Week 2 - Endocrine Disorders Flashcards
Describe the structure and microscopy of the pituitary gland.
• Normal pituitary gland - extension of hypothalamus.
• Anterior glandular portion and posterior neural portion.
• Anterior pituitary - develops from Rathke’s pouch - epithelium of the nasal cavity joins with the neural crest (diencephalon) - together they form pituitary gland.
Microscopy:
• Anterior pituitary - all endocrine glands. 3 types of cells - basophilic blue cells, acidophilic red cells and clear cells (chromophobes).
• Posterior pituitary - astrocytes and axons.
Describe the hypothalamo-pituitary axis.
- Hypothalamus controls pituitary. Hormones controlled by interconnected feedback mechanisms but there is a strong neural control - GHRH, CRH, TRH, GnRH, ADH, oxytocin.
- Hypothalamic nuclei controlled by a range of factors e.g. hunger, thirst, emotions etc. → control endocrine system.
- Anterior pituitary - through nerves and hypophyseal portal circulation → release anterior pituitary hormones - GH, ACTH, TSH, FSH, LH, PRL.
- Posterior pituitary - direct release of hormones into the capillaries (axons carry the NTs and hormones which are directly released into capillaries) - ADH, oxytocin.
Outline pituitary function and disorders.
CELL/ADENOMA - HORMONE - ASSOCIATED SYNDROME:
• Lactotroph - Prolactin (Prolactinoma):
- Galactorrhoea and amenorrhoea (females), sexual dysfunction, infertility.
• Somatotroph - GH:
- Gigantism (children), acromegaly (adults).
• Mammosomatotroph - GH + PRL:
- Combined features.
• Corticotroph - ACTH:
- Cushing’s disease.
- Nelson syndrome (post adrenolectomy - adenoma).
• Thyrotroph - TSH:
- Secondary hyperthyroidism.
• Gonadotroph - FSH, LH:
- Hypogonadism and hypopituitarism.
What is the commonest cause of hyperpituitarism?
Adenoma - Prolactinoma (most common adenoma).
Gonadotroph adenoma least common.
What is the commonest cause of hypopituitarism?
Injury/infarction - trauma, tumour.
Outline pituitary adenoma.
- Most common cause of hyperpituitarism in the anterior lobe.
- Classified based on the hormone(s) produced by the neoplastic cells - prolactin > GH > both > ACTH (Cushing’s) > TSH > FSH/LH. (Prolactin commonest producing hormone, least is gonadotropin).
- 95% sporadic, 5% familial.
- Due to G-Protein mutations - accumulation of genetic damage → formation of a tumour in the pituitary.
- Can be functional (symptoms associated hormone excess) or non-functional (no clinical symptoms).
Describe the morphology of pituitary adenoma.
Gross: • Microadenoma < 10mm (90%). - More common in females 10:1. - Functional - produce hormones. - Very small tumours, may get calcified. • Macroadenoma > 10mm (10%). - More common in males. - Non-functional (therefore, diagnosed at later stage - tumour has grown large). - Large non-functioning tumours may cause hypopituritarism as destroy adjacent tissue. Microscopy: • Uniform one type of cell. • Normal pituitary - lots of cells. Adenoma - only one type of cell.
What are the clinical features of pituitary adenoma?
- Signs and symptoms are related to both endocrine abnormalities (excess hormone secretion) and mass effects.
- Females - amenorrhoea, galactorrhoea, infertility (hormone features).
- Males - headache, visual loss (mass effects), hypogonadism and infertility.
- Excess hormone secretion e.g. hyperthyroidism, Cushing’s syndrome, gigantism/acromegaly, galactorrhoea.
- Mass effects e.g. headache, lethargy, nasal drainage, nausea/vomiting, change in sense of smell and vision.
Outline somatotroph adenoma.
- Second common.
- GH +/- prolactin. (GH hormone producing adenoma. Rarely can also produce both prolactin and GH).
- Produces gigantism/acromegaly.
- Persistently elevated levels of GH stimulates hepatic secretion of insulin like growth factor 1 (somatostatin C) → produces clinical features of excess growth e.g. large hands and feet, prominent lower jaw, enlarged head circumference, organomegaly, accelerated osteoporosis, hyperglycaemia.
- May also have diabetes mellitus, CCF, arthritis.
Outline the aetiology/pathogenesis of Sheehan’s syndrome.
Post partum anterior pituitary necrosis (hypopituitarism):
• Ischaemic necrosis of the anterior pituitary during childbirth → hypopituitarism.
1. During pregnancy, the anterior pituitary enlarges to almost twice its normal size.
2. The gland expansion is not accompanied by increase in venous blood supply (relative anoxia).
3. Further reduction in blood supply (due obstetric haemorrhage -bleeding/ shock) may precipitate infarction of the anterior lobe (not posterior as this receives blood from arterial branches).
4. Ischaemic area is reabsorbed & replaced by fibrosis tissue.
No arteries in the anterior pituitary (hypophyseal portal system only). Physiologic hypertrophy + shock/bleeding → necrosis → hypopituitarism.
Identify the clinical features and management of Sheehan’s syndrome.
• Symptoms (due to sudden loss of anterior pituitary hormones):
- Inability to breast-feed (due to lack of PRL).
- Severe fatigue, depression.
- Lack of menstrual bleeding (due to lack of FSH/LH).
- Loss of pubic and axillary hair (due to lack of FSH/LH).
- Low blood pressure (hypotension).
• Management - hormone replacement therapy - replace estrogen, progesterone, thyroid and adrenal.
Outline hypopituitarism.
- 75% of anterior pituitary loss and/or with posterior pituitary loss → decreased pituitary function (hypopituitarism).
- Combined anterior and posterior (diabetes insipidus) → hypothalamic (suspect hypothalamic disorder).
- Congenital or acquired (tumours, injury, necrosis). “Empty sella syndrome”.
- Craniopharyngioma (tumour of epithelium from Rathke’s pouch) or Glioma.
Identify the clinical features of hypopituitarism.
• Clinical features based on the hormone involved.
- GH: pituitary dwarfism (proportional dwarf) - hands and limbs equally affected, symmetric.
- FSH/LH: infertility, impotence.
- TSH: hypothyroidism.
- MSH: pallor (melanocytes) - MSH usually produced with ACTH - severe pallor (loss of melanocytes function).
- ACTH: hypo-adrenalism.
- Posterior pituitary loss: diabetes insipidus.
• Diabetes insipidus with any of the above - suspect hypothalamic disorder (combined).
What are the most common dwarfs?
- Achondroplasia.
- Turner syndrome.
- Pituitary dwarf - proportional.
What are the 2 types of posterior pituitary disorders?
- Syndrome of inappropriate ADH secretion (SIADH) - decreased urine.
- Diabetes insipidus - diuresis/polyuria - tasteless increased urine. Excessive thirst (polydipsia).
- Both conditions can occur with CNS injury, trauma, tumours.
Describe SIADH.
- Increased ADH.
- Water intoxication (water retention - body stores water).
- Low serum sodium.
- High urine osmolality (urine becomes too concentrated).
- Causes: drugs, ARDS, sepsis, tumours, trauma, CNS inflammation, stroke.
Describe diabetes insipidus.
• Decreased ADH.
• Dehydration (diuresis/polyuria - body loses water).
• High serum sodium.
• Low urine osmolality (low sodium).
• Causes (low ADH or decreased response to ADH):
- Central - CNS trauma, inflammation, stroke, tumour.
- Renal - tubular resistance to ADH. CRF, lithium, hereditary.
Outline the composition and function of the thyroid gland.
• Iodinated tyrosines (amino acids), stored in colloid - thyroglobulin.
• Breakdown of protein to release T3 and T4 is through endocrine control (TRH > TSH > T4, T3).
• Metabolism: increased BMR, increased oxygen, increased fat and carb mobilisation and utilisation.
• Growth and development:
- CVS - increased rate, increased blood flow.
- CNS - increased mental activity.
- GIT - increased motility.
• Iodine excess inhibits thyroglobulin proteolysis and release of T4 and T3 - therapy for thyrotoxicosis.
• C cells - calcitonin producing cells. Cluster of cells in between the follicles. Bone forming (opposite effect of PTH).
Describe the hypothalamic-pituitary-thyroid axis.
- Hypothalamus produces TRH → pituitary produces TSH → TSH binds to G protein receptors → Release of T3/T4 hormones → T3/T4 bind to nuclear receptors in the target cell (every cell in the body requires thyroid hormone).
- Thyroid hormone stimulates cellular gene expression and metabolism. Metabolism is a major activity of thyroid gland.
- T3 is the final metabolically active product. T4 gets converted peripherally (not in gland).
Outline the aetiology of hyperthyroidism.
• Hyperthyroidism (thyrotoxicosis) describes the clinical features arising from elevated levels of thyroid hormone (free T4 & T3).
Aetiology:
• Primary Hyperthyroidism → hyperfunciton of the thyroid gland (most common cause) due to:
- Graves Disease (causing diffuse hyperplasia of the thyroid - 85% of cases).
- Toxic Multinodular Goitre.
- Functioning adenoma of the thyroid.
• Secondary Hyperthyroidism → extrathyroidal cause (e.g. at level of pituitary/hypothalamus).
• Commonest cause of hyperthyroidism:
- Primary, autoimmune - Graves.
- Iodine deficiency, toxic change in a tumour (MNG).
Describe the pathogenesis of hyperthyroidism.
- Hyperfunction of the thyroid leads to increased levels of thyroid hormone (T4 & T3).
- Increased thyroid hormone causes increased cellular metabolism.
- This results in the clinical features observed.
What are the clinical features of hyperthyroidism?
Hypermetabolism which leads to:
• Weight loss despite increased appetite.
• Skin: soft, warm flushed, heat intolerance.
• CVS: increased HR/CO, palpitations, AF.
• Neuromuscular: tremor, hyperactivity, anxiety, inability to concentrate, insomnia, increased reflexes.
• GIT: diarrhoea, increased motility.
• Ocular: wide, staring gaze, lid lag/retraction, exophthalmos/proptosis - only in Graves.
• Reproductive: menorrhagia
• Musculoskeletal: osteoporosis, proximal myopathy.
• Other: acropachy (congenital clubbing), onycholysis, pretibial myxoedema, hair loss, goitre.
What is thyroid storm?
Acute condition - sudden severe hyperthyroidism in a patient with Grave’s or other hyperthyroidism - produces severe fever, tachycardia, AF, arrhythmia.
Outline the aetiology of hypothyroidism.
• Hypothyroidism describes the clinical features arising from low levels of thyroid hormone (free T4 & T3). Is common (with prevalence increasing with age & women).
Aetiology:
• Can be primary (thyroid), secondary (pituitary) or tertiary (hypothalamus).
• Caused by any structural/functional derangement interfering with production of thyroid hormone.
• Commonest cause of hypothyroidism:
1. Primary, autoimmune thyroiditis - Hashimotos.
2. Iodine deficiency.
Describe the pathogenesis of hypothyroidism.
- Hypofunction of the thyroid leads to decreased levels of thyroid hormone (T4 & T3).
- Decreased thyroid hormone causes decreased cellular metabolism.
- This results in the clinical features observed.
What are the clinical features of hypothyroidism?
- Dry, coarse, thin hair.
- Loss of outer third of eyebrows.
- Weight gain.
- Diminished sweating.
- Dry, cold skin - prone to hypothermia (cold intolerance).
- Constipation.
- Apathy, fatigue, mental sluggishness.
- Menstrual irregularities.
- Hoarse voice.
- Pretibial myxoedema.
- Periorbital oedema.
- Ischaemic heart disease, bradycardia.
- Muscle weakness.
- Decreased reflexes.
- Goitre.
- Yellow skin (carotene not jaundice).
- Carpal tunnel syndrome.
What is cretinism?
• Hypothyroidism in infancy/congenital leading to:
- Mental retardation
- Protruding tongue
- Short stature (dwarfism)
- Umbilical hernia
- Jaundice, dry skin, slow reflexes, hoarse voice.
• Endemic - iodine deficiency.
• Sporadic - enzyme deficiency/congenital.
• Used to be common in endemic areas due to iodine deficiency but now usually due to congenital atrophy/agenesis or enzyme deficiency.
- Cretinism - hypothyroidism which develops in infancy or early childhood.
- Myxedema - hypothyroidism developing in the older child or adult.
Outline Hashimotos thyroiditis.
- Commonest cause of non endemic goiter (endemic - iodine deficiency).
- Autoimmune destructive thyroiditis → hypothyroidism.
- Common in later age group (45-65yo), females more common (10-20:1) but can occur in any age, sex and children.
- Patients can also have other autoimmune disease - T1DM, RA.
- B cell lymphoma and papillary carcinoma can occur.
What is the aetiology of Hashimotos thyroiditis/Graves disease?
- Genetic - HLA DR3/5, CTLA4, PTPN22.
- Environmental - viral.
- Autoimmunity - TSI, ATG Ab, ATP, AMAb.
Describe the pathogenesis of Hashimotos thyroiditis.
- Production of antithyroid antibodies (antithyroglobulin Ab & antithyroid peroxidise Ab).
- Autoimmune destruction of the thyroid gland due to antibodies, CD8 cells and cytokines → gradual thyroid failure.
- Decreased thyroid hormone results in hypothyroidisim.
