Search

Last updated: Acute Gastroenteritis (incl C Diff)
on December 16, 2014

Acute Hyperthyroidism

Key facts:

Authors: Benjamin Harris and Andrew Stein 
Top Tip: Thyroid disease is very common. Look for it

Key Differential Diagnoses

  • Sepsis
  • Gastroenteritis
  • Cardiac arrhythmias
  • Drug intoxication
  • Psychosis, anxiety

Key Investigations

  • Thyroid Function Tests:
    • Serum TSH (0.1-6.0 miu/L)
    • Serum free T3 and free T4
  • FBC, U+E, LFT, Bone, Glucose
  • CXR
  • ECG (AF?)

Key Treatments

  • PO CARBIMAZOLE 15 mg tds
  • PO PROPRANOLOL 40 mg tds
    ± IV HYDROCORTISONE 100mg qds or IV DEXAMETHASONE 4mg qds (thyroid storm)

Key Management Decisions

  • Does the patient have thyroid storm?
  • Does the patient need ITU?

Background

15% of elderly patients presenting with new-onset AF will have hyperthyroidism

Introduction

  • Hyperthyroidism (thyrotoxicosis) is a common condition characterised by excess serum levels of thyroid hormones (T4 and/or T3)
  • It affects at least 2% of women, and 0.2% of men
  • It can manifest as a wide range of clinical presentations – from mild anxiety to rare but potentially fatal 'thyroid storm' (1-2% of patients)
  • It is an autoimmune disease asscoiated with thyroid stimulating immunoglobulins against the TSH receptor on the thyroid follicular cell membrane
  • Graves' Disease refers to the common form of hyperthyroidism in which eye signs and toxic symptoms accompany diffuse enlargement of the thyroid gland (with antibodies and occasional pre-tibial myxoedema). An ophthalmopathic immunoglobulin may be causative and independent
  • There is an association with HLA B8 and DR3
  • Self-administered T4 must not be forgotten, particularly in doctors and nurses
  • A gross persistent excess of iodine in health foods and some cough medicines may precipitate hyperthyroidism
  • 10-25% have AF
    Note: 15% of elderly patients presenting with new-onset AF will have hyperthyroidism

Atypical Presentations

  • The presence of symptoms and signs (and their severity) is dependent upon the duration of disease and age of the patient
  • Elderly - may present with atrial fibrillation, tachycardia or CCF
  • Children - may present with excessive growth or behavioural problems
  • Patients may get paradoxical features, eg weight gain when increasing appetite is not countered by increased metabolism
  • Another atypical presentation includes unexplained weight loss in apparently euthyroid patients
    Note: rare presentations include toxic manic confusion, severe proximal limb girdle myopathy or diarrhoea

Definition

  • A condition of excess levels of serum thyroid hormones

Epidemiology

  • Female to male ratio = 9:1
  • Prevalence is 2% in women; 0.2% in men
  • It may be alot higher. In a cross-sectional study in the USA, of 2,799 well-functioning adults aged 70–79, 9.7% of black women, 6% of white women, 3.2% of black men, and 2.2% of white men reported a history of hyperthyroidism (Kanaya, 2002)
  • 60-85% of cases are due to Graves' disease with a peak onset at 20-50 years; the remainder are due largely to nodular thyroid disease that appears later in life

Risk Factors (Associations)

  • Autoimmune thyroid disease may be associated with other autoimmune conditions – particularly Pernicious Anaemia, Addison’s Disease, Vitiligo and Type 1 DM
  • There are strong genetic factors
  • Grave’s Disease may be associated with infections by organisms that exhibit molecular mimicry to the TSH receptor, such E Coli
  • Atrial Fibrillation. Approximately 15% of elderly patients presenting with new-onset AF will have hyperthyroidism 

Causes

Intrinsic Thyroid Disease

Graves Disease

  • This is the most common cause of hyperthyroidism (it accounts for >60%) and has an autoimmune basis (IgG antibody that binds and stimulates TSH receptor). This has a stimulatory effect on the thyroid gland
  • Small-moderate, diffuse, firm goitre
  • 50% have ophthalmopathy
  • There may be a personal or family history of autoimmune disease
  • <5% have pretibial myxoedema (swelling above the lateral malleoli due to accumulation of glycosaminoglycans). This is usually associated with moderate-severe ophthalmopathy
  • Thyroid dermopathy can occur anywhere (particularly following trauma). It usually appears as non-pitting plaques with pink/purple colour. There are nodular and generalised forms
  • 10-20% have thyroid acropathy = clubbing with painful swelling of digits
  • There may also be lymphoid hyperplasia including splenomegaly and an enlarged thymus

Toxic multinodular goitre (15-20%) – this is characterised by multiple, thyroid hormone secreting nodules. Patients are commonly elderly or iodine-deficient

Toxic Adenoma – a solitary T3 / T4 producing nodule of the thyroid gland which is seen as a ‘hot’ nodule on isotope scanning. This usually causes the rest of the gland to be suppressed

De Quervains Thryoiditis – viral infection of the thyroid gland causes self-limiting inflammation leading to stimulation

Postpartum thyroiditis

Exogenous

  • Medications – eg amiodarone
  • Excessive replacement of thyroid hormones during the treatment for hypothyroidism (levothyroxine)
  • Intoxication with excess iodine (from sources such as contrast media) may also lead to over-stimulation of the thyroid

Malignant

  • Metastatic follicular thyroid carcinoma
  • TSH-secreting tumours such as pituitary adenoma
  • Ectopic tissue – choriocarcioma, ovarian teratoma

Thyroid Storm (Rare)

  • Patients are usually known to have pre-existing thyroid disease
  • A systemic insult may lead to a severe stimulation of the thyroid gland producing a potentially fatal surge in thyroid hormones
  • Common precipitants include non-compliance, thyroid surgery, radioiodine, trauma, infection and myocardial infarction
  • 10% mortality

Symptoms

Hyperthyroidism

  • Palpitations
  • Hyper-defecation or diarrhoea, vomiting
  • Tremor
  • Hyperpyrexia
  • Itching
  • Heat intolerance / sweating
  • Irritability ± behaviour change
  • Muscle weakness
  • Urinary frequency
  • Increased appetite and weight loss
  • Psychosis

Thyroid Storm

  • Hyperpyrexia
  • Agitation / confusion
  • Psychosis
  • Coma

Key Questions

  • How long have you had these symptoms for? 
  • Do you have any problems with your thyroid gland?

Signs

Hyperthyroidism

  • Tachycardia (± atrial fibrillation)
  • Hypertension
  • May be signs of heart failure
  • Tremor – fine
  • Warm peripheries
  • Palmar erythema (hot moist hands)
  • Goitre
  • Nodular thyroid / solitary nodule
  • Thyroid bruit on auscultation

MULTINODULAR GOITRE A large multi-nodular goitre

Signs Specific to Grave’s Disease

  • Eye signs: exophthalmos, ophthalmoplegia, conjunctival oedema, papilloedema and keratopathy. May be severe enough to cause visual loss
  • Pretibial myxoedema - swelling above the lateral malleoli due to accumulation of glycosaminoglycans
  • Thyroid acropachy - clubbing with painful swelling of digits
  • Grave’s dermopath

THYROTOXICOSIS Exopthalmos

Thyroid Storm

  • Severe tachycardia ±atrial fibrillation (rarely complete heart block)
  • Goitre
  • Bruit
  • Acute abdomen (may mimic)
    Note: rarely patients may present with an apathetic thyroid storm, then relapse into coma, with few other signs of hyperthyroidism

Investigation

Hyperthyroidism occurs in approximately 2% of women and 0.2% of men

Blood

  • FBC - may show normocytic anaemia with leucopenia
  • U+E, LFTs, Bone, Glucose
    Note: 10% of patients with thyroid storm will have hypercalcaemia; they may also have a low glucose

Thyroid function tests

  • Thyroid stimulating hormone (0.1-6.0 miu/L) – usually suppressed. Raised if TSH releasing tumour or thyroid hormone resistance
    Note: may also be suppressed in the first trimester of pregnancy
  • Thyroxine (T4; 10-25 pmol/L) will be raised
  • Triiodothyronine (T3; 1.0-2.5 nmol/L) will also be raised
  • Thyroid autoantibody screen. Common antibodies measured including anti-thyroid peroxidase (TPO), anti-thyroglobulin antibodies and TSH receptor antibodies. These will be positive in cases of autoimmune thyroid disease

Other

  • Thyroid ultrasound. This enables nodules to be looked at in more detail
  • CXR
  • Electrocardiography may show sinus tachycardia, atrial fibrillation as well as premature atrial beats and non-specific ST segment and T wave changes 

Key Investigations

  • TSH
  • T3 and T4

Specialist Investigations

  • Thyroid isotope uptake scan (using 123-Iodine or 99-Techtenium) to locate hot (overactivity) and cold (no activity) spots; and allows identification of the cause of hyperthyroidism. Nodules can be identified, as well as detecting ectopic thyroid tissue including thyroid metastases
  • Thyroid ultrasound
  • Visual acuity, fields and eye movements should be assessed if thyroid eye signs are present in Graves' Disease
  • CT scan of the orbit, in exophthalmos, may demonstrate thickened external ocular muscle 

Differential Diagnoses

  • Sepsis
  • Gastroenteritis
  • Cardiac arrhythmias
  • Drug intoxication
  • Psychosis, anxiety
    Note: hyperthyroidism is often difficult to differentiate from an anxiety state, particularly it is associated with a goitre (both are common). The palms tend to be moist but cold in anxiety states
  • Phaeochromocytoma
    Note: thyroid storm may be confused with severe sepsis or malignant hyperthermia

Treatment

Long-term antithyroid regimes should be initiated and monitored by a consultant endocrinologist

Treatment (First Line)

Drugs

  • Beta-blockers (eg PO PROPRANOLOL 40mg tds) are used to control symptoms
    • They block the effects of over-stimulation of the sympathetic nervous system
    • They also serve to inhibit peripheral conversion of T4 to T3
  • Anti-thyroid medications such as carbimazole are given usually in the form of long-term regimes. Carbimazole directly inhibits the biosynthesis of thyroid hormones
  • Long-term antithyroid regimes should be initiated and monitored by a consultant endocrinologist. Two strategies are commonly used:
    1. Titration of carbimazole, which is then adjusted based on 4-6 weekly thyroid function tests. Eg, PO CARBIMAZOLE 15 mg tds, for 4-8 weeks until the patient is euthyroid. After that a maintenance dose of 5mg tds is required for 12-18 months
    2. ‘Block and Replace’ – carbimazole and thyroxine used simultaneously

Thyroid Storm

  • This is rare but dangerous. You need senior help
  • Admit to ITU
  • Give OXYGEN
  • Pass NG tube if vomiting
  • Give broad spectrum antibiotics, if infection is present
  • Control fever with PO PARACETAMOL or aggressive peripheral cooling techniques
  • IV N Saline. Sweating is marked, so patients become severely dehydrated
  • To combat severe tachycardia, PO PROPRANOLOL 80 mg tds. Or IV PROPRANOLOL 1mg over 1 minute with intervals of at least 2 minutes. Repeat up to 9 times
  • PO CARBIMAZOLE 60-120 mg a day
  • IV HYDROCORTISONE 100mg qds or IV DEXAMETHASONE 4mg qds

Treatment (Second Line)

Drugs

  • Radio-iodine (given as PO SODIUM 131-IODINE) is sequestered in the thyroid gland and down-regulates thyroid function via local irradiation
    • Absolute contraindications include pregnancy and breast-feeding
    • Leads to permanent hypothyroidism in most patients in 4 – 12 months

Procedures

  • Thyroidectomy - is generally the last option when all other options have been considered
    • Complications include recurrent laryngeal nerve injury (1-2%), external laryngeal nerve injury and hypoparathyroidism (10-15%)

Treatment of Complications

Eye

  • Lid retraction (sclera visible below the upper lid) usually responds to treatment of hyperthyroidism
  • Exophthalmos (sclera visible above the lower lid) results from swelling of the retro-orbital tissues and may not improve and may progress
  • Treatment of malignant exophthalmos is difficult
  • Local intramuscular injection of Botulinum toxin (neurotoxin A) is used
  • Local or systemic steroids may be required, with tarsorrhaphy in severe cases
  • Orbital decompression may be required

Atrial fibrillation

  • This responds poorly to DIGOXIN; larger doses are often needed until the patient is euthyroid
  • Cardioversion may then be used
  • Severe tachycardia may be controlled by PROPRANOLOL or other beta blockers
  • CCF is unusual and responds to antithyroid drugs plus conventional treatment

Prescribing Issues

  • In pregnancy, advice should be sought from a consultant obstetrician
  • PROPYLTHIOURACIL is the usual first line of treatment in pregnancy as carbimazole rarely exerts teratogenic effects
  • An important side effect of carbimazole is agranulocytosis, which usually develops within 90 days
  • Patients on carbimazole therapy should be sufficiently educated about this issue; and advised to seek medical help (sore throat is usually the first symptom) if they develop a fever. Patients may present with neutropenic sepsis
  • Other side effects of carbimazole include loss of hair and skin rashes. Patients should be warned about these as as well
    Note: do not give ASPIRIN. This can exacerbate the problem by displacing thyroxine from thyroid binding globulin

Key Management Decisions

  • Does the patient have thyroid storm?
  • Does the patient need ITU?

Admit?

  • Usually
  • Thyroid Storm - always

Bed Plan

  • AMU then Endocrine Ward
  • ITU, if thyroid storm

Referrals

Medical

  • Endocrine ± ITU

Surgical

  • Ophthalmologist, if eye disease

 

The Rest

When drugs are stopped, relapse occurs in at least 2/3rds in 1-2 years

Maxim

  • "Just because the signs and symptoms of early thyroid disease can be vague, you do not have to be"

Complications

  • Angina
  • Atrial fibrillation
  • Congestive cardiac failure
  • Osteoporosis
  • Of treatment

Follow-up

  • Endocrine
  • Surgery, if has had thyroidectomy

Prognosis

  • When drugs are stopped, relapse occurs in >2/3rds in 1-2 years (then either surgery or radio-iodine is used)
  • Thyroid storm has a 10% mortality

2° Prevention + Health promotion

  • Screening is controversial
  • Because of the high prevalence of thyroid disease, and genetic factors, it may be appropriate to screen certain families (esp females) and at risk groups
  • Some suggest screening may be indicated in women over 50 years (Helfand, 1988)

Patient Information

  • Give patients information about the side effects of CARBIMAZOLE
  • British Thyroid Association (July 2007) has written a leaflet for patients with hyperthyroidism

Don't Forget

  • Prevalence is 2% in women, 0.2% in men
  • 15% of elderly patients presenting with new-onset AF will have hyperthyroidism
  • Patients on carbimazole may present with neutropenic sepsis
  • Thyroid storm may mimic an acute abdomen

Red Flags

  • Thyroid storm

References

international guidelines US/ATA-AACE Hyperthyroidism and Other Causes of Thyrotoxicosis: Management Guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists, 2011

national guidelines UK/ACB. UK Guidelines for the Use of Thyroid Function Tests from The Association for Clinical Biochemistry, July 2006

reviews Cooper DS. Hyperthyroidism. Lancet; 362(9382): 459-68, 2003

Pearce EN. Diagnosis and management of thyrotoxicosis. BMJ; 332(7554): 1369–1373, 2006

Cooper D. Approach to the Patient with Subclinical Hyperthyroidism. The Journal of Clinical Endocrinology & Metabolism; 92(1): 3-9, 2007

Abraham P et al. A systematic review of drug therapy for Graves’ hyperthyroidism. Eur J Endocrinol; 153: 489-498, 2005

Nygaard B. Hyperthyroidism. Am Fam Physician; 76(7): 1014-1016, 2007

Nygaard B. Hyperthyroidism (primary). Clin Evid (online). July 2010

Samuls MH, Franklin JA. Hyperthyroidism in Aging. Endotext, May 2012

Helfand M. Systematic Evidence Reviews, No. 23. Screening for Thyroid Disease [Internet]

articles Cobler JL et al. Thyrotoxicosis in Institutionalized Elderly Patients With Atrial Fibrillation. Arch Intern Med; 144(9): 1758-1760, 1984

Marx H et al. Hyperthyroidism and pregnancy. BMJ; 336(7645): 663–667, 2008

Helfand M, Redfern CC. Screening for Thyroid Disease: An Update. Ann Intern Med; 129(2): 144-158, 1988

Kanaya AM, Harris F, Volpato S, Perez-Stable EJ, Harris T, Bauer DC. Association between thyroid dysfunction and total cholesterol level in an older biracial population: the health, aging and body composition study. Arch Intern Med; 162: 773–779, 2002