UKMLA: Endocrinology

Addison’s Disease: What is it?

The insufficient production of glucocorticoids and mineralocorticoids from the adrenal cortex→ Primary adrenal insufficiency

Addison’s Disease: What are the causes?

• Autoimmune destruction of adrenal glands

• Trauma to adrenal glands

• Haemorrhage

• Infarction

Addison’s Disease: What is the pathophysiology?

Damage to the adrenal cortex is primary adrenal insufficiency

Dysfunction to HPA axis is secondary adrenal insufficiency

Addison’s Disease: What are the symptoms?

• Hypotension

• Fatigue and weakness

• Gastrointestinal symptoms

• Syncope

• Skin pigmentation due to increased ACTH which stimulates production of alpha melanocyte stimulating hormone (MSH)

• Always suspect Addison’s disease in patients with fatigue, postural dizziness, hyponatraemia, borderline hyperkalaemia, and mucosal pigmentation due to hypoaldesteronism

Addison’s Disease: What is the classic dermatological presentation?

• Acanthosis nigricans (hyperpigmentation of skin folds due to high ACTH → too much alpha melanocyte stimulating hormone)

• Tanned appearance

Addison’s Disease: What is the investigation?

1. 9am serum cortisol

2. Prolonged ACTH stimulation test → Synacthen test if 9am cortisol test is abnormal

Addison’s Disease: What is the management?

• Sick day rules→ carrying steroid card, medical alert bracelet

• Double hydrocortisone steroid dose, fludrocortisone dose remains the same

Addison’s Disease: What is addisonian crisis?

An Addisonian crisis, a life-threatening condition characterised by severe hypotension and electrolyte imbalances

Addison’s Disease: What is the management?

Should be managed with:

• Aggressive fluid resuscitation

• Administration of intravenous/IM (if no access) steroids STAT

• Glucose administration if hypoglycaemia is present

Addison’s Disease: Which part of the adrenal gland produces mineralcorticoids e.g. fludrocortisone?

Zona glomerulosa

Addison’s Disease: Which part of the adrenal gland produces adrenaline?

Adrenal medulla

Addison’s Disease: Which part of the adrenal gland produces androgens?

Zona reticularis

Addison’s Disease: Which part of the adrenal gland produces glucocorticoids e.g. cortisol?

Adrenal medulla

Cushing’s Syndrome: What is it?

Excess glucocorticoids

Cushing Syndrome: What is the difference between Cushing’s syndrome and disease?

Syndrome→ excess glucocorticoids

Disease→ ACTH pituitary tumour

Cushing’s Syndrome: What are the causes?

• ACTH-dependent→ excess production of ACTH due to pituitary tumour

• ACTH-independent→ excess cortisol due to adrenal adenomas/carcinomas

Cushing’s Syndrome: What is the most common cause?

Exogenous corticosteroid exposure

Cushing’s Syndrome: What are the clinical features?

• Proximal myopathy

• Buffalo hump

• Striae and easy bruising on abdomen

• Osteoporosis and fractures

• Obesity

• HTN

• Hyperkalaemia

• Hirsutism

• Erectile dysfunction

• Psychological issues

Cushing’s Syndrome: What are the investigations?

• 24 hour urinary free cortisol test

• Low-dose dexamethasone suppression test

Cushing’s Syndrome: What is the medical management?

Metryapone

Ketoconazole

Pasireotide

Diabetes Drugs Side Effects: What are the side effects of biguanides?

• Lactic acidosis

• GI disturbance

Diabetes Drugs Side Effects: What are the side effects of sulfonylureas?

Gliclazide:

• Hypoglycaemia→ leads to falls

• Weight gain

Diabetes Drugs Side Effects: What are the side effects of thiazolidinediones?

• Fluid retention

• Weight gain

• Worsens heart failure

Diabetes Drugs Side Effects: What are the side effects of SGLT2-inhibitors?

DKA

Diabetes Drugs Side Effects: What are the side effects of DPP4-inhibitors?

• Hypoglycaemia

• GI upset

DKA: What is the diagnostic criteria?

• Blood glucose over 11

• Ketones over 3

• PH <7.3 or HCO3 <15 (acidosis)

DKA: What is the pathophysiology?

DKA: What are the common triggers?

• Infections

• Dehydration and fasting

• Missing doses of insulin

• Medications e.g. steroid treatment or diuretics

• Surgery

• Stroke or myocardial infarction

• Alcohol excess or illicit drug use

• Pancreatitis

DKA: What is the criteria for severe DKA?

• Blood ketones > 6mmol/L

• Bicarbonate < 5mmol/L

• Blood pH < 7

• Anion gap above 16

• Hypokalaemia on admission

• GCS less than 12

• Oxygen saturations < 92% in air

• Systolic BP < 90mmHg

• Brady or tachycardia (heart rate < 60 or > 100bpm)

DKA: What are the symptoms?

• Nausea and vomiting

• Abdominal pain

• Polyuria

• Polydipsia

• Weakness

DKA: What are the signs?

• Dry mucous membranes

• Hypotension

• Tachycardia

• Altered mental state (drowsiness, confusion, coma)

• Kussmaul's breathing (deep, sighing breathing to compensate for metabolic acidosis by blowing off carbon dioxide)

• Fruit-like smelling breath (due to ketosis)

DKA: What is the management?

1. Fluid replacement with 500ml bolus of IV 0.9% saline solution asap (over a few minutes!!)

2. If the patient is hypotensive/doesn’t respond to the first bolus, give up to 1L bolus of IV 0.9% saline solution

3. Fixed rate of insulin IV (Actrapid) over one hour→ stop regular SHORT-ACTING doses they would have usually had in that time instead but continue LONG-ACTING doses as normal

4. Heparin for VTE prophylaxis

DKA: What is the most important complication to look out for in patients with DKA?

Cerebral oedema

Gestational Diabetes: What is the diagnostic criteria?

According to NICE guidelines, gestational diabetes mellitus is diagnosed if the woman has either:

• a fasting plasma glucose level of >5.6 mmol/L; or

• a 2-hour post-oral glucose tolerance test plasma glucose level of >7.8 mmol/L

Gestational Diabetes: What are the risk factors?

1. BMI >30

2. Previous macrosomic baby (>4.5kg)

3. History of stillbirth

4. Previous gestational diabetes

5. First Degree Relative with Diabetes

6. Family origin with a high prevalence of diabetes (South Asia,Black Caribbean and Middle Eastern)

Gestational Diabetes: What is the management?

1. Diet and exercise

2. If not under 7 within 2 weeks, give metformin

3. If still uncontrolled, start insulin therapy

Gestational Diabetes: What are the complications of uncontrolled gestational diabetes?

• Macrosomic baby (>4.5kg)

• Neonatal seizures due to hypoglycaemia

Gestational Diabetes: When is an OGTT offered?

24-28 weeks gestation period

Hyperthyroidism: What is it?

A condition in which the thyroid gland is overactive, leading to the production of excess thyroid hormones

Thyrotoxicosis: What is it?

The syndrome resulting from the presence of excessive thyroid hormones in the body, not always due to thyroid gland overactivity.

Hyperthyroidism: What are the main causes?

• Graves→ autoimmune stimulation of thyroid gland by TSH

• Toxic adenoma

• Goitre

• Amiodarone

• Lithium

• Pregnancy

• Radiation exposure

Hyperthyroidism: What are the signs and symptoms?

• ↑ Basal metabolic rate

• Heat intolerance

• Tachycardia and arrhythmias

• Weight loss

• Diarrhoea

• Sweaty skin

• Insomnia and sleep disturbances

• Restlessness and tremors

Thyroid Disease: What are the shared symptoms of hyper and hypo thyroidism?

• Mood changes

• Menstrual disturbances

Hyperthyroidism: What are the specific features of grave’s disease?

• Exophthalmos/proptosis→ bulging eyes

• Thyroid acropachy→ soft tissue swelling, clubbing and new bone growth

• Pretibial myxoedema

Hyperthyroidism: What is the side effect of using carbimazole to treat grave’s disease?

Treatment of Grave's disease with Carbimazole can lead to agranulocytosis and potentially to neutropenic sepsis, so prompt request of a full blood count (FBC) is essential in management.

Hyperthyroidism: What is the difference between De Quervain’s thyroiditis and grave’s disease?

De quervain’s thyroiditis→ painful neck, tender on palpation and occurs after viral infection

Hyperthyroidism: What are the investigations?

• TFT→ raised T3 AND T3

• TSIAb

• TRAb

• Thyroid US

• Radioidine uptake test → diffuse uptake indicates Graves’ disease

Hyperthyroidism: What is the management?

• Carbimazole ± prophylthiouracil

• Prophylthiouracil only if in first trimester of pregnancy

• Propanalol

• Radioiodine therapy→ a radioactive form of iodine that selectively concentrates in the thyroid gland. It damages the thyroid tissue, reducing its hormone-producing ability.

• Thyroidectomy

Hyperthyroidism: What are the features of thyroid storm?

Unrelated or poorly managed hyperthyroidism after surgery, trauma or infection:

• Restlessness and agitation

• High-output heart failure

• Profound tachycardia

• Fever

• Delirium and altered mental status

Hyperthyroidism: What is the management of thyroid storm?

• IV propanol and digoxin

• Prophylthioracil and lugol’s iodine

• Corticosteroids→ inhibits conversion of T4 to T3

Phaeochromocytoma: What is it?

A pheochromocytoma is a catecholamine-secreting tumour that originates in the adrenal medulla.

Phaeochromocytoma: What are the symptoms?

• Episodic

• HTN

• Anxiety

• Weight loss

• Fatigue

• Palpitations

• Excessive sweating

• Headaches

• Flushing

• Fever

• Difficulty breathing (dyspnea)

• Abdominal pain

Phaeochromocytoma: What factors can worsen symptoms?

• Stress

• Exercise

• Surgery

• Beta blockers

• Opiates

Phaeochromocytoma: What are the investigations?

1. Plasma metanephrines testing followed by urinary metanephrines.

2. Adrenal imaging should be pursued only after biochemical confirmation

Phaeochromocytoma: What is the management?

Surgical resection → do alpha blockade with phenoxybenzamine pre-surgery FIRST to prevent HTN crisis during surgery

Phaeochromocytoma: What are symptoms of the neurofibromatosis type 1? (NF1)

• Iris hamartomas (lisch nodules)

• Cafe-au-lait spots

• Scoliosis

• HTN

• Intermittent palpitations

• Raised metanephrine

T1D: What is the pathophysiology?y

Destruction of the insulin-producing beta cells within the pancreas, leading to insulin deficiency.

T1D: What are the symptoms?

• Polyuria

• Polydipsia

• Weight loss

• In severe cases, patients may present with diabetic ketoacidosis(DKA) characterised by hyperglycemia, metabolic acidosis, and ketonemia.

T1D: What is the diagnostic criteria?

If symptomatic, one of the following results is sufficient for diagnosis:

• Random blood glucose > 11.1mmol/l or Fasting plasma glucose >7mmol/l

• 2-hour glucose tolerance > 11.1mmol/l

• HbA1C > 48mmol/mol (6.5%)

If the patient is asymptomatic, two results are required from different days.

T1D: What is the management?

• Short-acting insulin → after meals/snacks (3/5th of daily dose)

• Long-acting insulin→ at night

• IM glucagon and dextrose for unconscious individuals (2/5th of daily dose)

T1D: What is the initial management?

Basal-bolus insulin therapy or insulin pump

T1D: What are the target glucose leaves?

• Pre-meal blood glucose: 4-7 mmol/L (72-126 mg/dL)

• Bedtime blood glucose: 6-10 mmol/L (108-180 mg/dL)

• HbA1c: Less than 7%

T1D: Which condition is most commonly associated with T1D?

Hyperthyroidism → ensure patient goes for routine TFT

T1D/T2D: What is the classic feature of chronic diabetic sensory neuropathy?

Glove and stocking sensory loss

T1D/T2D: What does the glycaemic index represent?

A measure of how quickly carbs affect blood sugars

T2D: What is the pathophysiology?

Inadequate insulin production from beta cells→ insulin resistance.

T2D: What are the symptoms?

• Polyuria

• Polydipsia

• Unexplained weight loss

• Blurry vision

• Fatigue

T2D: What is the diagnostic criteria?

If symptomatic, one of the following results is sufficient for diagnosis:

• Random blood glucose > 11.1mmol/l

• Fasting plasma glucose > 7mmol/l

• 2-hour glucose tolerance > 11.1mmol/l

• HbA1C > 48mmol/mol (6.5%)

If the patient is asymptomatic, two results are required from different days

T2D: What is the management?

1. Metformin

2. If HbA1c over 58→ combine metformine with pioglitazone or sulphonylurea

3. If dual therapy ineffective, start triple therapy → metformin + pioglitazone/sulphonylurea + empagliflozin

4. Triple therapy ineffective?→ GLP-1 agonist

5. Last resort?→ start insulin

T2D: What is the MOA of metformin?

Inhibits hepatic gluconeogenesis

T2D: What are the microvascular complications?

• Diabetic retinopathy - Leading cause of visual loss in adults.

• Diabetic nephropathy - Leading cause of chronic kidney disease, characterised by proteinuria.

• Diabetic neuropathy - Chronic hyperglycaemia leads to various neuropathies.

• Gastrointestinal Complications - Gastroparesis due to nerve damage.

• Foot Complications - High risk for ulceration and infection.

• Sexual Dysfunction - Related to multiple factors including neuropathy and microvascular complications

T2D: How can Muslims manage their diabetes during Ramadan?

Continue on 500mg, take the morning dose before Suhoor (pre-sunrise meal), combine afternoon dose with dose taken at Iftar (after sunset meal)

T1D/T2D: What is the DVLA’s guidance on driving?

• Insulin-treated diabetes:

  • Group 1 (car/motorcycle): Drive if well-controlled, monitor blood glucose before and during driving.

  • Group 2 (lorry/bus): Stricter rules, annual medical review required.

T1D/T2D: What is the target blood pressure?

<140/90

T1D/T2D: What is the pathophysiology of diabetic neuropathy?

Advanced glycation end products induced by hyperglycaemia damage nerve fibres through their effects on matrix metalloproteinases

T1D/T2D: What is the management of diabetic neuropathy?

Amitriptyline (tricyclic antidepressant)

T1D/T2D: Which drugs should diabetics avoid?

Thiazides→ increases blood sugars!!

T1D/T2D: What is the management of HTN in diabetics?

In diabetes, age or ethnicity doesn’t really matter like it’s usually does so give:

• White→ ACEi

• Black→ ARB (then CCB)