Week 19 Pathology

Hypothalamic–pituitary–thyroid axis

  • Decreased levels of T3 and T4 stimulate the release of thyrotropin-releasing hormone (TRH) from the hypothalamus and thyroid- stimulating hormone (TSH) from the anterior pituitary
  • Hypothalamus(TRH) -> pituitary(TSH) -> Thyroid(T3 and T4).
  • Elevated T3 and T4 levels, in turn, feed back to suppress the secretion of both TRH and TSH.
  • 90% of circulating hormone is T4. T4 is less active.
  • In the periphery, the majority of free T4 is deiodinated to T3.
  • T3 binds to thyroid hormone nuclear receptors in target cells with tenfold greater affinity than does T4 and has proportionately greater activity.

 

Hyperthyroidism

Thyrotoxicosis is a hypermetabolic state caused by ele­ vated circulating levels of free T3 and T4

  • High T3, T4, low TSH – primary hyperthyroidism
  • High T3, T4, high TSH – secondary hyperthyroidism – rare tumours.

Primary Hyperthyroidism

  • Graves disease
    • Antibody stimulates TSH receptor –> increased T3T4 production, growth of thyroid epithelium(goitre)
    • Anti thyroid peroxidase and anti-thyroglobulin.
    • Initially hyper–> later hypo
    • Diffuse uptake on NM scan
    • T cell mediated infiltrative ophthalmopathy.
  • MNG
    • Usually qiuet but can have hot nodules
  • Toxic adenoma or carcinoma.
  • Subacute granulomatous thyroiditis(de quervain)
    • Painful, post viral syndrome
    • Thyroid follicular cell destruction  by CD8 cells so no uptake on NM scan
    • Transient hyperthyroidism for 2-8wks followed by hypothyroidism also transient for 2-8wks.
    • Recovery is virtually always complete.
  • Subacute lymphocytic thyroiditis
    • Painfree.
    • Usually post partum. Thought to be autoimmune with Anti TG and TPO antibodies. Develops over 1-2wks and subsides over 2-8wks.
  • Facticious and iodine OD
    • White out on NM scan
  • Carcinoma- papillary, follicular, medullary
    • Adenoma- treat with radio iodine. Carcinoma- resect.

 

 

Hypothyroidism

  • Hypothyroidism is a condition caused by a structural or functional derangement that interferes with the production of thyroid hormone.
  • Hypothyroidism is a fairly common disorder. Overt hypothyroidism is 0.3%, while subclinical hypothyroidism can be found in greater than 4%.
  • The prevalence increases with age, and it is nearly tenfold more common in women than in men.

Congenital hypothyroidism

  • Endemic iodine deficiency

 Autoimmune hypothyroidism

  • Hashimoto’s Thyroiditis
    • Thyroid epithelial cell destruction – CD8 mediated and cytokine mediated, antibody mediated.
    • Lymphocytic and plasma cell infiltrate. Usually euthyroid or hypothyroid. Diffusely lights up on nuclear scan. Commonly women 60-70yo. Anti body titres are high- anit thyroglobulin, anti-TPO, anti TSH receptor. Painless Goitre. High TSH
  • Primary atrophic hypothyroidism(women, common, diffuse lymphocytic infiltrate, no goitre).
  • Both are autoimmune and associated with- Addison’s, DM1, pernicious anaemia.

Iatrogenic hypothyroidism

  • This can be caused by either surgical or radiation-induced ablation

 

Cushing’s syndrome.

  • Due to excess cortisol – exogenous(commonest) or endogenous(70-80% ACTH high, 10-20% adrenal neoplasms 10% secretion of ectopic ACTH from other tumours)
    • Insomnia, weakness
    • Skin fagility, hirsuitism, striae
    • Central adiposity, promimal myopathy, buffalo hump, moon facies,
    • Osteoporosis
    • Hyperglycaemia
    • Dyslipidaemia
    • HTN
    • Ammenorhoea

 

Addison’s disease

  • Adrenocortical insufficiency – low cortisol and aldosterone and sex hormones
  • Causes – autoimmune 60-70%, TB, AIDS, metastases(breast, lung GI), lymphomas, amyloidosis, sarcoid, haemachromatosis
    • Weakness and lethargy
    • LOA, nausea, vomiting, LOW, diarrhoea
    • Hyperpigmentation(ACTH)
    • Aldosterone lack – hyperkalaemia, hyponatraemia, hypotension(volume depletion)
    • Hypoglycaemia
    • Testicular atrophy, amenorrhoea

Adisonian crisis (when unwell, post surgery etc) – intractable vomiting, abdo pain, hypotension, coma, vascular collapse. Possible death.

 

Phaeochromocytoma

  • Adrenal medullar chromaffin cells – neoplasm
    • Synthesis and release catecholamines.
    • Abrupt precipitous HTN with associated tachycardia, palpitations, headache, sweating, tremor, sense of aprehension. May have abdo or chest pain. May –> CCF, MI, VF, CVA.
    • Precipitated by emotional stress, exercise, change in posture, palpation of the tumour.
    • 10% arise in association with familial syndromes, 10% are extra-adrenal, 10% of non familial are bilateral, 10% are malignant, 10% come in childhood.
    • Increased urinary excretion of free catecholamines, metanephrines, vanillamandelic acid.

 

Hyperaldosteronism.

  • Sodium retention
  • Potassium excretion
  • HTN and hypokalaemia
    • Causes – adrenocortical neoplasm (Conn’s syn), primary adrenocortical hyperplasia, glucocorticoid remediable hyperaldosteronism.
  • Secondary hyperaldosteronism – from high renin
    • Causes – reduced renal perfusion, arterial hypovolaemia, pregnancy.