1. Endocrinology

2. Endocrinology
Phase 2a Revision Session Rhys Watkins and David Rutherford 27/3/17
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3. Glucose
Range: mmol/L under all conditions Liver - Stores Glycogen - Glycogenolysis - Gluconeogenesis from fat, protein, glycogen Taken into cells by GLUT receptors (comes in different varieties based on location) Insulin: GlucoseGlycogen, Glucose into cells, supppresses glycogenolysis and gluconeogenesis
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4. Diabetes Mellitus (Type I)
B-cell destruction in Islet of Langerhans
Aetiology: Autoimmune
Acute presentation:
Polyuria Polydipsia Weight loss DKA
Subacute presentation:
Fatigue Polyuria/dipsia Visual change Balanitis/candida
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5. Type II – the metabolic syndrome
Central obesity
Elevated cholesterol/triglycerides
Requires Pokeflute to catch. That’s an important part of the syndrome
Raised BP
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6. Type II
Risk: Obese, advancing age, FH, certain ethnic groups Major Immediate Complication: HHS (Previously HONK) Major Long-term Complications: Kidney, Eye, Foot, Neuropathy Everything
HHS – Hyperosmolar Hyperglycaemic state
HONK – Hyperglycaemic Hyperosmolar Non-ketotic Coma
B cell mass about 50% at diagnosis! Wow that’s dramatic
Decreases life expectancy by 5 years as well as lowering QoL
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7. It’s the worst smell in the world

8. Diagnosis
HbA1C >48 (6.5%) -- Consider ‘pre-diabetes’ if ( %) Fasting glucose >7 (>6.5 = impaired GT) Oral >7.8 (>6.1 = Impaired)
Tend to use HbA!C now in practice – it’s easy, only need one, unequivocal, longer time frame
DON”T use in: pregnancy, children, haemolytic disease, type 1, pancreatic surgery (niche)
Basically it’s only for use in type 2 diabetics
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9. Management Stepwise METFORMIN SULFONYLUREA DPP-4 INHIBITOR
(caution glibenclamide/cholropropramide in eldery/renal impairment)
DPP-4 INHIBITOR
PIOGLITAZONE
(avoid with biggest CVD risk)
METFORMIN – GLUT4 receptors in liver, sensitises to insulin, also helps lose weight
SE anorexia, diarrhoea, nausea/discomfort
Stop when acutely unwell and don’t prescribe in renal or liver faiulre – Lactic acidosis is bad.
SULFONYLUREA – They’re the ones ending in ‘amide’ (usually). Tolbutamide, glibenclamide, gliclazide.
They work by opening channels in the B cell and they produce more insulin.
Need B cell reserve, can cause weight gain, don’t use in pregnancy or liver disease
DPP-4 inhibitors are the ones ending in ‘gliptin’. Prevent breakdown of GLP-1, mnost effective early when insulin production relatively preserved.
No hypos = good, but no weight loss.
A good choice when you need to avoid hypos
Triple Therapy
Insulin
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10. Stop this from happening, please
As in, seondary prevention:
Eye screening, foot screening, kidney tests, BP checks and appropriate aggressive management, put them on a statin, etc etc etc.
They’re at seriously increased risk of vascular events
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11. DKA
Features: Lethargy, polyuria, dehydration, confusion, coma, abdo pain, Kussmaul breathing Diagnose: Ketone ++, Glucose >11, venous pH <7.3, bicarb <16 First priority: Fluid balance and dehydration. 0.9% saline 500ml bolus then replacement regime, typically 100ml/kg (1L over 1hr, 2hr, 4hr, 6hr) Second: Actrapid 0,1u/kg/hr IV. Avoid SC
Uncontrolled hyperglycaemia and catabolic state. Ketones produced as body requires glucose in cells (ironically) so catabolises. pH very low hence nausea and vomiting and the breathing. Renal hypoperfusion occurs due to osmotic diuresis and is made worse by dehydration.
It’s blue because it’s a classic exam trigger
I have no idea why bicarb is relevant either. Roll with it
Aim for fall in ketones of 0.5mmol/hr and bicarb rise of 3mmol/hr. When glucose hits add some glucose in as well as the insulin to prevent hypos
Other things: electrolytes especially sodium can drop – replace as necessary. K will be high but should fall with treatment because insulin drives it into cells.
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12. Resolution: pH >7. 3 Bicarb >18 Ketones <0
Resolution: pH >7.3 Bicarb >18 Ketones <0.3 Ketones poorly discriminative
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13. THYROID DISEASE

14. THYROID ANATOMY Thyroid cartilage Isthmus 4th tracheal ring
Important structures that must be considered when operating on the thyroid gland include:
Recurrent laryngeal nerve
Superior laryngeal nerve
Parathyroid glands
Trachea
Common carotid artery
Internal jugular vein
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15. THYROID ANATOMY
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16. THYROID HISTOLOGY Colloid (thyroglobulin) Cuboidal epithelial cells
Follicle
Basement
membrane
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17. THYROID PHYSIOLOGY STEP 1:
Circulating I- is cotransported with Na+ ions across the follicular cell plasma membrane.
Once inside, the bulky I- ion cannot diffuse back into the interstitial fluid (iodide trapping). Na+ later leaves via Na+/K+-ATPase pumps.
STEP 2:
I- ions diffuse down electrical and concentration gradients to the luminal border of the follicular cells.
I- rapidly oxidised at luminal surface to iodine free radicals.
STEP 3:
Colloid contains large amounts of thyroglobulin (made by follicular cells), which essentially consists of a central strand of protein with tyrosine rings budding off.
I0s attach to tyrosine rings of thyroglobulin.
Oxidation and attachment to TG mediated by thyroid peroxidase (also made by follicular cells).
STEP 4:
Tyrosine with one iodine = monoiodotyrosine (MIT).
Tyrosine with two iodines = diiodotyrosine (DIT).
Phenolic ring of a molecule of MIT or DIT removed from remainder of the tyrosine and coupled to another DIT on the thyroglobulin molecule.
Mediated by thyroid peroxidase.
2 DITs coupled = T4.
1 MIT and 1 DIT = T3.
STEP 5:
When required in blood, colloid (containing iodinated thyroglobulin) is endocytosed by follicular cells.
STEP 6:
TG with coupled MITs and DITs encounters lysosomes in cell interior.
TG broken down releasing T3 and T4
STEP 7:
T3 and T4 diffuse out of the cell and interstitial fluid into the blood.
Free amino acids from proteolysis re-used for TG synthesis.
There is sufficient iodinated thyroglobulin stored within the follicles of the thyroid to provide thyroid hormone for several weeks even in the absence of dietary iodine.
This storage capacity makes the thyroid gland unique among endocrine glands but is an essential adaptation considering the unpredictable intake of iodine in the diets of most animals.
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19. HYPOTHYROIDISM: CAUSES
PRIMARY HYPOTHYROIDISM (↓T4)
Primary atrophic hypothyroidism
Hashimoto’s thyroiditis (anti-TSHR, anti-Tg, anti-TPO)
Iodine deficiency
Post-thyroidectomy / radioiodine / antithyroid drugs
Lithium / amiodarone
SECONDARY HYPOTHYROIDISM (↓TSH)
Hypopituitarism
TRAbs = TSH receptor antibodies
Anti-Tg = Thyroglobulilin antibodies
TPOAb = Thyroperoxidase antibodies
Hashimoto’s produces goitre, PAH does not.

20. HYPOTHYROIDISM SYMPTOMS SIGNS CVS: - RS: Hoarse voice GI: Constipation
Bradycardic
Reflexes relax slowly
Ataxia (cerebellar)
Dry, thin hair / skin
Yawning / drowsy / coma
Cold hands +/- ↓T°C
Ascites
Round puffy face
Defeated demeanour
Immobile +/- Ileus
CCF
CVS: -
RS: Hoarse voice
GI: Constipation
Int: Cold intolerance
Endo: Weight gain
UG: Menorrhagia
MSK: Myalgia, weakness
Neuro / Psych: Tired, low mood, dementia

21. HYPOTHYROIDISM ↓T3, ↓T4 = ↑TSH INVESTIGATIONS: TFT Lipids/cholesterol
(c) FBC (macrocytosis)

22. HYPOTHYROIDISM: ASSOCIATIONS
AUTOIMMUNE
Type 1 Diabetes Mellitus
Addison’s disease
Pernicious anaemia
Primary biliary cirrhosis
INHERITED
Turner’s syndrome
Down’s syndrome
Cystic fibrosis

23. HYPOTHYROIDISM: TREATMENT
Levothyroxine (T4) – review at 12 weeks, adjust 6 weekly
NB: give smaller doses if elderly as risk of angina or MI
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25. HYPERTHYROIDISM: CAUSES
1. GRAVES’ DISEASE:
IgG autoantibodies bind to and stimulate TSH receptors (triggers = infection, stress, childbirth)
Eye disease, pretibial myxoedema, thyroid acropachy
Autoimmune (vitiligo, type 1 DM, Addison’s)
2. TOXIC MULTINODULAR GOITRE
3. TOXIC ADENOMA
4. ECTOPIC THYROID TISSUE (mets / struma ovarii)
5. EXOGENOUS (Iodine / T4 excess)
6. DE QUERVAIN’S THYROIDITIS (post-viral)

26. Pretibial Myxoedema
Thyroid Acropachy

27. HYPERTHYROIDISM SYMPTOMS SIGNS CVS: Palpitations RS: - GI: Diarrhoea
Int: Heat intolerance
Endo: ↓Weight, ↑appetite
UG: Oligomenorrhoea +/- infertility
MSK: -
Neuro / Psych: Tremor, irritability, labile emotions
HANDS:
- Palmar erythema; warm, moist skin; fine tremor
PULSE:
- Tachycardia; SVT; AF
FACE:
Thin hair; lid lag / retraction
NECK:
Goitre; nodules; bruit

28. HYPERTHYROIDISM ↑T3, ↑T4 = ↓TSH INVESTIGATIONS: (a) TFT
(b) FBC (normocytic anaemia)
(c) ESR (↑)
(d) Calcium (↑)
(e) LFT (↑)
(f) Thyroid autoantibodies
(g) Visual fields, acuity, eye movements
Hyperthyroidism appears to be linked with liver failure.

29. HYPERTHYROIDISM: TREATMENT
(i) β-blockers:
- Propanolol (rapid control of symptoms)
(ii) Antithyroid medication:
Titration (carbimazole: SE = AGRANULOCYTOSIS)
Block and replace (carbimazole + thyroxine)
(iii) Radioiodine (131I)
(iv) Thyroidectomy
Carbimazole and propylthiouracil (PTU) inhibit thyroid peroxidase and prevent further synthesis of T4

31. THYROID EYE DISEASE 25-50% have Graves’ disease
Main risk factor = smoking
Eye and thyroid disease may not correlate
SYMPTOMS: Eye discomfort, grittiness, diplopia
SIGNS: Exophthalmos, proptosis, ophthalmoplegia
TESTS: Clinical diagnosis +/- CT/MRI orbits
MANAGEMENT: Conservative measures (stop smoking, sunglasses, Fresnel prism); IV methylprednisolone; Surgical decompression; Eyelid surgery

32. CAUSE OF GOITRE THYROID CANCERS EMERGENCIES DIFFUSE Physiological
Graves’ disease
Hashimoto’s thyroiditis
De Quervain’s
NODULAR
Multinodular
Adenoma / cyst
Carcinoma
Papillary (60%)
Follicular (≤25%)
Medullary (5%)
Lymphoma (5%)
Anaplastic
EMERGENCIES
1. Myxoedema coma (↓T4)
2. Thyrotoxic storm (↑T4)

33. ADRENAL DISORDERS

34. ADRENAL GLANDS

35. ADRENALS HISTOLOGY
GFR: Glomerulosa
Fasciculatum
Reticularis

37. CUSHING’S SYNDROME CHRONIC glucocorticoid excess
LOSS of normal feedback mechanisms
LOSS of circadian rhythm.
Most common cause = IATROGENIC
If due to pituitary adenoma = Cushing’s DISEASE
“Lemon on sticks” appearance
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38. CUSHING’S SYNDROME: CAUSES
ACTH DEPENDENENT (↑ACTH)
ACTH INDEPENDENT (↓ACTH DUE TO NEGATIVE FEEDBACK)
CUSHING’S DISEASE
Bilateral adrenal hyperplasia from ACTH-secreting pituitary adenoma
ADRENAL ADENOMA / CARCINOMA
Abdo pain +/- virilisation in females
ECTOPIC ACTH PRODUCTION
Small cell lung Ca and carcinoid tumours
ADRENAL NODULAR HYPERPLASIA
ECTOPIC CRH PRODUCTION
Thyroid medullary and prostate cancers
IATROGENIC
Steroids (common)

39. CUSHING’S SYNDROME SYMPTOMS SIGNS Int: Acne Endo: ↑ Weight
UG: Gonadal dysfunction
MSK: Proximal weakness
Psych: Mood change
FAT DISTRIBUTION:
Central obesity
Moon face
Buffalo neck hump
Supraclavicular fat distribution
SKIN CHANGES:
Skin and muscle atrophy
Bruises
Purple abdominal striae
OTHER:
Osteoporosis
Hypertension, hyperglycaemia
Infection-prone / poor healing
Gonadal dysfunction = irregular menses, hirsutism, ED, virilisation
Mood change = depression, lethargy, irritability, psychosis
Also recurrent Achilles’ tendon rupture

40. BASIC RULES OF ENDOCRINOLOGY: 1. EXCESS hormone – INHIBIT the gland
2. LOW hormone – STIMULATE the gland
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42. CUSHING’S SYNDROME: INVESTIGATIONS
1. Bloods (↑plasma cortisol)
2. Overnight dexamethasone suppression test
Dexamethasone 1mg PO at 00:00
Measure serum cortisol at 08:00
Normal <50nmol/L (no suppression in Cushing’s)
3. 48h dexamethasone suppression test
- Dexamethasone given qds for 2 days
Measure cortisol at 0h and 48h
No suppression in Cushing’s

43. LOCALISING THE LESION If above tests +ve → PLASMA ACTH
ACTH undetectable → ADRENAL TUMOUR → CT ADRENAL GLANDS
ACTH detectable → PITUITARY vs ECTOPIC:
- 48h HIGH-DOSE dexamethasone suppression test
- CRH TEST (measure cortisol at 120 mins)
If no mass when do CT adrenals, proceed to adrenal vein sampling or adrenal scintigraphy
High-dose suppression test = 2mg/6h for 48h. Pituitary = suppression. Other causes = no/part suppression
CRH test = 100ug IV CRH (ovine or human). Cortisol rises with pituitary but NOT ectopic ACTH secretion.
Other tests = MRI and bilateral inferior petrosal sinus sampling
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44. CUSHING’S SYNDROME: TREATMENT
Iatrogenic – stop steroids
Cushing’s disease – trans-sphenoidal surgery or bilateral adrenalectomy (caution Nelson’s syndrome)
Adrenal adenoma – adrenalectomy
Adrenal carcinoma – adrenalectomy, RT and adrenolytics (mitotane)
Ectopic ACTH – surgery (if localised)
Ectopic ACTH:
Surgery if tumour located and hasn’t spread.
Metyrapone, ketoconazole and fluconazole decrease secretion of cortisol pre-op or if awaiting effects of radiation.
Intubation + mifepristone (competes with cortisol at receptors) and etomidate (blocks cortisol synthesis) may be needed (e.g. in severe ACTH-associated psychosis)

45. YOU HAVE NO ADRENAL GLANDS
Nelson’s syndrome – increased skin pigmentation due to raised ACTH from an enlarging pituitary tumour as adrenalectomy removes negative feedback; responds to pituitary radiation.
YOU HAVE NO ADRENAL GLANDS

46. ADDISON’S DISEASE
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47. ADDISON’S DISEASE Primary adrenocortical insufficiency
Destruction of adrenal cortex
↓Glucocorticoids and ↓Mineralocorticoids
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48. ADDISON’S DISEASE: CAUSES
Autoimmune (80%) – commonest in UK
TB – commonest worldwide
Adrenal metastases (lung, breast, kidney)
Lymphoma
Opportunistic infections in HIV (e.g. CMV)
Adrenal haemorrhage (e.g. SLE, APS)
Congenital adrenal hyperplasia (late-onset)
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49. ADDISON’S DISEASE SYMPTOMS SIGNS
GI: N/V, abdo pain, constipation / diarrhoea
Int: Tanned skin
Endo: Lean build
MSK: Weakness, flu-like arthralgias, myalgias
Neuro: Dizzy, faints
Psych: Tired, tearful, anorexia, depression, psychosis
SKIN:
Pigmented palmar creases and buccal mucosa
Vitiligo
CVS:
Postural hypotension
Shock (↑BP, ↓HR, coma)
Consider Addison’s in all with unexplained abdominal pain or vomiting

50. BASIC RULES OF ENDOCRINOLOGY: 1. EXCESS hormone – INHIBIT the gland
2. LOW hormone – STIMULATE the gland
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52. ADDISON’S DISEASE: INVESTIGATIONS
1. Bloods:
- FBC (anaemia, eosinophilia)
- U&E (↓Na+, ↑K+, ↑Ca2+, ↑Urea)
- BM (↓)
2. Short ACTH Stimulation Test:
Measure plasma cortisol before and 30mins after IM Tetracosactide (SynACTHen)
Addison’s excluded if 30min cortisol >550nmol/L
3. 9AM ACTH levels: inappropriately high in Addison’s
4. 21-hydroxylase adrenal autoantibodies
Corticosteroids sequester eosinophils so a lack of corticosteroids in Addison’s produces an eosinophilia.
Hypercalcaemia is due to increased Ca2+ input into the extracellular space and reduced renal secretion of calcium. Volume depletion found in Addison's (due to lack of aldosterone and therefore lack of fluid retention) means that there is reduced GFR and increased tubular calcium reabsorption. 

53. ADDISON’S DISEASE: TREATMENT
Replace steroids with 15-25mg Hydrocortisone daily
Replace mineralocorticoids with Fludrocortisone
Drug card and bracelet
DOUBLE dose if febrile illness, injury or stress
IV fluids if dehydrated
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54. SECONDARY ADRENAL INSUFFICIENCY:
Lack of ACTH (and therefore cortisol)
Commonest cause = IATROGENIC
Long-term steroid therapy suppresses HPA axis
Other rare causes include hypothalamo-pituitary disease (no hyperpigmenation as ↓ACTH and mineralocorticoid levels normal)
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55. CONN’S SYNDROME Excess aldosterone independent of RAAS
Solitary aldosterone-producing adenoma
↑ retention of Na+ and water
Often asymptomatic. May have signs of ↓K+
Ix: U&E, renin, aldosterone
Tx: Laparoscopic adrenalectomy. Spironolactone for 4 weeks pre-op to control BP and K+

57. ACROMEGALY
Excess GH from pituitary tumour (99%) or hyperplasia (e.g. ectopic GHRH carcinoid tumour)
Male : Female = 1:1
5% associated with MEN-1
If before epiphyses fuse – GIGANTISM
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58. ACROMEGALY SYMPTOMS SIGNS CVS: - RS: Snoring
GI: “Wonky bite” (malocclusion)
Int: ↑Sweating
Endo: ↑Weight
UG: ↓libido; amenorrhoea
MSK: Arthralgia; backache
Neuro: Acroparaesthesia; headache
Skin darkening
Acanthosis nigricans
Big supraorbital ridge
Interdental separation
Macroglossia
Prognathism
Laryngeal dyspnoea
OSA
Spade-like hands and feet
Tight rings
Carpal tunnel syndrome
Acroparaesthesia = a condition of burning, tingling, or pricking sensations or numbness in the extremities present on awaking and of unknown cause or produced by compression of nerves during sleep

59. ACROMEGALY: COMPLICATIONS
Impaired glucose tolerance (40%) and Diabetes Mellitus (15%)
Vascular: HTN; LVH; cardiomyopathy; arrhythmias; IHD; stroke
Colon cancer
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60. ACROMEGALY: INVESTIGATIONS
GOLD STANDARD = IGF-1 and OGTT
Don’t rely on random GH: pulsatile secretion
↑Glucose, ↑Ca2+, ↑PO43-
MRI pituitary fossa, visual field and acuity
Old photos

61. ACROMEGALY: TREATMENT
Trans-sphenoidal surgery to remove tumour
Somatostatin analogue (SSA) – e.g. IM octreotide or lanreotide (NB GI side effects)
Radiotherapy
Pegvisomant (recombinant GH analogue)
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62. ADH (AVP)
Action of ADH This is the collecting duct in water-rich conditions
Collecting duct
300
H20
AVP stands for arginine vasopressin and is the preferred American term as far as I can tell
1200

63. ADH (2)
Action of ADH ADH increases expression of Aquaporins in collecting duct and therefore the retention of water
Collecting duct
300
H20
1200

64. Diabetes Insipidus Lack of ADH
Diabetes Insipidus is lovely because you can work out all the symptoms just by knowing what ADH does
Lack of it is like taking a strong diuretic all the time

65. Diabetes Insipidus
Lack of ADH Water not sufficiently reabsorbed from collecting duct Large amounts of undilute urine
Collecting duct
300
H20
AVP stands for arginine vasopressin and is the preferred American term as far as I can tell
1200

66. Diabetes Insipidus Lack of ADH = Polydipsia = Polyuria
Glucose metabolism preserved
Dehydration
Hypernatremia
Fluid restriction has minimal effect on urination
Diabetes Insipidus is lovely because you can work out all the symptoms just by knowing what ADH does
Lack of it is like taking a strong diuretic all the time

67. Diabetes Insipidus Desmopressin stimulation
Urine output falls, osmolarity increases
Central = lack of ADH
Central causes:
Tumour, lack of blood supply (inc Sheehan’s), Impact/fracture, surgical, autoimmune
Nephrogenic:
Lithium toxicity, release of obstruction, hypercalcemia, hypokalaemia
No change
Nephrogenic DI
Rare causes
(dipsogenic, gestational)

68. Diabetes Insipidus
Treat with Desmopressin if neurogenic (central) Thiazide diuretics (hydrocholorothiazide) and amiloride are useful if nephrogenic And of course, if there’s a detectable underlying cause, you should treat that too
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69. SIADH It’s exactly the opposite of DI  excessive ADH production
Syndrome of Inappropriate ADH production
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70. SIADH Excess ADH production Very small volumes of concentrated urine
Collecting duct
300
H20
1200

71. SIADH - symptoms
Varied and generic Anorexia/nausea Aches and weakness Neuromuscular (myoclonus, reflex changes, tremor, ataxia…) Respiratory (cheyne-Stokes respiration, apparently) Neurological
Syndrome of Inappropriate ADH production
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72. Natural causes fall into three main camps
SIADH - Causes
Natural causes fall into three main camps
Central Nervous System
Infection
Mass/bleed
GBS/MS
Really rare stuff
Pulmonary
Infection
Abcess
Asthma CF
Paraneoplastic
First described in small cell lung cancer
Other types too e.g. Ewing Sarcoma, GI and GU
Syndrome of Inappropriate ADH production
Uncommon side effect of most of these things, central nervous systemmost common
Drugs include SSRIs, MDMA, morphine, amitriptyline, CMZ and many of the nasty chemo/suppression type ones
DRUG SIDE EFFECTS
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73. Diagnosis & Treatment
Euvolaemic with Hyponatraemia
Urine osmolarity > 100mOsm/kg
Urine Sodium >40mEq/L
Fluid restriction – increases Na concentration Tolvaptan – V2 vasopressin blocker
Don’t worry much about the clinical findings
Conivaptan – V1 and V2 blocker
Demococycline is most potent ADH blocker but 2-3 days needed for onset and steep side effect profile including nephrotoxicity and photosensitity
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74. I hope you all like arrows
(I’m very sorry)

75. Calcium Homeostasis Serum Calcium Bone deposition
Thyroid releases Calcitonin
Ca absorption decreased
Calcium rises
Calcium falls
Serum Calcium
Approx 9-10mg/dL
Calcium falls
Calcium rises
Bone resorption
PTH level rises
Increased GI uptake
Ca absorption up
Vit D production up
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76. Calcium Homeostasis Serum Calcium Approx 9-10mg/dL Calcium falls
Calcium rises
PTH level rises
Bone resorption
Increased GI uptake
Ca absorption up
Vit D production up
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77. Calcium Homeostasis (PTH only)
Serum Calcium
Approx 9-10mg/dL
Calcium falls
Calcium rises
PTH level rises
Bone resorption
Increased GI uptake
Ca absorption up
Vit D production up
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78. Hyperparathyroidism Primary 80% due to adenoma
Serum calcium RAISED – STONES BONES MOANS GROANS, as well as weakness and fatigue, muscle symptoms polyuria, polydipsia
Asymptomatic actually most common
Lab results
PTH High Calcium High
Phosphate (usually) low Phosphatase (usually) High
Treat underlying cause (usually surgical) if symptomatic or asymptomatic with grossly abnormal test results (urine calcium or bone weakess)
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79. Hyperparathyroidism Secondary
PTH is high to attempt to correct persistently low calcium levels
CKD and vit D deficiency most common – GI disease such as bypass and Crohn’s are also possible
PTH High Calcium Low Phosphate High Phosphatase High
Usually asymptomatic in early stages  ymptoms are predominantly bony – osteomalacia, joint pain
Since the cause of the high PTH is the inappropriately low calcium, find the underlying cause and fix that and the PTH levels will return to normal
For any hyperPTH problem, bisphosphonates can protect the bones and reduce Ca levels by reducing bone turnover
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80. Hyperparathyroidism Tertiary
After many years of uncorrected secondary hyperparathyroidism
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81. Differentiating blood results
Hyperparathyroidism
Differentiating blood results
PTH
Calcium
Phosphate
Alk Phos
Primary  
Secondary
Tertiary
The best way to differentiate primary and tertiary is from the history of prolonged (usually kidney disease). You’d have had to have had symptoms with tertiary so you’d know it had been going on for a long time
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82. Hypoparathyroidism
LOW CALCIUM --- Parasthaesia (especially around mouth and lips)
--- Tetany (Chvostek’s sign & Trousseau’s sign)
--- Increased reflexes
--- QT elongation as well as reduced rate and contractility
Convulsions
Arrhythmia
Tetany
Go numb
Don’t forget there are many other potential reasons that calcium might be low
Kidney failure, pancreatitis, tumor lysis syndrome, CCB overdose, Rhabdomyolysis, Bisphosphonates
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83. Yes, this was available with a simple Google search

84. Hypoparathyroidism Surgical  the big one Autoimmune
DiGeorge (and other, rarer causes of Parathyroid absence)
Haemochromatosis
Familial forms
Pseudohypoparathyroidism – PTH levels OK, peripheral resistance
Pseudopseudo (RARE) – skeletal defects, inherited via father, biochemically normal
Differentials – Kidney disease, vit D malabsorption or deficiency, drugs (including steroids and diuretics)
Treatment is with Calcium if they’re severly calcium deficient (IV, central if possible), and vit D and calcium supplementation longer term
For the most chronic and insensitive apparently PTH analogues are available
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85. Thanks, Wiki
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86. Oh, whilst we’re here
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87. Hypocalcaemia
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88. There are an unbelievable number of possible causes
Hypocalcaemia
There are an unbelievable number of possible causes
Drug therapy – bisphosphonates calcitonin included, as well as other weird stuff
REDUCED INTAKE Alkalosis
Dietary insufficiency Because the albumin dissociates
Malabsorption from hydrogen and picks up calcium
Reduced Vit D
Lack of sunlight Kidney failure
Vit-D dependent rickets Rhadomyolysis
Anticonvulsant therapy
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89. Hypocalcaemia
I wrote all that then found that Derbyshire NHS trust has conveniently already done this…
This shows the value of research, everyone
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90. Hypocalcaemia
Admit if severe - <1.8mmol or <2.0mmol/L with symptoms
Calcium replacement with calcium glucoronate – IV for severe
Out in general practice everyone* takes Adcal (Calcium + Vit D3)
*I’m exaggerating, obviously**
**Although not much
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91. HYPOKALAEMIA K+ < 3.5mmol/L (severe <2.5mmol/L)
Muscle weakness, cramps, ↓tone, ↓reflexes, palpitations, arrhythmias, constipation
ECG: In ↓K+, U have no Pot and no Tea but a long PR and a long QT
Causes = Diuretics; V/D; Cushing’s; Conn’s; Pyloric stenosis; Alkalosis
Treatment: If mild (>2.5mmol/L, no symptoms), give oral K supplements (>=80mmol/24h e.g. Sando-K 2 tabs / 8h). Review K after 3 days. If taking a thiazide diuretic and K >3mmol/L, consider repeating and/or K+ sparing diuretic.
If severe (<2.5mmol/L and/or dangerous symptoms) give IV K+ cautiously, not more than 20mmol/h and not more concentrated than 40mmol/L. Do NOT give K+ if oliguric. NEVER give K+ as a fast stat bolus dose

92. HYPERKALAEMIA K+ > 5.5mmol/L (severe >6.5mmol/L)
Myocardial excitability → VF and cardiac arrest
ECG: Tall tented T waves, small P waves, wide QRS (eventually becoming sinusoidal), VF
CAUSES: Oliguric renal failure; K-sparing diuretics; Rhabdomyolysis; Addison’s; Burns; Metabolic acidosis (DM); ACEi
Concerning signs and symptoms: Fast irregular pulse, chest pain, weakness, palpitations, light-headedness

93. HYPERKALAEMIA: TREATMENT
NON-URGENT:
Treat underlying cause, review meds, polystyrene sulfonate resin (binds K+ in gut)
EMERGENCY:
Stabilize cardiac membrane: 10ml 10% Calcium Gluconate
Drive K+ into cells: 10U Actrapid (insulin) in 50ml 20% glucose (salbutamol nebs, NaHCO3-)
Insulin given to facilitate glucose uptake into the cell which brings K+ with it. Glucose given as well to prevent hypoglycaemia.
Only give bicarbonate if the patient is acidotic.
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94. CARCINOID TUMOURS
Diverse group of tumours of enterochromaffin cell (neural crest) origin
Produce 5HT (serotonin)
May also secrete bradykinin, tachykinin, substance P, VIP, insulin, etc
Appendix (45%), ileum (30%), rectum (20%)
Consider all as malignant

96. QUESTION 1
A 46-year-old woman is referred to endocrine with a tender neck swelling. Blood results are as follows:
TSH
<0.1 mU/l T4
188 nmol/l Hb
14.2 g/dl
Plt
377 * 109/l
WBC
6.4 * 109/l
ESR
65 mm/hr
Technetium thyroid scan shows decreased uptake globally
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97. QUESTION 1
What is the most likely diagnosis? (a) Sick thyroid syndrome (b) Acute bacterial thyroiditis (c) Hashimoto’s thyroiditis (d) Subacute thyroiditis (e) Toxic multinodular goitre
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98. QUESTION 1
What is the most likely diagnosis? (a) Sick thyroid syndrome (b) Acute bacterial thyroiditis (c) Hashimoto’s thyroiditis (d) Subacute thyroiditis (e) Toxic multinodular goitre
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99. QUESTION 1: RATIONALE
Subacute thyroiditis (also known as De Quervain’s thyroiditis) is suggested by the tender goitre, hyperthyroidism and raised ESR.
The globally reduced uptake on technetium thyroid scan is also typical
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100. QUESTION 2

101. QUESTION 2 What does the ECG show? Hypokalaemia Hyperkalaemia
Hypercalcaemia
Hyponatraemia
WPW syndrome
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102. QUESTION 2 What does the ECG show? Hypokalaemia Hyperkalaemia
Hypercalcaemia
Hyponatraemia
WPW syndrome
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103. RATIONALE FOR QUESTION 2
This ECG displays many of the features of hyperkalaemia:
Prolonged PR interval.
Broad, bizarre QRS complexes — these merge with both the preceding P wave and subsequent T wave.
Peaked T waves.
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104. QUESTION 2

105. QUESTION 3

106. QUESTION 3 What does the ECG show? Hypokalaemia Hyperkalaemia
Hypercalcaemia
Hyponatraemia
WPW syndrome
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107. QUESTION 3 What does the ECG show? Hypokalaemia Hyperkalaemia
Hypercalcaemia
Hyponatraemia
WPW syndrome
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108. RATIONALE FOR QUESTION 3
Hypokalaemia:
ST depression.
T wave inversion.
Prominent U waves.
Long QU interval.
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109. QUESTION 3

110. QUESTION 4 Patient comes in with: Low sodium Raised potassium
Raised calcium
Eosinophilia
What is the diagnosis?

111. QUESTION 4 Addison’s disease RATIONALE:
Destruction of the adrenal cortex leads to loss of mineralocorticoid and corticosteroid production. Sodium is therefore not retained as normal and potassium not expelled.

112. What is the treatment for HYPERthyroidism?
QUESTION 5
What is the treatment for HYPERthyroidism?

113. HYPERTHYROIDISM: TREATMENT
(i) β-blockers:
- Propanolol (rapid control of symptoms)
(ii) Antithyroid medication:
Titration (carbimazole: SE = AGRANULOCYTOSIS)
Block and replace (carbimazole + thyroxine)
(iii) Radioiodine (131I)
(iv) Thyroidectomy
Carbimazole and propylthiouracil (PTU) inhibit thyroid peroxidase and prevent further synthesis of T4