Endocrinology Flashcards
1
Q
What are the three main causes of Addison’s disease
A
- Autoimmune (more developed countries)
Tuberculosis (more common worldwide)
May also be caused by metastases (eg. bronchial carcinoma)
2
Q
What are the clinical features of Addison’s disease
A
- Fatigue
- Abdominal Pain
- Weight Loss
- Hyperpigmentation → -ve feedback causes increased ACTH leading to increased POMC, leading to increased α-MSH
- Nausea, Vomiting, Hypotension
- Hypoglycaemia → may cause dizziness and falls
3
Q
What are the clinical features of Addisonian Crisis
A
severe hypovolaemia and hyponatraemia
4
Q
What are the investigations for Addison’s disease
A
Short Synacthen test
Morning Serum Cortisol → If short synacthen test unavailable
- Serum Electrolytes (Due to Aldosterone Deficiency) → hyponatraemia + hyperkalaemia
- Hypoglycaemia
- Metabolic Acidosis with normal anion gap
- FBC → anaemia
5
Q
What are the managements for Addison’s disease
A
Stable (Glucocorticoid + Mineralocorticoid) → Hydrocortisone (given in 2 or 3 divided doses) + Fludrocortisone
Intercurrent Illnesses ⇒ hydrocortisone (glucocorticoid) dose should be doubled and fludrocortisone dose should stay the same.
6
Q
What are the managements for Addisonian Crisis
A
- Addisonian Crisis → IV hydrocortisone, Fluid Resusitation, Glucose (if hypoglycaemia)
- Precipitated by sudden withdrawal of steroids, illness or surgery.
7
Q
What are the main causes of Cushing’s Syndrome
A
ACTH Dependent (80%)
- excess ACTH from pituitary adenoma (Cushing’s Disease) (most common endogenous cause)
- ectopic ACTH (Small Cell Lung Cancer)
ACTH Independent (20%)
- Adrenal adenoma
- Adrenal carcinoma
8
Q
What are the risk factors of Cushing’s Syndrome
A
exogenous corticosteroid use (most common cause overall), pituitary or adrenal adenoma, or adrenal carcinoma
9
Q
What are the clinical features of Cushing’s Syndrome
A
- Thin, easily bruisable skin with ecchymoses
- Stretch marks (striae)
- Proximal Myopathy (Muscle Weakness)
- Central Adiposity
- Fatigue
- Hirsutism, Acne
- Hyperpigmentation (if ACTH dependent)
- Lethargy & Depression
- Osteopenia & Osteoporosis
- Hypertension, Hyperglycaemia
- Increased susceptibility to infection
10
Q
What are the investigations for Cushing’s Syndrome
A
- Low Dose (1mg) overnight dexamethasone suppression test → most sensitive and 1st line test. Patients with Cushing’s syndrome do not have their morning cortisol spike suppressed.
- 24-hour urinary free cortisol or Late-night salivary cortisol → elevated
11
Q
What test distinguishes between Cushing’s disease and ectopic ACTH production
A
-
High Dose dexamethasone suppression test
- Cushing’s Disease (Pituitary Adenoma) ⇒ will suppress cortisol in high dose dexamethasone suppression test.
As excess ACTH production from the pituitaries can be inhibited by high doses of dexamethasone, however autonomous cortisol production from the adrenals will not be affected
12
Q
What re the blood results for someone with Cushing’s Syndrome?
A
- Bloods → Hyperglycaemia, Hypokalaemia, Hypernatraemia, Metabolic Alkalosis (due to increased H+ excretion and bicarbonate reabsorption)
- Ectopic ACTH production (ie. due to small cell lung cancer) is associated with very low potassium levels.
13
Q
What is the management for Cushing’s Syndrome
A
- If Iatrogenic → discontinue steroids or use lower dose
- Medical → metyrapone or ketoconazole (inhibit cortisol synthesis)
- Surgical → transsphenoidal pituitary adenomectomy (if pituitary tumour), adrenalectomy (if adrenal adenoma or carcinoma)
14
Q
What is Diabetes Insipidus
A
Condition in which kidneys are unable to concentrate urine due to inadequate secretion or sensitivity to ADH, resulting in the production of large quantities of dilute urine
15
Q
What are the causes for Diabetes Insipidus
A
Central DI (More common)
insufficient levels of ADH from posterior pituitary.
- Causes = pituitary tumour/surgery, traumatic brain injury, infection (meningitis), sarcoidosis, TB, SAH, hereditary haemochromatosis
Nephrogenic DI → defective ADH receptors in the distal tubules and collecting ducts.
- Causes = lithium therapy, electrolyte imbalances (hypercalcaemia or hypokalaemia), idiopathic, inherited (AVP2 gene)
16
Q
What are the clinical features for DI
A
- Polyuria → with very dilute urine
- Nocturia → restless sleep, daytime sleepiness
- Polydipsia → excessive thirst
- Dehydration → tachycardia, reduced tissue turgor, dry mucous membranes
(No symptoms suggestive of DM)
17
Q
What is the first line investigation to confirm DI?
A
- Water Deprivation Test → confirmatory test. If osmolality corrects itself then may be psychogenic polydipsia.
If not, after 8 hours administer desmopressin to differentiate between CDI and NDI.
Urine osmolality will rise in CDI but remain low in NDI.
18
Q
What are other investigations for DI
A
- Low urine osmolality + High serum osmolality
- Hypernatraemia and Hypokalaemia
MRI → look for brain/pituitary tumour
- If Low Sodium → psychogenic polydipsia (in context of low urine osmolality)
- Normal blood glucose → exclude DM
19
Q
What is the management for DI
A
-
Hypernatraemia → manage with oral or IV fluids (prevent dehydration)
- Correction of chronic hypernatraemia too fast predisposes to cerebral oedema
- Central DI → intranasal Desmopressin
- Nephrogenic DI → discontinue causative agent if medication induced (lithium), Thiazide Diuretics, sodium restriction
20
Q
What genetic component is T1DM most strongly associated with?
A
Associated with HLA DR3/4.
21
Q
What are the clinical features for both T1DM and T2DM
A
- Polyuria and Polydipsia
- Polyphagia (Excessive Appetite)
- Unexplained Weight Loss
- Fatigue
- Increased Susceptibility to Infections
- Acanthosis Nigracans (hyperpigementation) → T2DM
22
Q
What is the first presentation in 1/3 of T1DM cases
A
DKA is first manifestation in around 1/3 of cases.
N&V, abdominal pain, kussmaul breathing, sweet smelling breath.
23
Q
What are the investigations for DM
A
Measuring Blood Glucose
- finger-prick, one-off blood glucose (fasting or non-fasting)
- HbA1c (average blood glucose over last 2-3 months
-oral glucose tolerance test (measurement of glucose 2 hours after consumption of 75g of glucose)
C-Peptide (distinguish type 1 vs type 2) → decreased in type 1, increased in type 2
Urinalysis (Urine Dip)
- glucosuria
- ketone bodies (T1DM)
-microalbuminuria (early signs of nephropathy)
Antibodies in T1DM → Anti-GAD Antibodies and Islet Cell Antibodies
24
Q
What is the diagnostic criteria for DM
A
Symptomatic
- **fasting glucose ≥7.0mmol/L** - OR **random glucose ≥11.1mmol/L**
Asymptomatic → above criteria must be demonstrated twice (on two separate days)
HbA1c ≥48 mmol/mol
- 42-47 is pre diabetic
25
What is the management plan for T1DM?
Basal-Bolus Insulin ⇒
**long acting** (eg. insulin glargine, subcutaneous injection OD)
**+ short acting** (eg. insulin lispro or aspart, before meals)
26
What is the management plan for T2DM?
Diet and lifestyle advice
Glycaemic control
blood pressure management
lipid control
27
What is the first step of glycaemic control for T2DM?
**Metformin** if **HbA1C ≥48 despite lifestyle advice**
- **contraindicated in those with eGFR <30**. May accumulate if in renal impairment leading to increased risk of lactic acidosis.
28
What is the second step of glycaemic control for T2DM?
Add another drug →
DPP4i’s (-gliptins)
sulfonylureas (gliclazide)
SGLT-2i’s (-flozins)
pioglitazone
Step 3: Add further drug or try insulin based treatment (basal insulin)
29
What are the HbA1C target
48 mmol/mol if managed by diet and lifestyle alone, or a single antidiabetic drug.
53 mmol/mol if two or more antidiabetic drugs, or single drug that may cause hypoglycaemia (eg. sulfonylurea).
30
Why does DKA occur in T1DM
no insulin to suppress lipolysis → ketone formation → acidosis
31
What are the risk factors for DKA
infection (most common precipitating factor), inadequate insulin therapy (non-compliance), undiagnosed T1DM, MI
32
What are the clinical features of DKA
- Features of Diabetes → increased thirst (polydipsia), polyuria, weight loss, excessive tiredness
- **Nausea & Vomiting**
- Severe **Abdominal Pain**
- **Dehydration** → dry mucous membranes, decreased skin turgor, slow CRT, tachycardic, hypotensive
- **Hyperventilation** → **Kussmmaul breathing**
- **Reduced Consciousness**
- **Fruity Breath**
- **Rapid Onset** (<24 hrs)
33
What investigations are required with DKA
- **Venous Blood Gas** → **metabolic acidosis with raised anion gap (>16), with partial respiratory compensation (hyperventilation)**
- Blood **Ketones** → raised
- Blood **Glucose** → raised
- U&Es → **hyponatraemia** and **hyperkalaemia** (due to lack of insulin)
34
What is the management plan for DKA?
Two Key Parts to Treatment
1) Rehydrate:
- **IV Fluids (Isotonic Saline - 10ml/kg 0.9% NaCl)**
- **With Electrolyte repletion** (especially K+ as insulin will drive it into cells) → **Potassium Chloride**
2) Reduce Ketones
- **fixed rate IV Insulin (0.1 units/kg/hour)** (AFTER FLUIDS)
- Once glucose falls, give **5% dextrose**
- Regular Insulin Medication ⇒ continue long acting insulin, stop short acting insulin
**IV Bicarbonate** → only in **severe metabolic acidosis**
35
What is a important complication to consider when fluid resus?
- Important complication of fluid resuscitation in DKA = **cerebral oedema** (may cause headache, reduced consciousness, rise in BP, seizures)
36
What is Diabetic Nephropathy
clinical diagnosis in patient with long-standing diabetes (>10 years) with albuminuria and/or reduced estimated glomerular filtration rate (eGFR)
37
What are the clinical features of Diabetic Nephropathy
- **Hypertension**
- **Oedema** → in advancing diabetic nephropathy
- **Polyuria**
- **Lethargy**
- Signs of **Retinopathy** → usually develops alongside nephropathy. Blot haemorrhages, microaneurysms, neovascularisation
Major Histological Changes → mesangial expansion, glomerular basement membrane thickening, glomerulosclerosis
38
What are the investigations for Diabetic Nephropathy?
First Line: **Urinalysis** → **increased albumin:creatinine ratio (ACR)**- ACR >2.5 = microalbuminuria
- **All patients should be screened annually using urinary ACR**
Gold Standard: **Renal Biopsy** → shows **kimmelstiel-wilson nodules (also mesangial expansion and GBM thickening)**
Serum Creatinine & estimated GFR → GFR raised in early disease but reduced in late disease
39
What is the management plan for Diabetic Nephropathy?
- **Antihypertensive Treatment** → **ACE inhibitors or ARBs** are first line (renoprotective effect). Add CCB or Thiazide Diuretic as 2nd line.
- **Tight** **Glycaemic Control**
- **Control Dyslipidaemia** → **Statins** (atorvastatin)
- **Dietary Modification** → reduce protein and salt intake
- **Smoking Cessation**
40
How is HHS characterised
profound hyperglycaemia (>30), hyperosmolality (>320), and volume depletion (dehydration) in the absence of significant ketoacidosis
41
What are the risk factors for HHS
Infection (most commonly pneumonia or UTI), surgery, inadequate insulin therapy, acute illness (MI, sepsis, stroke), non-adherence to diabetes medications
42
What are the clinical features of HHS
**Acute Cognitive Impairment** → may be recorded via GCS (due to Hypernatremia)
**Polyuria**, **Polydipsia**, **Weight Loss**, **N&V**
**Dry Mucous Membranes** & **Decreased Skin Turgor** → signs of volume depletion
More **insidious onset (over days)**
(DKA DISTINGUISHING FEATURES → rapid onset, abdominal pain, fruity breath odour, kussmaul respirations)
43
What are the investigations for HHS?
Severe Hyperglycaemia (>30) + Hypotension + Hyperosmolality (>320)
- **Hypovolaemia**
- **Blood** **Glucose** → **markedly raised (>30 mmol/L)** without ketonaemia/acidosis
- **Blood Ketones** → negative (distiguish DKA vs HHS)
- **Serum Osmolality** (normal in DKA)
43
What is the management plan for HHS?
**Fluid Resuscitation (IV Fluids)** → **Isotonic Saline solution** (**0.9% NaCl**)
**Electrolyte Repletion** (if needed) → add **potassium (KCl)** to infusion
**IV Insulin (0.05 units/kg/hr) → not given first, as can result in cerebral oedema due to quick shift in glucose.**
If Glucose falls → **5% Dextrose**
VTE Prophylaxis → patients at high risk due to dehydration
43
What are the clinical features of Hypoglycaemia
Increased Sympathetic Activity → **sweating**, **anxiety**, **tachycardia**, **tremor**, **palpitations**, **pallor**
Increased Parasympathetic Activity → **hunger**, **nausea**, **vomiting**, **paraesthesia**
Neuroglycopenic → **confusion**, **seizures**, **agitation**
44
What are the investigations for Hypoglycaemia
- **Serum Glucose** → <2.8 mmol/L causes neuroglycopenic symptoms, <3.3 mmol/L causes autonomic symptoms
- **Serum Insulin** → elevations may suggest insulinoma
- **Serum C-Peptide** → **elevated if endogenous insulin**, suggests insulinoma (low if exogenous insulin)
45
What is the management plan for Hypoglycaemia
If Patient **Conscious** (and able to swallow) → **oral glucose 15-20g (liquid, gel or tablet)** & **fast-acting carbohydrates** (glucose tablets, candy, juice)
If Patient **Unconscious** → **IM Glucagon** (takes hours to work) & **IV Dextrose (20% Glucose)** (more rapid or if glucagon doesnt improve symptoms)
Insulinoma → **surgical excision**
46
What is Whipple's Triad
low blood glucose concentration, hypoglycaemic symptoms & resolution of symptoms after raising blood glucose concentration to normal
47
What are clinical features of Peripheral Neuropathy
**Pain**→ Often **worse at night** and may disturb sleep. Burning/sticking/aching
**Loss of Sensation** → Eventually causes a symmetrical distal sensory loss in a **'glove and stocking distribution’**
**Dysaesthesia** (Peripheral) → **burning sensation** in feet
**Reduced/Absent Ankle Reflexes**
**Painless Injuries** (Peripheral) → occur at **pressure points**.
Infection is a common complication, followed by gangerene if vascular compromise.
48
What are clinical features of Mono Neuropathy
sudden motor loss (eg. wrist drop, foot drop, 3rd nerve palsy - down and out eye)
49
What are clinical features of Autonomic Neuropathy
resting **tachycardia**
**urinary frequency/ urgency**/ nocturia/ incontinence /hesitancy/ weak stream/ retention
**erectile dysfunction**
**constipation**
**difficulty swallowing**
**postural hypotension**
50
What are clinical features of GI Autonomic Neuropathy
Gastroparesis (GI Autonomic Neuropathy) ⇒ diabetics with upper GI symptoms and erratic glucose control due to gastric emptying dysfunction.
Tx with metoclopramide (pro-kinetic that improves gastric emptying).
51
How does Diabetic Neuropathy occur
blockage of vasa nervorum
most common diabetic complication
52
What are the causes for Hypothyroidism
- **Congenital** → thyroid dysplasia or aplasia
- **Acquired** → **hashimoto's thyroiditis**
(autoimmune), postpartum thyroiditis, de quervain thyroiditis, Iatrogenic (post-surgery)
- Secondary Hypothyroidism → pituitary disorders (eg. pituitary adenoma) → TSH deficiency
- **Lithium Toxicity** can cause hypothyroidism
53
What are the clinical features of hypothyroidism
- Decreased Basal Metabolic Rate → **dry skin**, **cold intolerance**
- Decreased Sympathetic Activity → decreased sweating, **constipation**, **bradycardia**
- **Fatigue**, **hair loss**, **weight gain** (despite **poor appetitie**)
- **Depression**
- **Menorrhagia** (heavy periods)
54
Apart from the usual hypothyroid symptoms, what else does Hashimotos present with?
goitre (firm, non-tender)
55
What investigations are needed for Hypothyroidism
- **TFTs**
- Decreased T4 & T3 levels
- If **increased TSH → primary hypothyroidism**
- If **decreased TSH → secondary hypothyroidism**
- Pituitary Insufficiency (may need MRI)
- **Antibody testing** → in autoimune hypothyroidism
- **Anti-TPO** → occurs in **hashimoto**
56
What is the treatment for Hypothyroidism
**Levothyroxine** → **lifelong** replacement, adjust dose based on TFTs
TSH should be checked annually following stabilisation of dose
- Raised TSH and Normal T4 suggests poor compliance with levothyroxine
- Dose should be increased by up to 50% in pregnancy (as early as 4-6 weeks of pregnancy)
- Overreplacement with thyroxine increases risk of osteoporosis
57
What is Myxoedema Coma
severe hypothyroidism causing impaired mental status, hypothermia, hypotension
58
What is the treatment for Myxoedema Coma
IV levothyroxine (T4) & liothyronine (T3) + IV hydrocortisone, oxygen + rehydration
59
What is obesity defined as
Defined as BMI ≥30kg/m², can be grouped into classes 1-3
BMI → (weight in kg) / (height in m)²
60
What is the management plan for obesity
**Class 1** (BMI ≥30kg/m²)
- **dietary changes** + **increase in physical activity** are first line.
- Consider medication - **Orlistat (pancreatic lipase inhibitor)**
**Class 2 with comorbities** OR **Class 3** OR **Other measures innefective**
- **surgical therapy** (**bariatric surgery** - sleeve gastrectomy)
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