Endocrine

Endocrine

1. Diabetes mellitus

   • T1DM
     • Autoab -- glutamic acid decarboxylase (GAD 65) Islet cells Tyrosine phosphatases Zinc transporter *HLA DR4 or DR3
   • T2DM
     • polygenic not insulin dependent but insulin requiring 
   • LADA
     • Auntoab to B cell antigens Share genetic features with Type 1 or Type 2  *may develop insulin dependence
   • MODY
     • transcription factor (67%) --HNF Ia (pancreas & islet) --HNF 4a HNF 1b glucokinase (32%)--loss of glucose sensing function
     • treatment
       • HNF 1a & HNF 4a --low dose sulphonylurea (first line) eg; glicazide, glibenclamide *Insulin can be stopped
     • features
       • -residual insulin secretion at least 3 years after diagnosis of T1DM -young onset -lack of metabolic syndrome in those presumed T2DM
   • HIV
     • increased in men on HAART (x4 greater) protease inhibitors & NRTIs; indanavir (blocks insulin mediated GLUT-4 & increases hepatic glucose production)

2. Thyroid

   • Hyperthyroidism
     • Low TSH High T3 & T4
     • subclinical
       • Low TSH Normal T3 &T4
     • Graves
     • Toxic Multinodular Goitre
     • Toxic adenoma
     • thyroiditis
       • intially presented with hyperthyroidism, and over time becomes hypothyroidism
       • Post-partum
       • de-Quarvain (viral)
       • Amiodarone
     • Treatment
       • 1. Symptomatic Mx: --beta-blockers 2. Anti-thyroid drugs: PTU (given in pregnancy), Carbimazole (s/e of agranulocytosis) Radioiodine therapy (kill thyroid cells using radioactive substance)3. Surgery
   • Hypothyroidism
     • High TSH Low T3 & T4
     • Subclinical
       • High TSH Normal T3 & T4 *Thyroidectomy can mimic such pattern-- when patient who is non-compliance to med
     • Secondary hypoT
       • Low TSH, T3 and T4
     • Hashimoto
       • common cause in UK
     • Iodine deficiency
       • commonest worldwide
     • iatrogenic (thyroidectomy)
       • recurrent laryngeal nerve  -hoarse voice Hypercalcemia - parathyroid gland resected along with the thyroid
     • thyroiditis
       • tender raised ESR viral / post-partum / drug-induced
     • treatment
       • Levothyroxine 100-250 micrograms/day caution in elderly, previous IHD, severe hypothyroidism --> can form clots in coronary artery (leading to MI) Thus, start low and go slow (50 micrograms)
   • goitre
     • diffuse
     • nodule
     • cancer
       • cold nodules (radioisotope scan) -not producing thyroid hormones -undifferentiated cells
       • Papillary
         • most common better prognosis
       • Follicular
       • Medullary
         • high calcitonin release
       • Anaplastic
         • poorest prognosis least common

3. Adrenal

   • Cushing's
     • decrease in muscle mass, increase in fats activation of collagenase--> striae, osteoporosis HTN, DM low K and H+ --> metabolic alkalosis
     • Cushing syndrome
       • cause: 2/3--adenoma 1/3-- bilateral hyperplasia
     • cushing disease
     • treatment
       • steroidogenesis inhibitors -ketaconazole, metyrapone
   • Conn's syndrome
     • high BP Low K, thus Low H+  --metabolic alkalosis
     • features
       • HTN, Hypokalemia, Alkalosis, Suppressed renin
       • Gitekman;s syndrome (thiazide-like defect in DCT Na/Cl transpory)
         • elevated renin & aldosterone, metabolic alkalosis, hypokalemia, hypocalcuria, hypomagneseamia, NOMRAL BP
     • aetiology
       • adenoma, hyperplasia, FH 1 (GRA), FH II (familial adenoma)
   • Phaeochromocytoma
   • Adrenocortico-insufficiency
     • primary vs secondary --primary (Addisons) -- Secondary: low ACTH, low cortisol but normal aldosterone (RAAS), no pigmentation
     • Addison's disease
       • commonest cause in UK -- autoimmune commonest in Msia-- TB High ACTH, low cortisol and aldosterone [all parts of adrenal are destroyed]
       • 5P's
         • Pain
         • Pigmentation
           • high ACTH seen in primary adrenocortico- insufficiency
         • postural hypotension
         • Potassium (high)
         • Psychosis
       • Synacthen test
     • Treatment
       • Primary (adrenal insufficiency) -hydrocortisone 5-25mg/day (glucorticoid) -fludrocortisone 0.1-0.2mg/day (mineralocorticoid) Secondary (adrenal insufficiency- pituitary problem) -only hydrocortisone 5-25mg/day *aldosterone release stimulated by RAAS

4. Pituitary

   • Acromegaly
     • OGTT
     • treatment
       • Somatostatin analogue receptor antagonist; pegvisomant Dopamine receptor agonists; bromocriptine, cabergoline, quinagolide
   • Prolactinoma
     • treatment
       • dopamine receptor agonists -bromocriptine
   • Pituitary apoplexy
     • caused by SAH --reduced blood flow to the pituitary
   • Diabetes insipidus
     • high sodium levels --can retain water (polyuria) leading to polydipsia [thirst centre in hypothalamus]
     • Central
       • treatment
         • Low ADH-- tablets / nasal inhalations
     • Nephrogenic
     • Water deprivation test
       • add Desmopressin (synthetic ADH) to differentiate neurogenic from nephrogenic DI
   • SIADH
     • low sodium levels --retain too much water by increase action of ADH
     • causes (3C 1D)
       • cancer
       • Cranial insult
       • Chest (SCLC)
       • Drugs (SSRI)
         • SSRI TCA opiates cyclophosphamide NSAIDS PPIs
     • euvolemic hyponatremia
       • Reduced serum osmolality <275 Increased urine osmolality >100 Increased urine sodium >30 *NO recent use of diuretics No hypotension & hypovolemia, oedema, adrenal/thyroid/renal insufficiency 
     • treatment
       • fluid restriction, democlocycline, tolvaptan
   • GH deficient
     • treatment
       • For children, injections recombinant HGH For adults, controversial use and some undergoing trials

5. Sexual

   • FSH, LH
     • oestrodiol (for low oestrogen)
     • prinary hypogonadism (gonadal failure)
       • Klinefelter, Turners
       • autoimmune(Premature ovarian failure), chemotherapy, surgery,infections(mumps, HIV), haemochromatosis, thalassemia, drug(ketaconazole)
     • secondary (pituitary gonadotophin deficiency)
     • tertiary (GnRH deficiency)
       • Kallman syndrome
   • testosterone
     • treatment
       • Patches, gel, injections *orally inactive use gonadotrophins for infertility

6. Parathyoid

   • Hyperparathyroidism
     • benign solitary parathyroid adenoma (85%) '4-gland' parathyroid hyperplasia (15%) parathyroid carcinoma <1%
     • treatment
       • surgery (definitive; 1st line) if surgery fail, cinacalcet (receptor antagonist)
     • biochemical features
       • increased serum calcium increased parathyroid hormone Raised urine calcium Low serum phosphate (negative feedback) Mild metabolic acidosis
     • USS of neck, MIBI scan, X-ray of hands, bone cysts (jaw)
   • Hypoparathyroidism
     • treatment
       • PTH injections (expensive) High dose vit D (monitor urine calcium)