• Hormones can be: modified amino acids (adrenaline), peptides (somatostatin), proteins (insulin), cholesterol derivatives (steroids).

  • Most hormones are stored in intracellular membrane-bound secretory granules, and are released by calcium-dependent mechanisms. Lipid-soluble hormones cannot be stored (unless they are thyroid hormones which are stored in the glycoprotein matrix) they come from SER and mitochondria rich cells.

  • Most protein and peptide hormones activate cell surface receptors coupled to G-proteins or have intrinsic tyrosine kinase activity. Receptors for lipid soluble hormones are usually within the cell and directly modify gene transcription.

  • Hormones are inactivated by metabolic transformation in the liver or at the site of action, usually the smaller the hormone, the faster it is inactivated.

  • Hormones: homeostasis, reproduction, growth and development, metabolism

  • Steroid proteins work with HSP (heat shock proteins) these are receptors which have hsp attached to their active site, preventing them from binding to DNA sequences. The function of steroid proteins is to bind to hsp and make them detach from the receptor, allowing it to bind to and cause changes in the transcription of DNA genes.

  • Only non-bound hormones are biologically active, so when considering the effect of a hormone, you don’t just want to know how much of it is produced, but also how bound it is.


  • Located on the anterior of the trachea just below the larynx.

  • Releases two hormones: thyroxine T4 and triiodothyronine T3 = their main effect is thermogenesis, inducing an increase in the metabolic rate. Also crucial in growth and development.

  • Thyroglobulin is a glycoprotein, the main constituent of colloid, to which T4 and T3 are attached to not escape. PENDRIN moves colloid back into the cell for release preparation.

  • An iodine and sodium symporter transports Iodide into the cell using the sodium gradient.

  • The amino acid tyrosine is iodinated to form either mono MIT or diiodotyrosine DIT, which are then coupled to form either thyroxine (DIT+DIT) or triiodothyronine (DIT+MIT).

  • Thyroid stimulating hormone TSH is released from the anterior pituitary, TSH is regulated by TRH from the hypothalamus in response to the thermoceptor, T3 and T4 levels.

  • T3 levels are around 1/6 of T4 levels, and most of them both are usually bound to TBP (thyroxine binding protein) anyways, so are usually unavailable to their receptors, which are inside their target cells. T3 is about 10 times as potent as T4 so it is rarely given to patients. T4 is more tightly bound to proteins. T3 has a much shorter half life than T4

  • Thyroid receptors are present in almost all tissues and are especially high in the liver and low in spleen and testes.

  • Primary role of the hormones is an increase in synthesis if Na+ K+ ATPase - you need ATP for this - so metabolic rate rises - oxygen consumption rises - erythropoiesis rises.


  • There is no expected value for T3 and T4 in people, great variation

  • SS: weight loss, warm skin/heat intolerance, diarrhoea, exophthalmos, lid lag, palpitations, anxiety, tremor, goitre (bruit), brisk reflexes (whole body in overdrive)

  • Ca: Grave’s disease, Toxic multi nodular goitre and toxic solitary nodule goitre, De Quervain’s thyroidits, cancer (very rare), amidarone induced

  • I: TFTs (thyroid function tests) low TSH, high T3 and T4, ultrasound scan of nodules, fine needle aspiration of solitary nodules to rule out malignancy, isotope scan to assess hot and cold thyroid

  • I: thyroid uptake scan: check how iodine goes in the gland: if it is overactive, it goes in very fast. If too much goes in, it is probably Grave’s disease

  • T: Conservative: patient education, smoking cessation. Medical: symptomatic control (palpitations and tremor: beta-blockers, eyes: drops for lubrication), antithyroid medication (carbimazole: the one most commonly used, but takes long to act, propylthiouracil: it prevents peripheral conversion of T4 to T3 too so it is very fast acting, rarely used. agranulocytosis (lowered white blood cell count) is a common side effect, needs monitoring, more susceptible to infection), Radioactive iodine ablation (definitive treatment, patients must be euthyroid before treatment) Surgical: subtotal thyroidectomy (patients must be euthyroid (their levels of thyroid hormones checked?) before surgery. Potassium iodide before surgery decreases thyroid gland vascularity so it is done)

  • Co: Atrial fibrillation, high output heart failure, cardiomyopathy, osteoporosis

  • Grave’s disease: most common cause, autoimmune, ocular changes distinguish it from others, associated with other autoimmune conditions (pernicious anaemia)

  • Toxic multi nodular goitre and toxic solitary nodule goitre: second most common cause, increased risk with age, more common in females, single nodule is suggestive of thyroid neoplasia.

  • De Quervain’s thyroiditis: transient hyperthyroidism after viral infection, goitre is often painful, period of hypothyroidism may follow

  • HCG induced hyperthyroidism: HCG and TSH share the same structure, so too much HCG can cause overproduction of Thyroid hormones, this is what you see in early pregnancy

  • Amiodarone induced - some medication containing iodine increases thyroid hormone production

  • Extra: because there is a lot of storage of thyroid hormones, it does take a long time in general before the effect of medication for hyperthyroidism to kick in

  • Young women: are usually resistant to anti-thyroid medication (surgery first), large goitre probably won’t respond well/sufficiently to medication (surgery), cosmetic reasons (surgery)

  • TEMPORARY TREATMENT for hyperthyroidism: you give treatment for 12-18 months, you slowly reduce it, then you stop. If treatment hasn’t started working in 3-6 months then you need to consider surgical options, because it won’t work.


  • SS: weight gain, cold skin/cold intolerance, constipation, dry skin, thinning of hair, bradycardia, depression, delayed reflexes (everything slows down)

  • Ca: Primary (issue within the thyroid gland itself) iodine deficiency, Hashimoto’s autoimmune thyroiditis, post-thyroidectomy/radioactive iodine, drug-induced (lithium, hyperthyroidism overtreatment) Secondary (issue with the hypothalamic-pituitary axis): pituitary adenoma, Sheehan’s syndrome (ischaemic necrosis of the pituitary gland after childbirth), infiltrative disease (tuberculosis, haemochromatosis)

  • I: TFTs (High TSH, low T3 and T4), thyroid antibodies, FBC (anaemia) U&Es (urea and electrolytes, checking kidney function), LFTs (liver function tests), creatinine, cholesterol, Guthrie test for congenital screening

  • T: Conservative: patient education (diet change), medical (LIFELONG replacement of thyroid hormone with levothyroxine)

  • Co: Hypercholesterolaemia, pre-eclampsia, hyperthyroidism from over treatment of hypothyroidism, myxoedema coma (coma caused by sever hypothyroidism)

  • Hashimoto’s thyroiditis: production of antibodies against thyroglobulin or thyroid peroxidase

  • GOITRE: low levels of thyroid hormones will stimulate the HPA and get stimulation of the thyroid, overgrowth

  • Can cause fluid retention: oedema and heart failure.

  • Has an effect on GAGs which is why hair and skin are affected

  • LIFELONG TREATMENT as oppose to temporary for hyperthyroidism


  • Cancer that originates from follicular or parafollicular cells. Caused by malignant neoplasm, increased risk with childhood neck irradiation.

  • SS: thyroid nodules/solitary nodule, rarely: hypothyroidism/hyperthyroidism

  • I: good family history (also for them, it is autosomal dominant), lumps (which can vary in size and increase very fast-weeks or months, and usually painless), TFTs, calcitonin (tumour marker), ultrasound (you can tell if it is benign or malignant: hypoechoic=bad, microcalcifications=bad, increased vascularity=bad

  • Types: papillary (70%, young, spreads to cervical lymph nodes, good prognosis), follicular (20%, low iodine areas, spreads to bone and lungs, good prognosis), medullary (from parafolicular cells, calcitonin marker, MEN syndrome, spreads to lymph), anaplastic (older patients, aggressive, spreads, poor prognosis)

  • Treatment: usually thyroidectomy and lifelong levothyroxine and annual thyroglobulin measurements. (anaplastic usually just palliative care)


  • Has three layers: Glomerulosa (aldosterone), Fasiculata (glucocorticoids), Reticularis (sex hormones).

  • If there is over function of adrenal gland: Cushing’s, if there is under function: Addison’s.

  • Pituitary gland produced ACTH - stimulates the Adrenal cortex to produce Cortisol

  • Cortisol: mAkes glucose in the liver, Antistress pathways, Anti-inflammatory pathways


  • Collection of signs and symptoms occurring when a patient has long-term exposure to cortisol (has exogenous or endogenous causes), difficult to diagnose.

  • SS: Buffalo hump, acne, moon face, central obesity, hypertension, hyperglycaemia, striae (different to stretch marks because they are depressed on their surface, fresh so dark, there is bruising), vertebral collapse, proximal muscle wasting (this does not happen with metabolic syndrome, so it is a good way to rule this out if other symptoms look like metabolic syndrome), psychosis, thinning of skin (also not in metabolic syndrome)

  • I: Diagnostic: urinary free cortisol, low dose and high does dexamethasone (not given to people on antiepilepsy medication because they would metabolise it anyways) suppression test Bloods: FBC, U&Es, LFTs, glucose, lipid levels Radiology: CXR (looking for lung cancer and vertebral collapse) Other: Dual energy X-ray Scan Note- it is a very difficult condition to diagnose because no one test can fully confirm or disprove Cushing’s

  • T: Conservative: education about the condition, decrease alcohol consumption (alcohol increases cortisol levels) Medical: ketoconazole, metyrapone, mitotane, treat complications: hypertension and diabetes mellitus Surgical: trans-sphenoidal surgery to remove pituitary adenoma or bilateral adrenalectomy to remove adrenal adenoma if indicated

  • Exogenous causes: iatrogenic (eg prescription of glucocorticoids for asthma)

  • Endogenous: either adrenocorticotrophic hormone dependent (ACTH) or ACTH independent ACTH dependent: Cushing’s disease (from pituitary) too much is produced from an adenoma, low dose dexamethasone test is used to confirm. Ectopic ATCH production in Ectopic Cushing’s (usually from a small cell lung cancer). ACTH independent: CARS: Cancer (adrenal adenoma), Adrenal nodular hyperplasia, Rare causes (McCune - Albright syndrome), Steroid use.

  • Cushing’s disease = pituitary problem Cushing’s syndrome = adrenal problem Ectopic Cushing’s = being produced elsewhere (eg small cell carcinoma of lung)


  • Arenal insufficiency, wherein the adrenal glands do not produce enough steroid hormone. A type of primary adrenal failure. Usually under diagnosed.

  • SS: unintentional weight loss, skin pigmentation (hand folds), body hair loss, constipation, abdominal pain,

  • Causes: MAIL: Metastasis from breast, lung, renal cancers; Autoimmune, Infections (tuberculosis most common, and opportunistic in HIV), Lymphomas (Inflammation, infiltration, infection, ischemia)

  • Random cortisol is enough to confirm suspicions for Addison’s to the extent that you can start treatment, this is a medical emergency, you do not wait for a full set of tests.

  • If you have adrenal insufficiency, you need to replace all hormones that are produced by the glands, hydrocortisone and glucocortisone - you cannot have an Addison’s patent who is not on glucocortisone

  • Hyperkalaemia can be a slight effect of Addison’s.

  • T: Conservative: education, carry a steroid alert card. Medical: replace glucocorticoids and mineralocorticoids with hydrocortisone and fludrocortisone, treat complications Surgery: surgical excision of tumour, if indicated.


  • Germ layers: ectoderm (epidermis, nervous system), mesoderm (muscles, bones, connective tissue), endoderm (other organs, GIT, respiratory tract)

  • Important dates in embryology: DAY 6 (implantation-enters uterine cavity), DAY 9 (blastocyst-16 cells embedded in endometrium, lacunae formation), DAY 15 (gastrulation)

  • Day 8: division of embryoblast (forms embryo: hypoblast, epiblast) and trophoblast (forms chorionic sac: syncytiotrophoblast - implantation enzymes and cytotrophoblast)

  • Peak vulnerability is weeks 3-8 (embryonic period) when the majority of organs are developing, after that the foetal period will have less of an impact.

  • Causes of embryonic defects: 54% unknown

14% genetic factors (mutations in genes, chromosomal aberrations, trisomy Down’s-accumulations of lymph just below the neck, palmar crease, disposition of ears, deletions DiGeroge, translocations sex-reversal syndromes with SRY_mutations with loss or gain in function in coding regions Apert’s syndrome, achondroplasia-dwarfism or in promoter/enhancer sequences, Lieberberg syndrome, sex-reversal syndromes)

7% environmental factors (drugs, chemicals, infections, diabetes, obesity)

35% multifactorial inheritance (interaction of multiple genes with environmental factors, eg folate intake)

  • Alcohol causes decreased expression of shh, DNA mutations, metabolic changes due to trying to remove the alcohol, cellular death

  • Anencephaly (open brain), spina bifida (failure of spinal closure)

  • If you have spina bifida, 10% die in their first year, so in utero surgery is required before 26 weeks (otherwise the open contents of the spine will be exposed to the urine and toxins in the amniotic fluid, and the neural tube will degenerate) By day 24 the brain and neural tube are closed

  • Spina bifida occulta is a malformation of one or more vertebra: can be a birthmark, dimple, but the spinal chord can also be tethered to the vertebra and can be damaged as the child grows

  • Folic acid (VitB) can reduce the occurrence of spina bifida by up to 70% (otherwise combination of low folate with a folate metabolism genetic mutation can cause pathologically low levels of folate in the embryo)