Endocrinology Flashcards
Name the main types of receptor and hormone.
Hormone: gene-encoded made of polypeptides (oxytocin, GH, FSH); amino acid modification (adrenaline, melatonin); steroid (cholesterol, testosterone).
Receptors: GPCRs; tyrosine kinase (RTKs); those associated with tyrosine kinase activity (cytokines); steroid receptors
Describe the hypothalamus-pituitary-thyroid axis, and the -adrenal gland axis.
Hypo (TRH) -> AP (TSH) -> Thy (T3, T4, calcitonin)
Hypo (CRH) -> AP (ACTH) -> Adr (cortisol)
TSH/ACTH and T3/4/cortisol act in a negative feedback loop on their target organs and the hypothalamus
Describe the special considerations needed for measuring cortisol.
Cortisol follows a Circadian rhythm, meaning it is highest at 9am and lowest at 10pm. Requires suppression test (if too much; Cushing’s) or stimulation test (if too little; Addison’s)
Describe the basic diagnostic pathway of endocrine disease.
History and exam
Screening biochemistry panel (9am cortisol, hormones including thyroid, U&Es and osmolality)
Dynamic testing (e.g. suppression or stimulation)
Imaging (if necessary to localize problem)
Management
Describe the regions of the cranial fossae.
Anterior cranial fossa: frontal and ethmoid
Middle: sphenoid, part of temporal. Contains sella turcica
Posterior: occipital, part of temporal
Sella turcica contains pituitary fossa
Describe the contents and surrounding contents of the cavernous sinus.
Contents: internal carotid, occulomotor, trochlear, abducens, V1 nerves
Superior: pituitary, diaphragma sella
Inferior: sphenoid sinus
Describe the course of the optic nerve (CN III) and how pituitary adenoma may impact on function.
Temporal and nasal fields cross over at the optic chiasm.
Pituitary sits immediately inferior to the optic chiasm, so impedes on temporal flow: bitemporal hemianopsia
Describe the fascia of the neck at vertebra C7.
Platysma - superficial, in subcutaneous tissue
Investing fascia - invests SCM and trapezius, and all other fascia
Pretracheal - contains trachea, oesophagus, and thyroid
Carotid sheath - contains common carotid, vagus, IJV
Alar fascia - connects carotid sheaths
Retropharyngeal space between alar and pretracheal fascia
Prevertebral fascia - invests vertebral column and muscles
Name the infrahyoid (thyroid) muscles.
Omohyoid (shoulder)
Sternothyroid
Thyrohyoid
Sternohyoid
Describe how a thyroglossal cyst may arise.
Thyroid begins as midline epithelial proliferation between the anterior 2/3 and posterior 1/3 of the tongue (foramen caecum) then descends in the thyroglossal ducts; remnants and pyramidal lobe can cause cysts
Describe the arterial and venous supply of the thyroid.
External carotid -> superior thyroid art.
Thyrocervical trunk (subclavian) -> inferior thyroid art.
Superior, middle thyroid veins -> internal jugular
Inferior thyroid vein -> brachiocephalic trunk
Describe the pituitary-thyroid axis, and how T4/T3 is synthesized. Name the carrying proteins used to transport T4/3 to tissues.
Hypothalamus (TRH) -> anterior pituitary (TSH) -> thyroid
Iodide (I-) -> Iodine (I), then binds with thyroglobulin (Tg) to form MIT or DIT. 2xDIT = T4; DIT + MIT = T3.
Thyroid binding globulin (TBG), Thyroxine-binding pre-albumin (TBPA), albumin
Name the effects of T4/3 on peripheral tissues.
Acts via the GsPCR to increase cAMP
Glycogenolysis, gluconeogenesis
Lipolysis (fatty acid oxidation)
Increased heart, respiratory rates (B1, 2)
Increased mitochondrial synthesis, resp enzymes
Increased thermogenesis (B3)
Myelinogenesis
Describe the degradation of T4/3.
Three types of de-iodinase (D1, D2, D3)
D1 (liver, kidney), D2 (most other organs), D3 (brain except the pituitary; majority of degradation)
Regarding the presentation of thyroid nodules:
- describe the differential diagnosis
- describe important aspects of the history
- describe the main investigations
Most are benign adenomas, but may be goitres (e.g. Graves’) or carcinoma.
Is there a lump? Does it move on swallowing? Is it painful? (it shouldn’t be - indicates bleeding). Check PMHx of irradiation, and symptoms of mass effect (e.g. dysponea, stridor, dysphagia etc.)
US-guided fine needle aspiration (FNA), bloods (TSH, Tg)
Describe the classification of thyroid carcinomas, and the grading system.
Papillary, follicular, anaplastic (3x thyroid epithelium), and medullary (parafollicular).
(papillary spreads via lymph, follicular via blood. 30% of MTC due to MEN syndromes)
Thy1 (not enough sample to tell)
Thy2/U2 - benign
Thy3/U3 - further investigation needed
Thy4/U4 - probably malignant
Thy5/U5 - malignant
Describe the management of thyroid carcinoma.
(most carcinomas take up iodine, and secrete Tg)
- Surgery is the management of choice. 3 options - hemithyroidectomy, subtotal, and total thyroidectomy.
- Whole body iodine scan is done in conjunction, to assess whether there is residual tissue/mets
- thyroid remnant ablation (TRA) for refractive cases (3.3 GBq Iodine). Requires inpatient admission in lead lined room
- sorafenib, lenvatinib (tyrosine kinase inhibitors)
Describe the main causes, symptoms, and treatment for thyrotoxicosis.
Graves’ (85%), adenoma (10%), ectopic production
- autoantibodies against the TSH receptor, causing overstimulation
- anxiety, tremor, irritability, trouble sleeping
- exopthalamos, ptosis, lid lag
- tachycardia, palpitation, AFib, intolerance to heat, pretibial myxoedema
- weight loss (despite increased appetite)
- irregular menstrual cycle
- beta-blockers with symptomatic relief, carbimazole or PTU for thyroid suppression
Describe the main causes, symptoms, and treatment for hypothyroidism.
Hashimoto’s, iodine deficiency, lithium, surgery for thyrotoxicosis
- autoantibodies with CD8+ mediated destruction against Tg, peroxisomes
- depression, mental/motor slowing, psychosis
- periorbital puffiness
- bradycardia, cold intolerance, lipidaemia
- weight gain, diarrhoea, risk of ascites/megacolon
- oligo/amenorrhoea, hyperprolactinaemia
- levothyroxine 25-50mg
Describe the major hyperthyroid and hypothyroid emergencies.
Hyper - thyroid storm. resp/cardiac failure, hyperthermia. Treat with iodine, steroids, PTU, B-blockers, fluid, and ventilation.
Hypo - myxoedema. bradycardia, low voltage complexes, heart block, T wave inversion. Treat with ABCDE and passively rewarm
Briefly describe the six major endocrine genetic disorders.
MEN1 (MEN1 - 11q13): 3 P’s (hyperparathyroidism, pituitary, pancreas). regular screening required
MEN 2 (RET - 10q): associated with medullary thyroid carcinoma and phaeochromocytoma. MEN2B also associated with marfans, mucosal tumours. prophylactic thyroidectomy suggested (risk of MTC)
Von-Hippel-Lindau (VHL). accumulation of HIF (aberrant oxygen sensing). Retinal/CNS blastomas, and phaechrom.
Carney complex - PKA signalling with GPCR. Causes myxomas (e.g. atrial), Cushings’, acromegaly
McCune-Albright - somatic mutation to GNAS (cAMP)
Phaeochromocytoma - succinate dehydrogenase.
Name the layers of the adrenal gland and what each produces.
Capsule Zona glomerulosa - mineralocorticoids (e.g. aldosterone) Zona fasciculata - glucocorticoids Zona reticularis - androgens Medulla - catecholamines
Describe the pathology, symptoms, biochemistry, diagnosis, and management of Addison’s disease.
Primary adrenal insufficiency - can produce a crisis if infection etc. is superimposed
Anorexia, weight loss,, fatigue, hypotension, pigmentation, vomiting, diarrhoea
Low Na, high K, hypoglycaemia
Short synacthen test (<55nmol)
IV hydrocortisone, fludrocortisone, sick day rules
How does secondary adrenal deficiency differ from Addison’s?
aldosterone is preserved (controlled by RAAS system). pigmentation (POMC)/hypotension do not occur. no fludrocortisone is needed
