My Clinical Notes

• Thyrotoxicosis is a hypermetabolic state caused by elevated circulating levels of T3 and T4

 

Disorders associated with thyrotoxicosis

• Associated with hyperthyroidism
  • Primary
    • • Diffuse toxic hyperplasia (Graves disease)
      • Hyperfunctioning multinodular goiter
      • Hyperfunctioning adenoma
      • Iodine-induced hyperthyroidism
      • Neonatal thyrotoxicosis associated with maternal Graves disease
  • Secondary
    • • TSH-secreting pituitary adenoma (rare) **
• Not associated with hyperthyroidism
  • Subacute granulomatous thyroiditis (painful)
  • Subacute lymphocytic thyroiditis (painless)
  • Struma ovarii (ovarian teratoma with ectopic thyroid)
  • Exogenous thyroxine intake

** associated with increased TSH, the rest are associated with decreased TSH. Tested by the TRH stimulation test. If TSH increases following injection of TRH, this excludes secondary hyperthyroidism

 

Clinical course

• Clinical manifestations due to excess thyroid hormone and over activity of the sympathetic nervous system
• Skin becomes warm and flushed due to peripheral vasodilation
• Heat intolerance
• Weight loss despite increased appetite
• Increased cardiac output die to increased cardiac contractility and increased peripheral oxygen requirements
• AF can occur – more commonly in the elderly
• Congestive heart failure may develop
• Some patients may develop a reversible diastolic dysfunction and a low output failure called thyrotoxic dilated cardiomyopathy
• In the neuromuscular system there is tremor, hyperactivity, emotional lability, anxiety, inability to concentrate and insomnia. There may be proximal muscle weakness and decreased muscle mass (thyroid myopathy)
• Ocular changes can occur such as lid lag due to over stimulation of levator palpebrae superioris however true thyroid ophthalmopathy associated with proptosis is only a feature of Graves disease
• In the GI system there may be hypermobility, malabsorption and diarrhoea
• In the bone, thyroid hormone stimulates bone reabsorption and causes osteoporosis
• Patients with Graves disease can develop lymphadenopathy

 

• Thyroid storm describes the abrupt onset of hyperthyroidism
  • Most commonly occurs in patients with underlying Graves disease and results from an increase in catecholamine levels such as seen after surgery or infection
  • Patients present febrile and with a tachycardia
  • Considered a medical emergency

 

• Apathetic hyperthyroidism is seen in the elderly when old age and comorbidities may blunt the typical features of thyroid hormone excess

 

Investigations

• Generally TSH is low and T4 is high
• Only in secondary hyperthyroidism is the TSH also high (see above)
• Occasionally the T3 is high and T4 levels may be reduced
• Radioactive iodine uptake can be used to determine the cause of the thyrotoxicosis, e.g. thre may be diffuse uptake in the whole gland (Graves disease), increased uptake in solitary nodules (toxic adenoma) or decreased uptake (thyroiditis)

 

Treatments

• b-blockers
• Thionamide to block new hormone synthesis
• Iodine solution to block the release of hormone
• Radioiodine ablates thyroid function over a period of 6 to 18 weeks

 

Hypothyroidism

 

• Can result from a defect anywhere in the hypothalamic-pituitary-thyroid axis

 

Causes of hypothyroidism

• Primary
  • Developmental (thyroid dysgenesis, PAX-8 (Transcription factor), TTF-2 (transcription factor, also associated with a cleft palate), TSH-receptor mutations)
  • Thyroid hormone resistance syndrome (TRb mutation)
  • Postablative (surgery, radioiodine therapy, external radiation)
  • Autoimmune hypothyroidism (Hashimoto thyroiditis) **
  • Iodine deficiency **
  • Drugs (propylthiouracil, lithium, iodides, p-aminosalicyclic acid) **
  • Congenital biosynthetic defect (dyshormonogenetic goiter) **
• Secondary
  • Pituitary failure (TSH deficiency)
• Tertiary
  • Hypothalamic failure (TRH deficiency - rare)

** associated with enlargement of the thyroid “goitrous hypothyroidism”

 

• Autoimmune hypothyroidism is the most common cause of goitrous hypothyroidism in iodine-sufficient areas of the world. The vast majority are due to Hashimoto thyroiditis associated with anti-TSH receptor autoantibodies

 

• Dyshormonogenetic goiter can be caused be deficiencies in;
  • Iodide transport
  • Organification (organification of iodine involves binding of oxidised iodide with tyrosyl residues in thyroglobulin). This is deficient in patients with Pendred syndrome wherein goitrous hypothyroidism is associated with sensorineural deafness)
  • Dehalogenase
  • Iodotyrosine coupling

 

• In patients with mutations in the thyroid hormone receptor, the levels of T3 and T4 are high but because the pituitary is also is also resistant to the feedback from thyroid hormones, the levels of TSH are also high

 

• Secondary hypothyroidism can result from;
  • Pituitary tumour
  • Postpartum pituitary necrosis
  • Trauma
  • Non pituitary tumours

 

• Tertiary hypothyroidism can be due to;
  • Hypothalamic damage from tumours
  • Trauma
  • Radiation therapy
  • Infiltrative diseases

 

Clinical presentation of hypothyroidism

• Cretinism
  • Refers to hypothyroidism that develops in infancy or early childhood
  • Used to be due to iodine deficiency, it is now more commonly due to inborn errors of metabolism that interferes with the biosynthesis of normal levels of thyroid hormone
  • Clinical features include;
  • Severe mental retardation
  • Short stature
  • Coarse facial features
  • A protruding tongue
  • Umbilical hernia
• Myxedema
  • Refers to hypothyroidism developing in the older child or adult
  • Clinical features include;
  • Slowing of mental and physical activity
  • Cold intolerance
  • Weight gain
  • Reduced cardiac output resulting in breathlessness and exercise intolerance
  • Constipation
  • Decreased sweating
  • Histologically there is accumulation of matrix substances such as glucosaminoglycans and hyaluronic acid, in the skin, subcutaneous sites and a number of visceral sites. This results in oedema, coarsening of facial features, enlargement of the tongue and deepening of the voice

 

 

 

This entry was posted on Sunday, December 30th, 2007 at 2:05 pm and is filed under Endocrine. You can follow any responses to this entry through the RSS 2.0 feed. You can leave a response, or trackback from your own site.