Endocrinology

Countdown to finals lecture 14/03/2014 Kate Hargreaves (FY1, respiratory)

Aims and objectives

Outline core endocrine topics Diabetes Thyroid disease Adrenal disease Pituitary disease
Other conditions listed but not covered Questions

Diabetes Mellitus
Type 1 DM:

Type 2 DM:

B cell autoimmune destruction Reduced insulin production

and insulin resistance insulin insufficiency Characterised by weight loss, Impaired glucose tolerance, hyperglycaemia, often hyperglycaemia, ketoacidosis, asymptomatic, associated polydipsia, thirst with complications Typically juvenile onset Typically later onset

Other causes of diabetes:

Drug induced: steroids, thiazides

Pancreatic surgery, trauma, pancreatitis

Cushings disease, acromegaly, glycogen storage diseases

Diabetes Mellitus
WHO criteria diagnosis Symptoms of hyperglycaemia AND fasting BM >7mmol/L OR random BM >11.1mmol/L 2x fasting BM >7mmol/L OR random BM >11.1mmol/L Oral glucose tolerance test >11.1mmol/L (2 hour value)

Diabetes Mellitus
Treatment: T1DM insulin T2DM diet control, oral hypoglycaemics, insulin
Biguanides: Eg metformin Increases insulin sensivity, maintains weight loss Does not cause hypoglycaemia Caution in creatinine >150 lactic acidosis Exenatide: Used in addition to metformin and a Sulfonylureas: Sitaglipin: sulfonylurea in high Eg gliclazide Increases insulin Increases insulin BMI or insulin secretion inappropriate secretion Increases insulin May cause weight Suppresses glucagon release secretion, gain S/E suppresses S/E hypoglycaemia glucagon release, hypoglycaemia slows gastric emptying, reduces appetite.

Diabetes Mellitus
Complication management: Micro and marcro vascular disease Kidney damage annual albumin creatinine ratio, creatinine and eGFC measurement, blood pressure control Retinopathy - yearly retinal screening , include visual acuity Neuropathic complications annual foot examination, think about gastroparesis, erectile dysfunction, bladder dyfunction Depression as with all chronic diseases consider secondary depression

Diabetic emergencies hypoglycaemia

BM <3.0mmol/L
Causes drugs (eg insulin, sulphonylureas),

pituitary insufficiency, liver failure, islet cell tumours. Symptoms sweating, anxiety, tremor, confusion, drowsiness, seizures, coma, restlessness

Diabetic emergencies hypoglycaemia

Management:
If conscious and able to swallow give 15-20g quick acting carbohydrate 200ml fruit juice, 120ml lucozade, 5 glucotabs Follow with long acting carbohydrate.

If conscious and confused/disorienta ted but able to swallow give 3 tubes of glucogel or 1mg IM glucagon. Follow up with long acting carbohydrate.

If unconscious/having seizures check ABC. Give 1mg IM glucagon or 80ml of 20% glucose IV. Follow this up with long acting carbohydrate.

Diabetic emergencies - DKA

Triad of hyperglycaemia, acidosis, ketonuria Presentation: polyuria, polydipsia, dehydration,

lethargy, hyperventilation, vomiting, abdominal pain, coma Investigation: BM, ABG, FBC, cultures, urine dip, MSU Management: IV access 0.9% NaCl (1L STAT, 1L in 1 hour, 1L in 2 hours, 1L in 4 hours, 1L in 6 hours), added K Fast acting insulin (5-10 units) Investigate underlying causes Insulin sliding scale check BM, HCO3, U+E regularly

Diabetic emergencies hyperglycaemic, hyperosmolar state.

Hyperglycaemia, severe dehydration,

hyperosmolarity (differentiated from DKA by lack of ketonuria) Presentation: confusion/altered consciousness, neurological signs (focal signs, seizures), polydipsia, polyurea. Usually triggered by intercurrent acute event: eg infection, MI, stroke.

Diabetic emergencies hyperglycaemic, hyperosmolar state.

Management
IV rehydration may need 8-10L over first 24

hours Electrolyte replacement often severely hypokaleamic Insulin 0.1units/kg infusion

Hypothalamic-pituitary axis
Hypothalamus: TRH CRH GHRH GnRH Somatostatin Dopamine Pituitary: TSH ACTH GH FSH/LH End organ: Thyroid thyroxin Adrenals Liver IFG-1 Ovaries/testes

Thyroid disease:
Thyroxin increases cell metabolism plays a role in growth and mental development.

Controlled by this feedback loop.

Thyroid disease usually caused by problems within the thyroid gland, rarely by disorders of the hypothalamus/pituitary

Hyperthyroidism:
High T3/4, low TSH

Signs and symptoms: so many!

weight loss heat intolerance tremor irritability diarrhoea oligomenorrhoia

tachycardia/AF warm peripheries fine tremor palmar erythema lid lag thyroid nodules goitre

Hyperthyroidism:
Causes Graves disease Toxic multi-nodular goitre Toxic adenoma Sub-acute thyroiditis - de Quervians Drugs eg amiodarone, lithium Ectopic thyroid tissue

Graves disease
Autoimmune disease caused by TSH-receptor antibodies, commonly associated with other autoimmune diseases Characterised by: Eye disease exopthalmus, optic nerve compression, opthalmoplegia, eye discomfort/grittiness Pretibial myxoedema Thyroid acropachy finger clubbing, painful periosteal reactions in limb bones Thyroid bruit

Hyperthyroidism:
Management: Symptom relief propanolol Drug treatment carbimazole, propylthiouracil Radioactive iodide Thyroidectomy

Hypothyroidism:
Signs: bradycardia dry skin and hair non pitting oedema slow relaxing reflexes peripheral neuropathy Symptoms: tiredness, lethargy depression dislike of cold weight gain menorrhagia hoarse voice

Diagnosis: raised TSH, reduced T4

Hypothyroidism:
Causes:
Autoimmune: Primary atrophic hypothyroidism Hashimotos thyroiditis
Acquired: Iodine deficiency Drug induced amiodarone, lithium Sub-acute thyroiditis Post thyroid iodine therapy or surgery

Treatment: titrate up dose of levothyroxine from 25 micrograms/day.

Adrenal disease:
Adrenal glands produce steroids (stimulated by ACTH) ... Glucocorticoids cortisol Mineralocorticoids aldosterone Androgens Excess Deficiency insufficiency) Cushings syndrome Addisions disease (adrenal

Cushings syndrome
Causes:
ACTH dependent: Cushings disease pituitary adenoma secretes ACTH causing bilateral adrenal hyperplasia Ectopic ACTH production eg small cell lung cancer, carconoid ACTH independent: Iatrogenic steroid administration Adrenal adenoma/carcinoma Adrenal nodular hyperplasia

Iatrogenic ACTH administration

Cushings syndrome:
Signs and symptoms ...
Also: proximal muscle weakness gonadal dysfunction (menstrual disturbance/ impotence) impaired glucose tollerance poor wound healing visual field defect if pituitary adenoma is the cause

Cushings syndrome
Investigation: Random cortisol, 9am cortisol Dexamethasone suppression test 24 hour urinary cortisol measurement

If these are abnormal, the cause can be identified by: Plasma ACTH High dose dexamethasone suppression MRI head CT abdomen

Cushings syndrome:
Treatment depends on cause:
Iatrogenic stop steroids if possible Cushings disease transphenoidal pituitary

adenoma removal Adrenalectomy for adenoma/carcinoma of the adrenals Ectopic ACTH surgery to remove tumour if it can be identified and has not spread Medical management to reduce cortisol metyrapone/ketoconazole

Hyperaldosteronism:
Excess aldosterone (independent of renin-

angiotensin system) Causes water and sodium retention hypertension, hypokaleamia, moderately raised sodium
Conns syndrome = solitary adenoma Bilateral adrenal hyperplasia Management :

Medical spirololactone, amiloride, eplernone Surgical removal of solitary adenoma

Phaeochromocytoma
Catecholamine producing tumours from sympathetic

paraganglia cells (adrenal medulla) Clinically: all signs and symptoms episodic Intermittent hypertension (refractory) Sweating, heat intolerance, flushing, palpitations, chest tightness Feeling of apprehension, headaches, visual disturbance

Investigation 3x 24h urinary catecholamine collection, abdomen CT Treatment : Medical a and b blockade Surgical removal of tumour

Addisons disease adrenal insufficiency

Causes:
Autoimmune (most common in UK) TB, adrenal mets, lymphoma, adrenal haemorrhage
Also: hyponatraemia hyperkalaemia hypoglycaemia

Addisons disease
Investigations: U+Es, calcium, BM Short Synacthen test 9am ACTH level 21-Hydroxylase adrenal autoantibodies AXR Treatment: Steroid replacement hydrocortisone and fludrocortisone

Addisonian crisis:
Causes: infection, trauma, surgery Presentation: shock, weakness, confusion, coma, hypoglycaemia Management: ABCDE assessment Bloods for cortisol, ACTH Hydrocortisone 100mg IV Septic screen IV empirical antibiotics

And ...
Other endocrinological conditions to be aware of but not covered today ... Parathyroid disorders MEN 1 and 2 Hyperprolactinaemia Acromegaly Diabetes insipidus

Question 1: diabetic retinopathy

a.
b. c.

3 features of background retinopathy

Defining feature of proliferative retinopathy How often should retinal screening be carried out?

Question 1: diabetic retinopathy

a.

dots (microaneurysims), blots (haemorrhages), hard exudates (lipid deposits)

New vessel formation needs urgent specialist referral Annually

b.

c.

Question 2: Thyroid function tests

TSH
a. b. c. High High Low Low Normal High

T3
Low

T4
Normal High

d.
e.

Low
Low

Low
Normal

Low
normal

Question 2: Thyroid function tests

TSH
a. Hypothyroid b. Subclinical hypothyroid High High Low Normal High Low

T3
Low

T4
Normal High Low

c. Hyperthyroid Low d. Sick euthyroid/ pituitary disease e. Subclinical hyperthyroid Low

Low

Normal

normal

Question 3: hypokaleamia
A 46 year old man is seen in clinic, referred from his GP with resistant hypertension. His U+Es are abnormal ... K 2.6 Na 151 C 52 U 4.6 He is found to also have an abnormal ECG. What is the most likely diagnosis? b. What are the ECG findings in hypokalaemia c. Give some common causes of hypokalaemia.
a.

Question 3: hypokaleamia
a.

Hyperaldosteronism commonest causes are Conns disease (an adrenal adenoma) or bilateral adrenal hyperplasia
Flattened or inverted T waves, a U wave, ST depression, wide PR interval, peaked P waves

b.

c.

Diuretics (thiazide and loop), DKA, diarrhoea, salbutamol nebs