Hypothyroidism

Question 1

What is hypothyroidism?

Answer 1

Clinical syndrome resulting from insufficient secretion of thyroid hormones

Question 2

What is subclinical hypothyroidism

Answer 2

• state of usually asymptomatic,
• mild thyroid failure,
• with normal levels of T4 and T3,
• and minimal elevation of TSH

Question 3

What is the aetiology of primary hypothyroidism?

Answer 3

Reduced thyroid hormone production:

Acquired:

• Autoimmune (Hashimoto’s) thyroiditis (cellular and antibody-mediated
  
  • most common cause of primary hypothyroidism
• Iatrogenic (post-surgery, radioiodine, medication for hyperthyroidism)
• Severe iodine deficiency or iodine excess (Wolff-Chaikoff effect)
• Thyroiditis
  
  • e.g. Sub-acute granulomatous (De Quervain’s) thyroiditis causes transient primary hypothyroidism
  • e.g. post-partum women develop lymphocytic thyroiditis, which causes transient primary hypothyroidism​
• Infiltrative diseases: sarcoidosis, haematochromatosis
  
  • uncommon causes

Congenital:

• Thyroid dysgenesis
• majority of hypothyroidism cases (95%) are due to primary hypothyroidism, a failure of the thyroid gland to produce thyroid hormones*

Question 4

What is the aetiology of secondary/central hypothyroidism?

Answer 4

Pituitary or hypothalamic disease (e.g. tumours) resulting in reduced TSH or TRH and reduced stimulation of thyroid hormone production

reflect dysfunction of the:

• pituitary
  
  • Pituitary mass lesions, especially pituitary adenomas, are the most common cause
  • mass lesions: primary tumours, such as growth hormone (GH)- or ACTH-secreting adenomas, craniopharyngiomas, cysts, meningiomas, dysgerminomas, tumour mets
  • infiltrative disorders: infectious (tuberculosis, syphilis, fungal infections, toxoplasmosis) and non-infectious aetiologies (sarcoidosis, haemochromatosis, histiocytosis)
  • catastrophic: head trauma, pituitary apoplexy, and Sheehan’s syndrome (postpartum pituitary necrosis).
• hypothalamus
  
  • mass lesions: cysts, meningiomas, dysgerminomas, tumour mets
  • infiltrative disorders: infectious (tuberculosis, syphilis, fungal infections, toxoplasmosis) and non-infectious aetiologies (sarcoidosis, haemochromatosis, histiocytosis)
  • catastrophic: head trauma
• hypothalamic-pituitary portal circulation

Question 5

What are the risk factors for:

a) primary hypothyroidism
b) secondary/central hypothyroidism

Answer 5

a) primary hypothyroidism

• female sex
• middle age
• FHx
• autoimmune disorders
  
  • e.g. Addison’s disease, T1DM, pernicious anaemia and pre-mature ovarian failure
• Graves’ disease
• post-partum thyroiditis
• Turner’s and Down’s syndromes
• primary pulmonary hypertension
• multiple sclerosis
• radiological procedure
• Hx of surgery or radioiodine therapy for hyperthyroidism
• diet: iodine deficiency
• drugs: amiodarone, lithium

weak:

• type 1 diabetes
• infiltrative disease
• iodine excess
• textile workers

b) secondary/central hypothyroidism

• multiple endocrine neoplasia (MEN) type I
• head and neck irradiation
• traumatic brain injury.

weak

• age - between 5-14 years and older than 65 (craniopharyngiomas)
• age - second to fifth decades (prolactinomas)
• age - fourth to eighth decades (non-functioning pituitary adenomas)
• sarcoidosis
• histiocytosis
• haemochromatosis
• pregnancy
• family history of central hypothyroidism

Question 6

What is the epidemiology of hypothyroidism?

Answer 6

• Females to males: 6:1
• Age of onset commonly over 40 years, but can occur at any age
• Iodine deficiency is seen in mountainous areas e.g. Alps, Himalayas
• majority of cases (95%) are due to primary hypothyroidism, a failure of the thyroid gland to produce thyroid hormones

Question 7

What are the presenting symptoms of hypothyroidism?

Answer 7

• Onset is usually insidious
• • Cold intolerance
• lethargy,
• weight gain,
• constipation,
• dry skin hair loss,
• hoarse voice,
• - Mental slowness,
• depression,
• dementia,
• cramps,
• ataxia,
• paraesthesia
• - Menstrual disturbances (irregular cycles, menorrhagia) in females
• Myxoedema coma (severe hypothyroidism usually seen in the elderly): Hypothermia, hypoventilation, hyponoatreamia, heart failure, confusion and coma

Question 8

What are the signs of hypothyroidism on examination?

Answer 8

• • Hands: Bradycardia, cold hands
• • Head/neck/skin: Pale puffy face, goitre, oedema, hair loss, dry skin, vitiligo
• • Abdomen: Ascites
• • Neurological: Slow relaxation of reflexes, signs of carpal tunnel syndrome

Question 9

What are the investigations for hypothyroidism?

Answer 9

Bloods

• TFT
  
  • = Primary: Reduced T4/T3 and raised TSH (due to reduced negative feedback)
  • = Secondary: Reduced T3/T3 and reduced and inappropriately normal TSH (Subclinical hypothyroidism is characterised by normal serum free T3/T4 and raised TSH)
• FBC
  
  • ​= Normocytic anaemia
• U&E’s
  
  • = May show reduced Na+
• Cholesterol
  
  • = May be raised
• In suspected secondary cases: Pituitary function tests, pituitary MRI and visual field testing

Question 10

How is hypothyroidism managed?

Answer 10

- Chronic:

• Levothyroxine
  
  • Rule out underlying adrenal insufficiency and treat before starting thyroid hormone replacement to avoid Addisonian crisis.
  • Adjust dosage depending on TFT and clinical picture.
  • In patients with ischaemic heart disease, start at low dose and gradually increase at 6 week intervals if ischaemic symptoms do not deteriorate

- Myxoedema coma:

• Oxygen
• rewarming
• rehydration
• IV T4/T3
• IV hydrocortisone (in case hypothyroidism is secondary to hypopituitarism)
• treat the underlying disorder e.g. infection

Question 11

What are the possible complications of hypothyroidism?

Answer 11

• Myxoedema coma,
  
  • multi-organ failure
  • Myxoedema coma is a rare life-threatening state in which severe hypothyroidism markedly worsens.
  • n general, it occurs in older people and is usually precipitated by an underlying medical illness.
  • Patients with myxoedema coma should be treated in the intensive care unit under the supervision of an endocrinologist.
• myxoedema madness
  
  • (psychosis with delusions and hallucinations or dementia) in severe hypothyroidism (may be seen in the elderly after starting levothyroxine treatmen
• adrenal crisis
  • Adrenal crisis may occur if levothyroxine therapy is initiated in the setting of adrenal insufficiency.
  • Patients with adrenal crisis present with nausea, vomiting, dizziness due to hypotension, and possible loss of consciousness.
  • Adrenal insufficiency should be treated with glucocorticoids prior to the start of thyroid hormone replacement therapy.
• treatment-related bone loss
  
  • Chronic over-replacement of thyroid hormone may induce osteoporosis, particularly in post-menopausal women
• treatment-related thyrotoxicosis
  
  • ​Thyrotoxicosis can occur from overdose of levothyroxine.
  • An appropriate management strategy includes discontinuation for 3 days, followed by resumption of replacement therapy at a lower dose.
• Treatment-related AF, angina
  
  • May occur with high initial dose of levothyroxine in patients with coronary artery disease.

Question 12

What is the prognosis of hypothyroidism?

Answer 12

Lifelong levothyroxine replacement therapy required.

Myxoedema coma has a mortality of up to 80%

primary

• Prognosis is generally excellent with full recovery upon adequate replacement of thyroid hormones
• The levothyroxine replacement dose may change over a period of years as the disease progresses or other conditions affecting thyroid hormone metabolism develop, but achieving excellent control of the disease is generally easily accomplished

secondary

• Prognosis is dependent on the underlying aetiology of central hypothyroidism.
• The prognosis for pituitary adenomas is dependent on the size (micro- versus macro-adenoma) and functionality (prolactinoma, growth hormone-secreting, adrenocorticotropic hormone-secreting, or non-functional). Long-term remission rates for prolactinomas are good: 54% to 86% after surgery