperactivity, Irritability, Dysphoria, Insomnia *Heat Intolerance, Sweating Palpitations Fatigue, Weakness Weight Loss, Hyperphagia, Frequent bowel movements Oligo- or amenorrhea Tremor, Insomnia [quizlet.com]

  Symptoms of Graves Disease, Hyperthyroid & Thyrotoxicosis Insomnia Hand Tremor Anxiety Restlessness Weight Loss Sweating Fine Hair Rapid Heart Beat or Arrythmia Loose Stool Muscle Wasting Increased Appetite Agitation Fine, Warm, and Moist Skin Menstrual [whitelotusclinic.ca]

  Symptoms associated with more severe cases include: Nervousness Irritability Fatigue Fast heartbeat Weight loss Insomnia Hair loss Thin skin Intolerance to heat Increased perspiration Muscle aches Weakness in upper arms and thighs Increased bowel movements [virginiamason.org]

  […] years of age Osteopathy: osteoporosis, fractures (in the elderly) Endocrinological ♀ : Oligo/ amenorrhoea and anovulatory infertility ♂ : Gynecomastia, decreased libido, erectile dysfunction Neuropsychiatric system : anxiety ;, agitation, depression, insomnia [amboss.com]

  Neuromuscular symptoms and signs of hyperthyroidism include nervousness, hyperactivity and restlessness, anxiety and irritability, insomnia, tremor, and muscle weakness. [britannica.com]

• Apathy

  Overt thyrotoxic crisis : Fever; extreme agitation and worsening of psychotic symptoms; sometimes somnolence, apathy, or even coma; in some cases, status epilepticus; sudden worsening of cardiovascular symptoms (severe tachycardia, atrial fibrillation [empendium.com]

  ("Apathy" as the mental status change to diagnose thyroid storm.) LaFranchi, SH, Hanna, CE, Braverman, LE, Utiger, RD. “Graves’ disease in the neonatal period and childhood”. 2005. pp. 1049-1059. [clinicaladvisor.com]

• Memory Impairment

  AIMS: Disturbed levels of thyroid hormones are associated with neuropsychiatric disorders, including memory impairments. The aim of this study was to evaluate effects of mild induced thyrotoxicosis on working memory and its neural correlates. [ncbi.nlm.nih.gov]

The workup in thyrotoxicosis comprises of a thorough history of the symptoms, their onset, duration, progress, whether residing in iodine deficient regions, dietary and medication intake, exposure to toxic radiation/chemicals, family and occupational history. Patients with Graves' disease may provide a family history of autoimmune disorders like rheumatoid arthritis or vitiligo. Physical examination is likely to show a single thyroid nodule or a multinodular goiter [2] with resting tachycardia, visible pulsations, myxedema and skin changes. On palpation there may be thyroid tenderness in patients with thyroiditis and auscultation may reveal a bruit. Ophthalmopathy features are rarely noticed in toxic nodular goiter but are a frequent finding in Graves' disease [2].

Laboratory tests include complete blood cell count, serum thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3) levels and tests for specific autoantibodies if autoimmune etiology is suspected. TSH levels are diminished in overt as well as subclinical thyrotoxicosis while FT4 and/or FT3 levels are elevated only in case of overt thyrotoxicosis. Only T3 levels may be elevated in mild thyrotoxicosis.

A radioactive iodine uptake or scintigraphy scan is indicated if the cause of thyrotoxicosis is not revealed by either history or examination [2]. It provides a differential diagnosis and helps in the subsequent treatment of the patient [5] [6] [7] [8] [9] [10]. Increased uptake is seen in Graves' disease, toxic nodular goiter, and toxic multinodular goiter while low uptake is seen in thyroiditis.

If scintigraphy is contraindicated, then color doppler ultrasonography can be performed for diagnosing thyrotoxicosis [6] and will show increased vascularity in most cases. Ultrasonography, if performed shows a normal sized gland or moderate thyromegaly in Graves' disease.

An electrocardiogram is obtained to detect AF while more tests can be ordered if indicated by clinical findings and laboratory studies.

The selection of treatment differs according to the cause of thyrotoxicosis and the wishes of the individual patient. The preferred treatment for Graves disease is usually antithyroid drug therapy, almost always carbimazole. [ncbi.nlm.nih.gov]

Gly389Arg and Ser49Gly polymorphisms of β 1-adrenoreceptors ( β 1-AR) can influence the cardiovascular prognosis. However, the possible effect of Gly389Arg and Ser49Gly polymorphisms on heart function in thyrotoxicosis has not been studied. [ncbi.nlm.nih.gov]

Other population groups at risk include: elderly (due to the increased prevalence of nodular thyroid disease) people living in areas of endemic iodine deficiency Treatment and prognosis Various treatment schedules have been proposed for prophylaxis 4, [radiopaedia.org]

Myocardial viability testing and impact of revascularization on prognosis in patients with coronary artery disease and left ventricular dysfunction: a meta-analysis. J Am Coll Cardiol. ‎ Página 50 - McCrohon JA, Moon JC, Prasad SK, et al. [books.google.es]

Prognosis Good with treatment but remission and relapse common Increased incidence of other autoimmune diseases: SLE, T1DM, Addison’s Treatment Medical B-blockers for rapid symptom control Titration of carbimazole (reduces T3 and T4 by inhibiting thyroid [alancam.com]

Presence of jaundice suggests especially poor prognosis. Ultimately, thyroid storm is a clinical diagnosis and requires prompt recognition and treatment. [mdcalc.com]

BACKGROUND: Thyrotoxicosis has multiple etiologies, manifestations, and potential therapies. Appropriate treatment requires an accurate diagnosis and is influenced by coexisting medical conditions and patient preference. [ncbi.nlm.nih.gov]

and thyroidectomy, are common treatment modalities depending on the etiology and severity of the thyrotoxicosis. [medlink.com]

Serological thyroid hormone assay confirms hyperthyroidism, while measurement of antithyroid antibodies, thyroid ultrasonography, and radio-active iodine uptake tests help identify the etiology. [amboss.com]

Epidemiology 1% of the population peak incidence 30-50y F>M Most common cause of endogenous hyperthyroidism Aetiology Unknown Genetic predisposition: HLA-DR3, -B8, DR2 CTLA-4 polymorphisms Potentially environmental factors: viral or bacterial infection [alancam.com]

Epidemiology References: [1] [2] [3] [4] Epidemiological data refers to the US, unless otherwise specified. [amboss.com]

The high discordant rate of 44% between the provisional with the final diagnosis is consistent with an epidemiological study of acute abdominal pain concluding that the overall sensitivity of history taking and physical examination in making a diagnosis [academic.oup.com]

These antibodies stimulate the thyroid gland to produce more T3 and T4 Epidemiology Can occur at any age Peak onset age 40-60 F:M 5-10 : 1 Aetiology Environment triggers include: High iodine intake Stress Smoking Smoking is also a major risk factor in [almostadoctor.co.uk]

These findings suggest a possible role of thyroid-hormone excess in the pathophysiology of some patients who have takotsubo cardiomyopathy. [ncbi.nlm.nih.gov]

Levine and his coworkers, on the basis of their clinical observations of patients in whom thyrotoxicosis was the sole or principal factor leading to cardiomegaly, atrial fibrillation, or congestive heart failure. 5, 6 In this report, I shall address the pathophysiology [nejm.org]

Psychiatric manifestations of Graves' hyperthyroidism: pathophysiology and treatment options. CNS Drugs. 2006; 20 (11): 897-909[ PubMed ] 17. Whybrow PC, Prange AJ. A hypothesis of thyroid-catecholamine-receptor interaction. [endometabol.com]

Thyroid imaging and radiotracer thyroid uptake measurements, combined with serologic data, enable specific diagnosis and appropriate patient treatment. [3, 4, 5, 6] The common causes of thyrotoxicosis have different pathophysiologic features and include [emedicine.medscape.com]

Thioamide preventive treatment could be useful to prevent type 1 AIT recurrence. In conclusion, AIT recurrence after amiodarone reintroduction is 4 times more frequent in patients with type 1 AIT history. [ncbi.nlm.nih.gov]

In brief: The management strategy for thyroid storm revolves around preventing peripheral effects of raised thyroid hormone levels, and preventing the ongoing increase of said levels by inhibiting the synthesis and release of thyroid hormone. [derangedphysiology.com]

1. Ross DS, Burch HB, Cooper DS, et al. 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis. Thyroid. 2016 Oct. 26;(10):1343-1421.
2. Pearce EN. Diagnosis and management of thyrotoxicosis. BMJ. 2006 Jun10; 332(7554):1369-1373
3. Cooper DS. Hyperthyroidism. Lancet 2003;362: 459-68.
4. Frost L, Vestergaard P, Mosekilde L. Hyperthyroidism and risk of atrial fibrillation or flutter: a population-based study. Arch Intern Med. 2004 Aug 9-23; 164(15):1675-8.
5. Hari Kumar KV, Pasupuleti V, Jayaraman M, et al. Role of thyroid Doppler in differential diagnosis of thyrotoxicosis. Endocr Pract. 2009 Jan-Feb; 15(1):6-9.
6. Donkol RH, Nada AM, Boughattas S. Role of color Doppler in differentiation of Graves' disease and thyroiditis in thyrotoxicosis. World J Radiol. 2013 Apr 28; 5(4):178-83.
7. Zhao X, Chen L, Li L, et al. Peak systolic velocity of superior thyroid artery for the differential diagnosis of thyrotoxicosis. PLoS One. 2012; 7(11):e50051.
8. Alzahrani AS, Ceresini G, Aldasouqi SA. Role of ultrasonography in the differential diagnosis of thyrotoxicosis: a noninvasive, cost-effective, and widely available but underutilized diagnostic tool. Endocr Pract. 2012 Jul-Aug; 18(4):567-78.
9. Piga M, Cocco MC, Serra A, et al. The usefulness of 99mTc-sestaMIBI thyroid scan in the differential diagnosis and management of amiodarone-induced thyrotoxicosis. Eur J Endocrinol. 2008 Oct;159(4):423-9.
10. Rosario PW, Santos JB, Nunes NS, et al. Color flow Doppler sonography for the etiologic diagnosis of thyrotoxicosis. Horm Metab Res. 2014 Jun; 46 (7):505-9.